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You Must Remember Meeting Clara: Remembering Clara Derber Bloomfield (1942-2020)




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Highlights from Recent Cancer Literature




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Cancer Research




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[PERSPECTIVES] Myeloid Cells in Metastasis

Metastatic disease is the leading cause of death in patients with solid cancers. The progression to metastasis is a multistep process that involves detachment of tumor cells from their constraining basement membrane at the primary site, migration and intravasation into the circulation, survival in the circulation, extravasation into the secondary organ, and survival and growth at the secondary site. During these steps, tumor and immune cells interact and influence each other both within the tumor microenvironment and systemically. In particular, myeloid cells such as monocytes, macrophages, neutrophils, and myeloid-derived suppressor cells (myeloid regulatory cells) have been shown to play important roles in the metastatic process. These interactions open new avenues for targeting cancer metastasis, especially given the increasing interest in development of cancer immunotherapies. In this review, we describe the currently reported pathways and mechanisms involved in myeloid cell enhancement of the metastatic cascade.




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[PERSPECTIVES] Brain Metastasis Organotropism

Brain metastases are associated with poor prognosis irrespective of the primary tumor they originate from. Current treatments for brain metastases are palliative, and patients with symptomatic brain metastasis have a one-year survival of <20%. Lung cancer, breast cancer, and melanoma have higher incidences of brain metastases compared with other types of cancers. However, it is not very clear why some cancers metastasize to the brain more frequently than others. Studies thus far suggest that brain-specific tropism of certain types of cancers is defined by a winning combination of the following factors: unique genetic subtypes of primary tumors or its subclones enabling detachment, dissemination, blood–brain barrier penetration, plus proliferation and survival in hypoxic low-glucose microenvironment; specific transcriptomic and epigenetic changes of colony-forming metastatic cells, allowing their outgrowth; favorable metastasis-permissive microenvironment of the brain created by interactions of cancer cells and cells in the brain through triggering inflammation, recruiting myeloid-derived suppressor cells, and promoting metabolic adaptation; immunosuppression resulting in the failure of adaptive immune response to recognize or kill cancer cells in the brain. Here, we briefly review recent advances in understanding brain metastasis organotropism and outline directions for future research.




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[PERSPECTIVES] Toward Systems Pathology for PTEN Diagnostics

Germline alterations of the tumor suppressor PTEN have been extensively characterized in patients with PTEN hamartoma tumor syndromes, encompassing subsets of Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, Proteus and Proteus-like syndromes, as well as autism spectrum disorder. Studies have shown an increase in the risk of developing specific cancer types in the presence of a germline PTEN mutation. Furthermore, outside of the familial setting, somatic variants of PTEN occur in numerous malignancies. Here we introduce and discuss the prospect of moving toward a systems pathology approach for PTEN diagnostics, incorporating clinical and molecular pathology data with the goal of improving the clinical management of patients with a PTEN mutation. Detection of a germline PTEN mutation can inform cancer surveillance and in the case of somatic mutation, have value in predicting disease course. Given that PTEN functions in the PI3K/AKT/mTOR pathway, identification of a PTEN mutation may highlight new therapeutic opportunities and/or inform therapeutic choices.




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[TECHNIQUE] Animal Models of Hepatitis C Virus Infection

Hepatitis C virus (HCV) is an important and underreported infectious disease, causing chronic infection in ~71 million people worldwide. The limited host range of HCV, which robustly infects only humans and chimpanzees, has made studying this virus in vivo challenging and hampered the development of a desperately needed vaccine. The restrictions and ethical concerns surrounding biomedical research in chimpanzees has made the search for an animal model all the more important. In this review, we discuss different approaches that are being pursued toward creating small animal models for HCV infection. Although efforts to use a nonhuman primate species besides chimpanzees have proven challenging, important advances have been achieved in a variety of humanized mouse models. However, such models still fall short of the overarching goal to have an immunocompetent, inheritably susceptible in vivo platform in which the immunopathology of HCV could be studied and putative vaccines development. Alternatives to overcome this include virus adaptation, such as murine-tropic HCV strains, or the use of related hepaciviruses, of which many have been recently identified. Of the latter, the rodent/rat hepacivirus from Rattus norvegicus species-1 (RHV-rn1) holds promise as a surrogate virus in fully immunocompetent rats that can inform our understanding of the interaction between the immune response and viral outcomes (i.e., clearance vs. persistence). However, further characterization of these animal models is necessary before their use for gaining new insights into the immunopathogenesis of HCV and for conceptualizing HCV vaccines.




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[PERSPECTIVES] Regulating Preimplantation Genetic Testing across the World: A Comparison of International Policy and Ethical Perspectives

Preimplantation genetic testing (PGT) is a reproductive technology that, in the course of in vitro fertilization (IVF), allows prospective parents to select their future offspring based on genetic characteristics. PGT could be seen as an exercise of reproductive liberty, thus potentially raising significant socioethical and legal controversy. In this review, we examine—from a comparative perspective—variations in policy approaches to the regulation of PGT. We draw on a sample of 19 countries (Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, South Korea, Switzerland, United Kingdom, and the United States) to provide a global landscape of the spectrum of policy and legislative approaches (e.g., restrictive to permissive, public vs. private models). We also explore central socioethical and policy issues and contentious applications, including permissibility criteria (e.g., medical necessity), nonmedical sex selection, and reproductive tourism. Finally, we further outline genetic counseling requirements across policy approaches.




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[PERSPECTIVES] Discouraging Elective Genetic Testing of Minors: A Norm under Siege in a New Era of Genomic Medicine

Consistently, the field of genetic counseling has advocated that parents be advised to defer elective genetic testing of minors until adulthood to prevent a range of potential harms, including stigma, discrimination, and the loss of the child's ability to decide for him- or herself as an adult. However, consensus around the policy of "defer-when-possible" obscures the extent to which this norm is currently under siege. Increasingly, routine use of full or partial genome sequencing challenges our ability to control what is discovered in childhood or, when applied in a prenatal context, even before birth. The expansion of consumer-initiated genetic testing services challenges our ability to restrict what is available to minors. As the barriers to access crumble, medical professionals should proceed with caution, bearing in mind potential risks and continuing to assess the impact of genetic testing on this vulnerable population.




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[PERSPECTIVES] PTEN Nuclear Functions

For years, clinical and basic researchers have been aware of the presence of PTEN in the nucleus in cell culture, animal models, and both healthy and diseased human tissues. Despite the early recognition of nuclear PTEN, the understanding of the mechanisms of its nuclear localization, function in the nucleus, and importance in biology and human disease has been lacking. Over the last decade, emerging concepts for the complex involvement of nuclear PTEN in a variety of processes, including genome maintenance and DNA repair, cell-cycle control, gene expression, and DNA replication, are illuminating what could prove to be the key path toward a full understanding of PTEN function in health and disease. Dysregulation of nuclear PTEN is now considered an important aspect of the etiology of many pathologic conditions, prompting reconsideration of the therapeutic approaches aimed at countering the consequences of PTEN deficiency. This new knowledge is fueling the development of innovative therapeutic modalities for a broad spectrum of human conditions, from cancer and metabolic diseases, to neurological disorders and autism.




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[PERSPECTIVES] RNA Regulators in Leukemia and Lymphoma

Posttranscriptional regulation of mRNA is a powerful and tightly controlled process in which cells command the integrity, diversity, and abundance of their protein products. RNA-binding proteins (RBPs) are the principal players that control many intermediary steps of posttranscriptional regulation. Recent advances in this field have discovered the importance of RBPs in hematological diseases. Herein we will review a number of RBPs that have been determined to play critical functions in leukemia and lymphoma. Furthermore, we will discuss the potential therapeutic strategies that are currently being studied to specifically target RBPs in these diseases.




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Map: Confirmed coronavirus cases, worldwide

More than 3.9 million people have been sickened and more than 270,000 killed by the coronavirus around the world. This map is updated daily.




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Blueprint to protect the mental health of frontline medical workers

Researchers have developed a set of recommendations to manage the mental health of frontline medical workers during viral outbreaks, such as COVID-19.




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Could hotel service robots help the hospitality industry after COVID-19?

A new research study, investigating how service robots in hotels could help redefine leadership and boost the hospitality industry, has taken on new significance in the light of the seismic impact of the Covid-19 outbreak on tourism and hospitality.




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'Terrible twos' not inevitable: With engaged parenting, happy babies can become happy toddlers

Parents should not feel pressured to make their young children undertake structured learning or achieve specific tasks, particularly during lockdown. A new study of children under the age of two has found that parents who take a more flexible approach to their child's learning can - for children who were easy babies - minimize behavioral problems during toddlerhood.




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Towards antibodies against COVID-19

Researchers have announced the isolation and characterization of a unique antibody that can bind to the virus that causes COVID-19 (SARS-CoV-2). The team has established that the antibody binds to a conserved epitope on the spike protein of SARS-CoV-2.




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Trial questions benefits of organic nitrates for bone health

A new study found that organic nitrates do not have clinically relevant effects on bone mineral density or bone turnover in postmenopausal women, and the medications caused significant side effects.




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New computational method unravels single-cell data from multiple people

A new computational method for assigning the donor in single cell RNA sequencing experiments provides an accurate way to unravel data from a mixture of people. The Souporcell method could help study how genetic variants in different people affect which genes are expressed during infection or response to drugs, and help research into transplants, personalized medicine and malaria.




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Tiny devices promise new horizon for security screening and medical imaging

Miniature devices that could be developed into safe, high-resolution imaging technology, with uses such as helping doctors identify potentially deadly cancers and treat them early, have been created.




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Unique 3D-images reveal the architecture of nerve fibers

Researchers have used synchrotron light to study what happens to the nerves in diabetes. The technique shows the 3D-structure of nerve fibers in very high resolution.




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Sewage poses potential COVID-19 transmission risk, experts warn

Environmental biologists have warned that the potential spread of COVID-19 via sewage 'must not be neglected' in the battle to protect human health.




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Dual personalities visualized for shape-shifting molecule

Researchers have made a breakthrough in understanding the structure of a key genetic molecule, called RNA, and revealing for the first time how these changes impact RNA's function. The research team developed a bioinformatics technique to resolve separate structures of RNA rather than viewing them as a 'blur' that averaged multiple structures. This underpinned their discovery that the structure of RNA can influence how cells function.




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Bat 'super immunity' may explain how bats carry coronaviruses, study finds

Researchers have uncovered how bats can carry the Middle East respiratory syndrome (MERS) coronavirus without getting sick -- research that could shed light on how coronaviruses make the jump to humans and other animals.




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Regularly attending religious services associated with lower risk of deaths of despair, study finds

People who attended religious services at least once a week were significantly less likely to die from 'deaths of despair,' including deaths related to suicide, drug overdose, and alcohol poisoning, according to new research.




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Obesity is linked to gut microbiota disturbance, but not among statin-treated individuals

Scientists set out to investigate a potential role of the gut microbiota in the development of cardio-metabolic diseases. They ended up identifying the common cholesterol-lowering drug statins as a potential microbiota-modulating therapeutic.




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First-in-kind study reveals genetic markers of type 2 diabetes in East Asians

This research shows how different populations of people share most of the genetic susceptibilities to developing type 2 diabetes but do have some different genetic variations that can make them more or less susceptible to developing the condition.




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Safely relaxing social distancing comes down to numbers

Your house number could be the key to the safe relaxation of COVID-19-related restrictions if governments follow a new exit strategy, which proposes the use of an 'odds-and-evens' approach to allowing people to head back to work and enjoy other activities after weeks of lockdown.




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Cholesterol lowering drugs linked to improved gut bacteria composition in obese people

Obese Europeans who are treated with cholesterol lowering drugs have not only lower values of blood LDL cholesterol and markers of inflammation but in addition a more healthy gut bacteria profile than those obese who are not prescribed statins.




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Focused ultrasound opening brain to previously impossible treatments

Focused ultrasound, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors -- and even help repair the devastating damage caused by stroke.




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Certain foods common in diets of US adults with inflammatory bowel disease

Foods, such as French fries, cheese, cookies, soda, and sports and energy drinks, are commonly found in the diets of United States adults with inflammatory bowel disease, according to a new study.




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Most critically ill patients with COVID-19 survive with standard treatment, study reveals

Clinicians from two hospitals in Boston report that the majority of even the sickest patients with COVID-19 -- those who require ventilators in intensive care units -- get better when they receive existing guideline-supported treatment for respiratory failure.




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For better migraine treatment, try adding some downward dogs

Adding yoga to your regularly prescribed migraine treatment may be better than medication alone, according to a new study. The new research suggests yoga may help people with migraines have headaches that happen less often, don't last as long and are less painful.




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Novel way to treat snakebite

Scientists demonstrate a completely new way of treating snakebites. The team have shown that the repurposing of an existing medicine, commonly used to treat mercury poisoning, is an effective oral therapy for the treatment of certain hemotoxic snakebites.




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Position statement addresses difficult issue: allocating scare resources in COVID-19 era

The COVID-19 pandemic has placed unprecedented pressure on societies worldwide, given the pandemic's rapid, often deadly spread. In health care, the pandemic has raised the pressing question of how society should allocate scarce resources during a crisis.




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Outpatient COVID-19 clues

A new report offers insights that can help clinicians distinguish between patients with COVID-19 infections and those with other conditions that may mimic COVID-19 symptoms.




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Police stop fewer black drivers at night when a 'veil of darkness' obscures their race

After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, researchers concluded that 'police stops and search decisions suffer from persistent racial bias.'




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Middle age may be much more stressful now than in the '90s

A new study found that life may be more stressful now than it was in the 1990s, especially for people between the ages of 45 and 64.




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Sleep difficulties linked to altered brain development in infants who later develop autism

New research finds that sleep problems in a baby's first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.




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Clay layers and distant pumping trigger arsenic contamination in Bangladesh groundwater

To avoid arsenic contamination, many Bangladeshi households access water via private wells drilled to 300 feet or less, beneath impermeable clay layers. Such clay layers have been thought to protect groundwater in the underlying aquifers from the downward flow of contaminants. However, a new study suggests that such clay layers do not always protect against arsenic, and could even be a source of contamination in some wells.




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Accumulation of gene mutations in chronic Graft-versus-host disease

Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.




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Fighting autoimmunity and cancer: The nutritional key

Scientists have revealed a novel mechanism through which the immune system controls autoimmunity and cancer. In the special focus of the researchers were regulatory T cells -- a type of white blood cells that act as a brake on the immune system.




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Killing 'sleeper cells' may enhance breast cancer therapy

The anti-cancer medicine venetoclax could improve the current therapy for estrogen receptor-positive (ER+) breast cancer, according to preclinical studies. The promising preclinical results for this 'triple therapy' have underpinned a phase 1 clinical trial in Melbourne, Australia, that is combining venetoclax with hormone therapy and CDK4/6 inhibitors in patients with ER+ breast cancer.




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Survey: Half of Americans concerned about new moms, babies being in public amid COVID-19

A new national U.S. survey finds that nearly 80 percent of respondents would be concerned about themselves or an expectant mother in their life in the midst of the current COVID-19 outbreak, with almost half expressing fear of going to a scheduled prenatal appointment.




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Skin-to-skin 'kangaroo care' shows important benefits for premature babies

A world-first study has demonstrated significant benefits to a premature baby's heart and brain function when held by the parent in skin-to-skin contact. Parent-infant skin-to-skin care (SSC) or kangaroo care, started in the late 1970s in Columbia when incubators to keep babies warm were not available. It is now widely recognized as a beneficial component of holistic care provided for pre-term infants.




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UK's scientific advice on coronavirus is a cause for concern

The UK government has published details of the scientific advice behind its strategies to tackle the covid-19 outbreak, but outside experts say it is missing key points and hasn't been implemented properly




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Higher step count linked to lower yearly risk of death, up to a point

An analysis of the daily steps taken by about 5000 people in the US has found that a higher step count is linked to a lower yearly risk of death, although the effect tails off above 12,000 steps




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The bacteria in a mother’s gut may protect babies from food allergies

The presence of bacteria that break down fibre in a mother’s gut is linked to a reduced risk of food allergies in her child’s first year of life




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Greta Thunberg says she may have had covid-19 and has self-isolated

Greta Thunberg says she and her father, Swedish actor Svante Thunberg, appear to have been infected by the coronavirus, though they have not been tested as their native Sweden is only doing so for severe cases




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Why US society is so vulnerable to the coronavirus pandemic

The economic and healthcare policies pursued by the US in recent years have failed to prioritise public health and made it vulnerable to a pandemic. Could things be different?




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We haven’t identified any new drugs for severe covid-19 cases yet

A number of potential drugs for treating the coronavirus are in trials. There are some promising candidates but it’s unclear if they’ll help those who need them most