Newtown Aug 13, 2020 (Thomson StreetEvents) -- Edited Transcript of Onconova Therapeutics Inc earnings conference call or presentation Wednesday, August 12, 2020 at 8:30:00pm GMT

* Abraham N. Oler

Onconova Therapeutics, Inc. - Senior VP of Corporate Development & General Counsel

Onconova Therapeutics, Inc. - CFO

Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development

* Steven M. Fruchtman

Onconova Therapeutics, Inc. - CEO, President & Director

Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

Good afternoon, and welcome to Onconova Therapeutics corporate update and 2Q 2020 financial results conference Call. (Operator Instructions) As a reminder, this call may be recorded. At this time, I would like to turn the call over to Avi Oler, Senior Vice President of Corporate Development and General Counsel.

Abraham N. Oler, Onconova Therapeutics, Inc. - Senior VP of Corporate Development & General Counsel [2]

Thank you, operator. Good afternoon, and welcome to Onconova's second quarter 2020 corporate update and financial results conference call. Earlier this afternoon, we issued a press release outlining our financial results and business progress during the quarter. If you have not seen this press release, it is available on the Investor Relations page of our website at http://www.onconova.com. On today's call, Dr. Steve Fruchtman, President and CEO, will discuss the company's recent highlights and anticipated clinical and business milestones. After Steve completes his opening remarks, Mark Guerin, our Chief Financial Officer, will review second quarter financial results. Following Mark's report, we will move to the Q&A portion of the call, which will be joined by Dr. Rick Woodman, our Chief Medical Officer. Lastly, Steve will come back with some final comments and a review of our upcoming milestones.

Before we begin, I remind everyone that statements made today during this conference call will include forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, which involve risk and uncertainties that can cause actual results to differ materially. Forward-looking statements speak only as of the date they are made, as the underlying facts and circumstances may change. Except as required by law, Onconova disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. Please see the forward-looking statements disclaimer in the press release issued this afternoon and the risk factors in the company's current and future filings with the SEC.

With that, it is now my pleasure to turn the call over to Steve.

Thank you, Avi. Good afternoon, everyone, and thank you for joining today's call. First, as the COVID pandemic continues to evolve in the U.S. and abroad, we wish all safety and good health to you and your love ones. We remain committed to executing our goals with INSPIRE and beyond. We remain focused on INSPIRE data readout and we'll speak more about the COVID pandemic shortly. Onconova has had a productive second quarter and exited the quarter carrying a significant momentum into the second half of 2020. As previously indicated, our pivotal Phase III INSPIRE trial recently achieved required number of survival events to allow for data analysis, and we anticipate top line data readout by the end of September. COVID has made access to hospitals and clinics more difficult, so data verification of key dates such as survival and the most recent clinical encounters are more difficult to verify, but verify, we must and we shall. Following top line data readout, we expect to present more detailed data at a major medical meeting later this year. The meeting to be identified based on time lines. Of note, most, if not all, major medical meetings are now virtual. To shorten the time lines for our anticipated new drug application or NDA submission to the FDA, we have already begun NDA preparation prior to data readout. We are working also with regulatory consultancy experts on our NDA document for the U.S. FDA for both the clinical and manufacturing modules of the NDA as well as on the marketing authorization application, or MAA, document for the European Medicines Agency. We anticipate that this initial work will put us in a position to expedite our health authority applications when data becomes available. As part of this process, our clinical team under Rick Woodman's leadership is preparing for a pediatric investigational plan, or PIP, an important component of the MAA. We are also advancing our plans to be ready for commercialization, including the recent announcement of the election of a commercial expert, Ms. Terri Shoemaker, to our Board of Directors. Terri carry was instrumental in the successful commercialization of azacitidine, the most commonly used hypomethyl agent in the world for high-risk MDS.

As you recall, INSPIRE is an open-label, randomized, controlled, international study designed to determine the efficacy, safety and tolerability of single agent intravenous rigosertib in the treatment of patients with second-line, high-risk MDS. Patients in this study are less than 82 years of age and have progressed or relapsed or failed to respond to previous treatment with the standard of care, a hypomethylating agent, also called an HMA. The study randomized patients to receive either rigosertib with best support of care or the physician's choice of therapy with support of care. The primary endpoint of this study is overall survival of all randomized patients in the intent-to-treat population. There is a second opportunity for an FDA approval, which is the sequential analysis of the overall survival of the very high-risk MDS subs as defined by the revised International Prognostic Scoring System. Should intravenous rigosertib demonstrate a survival advantage compared to physician's choice of therapy on the INSPIRE trial in a statistically significant manner, we believe rigosertib could be a major advance for high-risk, second-line MDS patients with a novel mechanism of action. Hopefully, broader and additional novel indications will follow.

Beyond our progress with INSPIRE, a highlight of the quarter was the initiation of an investigator-initiated Phase I/II trial of oral rigosertib plus the immune checkpoint inhibitor, nivolumab, in advanced metastatic KRAS positive lung adenocarcinoma. Over half of non-small cell lung cancers are classified at lung adenocarcinoma. And of these, the largest subset has a KRAS mutation as the predominant genetic driver. Given their utility in multiple cancer setting, checkpoint inhibitors are among the world's top-selling pharmaceutical products. And continue to obtain FDA approval for broader indications. In our view, this makes our novel combination approach with rigosertib a potentially meaningful option to pursue in lung cancer. We hope this will offer patients who have progressed on first-line therapy, a second-line approach. We are also initiating studies in other RAF pathway-driven cancers as part of our investigator-initiated development program.

Onconova has also recently featured pipeline developments in multiple venues. At the European Hematology Association's virtual conference in June, we announced updated aggregated baseline genomic data for HMA failure patients screened and entered into the INSPIRE trial. Briefly, the presentation show that RAF pathway mutations in these higher-risk MDS patients were observed more frequently in patients who progressed on HMA therapy as defined by the international working group's definition of progression compared to those who failed to respond to HMA therapy. In fact, in this study, patients with mutations of the RAF pathway had a higher likelihood of progression on hypomethylating agents than those with TP53 mutations, a well-recognized genomic abnormality predicting for progression in a number of cancers. We believe this is informative to the potential role of RAF targeting agents such as rigosertib. And to our knowledge, this mutational analysis is among the largest such databases to be collected. Patients on the rigosertib and physician's choice arms will have repeat analysis of their genomic status performed as part of the INSPIRE trial.

Following the close of the second quarter, Onconova also announced a publication of Phase I data with the combination of oral rigosertib plus azacitidine and higher-risk MDS and AML in the journal, Leukemia Research. A key strategy emerging in the treatment of MDS is the identification of safe and effective combination, particularly those involving oral agents. We anticipate meeting with the FDA in conjunction with the pivotal data readout from the INSPIRE trial for alignment with the agency on a registration trial for the combination of oral rigosertib plus azacytidine and HMA-naive, high-risk MDS. We look forward to these interactions with the agency. In the journal, Molecular Cell, we also announced the publication of additional preclinical data, supporting rigosertib's mechanism of action as a RAS-targeted anticancer therapy. Onconova believes this data sheds light on the ability of rigosertib to modulate the RAS pathway.

We also disclosed that we have embarked on early preclinical work exploring legal service potential in COVID-19. The background for this is as follows: these preclinical studies follow a presentation at ASH in 2019, suggesting the ability of rigosertib to upregulate viral defense pathways such as interferon. It is hypothesized that the immune system may play a role in the pathogenesis of MDS and immune modulation has been studied in MDS. More recent preclinical studies conducted with rigosertib demonstrated impressive inhibition of SARS-CoV-2 replication in vero cells when compared to controls, and provide the company with optimism that further research in humans infected with SARS-CoV-2 is warranted. In late July, Onconova announced that it has applied to the National Institute of Allergy and Infectious Diseases, or NIAID; and also to BARDA, the Biomed Advanced Research and Development Authority, to seek funding and to participate in therapeutic trials under the NIH umbrella to conduct human studies with rigosertib. We caution that our work in COVID-19 is very early, and the need for therapeutics and effective vaccines is evolving rapidly as the pandemic continues in various geographies across the globe. Hence, we cannot predict what the outcome of our efforts will be. We hope to provide greater clarity sometime during the second half of this year. In addition to the U.S., we have the rights to rigosertib in Europe and China and other key markets around the world. Beyond rigosertib, ON 13300 (sic) [ON 123300] is our first-in-class inhibitor of CDK4/6 and ARK5. We believe ON 123300 has the potential to treat numerous cancers, including refractory metastatic breast cancer, where CDK4/6 inhibitors are already commercially available. CDK inhibitors have emerged as promising products and compounds targeting very large cancer indications such as hormone receptor positive metastatic breast cancer. Due to its unique targeting of ARK5 as well as CDK4 and 6, we believe ON123300 could overcome many of the existing product's limitations, potentially making it suitable for certain cancers that may not be responsible -- responsive, sorry, to the current generation of CDK4/6 inhibitors. If successful, we believe this product candidate could address this very large market opportunity. We maintain global rights for ON 123300 outside of China. Our partner in China for this compound is HanX Biopharmaceuticals. HanX funded the Chinese IND-enabling studies. The Chinese IND was approved in January 2020 by the Chinese health authorities. We anticipate a Phase I study may begin in China in the second half of 2020. We also intend for the Chinese IND-enabling studies to comply with FDA regulations. To the U.S., we plan to file a U.S. IND in the fourth quarter of 2020.

And now I'd like to turn the call over to Mark Guerin, our Chief Financial Officer, for a discussion of our financial results for second quarter 2020. Mark?

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Mark Patrick Guerin, Onconova Therapeutics, Inc. - CFO [4]

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Thanks, Steve, and good afternoon, everyone. First, as a reminder, early this month, Onconova received a letter from NASDAQ stock market stating that it had regained compliance with the minimum bid price requirement of the NASDAQ listing rule 555-082 because its common stock had a minimum closing price of at least $1 per share for a minimum of 10 consecutive business days.

Our cash and cash equivalents as of June 30, 2020, totaled $27.2 million compared to $22.7 million as of December 31, 2019. Common stock warrant exercises since our financing transactions in November and December 2019 have added $9.8 million to our balance sheet since January 1, 2020. And as of August 12, 2020, we have 183,568,267 common shares outstanding. Additionally, of the almost -- of the warrants outstanding as of June 30, 2020, over 80% of them were in the money as of August 12. Based on our current projections, we expect that our cash and equivalents will be sufficient to fund ongoing trials and operations into the fourth quarter of 2021. Our net loss was $7.4 million for the quarter ended June 30, 2020, compared to $3.6 million for the comparable period in 2019. Research and development expenses were $4.8 million for the quarter ended June 30, 2020, and $3.9 million for the comparable period in 2019. General and administrative expenses were $2.6 million for the quarter ended June 30, 2020, and $1.8 million for the comparable period in 2019. Our operating cash burn in the second quarter of 2020 was approximately $5.4 million. This completes my financial review.

I'll now turn the call back to Steve.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [5]

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Thank you so much, Mark. With that, we'd like to open the call for questions. After the questions and answers, I'll finish with some closing comments. Operator, please open the Q&A session.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Joe Pantginis from H.C. Wainwright.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [2]

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First, I'd like to ask about your initial comments about the data verification process for the study. What do you think are the real rate-limiting steps now, either COVID related or unrelated? And then secondly, with that, I think this is more of a what-if question, do you have any visibility now with regard to any potential patients lost due to COVID that might impact the statistics? And have you had any discussions with the FDA about this and they have put out a recent public guidance a couple of months ago about being a little more amenable to adjusting statistical plans due to COVID.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [3]

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Joe, thanks for that question, and I'll ask Rick to please provide the answers.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [4]

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Thank you, Steve, and thank you, Joe. So all along, the biggest challenge that we observed with our study related to COVID was access to documents and -- at the sites. And this is not necessarily physically being able to get to sites, but even having remote monitoring opportunities. We have been able to overcome almost all of those difficulties and challenges. Now we are still in database lock, and so we are continuing to clean data and monitor and source data verify. But to date, it's gone very well. And I think it's in part, the understanding by the sites regarding where we are in the life cycle of the study and the importance of this data to the outcome of the study and to this disease. We have not lost any patients due to COVID at this time. The commonest challenge we see is that patients are -- have symptoms suggestive of COVID and then undergo testing and then report to us the results, negative or positive.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [5]

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Got it. And as things continually get more exciting for you guys coming into the data, I guess I'll ask the question at this point, again, and I know I do ask this a lot about what you feel is outstanding with regard to the oral study ahead of your upcoming FDA meeting?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [6]

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Well, I think the primary challenges are related to the unique adaptive design we're proposing to the FDA and that will require some discussion between us and the agency. I think that the timing of INSPIRE, if positive, could very much support their interest in an adaptive study design that has an expedient execution and conduct with oral rigosertib.

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Joseph Pantginis, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [7]

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Good luck for this major thing coming up for you guys. Real exciting.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [8]

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Thank you.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [9]

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Thank you, Joe.

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Operator [10]

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Our next question comes from the line of Naureen Quibria from Maxim Group.

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Naureen Quibria, Maxim Group LLC, Research Division - Senior Equity Research Associate [11]

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Steven, congrats on the quarter. So I guess I want to start off with the KRAS study that's going on right now, obviously. So I was just wondering, it's an open-label study, do you have any idea if we'll have any updates this year on that? And then what kind of response rates would you -- would give you some confidence in terms of you feel there's activity in this tumor type? I know it's a long ways away, but I'm curious about that as well.

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [12]

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So thank you. And I just want to point out that this is a Phase I study, and I'll ask Rick to give -- offer the more details that we may have.

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Richard Charles Woodman, Onconova Therapeutics, Inc. - Chief Medical Officer and Senior VP of Research & Development [13]

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Thank you, Steve. So we're in the early phases of enrollment with this study. I think, obviously, with these studies, data can become available sooner than anticipated. Or conversely, take much longer than anticipated depending upon dosing and development DLTs. Because this is a Phase I study, Steve mentioned safety, DLT determination and determination of a recommended Phase II dose for the combination is the priority. I think like all Phase I studies, we are always excited about responses, but that is not what's going to determine the success of the study or the ability to proceed with other studies. It will be dosing and safety.

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Naureen Quibria, Maxim Group LLC, Research Division - Senior Equity Research Associate [14]

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Sure. That's helpful, actually. And then in terms of moving oral or looking at oral rigosertib in COVID, and you mentioned that you'd applied for a grant. I was just wondering what's the turnaround time for that. And, a, when will you know anything? And then in terms of the economics, is this just -- would it be sufficient for IND-enabling studies or actually for a clinical trial?

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Steven M. Fruchtman, Onconova Therapeutics, Inc. - CEO, President & Director [15]

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So I'll take that and thank you. So you mentioned oral rigosertib. So why we believe rigosertib should be studied in COVID disease is because we have oral and intravenous rigosertib. So as you know, there's different levels of disease with COVID infections, some relatively mild and some pent demand to pulmonary [cell]. So based on the inhibition of SARS-CoV-2 in cell culture systems. As you mentioned, we've applied for funding through the NIH federal mechanism of studying COVID disease. Early in the disease, ideally, it would be with oral rigosertib to see if it would prevent progression to pulmonary insufficiency for patients who have already reached, unfortunately, the stage of pulmonary insufficiency, requiring ventilatory support, that would be a group of patients who could be studied with intravenous rigosertib. Because the global pandemic is changing rapidly, it is unclear to us how NIH and the federal funding agencies will make decisions regarding both therapeutics and vaccines. We believe as long as the pandemic continues to rage, there is a great need for the development of additional efficacious therapeutics. So thus, we believe, based on the preclinical studies, we would like to participate in any clinical trials that the NIH may be considering for therapeutics. But clearly, the NIH is appropriately focused on the development of vaccines, and thus, it's unclear to us where NIH stands on the issue in question of the role of therapeutics during the pandemic and the role of vaccines. Any information we have going forward, we will be happy to share that with the investment community.

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Operator [16]

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Our next question comes from the line of Ahu Demir from NOBLE Capital.

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Ahu Demir, NOBLE Capital Markets, Inc., Research Division - Biotechnology Research Analyst [17]

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View post:
Edited Transcript of ONTX.OQ earnings conference call or presentation 12-Aug-20 8:30pm GMT - Yahoo Finance

Recommendation and review posted by Bethany Smith

Building muscle is a slow but worthwhile process.

Many people start workout routines to look toned or lean. Lifting weights can help you achieve those goals, but it's important to start a new workout plan with the right expectations.

Building muscle takes much longer than most people realize. It's a slow -- almost excruciatingly slow -- process that can feel discouraging when you don't see the muscle definition you want.

Here you'll learn how long it takes to build muscle and what factors influence your ability to get stronger, leaner and fitter from weight training.

Our Health & Wellness newsletter puts the best products, updates and advice in your inbox.

Each muscle is made up of muscle fibers, which are cylindrical cells. Weight training breaks them down and recovery helps them grow.

Building muscle involves the repair of microtraumas in your muscle fibers. Here's a breakdown of this extremely complex process:

1. Each muscle is made up of thousands of tiny muscle fibers.

2. When you lift weights (or do body weight exercises), your muscles endure tiny injuries throughout their fibers.

3. Then, when you rest your muscles, your body begins repairing your damaged muscle cells.

4. The repair process involves fusing torn muscle fibers back together, as well as laying down new proteins within each muscle cell.

5. Your muscles become bigger and stronger as a result of the repair process.

Keep in mind that the above is a tremendously simplified version of what actually happens in your body after a weight training workout. In reality, the process includes more than just your muscles -- your nervous system, circulatory system and endocrine system all contribute to muscle repair and growth.

Building muscle is super hard. If it was easy, we'd all be ripped.

There's no one muscle-building timeline, because several factors affect your ability to build muscle mass, including:

Your protein intake: While all macronutrients have their roles, protein is king when it comes to building muscle. Your muscles need adequate protein to repair themselves after the stress of weight training. Without enough protein, muscle growth stagnates.

Your calorie intake: If you don't eat enough calories on a daily basis, you won't build muscle even if you eat a lot of protein. To build muscle, your body must create new tissue, and it can't create something from nothing. Extra fuel from extra calories expedites muscle recovery and growth. This is one reason many people never reach their muscle growth goals -- they aren't willing to deal with the extra body fat that comes along with a muscle-building phase.

Your sleep schedule: Lifting weights while sleep-deprived isn't a smart strategy. You might see some gains, but you definitely can't optimize muscle growth when you don't give your body a fighting chance to recover.

Your lifting routine: If you're trying to build muscle, you should know about two key strength training concepts: frequency and volume. Frequency refers to how often you train a muscle or muscle group, while volume refers to the total load you stress a muscle with.

For example, if you perform three sets of 10 reps on squats using 100 pounds, your total volume is 3,000 pounds. More volume and higher frequency typically equate to more muscle, unless you reach the point of overtraining.

Your training age: The more advanced you are, the less muscle growth you'll see (yeah, that sounds backward). Everyone has a maximum genetic potential for muscle growth, and the closer you get to yours, the harder it gets to build more muscle.

Your actual age: Like a lot of things, building muscle gets harder as you get older. Sarcopenia, or loss of muscle mass and function, is actually a big problem in older adults. That's one reason why it's so important to stay active as you get older.

Other major factors include your genetic potential for building muscle (which is impossible to quantify without lab testing, and even then, kind of wishy-washy) and your testosterone levels -- which is why men typically have more muscle than women. Other hormones, including human growth hormone and insulin growth factor also play a role in muscle growth.

All that said, the muscle-building process starts the moment you challenge your muscles to do something. True beginners might see muscle growth within six weeks of starting a resistance training program, and advanced lifters may see results within six to eight weeks of switching up their usual strength training regimen.

Regardless of fitness level, building muscle takes several weeks, even when your diet, sleep and training regimen are all dialed in to optimize muscle growth.

Cardio that involves high-volume weight training can help you build muscle.

This depends on your definition of cardio and your training age. Most people won't build much muscle from traditional cardio, such as walking or jogging, and people who've been training for a long time definitely won't build new muscle through traditional cardio. It doesn't recruit your muscles in a way that sends a muscle-building signal to your body.

However, cardio that involves high-intensity exercises like plyometrics (think jump squats) or high-volume weight training can help you build muscle to an extent. Sprinting hills, hiking, skiing and other outdoor cardio can also contribute a small amount to muscle mass, especially for beginners. People with a long training history may not see as much success with cardio.

Although cardio can improve your overall fitness and help build muscle in select scenarios, strength training remains the best way to build muscle mass.

The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.

See original here:
How long does it take to build muscle? - CNET

Recommendation and review posted by Bethany Smith

Global Endocrine Testing Market was valued US$ XX Bn in 2018 and is expected to reach XX Bn by 2026, at a CAGR of 8.00% during a forecast period.

REQUEST FOR FREE SAMPLE REPORT:https://www.maximizemarketresearch.com/request-sample/33711

The endocrine system plays a vital role in reproduction, growth and sexual development, retorts to injury and stress, body energy level, bone and muscle strength, and also internal balance of the body.

The report study has analyzed revenue impact of covid-19 pandemic on the sales revenue of market leaders, market followers and disrupters in the report and same is reflected in our analysis.

The growing incidence of hormonal imbalances in individuals is one of the key drivers in the global endocrine testing market. Changing lifestyles, growing stress, and unhealthy food habits result in obesity and disturbed hormonal changes, these are some of the driving factors under the growth in global endocrine testing market.

The software has been designed to accomplish the workflow in the laboratories, like new mobile apps have been developed so that patient can be reminded about his appointment or test, and he will be able to contact a physician. These advancements in technology are projected to propel the global endocrine testing market growth over the forecast period.On the other hand, the high cost of technology is projected to be the key restrain for the growth of the global endocrine testing market. Furthermore, an increase in the investment in research and technology is measured as a major opportunity for the growth of the global endocrine testing market.

The thyroid-stimulating hormone (TSH) test is expected to share significant growth in the global endocrine testing market. The significant growth in the market is attributed to the growing incidences of TSH-related disorders, and rising awareness regarding the correlation between variations in the thyroid hormone level and cardiovascular disorders. Furthermore, the Insulin test is expected to grow at a XX % rate of CAGR during the forecast period. The considerable rise in the diabetic population and the rising awareness about diagnosis are expected to contribute towards the demand for an insulin test.

The tandem mass spectrometry is estimated to hold a dominant position in the global endocrine testing market followed by sensor technology segment. The growing use of tandem mass spectrometry in combination with liquid chromatography, which also helps in overcoming challenges associated with traditional techniques are expected to increase the demand for tandem mass spectrometry. On the other hand, sensor technology is projected to grow at a XX % rate of CAGR during the forecast period owing to the increasing use of biosensors in glucose monitoring for diabetes which is used on routine basis by the individuals to monitor their blood sugar level.

Geographically, North America region is estimated to contribute a significant share in the global endocrine testing market. Growing incidence of several types of endocrine diseases, rapid adoption of novel testing techniques supported by regulatory infrastructure and positive recompense scenario are some of the prominent factors behind the growth in the global endocrine testing market.

The objective of the report is to present a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, industry-validated market data and projections with a suitable set of assumptions and methodology. The report also helps in understanding dynamics, structure by analyzing the market segments and, project the global endocrine testing market. The report also provides a clear representation of competitive analysis of key players by product, price, financial position, product portfolio, growth strategies, and regional presence in the global endocrine testing market. The report also provides PEST analysis, PORTERs analysis, SWOT analysis to address the question of shareholders in arranging the efforts and investment in the near future to a particular market segment.Scope of the Report for Global Endocrine Testing Market

Global Endocrine Testing Market, By Test

Follicle stimulating hormone (FSH) Human Chorionic Gonadotropin (hCG) Thyroid Stimulating Hormone (TSH) Dehydroepiandrosterone sulphate (DHEAS) Prolactin Progesterone Insulin Cortisol Testosterone Estradiol (E2) Luteinizing Hormone (LH)Global Endocrine Testing Market, By Technology

Immunoassay Clinical Chemistry Monoclonal and Polyclonal Antibody Sensor technology Tandem Mass SpectroscopyGlobal Endocrine Testing Market, By End User

Hospitals Physician Offices Health Care Centers Commercial LaboratoriesGlobal Endocrine Testing Market, By Region

North America Europe Asia Pacific Middle East & Africa South AmericaKey players operating in Global Endocrine Testing Market

Thermo Fisher Scientific, Inc. Quest Technology Biomedical Technologies. Sysmex Corporation Abbott Laboratories AB Sciex Pte. Ltd. Agilent Technologies Siemens Healthcare Ortho Clinical Technology BioMerieux SA Bio-Rad Laboratories DiaSorin S.p.A F. Hoffmann-La Roche Ltd. Laboratory Corporation of America Holdings

Browse Full Report with Facts and Figures Report at:https://www.maximizemarketresearch.com/market-report/global-endocrine-testing-market/33711/

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Global Endocrine Testing Market: Industry Analysis and Forecast (2019-2026) By Test, Technology, End Use and Region. - Good Night, Good Hockey

Recommendation and review posted by Bethany Smith

Ive written lots of articles about probiotics, microbiota, and the health of your gut, especially in relation to things like heartburn, mental well-being, and simple overall health. As Im currently nine months pregnant, Ive been dealing with quite a few unpleasant gut changes, which led me down a fascinating road of gut types. Who knew that there were actually differenttypes of gut that present physically, mentally, and emotionally!

Each human body is individual and therefore requires individual attention and this goes for your gut too. While probiotics, a plant-based diet, and a physically active lifestyle are all great places to start when boosting your gut health, discovering the exact type of issues going on within your gut will help to tailor the food you eat, the type of exercise you take part in, and what type of supplements may help to alleviate any digestive discomfort.

Lets take a little explorative session into the digestive system, the microbiome, the different types of gut, and how we can care for ourselves as individuals!

When you talk about the gut, youre actually referring to an incredibly complicated system that extends between your mouth all the way to your rectum. This system is the main source of nutrient absorption and storage, its how we energize, and how we get nourishment. Alright, so what makes up your digestive system?

The digestive system includes your mouth, esophagus, stomach, small intestine, large intestine (also called your colon), pancreas, liver, gallbladder, rectum, and anus. As you can tell, the digestive system isnt just located in your mid-section generally where you feel most digestive discomfort such as bloating, gas, or upset stomach but its an entire body, top to bottom, network.

On top of that, your gut or digestive system is riddled with good and bad bacteria called microbiota that make up the microbiome, yet another incredibly complicated ecosystem within your body. Yet, this microbiome has been found to play an integral role in not only your digestive health but also your mental health, the efficacy of nutrient absorption, energy level pretty much your overall bodily health.

Each part of the digestive system has an important part to play! Lets take a look at how your food is processed through this amazing network. Digestion begins in the mouth as your salivary glands get active when you see and smell food. Your saliva then mixes with the food to begin to break it down into a form your body can absorb and use.

Next, your esophagus receives food from your mouth [and] a series of muscular contractions within the esophagus called peristalsis delivers food to your stomach. Finally, weve made it to the stomach! This hollow organ holds food while it is being mixed with stomach enzymes [and strong acid] [that will] continue the process of breaking down food into a usable form.

From there, this new conglomeration of enzyme, acid, and nutrients moves into the small intestine where the work really starts! Your small intestine is a 22-foot long muscular tube made of three segments the duodenum, jejunum, and ileum where your food is further broken down using enzymes released by the pancreas and bile from the liver, as well as peristalsis, which aids the food to move through and mix with digestive juices from the pancreas and liver. The first segment of your small intestine the duodenum is responsible for the continuous breaking-down process, while the lower sections the jejunum and ileum are responsible for absorption of nutrients into the bloodstream.

The resulting semi-solid mixture water, bile, enzymes, and mucus passes into the colon (of the large intestine). The colon is a 6-foot long muscular tube that connects the small intestine to the rectum and its primary goal is to separate the necessary from the waste. While the colon may be shorter than the small intestine, its made up of more parts including the cecum, the ascending (right) colon, the transverse (across) colon, the descending (left) colon, and the sigmoid colon, which connects to the rectum. Once all the nutrients and water have been removed from the mixture, youre left with waste matter, which is stored in the sigmoid (S-shaped) colon until a mass movement empties it into the rectum once or twice a day.

While we dont reallywantto talk about waste, its important to note that theres a lot more going on there than meets the eye. Your waste or stool is mostly food debris and bacteria. Its the bacteria that you want to focus on. These good bacteria perform several useful functions, such as synthesizing various vitamins, processing waste products, and food particles, and protecting against harmful bacteria.

I covered, very briefly, the difference between microbiota referring to the collection of microbes that live in and on the human body and microbiome referring to the complete set of genes within these microbes. One is talking about the entirety and the other refers to the individual or more detailed version of the former. In another of my gut-related articles Understanding the Gut-Hormone Connection I break down the microbiome:

Themicrobiomeis very similar to a mini-ecosystem in which microscopic organisms thrive. These microscopic organisms, also called microorganisms, create a symbiotic environment called themicrobiome and they includebacteria, pathogens infections agents, archaea prokaryote microorganisms, which lack a nucleus, and eukaryotic microbes microorganisms that have a nucleus. Your microbiome is built from yourpersonal environment and lifestyle, such as geography, health status, stress, diet, age, gender, and everything you touch, therefore every humans microbiome isspecial and uniqueto them.

When it comes to the health of your gut or digestive system there are lots of factors that play an important role including exercise, stress, and medication. Yet, one of the most influential factors is your diet. The effects of diet are probably what you would expect.

A diet thats loaded with highly processed and ultra-processed foods which include refined carbs, sugars, hydrogenated oils, and trans fats is severely detrimental to your gut health, while a diet rich in whole, plant-based foods is linked to a healthy gut. This isnt just hearsay, there have been multiple studies conducted at different institutions and within different parameters that come to similar conclusions such as this study published in the European Cardiology Review or this multi-institutional study entitled The Effects of Vegetarian and Vegan Diets on Gut Microbiota.

So, what is it about a plant-based diet that improves gut health? A lot of it has to do with the fact that plant-based diets are naturally anti-inflammatory, yet the other large part is due to the fact that plants are rich in a variety of gut-sustaining nutrients such as dietary fiber, antioxidants, healthy fats, and a diverse range of all the vitamins and minerals. For instance, dietary fiber is known to promote the growth of beneficial bacteria that reduce inflammation and cardiovascular disease risk, as well as increases short-chain fatty acids linked to improved immunity and improved intestinal function.

While fiber is important, its also about incorporating a balanced intake of the proper amount of vitamins, minerals, and macronutrients, while excluding the toxic ingredients of processed foods and high amounts of added sugar. All of these play a factor in your gut health!

Alright, now that we know as much as we can about gut health in as short a period as possible, that is! its probably a good idea to take stock of your own gut health. Digestive issues are a pervasive issue in the states. Per the Centers for Disease Control and Prevention, 22.4 million people were diagnosed with a digestive disorder or disease by their physician, while 8.3 million people were separately diagnosed in the emergency room.And this doesnt account for physician or emergency room visits for less severe digestive disorders such as painful gas, diarrhea or constipation, excessive bloating, or upset stomachs.

Most likely, everyone reading this article has one or two gripes about their digestive system! Where do you start? Figure out what type of gut youve got and learn how to properly care for it so you can balance out that microbiome and avoid products and foods that may cause disrupt.

Candida is a genus of yeasts that is typically found in small amounts in the mouth and intestines and on the skin. Its actually quite normal to have small amounts of candida throughout your life, yet when that amount begins to grow uncontrollably, it can cause an infection known as candidiasis, which happens to be the most common cause of fungal infections in humans.

This condition can manifest in weight gain, phlegmy coughs and sniffles, and a white coating on the tongue.Those with a candida gut generally desire foods rich in sugar, dairy, and wheat and are generally incredibly worrisome, anxious, and obsessive.

If youre looking to heal yourself, its recommended to eat a lot of soups, stews, and warm starchy veggies, such as this Chickpea Miso Noodle Soup or these Cinnamon Turmeric Sweet Potatoes fermented foods, such as these Potato Kimchi Pancakes or this Homemade Raw Sauerkraut and incorporate a good probiotic such as this Garden of Life Whole Food Probiotic Supplement, this Florastor Daily Probiotic Supplement, or this Hyperbiotics PRO-15 Probiotic. On the other hand, make sure to avoid dairy, sugar, refined grains, raw foods, and yeast.

A gastric gut is directly linked to your lifestyle, self-care routine, and a slow-moving digest system. In particular, it means that youre overworking and overexerting yourself. This mixture overworking and a slow-moving digestive system leads to habits that cause poor digestion such as not chewing properly, overeating, and taking antacids.

This condition manifests with issues such as gas, bloating, and acid reflux, as well as habits such as eating your food too fast. If youve got this gut type, you most likely are a fiery, passionate, and reactive personality type as well!

If youre looking to heal, try to eat several small meals and stop before youre full, load up on bitter veggies, herbs, and citrus, drink mineral water, [and] supplement with digestive enzymes, such as this Pure Vegan Digestive Enzyme Complex, these Mary RuthsVegan Digestive Food Enzymes, or this Garden of Life Organic Chewable Enzyme Supplement. On the other hand, youll want to avoid alcohol, caffeine, fried foods, and spicy foods. Try a few of these plant-based recipes that are rich in bitter veggies, herbs, and citrus: 10-Minute Seitan Beef and Broccoli, Braised Kale, Cilantro Lime Tacos, Alkaline Green Juice, or this Avocado Grapefruit Jicama Salad.

You may think that a gastric and stressed gut are the same thing and while they may have similarities, theyre actually quite different! A stressed gut is caused by the constant circulation of stress hormones, which diverts blood flow away from your gut and impairs the growth of good bacteria and digestive enzyme production.

The condition usually manifests in adrenal fatigue, which causes sleep issues, decreased libido, and trouble focusing. These folks tend to consume too much coffee and/or too much alcohol and generally have a type-A workaholic personality.

If youre looking to heal, incorporate salty, dark-colored foods, such as this Vietnamese Purple Yam Soup or these Homemade Dark Chocolates supplement with B vitamins, and look into getting some adaptogens into your life such as these Natures Way Astragalus Root Capsules, these Pure Mountain BotanicalsHoly Basil Capsules, or this NaturaLife LabsOrganic Maca Root Black, Red, Yellow.

Make sure to avoid alcohol, caffeine, refined grains, and sugar.

One of the main culprits behind an immune gut is food sensitivities most commonly, gluten and dairy. Unfortunately, there are a few factors that are somewhat unavoidable that can cause an immune gut including longtime use of antibiotics, birth control pills, and steroids.

An immune gut is treatable, but at its worst results in autoimmune disorders and inflammatory bowel diseases. Those with this type of gut generally have a habit of going for the antibiotics on a regular basis and are usually perfectionists, insecure, and detail-oriented personality types.

If youre looking to heal an immune gut, its a bit more complicated than other types. First off, youll want to pair up with your doctor, nutritionist, or dietitian in order to work out an elimination diet in order to find out exactly what youre sensitive too. Next, its recommended to focus on reestablishing the health of your gut through supplemental digestive enzymes, soil-based (SBO) probiotics, and L-glutamine. Also, think about incorporating healthy fats on a daily basis think avocado, nuts, seeds, and coconut oil! On the other hand, steer clear of alcohol, dairy, raw foods, and packaged foods.

Find the perfect probiotic and digestive enzyme for your body using the following guide articles 10 Vegan Digestive Enzyme Supplements and Vegan Probiotics: How To Get Them From Supplements and Food

And then try out some of these healthy fat-filled recipes: Garden Green Soup, Peach, Raspberry and Coconut Yogurt Chia Pudding, Brussels Sprouts Salad with Macadamias and Apple, Avocado Pesto Pasta, or this Super Quick Chocolate Porridge.

Last, but not least, the toxic gut!

This type of gut is actually caused by the Standard American Diet basically, eating processed or fast food. As mentioned earlier, processed and ultra-processed foods are incredibly detrimental to your gut microbiome, so much so that eating too many are referred to as toxic. By eating processed foods, youre actually eating unhealthy fat, sugar, and chemicals.

This condition manifests in an inflammatory chain reaction from our liver to our intestines, leading to symptoms ranging from gallstones to rosacea to neurological distress. People who suffer from toxic gut generally are impatient, frequently frustrated, and quick to anger personality types. If youre looking to heal a toxic gut, incorporate an abundance of raw, green, and/or sour foods, drink dandelionormilk thistle tea, [and]get more sleep. On the other hand, avoid alcohol, non-organic produce, fried foods, nut butter, [and] oils.

Try some of these recipes that are rich in raw, green, and sour foods: Raw Cranberry Coconut Energy Bars, Carrot Ginger Soup With Curried Raisin Relish, Spinach Potato Soup, Thai Tempeh Collard Greens Wraps, Fizzy Pink Grapefruit Lemonade, or these Super-Easy Refrigerator Dill Pickles.

Learning everything you can about gut health is an excellent step towards a better functioning body! From boosting energy to smoothing out digestion to absorbing more nutrients and even conquering mental health issues, starting with the gut is a great idea!

Homemade Probiotic Cashew Yogurt/One Green Planet

Reducing your meat intake and eating more plant-based foods is known to help withchronic inflammation,heart health,mental wellbeing,fitness goals,nutritional needs,allergies,gut health,andmore! Dairy consumption also has been linked to many health problems, includingacne,hormonal imbalance,cancer,prostate cancerand has manyside effects.

For those of you interested in eating more plant-based, we highly recommend downloading theFood Monster App with over 15,000 delicious recipes it is the largest plant-based recipe resource to help reduce your environmental footprint, save animals and get healthy! And, while you are at it, we encourage you to also learn about theenvironmentalandhealth benefitsof aplant-based diet.

Here are some great resources to get you started:

For more Animal, Earth, Life, Vegan Food, Health, and Recipe content published daily, subscribe to theOne Green Planet Newsletter! Lastly, being publicly-funded gives us a greater chance to continue providing you with high-quality content. Please considersupporting usby donating!

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A Guide to Your Gut Type and What This Means for Your Diet - One Green Planet

Recommendation and review posted by Bethany Smith

New Jersey, United States,- The most recent Male Hypogonadism Therapy Market Research study includes some significant activities of the current market size for the worldwide Male Hypogonadism Therapy market. It presents a point by point analysis dependent on the exhaustive research of the market elements like market size, development situation, potential opportunities, and operation landscape and trend analysis. This report centers around the Male Hypogonadism Therapy business status, presents volume and worth, key market, product type, consumers, regions, and key players.

The COVID-19 pandemic has disrupted lives and is challenging the business landscape globally. Pre and Post COVID-19 market outlook is covered in this report. This is the most recent report, covering the current economic situation after the COVID-19 outbreak.

Key highlights from COVID-19 impact analysis:

Unveiling a brief about the Male Hypogonadism Therapy market competitive scope:

The report includes pivotal details about the manufactured products, and in-depth company profile, remuneration, and other production patterns.

The research study encompasses information pertaining to the market share that every company holds, in tandem with the price pattern graph and the gross margins.

Male Hypogonadism Therapy Market, By Type

Male Hypogonadism Therapy Market, By Application

Other important inclusions in the Male Hypogonadism Therapy market report:

A brief overview of the regional landscape:

Reasons To Buy:

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Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations with the aim of delivering functional expertise. We provide reports for all industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverage, and more. These reports deliver an in-depth study of the market with industry analysis, the market value for regions and countries, and trends that are pertinent to the industry.

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Male Hypogonadism Therapy Market 2020 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies and Forecast to 2027...

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Global Stem Cell Therapy Market is expected to reach an approximate CAGR of 10.3% during the forecast period. The use of stem cell for treating medical conditions is referred to as stem cell therapy. Stem cells are undifferentiated cells and differentiate into specialized cell types.

This ability of stem cells to differentiate into cells of interest is used to treat diseases like diabetes, heart disease, hematopoietic disorders (for example leukemia, thalassemia, and others), degenerative disorders (osteoarthritis, Alzheimers disease, Parkinsons disease, chronic renal failure, congestive cardiac failure,) and others.

Some of the key players are Osiris Therapeutics, Inc. (US), MEDIPOST Co., Ltd. (South Korea), Anterogen Co., Ltd. (South Korea), Pharmicell Co., Ltd. (South Korea), Holostem Terapie Avanzate S.r.l. (Italy), JCR Pharmaceuticals Co., Ltd. (Japan), NuVasive, Inc. (US), RTI Surgical, Inc. (US), and AlloSource (US), Thermo Fisher Scientific are some of the key players operating in the global stem cell therapy market.

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Global Stem Cell Therapy Market, by Technique,

Global Stem Cell Therapy Market, by Product Type

Global Stem Cell Therapy Market, by Application

Global Stem Cell Therapy Market, by End-User

Geographically, Americas is the largest in the market owing to the increasing prevalence of heart diseases and growing healthcare expenditure. According to the Centers for Disease Control and Prevention in November 2017, report every year 735,000 Americans have a heart problem. Such a high number of heart patients in the Americas drives the market growth in this region.

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Europe (UK, Belgium, France, and Netherlands) is the second largest global stem cell therapy market during the forecast period. The increasing occurrence of stroke, cancer, and osteoarthritis drives the market in this region. According to Anthony Nolan organization 2017, annual review 1.4million people register for donating stem cell in 2017. Also, more than 2,200 searches for a lifesaving stem cell transplant were made in 2017 by UK people. Such a high demand for Stem cell transplantation in this region promotes the market.

Asia-Pacific was projected to be the fastest growing region for the global stem cell therapy market in 2017. The market is expected to witness growth owing to the rising prevalence of smoking in this region.

According to the American Cancer Society, Inc 2018, report China 48.9%, India 16.2%, Japan 11.2% accounts of cancer cases in this region. Such a high cancer rate in this region favors the stem cell therapy market in this region.

The Middle East and Africa accounts for the least share due to low per capita income and lack of availability of well-trained healthcare professionals. However, the rising oncology and technology both at the hospital level and in the community are expected to influence the market in a positive way.

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Key factors responsible for the market growth are the rising awareness for therapeutic application of stem cells in disease management, rising research for stem cell therapy applications, development of advanced genetic analysis techniques, increasing public-private investments for stem cell research, growing research in identification of new stem cell lines, and new developments in stem cell banking infrastructure are driving the growth of the global stem cell therapy market. Stem cells are used in the treatment of Alzheimers by replacing the diseased cells with stem cells

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Stem Cell Therapy Market Application Growth, Technology, Trends and Key Players Developments on Regional Industry Size Till 2023 - eRealty Express

Recommendation and review posted by Bethany Smith

This briefing has ended. Read live coronavirus updates here.

At least 97,000 children in the United States tested positive for the coronavirus the last two weeks of July alone, according to a new report from the American Academy of Pediatrics and the Childrens Hospital Association. The report says that at least 338,000 children have tested positive since the pandemic began, meaning more than a quarter have tested positive in just those two weeks.

The report comes as parents and education leaders grapple with the challenges of resuming schooling as the virus continues to surge in parts of the country.

More than seven out of 10 infections were from states in the South and West, according to the report, which relied on data from 49 states along with Washington, D.C., Puerto Rico and Guam. The count could be higher because the report did not include complete data from Texas and information from parts of New York State outside of New York City.

Missouri, Oklahoma, Alaska, Nevada, Idaho and Montana were among the states with the highest percent increase of child infections during that period, according to the report.

New York City, New Jersey and other states in the Northeast, where the virus peaked in March and April, had the lowest percent increase of child infections, according to the report.

In total, 338,982 children have been infected, according to the report.

Not every locality where data was collected categorized children in the same age range. Most places cited in the report considered children to be people no older than 17 or 19. In Alabama, though, the age limit was 24; in Florida and Utah the age limit was 14.

The report noted that children rarely get severely sick from Covid-19, but another report, from the Centers for Disease Control and Prevention, highlighted how the threat from a new Covid-19-related condition, called Multisystem Inflammatory Syndrome in Children or MIS-C, has disproportionately affected people of color.

The C.D.C. said that from early March through late July, it received reports of 570 young people ranging from infants to age 20 who met the definition of MIS-C. Most of those patients were previously healthy, the report said.

About 40 percent were Hispanic or Latino; 33 percent were Black and 13 percent were white, the report said. Ten died and nearly two-thirds were admitted to intensive care units, it said. Symptoms include a fever, rash, pinkeye, stomach distress, confusion, bluish lips, muscle weakness, racing heart rate and cardiac shock.

A reopened high school in Georgia that drew national attention over images of its crowded hallways has had at least nine coronavirus cases reported in the last week, and is switching to online-only instruction for at least the next two days while the school is disinfected and officials assess the situation.

At this time, we know there were six students and three staff members who were in school for at least some time last week who have since reported to us that they have tested positive, Gabe Carmona, the principal of North Paulding High School in Dallas, Ga., said in a letter to parents and guardians of the schools students on Saturday.

The superintendent of the Paulding County School District, Brian Otott, sent them another letter Sunday advising them about the switch to online instruction for Monday and Tuesday, at the least.

Both letters encouraged parents to check their childrens temperature twice daily and to monitor them for symptoms. Neither letter made any mention of social distancing or wearing masks, which the school has said are encouraged but not mandatory.

Photos circulated widely online last week showed North Paulding students crowded in a school hallway with few in masks. Hannah Watters, a 15-year-old student who posted one of the images, was initially suspended for doing so but the suspension was rescinded.

After the photo spread over social media, Mr. Otott said masks were not required at the school, which has about 2,000 students, because there is no practical way to enforce a mandate to wear them.

But Dr. Gary Voccio, the health director for Paulding County and nine other counties in Northwest Georgia, said that masks were crucial to containing the spread of the virus.

Of course you have to change classrooms, and its going to be very difficult to physically distance when that occurs, Dr. Voccio said in a video posted on Facebook. But the masks, again, are the important part of this problem. And we will have significant cases within the schools, Im sure.

At least 66 new coronavirus deaths and 4,032 new cases were reported in Georgia on Saturday, according to a New York Times database.

Governor DeWine got the positive result when he was screened before President Trump arrived in Ohio for campaign appearances.

That test was an antigen test manufactured by the diagnostic health care company Quidel, one of two such tests given emergency use authorization by the Food and Drug Administration. These tests, while fast and convenient, are known to be less accurate than PCR tests, which were used to retest Governor DeWine twice on Thursday and once more on Saturday. All three PCR tests came back negative, confirming that the governor is not infected.

His experience could raise concerns about how much states will rely on antigen tests to augment other forms of testing that are in short supply. Ohio is one of seven states that said this week that they were banding together to purchase a total of 3.5 million rapid coronavirus tests, including antigen tests, along with other vital supplies. Governor DeWine said on CNN Sunday that he had already been in touch with Gov. Larry Hogan of Maryland to talk about the tests and the seven-state agreement.

If anyone needed a wake-up call with antigens, how careful you have to be, we certainly saw that with my test, Governor DeWine said. And were going to be very careful in how we use it.

He added that he would direct any funding from a new federal relief package to expanded testing and helping schools adapt.

We have doubled our testing in the last four weeks, he said. We need to double it again and then double it again. And so that is not going to be cheap to do.

PCR tests are in short supply nationwide, and turnaround times for results have stretched past two weeks in some parts of the country, rendering the information useless.

Compared with PCR tests, Quidels antigen test is more likely to return a false negative result, missing up to 20 percent of cases that PCR detects, though the figure may drop below 5 percent for patients with high virus levels. But Governor DeWines antigen test produced the opposite error: a false positive.

He noted on Sunday that antigen tests function especially well as screening tests, delivering a quick preliminary indication that can be confirmed by the more accurate but slower PCR tests.

Virus cases have surged in the United States in recent weeks, particularly in the Sun Belt states and in communities where officials moved quickly to reopen. According to a New York Times database, the United States leads the world in confirmed cases with more than five million a milestone reached on Saturday followed by Brazil and India. Experts have warned that the actual number of people infected is far greater than the confirmed case count. Brazil also reached a milestone of 100,000 deaths on Saturday.

Trumps moves on economic aid draw fire on the Sunday news shows.

Administration officials struggled in television appearances on Sunday to explain President Trumps attempts to circumvent Congress in the absence of an agreement on a coronavirus aid package, sowing further confusion over whether tens of millions of Americans will receive the promised relief.

The president announced executive steps on Saturday that he said were intended to address lapsed unemployment benefits, reinstate an eviction ban, provide relief for student borrowers and suspend collection of payroll taxes. They came after crucial benefits provided under earlier aid bills had lapsed, and after two weeks of talks between congressional Democrats and administration officials failed to yield an agreement on a broader relief package.

But Mr. Trumps steps appeared unlikely to have a meaningful impact on the sputtering economy, raising questions about whether Mr. Trump had taken them mainly to gain more leverage in his face-off with Congress.

Democrats criticized the actions on Sunday as executive overreach, and warned that the nations social safety net could be jeopardized.

The presidents meager, weak and unconstitutional actions further demand that we have an agreement, Speaker Nancy Pelosi of California said on Fox News Sunday.

She, along with Senator Chuck Schumer of New York, the minority leader, urged administration officials to resume talks and seek a compromise on a broad relief package.

The presidents executive orders, described in one word, could be paltry; in three words, unworkable, weak and far too narrow, Mr. Schumer said on the ABC program This Week.

Mr. Trumps top economic advisers were on the defensive Sunday about whether the president had the authority to bypass Congress, which retains the constitutional power of the purse, and redirect billions of dollars in spending. But there was some acknowledgment that the measures were not as potent as congressional action would be.

The downside of executive orders is, you cant address some of the small business incidents that are there, said Mark Meadows, the White House chief of staff, in a prerecorded interview that was broadcast Sunday on Gray Television. You cant necessarily get direct payments, because it has to do with appropriations. Thats something that the president doesnt have the ability to do. So, you miss on those two key areas. You miss on money for schools. You miss on any funding for state and local revenue needs that may be out there.

Kansas City, a potential hot spot, needs federal aid to cope, the mayor says.

Like many communities, Kansas City, Mo., has been having a tough time lately, and it will get tougher if Congress and the White House cant reach a deal on more aid, the citys mayor, Quinton Lucas, said on Sunday.

Dr. Deborah Birx, the White House coronavirus coordinator, recently named Kansas City as one of 10 potential coronavirus hot spots around the country because of troubling signs in its testing data. Daily case counts have been declining, but the city is experiencing huge backlogs in testing that are delaying results by as much as two weeks, making them nearly useless in heading off the spread of the disease.

What will it take to address the problem? Money, Mr. Lucas said Sunday on the CBS program Face the Nation. We need more resources to get more testing, to get faster testing through.

Kansas Citys Covid-19 response has already cost the city millions, and without federal aid, a growing budget deficit may soon force officials to start furloughing workers and eliminating jobs.

This isnt just theoretical for us, he said. These are issues that are significant and in the now, and so we are looking for a deal.

Kansas City has delayed the start of its school year until after Labor Day to buy more time to make its schools safe to reopen. But the schools need more money to buy protective equipment and implement social distancing measures, Mr. Lucas said.

He said it was difficult to make the right decisions locally without clear guidance from the federal government: Im a lawyer by training. I talk to doctors and health care professionals here, but these are calls necessarily that sometimes mayors may not be equipped to make, or some governors.

With the number of severely ill patients rising and with remdesivir, the only drug shown to speed recovery, in short supply, an urgent need to quickly increase remdesivir production has arisen. Some U.S. hospitals have been forced to ration the drug, using various systems to decide who should get it.

Now, in a rare agreement between drug companies, Pfizer has entered into an agreement with Gilead Sciences, the maker of remdesivir, to manufacture the drug at a facility in Kansas. It is meant to be part of an effort to quickly increase the drugs supply.

Pfizer will be one of 40 companies in North America, Europe and Asia that will be making the drug. Gilead says it plans to produce more than two million courses of treatment by the end of 2020. It says it also will produce another several million doses of remdesivir in 2021 if they are needed.

Remdesivir is an anti-viral drug that failed as a treatment for hepatitis C but was tested in Covid-19 patients because it seemed effective against the virus in laboratory studies and because its safety had already been determined. It is supplied intravenously.

The evidence of its effectiveness against the new coronavirus comes from a federal study of 1,000 hospitalized patients who received remdesivir or a placebo. Preliminary results were announced on April 27, and on May 1, the Food and Drug Administration gave the drug emergency use authorization, allowing Gilead to sell remdesivir even though it has not yet been approved. The price for a five-day course is $3,120.

Gilead explains the supply problems by saying it is difficult and time consuming to make remdesivir. The company says manufacturing is a long, linear chemical synthesis process that must be completed sequentially and includes several specialized chemistry steps and novel substances with limited global availability.

Your immune system may already recognize the coronavirus.

Eight months ago, the new coronavirus was unknown. But to some human immune cells, it was already something of a familiar foe.

A flurry of recent studies has revealed that a large proportion of the population in some places, 20 to 50 percent of people may harbor immunity assassins called T cells that recognize the new coronavirus despite having never encountered it before.

These T cells, which lurked in the bloodstreams of people long before the pandemic began, are most likely stragglers from past scuffles with other related coronaviruses, including four that frequently cause common colds. Its a case of family resemblance: In the eyes of the immune system, germs with common roots can look alike, such that when a cousin comes to call, the body may already have an inkling of its intentions.

The presence of these T cells has intrigued experts, who say it is too soon to tell whether the cells will play a helpful, harmful or entirely negligible role against the current coronavirus.

Updated August 12, 2020

But should these cross-reactive T cells exert even a modest influence on the bodys immune response, they might make the disease milder and perhaps partly explain why some people who catch the germ become very sick while others are dealt only a glancing blow.

This contact tracer is fighting two contagions: the virus and fear.

Radhika Kumar goes to work every morning hoping to save lives. As a contact tracer for Los Angeles County, her job, at least on paper, entails phoning people who have tested positive for the coronavirus, along with others they may have exposed, and providing them with guidance on how to isolate so as not to infect others.

If that sounds easy, it is not.

To persuade people to cooperate, she has to get them to trust her. She has to convince them that they might be infected, even if they have no symptoms. She has to let people curse at her and hang up, then she has to call them back the next day.

And if she wants them to heed her advice, she has to listen, really listen, to how scared they are that if they stay home from their jobs, they might not be able to feed their families.

Sometimes it can really get to you, she said. The other day I had one young lady, and she was screaming on the phone, You dont understand I have three kids. I have to go to work.

I kept calling back and calling back, Ms. Kumar said. Im very relentless like that. I thought about it all night what am I going to do? I called her again first thing in the morning, and I was so relieved when she picked up.

Even as officials at the Centers for Disease Control and Prevention continue to tout the effectiveness of contact tracing, and state and local health agencies across the United States deploy new armies of tracers, tracking down everyone with the coronavirus is proving to be a Sisyphean task.

France is imposing a new requirement that people wear face masks outdoors in crowded areas of Paris and other major cities beginning on Monday as the number of coronavirus infections rises at the fastest rate since a national quarantine ended in mid-May.

The country had gotten the number of infections under control, but the pandemic is creeping back, with 2,288 new Covid-19 cases reported on Friday the third consecutive day of sharp increase. In the Paris Ile-de-France region, the rate of infections reached 2.4 percent on Friday, compared with a 1.6 percent national average.

The rise of new clusters has led the government to warn of the possibility of a second wave of infections in the autumn. In an effort to stem the spread of the virus, masks will now be mandatory for people age 11 and above in high-traffic areas, from the tourist havens of Saint Tropez and Biarritz to the Seine river in Paris, Montmartre and other popular sites, as well as at outdoor food markets and in Pariss crowded suburbs.

The police will be enforcing the measures which will be in place for at least a month in Paris and are subject to review in other areas with a fine of 135 euros ($159).

The authorities are especially concerned about the popularity of free parties, in which hundreds of young people gather in the Parisien woods and other areas, often without wearing masks.

Wearing a mask in crowded enclosed spaces, including museums, shopping malls and on public transportation, has been compulsory in France since mid-July.

Here is what else is happening around the world:

At least nine people were killed after a fire broke out on Sunday at a hotel in southern India that was being used as a makeshift facility for Covid-19 patients, officials said. The police attributed the accident to a short circuit in an air-conditioner on the ground floor of the Swarna Palace.

New Zealand on Sunday marked 100 days without any new reported cases of local transmission of the coronavirus, a milestone as the pandemic continues to devastate countries across the world. New Zealand, a nation of five million people, reported in March that it had stamped out the virus after strict lockdown measures were implemented. Dr. Ashley Bloomfield, the countrys top health official, said it was a significant milestone but added we cant afford to be complacent.

BUSINESS ROUNDUP

In 2009, when H1N1, better known as swine flu, was stoking fears of a devastating pandemic, a small biotech company named Inovio Pharmaceuticals rushed to create a vaccine. After announcing promising early results, the companys stock soared more than 1,000 percent.

In the years since, Inovio has announced encouraging news about its work on vaccines for malaria, the Zika virus and even a cancer vaccine. The declarations have caused the companys stock price to leap, enriching investors and senior executives.

There is a catch, though: Inovio has never brought a vaccine to market.

Now, Inovio is working on a vaccine for the coronavirus, and a flurry of positive news releases about its funding and preliminary results have helped the company attract money from the U.S. government and investors.

But some scientists and financial analysts question the viability of Inovios technology. While there are some early signs of promise with its vaccine, Inovio has released only bare-bones data from the first phase of clinical trials. It is locked in a legal battle with a key manufacturing partner that claims Inovio stole its technology.

And while the company has said that it is part of Operation Warp Speed the flagship federal effort to quickly produce treatments and vaccines for the coronavirus Inovio is not on the list of companies selected to receive financial support to mass-produce vaccines.

The absence of that funding, coupled with their ongoing litigation, coupled with the need to scale a device, coupled with the absence of complete Phase 1 data, makes people skeptical, said Stephen Willey, an analyst at Stifel, an investment firm.

Inovio could provide an update on its progress with the vaccine when it releases its second-quarter financial results on Monday.

In other business news:

Saudi Aramco, the worlds largest oil company, said on Sunday that its quarterly earnings had plunged more than 73 percent compared with a year ago, as lockdowns imposed to curb the pandemic drastically cut the demand for oil. Despite the steep fall in earnings, to $6.6 billion from $24.7 billion, the company said it would continue paying a quarterly dividend of $18.75 billion nearly all of which will go to the Saudi government.

Meet the people at the big biker rally, undaunted by the virus.

Despite the coronavirus pandemic, tens of thousands of motorcycle enthusiasts converged over the weekend outside the small South Dakota community of Sturgis for the 80th annual Sturgis Motorcycle Rally. Officials said about 250,000 enthusiasts were expected this year about half the number who attended last year, but a figure that would still make the rally one of the countrys largest public gatherings since the first coronavirus cases emerged in the spring.

Many in attendance said they were not concerned about the virus as they walked around without masks.

A New Hampshire poet laureate brightens up her citys Covid-19 advisories.

On Sundays, thousands of residents of Portsmouth, N.H., find a poem nestled inside the citys Covid-19 newsletter.

The poems, written by Tammi J. Truax, the citys poet laureate, help offset the gloom of the pandemic while giving residents a chance to pause briefly and reflect on something other than the coronavirus.

Since the beginning of the pandemic, there have been more than 6,800 cases and at least 419 deaths in New Hampshire, according to a New York Times database, with a recent average of 28 cases per day.

The idea for featuring the poems came from Stephanie Seacord, the public information officer in Portsmouth, a city of about 21,000 residents about 60 miles north of Boston. Ms. Seacord was compiling information about the virus and health updates in a weekly city newsletter sent to about 5,000 email subscribers and circulated on social media.

When the pandemic hit, it became quickly clear that people needed information more than once a week, Ms. Seacord recalled in an interview last week, adding that things were changing almost on a daily basis.

In mid-March, the newsletter turned into a daily advisory of coronavirus cases and tips, like where to find personal protective equipment. Around that time, Ms. Seacord had the idea that including a poem in the Sunday newsletter would be a good calm moment in the middle of the intensity, she said.

If you are feeling ready to go somewhere slightly out of the way, you may be worried about the buses, trains or planes you need to get there. Heres some information to help ease your anxiety and remain safe on mass transit.

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At Least 97,000 Children in the U.S. Tested Positive in Last 2 Weeks of July - The New York Times

Recommendation and review posted by Bethany Smith

EUSTACEThe Eustace ISD Board of Trustees met Aug. 3 to discuss and consider district schools reopening. A plan was developed for the 2020-2021 school year that the Board released to parents Aug. 6. Additionally, EISD states that it will develop a plan for on-campus activities and instruction and provide it to parents and the public no later than one week prior to the start of on-campus activities and instruction.School Board President Ashley McKee said that this was a fluid plan that the board can come back and address in a later date if the situation changes. At this time, we are planning for the start of the 2020-2021 school year to take place on Wednesday, Aug. 19 for both in person learning and remote learning, the districts plan states.For the first 13 days of instruction, from Aug. 19 through Sept. 4 Eustace ISD will be operating on an early release schedule releasing at 1:30 p.m. This is to help students get back into a school schedule as they have been out since the middle of March. Eustace ISD is planning on resuming full day instruction Tuesday, Sept. 8.RemoteLearning PlanEustace ISD will be offering Remote Asynchronous Instruction as defined by the Texas Education Agency (TEA). (Instruction that does not require having the instructor and student engaged at the same time.) This method allows Eustace ISD the flexibility to earn daily attendance through an approved plan. Depending on grade level, students may have one teacher that provides all their remote learning, however in higher levels such as middle school and high school students will be receiving instruction from multiple teachers. The grading scale for remote learning will be the same as in-person learning.The middle school and high school have designated certain classes for in-person learning only. These are classes that will require multiple activities that can only be accomplished by in-person learning. A complete list of these classes is provided on page 12 of their learning plan.Attendanceand EnrollmentPer the Texas Education Code, students must attend 90% of the days a course is offered in order to be awarded credit for the course and/or be promoted to the next grade. Student attendance may be earned through the delivery of virtual instruction.StaffConsiderationsAll staff members are required to complete the training provided by Texas Agri-Life Extension for Special Considerations for Infection Control during COVID-19. Staff is also required to wear face masks and face shields throughout the instructional day, self-screen for COVID-19 symptoms before coming to campus each day and must report if they have come into close contact with an individual who is lab-confirmed with COVID-19.Visitorson CampusEISD is not allowing visitors on campus. However maintenance personnel or outside contractors that may be required entry to perform a repair function, EISD will require they be screened and have their temperature measured. Those individuals will be required to wear a mask, face shield and asked about any close contact that may have occurred.Students/Parents ConsiderationsAll students in grades third through 12th will be required to wear a mask unless they meet one of the exceptions in Governor Abbots order. This will include some students that are younger than 10 when school starts. Unlike many districts, EISD is allowing students that are doing remote learning to participate in extracurricular activities if they are present for all practices and required activities.TransportationParents are encouraged to bring their students to school and pick them up in the afternoon however Eustace ISD is planning on running all bus routes and students will be required to have a mask and/or face shield to ride the bus. You can find more details on the transportation and the drop off and pick up for car riders on page seven of the districts plan.For more information on Eustace ISDs district plan or to read it in its entirety, visit the districts Facebook page at http://www.facebook.com/EustaceISD.

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Eustace ISD releases plans to return to school - Monitor Online

Recommendation and review posted by Bethany Smith

HMCS Fredericton, a Halifax-class Canadian frigate, returns to its home port of Halifax on Tuesday, July 28, 2020 after completing a six-month deployment in the Mediterranean Sea. HMCS Oriole, left, and Bluenose II, centre, escorted the warship up the harbour. (Andrew Vaughan/THE CANADIAN PRESS)

The federal government announced Tuesday a $1.5-billion program for maintenance contracts with shipyards in three provinces to keep Canadas fleet of 12 frigates operational until a new generation of warships replaces them in the 2040s.

The Davie shipyard in Quebec and Seaspan Victoria Shipyards in British Columbia were each awarded a $500-million contract for maintenance work on the countrys fleet of Halifax-class frigates.

These frigates were brought into service beginning in 1992 and now form the backbone of the Royal Canadian Navy, Public Services and Procurement Minister Carla Qualtrough said in Victoria, B.C., Tuesday.

The workers here at this shipyard will be using your skills and talents to support the Royal Canadian Navy, making sure our women and men in uniform have the ships they need to carry out important missions at home and abroad.

A similar deal with Irving Shipyards in Nova Scotia is being finalized now, the government said.

The contracts announced Tuesday cover a five-year period, with the value expected to rise as the government adds more work, officials said.

Jeff Collins, a Fellow with the Canadian Global Affairs Institute and a researcher on Canadian defence procurement, said these refits are designed to ensure that the Royal Candian Navy (RCN) maintains a combat capable surface fleet to the 2040s, when the first of the new Canadian Surface Combatants to be built by Irving in Halifax begin entering into service.

The Halifax-class are now arguably past the mid-life point of their operational lives, especially when looking at those initial ships that rolled out in the early 1990s, Collins said.

As we know from the Iroquois class destroyers and original Protecteur class replenishment ships, the older the ships the higher the maintenance costs will be.

A Navy ship undergoes a mid-life refit at the Irving Shipbuilding facility in Halifax on July 3, 2014. Halifax-based Irving Shipbuilding Inc., has been awarded a $500 million contract by the federal government to carry out maintenance work for the Royal Canadian Navy. (Andrew Vaughan/THE CANADIAN PRESS)

Docking maintenance work periods are critical to ensure the RCN has at least eight of its 12 patrol frigates ready for deployment at all times, officials said Tuesday.

This contract is different from the $4.3 billion modernization and frigate life extension program that took place in Irving and Seaspan between 2010-2018, Collins said.

The Halifax-class Modernization/Frigate Life Extension (HCM/FELEX) program saw the replacement and updating of combat and operational equipment, Collins said.

The Canadian frigates, which were commissioned between 1992 and 1996, also got a new sea-to-land strike missile capability, something the warships did not have initially, he said.

The new strike capability was added based on operational experiences of the RCN and other allied navies, particularly after the 2011 Libya campaign, Collins said.

HMCS Ville de Quebec sails up the Halifax harbour in this Sept. 6, 2005 file photo. (Andrew Vaughan/THE CANADIAN PRESS)

Timothy Choi, a maritime strategy expert at the University of Calgarys Centre for Military, Security and Strategic Studies, said that while the life extension program focused on the weapons and certain electronic systems, they left the more mundane hull, mechanical, and engineering improvements mostly untouched.

Thats what these latest batch of refits will focus on, though some combat systems improvements will also be carried out such as the Naval Remote Weapon System, Choi said.

The deal is another major win for Davie shipyard, which bills itself as Canadas largest, longest-established and highest capacity shipbuilder.

Davie was left out of Canadas massive naval procurement program in 2011 because it was suffering from financial troubles at the time.

But it has since advocated to be allowed to participate in the wider program.

Canadian frigate HMCS St. Johns docs at Davie Shipyard in Lvis, Quebec. (Photo courtesy of Davie Shipyard)

Cabinet minister and Quebec City Liberal MP Jean-Yves Duclos, who delivered the government announcement at the Davie facilities across the St. Lawrence River in Levis, Que., said parts of the National Shipbuilding Strategy have been delayed because the Davie shipyard was excluded from the Conservative strategy for naval construction.

Collins said one of the unanswered questions for him is what happens if work on the new Canadian Surface Combatants is delayed and the Halifax-class frigates require another round of comprehensive modifications to their combat and operating systems similar to work carried out in 2010-2018.

Such work is very complex, involves multiple prime contractors and a careful dance of rotating ships in and out to ensure RCN operational capability, Collins said.

Irving and Seaspan have the institutional knowledge and relationships in place to undertake this but both, especially Irving, will be busy with completing their existing orders for the navy and the Canadian Coast Guard, Collins said.

There will likely be a premium to be paid to move that work to Davie and in a time of massive government spending and, I am sure, later, deficit reductions, is that a premium a government of any stripe will pay? Collins said.

With files from The Canadian Press

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Canada to spend $1.5B to maintain its fleet of frigates well into 2040s - Radio Canada International - English Section

Recommendation and review posted by Bethany Smith

2020 will be remembered as the year the COVID-19 pandemic brought the world to a standstill, as national lockdowns were instituted across the globe. As sectors of the global economy have endured lockdown, curfews and structural changes to combat the virus, global businesses have been forced to adapt and overcome unforeseen challenges and circumstances.

Despite such fundamental changes, some of the brightest minds in the investment world have carried on with their innovations, whether it be in fintech, space exploration, biomedical research or other sectors.

After extensive research and evaluation, here is our list outlining the top 5 investors making the biggest impact in 2020:

Andreessen Horowitz (a16z) was founded in 2009 by Marc Andreessen and Ben Horowitz. Based in Silicon Valley, the company has been massively successful under the leadership of Marc and Ben. Ben has overseen investment across several industry sectors, including crypto, fintech, healthcare and consumer goods. With respect to crypto, a16z has made a large bet on Ripple, which with the sole exceptions of Bitcoin and Ethereum, is the most valuable crypto by market capitalization. Bens firm currently manages over $12 billion in assets and continues to grow rapidly. As if that wasnt enough, Ben is now a New York Times best-selling author. 2020 has not slowed Ben or a16z down, and Ben continues to be one of the leading investors in the world.

Peter Thiel is number 2 on the list, and he is known as a prolific entrepreneur and venture capitalist with an estimated worth of $2.3 billion USD. He is a co-founder of PayPal, and also took the company public after leading it as CEO. He also serves as chairman of Palantir Technologies which, alongside PayPal and Facebook, is rumoured to be the main source of his current wealth. His is a partner of Silicon Valley venture capital firm Founders Fund and has a passion for investing in startups that he sees potential in. He is also a New York Times bestselling author for his books How to Build the Future and Zero to One: Notes on Startups.

Coming in at number 3 on our list is Dylan Taylor, who is an active pioneer in the super-hot industry of space exploration. Taylor is regarded as a super angel investor in the NewSpace industry but more recently, he has turned his attention to controlling interest investments. Taylor is the CEO and Chairman of Voyager Space Holdings, which is an international corporation focused on acquiring and integrating space exploration enterprises on a global level. Earlier in 2020, Dylan was awarded the space industrys top honour by the Commercial Spaceflight Federation for his contributions to business and finance.

Number 4 on our list, Laura Deming is a New Zealand born venture capitalist who has focused her investments on biological research with the aim of reversing, or at least reducing, the effects of aging. At a very young age, she showed interest in the possibilities of genetic engineering to extend lifespans, and she was accepted into MIT at the age of 14 to study physics. She dropped out of MIT after receiving a $100,000 investment from Peter Thiel (number 2 on our list) to start her own venture capital firm, The Longevity Fund. As the name implies, The Longevity Fund is focused on investments in aging and life extension, and as its founder, Laura is considered a leader in the anti-aging field and has been a keynote speaker on the topic.

Lee Fixel is an American venture capitalist who has had a range of outstanding successes. He joined Tiger Global in March 2006 and established himself as one of the pre-eminent investors in software and internet-based companies. Fixel has backed companies like Flipkart and Peloton, both of which have been incredibly successful and have achieved unicorn status. After leaving Tiger Global in 2019, Fixel has set his sights on a new target, having spent much of his recent time away from the public eye. Whether this is because of COVID-19 or personal reasons remains to be seen; however, Fixel has announced the formation of a multi-stage venture capital firm called Addition. The VC firm has already raised more than $1.3 billion and is backing well-known companies like Fauna.

Cameron Dickerson is a seasoned journalist with nearly 10 years experience. While studying journalism at the University of Missouri, Cameron found a passion for finding engaging stories. As a contributor to Kevs Best, Cameron mostly covers state and national developments.

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Top 5 Investors That You Should Certainly Know About in 2020 - Kev's Best

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WASHINGTON: Xtar is a satellite communications service provider to the U.S administration, and it has sold one of its satellites to Hisdesat-one of its shareholders.

Xtar is situated in Virginia, and it recently signed a contract agreement, which will allow it to maintain the exact volume of satellites.

Both Hisdesat and Xtar stated that agreement and the leaseback approvals illustrate the kind of administrative system the entity will have in the future.

In a statement, Icard affirmed that Xtar would proceed to provide service by use of the 15-year-old Xtar-Eud and one haul it rents out on an old SpainSat NG satellite, which was developed fifteen years ago.

In a statement, Icard stated that Xtar has improved in terms of structures, like any other satellite communications firm. Here, a single operator possesses the satellites and keeps a skilled group committed to the authority and insurance sales.

Icard asserted that there is no shift in orbital space custody as Xtar-Eur uses a slot provided by the Spanish authorities. The satellite will deliver the X-band range of Europe, the Atlantic Ocean, Southeast Asia, Africa, and Singapore. Possession of Hidestars Xtar-Eur streamline decision-making revolves around the life extension of the aging geostationary caravan.

The reason why Hisdesat made a decision was to gain the power to make decisions concerning the way forward of both Xtar-Eur and Spainsat satellites. That will enable their clients to get excellent services from the spacecraft, which will be possible for life expansion operations.

Xtar and Hisdesat have already chatted with Northrop Grumman concerning life expansion. Hisdesat opted for Xstar in life expansion as it is an old satellite.

Another main factor was the unwillingness of Loral Space and Communications in making other ventures concerning the future of Xtar. Loral Space and Communications started to function in 2016, and it seems to lack interest in providing financial support for Xtar. As a result, Hisdesat automatically becomes more useful for all forthcoming satellites Xtar is a combined investment of Loral (56%) and Hisdesat (44%).

Despite the outbreak of Coronavirus pandemic, Hisdesats SpainSat NG satellites remain on the list, having the first satellite set for November 2023 release.

The little time between release and the end of 2024 could make launch to occur the following year (2024). On the other hand, Hisdesat has not disclosed the launch providers for Spainsat NG satellites.

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Xtar switches to leasing agreement following its sale of a satellite to Hisdesat. - The Market Correspondent

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The shelf life of frozen food could be extended to up to 18 months under new industry guidance.

The guidance is from the British Frozen Food Federation in collaboration with Defra, Primary Authority and Wrap, and backed by the Federation of Wholesale Distributors, UKHospitality and the Provision Trade Federation.

It aims to help businesses manage unprecedented levels of frozen stock approaching the end of its shelf life by extended best before dates. Its targeted at businesses supplying hospitality and foodservice, who are holding excessive stocks of frozen food because of the sectors shutdown in the pandemic.

EU regulations require that frozen foods are marked with a best before date, but the sale of a product beyond that date is not illegal.

The guidance sets out suggested safe shelf lives for foods that are blast frozen at very low temperatures, which may be well beyond the standard storage life. They include 18 months for beef cuts, chicken, and all prepared meat meals.

Others, including several types of fish such as salmon steaks, herring, sardines and mackerel, are given a 12-month recommendation.

A key aim of the guidance was to encourage importers, suppliers, wholesalers and customers to work together to manage the problem, the BFFF said.

Under normal circumstances, the various parties would agree any shelf life extension and relabelling or repackaging would take place at an importers cold store, the guidance said. However, due to the sheer number of pallets currently being held in the system awaiting distribution, the usual process could be unmanageable.

The guidance suggests sharing responsibility for relabelling.

The sectors recovery depends on all parties working together to manage this challenge and the costs associated with this issue in the coming months, said BFFF CEO Richard Harrow.

The guidance also includes advice on how to relabel products, including what information should be shown on new stickers.

Effective communication and greater collaboration across the supply chain will be vital in the months ahead to ensure the safe and appropriate use of frozen food currently held in storage and to reduce unnecessary waste, added Harrow.

This new guidance is designed to help businesses facing unprecedented challenges as a result of the pandemic mitigate severe losses without compromising consumer safety, while also maintaining the already excellent levels of traceability and transparency across the supply chain.

Defra food minister Victoria Prentis said: Throughout the coronavirus pandemic, the BFFF and all its members have acted as a united front working innovatively to keep the supply chain moving and keep our country fed and I thank them for their hard work and commitment.

Now, as restrictions continue to ease, we all need to work together to do all we can to ensure good, nutritious food does not go to waste. All food that is safe and suitable to eat should be made available for sale or redistributed. We in government are firmly committed to supporting this effort alongside industry.

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Shelf life of frozen meat could be extended by over a year, says new BFFF guidance - The Grocer

Recommendation and review posted by Bethany Smith

The Withania Somnifera Extract market analysis is provided for the international markets including development trends, competitive landscape analysis, and key regions development status. The report provides key statistics on the market status of the Withania Somnifera Extract manufacturers and is a valuable source of guidance and direction for companies and individuals interested in the industry.

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Our industry professionals are working reluctantly to understand, assemble and timely deliver assessment on impact of COVID-19 disaster on many corporations and their clients to help them in taking excellent business decisions. We acknowledge everyone who is doing their part in this financial and healthcare crisis.

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The report focuses on global major leading industry players of Withania Somnifera Extract market providing information such as company profiles, product picture and specification, capacity, production, price, cost, revenue and contact information. Upstream raw materials and equipment and downstream demand analysis is also carried out. The Withania Somnifera Extract market development trends and marketing channels are analyzed. Finally the feasibility of new investment projects are assessed and overall research conclusions offered.

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Withania Somnifera Extract Market: Overview, Opportunities, Analysis of Features, Benefits, Manufacturing Cost and Forecast To 2025 - Owned

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According to latest research report on Global Stem Cell Banking Market report provides information related to market size, production, CAGR, gross margin, growth rate, emerging trends, price, and other important factors. Focusing on the key momentum and restraining factors in this market, the report also provides a complete study of future trends and developments in the market.

The Stem Cell Banking report contains all the details of the expected market dynamics and new market opportunities due to the COVID-19 outbreak. Stratagem Market Insights tried to cover all the market analysis of annual economic growth in the latest report on the Stem Cell Banking market.

According to analysts, the growth of the Stem Cell Banking market will have a positive impact on the global platform and will witness gradual growth over the next few years. This report study incorporates all the market growth and restraining factors along with the important trends mentioned between 2020 and 2025.

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Market segmentation:

The Stem Cell Banking market has been segmented into a variety of essential industries including applications, types, and regions. In the report, each market segment is studied extensively, taking into account market acceptance, value, demand, and growth prospects. Segmentation analysis allows customers to customize their marketing approach to make better orders for each segment and identify the most potential customers.

Global Stem Cell Banking Market Segmentation by Application:

Global Stem Cell Banking Market Segmentation by Product:

Competitive Landscape

This section of the report identifies various major manufacturers in the market. It helps readers understand the strategies and collaborations players are focusing on fighting competition in the marketplace. The comprehensive report gives a microscopic view of the market. The reader can identify the manufacturers footprint by knowing about the manufacturers global revenue, the manufacturers global price, and the manufacturers production during the forecast period.

The major manufacturers covered in this report:

Regional Insights of Stem Cell Banking Market:

In terms of geography, this research report covers almost all major regions around the world such as North America, Europe, South America, Middle East, Africa, and the Asia Pacific. Europe and North America are expected to increase over the next few years. Stem Cell Banking markets in the Asia-Pacific region are expected to experience significant growth during the forecast period. Advanced technology and innovation are the most important characteristics of North America and the main reason why the United States dominates the world market. The Stem Cell Banking market in South America is also expected to expand in the near future.

Years considered for this report:

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Stem Cell Banking Market Applications, Types and Future Outlook Report 2020-2025 - express-journal.com

Recommendation and review posted by Bethany Smith

METUCHEN, N.J., Aug. 10, 2020 /PRNewswire/ --Tevogen Bio announces a joint partnership with renowned bone-marrow transplant expertNeal Flomenberg, M.D., Professor and Chair of the Department of Medical Oncology at Thomas Jefferson University, with the intent to evaluate Tevogen' s proprietary antigen-specific T cell technology as a potential treatment for COVID-19 and influenza-A patients.

This collaboration aims to harness Tevogen's proprietary immunotherapy platform and Dr. Flomenberg's expertise and research prowess to investigate potential treatments for viral infections.

Dr. Flomenberg has been at the forefront of immunogenetics and immunology for more than four decades. "Tevogen's technology resonated with me as there have been several groups who have used T cells to treat patients after bone-marrow transplants. The idea of utilizing T cell therapies to potentially treat COVID-19 and other viruses is truly remarkable," Flomenberg said. "I'm enthusiastic about moving forward with an investigation of Tevogen's technologies."

Tevogen CEO Ryan Saadi, M.D., M.P.H., is leading the new biotech's efforts. "Our work has been to pioneer T cell therapies that can be abundantly and efficiently reproduced to develop an affordable and scalable cellular treatment for the biggest global health threats, including COVID-19, influenza, and a variety of cancers. We are very excited about Dr. Flomenberg's contribution to our efforts and hope to initiate our investigational study soon."

In addition to developing its potential therapies, Tevogen is committed to organizational and manufacturing efficiency. This should allow it to engage in affordable innovation to the benefit of all patients.

About Tevogen Bio

Tevogen Bio was formed after decades of research by its contributors to concentrate and leverage their expertise, spanning multiple sectors of the health care industry, to help address some of the most common and deadly illnesses known today. The company's mission is to provide curative and preventative treatments that are affordable and scalablein order to positively impact global public health.

About Dr. Neal Flomenberg

Dr. Neal Flomenberg is the Chairman of Medical Oncology at Jefferson University in Philadelphia and also heads the Hematologic Malignancies, Blood and Marrow Transplantation (BMT) Program. Throughout his more than four decades of practice, he has maintained a longstanding interest in the immunogenetics and immunology of stem cell transplantation, with the goal of making transplantation safer and more widely available. Dr. Flomenberg developed an approach to bone-marrow transplants that uses half-matched relatives as donors, a breakthrough that assures that the majority of blood and bone-marrow cancer patients can benefit from this potentially curative treatment.

Media Contacts:

Mark Irion[emailprotected]

Katelyn Petroka [emailprotected]

SOURCE Tevogen Bio

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Tevogen Bio Announces Partnership With Preeminent Scientist Professor Neal Flomenberg, MD, to Investigate Proprietary T-Cell Therapy for Treatment of...

Recommendation and review posted by Bethany Smith

TEL AVIV, Israel, Aug. 12, 2020 /PRNewswire/ -- Cellect Biotechnology Ltd. (NASDAQ: APOP), a developer of innovative technology which enables the functional selection of stem cells, today reported financial and operating results for the second quarter ended June 30, 2020. The Company's six-month progress includes the development of several strategic initiatives, including growth-oriented opportunities in pain management and COVID-19 related therapeutics.

"Despite the COVID-19 pandemic business disruptions and the near-term delays to completing and commencing our clinical programs in Israel and the U.S., respectively, we acted swiftly over the past few months to leverage our sought-after technology to create several long-term business initiatives to enhance our value," commented Dr. Shai Yarkoni, Chief Executive Officer. "In addition to pursuing a potential merger with a global leader in the high growth medical-grade cannabis market, which is being delayed due to COVID-19, we have either initiated or are contemplating other business development activities that will greatly benefit from our innovation, technology and know-how. I believe each of these opportunities represents meaningful catalysts for Cellect in multi-billion-dollar markets, subject to resolution of the COVID-19 pandemic and return to normal course of business."

Notwithstanding the continued delays due to COVID-19, the Company remains focused on the following operational and clinical objectives:

The Company's cash and cash equivalents totaled $7 million as of June 30, 2020, which includes the approximately $1.5 million (gross before expenses)resulting from several investors exercising certain warrants that were issued in February 2019.

SecondQuarter 2020 Financial Results:

*For the convenience of the reader, the amounts above have been translated from NIS into U.S. dollars, at the representative rate of exchange on June 30, 2020 (U.S. $1 = NIS 3.466).

About Cellect Biotechnology Ltd.

Cellect Biotechnology (APOP) has developed a breakthrough technology, for the selection of stem cells from any given tissue, that aims to improve a variety of stem cell-based therapies.

The Company's technology is expected to provide researchers, clinical community and pharma companies with the tools to rapidly isolate stem cells in quantity and quality allowing stem cell-based treatments and procedures in a wide variety of applications in regenerative medicine. The Company's current clinical trial is aimed at bone marrow transplantations in cancer treatment.

Forward Looking Statements

This press release contains forward-looking statements about the Company's expectations, beliefs and intentions. Forward-looking statements can be identified by the use of forward-looking words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. For example, forward-looking statements are used in this press release when we discuss Cellect's expectations regarding timing of the commencement of its planned U.S. clinical trial and its plan to reduce operating costs. These forward-looking statements and their implications are based on the current expectations of the management of the Company only and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. In addition, historical results or conclusions from scientific research and clinical studies do not guarantee that future results would suggest similar conclusions or that historical results referred to herein would be interpreted similarly in light of additional research or otherwise. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: the Company's history of losses and needs for additional capital to fund its operations and its inability to obtain additional capital on acceptable terms, or at all; the Company's ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; the Company's ability to obtain regulatory approvals; the Company's ability to obtain favorable pre-clinical and clinical trial results; the Company's technology may not be validated and its methods may not be accepted by the scientific community; difficulties enrolling patients in the Company's clinical trials; the ability to timely source adequate supply of FasL; risks resulting from unforeseen side effects; the Company's ability to establish and maintain strategic partnerships and other corporate collaborations; the scope of protection the Company is able to establish and maintain for intellectual property rights and its ability to operate its business without infringing the intellectual property rights of others; competitive companies, technologies and the Company's industry; unforeseen scientific difficulties may develop with the Company's technology; the Company's ability to retain or attract key employees whose knowledge is essential to the development of its products; and the Company's ability to pursue any strategic transaction or that any transaction, if pursued, will be completed. Any forward-looking statement in this press release speaks only as of the date of this press release. The Company undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. More detailed information about the risks and uncertainties affecting the Company is contained under the heading "Risk Factors" in Cellect Biotechnology Ltd.'s Annual Report on Form 20-F for the fiscal year ended December 31, 2019 filed with the U.S. Securities and Exchange Commission, or SEC, which is available on the SEC's website, http://www.sec.gov, and in the Company's periodic filings with the SEC.

Cellect Biotechnology Ltd.

Consolidated Statement of Operation

Convenience

translation

Six months

ended

Six months ended

Three months ended

June 30,

June 30,

June 30,

2020

2020

2019

2020

2019

Unaudited

Unaudited

U.S. dollars

NIS

(In thousands, except share and per

share data)

Research and development expenses

837

2,901

7,086

1,364

3,564

General and administrative expenses

1,356

4,703

5,064

2,116

2,709

Operating loss

2,193

7,604

12,150

3,480

6,273

Financial expenses (income) due to warrants exercisable into shares

1,098

3,807

(7,111)

4,697

(5,919)

Other financial expenses (income), net

(15)

(55)

880

627

462

Total comprehensive loss

3,276

11,356

5,919

8,804

816

Loss per share:

Basic and diluted loss per share

0.010

0.034

0.029

0.024

0.004

Weighted average number of shares outstanding used to compute basic and diluted loss per share

338,182,275

338,182,275

200,942,871

365,428,101

224,087,799

Cellect Biotechnology Ltd.

Consolidated Balance Sheet Data

Convenience

translation

June 30,

June 30,

December 31,

2020

2020

2019

Unaudited

Unaudited

Audited

U.S. dollars

NIS

(In thousands, except share and per

share data)

CURRENT ASSETS:

View post:
Cellect Biotechnology Reports Second Quarter Financial and Operating Results; First Half 2020 Strategic Developments Create Long-Term Revenue...

Recommendation and review posted by Bethany Smith

Poverty, Government apathy and Covid-19 induced-lockdown restricting travel proved fatal for little Kishan, a 11-year-old boy suffering from Aplastic anemia, a life-threatening blood disorder condition in which the bone marrow and stem cells do not produce enough blood cells

Facing severe financial constraints and waiting timely medical aid, first at Safdarjung Hospital and then AIIMS, both Government hospitals in Delhi, Kishans life was cut short in March this year amid Covid-19 pandemic.

However, Kishans is not a lone case. Dr Nita Radhakrishnan, paediatric haemato-oncologist at Super Speciality Paediatric Hospital, Noida, Uttar Pradesh says that as the deadly Coronavirus captured the attention of the nation in the most unprecedented manner, the non-Covid patients particularly those with the Aplastic anemia have suffered the most in the crisis.

She gave instances of her two teenage patients who succumbed to blood disorder in the Covid catastrophe. Manish (name change), a 17-year-old was suffering with on-and-off fever, gum bleeding, and melena for three months, he came to us in December last year just when Coronavirus had started spreading its tentacles from China to other parts of the world.

The boy was diagnosed with severe Aplastic anemia and was recommended requisite treatment like regular hospital visit for red cell transfusion before he could be given bone marrow transplant (BMT), a life saving treatment.

However, while the family was not able to visit our hospital in Noida due to the covid-lockdown, no blood products were available at the hospital near to the patients locality. In want of blood, Manish could not survive more days.

13-year-old Suresh (name change) too faced similar fate. While Government funds could not be sanctioned for his BMT in time the boy could not visit the Noida hospital for further follow-up due to travel restrictions. Two weeks later, Suresh died due to hemorrhage at his native place, lamented the doctor.

These are just two reported cases from the NCR hospital located near the countrys capital. Several have gone unreported. The Government has no policy nor any long-term plan for such patients.

The prognosis of severe aplastic anemia in our country is dismal. The incidence of 46 per million population of childhood aplastic anemia in India and other Asian countries is higher than what is observed in the West, explains Dr Radhakrishnan. The scenario is gloomy for the patients afflicted with the disease as they need blood transfusion almost every 20 days.

A significant proportion of patients of aplastic anemia (around 30 per cent) die before any definitive treatment is initiated. A study by AIIMS based on a recent series of patients follow-up showed that out of 1501 patients diagnosed over last seven years, only 303 ie 20 per cent received the definitive treatment modalities through either BMT or IST with ATG and cyclosporine, says Dr Radhakrishnan in her case report Aplastic anemia: Non-COVID casualties in the Covid-19 era, published in the latest edition of Indian Journal of Palliative Care.

The doctors have sought urgent intervention. Dr Radhakrishnan says that as we await the peak of Covid-19 in our country and possibly secondary and tertiary waves thereafter, patients with aplastic anemia who are the sickest among all hematological illnesses would benefit greatly from urgent intervention from the Government to ensure timely treatment.

Those suffering with Aplastic anemia, there is mostly delay in diagnosis, delay in initiation of treatment due to monetary constraints, non-inclusion of the disease under government schemes such as Ayushman Bharat and NHM and delay in sanction of money from other Government schemes such as Rashtriya Arogya Nidhi, Chief Minister and Prime Ministers relief fund often due to lack of proper documents, she added.

Delay means, risk of contracting fungal infections and increase in drug-resistant bacterial infections increase which further hamper the treatment, point out Dr Ravi Shankar and Dr Savitri Singh in the study.

Though the Union Health Ministry, after few days of lockdown period, issued directions for continuing treatment for essential health services including reproductive and maternal health services, newborn care, severe malnutrition, and NCDs including cancer care, palliative care, dialysis, and care of disabled, unfortunately those with Aplastic anemia got ignored.

This despite of the fact that these patients are at the highest risk of death following a break in the treatment of few weeks, notes Dr Radhakrishnan.

Because of the closure of offices and absence of staff, during the lockdown period, there was delay in sanction of usual grants due to the lockdown of offices and inability in generating documents such as income certificate from the tehsils.

For instance, Suresh and Manish, both our patients received the Government grant after around 34 months of applying for the same. But both had died before they could reach the hospital for treatment, lamented the hematologist.

Read the original:
Covid-19 Impact: Patients with aplastic anemia at receiving end - Daily Pioneer

Recommendation and review posted by Bethany Smith

New Jersey, United States,- The Stem Cell Therapy Market research report added by Verified Market Research is an in-depth analysis of the latest trends, market size, status, upcoming technologies, industry drivers, challenges, regulatory policies, with key company profiles and strategies of players. The research study provides market introduction, Stem Cell Therapy market definition, regional market scope, sales and revenue by region, manufacturing cost analysis, Industrial Chain, market effect factors analysis, Stem Cell Therapy market size forecast, 100+ market data, Tables, Pie Chart, Graphs and Figures, and many more for business intelligence.

The Stem Cell Therapy Market report includes an in-depth analysis of the Stem Cell Therapy market for the present as well as the forecast period. The report encompasses the competition landscape entailing share analysis of the key players in the Stem Cell Therapy market based on their revenues and other significant factors. Further, it covers several developments made by the prominent players of the Stem Cell Therapy market. The Stem Cell Therapy Market report is a beneficial source of perceptive data for a business approach. It presents the market overview with growth analysis together with historical & futuristic costs. Further identifies the revenue, specifications, company profile, demand, and supply data.

Global Stem Cell Therapy Market was valued at USD 117.66 million in 2019 and is projected to reach USD 255.37 million by 2027, growing at a CAGR of 10.97% from 2020 to 2027.

Leading Key players of Stem Cell Therapy Market are:

Stem Cell Therapy Market: Competitive Landscape

This section of the report identifies various key manufacturers of the market. It helps the reader understand the strategies and collaborations that players are focusing on combat competition in the market. The comprehensive report provides a significant microscopic look at the market. The reader can identify the footprints of the manufacturers by knowing about the global revenue of manufacturers, the global price of manufacturers, and sales by manufacturers during the forecast period of 2015 to 2019.

Stem Cell Therapy Market: Segment Analysis

The research report includes specific segments by region (country), by company, by Type and by Application. This study provides information about the sales and revenue during the historic and forecasted period of 2019 to 2027. Understanding the segments helps in identifying the importance of different factors that aid the market growth.

1.Stem Cell Therapy Market, By Cell Source:

Adipose Tissue-Derived Mesenchymal Stem Cells Bone Marrow-Derived Mesenchymal Stem Cells Cord Blood/Embryonic Stem Cells Other Cell Sources

2.Stem Cell Therapy Market, By Therapeutic Application:

Musculoskeletal Disorders Wounds and Injuries Cardiovascular Diseases Surgeries Gastrointestinal Diseases Other Applications

3.Stem Cell Therapy Market, By Type:

Allogeneic Stem Cell Therapy Market, By Application Musculoskeletal Disorders Wounds and Injuries Surgeries Acute Graft-Versus-Host Disease (AGVHD) Other Applications Autologous Stem Cell Therapy Market, By Application Cardiovascular Diseases Wounds and Injuries Gastrointestinal Diseases Other Applications

Stem Cell Therapy Market: Regional Analysis

The research report includes a detailed study of regions of North America, Europe, Asia, and South America. The report has been curated after observing and studying various factors that determine regional growth such as economic, environmental, social, technological, and political status of the particular region. Analysts have studied the data of revenue, sales, and manufacturers of each region. This section analyses region-wise revenue and volume for the forecast period of 2015 to 2026. These analyses will help the reader to understand the potential worth of investment in a particular region.

North America(United States, Canada, and Mexico)Europe(Germany, France, UK, Russia, and Italy)Asia-Pacific(China, Japan, Korea, India, and Southeast Asia)South America(Brazil, Argentina, Colombia, etc.)The Middle East and Africa(Saudi Arabia, UAE, Egypt, Nigeria, and South Africa)

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Verified Market Research is a leading Global Research and Consulting firm servicing over 5000+ customers. Verified Market Research provides advanced analytical research solutions while offering information enriched research studies. We offer insight into strategic and growth analyses, Data necessary to achieve corporate goals, and critical revenue decisions.

Our 250 Analysts and SMEs offer a high level of expertise in data collection and governance use industrial techniques to collect and analyze data on more than 15,000 high impact and niche markets. Our analysts are trained to combine modern data collection techniques, superior research methodology, expertise, and years of collective experience to produce informative and accurate research.

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Stem Cell Therapy Market 2020 by Manufacturers, Regions, Type and Application, Forecast to 2027 - Owned

Recommendation and review posted by Bethany Smith

His name means brave in Hindi. And for four year-old Veer Gudhka that couldnt be more appropriate.

For while the bubbly little boy might look fighting fit, he actually has just months to live.

Veer suffers from a rare blood disorder called Fanconi anaemia, which results in a decreased production of all types of blood cells.

But a stem cell donor will save his life.

In a heartfelt video message, the plucky toddler asks Sunday Mirror readers: Please be my life-saver? Will you be my superhero?

And today his family are appealing to those from BAME communities to help by signing up to the Anthony Nolan stem cell register.

Mum Kirpa and dad Nirav know the odds are stacked against them getting that all-important call because they are of Indian descent.

While 69 per cent of Northern European patients find the best possible stem cell match from a stranger, this drops to just 20 per cent for those with black, Asian or ethnic minority backgrounds.

Currently only two per cent of the population is on the UK stem cell register.

And with Asians making up just six per cent of the UK population, there is a smaller pool of potential donors.

Veer was diagnosed with the blood disorder last August, after he started suffering from extreme fatigue, and was referred for tests.

Doctors said he would need a stem cell transplant within three years for a chance of survival.

They hoped to buy Veer some time by putting him on steroids to boost his blood counts. But his condition has deteriorated fast.

Recent tests at Great Ormond Street Hospital in London show he now has just three to four months to find a donor.

Kirpa and Nirav were both tested, along with Veers six-year-old sister Suhani, but none of them were a match.

A search on the global stem cell register also drew a blank.

And his dad has been trying to encourage his fellow countrymen and women in India to join the register.

They have even signed up a female battalion of the Indian Army.

Kirpa, 37, from Harrow, London, said: We just feel so scared were going to lose our cheeky, amazing little boy. To look at Veer you wouldnt know hes critically ill.

Like his name, hes been brave from the start. Hes undergone countless tests and hospital visits but has had a constant smile on his face.

"He knows he needs a superhero to step forward, but his optimism and enthusiasm are infectious and keep us all going.

She added: Going on the register is incredibly quick and donating cells if you match someone in need is painless.

You can join the Anthony Nolan stem cell register today.

Nine out of 10 people donate their stem cells through the bloodstream in a simple IV process called peripheral blood stem cell collection.

One in 10 will have their stem cells collected via the bone marrow itself, while under general anaesthetic. Doctors transplant the new, healthy cells via the patients bloodstream, where they begin to grow and create healthy red blood cells, white blood cells and platelets.

A perfect match from a donor can mean a lifelong cure.

Veers dad Nirav, 40, said: I only learned about the Anthony Nolan stem cell register two years ago and even then I assumed it would involve long and painful procedures.

We need to raise awareness to save lives in every community.

Continued here:
Boy, 4, may look fighting fit but only has months to live - unless you can save him - Mirror Online

Recommendation and review posted by Bethany Smith

INTRODUCTION

The ability to regenerate complex body parts varies considerably in the animal kingdom. While planarian and hydra are able to regenerate their entire bodies, many avian and mammalian species mostly stop at the wound healing stage without a reparative regeneration process (1). This disparity may result from complexity differences among organisms by nature, yet it leaves us the hope that we may learn from highly regenerative species to improve our own regenerative potential.

Zebrafish is known for its ability to regenerate multiple complex body structures (2). Among regenerable tissues, the caudal fin serves as a great model due to its faithful and rapid regeneration, ease of manipulation, and relatively low complexity. A key step in regeneration is the formation of the blastema, a layer of proliferative and undifferentiated cells that accumulates between the wound site and the wound epidermis following initial wound closure. This step occurs in response to appendage loss and is one of the key features that separates regenerative systems from nonregenerative systems. At later stages of regeneration, the blastema further proliferates and differentiates to regenerate the missing complex structures.

However, the molecular signatures of blastemal cell state transitions during regeneration in zebrafish remain elusive. The state of a cell can be represented by its collective gene expression profile, which has only been measured in bulk for all genes or in specific lineages of cells for a subset of genes during caudal fin regeneration. Prior work has shown that both proliferation of progenitors and dedifferentiation of adult lineage cells contribute to the blastema (38). Progenitors respond to injury cue and proliferate as in normal development. Cells derived from mature adult lineages, however, lose their lineage-specific markers while obtaining progenitor-like markers when they proliferate. Neither type of cell gains multipotency, but rather, they proliferate and regenerate with lineage restrictions. The limited resolution and throughput of these approaches have prevented a more systematic understanding of blastema cells. The advent of single-cell transcriptomic technologies promises to reveal signals masked at the bulk tissue level (9), granting us an opportunity to define and monitor cellular state transition in regenerating fin at an unprecedented resolution.

In this study, we generated single-cell transcriptomic maps of regenerating fin tissue. These maps allowed us to separate the contribution from different cell types and track the transcriptomic dynamics in cell state transitions during regeneration. By comparing with the profiles obtained from uninjured fin tissue, we identified cell types involved in regeneration. We demonstrated the activation of cell cyclerelated programs shared across cell types as well as cell typespecific programs. Furthermore, we defined the heterogeneity in both epithelial and blastemal populations and their functional relations to the regeneration process.

To better understand cell type involvement in fin regeneration, we characterized single-cell transcriptional landscapes for both preinjury and regenerating caudal fin tissues using the 10x Genomics platform (see Materials and Methods and table S1) (9). We sampled regenerating fins from 1, 2, and 4 days post-amputation (dpa) time points to interrogate the stages of blastema formation, outgrowth, and maintenance (Fig. 1A). Fin samples were collected from multiple fish to control for individual variation while at the same position along the proximal-distal axis to avoid positional effects. To establish the transcriptional ground states for each cell type in the fin tissue, we first focused on cells collected from the preinjury time point. Via an unsupervised clustering of 4134 cells, we identified epithelial cells (epcam and cdh1), hematopoietic cells (mpeg1.1 and cxcr3.2), and mesenchymal cells (msx1b and twist1a) (fig. S1, A and B) (1014). Epithelial cells are from three transcriptionally distinct subgroups, representing the superficial (krt4), intermediate (tp63), and basal layers (tp63 and krtt1c19e) of the epithelium (fig. S1, A and B) (15, 16).

(A) General experimental design. Zebrafish caudal fin tissues at preinjury and 1/2/4 dpa stages were collected. (B) Clustering assignments for caudal fin cells collected from each stage. Uniform Manifold Approximation and Projection (UMAP) axes were calculated from the integrated cells dataset as in (C). (C) Clustering assignments for caudal fin cells collected from both preinjury and regenerating stages. Cells were plotted on UMAP axes. Color coding is the same as in (E). (D) Percentage distribution of the major cell types captured in caudal fin, grouped by their stage of collection. Color coding is the same as in (E). (E) Differential expressions of the key marker genes by the identified major cell types. Color gradient: normalized relative expression level. Dot size: percentage of cells in the cluster that express the specified gene.

To determine whether the same cell types existed in the regenerating stages, we performed analysis using two different approaches: (i) Cells from each stage were clustered independently, and (ii) cells from both uninjured fins and injured fins were integrated through the anchoring approach (see Materials and Methods; Fig. 1, B, C, and E; and table S2) (17). For both approaches, we regressed out cell cycle effects before principal components analysis (PCA). Agreement between cluster assignments was measured using Hubert and Arabies adjusted Rand index (ARI). An average ARI of 0.86 (preinjury, 0.86; 1 dpa, 0.85; 2 dpa, 0.90; and 4 dpa, 0.83) indicated that clustering results generated using the two approaches were highly consistent. Cell types identified in the preinjury cells presented consistently across all regenerating stages, suggesting that regenerating fins contain the same cell types as the preinjury fins.

New regenerates are built up by the proliferation and migration of cells located at a number of fin segments away from the amputation plane (2). In response to injury cues, these cells gained the ability to detach from local tissue, enter cell cycle, and migrate toward the wound site while undergoing transcriptional reprogramming. We computationally separated S phase, G2-M phase, and G1-phase cells based on the expression level of cell cyclerelated genes and performed clustering analysis using only S phase cells (see Materials and Methods and fig. S2A). In this cycling cell population, we identified epithelial, mesenchymal, and hematopoietic cell groups as before (Fig. 2, A to C, and table S3). Our data support a model in which cells likely keep their original identities during proliferation.

(A) Cell type clustering of S phase cells plotted onto UMAP axes calculated by S phase cell only. Cells are colored by the general cell types merged from major cells types in Fig. 1B. (B) Stage distribution of S phase cells. Cells were plotted on the same UMAP axes as in (A) and colored by stage when the cells were collected. (C) Relative expression levels of the top 30 differentially expressed genes from each cluster of only S phase cells. (D) Venn diagrams of numbers of genes shared between the cell cycleactivated genetic programs. Left, included all genes; right, included only cell cyclerelated genes (see Materials and Methods).

Next, we asked whether different regenerating cell types exhibited similar or distinct cell cycle regulations. To this end, we identified genes up-regulated in S phase cells compared to G1 phase cells in each cell type, respectively (logFC, >0.25; minimum percentage, >10%). Of the 1098 differentially expressed genes, 161 were shared across all three groups of comparisons (Fig. 2D and table S4). Of these shared genes, at least 54 genes were related to cell cycle regulation, underscoring a shared program governing cell cycle reentry (criteria described in Materials and Methods). In contrast, hundreds of genes differentially highly expressed in S phase exhibited cell typespecific pattern, of which dozens were related to cell cycle (Fig. 2D). We next evaluated the degree of conservation of these enriched genes by asking what fraction did not have human orthologs that had been curated in the Metascape database (18). Twenty-five percent of genes in the epithelial cellspecific group had no human ortholog, whereas all shared groups had at most 15% genes without a human ortholog, suggesting that enriched genes shared by cell types were more evolutionarily conserved (fig. S2C).

Some cell typespecific S-G1 enriched genes were also expressed in a cell typespecific manner regardless of their cell cycle phases: For example, psmb8a and psmb9a shared similar epithelial-hematopoietic enrichments (fig. S2D). The human homologs of these genes (PSMB8 and PSMB9) encode 5i and 1i subunits of the immunoproteasome (19). Together with 2i and PA28 subunits of the proteasome, they turn the proteasome into immunoproteasome and take part in immune response (20). Immunoproteasome digests peptides more efficiently, promoting antigen presentation by a major histocompatibility complex (MHC) class I molecule. Although they did not pass the differential expression criteria in the S-G1 comparison, zebrafish psmb10, psme1, and psme2 shared a differential expression signature similar to that of psmb8a and psmb9a, suggesting that zebrafish might use the same group of subunits for the assembly of immunoproteasomes that might help increase immune responses during regeneration, especially in epithelial and hematopoietic cells (fig. S2, D and E). In addition, we found three genes that shared the same expression signature with the immunoproteasome subunits (psmb13a, psmb12, and psma6l) (fig. S2E) without known human or mouse homologs, suggesting that they might form zebrafish-specific proteasomes with functional relevance to regeneration (19).

Consistent with current knowledge, we observed three transcriptionally distinct subgroups in the preinjury epcam+ epithelial cells, representing the superficial, intermediate, and basal layers of the adult zebrafish epithelium (Fig. 3A and fig. S1B) (15, 16). By integrating cells from all stages during regeneration, we found clusters of cells that corresponded to all three layers of the epithelium after injury (Fig. 1, B and C). In addition, we captured a rare agr2+ population (referred to as mucosal-like epithelium herein) that was too small to be clustered by itself in the preinjury stage (Fig. 1E). These cells shared general epithelial features with the other epithelial layers but exhibited higher expression of a unique set of 200 genes. We examined the expression distribution of the orthologs of these genes in human tissues (The Human Protein Atlas, http://proteinatlas.org/) (21). Among the top 30 genes with human orthologs, 11 showed enriched expressions in proximal digestive or gastrointestinal tract and another 11 in bone marrow of blood lineages, suggesting that this population is analogous to cells in the mucosa in mammalian systems (table S2). In zebrafish, agr2 is required for the differentiation of the mucosal-producing goblet cells in the intestinal epithelium (22). To confirm the cell typespecific expression pattern of this gene in the fin tissue, we performed in situ hybridization on agr2 in both uninjured and regenerating fin tissues (see Materials and Methods). agr2 transcripts are scattered within the epithelium regardless of the sample collection stage and reflect a round morphology of the cell expressing it (fig. S3, A, C, E, and G to I). A proportion of agr2+ cells overlap with positive dark blue staining of Alcian blue in serial sections, suggesting that these cells are mucous cells that are known to exist in the caudal fin epithelium (fig. S3, B, D, and F) (23).

(A) Diagram of the stratified adult zebrafish epithelium. (B) Differential expressions of claudin family and keratin family genes in epithelial subgroups shown as a dot plot. Known epithelial markers krt4, fn1b, tp63, and krtt1c19e were included for comparison. Cells were first grouped by major cell types and then separated into preinjury and regenerating stages. Darkness of dot color: relative expression level. Dot size: percentage of cells in the cluster that express the specified gene. (C) In situ hybridization targeting krt1-19d, cldna, cldn1, and krt4 of 4-dpa fin tissues. Brown dots indicate positive RNA signals from target genes, while pale blue blocks represent hematoxylin-stained cell nuclei. Zoomed-in views are presented. Original images can be found in fig. S4. All epithelial layers are above the black dotted lines. (D) Clustering assignment of epithelial cells plotted on UMAP axes calculated with only epithelial cells. Cells are colored by their epithelial layer identity as in (A). (E) The same UMAP visualization as in (D), with cells colored by stage of collection. Arrows connect the groups of comparison, with a direction from preinjury stage to regenerating stages (1, 2, and 4 dpa). Numbers next to the green triangle: number of genes up-regulated in regenerating stage. Numbers next to the red triangle: number of genes down-regulated in regenerating stage. (F) Clustered GO enrichment for genes up-regulated in regenerating basal, intermediate, and superficial epithelial cells comparing to their preinjury counterparts. GTPase, guanosine triphosphatase; ER, endoplasmic reticulum; PKN, protein kinases N; snRNP, small nuclear ribonucleoprotein.

Although the same three-layer classification of epithelial cells could be defined when cells from regenerating stages were integrated with the preinjury cells, the expression of the commonly used layer-specific marker genes changed dramatically during regeneration: Superficial epithelial marker krt4 expanded into basal and intermediate layers of the epithelium, the intermediate layer marker fn1b was also highly expressed in the basal layer, and the basal epithelial marker krtt1c19e was barely detectable in the postinjury cell populations (Fig. 3B) (15, 16). To better understand the molecular features of the epithelial populations, we identified genes significantly more highly expressed in epithelial cells than in hematopoietic and mesenchymal cells and found that cell-cell junction genes ranked high in the list. Among these, genes from the claudin and keratin families were detected at a ratio 20-fold higher than that in randomly selected detectable genes (2 test, P value of <0.0001). We focused on expression patterns of all claudin and keratin genes in zebrafish and found that cldne, cldnf, krt1-19d, and krt17 labeled the superficial cluster; cldnh labeled the mucosal-like cluster; cldna, krt93, and krt94 labeled the intermediate cluster; and cldn1 and cldni labeled the basal cluster (Fig. 3B). Claudin genes are expressed in a tissue-specific manner in zebrafish and are generally considered to be the proteins responsible for regulating the paracellular permeability in the vertebrate epithelium (24). Their differential expression signature in both uninjured and regenerating tissues suggests that they might play important roles in maintaining the permeability in each epithelial population. On the other hand, the expression of keratin genes displayed less restriction across the three layers relative to claudin genes but stronger dependence on regenerating states (Fig. 3B). The differential expression signature suggests that they might perform epithelial subtyperelated function in regeneration. To verify their expression pattern, we performed RNA in situ hybridization targeting the known marker krt4 and new candidates, including krt1-19d, cldna, and cldn1 (Fig. 3C) as well as cldne, krt94, and cldni (fig. S4, A to H). Comparing with the known marker krt4, these genes exhibited more restricted expression patterns in epithelial layers, better representing the molecular signatures of different epithelial populations in the fin tissue regardless of regeneration status (Fig. 3, B and C).

The three epithelial layers were present across the regeneration stages albeit with varying proportions (Fig. 1D). The proportion of basal epithelial cells peaked at 2 dpa, reaching up to 42%, whereas the superficial layer epithelial cells decreased from 27 to 6% at 2 dpa (the coefficient of variations of cell proportions between biological replicates is below 15%). The observed compositional change of the two epithelial populations is consistent with a previous finding that the initial migration of superficial layer cells to the new regenerates is followed by replenishment by basal epithelial cells (25). This basal replenishment was also reflected in the two-dimensional Uniform Manifold Approximation and Projection (UMAP) calculation from only epithelial cells, in which preinjury cells were separated by their respective layers, whereas regenerating cells were closer in the projection space (Fig. 3, D and E). Superficial layer cells from before and after injury stages were in juxtaposition to each other, consistent with our knowledge that this layer of epithelial cells directly migrates to and covers the wound site (25). On the other hand, basal layer cells from before and after injury stages were more distantly separated, suggesting more dramatic changes between resting and regenerating basal epithelial cells.

To understand the mechanisms of epithelium regeneration, we compared the transcriptome between preinjury and regenerating cells for the three epithelial layers. Basal layer cells up-regulated 1271 genes and down-regulated 198 genes during regeneration; both were the highest numbers across all comparisons (numbers of differentially expressed genes were from Wilcoxon rank sum test, adjusted P value of < 0.01; Fig. 3E). We performed gene ontology (GO) enrichment analysis on genes up-regulated in the regenerating stage by layer and found both common and layer-specific programs associated with regeneration (18). All three layers were enriched for oxidative phosphorylation (dre00190), proteasome (dre03050), and cell redox homeostasis (GO:0045454). While basal and intermediate layer cells could be regulated by Rho guanosine triphosphatasemediated Wnt signaling for extracellular matrix organization and actin filament depolymerization, respectively (R-DRE-195258, R-DRE-5625740, R-DRE-195721, GO:0030198, and GO:0030042), superficial layer cells showed enrichment mainly for general transcriptional and translational regulations (Fig. 3F). When comparing the expression profiles between regenerating superficial epithelial and basal epithelial, we saw enrichment for antigen presentation and apoptosis features in the superficial layer (table S5). In addition, the superficial layer contained the lowest proportion of cells in S phase or G2-M phase, further supporting that superficial layer epithelium was most likely maintained by migration and proliferation from other layers (fig. S2B).

Subcluster identification within regenerating basal epithelial cells revealed two subgroups that represented different functionalities during regeneration, one labeled by distally distributed fgf24, while the other by proximally distributed lef1 (fig. S5, A to C) (26, 27). We compared expression profiles between group I (distal) and group II (proximal) cells and found that their suggested functionalities were consistent with their expected roles in regeneration: The distal subgroup (or distal wound epidermis) up-regulated genes associated with extracellular matrix degradation, and the proximal subgroup (or proximal wound epidermis) up-regulated genes associated with organization of extracellular matrix, skeletal system development, and negative regulation of locomotion (fig. S5, D and E). In addition, the increase of proximal cell proportion was accompanied by the decrease of distal cell proportion, suggesting that basal layer epithelium become gradually active in promoting blastema proliferation and differentiation during the initial regeneration process (fig. S5C). To confirm the distribution of these cells, we performed RNA in situ hybridization targeting two candidate genes, stmn1b and sema3b, one from each cluster. The expression of stmn1b was first observed at the basal layer of the wound epidermis at 1 dpa but diminished as regeneration proceeded (fig. S4, I to K). On the contrary, sema3b showed expression at later stages and was enriched in the relatively proximal portion of the basal layer epithelium (fig. S4, L to N). The expression dynamics of these two genes matched the predicted proportion changes of the two clusters (fig. S5C). While sema3b was more restricted to the basal layer, stmn1b showed low expression levels in the intermediate layer as well, potentially suggesting that this subpopulation could be labeling cells transitioning from the basal layer to the other layers of epithelium.

We next performed subcluster analysis within the hematopoietic cluster and found four subpopulations (Fig. 4, A to C and table S6). The first three populations were enriched for the macrophage marker mpeg1.1, with the cluster H1 being M1-like (lgals2+ and lcp1+) and the cluster H3 M2-like (ctsc+ and lgmn+) (Fig. 4D) (12). We speculated that the cluster H2 represented a transition state between M1-like and M2-like or a state before the macrophages differentiate toward M1-like or M2-like. From 1 to 4 dpa, the proportion of M1-like macrophages remained at a constant level, while that of M2-like macrophages expanded (Fig. 4B), potentially suggesting a shift in the function of macrophages in the new regenerates from pro-inflammatory toward anti-inflammatory as regeneration proceeded. Macrophages are important for proper blastema proliferation (28). The change in the proportions of M1/M2-like macrophage in our data matched with that observed in the larvae fin, suggesting that the adults followed a similar rule for immune cell recruitment after injury.

(A) Subcluster assignments of the hematopoietic cells. Cells were plotted on UMAP axes. The same color code is used for (B) to (D). (B) Proportion of subgroups of hematopoietic cells. (C) Expression enrichment of the top 30 differentially expressed genes in the four subclusters within hematopoietic cluster shown as a heatmap. (D) Expression distribution of genes associated with macrophage activation grouped by subclusters. Expression levels were log normalized by Seurat. y axis: cluster identity. z axis: cell density. (E) Expressions of pigment cell markers gch2 and mlpha in the hematopoietic population.

The cluster H4 enriched for genes including mlpha and gch2, both well-characterized markers for the chromatophore lineages in zebrafish (Fig. 4E) (29). Chromatophores are derived from neural crest lineage, yet here, they clustered with macrophages that were from hematopoietic lineage. One possibility is that this clustering result could be driven by features related to antigen presentation via MHC class II, a feature of pigment cells based on studies using human melanocytes (30). The proportion of this cluster decreased as regeneration started, agreeing with the known pattern of fin stripe recovery after amputation (Fig. 4B) (31).

To understand the component and function of the cells in the mesenchymal cell cluster before and during fin regeneration, we focused on genes enriched in this cluster and found previously identified blastema marker genes that are required for fin regeneration, including the muscle segment homeobox family members msx1b and msx3 and the insulin-like growth factor signaling ligand igf2b (logFC, >0.25; minimum percentage, >25%; and adjusted P value of <1 105, as listed in table S1) (2, 13). The mesenchymal cluster expressed these genes nearly exclusively, confirming their blastema identity in regenerating stages (fig. S6A). In addition, we found key genes involved in zebrafish bone development and regeneration: twist1a, the transcription factor that controls the skeletal development by regulating the expression of runx2 (14); cx43, the gap junction protein required for building the fin ray up to the right length; and hapln1a and serpinh1b, two genes downstream of cx43 (32, 33). By performing conserved marker analysis using Seurat, we found that msx1b and twist1a were also among the markers conserved across all stages, underscoring shared features that existed between regenerating and preinjury mesenchymal cells (maximum P values across stages: 4.72 1010 and 2.84 109 for msx1b and twist1a, respectively). This theme of building and supporting bone tissues in mesenchymal cells was not only reflected by a handful of genes: GO analysis of all the detected up-regulated genes in this cluster revealed significant enrichment of genes associated with GO terms, including fin regeneration (GO:0031101) and skeletal system development (GO:0001501) (fig. S6B). When more stringent criteria for differential expression were used, genes were also significantly enriched for GO terms, including skeletal system morphogenesis (GO:0048705) and extracellular matrix organization (GO:0030198) (fig. S6C).

Previous work has shown that blastema comprises bone cells and non-bone cells but has not defined the cell types and the regeneration process of each type (23, 34, 35). To better understand the regeneration process by cell type, we performed clustering analysis within the mesenchymal cluster and identified nine distinct subgroups (Fig. 5A and fig. S6D). Of the two preinjury subgroups, M-2 represented the mature bone lineage, which was enriched for expressions of bglap, mgp, and sost (fig. S6E) (36, 37). Comparing to M-2, cluster M-1 presented low expression levels of bglap, mgp, and sost and high expression levels of a group of other genes, including fhl1a, fhl2a, and tagln (fig. S6E). Mammalian orthologs of these genes are required for chondrogenesis and osteogenesis, leading us to speculate that cluster M-1 could represent the supporting non-bone cell lineage in the preinjury state (38, 39).

(A) Subclustering assignments of mesenchymal cells shown on UMAP axes. Cells are colored by their cluster assignments and connected by Slingshot-reconstructed trajectories. Lineage 1: 1-2-3-4; lineage 2: 1-2-3-5-6; lineage 3: 1-2-3-5-7-8; lineage 4: 1-2-3-5-9. (B) By-lineage highlighting of mesenchymal cells. Cells with colors other than gray represent the cells included in each corresponding lineage in (A). (C) Expression distribution of genes labeling cell lineages and cell states in mesenchymal cells. Gene feature plots were connected by estimated lineages using the same lineage color code as in (A). (D to G) In situ hybridization targeting the tnfaip6 gene in (D) preinjury, (E) 1-dpa, and [(F) and (G)] 4-dpa fin tissues. Brown dots indicate positive RNA signals from target genes, while pale blue blocks represent hematoxylin-stained cell nuclei. A zoomed-in view for the region inside the focused rectangle is provided within (D). (G) Zoomed-in view for the region highlighted by a rectangle in (F). Dotted lines indicate the amputation plane. All scale bars, 100 m.

The remaining seven populations came from regenerates. Pseudotime analysis via Slingshot (40) suggested that these subgroups formed four trajectories, all initiated from the tnfaip6+ cluster (M-3), which was composed mainly of 1-dpa cells (Fig. 5, B and C, and fig. S6D). tnfaip6 was ranked top by an adjusted P value in the differentially expressed genes labeling the regeneration initiation cluster and was also expressed exclusively in the mesenchymal cluster (Fig. 5C and fig. S6A). The mammalian ortholog of this gene is required for proliferation and proper differentiation of mesenchymal stem cells (MSCs) and balances the mineralization via osteogenesis inhibitions (41). The expression of tnfaip6 in the postinjury zebrafish fin suggested that it could also be required in the early stages of regeneration for promoting mesenchymal proliferation. To confirm the expression pattern of tnfaip6, we performed RNA in situ hybridization for uninjured and regenerating fin tissues targeting this gene (Fig. 5, D and E). In the uninjured fin, tnfaip6 was expressed in a segmental pattern, presumably enriching at joints between bone segments. At 1 dpa, tnfaip6 was expressed not only near the bony rays but also in the cavity, showing a general activation in the mesenchymal population. As regeneration proceeded from 1 to 4 dpa, mesenchymal cells divided into cdh11+ (M-4) and tph1b+ (M-5) branches, with the latter further divided into mmp13a+ (M-6), tagln+ (M-7), and vcanb+ (M-9) branches (Fig. 5C and fig. S6D). The mmp13+ (M-6) cluster maintained a high-level tnfaip6 expression, whereas all other branches had a lower but detectable tnfaip6 expression. This was consistent with the observation we made from in situ hybridization at 4 dpa targeting tnfaip6: the broad expression in the mesenchymal population and segmental enrichments similar to that in the uninjured fin (Fig. 5, F and G).

The four trajectories initiated from the tnfaip6+ cluster revealed four putative lineages representing bone and non-bone cells in the blastema. cdh11+ lineage 1 specifically expressed runx2 and osterix/sp7, which are the key transcription factors regulating osteogenesis (fig. S6E) (42). Mammalian ortholog of cdh11 could induce Sp7-dependent bone and cartilage formation in vivo, suggesting that the cdh11+ branch in the blastema represented the regenerating osteoblasts (43). Genes highly expressed at the end of this lineage (M-4) compared to the initiation point (M-3) were associated with bone mineralization and skeletal system development, further supporting their bone cell identity (table S7).

Mesenchymal cells outside the osteoblast branch shared enrichment for tph1b and aldh1a2 expressions at 2 dpa, followed by and1 expression at 4 dpa (Fig. 5C and fig. S6F). These three genes had been suggested to label joint fibroblasts, fibroblast-derived blastema cells, and actinotrichia-forming cells in the blastema, respectively (34, 35, 44). However, their expression signatures implied that instead of labeling separate populations in the blastema, they might be labeling different states of the same non-osteoblastic cells at the early stage of fin regeneration.

Upon 4 dpa, these non-osteoblastic cells diverged into three groups (Fig. 5C and fig. S6D). To understand this separation, we performed differential expression analysis for each branch between cells at the end of the lineage tree (lineage 1, M-4; lineage 2, M-6; lineage 3, M-7 and M-8; and lineage 4, M-9) and cells in the initiation cluster (M-3). Genes highly expressed at the lineage end points were included for GO analysis for functional predictions (logFC, >0.25; minimum percentage of >25%; and adjusted P value of <0.01). These three lineages were also associated with skeletal system development or extracellular matrix organizations as were the bone cell lineage; however, the association was driven by a nearly completely different set of genes (table S7). Unlike the osteoblast lineage, none of these three non-bone cell lineages showed enrichment for bone mineralization, suggesting that these cells might indirectly contribute to bone formation. In lineage 2, top differentially expressed genes mmp13a and ogn both have mammalian orthologs that are associated with bone formation (Fig. 5C and fig. S6F) (45, 46). In addition, this lineage presented up-regulation of DLX family genes, especially dlx5a, suggesting the reactivation of fin outgrowthrelated developmental programs during regeneration (fig. S6F and table S7) (47). Lineages 3 and 4 both enriched for estrogen response and expressed the retinoic acid (RA) synthesis gene aldh1a2. However, only lineage 3 displayed up-regulation of the RA-degrading enzyme cyp26b1 (fig. S6F and table S7). The cyp26b1high-aldh1a2low pattern helped to reduce RA levels in the blastema, promoting redifferentiation of the osteoblasts (44). The differentiation-promoting signature was also reflected in the enrichment of genes, including col6a1 and tagln, whose mammalian orthologs are essential for bone formation (fig. S6F and table S7) (39, 48). These genes were also enriched in the preinjury non-bone cell population, suggesting a connection between this subset of the non-bone cells and their preinjury counterparts (Fig. 5C and fig. S6F). Top up-regulated genes in lineage 4, on the other hand, were main contributors of the extracellular matrix, including and1/2, loxa, and vcanb (35, 49, 50). Enriched expression of these genes suggested that this lineage could be responsible for creating and organizing the fibrous environment. Together, the various non-osteoblastic cells could potentially work collaboratively with the osteoblasts in creating the environment for bone tissue regeneration.

Genes that had been suggested to label progenitors contributing to fin regeneration (mmp9 and cxcl12a) and several orthologs of known mammalian MSC markers (lrrc15, prrx1a/b, and pdgfra) (6, 7, 51, 52) were expressed almost exclusively in the mesenchymal cluster (fig. S6A). Consistent with the observations made in the lineage-tracing study, the mmp9 expression was associated with the regenerating bone cell lineage (lineage 1; Fig. 5B and fig. S6E) (7). However, mmp9 was detected only in a small portion of the mesenchymal cells and was highly expressed in the basal epithelium cells at similar proportions. On the other hand, we observed coenrichment of cxcl12a (previously known as sdf-1) and orthologs of the known mammalian MSC markers in the preinjury population (fig. S6E). cxcl12a-expressing cells in zebrafish were found to carry osteogenic, adipogenic, and chondrogenic characteristics in vitro like MSCs would do and contributed to the mesenchyme of the newly developing bony rays during fin regeneration (6, 53). The coenrichment pattern suggested that some of the preinjury cxcl12a-expressing cells could be MSCs in the fin tissue, which contribute to fin regeneration.

Zebrafish caudal fin is a unique regeneration system to model the injury response and regeneration of vertebrate appendages despite being a simple structure without muscular and adipose tissues. Major components of the regenerating caudal fin are epithelial cells covering the wound site and blastemal cells producing the connective tissue and bone matrices. Early studies established that actively proliferating blastema is the key to regeneration. Formed by cell migration and proliferation, this layer of cells continues in outgrowth and differentiation, rebuilding the complex body structure. Despite efforts in understanding its importance, basic questions regarding the formation of blastema remained: (i) Which type of cells contributes to the blastema and (ii) how do they shape the regeneration process?

Using single-cell transcriptomes, we defined cell types in both preinjury and postinjury fin tissues. Although regenerating cells were drastically different from their preinjury counterparts, both stage-specific and integrated clustering analysis revealed the same major cell type compositions in the fin tissues regardless of their time of collection. Common cell types detected include epithelial cells from all three layers, hematopoietic cells, and mesenchymal cells. Our data lay a foundation for lineage-targeted analysis to investigate the role of epithelial layers and subtypes in fin regeneration.

For each cell type to be a consistent component in the regenerated fin, cell cycle entry is required. We found that both common and unique cell cycle programs activated in the regenerating fin, with the shared ones appearing to be more evolutionarily conserved than the unique ones. Among the genes showing cell typespecific S phase enrichment, several immunoproteasome subunits also showed a clear cell typespecific expression. We speculated that the increasing level of immunoproteasome subunits in epithelial and hematopoietic cells specifically might accelerate antigen processing and presentation, which could be important for immune cell recruitment and tumor necrosis factorinduced blastemal proliferation (54).

Epithelial cells were the most abundant cell type in the profiled fins and could be clustered into four different subgroups, including the three layers in the adult fish epithelium and the mucosal-like cells within the intermediate layer. However, markers labeling these layers did not perform well in separating cell groups when only regenerating cells were considered. An unbiased differential expression test suggested that some members of the krt and cldn families were expressed in specific layers more consistently throughout regeneration. RNA in situ hybridization targeting cldne, krt1-19d, cldna, krt94, cldni, and cldn1 confirmed their exclusive layer-specific expression pattern, underscoring their potential to serve as markers for the distinct epithelial layers during regeneration. Our epithelium-specific analysis suggested that basal layer epithelial cells proliferate and could be the main source for replenishing the other two layers of the epithelium, similar to findings in a previous study based on genetic lineage tracing in zebrafish and echoing findings made using the axolotl limb regeneration model (25, 55). We observed higher apoptosis and lower proliferation features in the superficial epithelial layer compared to the other layers. At the same time, we observed transition patterns in gene expression, connecting the basal to the intermediate and the superficial layer during regeneration.

The behavior of mucosal-like cells during regeneration had been rarely reported for zebrafish in literature. We found in this study that this group of cells was an integral part of the regeneration process. Enrichment of foxp1b in this population and enrichment of foxp4 in basal and intermediate epithelial cells supported that zebrafish foxp homologs could be involved in regulating agr2 expression as does the Fox family in mice and, furthermore, the mucin production in the epithelium during regeneration (Fig. 1E) (56). The protein encoded by amphibian homologs of agr2, nAG (from newts) and aAG (from axolotl), are necessary and sufficient for salamander limb regeneration (57, 58). They are expressed in both dermal glands and the nerve sheaththe pattern of which has also been recovered from single-cell RNA sequencing (scRNA-seq) analysis (55). Regeneration deficiencies caused by denervation before amputation can be rescued by the ectopic expression of nAG. Although we do not have data supporting the nerve sheath expression pattern, as shown for the amphibian models, we hypothesize that agr2 could similarly mediate neuronal signals in zebrafish during regeneration.

Macrophages are critical players in the zebrafish caudal fin regeneration (28, 54). We observed subgroups of the mpeg1.1+ macrophage population in the regenerating fin tissue, resembling M1 and M2 macrophages in mammalian systems. However, we were not able to recover other immune cell population in the hematopoietic cells. This could potentially be due to the systematic bias against certain cell types during tissue dissociation and droplet incorporation in the microfluidic device. The same bias might also explain why we were not able to recover some other known players in the regenerating fin tissue, including neurons and endothelial cells (4). Increasing the number of cells sampled for scRNA-seq or performing scRNA-seq on sorted hematopoietic lineage cells would help to better understand the involvement of these populations in the regeneration process.

The expression profiles of mesenchymal cells captured from the postinjury stages resembled those of blastema in histology studies. We found four connected but distinct lineages representing both bone and non-bone cells in the blastema. All four lineages initiated from one cluster mostly consisted of 1-dpa cells and enriched for the tnfaip6 expression. A similar scenario has been observed in the axolotl limb regeneration model. By using scRNA-seq on a lineage-labeled axolotl model, Gerber et al. (58) found that connective tissue cells funnel into a progenitor state at initiation. Whether the cluster identified in our study represented a shared cell origin for the blastema or a shared state across mesenchymal cell types in the initial blastema-formation stage requires further investigation. High proportion of epithelial population in the fins could also hamper the discovery of relatively rare population with multipotency. Finer dissection before single-cell profiling might help in future study designs in capturing these populations.

While the bone cell lineage has been well studied in the regenerating fin, non-bone cells had been labeled by different markers and given different names and their intercorrelations left to be clarified. We found that tph1b, aldh1a2, and and1/and2 genes were shared among the non-bone cell lineages and could be labeling states instead of types of blastemal cells during regeneration. Meanwhile, differential analysis revealed similar enrichment for bone formation in all lineages yet distinct associations with reactivation of developmental programs, RA signaling, and collagen metabolism, underscoring their collaborative and complementary roles in the regeneration process.

Our scRNA-seq data also provided more details about the fish system we are working with. For all sample collections, we used the transgenic strain Tg(sp7:EGFP)b1212, which specifically labels osteoblast lineage in the fish (59). It was reported that green fluorescence signal could be detected in the fish skin after 72 hours post-fertilization. This ectopic expression, however, does not interfere with confocal imaging of skeletal structures of fish at any stage due to the fact that they lie in different planes of focus. What these cells are and why they expressed the transgene were unclear. In this study, we obtained a holistic view of the transgene expression pattern in the fin region regardless of whether that was associated with the cell type of interest, i.e., osteoblasts in this context. Unsupervised clustering on the expression profiles from single fin cells suggested that green fluorescent protein (GFP) is not only expressed in the mesenchymal but also highly enriched in the superficial layer epithelium (table S2). A closer examination of this classic reporter gene construct revealed that the regulatory region of sp7 used for the construction of the transgene did not exactly represent the endogenous sp7 regulatory region. Tg(sp7:EGFP)b1212 was generated from bacterial artificial chromosome transgenesis using CH73-243G6 as the backbone, which did not contain the first exon of sp7 according to the annotation of the current genome assembly (chr6:58630884-58720045 and GRCz10), leading to the usage of a regulatory sequence different from the endogenous version. Whether this usage difference contributed to the ectopic expression pattern of the transgene requires further study. This finding points to the potential of using single-cellbased approaches in reporter line validation and more thorough analysis of the transgene behavior.

All zebrafish were used in accordance with protocol no. 20190041 approved by the Washington University Institutional Animal Care and Use Committee. Wild-type and Tg(sp7:EGFP) strains are maintained under standard husbandry in the Washington University Fish Facility, with the system water temperature at 28.5C and a day-night cycle controlled as 14-hour light/10-hour dark. For fin amputation, we anesthetized 1-year-old fish with MS-222 (0.16 g/liter) in the system water and then removed the distal half of their caudal fin with sterilized razor blades. The fish were then sent back to circulating water system for recovery. We collected regenerating fin tissue from 39 fish by doing secondary fin amputation at the primary cutting plane with the same anesthesia and recovery procedures.

Collected fin tissues were digested by Accumax (Innovative Cell Technologies), filtered through 40-m cell strainers, and washed with 1 Dulbeccos phosphate-buffered saline (DPBS)0.04% bovine serum albumin to generate single-cell suspensions. Libraries were constructed from these cell suspensions following the instruction of the Chromium Single Cell Gene Expression Solution 3 v2 (10x Genomics) and were subsequently sequenced on HiSeq2500 (Illumina) with read lengths of 26 + 75 (Read1 + Read2). Raw reads were processed by Cell Ranger (10x Genomics) with default parameters for read tagging, alignment to zebrafish reference genome (GRCz10), and feature counting based on Ensembl release 91 (cellranger count). EGFP sequence was added into the reference genome as a separate chromosome for mapping reads from the reporter gene.

We performed unsupervised clustering using Seurat v3.0 following the procedure of normalization (SCTransform), highly variable gene detection, dimensional reduction (principal components analysis), and cells clustering (Louvain clustering at resolutions from 0.1 to 0.6) (17). For integrating the four stages in finding conserved cell types, we used the anchoring approach provided by Seurat v3. Cell clustering was based on the top principal components that account for most of the cell-cell variances. The same set of principal components was used in UMAP calculation for visualization as well.

We found differentially expressed genes in each cluster by comparing the expression profiles of them with those of the rest of the cells using Wilcoxon rank sumbased approach with the criteria of log fold change more than 0.25 and a minimum cell percentage of 0.25. The same criteria were applied to all pairwise comparisons, unless stated otherwise. We made functional connections between the list of differentially expressed genes and the type of cell that they most likely represent by testing for GO term enrichment (18) and manual curation by searching The Zebrafish Information Network database and PubMed. Certain cell clusters were taken as independent samples for secondary clustering following the same unsupervised clustering procedures.

We calculated the by-cell average expression level of a set of S phase or G2-M phase markers suggested by Seurat that are detected in our zebrafish dataset and normalized by subtracting aggregated expression of control genes. Although G1 phase cells are also within cell cycle, they are hardly separable from G0 cells. To avoid false-positive labeling for active cycling cells, we set stringent thresholds and only included cells with |S.score G2M.score| > 0.1 in the S or G2-M group, while cells with both S.score and G2M.score below zero as G1. Other cells were not included in this part of the analysis. Differentially expressed genes were also identified by Wilcoxon rank sumbased approach. These differentially expressed genes were considered to be cell cycle related if they were in the list of genes associated with R-DRE-1640170 Cell Cycle and/or cycling marker genes used for cell cycle phase score calculations.

We collected uninjured and regenerating fin tissues from casper (nacrew2/w2;roya9/a9) fish and fixed in 4% paraformaldehyde overnight (60). Fixed tissues were subsequently submerged in 10% sucrose in 1 PBS, 20% sucrose in 1 PBS, and 30% sucrose in 1 PBS for 4 hours each. After sucrose exchange, tissues were embedded in Optimal Cutting Temperature (O.C.T.) compound (Fisher Healthcare Tissue-Plus) and snap frozen on dry ice. The frozen tissue blocks were then processed into 15-m sections on a Leica CM1950 cryostat. We performed RNA in situ hybridization targeting krt4, cldne, krt1-19d, cldna, krt94, cldni, cldn1, agr2, sema3b, stmn1b, and tnfaip6 for mRNA detection using an RNAscope kit (Advanced Cell Diagnostics, Hayward, CA, USA). Alcian blue/periodic acidSchiff (PAS) staining was subsequently performed on the same section or separately on a consecutive serial section following the manufacturers protocol (Newcomer Supply). Microscopic images were taken by ZEISS Axio Observer.

Cell trajectories were constructed using Slingshot v1.3.1 (40). Through initial subclustering and cell type identifications, we found one subcluster with high epcam expression, potentially a doublet cell contamination from the major cell type classifications. We removed this group of cells from all downstream analysis within the mesenchymal cluster. We used UMAP embedding and subclustering assignments as input for the Slingshot calculation.

We performed nonparametric Wilcoxon rank sum test to identify differentially expressed genes across cell groups as implemented in Seurat. P values were adjusted by all features in the dataset using Bonferroni correction.

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Cellular diversity of the regenerating caudal fin - Science Advances

Recommendation and review posted by Bethany Smith

KUANTAN, Malaysia Some skin, eggs and tissue samples are all that remain of Malaysia's last rhino, Iman, who died last November after years of failed breeding attempts.

Now scientists are pinning their hopes on experimental stem cell technology to bring back the Malaysian variant of the Sumatran rhinoceros, making use of cells from Iman and two other dead rhinos.

"I'm very confident," molecular biologist Muhammad Lokman Md Isa told Reuters in his laboratory at the International Islamic University of Malaysia.

"If everything is functioning, works well and everybody supports us, it's not impossible."

The smallest among the world's rhinos, the Sumatran species was declared extinct in the wild in Malaysia in 2015. Once it had roamed across Asia, but hunting and forest clearance reduced its numbers to just 80 in neighbouring Indonesia.

Iman, 25, died in a nature reserve on Borneo island, following massive blood loss caused by uterine tumours, within six months of the death of Malaysia's last male rhino, Tam.

Efforts to get the two to breed had not worked.

"He was the equivalent of a 70-year-old man, so of course you don't expect the sperm to be all that good," said John Payne of the Borneo Rhino Alliance (BORA), who has campaigned for about four decades to save Malaysia's rhinos.

"It was obvious that, to increase the chances of success, one should get sperm and eggs from the rhinos in Indonesia. But right till today, Indonesia is still not keen on this."

ACROSS THE BORDER

Indonesia's environment ministry disputed accusations of cross-border rivalry as a reason why Malaysia's rhinos died out, saying talks continue on ways to work with conservationists in the neighbouring southeast Asian nation.

"Because this is part of diplomatic relations, the implementation must be in accordance with the regulation of each country," said Indra Exploitasia, the ministry's director for biodiversity conservation.

The Malaysian scientists plan to use cells from the dead rhinos to produce sperm and eggs that will yield test-tube babies to be implanted into a living animal or a closely related species, such as the horse.

The plan is similar to one for the African northern white rhinoceros, which number just two. Researchers in that effort reported some success in 2018 in producing embyronic stem cells for the southern white rhino.

But the process is still far from producing a whole new animal, say Thomas Hildebrandt and Cesare Galli, the scientists leading the research.

And even if it worked, the animals' lack of genetic diversity could pose a threat to long-term survival, Galli told Reuters.

Indonesian scientist Arief Boediono is among those helping in Malaysia, hoping success will provide lessons to help his country's rhinos.

"It may take five, 10, 20 years, I don't know," Arief added. "But there has already been some success involving lab rats in Japan, so that means there is a chance."

Japanese researchers have grown teeth and organs such as pancreas and kidneys using embryonic stem cells from rats and mice in efforts to grow replacement human organs.

For now, however, Iman's hide will be stuffed and put on display alongside Tam in a Borneo museum.

(Editing by Matthew Tostevin and Clarence Fernandez)

Continued here:
Back From the Dead? Stem Cells Give Hope for Revival of Malaysia's Extinct Rhinos - The New York Times

Recommendation and review posted by Bethany Smith

In 2007, a group of researchers reported a startling discovery: They had created sperm-like cells out of stem cells taken from the bone marrow of human men. Two years later, however, the study was retracted due to charges of plagiarism. Thirteen years later, the ability to create functional human sperm out of stem cells remains elusive.

Scientists have been trying to figure out how to create functioning human gametes eggs and sperm from stem cells for 20 or 30 years, says Vittorio Sebastiano, a stem cell biologist at Stanford University whose research focuses on reproductive biology. Doing so would help people struggling with infertility have children and help scientists unlock the secrets of human development. Since 2007, scientists have made considerable progress on this front, creating healthy mouse pups from stem cell-generated gametes and even immature human egg cells. But there is still a long road ahead before scientists will be able to convert skin or bone marrow into babies.

We are trying to really find ways to efficiently, robustly generate germ cells that can be, in the short term, used to understand the biology of these concepts, but in the long term [used to be] able to restore fertility, says Sebastiano.

When the first baby conceived via in vitro fertilization (IVF) was born in 1978, it was a major step forward for reproductive science and a precursor to the stem cell research conducted by Sebastiano and others today, he says. But IVF is not an option for every individual or couple trying to have a biological child, including those who are born without gametes or who receive aggressive cancer treatments at a young age. This scientific technique would offer these individuals a new shot at reproduction.

The next major step came in the 2000s, with the creation of induced pluripotent stem cells (iPSCs). These cells are taken from blood or skin cells and reprogrammed to behave like embryonic cells, which have the ability to develop into any type of cell in the body. Since then, researchers have been trying to figure out how to turn these embryonic-like cells into functional sperm and eggs.

A colony of induced pluripotent stem cells used to treat the rare genetic disorder Fanconi anemia. (Credit: Juan Carlos Izpisua Belmonte, Salk Institute for Biological Studies)

Part of what has made this work so challenging is that scientists havent been able to fully grasp what happens in a human embryo during normal development, says Sebastiano. Scientists understand this process in mice because the rodents are easy to study in the lab. But ethical restrictions and technical factors (like having access to the embryos at just the right point in time) make this phenomenon hard to study in people, he says.

Despite the roadblocks, scientists have made significant progress in the last 10 years. In 2012, a group of researchers in Japan created fertile mouse eggs from iPSCs and used those eggs to breed healthy mouse pups. In [the] mouse, the whole circle has already been completed, says Sebastiano. Now it has been shown by a couple of groups in the UK and in Japan that you can generate embryonic-like cells from mice and then you can actually push these cells to become eggs or sperm, fully functional.

In 2018, the same group of Japanese scientists made another major breakthrough. Using human blood cells and the pluripotent stem cell technique, they managed to produce immature human eggs.

Similar efforts to create sperm are not as far along, says Sebastiano. Several efforts over the years have purported to create sperm-like cells, including the 2007 blood marrow study. A much-heralded study published in 2014 also made major news, but Sebastiano says the development of the cells in that study didnt go far beyond the earliest stages of differentiation.

But, we are actively working on it, says Sebastiano. Probably in the next few years we will be able to generate fully functional sperm and fully functional oocytes. Then, the question will be how do scientists test the quality of these gametes, he says.

The only way to fully assess the quality and functionality of a sperm or egg is to use it to, well, try to fertilize another gamete and produce a baby. Thats why this work has to be approached with the utmost care, says Sebastiano. He hypothesizes that once scientists have developed techniques that they think produce mature human oocytes and sperm, the next step will be testing these techniques in primates. That way, researchers can follow the entire life of individual animals produced from this technique to see if any unexpected problems develop, he says.

Sebastiano has no doubt that one day, these stem cells could help individuals struggling with infertility to produce healthy children. This, along with a fascination with biological development, is what drives Sebastianos work. There are also, of course, significant ethical considerations that have to be carefully considered. This technique has the potential to affect human life on a generational level, he notes. And many people also raise concerns about other future consequences, like the ability to create designer babies or produce offspring from hairs stolen from unsuspecting celebrities. Bioethics experts have written about the need to start working through the medical and legal issues around this technique now, before it is viable.

There is a need actually to develop this, but since we are really dealing with a very unique cell type we need to be cautious, says Sebastiano.

Read the original here:
How Close Are We To Making Babies from Bone Marrow? - Discover Magazine

Recommendation and review posted by Bethany Smith

This rebrand symbolizes our growth as a company and an opportunity to show our customers that we understand and are responding to their evolving skincare needs, Connie Lo, Three Ships Co-Founder, tells the press.

We invite anyone, adds Lo,interested in a more revitalized complexion to try our products and embark on their journey to better skin.

Connie Lo and Laura Burget founded NIU Body in early 2017 as an unpretentious, clean, and affordable skin care brand for their fellow millennials. We aspire to be an approachable option without the fancy fluff, at affordable prices so everyone can enjoy everything green beauty has to offer. Our products are simple in both design and formulation, explained Burget in her 2018 Indie Beauty Profile.

And those core brand qualities havent changed now that NIU Body is Three Ships: While our look has changed, says Burget in a press release shared with Cosmetics Design, we remain meticulous in our approach to sourcing sustainable ingredients and creating formulations that provide tangible benefits.

Our philosophy, she says,has and always will be to be the change we want to see in the beauty industry: natural, effective and affordable skincare with a conscience.

As with any thorough rebrand, the change from NIU Body to Three Ships is about more than just a new name. As the brand explains in a recent LinkedIn update, It really was a culmination of how we felt about our years-long journey discovering affordable skincare ingredients that actually worked for us. The destination always seems further than it appears, but as we journey towards it, we start to see the full picture. Three Ships is about the journey to better skin.

The brand has new packaging and labeling, based primarily on consumer feedback. And now the brands portfolio is full of skin care product names that highlight key ingredients and benefits, such as Clarify Tea Tree + MCT Cleansing Oil, Hydrate 49% Almond Oil Serum, and Awake Rose Hydrosol Toner.

In conjunction with the rebranding, Three Ships also launched a new day cream. The Radiance Grape Stem Cell + Squalene Day Cream is, according to the brands press release, a highly-requested product formulated with revolutionary grape stem cells to protect from UV damage throughout the day and fight photo-aging. Hydrating prickly pear and argan oils along with natural squalene lock in moisture leaving skin soft and radiant.

Radiance is made for all skin types to help even and balance skin tone. It's also packaged in an airless pump top jar, which prevents air exposure and helps protect the cream, increasing the shelf life naturally, notes the release.

Follow this link:
The NIU BODY Rebrand: millennials have grown up and so has their skin care - CosmeticsDesign.com USA

Recommendation and review posted by Bethany Smith

After months of reviewing close to 300 beauty products and wellness facilities, and tallying, here are the best skincare products of this year, and lest we forget, your top pick! And so without further ado, here are the Beauty & Wellness Awards winners.

As technology continues to advance and discoveries are made each day,we do our part in dipping our toe in the proverbial pool of beauty toexplore the latest and greatest. Embracing the new is part of our job asinvestigative beauty aficionados, and as we dig through the recentdebuts, weve found some newbies that have found a permanent spot onour top shelf that we highly recommend checking out.

1

Best Face Cream: First Aid Beauty Ultra Repair Cream

For even the most sensitive skin, FAB delivers animpressive amount of hydration without anyirritation. The luscious whipped-cream texturespreads easily over the face, yet still holds wellenough for make-up to sit over nicely.

Ultra Repair Cream

HK$249/170g; HK$109/56.7G

2

Best Hydrating Serum: Skin Need 100% Hyaluronic Acid B5

The ultimate water magnet, thisserum locks in all the hydration youneed. Its easily absorbed, so yourskin feels fresh and clean without atrace of stickiness. The heavy doseof hyaluronic acid binds and trapsmoisture to the skin.

100% Hyaluronic Acid B5

HK$598

3

Best Reparative Formula: Wildsmith Skin Active Repair Radiance Polisher

Exfoliate to your hearts content and skinsneed the gentle grains of walnut shell androsehip-seed powder sloughs away deadskin cells and polishes the skins surface. Mixthe desired amount with any facial cleanserto create your very own scrub.

Skin Active Repair Radiance Polisher

HK$254

4

Best Body Cream: Augustinus Bader The Body Cream

A fresh launch from world-leadingstem cell and biomedical pioneerand scientist, Professor AugustinusBader, The Body Cream is officiallythe newest must-have item in bodyand skin care. Powered by thebrands patented Trigger FactorComplex (TFC8), this cellularrenewal cream reawakens dormantstem cells and results in firmer,toned skin with a reduction incellulite and stretch marks.

5

Readers Choice: Drunk Elephant F-balm

Electrolytes pump us full of hydration. And if its good to ingest. Why wouldnt it be topically? This waterfacial masque hydratant nourishes and repairs parched skin while you sleep. Its cooling effects are especially appreciated this season.

All of the Drunk Elephant products are naturally formulated and cater directly to your skins health. Oi Tak Kan, Prestige Reader

Original post:
Beauty & Wellness Awards 2020: New Kids on the Block - Prestige Online

Recommendation and review posted by Bethany Smith

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Excerpt from:
Going On At The Greenville Library - WSPA 7News

Recommendation and review posted by Bethany Smith