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Irvine, Calif., June. 25, 2020 -- Researchers from the University of California, Irvine, in collaboration with their colleagues from Beijing, China, have gained new insights into the development of poorly understood malignant skin cancers collectively known as Paget's disease. The team identified new biomarker genes that highly correlate with Paget's disease. The group then used a Food and Drug Administration (FDA) approved drug to target one of the newly identified molecular features of Paget's disease, leading to prominently improved clinical symptoms in a small cohort of Chinese patients. Their results have been published online in Cell Research.

"This is a prime example on how sophisticated computational analysis and interdisciplinary collaborations facilitate biomedical discoveries. Single-cell genomics is becoming a major emerging tool to delineate cellular and molecule machineries that encode diseases, and recently UCI has made tremendous stride in this fast-growing research area," said Qing Nie, a study co-author and Chancellor's Professor of mathematics and developmental & cell biology at UCI.

Paget's disease are rare skin cancers. At the cellular level, these cancers manifest themselves as having easily identifiable large, "clear"-looking cells, called Paget cells. The origin of these unique looking cancer cells is currently under debate, but their emergence in skin is a useful feature marker that helps with Paget's disease diagnosis.

Very little is known about the underlying workings of this disease, and unsurprisingly, there are no known drugs that can efficiently slow down or revert the condition. The primary approach to treating Paget's disease consists of trying to surgically remove it, or destroy it with chemotherapy, radiotherapy or laser ablation- approaches that are not very effective and associate with disease recurrence.

"Developing a new understanding of the 'molecular nature' of Paget's disease will undoubtedly uncover novel 'disease genes.' At least some of these genes might be targeted using medicines that are already FDA-approved for unrelated conditions. This approach could dramatically speed up the development time frame for Paget's disease medicines," said Maksim Plikus, study co-author and associate professor of developmental & cell biology at UCI.

To study how Paget's disease develops at the molecular level, the Beijing- and Irvine-based researchers comprehensively examined gene features of Paget's disease tissue samples from human patients using a new technique called single-cell RNA-sequencing. The technique allows for the identification of all extant cell types based on their unique genes. This helped the team identify previously unrecognized but prominent new disease biomarkers. One such biomarker was the gene called MSI1, or Musashi-1. Inside of cells, MSI1 binds to many RNA molecules, regulating how they encode diverse proteins.

Because studying the roles of new biomarker genes in humans has limitations, the team of researchers developed new transgenic mice, whose skin was made to have high amounts of MSI1, potentially imitating human Paget's disease. Strikingly, just after a few days, these mice developed prominent changes in their skin that closely resembled human Paget's disease, including the formation of large and "clear"-looking Paget-like cells. Further molecular studies with the new model uncovered many more previously unappreciated gene changes that are likely relevant to Paget's disease cancers in human patients.

Extrapolated from mutant mouse studies, the scientists identified one specific molecular change - highly overactive mTOR signaling, which stands for the mammalian target of rapamycin. Activation of mTOR has been previously and conclusively identified as a key molecular feature of other cancer types, including certain intestinal cancers.

Because mTOR is so involved in other diseases, FDA-approved drugs, such as rapamycin, currently exist which efficiently block mTOR signaling. Using this information, the researchers conducted a small-scale clinical study, in which Paget's disease patients were treated topically with rapamycin cream. A few weeks of rapamycin treatment lead to a clinically positive response in all enrolled patients, including a reduction on the number of Paget cells; thickness of epidermis in lesioned skin; as well as the morphology and organization of epidermis became normal. While this result is very preliminary and a larger-scale clinical study is clearly needed, it is nonetheless encouraging.

"We have made the exciting discovery of a new gene that drives the pathogenesis of Paget's disease. In the future, we want to further explore and uncover new gene regulators of MSI1 to better understand the upstream molecular drivers of this rare, yet debilitating disease," said Dr. Christian F. Guerrero-Juarez, co-first author of the article and Chancellor's ADVANCE Postdoctoral Fellow of mathematics and developmental & cell biology at UCI.

Climate change leads to longer growing seasons in the Arctic. A new study, which has just been published in Proceedings of the Royal Society B, show that predators like wolf spiders respond to the changing conditions and have been able to produce two clutches of offspring during the short Arctic summer.

Arctic spiders are at the top of the food chain among invertebrates and are numerous on the Arctic tundra. They typically take several years to become adults, and only produce offspring .

But something is happening in the high north in these years. A lot, actually.

Climate change is more dramatic here than in no other place on Earth. The average temperature is increasing significantly and this affects the ecosystems.

Researchers have previously reported how plants bloom earlier and earlier in the season. There are also signs that species move farther north and up into the mountains.

A team of researchers led by senior researcher Toke T. Høye from the Arctic Research Centre and Department of Bioscience at Aarhus University has now shown that changes are also occurring in the reproduction of invertebrates.

For almost 20 years, researchers at the Zackenberg Research Station in north-eastern Greenland have caught wolf spiders as part of the monitoring programme Greenland Ecosystem Monitoring. The spiders were caught in small pitfall traps set up in different vegetation types.

Wolf spiders carry their eggs in a so-called egg sac. The researchers counted the number of eggs in the individual spider's egg sacs and compared this information with the time of the season that the animal was caught. By looking at the distribution of the number of eggs in the egg sacs throughout the season, it became clear that in some summers the spiders produced two egg sacs - a phenomenon that is known from warmer latitudes, but which has not previously been observed in the Arctic.

Arctic ecosystems are changing

"We now have the longest time series of spiders collected the Arctic. The large amount of data allows us to show how small animals in the Arctic change their life history in response to climate change," says Toke T. Høye.

The long time series tells the researchers that the earlier the snow disappears from the ground, the greater the proportion of spiders that can produce a second clutch of offspring.

"These changes in the life history have not been seen earlier and evidence suggests that the phenomenon plays an important role for Arctic insects and spiders," Toke T. Høye says.

The researchers see the spiders' response to climate change as an ability to adapt to the new conditions.

Wolf spiders feed on small organisms such as springtails in the soil. If there are more spiders - or insects - in the future Arctic, it can have an influence on the food chains on land.

"We can only speculate about how the ecosystems change, but we can now ascertain that changes in the reproduction of species are an important factor to include when we try to understand how Arctic ecosystems react to the rising temperatures on the planet," Toke T. Høye says.

Led by the Ikerbasque professor Luis Liz-Marzán, researchers at the Centre for Cooperative Research in Biomaterials CIC biomaGUNE have developed a mechanism by which gold atoms are deposited by means of chemical reduction onto previously formed gold nanorods to produce a quasi-helicoidal structure (the particles acquire chirality). This geometry enables these "nanoscrews" to interact with circularly polarized light much more efficiently than what is achieved with any other known object. These properties could lead to the detecting of biomolecules in a very selective and very sensitive way. What we have here is a versatile, reproducible mechanism that is scalable for the fabrication of nanoparticles with strong chiral optical activity. This piece of research has been echoed by the prestigious scientific journal Science.

There are many fields in which the interaction between light and material is used to detect substances. Basically, light shines on the material and is absorbed or reflected either very brightly or very selectively, depending on the size and geometry of the particle and the type of incident light. The research group led by Luis Liz-Marzán, which works in the field known as nanoplasmonics, uses nanoparticles of noble metals, such as gold or silver, "because light interacts in a special way with particles of this type and size", explained Liz-Marzán, Scientific Director of CIC biomaGUNE. "In this case, we studied the interaction between these chiral gold nanoparticles and circularly polarized light."

Light is not normally polarized, in other words, the waves expand in practically any orientation within the beam of light. "When it is polarized, the wave only goes in one direction; when it is circularly polarized the wave rotates, either clockwise or anti-clockwise," added the researcher. "Chiral substances tend to absorb light with a specific circular polarization, rather than light polarized in the opposite direction."

Chirality is a phenomenon that occurs on all scales: a chiral object cannot have its mirror image superimposed on it; for example, one hand is the mirror image of the other, they are identical, but if one is superimposed on the other, the position of the fingers does not coincide. The same thing occurs "in some biomolecules; and the fact that a molecule cannot be superimposed on its mirror image gives rise to many biological processes. For example, some diseases arise due to the loss of recognition of one of the two forms of the chiral substance that is responsible for a specific action," said Liz-Marzán.

Three-dimensional fabrication onto a nanometric object

As the Ikerbasque professor explained, "what we have done is look for a mechanism to guide the deposition of gold atoms onto nanoparticles fabricated in advance in the form of a rod so that these atoms are deposited according to a practically helicoidal structure, a kind of 'nanoscrew'. That way the particle itself acquires a chiral geometry. This new strategy is based on a supramolecular chemical mechanism, in other words, on structures obtained through molecules associating with each other without forming chemical bonds". Liz-Marzán asserts that "this really means being able to control the structure of the material on a nanometric scale, but inside one and the same nanoparticle; in other words, it involves three-dimensional fabrication on top of a nanometric object. In actual fact, it is almost like deciding where they have to be positioned atom by atom to obtain a structure that is truly complicated".

To make these nanoparticles grow, "the cylindrical particles are surrounded by soap molecules, by a surfactant. In the middle of the ordinary soap molecules we have placed additives with molecular chirality, so that the supramolecular interaction causes them to become organised on the surface of the metal rod with an almost helicoidal structure, in turn guiding the growth of the metal with that same structure which gives it the chirality we are seeking. As a result, we can practically obtain the greatest efficiencies ever achieved in spectrometric detection with circularly polarized light".

Liz-Marzán confirmed that the process can be generalised to other types of materials: "We have seen that when the same strategy is applied, platinum atoms can be deposited onto gold nanorods with the same helicoidal structure. A whole host of possibilities is thus opened up both in applications of their optical properties and in others in the field of catalysis (platinum is a very efficient catalyst). At the same time, it could lead to a huge improvement in the synthesis of chiral molecules that would be of biological and therapeutic importance." This mechanism could also be applied to new biomedical imaging techniques, for the manufacture of sensors, etc. "We believe that this work is going to open up many paths for other researchers precisely because of the generalization of the mechanism that can be used with many different molecules. A lot of work lies ahead," he said.

The research was conducted and coordinated by CIC biomaGUNE, but they had the collaboration of research groups from other organisations. These include the Complutense University of Madrid (computer calculations showing the formation of the helicoidal structures when the two types of surfactants are blended), the University of Vigo and the University of Extremadura (theoretical calculations of the optical properties of the particles), and the University of Antwerp (obtaining of three-dimensional electron microscopy images and the animated reconstructions of the particles fabricated).

Mapping nano chirality in three dimensions

Essential to understanding the behaviour of these complex nanoparticle assemblies is to intimately understand their structure. When handling such intricate three-dimensional morphologies, imaging in two dimensions simply will not do. The EMAT team lead by Prof. Sara Bals at the University of Antwerp is the world leading electron microscopy group for imaging nanoparticles in three dimensions. By taking a series of two-dimensional images collected at many viewing angles they can be combined with specially designed computer code to generate a three-dimensional representation of the particle. This is the so-called transmission electron tomography method, which is an essential tool in nanoscience, helping researchers from around the world to visualize nanoparticles and understand their structure and how they are formed.

The EMAT team has gone one step further to understand the origin of the chiral properties these unprecedented nanorods display. By developing a method to study the three-dimensional periodicity of the individual particles using a 3D Fast Fourier Transform on the tomography previously obtained, repetitive patterns have been discovered in the structure. "The nanoparticles appeared to show a long-range chiral structure, but how can we identify this in a meaningful way to understand the nanoparticle's properties?"- asks Prof. Bals. By mapping the periodic structure using this technique, a characteristic X-shape appeared within the 3D FFT pattern. Scientists have seen this characteristic fingerprint before; in the revolutionary X-ray diffraction experiment leading to the discovery of the most known chiral structure - our DNA.

Using that characteristic pattern as an input, regions in the reconstruction with helicoidal features were identified. In addition, "Our developed technique not only allows us to identify a chiral structure, but can also tell us the chiral handedness of each individual nanoparticle" - says Prof. Bals.

The preparation and characterization of such complex chiral nanoparticles is an important step in reaching a key scientific milestone. It was once believed that the complexity of biological superstructures could not be artificially prepared. However, with increasing understanding of nanostructure design and growth, scientists can prepare atom-by-atom designed materials that are tailor-made for a desired application, and in doing so - continuously push the frontier of material design.

Scientists from the Center for Photonics and 2D Materials of the Moscow Institute of Physics and Technology (MIPT), the University of Oviedo, Donostia International Physics Center, and CIC nanoGUNE have proposed a new way to study the properties of individual organic molecules and nanolayers of molecules. The approach, described in Nanophotonics, relies on V-shaped graphene-metal film structures.

Nondestructive analysis of molecules via infrared spectroscopy is vital in many situations in organic and inorganic chemistry: for controlling gas concentrations, detecting polymer degradation, measuring alcohol content in the blood, etc. However, this simple method is not applicable to small numbers of molecules in a nanovolume. In their recent study, researchers from Russia and Spain propose a way to address this.

A key notion underlying the new technique is that of a plasmon. Broadly defined, it refers to an electron oscillation coupled to an electromagnetic wave. Propagating together, the two can be viewed as a quasiparticle.

The study considered plasmons in a wedge-shaped structure several dozen nanometers in size. One side of the wedge is a one-atom-thick layer of carbon atoms, known as graphene. It accommodates plasmons propagating along the sheet, with oscillating charges in the form of Dirac electrons or holes. The other side of the V-shaped structure is a gold or other electrically conductive metal film that runs nearly parallel to the graphene sheet. The space in between is filled with a tapering layer of dielectric material -- for example, boron nitride -- that is 2 nanometers thick at its narrowest (fig. 1).

Such a setup enables plasmon localization, or focusing. This refers to a process that converts regular plasmons into shorter-wavelength ones, called acoustic. As a plasmon propagates along graphene, its field is forced into progressively smaller spaces in the tapering wedge. As a result, the wavelength becomes many times smaller and the field amplitude in the region between the metal and graphene gets amplified. In that manner, a regular plasmon gradually transforms into an acoustic one.

"It was previously known that polaritons and wave modes undergo such compression in tapering waveguides. We set out to examine this process specifically for graphene, but then went on to consider the possible applications of the graphene-metal system in terms of producing molecular spectra," said paper co-author Kirill Voronin from the MIPT Laboratory of Nanooptics and Plasmonics.

The team tested its idea on a molecule known as CBP, which is used in pharmaceutics and organic light emitting diodes. It is characterized by a prominent absorption peak at a wavelength of 6.9 micrometers. The study looked at the response of a layer of molecules, which was placed in the thin part of the wedge, between the metal and graphene. The molecular layer was as thin as 2 nanometers, or three orders of magnitude smaller than the wavelength of the laser exciting plasmons. Measuring such a low absorption of the molecules would be impossible using conventional spectroscopy.

In the setup proposed by the physicists, however, the field is localized in a much tighter space, enabling the team to focus on the sample so well as to register a response from several molecules or even a single large molecule such as DNA.

There are different ways to excite plasmons in graphene. The most efficient technique relies on a scattering-type scanning near-field microscope. Its needle is positioned close to graphene and irradiated with a focused light beam. Since the needle point is very small, it can excite waves with a very large wave vector -- and a small wavelength. Plasmons excited away from the tapered end of the wedge travel along graphene toward the molecules that are to be analyzed. After interacting with the molecules, the plasmons are reflected at the tapered end of the wedge and then scattered by the same needle that initially excited them, which thus doubles as a detector.

"We calculated the reflection coefficient, that is, the ratio of the reflected plasmon intensity to the intensity of the original laser radiation. The reflection coefficient clearly depends on frequency, and the maximum frequency coincides with the absorption peak of the molecules. It becomes apparent that the absorption is very weak -- about several percent -- in the case of regular graphene plasmons. When it comes to acoustic plasmons, the reflection coefficient is tens of percent lower. This means that the radiation is strongly absorbed in the small layer of molecules," adds the paper's co-author and MIPT visiting professor Alexey Nikitin, a researcher at Donostia International Physics Center, Spain.

After certain improvements to the technological processes involved, the scheme proposed by the Russian and Spanish researchers can be used as the basis for creating actual devices. According to the team, they would mainly be useful for investigating the properties of poorly studied organic compounds and for detecting known ones.

As a founding member, the Institute for Quality and Efficiency in Health Care (IQWiG) has been involved in EUnetHTA, a European network for Health Technology Assessment (HTA), since 2006. The European Union supports the network. Following the outbreak of the corona pandemic, the EU Directorate of Health called on the EUnetHTA partners to make a scientific commitment to combating the pandemic. Against this background, IQWiG has now supported the Health Agency of the Emilia Romagna region in Bologna in an initial assessment of coronavirus diagnostics. Initiator of the HTA report was the Italian partner organisation, which also defined the topic. A Welsh partner co-authored the report in addition to IQWiG.

Two types of Corona tests

RT-PCR test: Rapidly after the outbreak of the corona pandemic, researchers developed methods to detect the virus directly. For this purpose, a smear is taken from the mouth, nose or throat area and examined for genetic traces of the virus. This method is known under the abbreviation RT-PCR and has a high accuracy. However, a few days after infection the body reacts to the virus. If the body's immune defence fights and destroys the virus, it is difficult or impossible to detect it with the RT-PCR test. The RT-PCR test is not subject of the EUnetHTA report that has been published now.

Antibody test: This second type of coronavirus test measures the body's immune response. The antibodies produced by the body are detected - usually by measuring the immunoglobulins M and G. Since the body needs several days to produce a measurable immune response, antibody tests only react with a strong delay after an infection. Antibody tests for the coronavirus are therefore too slow to detect or rule out an acute infection when relevant symptoms occur. However, antibody tests can be used in field studies to determine the proportion of the population having undergone a coronavirus infection (seroprevalence).

Neither immunity nor non-infectivity can be reliably detected

Having analyzed a total of 40 studies worldwide, the authors of the EUnetHTA report conclude that antibody tests can detect a past infection with the SARS coronavirus 2. However, the accuracy of the tests is not yet sufficient. Above all, it is still questionable whether a positive test result can be interpreted as a sign of immunity against re-infection. Moreover, a positive test result after recovery from an infection is no reliable proof that the person can no longer transmit the virus to other people.

Using corona diagnostics correctly

Due to the urgency of the matter, the EUnetHTA report that is now available was drawn up unusually quickly (within 6 weeks). As new study results are to be expected almost weekly, the assessment of the antibody tests will presumably be updated in about 3 months - again under the leadership of the Health Agency in Bologna and with the support of IQWiG.

The report results shall help to ensure that coronavirus diagnostics are properly used and developed in Europe and worldwide. However, the current EUnetHTA report has no direct consequences for the question of whether coronavirus antibody tests in Germany are paid for by the statutory health insurance (Gesetzliche Krankenversicherung [GKV]). At present, the tests are available as a benefit of the GKV, but the necessity of testing must be justified in each individual case. A positive test result must be reported.

University of Connecticut researcher Dr. George Wu recently published a paper in the Journal of Gastroenterology and Hepatology outlining his successful experiment delivering mitochondria to liver cells.

This groundbreaking experiment marks the first time researchers have ever successfully introduced mitochondria into specific cells in living animals.

Mitochondria generate energy from the conversion of fatty acids and carbohydrates to carbon dioxide and water, powering cells throughout the body. There is a significant link between mitochondrial damage and various liver diseases. When mitochondria are damaged, they cannot provide the liver with enough energy to function normally. This results in liver cell death and liver failure.

Currently, the only treatment for liver failure is a complete organ transplant. Surgeons perform approximately 8,000 liver transplants per year in the United States, but because of a shortage of donor livers, thousands more people on the waitlist for a transplant will die before receiving one.

Using their knowledge of a well-characterized receptor on the liver, Wu and his team previously showed mitochondria can be coated with certain carrier proteins which lead the liver to recognize them and take them up. These proteins have exposed galactose, a kind of sugar, on their surface. The galactose acts as a signal for the liver to internalize that protein.

"We took advantage of a normal, natural mechanism," Wu says.

This paper finds that healthy mitochondrial complexes can be delivered to the livers of living rats through simple intravenous injection.

The team harvested mitochondria from mouse specimens. The mitochondria were mixed with a protein carrier and purified to form complexes which could be taken into the liver.

Along with the mitochondria, Wu injected a peptide which facilitated the release of the mitochondria once they reached the cells. This peptide allowed the mitochondria to be taken up into the liver cells' cytoplasm rather than digested, which is what the liver does to most molecules it internalizes.

"If you don't have that, mitochondria might be targeted to liver cells, but they would be destroyed," Wu says.

At the end of the experiment, Wu and his colleagues found approximately 27% of the total injected mitochondria were detected in the liver, a significant proportion for therapeutic use.

Less than 2% were found in the spleen and less than 1% in the lungs, suggesting the uptake was not random and evenly distributed throughout all organs. In other words, the researchers were successful in creating a protein coating that made mitochondria specifically identifiable and internalized by the liver.

The achievement was far from a foregone conclusion, since mitochondria do not normally travel through the blood stream. The many potentially lethal obstacles made it a harrowing journey to the liver by way of veins to the heart, the lungs, and finally through arteries to the liver and the rest of the body. The coated mitochondria were apparently able to survive contact with blood cells, blood proteins, narrow blood vessels, and potential attacks from the immune system.

"To me, it's rather amazing that we could detect any donor mitochondria at all," Wu says. "When you consider all the obstacles that could get in the way."

While this experiment only measured the short-term effects of mitochondrial transplant, there are potential long-term benefits.

Mitochondria have their own DNA and RNA, meaning they can reproduce independently of the rest of the cell. The transplanted mitochondria may replicate with the cells during cell division.

All cells have a certain number of mitochondria they need to sustain their activities. Wu speculates that cells may gradually eliminate the damaged mitochondria as the healthy, donor mitochondria increase in number until they have the proper number of healthy mitochondria.

The next step for this research is to test the method with rats who have mitochondrial liver damage. This will display clinical relevance for potentially developing this technique for treatment of liver diseases.

This process has the potential to address a serious gap in treatment for liver diseases. It may even eventually be used to treat other maladies throughout the body affected by mitochondrial malfunction or damage.

Wu is now working with UConn's tech transfer group and has been issued a patent on targeted transplantation of mitochondria to hepatocytes. The University has filed patent protection on the proof of principle in animals. For more information about this technology for partnering and/or licensing contact Ana Fidantsef (fidantsef@uchc.edu).

A team of international researchers has learned that dose escalation of hydroxyurea treatment for children in Uganda with sickle cell anemia is more effective and has similar side effects than a lower fixed dose of the same drug.

The study, known as NOHARM MTD (Novel use Of Hydroxyurea in an African Region with Malaria - Maximum Tolerated Dose), focused on children in Uganda, but the results could impact use of hydroxyurea worldwide, including the United States and Europe. The findings are being published in the June 25 issue of the New England Journal of Medicine.

This clinical research milestone removes a major barrier to broadly expand the use of hydroxyurea in low-resource regions like sub-Saharan Africa, according to the physicians who led the study at Makerere University in Kampala, Uganda, Cincinnati Children's Hospital Medical Center, and the Indiana University (IU) School of Medicine.

For this study, 187 children with sickle cell anemia living in Uganda received hydroxyurea. About half received a fixed-dose of 20 mg per kilogram of body weight per day. The other half received an escalating dose, which started at 25 mg per kilogram of body weight per day and increased up to 35 mg per kilogram of body weight per day, if tolerated. Doctors evaluated the children every 2-3 months for laboratory and clinical benefits, as well as potential side effects.

While the study team was planning to keep the children on these separate treatment arms for two years, an independent data review panel changed the course about 18 months into the study, due to clear benefits of the higher dose.

"Our study's data safety and monitoring board noted a highly significant difference between the treatment groups, with the children on escalated dosing having superior clinical results, but the same number of side effects, so at their recommendation we halted the trial and moved all of the children to that escalated dosing strategy," said Robert Opoka, MMed, who oversaw the study at Makerere University and Mulago Hospital in Uganda.

Sickle cell anemia is a life-threatening blood disorder that distorts red blood cells into a sickle or crescent shape and leads to anemia, recurrent pain, organ damage, and early death. It is also a serious global health issue: in the United States, about 100,000 individuals are affected, but worldwide more than 300,000 children are born with the disease each year, with more than 80% born in sub-Saharan Africa. Yet most therapeutic developments for sickle cell have not been available to children in Africa, including hydroxyurea, which is FDA-approved and effectively reduces the acute and chronic disease manifestations.

Earlier studies in sub-Saharan Africa showed hydroxyurea to be safe, feasible to use, and effective for treating sickle cell anemia, according to Russell Ware, MD, PhD, a hematologist at Cincinnati Children's who led those studies and is senior investigator on the current NEJM paper. Ware said the drug boosts fetal hemoglobin, which reduces sickling of the red blood cells and improves anemia, lowers pain and other sickle-related events, and reduces clinical interventions such as transfusions and hospitalizations.

According to lead study co-investigator Chandy John, MD, a physician scientist at the Ryan White Center for Pediatric Infectious Diseases and Global Health at the IU School of Medicine, the optimal dosing and monitoring plan for hydroxyurea was unknown when the study started. Particularly for low-resource countries like Uganda, determining the hydroxyurea optimal dosing and monitoring plan was crucial.

John said the new study confirms that the dose escalation regimen is better than fixed dose, but expanding hydroxyurea treatment will require affordable drug costs, education of healthcare providers, and an increased drug supply. In addition, newborn screening for sickle cell anemia is needed to help identify those who will benefit from treatment as early as possible.

"There will be some additional costs associated with screening and increasing access to the drug, but they will be more than offset by benefits to patients," John explained. "Our data make it clear that children on a higher daily dose had substantially better clinical outcomes, with fewer adverse events."

"The study shows clearly that the optimized dosing strategy for hydroxyurea, though it requires more effort than a fixed-dose treatment regimen, results in far better outcomes for children with sickle cell anemia," Ware concluded. "We think this study can substantially benefit children with sickle cell anemia in Africa and throughout the world, by choosing the optimal hydroxyurea dose to decrease the disease complications."

"In Africa and other low-resource settings, children with sickle cell anemia have been a neglected population" said Opoka. "We are glad that our work together as African and US researchers has resulted in findings that will improve the health of all children with sickle cell anemia."

A group of scientists from Skoltech and Lomonosov Moscow State University (MSU) showed that nitrogen is not the only element that can help enhance the specific capacitance of supercapacitors.

The advancement of renewable energy sources calls for new materials with enhanced electrochemical performance. Electrodes in electrochemical current sources are most often made of carbon. The properties of carbons are improved using a whole panoply of surface modification techniques, such as adding metal oxides, creating multilayer coatings or expanding the specific surface area. Incorporating the doping atoms of nitrogen, fluorine, chlorine and other elements in the carbon lattice is a recent trend in surface modification that dramatically alters the material's electrochemical characteristics without "contaminating" the electrolyte solution during charging and discharging.

Earlier, Skoltech scientists showed that embedding nitrogen into the carbon lattice multiplies the electrochemical capacitance. Recently, the same team from the Skoltech Center for Design, Manufacturing and Materials (CDMM) and their colleagues from MSU have looked into the effect of nitrogen and oxygen heteroatoms on the material's electrochemical characteristics.

"We modified the carbon materials' surface using DC plasma in atmospheres of nitrogen, oxygen, and their mixture, so as to implant oxygen and nitrogen atoms in the carbon lattice. By changing the plasma contents, one can control surface functionalization," explains Stanislav Evlashin, the first author of the paper and a senior research scientist at Skoltech.

Modifying the carbon lattice by other atoms disrupts its structure and makes it less "perfect", which leads to a change in the electrochemical characteristics.

Electrochemical measurements in an acidic medium revealed the highest oxygen content and electrochemical capacitance in the samples modified in oxygen plasma. The results of the study suggest that nitrogen is not the only enhancer of the supercapacitors' specific capacitance and oxygen is sometimes even more effective. The scientists attribute the result both to surface functionalization (i.e. imparting new properties to the surface) and the changes in the crystal lattice. Unlike nitrogen, oxygen is much easier to insert in the crystal lattice.

The scientists' findings will contribute to the development of new generation supercapacitors.

The Kantor Center for the Study of Contemporary European Jewry at Tel Aviv University, published a special report, a summary of worldwide anti-Semitic phenomena associated with the COVID-19 pandemic. The report relies on hundreds of accounts from different locations around the globe from March-June.

The new wave of anti-Semitism includes a range of libels that have one common element: The Jews, the Zionists and/or the State of Israel are to blame for the pandemic and/or stand to gain from it.

The anti-Semitism generated by the coronavirus is intensive and fierce, has continued unremittingly for several months and reflects a high level of anxiety and fear in many populations.

Coronavirus-related anti-Semitism is manifested throughout Europe, in the Americas and in the Muslim world. This new type of anti-Semitism, which partly reiterates classic anti-Semitic themes, includes conspiracy theories alongside medieval blood libels, now renewed in a 21st century format.

Coronavirus-related anti-Semitism is propagated mostly by right-wing extremists, ultra-conservative Christians and Islamists, through their own media in various languages.

Islamists describe Israel as the COVID-1948 virus -- after the year in which the Jewish state was established, declaring that this is the most dangerous virus of all.

Activists in movements for delegitimizing Israel use the same argument. In addition, they accuse Israel of using the coronavirus as ammunition against the Palestinians.

An Oxford University study revealed that 19.1% of the British public believes that the Jews caused the pandemic.

The reports come from an international network of volunteers, living in 35 countries, who are trained to identify and classify acts of anti-Semitism and add the material to The Moshe Kantor Database on Anti-Semitism. The network was established by the Kantor Center over 30 years ago and today numbers 60 participants. The database is a real-time collection of materials and resources on trends and events related to contemporary anti-Semitism, which includes English summaries based on source materials in all languages and formats including texts, visuals and audiovisuals.

Professor Dina Porat, Head of the Kantor Center, says, "These common motifs perpetuate anti-Semitic accusations from previous generations and other global catastrophes, once again presenting the well-known image of the Jew. However, the anti-Semitism generated by the coronavirus is fiercer and more intensive, has continued unremittingly for several months, and reflects a high level of anxiety and fear in many populations. This having been said, the situation should be seen in its overall context -- in which others are also blamed for spreading the virus: first of all, the Chinese, 5G antennas and the authorities who allegedly are not doing enough to stop the epidemic. Countries close down their borders, every foreigner is a suspect, and no new immigrants are allowed."

Coronavirus-related anti-Semitism is manifested in many parts of the world: A significant portion comes from the US and from Middle Eastern countries such as Iran, Turkey and the Palestinian Authority, but also from Europe and South America. In the US, accusations come mainly from white supremacists and ultraconservative Christians, pointing the finger at Jews in general and Haredi Jews in particular, while accusers in the Middle East mostly blame Israel, Zionism and the Mossad for creating and spreading the virus and intending to make a vast fortune from medications and the vaccine they are already developing.

In the western world, the main elements promoting anti-Semitic discourse are civil society groups with various ideologies, while in the Middle East some of this discourse is put forth by the regimes themselves.

Dr. Giovanni Quer, director of the Kantor Center, adds, "Universal disasters have been attributed to the Jews and to Israel before, giving rise to anti-Semitic discourse -- such as conspiracy theories blaming Israel for 9/11, or false reports accusing Israeli soldiers of harvesting organs from the bodies of dead Palestinians. The current wave of anti-Semitism is unprecedented, however, because, spreading very swiftly through the social media, it focused at first on the COVID-19 crisis and then quickly moved on because of social and political changes: Just a few days passed between the coronavirus crisis and the racism-related social crisis in the US, but anti-Semitic discourse remained just as fierce, with its proponents simply adapting their anti-Semitic narratives to the changing social contexts."

The Kantor Center for the Study of Contemporary European Jewry, inaugurated in 2010 at Tel Aviv University, provides an academic framework for the interdisciplinary research of European Jewry from the end of World War II until the present day. The center offers a platform for the diverse needs of researchers, students, governmental and civil service personnel, professionals, activists, and the public at large, both in Israel and abroad, and cooperates with European Jewish communities and their leaders. For more information, visit https://en-humanities.tau.ac.il/kantor.

Syracuse, N.Y. - A new study published recently in ScienceDirect by researchers from Syracuse University and SUNY Upstate Medical University shows that people with intellectual and developmental disabilities (IDD) living in residential group homes are more likely to be diagnosed with COVID-19 and die from the virus than those without IDD.

According to the researchers, the disparity is likely related to a higher prevalence of comorbid diseases among those with IDD, and/or a higher percentage of people with IDD living in congregate residential settings.

Their study, "COVID-19 Outcomes among People with Intellectual and Developmental Disability Living in Residential Group Homes in New York State," was published in the Disability and Health Journal. Utilizing data from the New York Disability Advocates (NYDA) and the New York State Department of Health COVID-19 Tracker, the study compared COVID-19 outcomes between 20,431 people with IDD who live in residential group homes in the state of New York to the overall outcomes for New York State.

"The rates of COVID-19 diagnosis and death were substantially higher for people with IDD living in residential group homes," said researcher Scott Landes, an associate professor of Sociology at Syracuse University's Maxwell School of Citizenship and Public Affairs and a research affiliate for the Lerner Center for Public Health Promotion. "This may partly be due to many individuals in this population having pre-existing health conditions that are associated with more severe COVID-19 outcomes.

"However, we are concerned that these severe outcomes may be more related to the current design of the IDD service system in the United States, in which states rely heavily on providing care in congregate settings with limited support and resources," Landes said. "This is proving deadly during the current pandemic."

The study was conducted by: Landes; two researchers from SUNY Upstate Medical Center in Syracuse, N.Y., Dr. Margaret Turk, SUNY Distinguished Service Professor of Physical Medicine & Rehabilitation, and Dr. Margaret Formica, associate professor of Public Health & Preventative Medicine and associate professor of urology; Katherine McDonald, professor and Chair of the Department of Public Health in the David B. Falk College of Sport and Human Dynamics at Syracuse University; and Dalton Stevens, a sociology PhD candidate at Syracuse University. Here is a more detailed look at their findings:

People with IDD living in residential group homes in New York State were at greater risk of severe COVID-19 outcomes:

* Case rates (a measure of the number of people diagnosed with COVID-19):

o 7,841 per 100,000 for people with IDD.

o 1,910 per 100,000 for New York State.

* Case-fatality (a measure of the proportion of death among those who contract the disease indicating disease severity):

o 15 percent for people with IDD.

o 7.9 percent for New York State.

* Mortality rate (a measure of the rate of death from a disease among a total population indicating burden of deaths due to a specific disease):

o 1,175 per 100,000 for people with IDD.

o 151 per 100,000 for New York State.

The study also examined each of these COVID-19 outcomes across regions of New York State. The differences in cases and mortality rate were confirmed across all regions of the state. However, case-fatality rate was only higher for people with IDD in and around the New York City region.

"The results of this present study reinforce our initial study that showed higher case-fatality rates among people with IDD using the TriNetX COVID-19 Research Network platform," researcher Dr. Margaret Turk said. "People with IDD are a poorly recognized and vulnerable group that does not often receive adequate attention within society in general, and within our healthcare system in particular. Further research is needed to determine the possible effects that access to - or quality of - medical care has on COVID-19 outcomes for this group."

Although U.S. states have been collecting data on COVID-19 outcomes among people with IDD served by the residential group home system, very few have publicly shared any of this data, and those that have shared data have done so sparingly.

Due to the increased severity of COVID-19 outcomes among people with IDD found in this study, the authors conclude that: "In order for us to have a full accounting of COVID-19 on the IDD population, or other vulnerable populations living in congregate settings, it is imperative that the entities that provide services for or monitor any segment of this population begin to openly share all relevant data they have on COVID-19 outcomes among people with IDD."

While counties in populous metropolitan Atlanta had the highest number of COVID-19 cases in the initial weeks following Georgia's first reported case, it was rural Southwest Georgia counties, with a higher number of black residents and lower number of ICU beds, experiencing the highest rates of infection and death per capita, investigators report.

Among those counties with more than 10 cases, Terrell and Dougherty counties, both included in the Albany, Georgia Metropolitan Statistical Area, along with the Southwest Georgia counties of Randolph and Early, had the highest mortality rates in those first seven weeks ending April 24. By the end of their assessment period, Georgia counties with 50% or greater black residents had a 79% higher incidence rate than those with less than a 50% black population, and twice the mortality rate.

These more rural Georgia counties also had a lower number of intensive care beds and primary care physicians per 100,000 population, Dr. Justin Xavier Moore and his colleagues report in the Journal of the American College of Emergency Physicians. They also had more individuals age 60 and older earning under $20,000 compared to counties experiencing lower mortality rates.

It's likely that higher death rates in counties with less ICU beds are tied to treatment delays resulting from the need to transport patients elsewhere, investigators say. These counties identified as hotspots for COVID-19 are known as well for higher death rates from diseases like stroke and sepsis, corresponding author Moore and his colleagues say.

"Hospital critical care capacity represents the most important medical care factor for preventing deaths from COVID-19," they write. "Understanding the geographic areas that have the highest disease burden and morbidity will allow policy makers, public health professionals and critical care providers to appropriately allocate resources and adequately prepare for the disease pandemic for specific populations."

Race and rurality often are connected in disease, as they are in COVID-19, says Moore, epidemiologist in the Department of Population Health Sciences at the Medical College of Georgia at Augusta University. "It's like these are different ingredients of a horrible recipe."

That recipe also consistently includes poor social determinants of health, such as the conditions where you live, learn and work, mixed with a low proportion of health care services in many of these areas, which tends to have a multiplier effect that can overwhelm health services that are available and enable disease, Moore notes. An established history of distrust of health care systems by blacks, resulting from realities like the 40-year Public Health Service/Tuskegee Institute study in which black men with and without syphilis were followed for decades with some care but no actual treatment for syphilis, make some hesitant to seek care, Moore adds. Conflicting information that emerged and continues to emerge about COVID-19 likely also fuels that flame.

MCG investigators and their colleagues at Kaiser Permanente in Oakland, California, encouraged state and local governments to strongly support the southwestern portion of the state with more ICU beds, ventilators and emergency medical staff. "We can't just take our foot off the gas pedal," says Moore.

"As a nation, we need to really rethink how we approach public health," he says to dramatically reduce lost lives and to prevent already struggling economies from being decimated by disease. Systemic racism plays a huge role and work must be done to repair relationships, he says.

"I honestly believe a lot of people are afraid to seek certain care because of discrimination," so people may present with more advanced cases of all kinds of diseases, including COVID-19. Now is a good time to make permanent change, rather than a trend that passes like a hashtag, he says.

Initially one out of every two people who got seriously ill with COVID-19 died in Georgia's rural, largely black communities, he notes, while today death rates are closer to 10% and to those from other serious medical problems like sepsis in the rest of the country, he says.

"Lung cancer, sepsis, colorectal cancer, diabetes ... they all have a different pathophysiology in the sense of how they break down your body, but the problem is we have a persistent and long history of systemic racism disadvantages that have made it to where the social determinants of health are so heavily skewed in a negative way for blacks, Hispanics, the darker you are basically," Moore says. "It's not surprising; it's saddening and frustrating. The thing is, we just need better health care for people, period. I don't know how else to put it."

Through April 24, there were 22,147 confirmed cases and 892 confirmed fatalities from COVID-19 in Georgia. As of June 22, the Georgia Department of Public Health was reporting 64,701 cases and 2,643 deaths in the state; Moore is currently doing a data review to see if the clear disparities he saw early in the disease spread continue to hold. Looking at deaths per 100K population more recently, the Southwest Georgia counties of Turner, Terrell, Randolph and Early were leading the state in mortality rates, according to the Department of Public Health. In May, largely black and rural Hancock County in Central Georgia also emerged as a hotspot with high death rates.

Fulton County in metropolitan Atlanta --which has the largest population in Georgia and is about 45% black according the latest U.S. Census Bureau facts -- had the highest number of confirmed COVID-19 cases, in fact the first two cases reported in Georgia were in Fulton County, the Georgia Department of Public Health reported March 2. The two individuals lived in the same household and one had recently returned from Italy.

Georgia counties with a larger percentage of male residents also had significantly higher (19%) mortality rates from COVID-19 than those with higher percentages of females, investigators at MCG and their colleagues say. Other studies have suggested that males are more likely to have serious disease and to die.

The current study looked at the impact of COVID-19 in all 159 Georgia counties from March 3 through April 24 and got the county specific information on confirmed cases and deaths from the Johns Hopkins 2019 Novel Coronavirus Data Repository. Investigators then linked COVID-19 data with county-level data on related issues like socio-demographics, access to health care and hospital critical care infrastructures from sources like Centers for Medicare & Medicaid Services hospital reports, Moore says.

The latest issue of the journal Public Policy & Aging Report (PP&AR) from The Gerontological Society of America shows how aging is reshaping politics today in unprecedented ways, and how it will continue to do so for years to come.

Titled "Building Momentum for a New Future in Politics and Aging," the journal highlights existing studies as well as recommended areas for further research.

"Here, we see how equal amounts of policy progress and stagnation, as well as changing cultural views on aging, are fueling social, economic, and political changes in ways both expected and not," wrote PP&AR Associate Editor Michael Lepore, PhD, in his introduction. "Some of these societal changes raise concerns about limitations in current and future generations' abilities to live well into old age, at younger ages with disabilities, and as caregivers, whereas other shifts, like evolving cultural views on aging, nurture a more intergenerationally just society."

Among the seven articles that follow, the journal offers insight into major trends in the politics of aging; how generational political divides are influencing aging-related policies; the impact of aging on the economy; political impediments to aging in place; the importance of support for family caregivers; the longevity and health of U.S. presidential candidates; and how to build momentum through the frames we use to describe aging.

"Recognizing and grappling with the relevance of aging to politics is an essential step to ensuring that we are not weaving the last thread of the American social fabric but, rather, beginning a new national era that embraces aging and fully supports our interpersonal and transgenerational interdependences," Lepore wrote. "By achieving these goals, living well into and throughout old age -- despite physically or cognitively disabling conditions -- will be increasingly possible for all."

New Research: Mountain Meadow Restoration Can Bring Birds Back

In a new study led by scientists at Point Blue Conservation Science and in collaboration with The Institute for Bird Populations, authors evaluated the successes of mountain meadow restorations by analyzing eight years of bird data collected by field biologists. The authors concluded that, when "pond and plug" and similar techniques were followed, the number of birds of many species increased over time as habitat conditions improved.

The paper, published in Restoration Ecology, may prove of particular value to restoration practitioners, many of whom rely on peer-reviewed scientific journal articles to guide their work.

"This paper is the culmination of many years of work monitoring meadows. And it definitely increases the amount of evidence we have that one of the most commonly used approaches n is having the effects we want," says Brent Campos, a lead author of the study.

Restoration of degraded meadows and their streams aims to increase the amount of water flowing out of the stream channel during spring runoff and elevate groundwater levels in the dry season. Currently there are major efforts being made to restore meadows across the Sierra Nevada that have been degraded from overgrazing, agricultural use, or deliberate stream channel modifications. Evaluations of meadow restoration are needed to ensure objectives--such as increased biodiversity--are being met and identify modifications that may improve outcomes.

The study authors evaluated the expectation that meadow birds would increase in abundance following restoration. From 2009 to 2017 biologists sampled birds at 31 montane meadows in California previously restored using a common technique: partially filling the over-sized stream channel with meadow soils. The authors then assessed how the abundance of 12 species of meadow-associated birds changed from 1 to 18 years after restoration, and whether the amount of deciduous shrubs and trees (an indicator of bird habitat quality) at the time of restoration affected the rate of bird response.

According to the research, six of the twelve species studied increased in abundance after restoration, while five stayed roughly the same and one may have decreased. The amount of deciduous trees and shrubs at the restoration site at the time of restoration was a strong predictor of bird abundance. The study's authors concluded that both hydrologic measures (partially filling in degraded stream channels) and vegetative measures (planting shrubs and trees such as willows and cottonwoods at restoration sites) were helpful in creating habitat for birds, with the latter approach accelerating the positive impacts of restoration.

"Having access to one of the longest term datasets around for bird monitoring and meadow restoration was really essential to this paper," said Helen Loffland, a meadow bird specialist with The Institute for Bird Populations, and one of the paper's co-authors. "And it was heartening to see such positive responses from the birds in areas where both hydrologic and vegetative restoration measures were used."

"We know that restoration practitioners are out there trying to do the best job possible with limited funding," said Campos. "We hope that this new research will help them in their work restoring meadows' key functions of fostering biodiversity, reducing downstream flooding, purifying water, and storing carbon."

The study sites included areas throughout the Sierra including the Perazzo Meadows restoration site near Truckee, Red Clover Valley near Portola, and a restoration site in Tasmam Koyom (Humbug Valley) in Plumas County.

"It is pretty incredible to visit the Tasmam Koyom site, which is only 6 years out from the restoration completion and see such an abundance of birds," said Ryan Burnet, another co-author. "To see so many more song sparrows or yellow warblers is really encouraging. Normally, you'd need to wait 10 or even 20 years to see a biological response like that."

Scientists at Uppsala University have discovered a hitherto unknown function of blood platelets in cancer. In mouse models, these platelets have proved to help preserve the vascular barrier which makes blood-vessel walls selectively impermeable, thereby reducing the spread of tumour cells to other parts of the body. The study is published in the journal Cancer Research.

Platelets, or thrombocytes, as they are also termed, are tiny cell fragments that form in the bone marrow and circulate in the blood. If we are injured and start bleeding they clump together, sealing off the wound while also helping the blood to coagulate.

When the platelets are activated - which occurs not only in wounds but also in tumours - the substances known as growth factors contained in the platelets are released into their immediate surroundings. One is platelet-derived growth factor B (PDGFB).

In the study, the researchers investigated what happens when the PDGFB in platelets, but not in other cell types, is deleted in individuals with cancer. PDGFB from platelets was found to be essential, to attract supporting cells to the tumour blood vessels. In healthy tissue, on the other hand, the platelets did not to perform this function. If PDGFB was lacking in platelets, the quantity of circulating tumour cells increased and they spread to other parts of the body to a much higher degree.

Previous studies have shown that PDGFB from cells of another kind, endothelial cells that line the inside of blood vessels, is necessary to attract supporting cells to the vessels when they form. According to the new study, this function in tumours also requires PDGFB from platelets, which distinguishes them from healthy tissue.

From a medical point of view, it may be advantageous, in some situations, to reduce platelet activity in order to prevent blood clots, for example. Moreover, previous research shows that platelets can promote spread of tumour cells.

"Our data show that platelet activation in cancer is not altogether harmful. Instead, the PDGFB released when the platelets are activated can help to maintain the vascular barrier in tumours, thereby counteracting the spread of tumour cells. That makes it important for the specific functions of the various platelet-derived molecules to be taken into consideration when new therapies are developed," says Anna-Karin Olsson, who leads a research group at the Department of Medical Biochemistry and Microbiology at Uppsala University.

A new study by researchers at the RIKEN Center for Integrative Medical Science in Japan reports differences in blood cell mutations between Japanese and European populations. The study found that these pre-clinical mutations were strongly associated with different types of cancers and can explain why Europeans have higher rates of chronic lymphocytic leukemia, while Japanese have higher rates of T-cell leukemia. This study was published in Nature on June 24.

Our blood cells are continuously renewed from a stock of blood stem cells--called HSCs--located in bone marrow. These stem cells produce progenitor cells that give rise to the many different kinds of blood cells. Among these are important lymph cells that make up our immune system, such as T-cells and B-cells. Blood cells that come from the same stem cell or progenitor can be identified by looking at their DNA. For example, all T-cells derived from a particular HSC are clones of each other. If the HSC had a mutation, the same mutation will exist in all the T-cells in that lineage, but not in other T-cells that came from different HSCs.

Although these types of clonal mutations have been studied in European populations, Chikashi Terao and his team at RIKEN IMS suspected that they might find somewhat different results in their older Japanese population of almost 180,000 individuals. Their results showed that clonal mutations had occurred in over 35% of people in their 90s. Data from the UK BioBank yielded similar results, but the overall percentages were a bit lower. "Our findings strongly suggest that chromosomal alterations in hematopoietic clones is an inevitable event in the very old," says Terao. "The higher percentage of mutations in the Japanese population is likely related to the greater average age of the sample."

Nevertheless, more in-depth comparisons with the UK BioBank data revealed several differences. The team looked at all mutations in T-cell lineages and found that more than 80% of them occurred in the Japanese population. On the flip side, more than 90% of B-cell lineage mutations occurred in the European sample. These data are consistent with reported cases of leukemia. T-cell leukemia occurs 10 times more often in Japanese people than in Europeans, while chronic lymphocytic leukemia, a B-cell related leukemia, is 5 times more prevalent in Europeans. This does not mean that mutations selectively occurred in different genes depending on the population. Remember, the data only include clonal mutations that survived and replicated enough to be detectable. Terao explains, "We can infer that the advantage of a particular chromosomal mutation differs depending on the genetic and environmental context."

The researchers also found genetic components related to the risk of having clonal HSC mutations. They identified several locations on chromosomes for which genetic variations were associated with increased risk of clonal blood mutations in general, as well three locations related to specific mutations in B-cells. This means that the likelihood or risk of having one of the critical mutations now or in the future can be estimated by looking for these variations in a person's DNA.

Thus, although clonal HSC mutations might be inevitable, we can still do something about it. "Not everyone with these mutations gets cancer", emphasizes Terao. "However, a simple blood test that you can get at any regular health checkup will be able to identify people at risk of leukemia by checking for clonal HSC mutations. A DNA test based on the blood sample can also identify those at high risk of developing the critical HSC mutations in the future."