A Cuba and Thailand joint venture will soon start manufacturing cancer drugs, the Cuban media reported this Friday.

The enterprise is formed by the Thai pharmaceutical company Siam Bioscience (SBS) and the Cuban medicine industry and its operations will be initiated in the Association of South East Asian Nations (ASEAN), according to the official newspaper Granma, which quoted a tweet from Eduardo Ojito, director of Cubas Center for Molecular Immunology (CIM).

The publication affirms that the company emerged in 2017 to produce world-class drugs for complicated diseases, whereby the Thai SBS and the Cuban CIM agreed to jointly develop monoclonal antibodies to treat cancer and autoimmune diseases.

Songpon Deechongkit, general director of Siam Bioscience Group, to which SBS belongs, assured the Bangkok Post that by 2022 the enterprise plans to produce and sell three new drugs for cancer, kidney failure and autoimmune diseases, both in Thailand and abroad.

For his part, Agustn Lage Dvila, general director of CIM, told the publication itself that the agreement will help SBS produce other medicines when its patent expires, through the skills created in it.

Dos nuevos medicamentos para el cncer dan buenos resultados

The Thai pharmaceutical giant, according to the source, has as its main objective to reduce the costs of medicines with respect to imported products and seeks to reduce dependence on active ingredients and foreign components.

SBS has previously developed medications such as erythropoietin for patients with chronic renal failure and filgrastim for cancer patients receiving chemotherapy. Its operations have crossed Thailands borders to include ASEAN countries.

Established in 2009, Siam Bioscience has the mission of supporting and enhancing the countrys medical system and improving Thais quality of life, an objective that will now be extended to other ASEAN countries, which also include Indonesia, Malaysia Singapore and the Philippines.

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Cuba and Thailand joint venture to manufacture cancer drugs - OnCubaNews

Embryology

Incubation and Embryology Program – The Batavian

February 23, 2020 medical

February 22, 2020 - 12:43pm

Press release:

Registration is now open for the 2020 Genesee County Incubation and Embryology Program.

The program is open to classrooms and school groups throughout Genesee County.

Students and teachers that participate in this hands-on program will learn all about the process of hatching a chick.

To register or receive more information, please contact the Genesee County 4-H Office at[emailprotected]or (585) 343-3040, ext. 101.

More information about the program is also available here.

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Incubation and Embryology Program - The Batavian

Cell Biology

Researchers discover glial cells that control stress response, extend lifespan in worms – News-Medical.net

February 23, 2020 medical

While many of us worry about proteins aggregating in our brains as we age and potentially causing Alzheimer's disease or other types of neurodegeneration, we may not realize that some of the same proteins are aggregating in our muscles, setting us up for muscle atrophy in old age.

University of California, Berkeley, scientists have now found brain cells that help clean up these tangles and prolong life -- at least in worms (Caenorhabditis elegans) and possibly mice. This could lead to drugs that improve muscle health or extend a healthy human lifespan.

The research team's most recent discovery, published Jan. 24 in the journal Science, is that a mere four glial cells in the worm's brain control the stress response in cells throughout its body and increase the worm's lifespan by 75%. That was a surprise, since glial cells are often dismissed as mere support cells for the neurons that do the brain's real work, like learning and memory.

This finding follows a 2013 study in which the UC Berkeley group reported that neurons help regulate the stress response in peripheral cells, though in a different way than glial cells, and lengthen a worm's life by about 25%. In mice, boosting neuronal regulation increases lifespan by about 10%.

Together, these results paint a picture of the brain's two-pronged approach to keeping the body's cells healthy. When the brain senses a stressful environment -- invading bacteria or viruses, for example -- a subset of neurons sends electrical signals to peripheral cells to get them mobilized to respond to the stress, such as through breaking up tangles, boosting protein production and mobilizing stored fat. But because electrical signals produce only a short-lived response, the glial cells kick in to send out a long-lasting hormone, so far unidentified, that maintains a long-term, anti-stress response.

"We have been discovering that if we turn on these responses in the brain, they communicate to the periphery to protect the whole organism from the age onset decline that naturally happens. It rewires their metabolism, it also protects against protein aggregation," said Andrew Dillin, UC Berkeley professor of molecular and cell biology and Howard Hughes Medical Institute (HHMI) investigator. As a result of the new study, "We think that glia are going to be more important than neurons."

While the roundworm C. elegans is a long way evolutionarily from humans, the fact that glial cells seem to have a similar effect in mice suggests that the same may be true of humans. If so, it may lead to drugs that combat muscle wasting and obesity and perhaps increase a healthy lifespan.

If you look at humans with sarcopenia or at older mice and humans, they have protein aggregates in their muscle. If we can find this hormone, perhaps it can keep muscle mass higher in older people. There is a huge opportunity here."

Andrew Dillin, UC Berkeley professor of molecular and cell biology and Howard Hughes Medical Institute (HHMI) investigator

In a commentary in the same Jan. 24 issue of Science, two Stanford University scientists, Jason Wayne Miklas and Anne Brunet, echoed that potential. "Understanding how glial cells respond to stress and what neuropeptides they secrete may help identify specific therapeutic interventions to maintain or rebalance these pathways during aging and age-related diseases," they wrote.

Dillin studies the seemingly simultaneous deterioration of cells throughout the body as it ages into death. He has shown in worms and mice that hormones and neurotransmitters released by the brain keep this breakdown in check by activating a stress response in the body's cells and tuning up their metabolism. The response likely originated to fight infection, with the side effect of keeping tissues healthy and extending lifespan. Why our cells stop responding to these signals as we age is the big question.

Over the past decade, he and his colleagues have identified three techniques used by worms to keep their cells healthy and, consequently, longer-lived. Activating the body's heat shock response, for example, protects the cytoplasm of the cell. Stimulating the unfolded protein response protects the cells' energy producing structures, the mitochondria. The unfolded protein response is the cell's way of making sure proteins assume their proper 3D structure, which is crucial for proper functioning inside the cell.

His latest discovery is that glia, as well as neurons, stimulate the unfolded protein response in the endoplasmic reticulum (ER). The ER is the cellular structure that hosts the ribosomes that make proteins -- the ER is estimated to be responsible for the folding and maturation of as many as 13 million proteins per minute.

"A lot of the work we have done has uncovered that certain parts of the brain control the aging of the rest of the animal, in organisms from worms to mice and probably humans," Dillin said.

Two other interventions also increase lifespan in worms: diet restriction, which may call into play other anti-aging mechanisms, and reducing the production of a hormone called insulin-like growth factor (IGF-1).

Dillin's discoveries have already led to new treatments for diseases. He cofounded a company, Mitobridge Inc. (recently acquired by Astellas Pharma Inc.), based on the finding that certain proteins help tune up mitochondria. A drug the company developed is now in phase II clinical trials for treating the damage that occurs when kidneys restart after sudden failure, such as during an operation.

He cofounded another company, Proteostatis Therapeutics, to develop a treatment for cystic fibrosis that is based on activating the unfolded protein response to repair ion channels in people with the disease.

The new discovery about how neurotransmitter and hormones impact the ER could have implications for diseases that involve muscle wasting, such as Huntington's disease and forms of myocytis.

In 2013, Dillin and his colleagues discovered that boosting expression of a protein called xbp-1s in sensory nerve cells in the worm brain boosts the misfolded protein response throughout the worm's body. Shortly afterward, postdoctoral fellow Ashley Frakes decided to see if the glial cells enshrouding these neurons were also involved. When she overexpressed the same protein, xbp-1s, in a subset of these glia (cephalic astrocyte-like sheath glia, or CEPsh), she discovered an even larger effect on peripheral cells, as measured by how they deal with a high-fat diet.

Frakes was able to pinpoint the four CEPsh glia responsible for triggering the ER response, because the C. elegans body is so well studied. There are only 959 cells in the entire worm, 302 of which are nerve cells, and 56 are glial cells.

The CEP neurons and CEPsh glia work differently, but additively, to improve metabolism and clean up protein aggregates as the worms slim down and live twice as long as worms without this protection from a high-fat diet.

"The fact that just a few cells control the entire organism's future is mind-boggling," Dillin said. "Glia work 10 times better than neurons in promoting this response and about twice as good in extending lifespan."

Frakes is currently trying to identify the signaling hormone produced by these glial cells, a first step toward finding a way to activate the response in cells that are declining in function and perhaps to create a drug to tune up human cells and stave off the effects of aging, obesity or other types of stress.

Frakes also found that the worms slimmed down because their fat stores, in the form of lipid droplets, were turned into ER. Another research group in Texas has shown that activating xbp-1s in the neurons of mice also has the effect of reducing fat stores and slimming the mice, protecting them from the effects of a high-fat diet and extending their lifespan.

"When they activate it in the neurons, they see the liver getting rid of fat, redistributing metabolic demands," Dillin said. "I think we would see the same thing in humans, as well."

Source:

Journal reference:

Frakes, A.E., et al. (2020) Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans. Science. doi.org/10.1126/science.aaz6896.

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Researchers discover glial cells that control stress response, extend lifespan in worms - News-Medical.net

Cell Biology

Harmful levels of metal linked to DNA damage found in the urine of e-cigarette users – News-Medical.net

February 23, 2020 medical

Researchers at the University of California, Riverside, have completed a cross-sectional human study that compares biomarkers and metal concentrations in the urine of e-cigarette users, nonsmokers, and cigarette smokers.

They found that the biomarkers, which reflect exposure, effect, and potential harm, are both elevated in e-cigarette users compared to the other groups and linked to metal exposure and oxidative DNA damage.

Our study found e-cigarette users are exposed to increased concentrations of potentially harmful levels of metals -- especially zinc -- that are correlated to elevated oxidative DNA damage."

Prue Talbot, professor of cell biology, University of California, Riverside

Zinc, a dietary nutrient, plays key roles in growth, immune function, and wound healing. Too little of this essential trace element can cause death; too much of it can cause disease. Its deficiency, as well as its excess, cause cellular oxidative stress, which, if unchecked, can lead to diseases such as atherosclerosis, coronary heart disease, pulmonary fibrosis, acute lymphoblastic leukemia, and lung cancer.

Electronic cigarettes consist of a battery, atomizing unit, and refill fluid. Metals in e-cigarette aerosols come mainly from the metal components in the atomizer-- nichrome wire, tin solder joints, brass clamps, insulating sheaths, and wicks -- as well as the e-fluids that the atomizers heat.

The study, which appears in BMJ Open Respiratory Research, marks the first time researchers have examined and quantified urinary biomarkers of effect and potential harm in relation to metals in e-cigarette users.

A biomarker is a quantifiable characteristic of a biological process. Biomarkers allow researchers and physicians to measure a biological or chemical substance that is indicative of a person's physiological state. Previous e-cigarette studies with humans have examined biomarkers of exposure -- for example, nicotine or nicotine metabolites -- but none have studied biomarkers of potential harm or shown how this harm correlates with metal exposure.

The biomarkers studied by the UC Riverside researchers were 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage; 8-isoprostane, an indicator of the oxidative degradation of lipids; and metallothionein, a metal response protein. All three biomarkers were significantly elevated in e-cigarette users compared to the concentrations in cigarette smokers.

"Our findings reaffirm that e-cigarette use is not harm free," said Shane Sakamaki-Ching, a graduate student in the Cell, Molecular and Developmental Biology Graduate Program and the research paper's first author. "Indeed, prolonged use may lead to disease progression."

The researchers advise physicians to exercise caution when recommending e-cigarettes to their patients. Electronic cigarette aerosols contain potentially harmful chemicals, cytotoxic flavor chemicals, metals, ultrafine particles, and reaction products. E-cigarette use has been linked to adverse health effects such as respiratory diseases, increased risk for cardiovascular disease, and impaired wound healing following surgery.

"Pregnant women, especially, should not be encouraged to use e-cigarettes," Talbot said. "Excess of zinc in their bodies can lead to nausea and diarrhea. Given the recent deaths and pulmonary illnesses related to e-cigarette usage, everyone should be made aware of the potential health risks linked to e-cigarette usage."

Source:

Journal reference:

Sakamaki-Ching, S., et al. (2020) Correlation between biomarkers of exposure, effect and potential harm in the urine of electronic cigarette users. BMJ Open Respiratory Research. doi.org/10.1136/bmjresp-2019-000452.

Cell Biology

MIT Chemist Investigates How Diseases Are Linked to Flawed Protein Folding – SciTechDaily

February 23, 2020 medical

When proteins are first made in our cells, they often exist as floppy chains until specialized cellular machinery helps them fold into the right shapes. Only after achieving this correct structure can most proteins perform their biological functions.

Many diseases, including genetic disorders like cystic fibrosis and brittle bone disease, and neurodegenerative diseases like Alzheimers, are linked to defects in this protein folding process. Matt Shoulders, a recently tenured associate professor in the Department of Chemistry, is trying to understand how protein folding happens in human cells and how it goes wrong, in hopes of finding ways to prevent diseases linked to protein misfolding.

In the human cell, there are tens of thousands of proteins. The vast majority of proteins must eventually attain some well-defined three-dimensional structure to carry out their functions, Shoulders says. Protein misfolding and protein aggregation happen a lot, even in healthy cells. My research groups interest is in how cells get proteins folded into a functional conformation, in the right place and at the right time, so they can stay healthy.

In his lab at MIT, Shoulders uses a variety of techniques to study the proteostasis network, which comprises about a thousand components that cooperate to enable cells to maintain proteins in the right conformations.

Proteostasis is exceedingly important. If it breaks down, you get disease, he says. Theres this whole system in cells that helps client proteins get to the shapes they need to get to, and if folding fails the system responds to try and address the problem. If it cant be solved, the network actively works to dispose of misfolded or aggregated client proteins.

Growing up in the Appalachian Mountains, Shoulders was homeschooled by his mother, along with his five siblings. The family lived on a small farm near Blacksburg, Virginia, where his father was an accounting professor at Virginia Tech. Shoulders credits his grandfather, a chemistry professor at Ohio Northern University and Alice Lloyd College, with kindling his interest in chemistry.

My family had a policy that the kids helped clean up the kitchen after dinner. I hated doing it, he recalls. Fortunately for me, there was one exception: If we had company, and if you were in an adult conversation with the company, you could get out of cleaning the kitchen. So I spent many hours, starting at the age of 5 or 6, talking about chemistry with my grandfather after dinner.

Before starting college at nearby Virginia Tech, Shoulders spent a couple of years working as a carpenter.

Matthew Shoulders. Credit: Gretchen Ertl

Thats when I discovered that I really liked building things, he says. When I went to college I was thinking about fields to get into, and I realized chemistry was an opportunity to merge those two things that I had begun to find very exciting building things but also thinking at the molecular level. A big part of what chemists do is make things that have never been made before, by connecting atoms in different ways.

As an undergraduate, Shoulders worked in the lab of chemistry professor Felicia Etzkorn, devising ways to synthesize complex new molecules, including stable peptides that mimic protein functions. In graduate school at the University of Wisconsin, he worked with Professor Ronald Raines, who is now on the faculty at MIT. At Wisconsin, Shoulders began to study protein biophysics, with a focus on the physical and chemical factors that control which structure a given protein adopts and how stable the structure is.

For his graduate studies, Shoulders analyzed how proteins fold while in a solution in a test tube. Once he finished his PhD, he decided to delve into how proteins fold in their natural environment: living cells.

Experiments in test tubes are a great way to get some insight but, ultimately, we want to know how the biological system works, Shoulders says. To that end, he went to the Scripps Research Institute to do a postdoc with professors Jeffery Kelly and Luke Wiseman, who study diseases caused by protein misfolding.

Neurodegenerative diseases like Alzheimers and Parkinsons diseases are perhaps the best known protein misfolding disorders, but there are thousands of others, most of which affect smaller numbers of people. Kelly, Wiseman, and many others, including the late MIT biology professor Susan Lindquist, have shown that protein misfolding is linked to cellular signaling pathways involved in stress responses.

When protein folding goes awry, these signaling pathways recognize it and try to fix the problem. If they succeed, then all is well, but if they fail, that almost always leads to disease, Shoulders says.

Since joining the MIT faculty in 2012, Shoulders and his students have developed a number of chemical and genetic techniques for first perturbing different aspects of the proteostasis network and then observing how protein folding is affected.

In one major effort, Shoulders lab is exploring how cells fold collagen. Collagen, an important component of connective tissue, is the most abundant protein in the human body and, at more than 4,000 amino acids, is also quite large. There are as many as 50 different diseases linked to collagen misfolding, and most have no effective treatments, Shoulders says.

Another major area of interest is the evolution of proteins, especially viral proteins. Shoulders and his group have shown that flu viruses rapid evolution depends in part on their ability to hijack some components of the proteostasis network of the host cells they infect. Without this help, flu viruses cant adapt nearly as rapidly.

In the long term, Shoulders hopes that his research will help to identify possible new ways to treat diseases that arise from aberrant protein folding. In theory, restoring the function of a single protein involved in folding could help with a variety of diseases linked to misfolding.

You might not need one drug for each disease you might be able to develop one drug that treats many different diseases, he says. Its a little speculative right now. We still need to learn much more about the basics of proteostasis network function, but there is a lot of promise.

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MIT Chemist Investigates How Diseases Are Linked to Flawed Protein Folding - SciTechDaily

Cell Biology

These are 4 medical innovations coming out of Houston institutions – InnovationMap

February 23, 2020 medical

Houston home to one of the largest medical centers in the world isn't a stranger when it comes to medical innovations and breakthrough research discoveries.

In the latest roundup of research innovations, four Houston institutions are working on innovative and in some cases life-saving research projects.

If the germ,group A streptococcus, continues to grow resistant to antibiotics, it can have a profoundly negative affect on the millions who get the illness annually. Photo via houstonmethodist.org

Researchers at Houston Methodist have discovered some troubling information about the strains of group A streptococcus that cause strep throat and a flesh-eating disease are becoming more resistant to beta-lactams antibiotics like penicillin.

James M. Musser is the lead author of the study and chair of Methodist's Department of Pathology and Genomic Medicine. The study which received funding from grants from the Fondren Foundation, Houston Methodist Hospital and Houston Methodist Research Institute, and the National Institutes of Health appeared in the Jan. 29 issue of the Journal of Clinical Microbiology, according to a news release.

"If this germ becomes truly resistant to these antibiotics, it would have a very serious impact on millions of children around the world," Musser says in the release. "That is a very concerning but plausible notion based on our findings. Development of resistance to beta-lactam antibiotics would have a major public health impact globally."

Musser and his team found 7,025 group A streptococcus strains that have been recorded around the world over the past several decades. Of those strains, 2 percent had gene mutations that raised the alarm for the researchers and, upon investigation, Musser's team came to the conclusion that antibiotic treatments can eventually be less effective or even completely ineffective. This, Musser says, calls for an urgent need to develop a vaccine.

"We could be looking at a worldwide public health infectious disease problem," says Musser in the release. "When strep throat doesn't respond to frontline antibiotics such as penicillin, physicians must start prescribing second-line therapies, which may not be as effective against this organism."

University of Houston Professor Mehmet Orman is looking into cells that are able to persist and cause chronic illnesses. Photo via uh.edu

Mehmet Orman, assistant professor of chemical and biomolecular engineering at the University of Houston, is looking into a specific type of persister cells that have been found to be stubborn and drug-resistant.

The research, which is backed by a $1.9 million grant from the National Institute of Allergy and Infectious Diseases, could answer questions about chronic health issues like airway infections in cystic fibrosis patients, urinary tract infections, and tuberculosis, according to a news release.

"If we know how persister cells are formed, we can target their formation mechanisms to eliminate these dangerous cell types," says Orman in a news release.

Orman is looking into cells' self-digestion, or autophagy, process that is found to stimulate persister formation. Per the release, cells can survive periods of starvation by eating their own elements. Specifically, Orman will analyze self-digestion in E. coli.

"By integrating our expertise in bacterial cell biology with advanced current technologies, we aim to decipher the key components of this pathway to provide a clear and much-needed picture of bacterial self-digestion mechanisms," says Orman in the release.

Some patients are predisposed to kidney injury following surgery, this study found. Photo via bcm.edu

Scientists at Baylor College of Medicine are looking into the lead cause of kidney failure in patients who undergo surgery. Individuals who have heightened levels of suPAR protein soluble urokinase-type plasminogen activator receptor have a greater risk of this post-op complication, according to a news release.

"suPAR is a circulating protein that is released by inflammatory cells in the bone marrow and produced by a number of cell/organs in the body," says Dr. David Sheikh-Hamad, professor of medicine nephrology at Baylor College of Medicine and collaborating author of the study, in the release.

The study, which was published in The New England Journal of Medicine, conducted research on mice that were engineered to hive high suPAR levels in their blood. Compared to the control mice, the suPAR mice had more risk of kidney industry. These mice were given suPAR-blocking antibodies, which then helped reduce kidney injury.

"This protective strategy may be used in humans expressing high suPAR levels prior to contrast exposure, or surgery to decrease the likelihood of developing kidney failure," Sheikh-Hamad says in the release.

Christopher Fagundes of Rice University analyzed the emotions of 99 widows and widowers. Jeff Fitlow/Rice University

A new study done by researchers at Rice University finds that spouses that lose their husband or wife and try to suppress their grief are not doing themselves any favors. The study monitored 99 people who had recently lost a spouse, according to a news release.

"There has been work focused on the link between emotion regulation and health after romantic breakups, which shows that distracting oneself from thoughts of the loss may be helpful," says Christopher Fagundes, an associate professor of psychology and the principal investigator, in a news release. "However, the death of a spouse is a very different experience because neither person initiated the separation or can attempt to repair the relationship."

The study included asking participants to respond to how they felt about certain coping strategies, as well as blood tests to measure cytokines levels an inflammatory marker.

"Bodily inflammation is linked to a host of negative health conditions, including serious cardiovascular issues like stroke and heart attack," Fagundes says in the release.

The research, which was funded by a grant from the National Heart, Lung, and Blood Institute, found that the participants who avoided their emotions suffered more of this bodily inflammation.

"The research also suggests that not all coping strategies are created equal, and that some strategies can backfire and have harmful effects, especially in populations experiencing particularly intense emotions in the face of significant life stressors, such as losing a loved one," adss Richard Lopez, an assistant professor of psychology at Bard College and lead author of the study, in the release.

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These are 4 medical innovations coming out of Houston institutions - InnovationMap

Cell Biology

UAH research could have broad implications for immunotherapy and cancer treatment – News-Medical.net

February 23, 2020 medical

Research into engineering artificial organs that mimic the functions of human lymph nodes at The University of Alabama in Huntsville (UAH) has garnered one of its professors a $507,777 National Science Foundation (NSF) Faculty Early Career Development Program (CAREER) Award.

The award-winning research by Dr. Kyung-Ho Roh, a UAH assistant professor of chemical and materials engineering, could have broad implications for immunotherapy and cancer treatment. The NSF CAREER Award is the foundation's most prestigious honor for junior faculty members who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research.

When our body is infected with bacteria or viruses, some special immune cells are 'primed' within the lymph nodes to fight against these 'bugs'. More specifically, there are immune cells named B-cells that are responsible for producing a special set of molecules called antibodies that can recognize and bind to these 'bugs' so that our body can clear them out."

Dr. Kyung-Ho Roh, UAH assistant professor of chemical and materials engineering

The team at his Molecular and Cellular Immunoengineering Laboratory in the UAH Engineering Building is trying to achieve the priming of B-cells in an artificially created engineered system outside of the body.

"Once successful, this research can be useful for various critical biomedical applications," Dr. Roh says. "First, we can use such artificially primed B-cells as living therapeutics that can provide the useful antibodies for an extended period within the patient's body. Second, using the artificial lymph node, we can discover various antibody molecules that can recognize various pathogens or even our own cancers. Third, we can develop safer and cheaper vaccines. Lastly, the artificial system can be used as a critical research tool for studying the physiology of immune-cell related cancers such as lymphomas and leukemias."

Initial development of the hydrogels and microfluidic devices that are the basic foundation of the research project is complete. Now the project is moving forward to use and combine the individual engineering platforms to realize the collective system that can mimic the functions of the lymph nodes.

"For this project, we need a very diverse set of expertise spanning from biomaterials engineering and microfluidics to cellular and molecular biology and immunology," Dr. Roh says.

"For example, in order to mimic the mechanical properties of the physiological soft tissues we are developing novel biomaterials such as polymeric hydrogels," he says. "To culture the B-cells within a controlled chemical environment, we develop and utilize microfluidic devices. For the proper characterizations of the resulting B-cells, various methodologies from cellular and molecular biology are routinely employed."

In the lab, graduate students with diverse backgrounds are collaborating to tackle these challenging interdisciplinary research tasks. Dr. Roh's team is also collaborating with local and international partners such as the HudsonAlpha Institute for Biotechnology and CFD Research Corp.

"In addition to the research activities mentioned above, I will continue to improve my role as an educator. I will develop interdisciplinary educational curricula and continue to nurture the collaborative local networks that can provide a sustainable education and research environment for immunoengineering," Dr. Roh says.

He wants to encourage the participation of the next generation of students from broader socioeconomic groups of North Alabama and to enhance public knowledge of immunoengineering research activities and their applications.

"My primary goal as an educator is to train many undergraduate and graduate students in this highly multidisciplinary topic of immunoengineering to meet the increasing societal demands for such critical skill sets."

Dr. Roh says he received the news of his CAREER Award with a mixture of emotions.

"It was exciting because it assures me that I will be able to continue working on this very significant project and because this award in a way means that the research topics and ideas that we proposed to study are highly appreciated by the leaders in the field," he says. "And the name of the award, CAREER, made me look back and be grateful to everyone who has enabled me to become what I am in my career."

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UAH research could have broad implications for immunotherapy and cancer treatment - News-Medical.net

Biochemistry

Sleuths Uncover Web of Research Fraud in 400+ Papers From China – The Wire

February 23, 2020 medical

Elisabeth Bik, the microbiologist and research integrity consultant noted for unearthing evidence of research misconduct, tweeted on February 21that she and some others had uncovered over 400 scientific papers that all share a very similar title layout, graph layout, and (most importantly) the same Western blot layout indicating an organised web of potential fraud. She also expressed concern that there might be hundreds of papers more, and that she and her collaborators may just have spotted the obviously fraudulent ones.

Western blotting is a technique that microbiologists employ to identify the proteins present in a tissue sample. As an analytical technique involving real-world materials, no two images of western blots are supposed to look alike, and similarities suggest the image may have been manipulated, inadvertently or otherwise.

Guided by this and similar giveaways, Bik, @SmutClyde, @mortenoxe and @TigerBB8 (all Twitter handles of unidentified persons), report as written by Bik in ablog post that the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy-pasted from other sources or computer generated.

Bik also notes that most of the papers, though not all, were published in only six journals: Artificial Cells Nanomedicine and Biotechnology,Journal of Cellular Biochemistry,Biomedicine & Pharmacotherapy,Experimental and Molecular Pathology,Journal of Cellular Physiology, andCellular Physiology and Biochemistry, all maintained reputed publishers and importantly all of them peer-reviewed.

As a result, the discovery of the problem papers has prompted concerns about the ability of peer-review to check research misconduct in the scientific community.

Indeed, when Bik writes, Finding these fabricated images should not rely solely on the work of unpaid volunteers, she evidently means herself and her collaborators but her words also apply to peer-reviewers, who are unpaid for their work and often lack both the resources and the inclination to investigate each paper in close detail. As a result, peer-review is often not the insurmountable defence some proclaim it to be, nor are peer-reviewed journals as free of bogus science as they claim to be.

As Madhusudhan Raman, a postdoctoral scholar at the Tata Institute of Fundamental Research, Mumbai,wrote inThe Wire, any attempt to radically change the nature of peer-review must necessarily be accompanied by a change in the way the referees are compensated for their time and effort, especially within academia.

A PubPeer user who goes by Indigofera Tanganyikensis first identified the problem in two papers (thisandthis) both published by Chinese researchers. On February 17 this year, a little under a week before Bik published her blog post, two American researchers Jennifer A. Byrne and Jana Christopher published an articlediscussing similar research misconduct based on 17 papers they had discovered.

According to Bik, As it turns out, Byrne and Christophers publication describes the exact same set of papers that our small team of image forensics detectives had been working on in the past month.

These sleuths, as @SmutClydewrote on Leonid Schneiders blog, believe they have stumbled upon at least one paper mill. To quote (selectively) from Biks post,

A paper mill is a shady company that produces scientific papers on demand. They sell these papers to [people] who do not have any time in their educational program to actually do research. Authorships on ready-to-submit or already-accepted papers are sold to medical students for hefty amounts. Whether or not the experiments described in these papers has actually been performed is not clear. Some of these paper mills might have laboratories producing actual images or results, but such images might be sold to multiple authors to represent different experiments. Thus, the data included in these papers is often falsified or fabricated.

The mills seem to have been hired by Chinese clinicians affiliated to various medical colleges and hospitals in China (234 of the 400+ papers have been authored by people affiliated to institutions in Shandong province). The papers were all published between 2016 and 2020. @SmutClyde wrote that after they publicised their findings, including thedataset of papers they had identified as potentially fraudulent (and which they continue to update), an author of one of the papers wrote in:

Being as low as grains of dust of the world, countless junior doctors, including those younger [than] me, look down upon the act of faking papers. But the system in China is just like that, you cant really fight against it. Without papers, you dont get promotion; without a promotion, you can hardly feed your family. I also want to have some time to do scientific research, but its impossible. During the day, I have outpatient surgeries; after work, I have to take care of my kids. I have only a little bit time to myself after 10 pm, but this is far from being enough because scientific research demands big trunks of time. The current environment in China is like that.

Considering how the peer-review of all of those journals have failed, what the detectives have found effectively represents a large volume of unscientific data entering the scientific literature, funnelled predominantly by Chinese researchers who probably hired a paper mill to help meet the publishing requirements set by their respective institutions. Bik wrote that it is of great concern to see that this specific paper mill has successfully infected particular journals and that it is very alarming to see that journal editors do not appear to have noticed the similarities between dozens of papers published in their journals.

This said, the note from the unnamed Chinese author indicates the source of the problem is hardly new or even confined to China.

For example, until Prakash Javadekar, then the Union human resource development minister, said in mid-2017 that college teachers would not be required to undertake research to qualify for promotions, people who had not trained for research and have since been embedded in environments not properly equipped to support research were forced to conduct research, and publish papers.

Javadekar is to be loudly applauded and congratulated for taking this measure,Pushkar wrote forThe Wireat the time. The research requirement in the [Academic Performance Indicators] for college teachers was a travesty. All that it achieved was a proliferation of fake journals for college teachers to publish in.

Indeed, India has come to be known the fake journals capital of the world, partly as a result of requiring people who cannot undertake research to undertake research, and partly because research productivity has become one of the core measures of determining whether a country is a scientific superpower.

For another example, the journalNaturereportedthat Pakistans research output increased the most among all countries in the world by 21% in 2018, a feat that it dubbed a phenomenal success. However, as Anjum Altaf, former provost of Karachis Habib University and a famous teacher, subsequentlytoldThe Wire, The volume of third-rate publications in Pakistan has increased greatly simply because [Pakistans Higher Education Commission] introduced a tenure-track system and required publications for promotion.

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Sleuths Uncover Web of Research Fraud in 400+ Papers From China - The Wire

Genetics

Dr. Y. Edward ‘Ted’ Hsia is remembered as ‘father of medical genetics in Hawaii’ – Honolulu Star-Advertiser

February 23, 2020 medical

Dr. Yujen Edward Ted Hsia, a pioneer in medical genetics at the University of Hawaii who shepherded his patients and students through that challenging field with warmth and grace, has died at age 88.

Ted had an uncanny ability to praise, scold and teach in one sentence all with a smile on his face, said Janet Berg, a genetic metabolic nurse who was one of his protegees. He was passionate about his patients and his colleagues and treated us all as family.

Hsia suffered a brain bleed and fall Feb. 11 at his residence in Arcadia, where he had moved a few months ago, according to Duncan Hsia, one of his five sons.

He is definitely the father of genetics in Hawaii, said Dr. Laurie Seaver, a geneticist and former colleague. He essentially built the clinical genetics program at Kapiolani (Medical Center). He was as smart as anyone I have ever known.

Medical genetics involves diagnosing, treating and managing hereditary and metabolic disorders, from birth defects to genetic diseases.

Each patient that came to him was like a puzzle, and he was trying to put all the pieces together to figure out what was going on with them, Berg said. He was never afraid to try something new.

Its body, mind and spirit he told me that all the time, she added. We can do the science all we want, but if the rest isnt OK, we are not going to get very far.

Born in Shanghai on Nov. 24, 1931, Hsia was educated in England, earning his undergraduate and medical degrees from Oxford University. He taught genetics at Yale University for a decade before joining the University of Hawaii, where he was a professor of genetics and pediatrics.

He started and ran the medical genetics program in Hawaii from 1977 to 1998, teaching genetics to all the medical students and also treating and counseling many children and their families, Duncan Hsia said.

Ted Hsia helped launch Hawaii Community Genetics, a clinical collaboration among Kapiolani Medical Center, the Department of Health and the UH Medical School.

In retirement, Hsia shared his expertise with an eager set of learners often overlooked by society: the inmates at the Womens Community Correctional Facility.

For 18 years he visited the prison weekly, helping the women understand issues such as the genetic components of disease, from cancer to bipolar disorder, as part of the Total Life Recovery Program.

He was super dedicated, said Tammy Turcios, chaplain and director of that program. Even up to the last week before he passed away, he was trucking on up that hill.

He taught them about what drugs do to their brain, about any kind of disease, she said. He always came prepared with a lesson that captivated the women. They just loved his class.

His son Duncan said his personality as well as his intelligence set him apart: He was always smiling and so friendly and generous.

As word spread of his death, former patients weighed in with social media posts. Im alive because of him, wrote Jason Taylan.

Hsias faith anchored his life. He and his late wife, Juliet, a pioneering genetics counselor herself, joined Calvary-by-the-Sea Lutheran Church when they arrived in Honolulu. He gave keiki talks at services, calling children to the front of the sanctuary and offering lessons for them and the congregation.

A baritone, Hsia was a devoted member of the church choir, and he also performed with the Honolulu Symphony Choir.

Everybody just loves his smile, said Gordon Hsia, his youngest son. The main reason why my father was smiling was that he always had faith with God in his heart. The balance of being a geneticist and having such a strong faith in the Lord is just amazing.

Seaver, who visited Hsia a few weeks ago from her home in Grand Rapids, Mich., said he was proud to tell her that his former students were now taking care of him as doctors.

His survivors include sons Martin, Calvin, Franklin, Duncan and Gordon; and 12 grandchildren.

A memorial service will be held Sunday at 4 p.m. at Calvary-by-the-Sea Lutheran Church. In lieu of flowers, donations may be made to the Ted & Juliet Hsia Foundation, 1177 Queen St. No. 2002, Honolulu 96814.

Correction: An earlier version of this article misstated the location of Dr. Laurie Seavers home.

Genetics

Seattle Genetics and Astellas’ Padcev Wins Breakthrough Therapy Designation in Bladder Cancer – BioSpace

February 23, 2020 medical

Bladder cancer drug Padcev, which was approved by the U.S. Food and Drug Administration in December, secured Breakthrough Therapy designation for the treatment of patients with another type of bladder cancer.

Seattle Genetics and Astellas Pharma, the co-developers of Padcev (enfortumab vedotin-ejfv) said the new designation was awarded to the bladder cancer drug in combination with Mercks checkpoint inhibitor Keytruda for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting. The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase Ib/II trial EV-103, evaluating patients in this setting with the combination treatment. The FDAs Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition.

Initial results from the trial were presented at the European Society of Medical Oncology 2019 Congress, and updated findings at the 2020 Genitourinary Cancers Symposium. The data from the trial demonstrated the combination of Padcev and Keytruda shrank tumors in the majority of patients, resulting in a confirmed objective response rate of 73.3%. Responses included 15.6% of patients who had a complete response and 57.8% of patients who had a partial response. The median progression-free survival was 12.3 months and the 12-month overall survival rate was 81.6%, the companies announced at the 2020 symposium.

Padcev is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancers.

Andrew Krivoshik, Oncology Therapeutic Area Head at Astellas, said the Breakthrough Therapy designation awarded to the combination treatment reflects the encouraging preliminary evidence of Padcev and Keytruda in this bladder cancer indication. Krivoshik said the research teams are progressing their clinical development program as quickly as possible in hopes of providing another treatment possibility for patients who are in need of effective treatment options.

This is an important step in our investigation of PADCEV in combination with pembrolizumab as a first-line therapy for patients with advanced urothelial cancer who are unable to receive cisplatin-based chemotherapy, Roger Dansey, Chief Medical Officer at Seattle Genetics said in a statement. Based on encouraging early clinical activity, we recently initiated a phase 3 trial of this platinum-free combination and look forward to potentially addressing an unmet need for patients.

It is estimated that approximately 81,000 people in the U.S. will be diagnosed with bladder cancer in 2020. Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra. The recommended first-line treatment for patients with advanced urothelial cancer is a cisplatin-based chemotherapy. However, fewer than half of patients respond to carboplatin-based regimens and outcomes are typically poorer compared to cisplatin-based regimens, the companies noted.

In December, the FDA approved Padcev for adult patients who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. It was approved under the FDAs Accelerated Review Program based on tumor response rate. Accelerated approval was granted after the companies released data from a pivotal Phase II trial in June that showed Padcev rapidly shrank tumors in most patients.

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Seattle Genetics and Astellas' Padcev Wins Breakthrough Therapy Designation in Bladder Cancer - BioSpace