Culture

The spread of the Internet is shaping migration in profound ways. A McGill-led study of over 150 countries links Internet penetration with migration intentions and behaviours, suggesting that digital connectivity plays a key role in migration decisions and actively supports the migration process.

Countries with higher proportions of Internet users tend to have more people who are willing to emigrate. At the individual level, the association between Internet use and intention to migrate is stronger among women and those with less education. The same result was found for economic migrants compared to political migrants, according to the team of international researchers from McGill University, University of Oxford, University of Calabria, and Bocconi University.

"The digital revolution brought about by the advent of the Internet has transformed our societies, economies, and way of life. Migration is no exception in this revolution," says co-author Luca Maria Pesando, an Assistant Professor in the Department of Sociology and Centre on Population Dynamics at McGill University.

In the study, published in Population and Development Review, the researchers tracked Internet use and migration pathways with data from the World Bank, the International Telecommunication Union, the Global Peace Index, the Arab Barometer, and the Gallup World Poll, an international survey of citizens across 160 countries.

Their findings underscore the importance of the Internet as an informational channel for migrants who leave their country in search of better opportunities. Unlike political migrants, who might be pushed, for example, by the sudden explosion of a civil conflict, economic migrants' decisions are more likely to benefit from access to information provided by the Internet, and more likely to be shaped by aspirations of brighter futures in their destination countries.

"The Internet not only gives us access to more information; it allows us to easily compare ourselves to others living in other - often wealthier - countries through social media," says Pesando.

Case study of Italy

Looking at migration data in Italy - a country that has witnessed sizeable increases in migrant inflows over the past two decades - the researchers found a strong correlation between Internet use in migrants' countries of origin, and the presence of people from that country in the Italian population register in the following year. Tracking migrants including asylum seekers and refugees passing through the Sant'Anna immigration Centre in Calabria, the researchers also found a link between migrants' digital skills and knowledge of the Internet and voluntary departure from the Centre in search of better economic opportunities.

"Our findings contribute to the growing research on digital demography, where Internet-generated data or digital breadcrumbs are used to study migration and other demographic phenomena," says Pesando. "Our work suggests that the Internet acts not just as an instrument to observe migration behaviors, but indeed actively supports the migration process."

As next steps, the research team, which includes Francesco Billari of Bocconi University and Ridhi Kashyap and Valentina Rotondi of University of Oxford, will explore how digital technology and connectivity affect social development outcomes, ranging from women's empowerment to reproductive health and children's wellbeing across generations.

LA JOLLA, CA--Scientists at Scripps Research have demonstrated a promising new strategy for treating lymphomas, a group of cancers that begin in infection-fighting cells of the immune system called lymphocytes.

The new approach uses natural cancer-targeting immune cells, known as natural killer cells, that have been modified to selectively target lymphoma. As described in their study, published in the journal Angewandte Chemie, the modified natural killer cells brought about a dramatic reduction of lymphoma in a mouse.

"We found a way to achieve selectivity in targeting lymphoma cells, which is an important departure from existing therapies," says co-senior author Peng Wu, PhD, an associate professor in the Department of Molecular Medicine at Scripps Research.

Wu and his lab collaborated in the study with the lab of co-senior author James Paulson, PhD, the Cecil H. and Ida Green Professor and Chair of the Department of Molecular Medicine at Scripps Research.

More than 20,000 people in the United States die of lymphomas annually, while approximately 85,000 people are newly diagnosed. Most lymphomas arise from B cells, an important type of lymphocyte whose primary function is to make antibodies.

Some existing lymphoma treatments, including B-cell-killing antibodies and so-called CAR-T cell therapies, work by targeting B cells indiscriminately, largely wiping them out. However, this strategy brings many adverse side effects, including months of immunosuppression due to low antibody levels.

Wu, Paulson and their teams have developed a more specific approach using natural killer cells, which are immune cells that normally patrol the bloodstream and tissues, seeking and destroying virus-infected or cancerous cells. These immune-system warriors, also known as NK cells, are able to recognize certain tell-tale surface molecules that signify serious damage or malignancy within a cell; they can then kill that target cell through a variety of means, including by secreting proteins that punch holes in the cell's outer membrane.

Creating a super-powered NK cell

In the early 1990s, Canadian researchers developed a special type of NK cell, NK-92, from a patient with a rare NK-cell cancer. NK-92 cells are relatively easy to grow and multiply in the lab, compared with normal NK cells found in human blood.

The Canadian researchers and others have since shown that NK-92 cells are good at killing different kinds of cancerous cells, and can bring about dramatic results in some patients, with minimal side effects. NK-92MI cells, an easier-to-multiply version of NK-92 cells, are now being widely investigated for use against various cancers.

On their own, NK-92MI cells may not be ideal cancer-fighters, especially not for advanced malignancies, in part because they are dispersed throughout the body when infused into the bloodstream. In the new study, however, Wu and his team used chemistry techniques to modify NK-92MI cells to concentrate their cancer-fighting power against lymphoma.

Steering powerful cells where they're needed most

In an initial set of experiments, the Scripps Research scientists re-engineered NK-92MI cells to include a surface molecule that binds to a B-cell surface receptor called CD22, which is normally abundant on B-cell-derived lymphoma cells. Thus, in principle, the NK-92MI cells would selectively recognize cancerous B cells.

In cell-culture tests, the modification brought a big improvement in the NK cells' ability to kill lymphoma cells, and these killer cells did not harm healthy cells. In a mouse model of lymphoma, however, the strategy didn't work so well, apparently because the NK cells still did not go where they were needed.

"We found that after being injected, these NK cells tend to be found in the lungs and throughout the bloodstream--whereas in this mouse model and in human lymphoma patients, the lymphoma cells are mostly in the bone marrow," Wu says.

The team then added to their NK cells a new molecule called Sialyl-Lewis X, which made the cells gather in bone marrow amid the lymphoma cells. This led to a dramatic delay in the development of lymphoma in the mice. With this promising result, Wu and his lab now are continuing to develop this and related strategies for clinical use.

Wu and Paulson suspect that in general, adding homing molecules such as Sialyl-Lewis X to cell-based anticancer treatments enhances the cancer-killing power at the site of the cancer, and may be a key to these treatments' future success--particularly against solid tumors and other highly localized cancers.

Wu notes, too, that Sialyl-Lewis X, which made the NK-92MI cells gather in bone marrow, as well as the CD22-binding molecule that directed the cells to malignant B cells, are both sugar-like "glycan" molecules. Although such molecules are found on virtually all cells, and often have essential biological functions as well as crucial roles in disease, they are difficult to study and thus have been relatively neglected.

"People are only starting to appreciate the importance of glycans," says Senlian Hong, PhD, the first author of the study and a postdoctoral research associate in the Wu lab at Scripps Research.

LA JOLLA, CA--Made in clandestine laboratories and sold widely across the United States, the diverse class of drugs known as synthetic cannabinoids presents a growing public health threat.

In a new study, Scripps Research scientists have devised a way to deactivate these designer drugs after they've been administered--offering a potential path for treating addiction and overdose.

The research appears today in the American Chemical Society's open access journal JACS Au, with findings from the laboratory of Kim Janda, PhD, the Ely R. Callaway, Jr. professor of chemistry at Scripps Research. Janda and his team developed a vaccine that was able to broadly counter the effects of synthetic cannabinoids in rodents, sequestering the drug molecules before they could interact with the central nervous system. Importantly, the approach worked in models that simulated smoking and vaping, which is how the drugs are most commonly used in real life.

"Synthetic cannabinoids are much more powerful and toxic than users often realize, and their rising prevalence has led to serious health issues among young people and adults," Janda says. "We found a way to negate the dangerous effects of these drugs, even when they're consumed in impure forms, as is often the case. Our hope is that this may one day help treat cannabinoid use disorders or accelerate recovery for people who overdosed."

Not to be confused with marijuana

Synthetic cannabinoids act on the same brain cell receptors as THC, the mind-altering ingredient in marijuana. However, they're man-made in a laboratory, with chemical structures that don't look anything like THC. Moreover, their actual effects can be unpredictable and, in some cases, fatal, Janda says.

The synthetic drugs are often sprayed on dried plant materials so they can be smoked, or sold as vaping liquids to be inhaled using e-cigarettes. Manufacturers tend to sell the products in colorful foil packages and plastic bottles under a wide variety of brand names, including Spice, K2, Joker, Black Mamba and hundreds of others.

Synthetic cannabinoids are also sometimes mixed with other dangerous drugs such as fentanyl, which can make them more deadly. Overdoses are on the upswing, as evidenced by calls to poison control centers.

"The drugs often called synthetic marijuana are, in reality, very different from marijuana," the American Association of Poison Control Centers says. "They contain powerful chemicals and can cause severe, life-threatening health effects: severe agitation and anxiety, nausea, vomiting, seizures and hallucinations. The drugs are made specifically to be abused. Like many other illegal drugs, synthetic marijuana is not tested for safety, and users don't know exactly what chemicals they are putting into their bodies."

Expanding on a proven method

For the study, Janda says first author Mingliang Lin, a graduate student, wanted to explore whether a vaccine could work against synthetic cannabinoids, just as they have shown to do against some other drugs of abuse. Janda already has developed vaccine-based approaches to combat heroin, fentanyl and cocaine.

As an addiction treatment, Janda believes vaccines provide benefits over other therapeutics, as they don't require taking a daily pill and can reduce the risk of an overdose if the user relapses.

The newest vaccine differs from Janda's previous work in that it's composed of multiple drug-like antigens that stimulate "broadly neutralizing" antibodies within the body, which disable many types of cannabinoids. This is key, as synthetic cannabinoids encompass a wide range of man-made chemicals.

In behavioral experiments involving mice, the team found that even when exposed to a large amount of the drug, the vaccine offered broad protection against the psychoactive effects. The team also developed a version of the vaccine that could be inhaled, which could offer greater convenience.

"This work provides a solid foundation for future therapeutic development against synthetic cannabinoid abuse," Janda says. "The ultimate goal is to provide prolonged protection for those who may be struggling with substance abuse."

A common analogy used to describe the brain is that it consists of tiny interconnected computers. Each one of these computers, or neurons, process and relay activity from thousands of other neurons, forming complex networks that allow us to perceive our surroundings, make decisions, and guide our actions. Communication between neurons occurs through tiny connections called synapses, and each neuron integrates the activity across these synapses to form a single output signal. However, not all synapses are created equal. Synapses converging onto an individual neuron differ in size, and size is correlated with strength: larger synapses are stronger and have a greater influence on a neuron's output than smaller synapses. But why are some synapses stronger than others, and how does this impact individual neurons processing incoming signals?

One well-known theory has suggested an answer. The Hebbian model for circuit development posits that the strength of a synapse between two neurons is determined by similarity in their activity. Synapses between neurons that are highly co-active become stronger than those that are less frequently co-active. This relationship provides a clear prediction for the diversity of synapse sizes present in mature neurons.  Large synapses would be formed with other neurons that have very similar response properties, and these synapses have a dominant role in determining the output of the neuron.  In contrast, small synapses would arise from neurons with less similar response properties and have less impact on the neuron's response. Although there is some evidence in support of this model, a direct test requires measuring the activity of individual synapses, their size, and their neuron's output signal, a combination that has been challenging to achieve with existing technologies.

Now, for the first time, an interdisciplinary team of scientists at the Max Planck Florida Institute for Neuroscience (MPFI) report the results of a novel approach that allowed them to achieve these measurements. Published in the journal Nature, their work challenges predictions of the Hebbian model, demonstrating that synapse size is not correlated with response similarity and suggests neural response properties reflect the total number of active synapses, both weak and strong.

Benjamin Scholl, Ph.D., a postdoctoral researcher in the Fitzpatrick lab at MPFI, was inspired to explore this question in the visual cortex, where he could take advantage of the fact that individual neurons exhibit a high degree of selectivity in their response to different features in the visual scene, such as the orientation of edges or the direction of a moving object. This phenomenon, termed feature selectivity, arises through the integration of thousands of synapses conveying different signals, but exactly how this occurs is unknown. "We aimed to test the hypothesis that the strong synapses have responses that closely match the neuron's feature selectivity, while the weak ones do not," explained Scholl, who is co-first author of the study. To test this hypothesis, the scientists utilized a light microscopy technique to visualize the activity of a population of synapses on individual neurons in real time. But this technique alone has a severe limitation--only synaptic activity can be observed, not their strength.

To measure synapse strength, a collaboration was formed with another team of scientists from the Electron Microscopy Core Facility at MPFI, led by Naomi Kamasawa, Ph.D. "Electron microscopy captures incredibly detailed images of a synapse, at the nanometer scale, allowing us to make precise measurements of their structure", explained Connon Thomas, co-first author of the work and an electron microscopy specialist. "These structural measurements tell us how strong each synapse is. By first examining synapse activity with light microscopy, then measuring the strength of those same exact synapses with electron microscopy, we knew we could answer this question". The combination of these techniques, termed Correlated Light and Electron Microscopy (CLEM), allowed the researchers to measure the function (feature selectivity) and structure (strength) of populations of synapses from several neurons.

In their initial results, the team found nothing unexpected: some synapses shared feature selectivity with the neuron, while others were different; some synapses were small (weak), while others were large (strong). But when these data were put together, the authors were surprised to find that both strong and weak synapses exhibited a wide variety of functional properties: there was no strict relationship as theorized. However, by examining the activity of the whole synaptic population, the researchers recognized that they had uncovered the likely synaptic basis for feature selectivity. "We observed a 'strength-in-numbers' phenomenon. Our data suggest that the feature selectivity of a neuron is derived from the total number of synapses activated, including strong and weak," described Scholl. "In fact, we found many more weak synapses driving feature selectivity, which suggests they could have a predominant influence". In support of this, the team observed that neighboring weaker synapses were more often co-active, which could even enhance their influence on the neuron.

These results challenge the prevailing theory that strong synapses are exclusively found between neurons with similar response properties and play the dominant role in determining a neuron's feature selectivity. Instead, selectivity appears to derive from the total numbers of synapses, suggesting that a synaptic democracy (akin to the popular vote) is most important. This still leaves open the question of why some synapses are stronger than others and studies are underway using these technologies to explore what other aspects of synaptic connections might be important. "Combining both structural and functional measurements of neurons provides a more holistic understanding of how our brains compute information" says Thomas. "The CLEM technique is allowing us to push the boundaries of what we know about fundamental workings of the brain." This work emphasizes the creative synergy that results from bringing together curiosity-driven scientists from different disciplines, enabling new insights into neural circuit organization that could not have been anticipated, and laying the foundation for tomorrow's advances in understanding disorders of brain function.

OTTAWA, ON _The COVID-19 pandemic is seriously affecting the sleep habits of half of those surveyed in a new study from The Royal and the University of Ottawa, leading to further stress and anxiety plus further dependence on sleep medication.

The global pandemic's impact on daily routines extends to the bed, according to 'Profiles of sleep changes during the COVID?19 pandemic: Demographic, behavioural and psychological factors'. The study was led by Principal Investigator Rébecca Robillard, an Assistant Professor and co-director of the Sleep Laboratory of the School of Psychology at the University of Ottawa, and Head Scientist in the Sleep Research Unit at The Royal Institute of Mental Health Research and published in the Journal of Sleep Research.

Dr. Robillard and her team, which was comprised of nearly two dozen scientists from across North America, conducted an online survey of 5,525 Canadian during the early phase of the COVID-19 pandemic. She walked us through some of the study's most important findings.

How has the pandemic affected our sleep?

RR: "The pandemic is having a diverse impact on people's sleep, with clinically meaningful sleep difficulties having undergone a sharp increase. We found that half of our participants showed signs of serious sleep problems during the pandemic. Specifically, we identified three different profiles of sleep changes: those who sleep more; those whose sleep schedule was pushed to later bed and wake-up times; and those who are getting less sleep than they did before the pandemic."

How is this significant change in sleep pattern affecting people's daily lives?

"Active changes people made on sleep-related behaviors during the pandemic not only affected sleep quality and quantity, but it also affected their psychological response to this unprecedented situation. Compared to those who are sleeping more, those who have later sleep schedules or shorter sleep cycles showed increased symptoms of insomnia and worsening symptoms of stress, anxiety and depression."

Were you able to identify any factors associated with this disruption of sleep patterns?

"Yes. New sleep difficulties seem to be disproportionately affecting women, those with families and family responsibilities, the employed, and individuals with chronic illnesses. It also impacted individuals with earlier wake-up times, higher stress levels, heavier alcohol use, and extra television exposure."

How have people coped?

"We have seen an increase in the use of sleeping medications during the pandemic. Considering the known risks for the development of tolerance with these medications, this may forecast a surge in more complex chronic insomnia cases in the long run."

Overall, what can be read into people's sleep patterns during the pandemic?

"The large scale of sleep changes in response to the pandemic highlights the need for more accessible, yet tailored interventions to address sleep problems. Sleep and mental health issues are something to be expected with the current circumstances, but we never expected to see it hit this level. It is important to intervene to address the unique phenomenon that we are facing right now."

What are some ways people can improve their sleep, even during the pandemic?

"Some simple habits can help you to get a good night sleep. They include:

Getting up at the same time each morning (even on weekends). Even if you fall asleep very late, you should still get up at the same time each morning;

Develop relaxing pre-sleep rituals such as reading;

Avoid caffeine and alcohol within six hours of bedtime, and don't smoke at bedtime;

Exercise regularly. Get vigorous exercise such as jogging either in the morning or afternoon. Get mild exercise, such as walking, two to three hours before bedtime.

At some point, everyone experiences nausea. Whether it occurs after unwisely eating a week-old slice of pizza or as an accompaniment to a serious infection, that queasy, unsettling sensation centered around the stomach is a signal that something is amiss within the body and typically portends a bout of vomiting.

Most of the time, nausea is only temporary. But for some people, such as those on certain chemotherapy regimens, it can be severe, chronic and even life-threatening when it prevents patients from adhering to treatment.

In a new study published in Neuron, researchers at Harvard Medical School have now identified and characterized neurons that regulate nausea-like responses in mice. When these neurons are experimentally turned on, nausea-like responses can be activated regardless of exposure to nausea-triggering substances. Without these neurons, nausea-like responses to poisons are lost.

The results shed light on the sensation of nausea and present new targets for the design of improved, more precise antinausea medications.

"Everyone knows what nausea feels like, but it has been largely mysterious at a molecular and genetic level," said the study's corresponding author, Stephen Liberles, professor of cell biology in the Blavatnik Institute at HMS. "By identifying neuron types at the heart of this phenomenon, we can now investigate how it works and design better ways to control it in the future."

Liberles and colleagues, led by the study's first author, Chuchu Zhang, research fellow in cell biology at HMS, began their investigation of nausea by looking at a region of the brain called the area postrema.

Located in the brain stem, the area postrema has long been associated with vomiting and is one of the rare parts of the brain outside the blood-brain barrier that can monitor blood-borne chemicals. This is thought to allow the area postrema to detect harmful substances or danger signals in the bloodstream and act as an alarm bell when it does so.

Until now, the different types and functions of cells within the area postrema remained unclear. In their study, Zhang, Liberles and their team built an atlas of cell types, using single-nucleus RNA sequencing to characterize gene expression in thousands of individual area postrema cells from mice.

Fruity tricks

The atlas revealed that there were only a handful of different neuron types in the area postrema. Of particular interest were neurons that expressed GLP1R, a receptor protein on the cell surface that previous studies have linked to blood sugar and appetite control.

To probe whether these neurons play a role in nausea, the researchers had to first assess if mice were actually experiencing the sensation. They did so by adding cherry or grape flavoring to the animals' drinking water.

Then they gave the mice either an innocuous substance or one known to induce nausea. If a mouse felt malaise, it would quickly associate a fruit flavor with the negative sensation and avoid it, similar to how humans develop food aversions after eating something disagreeable.

The researchers tested several different substances, including lithium chloride and lipopolysaccharide, a toxin produced by bacteria associated with food poisoning. As expected, all tested substances led to strong flavor aversion in mice.

When GLP1R neurons were experimentally removed, however, mice stopped developing flavor aversions for most of the substances--an observation that suggested they no longer experienced malaise as normal.

The team also experimentally turned GLP1R neurons on. They found that mice with activated GLP1R neurons would acquire strong flavor aversions even when they had not been exposed to a nausea-inducing substance.

"We used a technique to activate these neurons, essentially tricking them into thinking there was a toxin present," Zhang said. "This led to conditioned flavor avoidance, which was strong evidence for a connection between these neurons and the nausea response."

Additional analyses revealed that GLP1R neurons connect to many other regions of the brain, including one called the parabrachial nucleus, which has been recognized as a hub for pain and aversion. This may be how area postrema neurons help induce conditioned flavor-aversion memories, Zhang said.

The team also found that GLP1R neurons expressed numerous other cell-surface receptors, such as the receptor GFRAL. Interestingly, removing this subset of neurons caused mice to stop developing flavor aversions for only lithium chloride and lipopolysaccharide.

This indicated a "division of labor" between area postrema neurons, with different neuron types responsible for detecting and raising the alarm for different substances.

Next generation

The study findings present a wealth of data to help scientists better understand nausea, how toxins or medicines trigger the sensation, and how it can be controlled to benefit patients, the authors said.

For example, the team found that certain neurons expressed a calcium-sensing receptor called CaSR. This receptor is a target for the drug cinacalcet, which is used to treat a hormonal imbalance in patients with chronic kidney disease and other conditions.

Nausea is a main side effect of this drug, and so the research team tested whether area postrema neurons were involved. Giving cinacalcet to mice led to flavor-aversion behaviors, which could be averted when GLP1R neurons were removed. This suggested that CaSR receptors may also play a role in nausea-like responses in area postrema neurons.

"Nausea is a very unpleasant sensation, and current antinausea drugs are not perfect," Zhang said. "Many people still experience nausea during cancer treatment, pregnancy and more, and so better understanding and treating nausea is a very important clinical need."

Numerous questions about these neurons and their role in nausea remain, the authors said. For example, it is still unclear which signals in the bloodstream area postrema neurons respond to. Their current working model is that toxins or medicines damage the body, triggering the release of chemicals into the bloodstream, which receptors on area postrema neurons detect.

In addition, the researchers note that their current work focused on excitatory neurons, which, when activated, go on to activate other neurons. Their atlas of area postrema cells identifies many other cell types, including inhibitory neurons, which dampen the activity of other neurons. The team is now investigating the function of these other cell types in the nausea response.

"Some of the most exciting and important discoveries in neuroscience have involved the identification of sensory receptors, both external and internal," said Liberles, who is a Howard Hughes Medical Institute Investigator. "While there has been a great deal of progress in understanding the neurons important for sensations like hunger, thirst and satiety, the neurons relevant for nausea have remained ill-defined."

"We still have a lot to do to understand how the sensation of nausea arises at the molecular, neural and cellular levels," Liberles added. "There are many next-generation questions enabled by these findings."

WASHINGTON--The Endocrine Society and the Pediatric Endocrine Society oppose legislative efforts to block transgender and gender diverse individuals from accessing gender-affirming medical and surgical care, the two medical societies said in a joint policy perspective published in The Journal of Clinical Endocrinology & Metabolism.

In the past three years, legislators in 17 states have proposed more than two dozen bills barring medical and surgical treatments for transgender and gender diverse youth and adults. Many of these bills reflect widespread misinformation about the nature of evidence-based gender-affirming medical care.

"For young children experiencing feelings that their gender does not match the one assigned at birth, known as gender dysphoria, an initial intervention is likely to be a new haircut or clothing," said the manuscript's first author and Co-Chair of the Pediatric Endocrine Society's Transgender Special Interest Group Advocacy Subcommittee, Abby Walch, M.D., of the University of California San Francisco and Benioff Children's Hospitals in San Francisco, Calif. "The first course of action is to support the child in living as their affirmed gender identity and to provide mental health support as needed."

After transgender and gender diverse minors start puberty, prescribing hormones to suppress puberty is the recommended strategy if desired and if diagnostic and treatment criteria are met. This treatment, which is completely reversible, gives adolescents more time to explore their options.

Only reversible treatments are recommended for adolescents until they demonstrate the ability to provide informed consent and experience sustained feelings of gender dysphoria. Even then, gender-affirming hormone therapy to help individuals experience puberty in a way that matches their gender identity is partially reversible.

Three High Court judges in the United Kingdom ruled Dec. 1 that minors under the age of 16 likely could not give informed consent for pubertal suppression. Though it is likely to be challenged, this decision is a problematic development that could prevent transgender and gender diverse minors from obtaining the medical care they need.

"Considering transgender and gender diverse individuals face a disproportionately high risk of suicide and other health disparities, it is crucial that they have access to essential and often life-saving, gender-affirming care from well-informed health care professionals," said senior author and Co-Chair of the Endocrine Society's Transgender Research and Medicine Special Interest Group, Sean J. Iwamoto, M.D., of the University of Colorado School of Medicine and Rocky Mountain Regional VA Medical Center, both in Aurora, Colo. "Barring gender-affirming medical and surgical care for transgender and gender diverse individuals would force many to go through distressing and even traumatic experiences in life related to misgendering. No bill should criminalize physicians who provide the standard of care for this vulnerable population."

The course of gender-affirming treatment should be determined by patients and their health care providers, not by policymakers. Experts should be consulted regarding any policies governing treatment for transgender and gender diverse individuals, the authors wrote.

Bottom Line: Esophageal adenocarcinoma is occurring more frequently in adults under age 50, and these younger adults are more likely to be diagnosed at advanced stages.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Prasad G. Iyer, MD, MSc, professor of medicine in the Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology; and Don C. Codipilly, MD, a gastroenterology fellow, both at the Mayo Clinic in Rochester, Minnesota.

Background: Esophageal cancer is a relatively rare cancer, with 18,440 cases expected to be diagnosed in the United States this year, according to the Surveillance, Epidemiology, and End Results (SEER) database. While those cases account for only about 1 percent of U.S. cancer diagnoses, esophageal cancer has poor survival outcomes, with a five-year survival rate of only 19.9 percent.

"Patients who present with late-stage esophageal cancer typically have poorer outcomes than those with early-stage disease. As such, it is important to understand the epidemiology of esophageal cancer to target our screening strategies," Iyer said.

Esophageal adenocarcinoma (EAC) is one of the most common types of esophageal cancer.

How the Study was Conducted: In this study, Iyer and colleagues sought to assess trends in incidence, stage, and survival outcomes in patients diagnosed with EAC before age 50 compared with those diagnosed at later ages.

The researchers used the Surveillance, Epidemiology, and End Results database to identify 34,443 cases of EAC diagnosed between 1975 and 2015. They calculated age-standardized incidence across three age groups: under 50; 50-69; and 70 and over.

Results: Incidence of EAC increased across all age groups, with the rate of incidence for patients under age 50 increasing an average of 2.9 percent per year between 1975 and 2015.

Younger patients were more likely to be diagnosed at advanced stages of the disease, with 84.9 percent of those under 50 diagnosed at regional or distant stages, compared with 67.3 percent of those 50 or older.

As a result, the younger age group also had poorer survival outcomes: In the most recent time period, 2000-2011, those under 50 had a five-year EAC-free survival rate of 22.9 percent, compared with 29.6 percent for both the 50-69 and the 70-and-over age groups.

Author's Comments: The authors cautioned that while EAC remains a rare cancer, especially in those under 50, clinicians and patients should be aware of the increasing incidence and the poor survival outcomes in younger patients.

"The magnitude of late-stage disease and poor cancer-related survival in this age group were surprising findings for us," Iyer said. "We are also concerned by the trend of increase over the past four decades."

The authors pointed out that the rising incidence of EAC in younger adults mirrors the trend in colon cancer. In both cases, physicians may attribute symptoms to other causes, delaying diagnosis and potentially leading to worse outcomes, said Codipilly.

The authors added that patients should be aware of risk factors and symptoms of esophageal cancer. Symptoms typically include difficulty swallowing, chest discomfort, or unintended weight loss. They added that certain high-risk groups, such as those with long-term reflux and those with a family history of esophageal cancer, should discuss screening with their health care providers.

"Physicians must keep in mind that EAC is not a disease of the elderly, and that outcomes for young people with EAC are dismal," Codipilly said. "Our findings suggest that physicians should have a low threshold of suspicion for patients who present with dysphagia (difficulty swallowing). While younger patients would typically not be at high risk for EAC, they may benefit from an upper endoscopy." This procedure, in which doctors examine the upper lining of the digestive tract, could rule out EAC or could help diagnose the disease at an earlier stage, when it is easier to treat, the authors said.

Study Limitations: The authors noted that a limitation of the study is that researchers could not examine individual-level data. Also, comorbidity information was not available in the SEER database.

Washington, December 16, 2020--When the emerging COVID-19 pandemic caused most U.S. schools to close and transition to distance learning last spring, many parents were forced into new roles as proxy educators for their children. A study published today in Educational Researcher, a peer-reviewed journal of the American Educational Research Association, finds that roughly 51 percent of all parents surveyed in March and April had at least one child struggling with distance learning and were themselves experiencing significantly higher levels of stress.

VIDEO: Watch the authors discuss study findings and implications: https://youtu.be/7khjJ-RPrxo

The study authors found that parents with at least one student struggling with distance learning were 19 percentage points more likely than other parents to report anxiety. These parents also were 22 percentage points more likely to experience depression, and were 20 percentage points more likely to have trouble sleeping. In addition, they were 20 percentage points more likely to feel worried and 23 percentage points more likely to have little interest or pleasure in doing things. The results of the analysis remain consistent even after accounting for other school and demographic characteristics.

The study found that these levels of heightened mental distress were felt by parents across all socioeconomic categories, regardless of family income, the number of children struggling (above one), or the number of days that had passed since school closure.

For this study, authors Cassandra R. Davis (University of North Carolina at Chapel Hill), Jevay Grooms (Howard University), Alberto Ortega (Indiana University Bloomington), Joaquin Alfredo-Angel Rubalcaba (University of North Carolina at Chapel Hill), and Edward Vargas (Arizona State University) analyzed data from the National Panel Study of COVID-19, a nationally representative survey of 3,338 U.S. households collected in March and April. The multi-wave survey was conducted by the authors in collaboration with researchers across multiple U.S. universities.

"Students' academic success ultimately relies on their parents' emotional health during this fragile time, which sets the learning environment for their children," said Ortega, an assistant professor at Indiana University Bloomington. "Without proper support, both parents and students will likely suffer."

Prior research has shown that stressful learning environments tend to stifle students' academic achievement.

"It is not clear when schools will return to normal," said Ortega. "Since students will likely rely on some form of distance learning for the foreseeable future, parents could face longer periods of elevated stress and mental health disruptions. Addressing parents' emotional needs during the pandemic has become essential for students' success."

According to the authors, schools can build a relationship with parents through ongoing check-ins to discuss how their children cope with distance learning and whether supplemental learning resources are needed to support students.

"Parents, as proxy educators, should be supported by their child's school during this period," said Ortega. "This was beneficial for student success before the COVID-19 pandemic, but now it is essential. Doing so also enables parents to reinforce the efforts of teachers, many of whom are stretched thin and may be experiencing burnout."

The authors note that they do not suggest that schools be re-opened to salvage parents' mental health. "Instead, schools and policymakers may want to create plans for providing mental health resources and virtual spaces to parents, in addition to helping them with questions about the schoolwork itself," Ortega said. "And it is crucial for parents to be open about their needs and to communicate with their schools when they need additional help."

The authors note that their study was conducted in spring 2020 and that the relationship between distance learning, mental health, and other demographic characteristics may change as the pandemic continues to unfold.

Researchers at Tohoku University have revealed further insight into the fetal development of our brain and the potential causes of Fragile X syndrome (FSX).

During brain development, the fetal period is vital in creating neurons from neural stem cells to build up a functional adult brain. Any impairment in the developmental program could result in severe defects in the brain.

FSX is a genetic disorder characterized by intellectual disability and autistic symptoms. Children with FSX will generally suffer from developmental delays as well as social and behavioral problems.

FSX patients have a defect in the fragile X mental retardation 1 (FMR1) gene, a gene that codes for the fragile X mental retardation protein (FNRP)--the critical factor in normal brain development.

"Our study illustrated the possible molecular mechanism that causes FXS in the fetal brain and furthers our understanding of hereditary developmental disorders in the brain's developmental stage," said Noriko Osumi, professor at the Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine.

Using next-generation sequencing, Osumi and her team identified hundreds of FMRP regulated molecules in mice fetal brains. These molecules were associated not only with neurogenesis but also autism and intellectual disability.

Their findings showed that specific groups of molecules were involved in the intracellular signaling pathways such as Ras/MAPK, Wnt/β-catenin, and mTOR.

The mTOR activity was significant in the fetal brain of FMR1 deficient mice, suggesting that increased mTOR activity may lead to abnormal proliferation and differentiation of neural stem cells in the fetal brain. Ultimately, these molecular mechanisms could be responsible for developing the brain during the fetal period and contribute to the causes of FXS.

The research team hopes this new information will serve as an essential resource for future studies of neurodevelopmental disorders.

RIVERSIDE, Calif. -- An astro-statistics course University of California, Riverside, graduate student Remington O. Sexton took three years ago taught him techniques that led him to develop free, open-source code benefiting astronomers everywhere.

Called BADASS, which stands for Bayesian AGN Decomposition Analysis for SDSS Spectra, the code in its current form fits astronomical spectra of active galactic nuclei, or AGNs, from the Sloan Digital Sky Survey, or SDSS, using advanced statistical methods.

"The code is unique in that it finally provides a way for astronomers to fit the stellar motions of stars simultaneously with many other components, is written in the popular programming language Python, and is versatile enough to fit not just AGNs, but normal galaxies as well," said Sexton, who earned his doctoral degree in physics and astronomy in September 2020.

Sexton's breakthrough work is published in the January 2021 issue of the Monthly Notices of the Royal Astronomical Society.

AGN is the general term used to describe a supermassive black hole in the center of a galaxy that is actively accreting material, usually in the form of interstellar gas, using its strong gravitational influence. AGNs are common; but not all galaxies have them at their centers. Each galaxy's center is believed, however, to have a supermassive black hole. Normal galaxies, such as the Milky Way, lack actively accreting black holes.

Different celestial objects produce different types of spectra. An object's spectrum helps astronomers identify what type of object it is. Light from a celestial body with no intervening matter produces a spectrum that appears as a continuum. A challenge in astronomy has been separating the contribution of stellar light and the contribution of AGN light from each other in the galaxy's main spectral continuum.

"The challenge is separating the two from each other, that is, isolating the stellar component from the AGN light contribution," Sexton said. "Aside from being versatile enough to fit many kinds of astronomical objects, which many codes aren't designed for, BADASS simultaneously fits stellar kinematics simultaneously with all other components in the spectra. Codes in the past used a two-step process of fitting stellar kinematics and other components independently. But this could introduce biases or uncertainties. The best way to perform spectral decomposition is to fit all components simultaneously. This is what BADASS does."

Sexton designed BADASS also to detect and fit ionized gas outflows typically seen in optical emission line features and is the first to incorporate a set of specific criteria for their detection. Ionized gas outflow refers to the bulk motion of interstellar gas capable of escaping the gravitational influence of its host galaxy and the blackhole.

"Ionized gas outflows have become a hot topic in the past decade and could explain how supermassive black holes and galaxies co-evolve with each other over cosmic time," said coauthor Gabriela Canalizo, a professor of physics and astronomy at UC Riverside and Sexton's doctoral advisor.

Currently, BADASS is only being used to fit AGN objects. Sexton emphasized, however, that the code is versatile, easy to use, and can fit other objects such as normal galaxies.

"BADASS can be used for fitting normal non-AGN host galaxies, and even individual stars," he said. "Currently, its usage is strictly for astronomical spectra, but the statistical framework BADASS is built on can be generalized for any kind of spectroscopy. That makes it extraordinarily versatile and useful."

One motivation Sexton had to develop BADASS was to phase out the need for proprietary software -- IDL programming language -- and replace it with a free open-source language such as Python.

"Now anyone can download BADASS for free and use it," he said. "It is ready to be run as long as you can install Python and all the packages it requires. Because this code can also detect and fit ionized gas outflows in optical spectra, it could greatly assist in the heightened interest in astronomy now in studying ionized gas outflows by creating larger samples for analysis."

ATLANTA - DECEMBER 16, 2020 - A new report finds that despite progress in the decline of cancer mortality, there are still critical gaps including the need to develop better tools and explore research opportunities that would lead to limiting cancer as a major health concern. This blueprint article completes an eight-part series outlining the American Cancer Society's (ACS) vision for the future control of cancer. The report focuses on highlighting research challenges and opportunities important to significantly change the future of cancer care. It appears in the ACS Journal, CA: A Cancer Journal for Clinicians.

Authored by Lynne W. Elmore, PhD, and colleagues, this piece integrates conversations with over 90 leading cancer experts to facilitate a comprehensive and diverse national research portfolio of new opportunities to advance evidence-based approaches for all cancer patients and communities. "Our overall goal is to motivate a strategy to develop innovative approaches for cancer prevention, interception, treatment, and improvement of quality of life for cancer survivors, and these findings present incredible potential for collaboration and clinical impact," write the authors.

The report highlights a gap in cancer care related to inconsistent coordination between researchers and caregivers. In the article, the authors point out the need to narrow knowledge gaps in understanding the biology of cancer development in early stages and its treatment resistance to ensure that all cancer patients can be provided cancer care that is effective, practical and affordable. They also believe that success depends on the need to develop the next generation of tools to understand, prevent, and better control all cancer types. In 2019, only about one-half of patients with cancer in the United States could be cured with existing therapies, and the remaining one-half were expected to die of their disease. In addition, while data shows that therapeutic interventions have improved significantly, chronic comorbidities often adversely affect cancer survivors and their quality of life.

The authors also note that maximizing opportunities for clinical impact requires a focus on broad-based integration of research efforts including data sets, cancer models, and testing combinatorial strategies to screen, detect and diagnose cancers. Other opportunities for research integration include forming transdisciplinary scientific teams, increasing the recruitment of ethnically and racially diverse populations in clinical trials, and testing innovative strategies to improve cancer prevention, diagnosis, treatment and survivorship in underserved communities.

"Our ability to manage cancer as a chronic disease will continue to grow and demand increased investments in survivorship research to maximize quality of life for people with cancer, their families and caregivers," said Elmore. "While it can appear daunting to consider all that needs to be done in research to conquer the hundreds of diseases we group together under the moniker of cancer, this report shows that if we continue to collaborate and leverage collective resources progress can continue to be made in the future of cancer care."

Tsukuba, Japan - Although schizophrenia is increasingly understood as a neurodevelopmental disorder, environmental factors are known to play an important role in the disease onset and progression. But now, researchers from Japan have found that exercise during a specific postnatal period may prevent the development of behaviors associated with schizophrenia.

In a study published this month in Biochemical and Biophysical Research Communications, researchers from the University of Tsukuba have revealed that low-intensity exercise during adolescence, which is a critical developmental period, significantly reduced abnormal behaviors in a mouse model of schizophrenia.

An enriched environment during development has been found to have a number of positive effects on brain function, including the prevention of neurodevelopmental disorders. Although exercise appears to have a particularly important effect, the combination of variables present in enriched environments can make it difficult to isolate the mechanisms underlying the beneficial effects. To address this, the researchers at the University of Tsukuba developed a new exercise model in which mice ran on a treadmill at a fixed speed. They then tested whether low-intensity treadmill running prevented abnormal behaviors in a mouse model of schizophrenia.

"Previous studies have shown that exercise can enhance neuronal transmission and have other beneficial effects," says lead author of the study Hikaru Koizumi. "However, the intensity, duration, and frequency of exercise have varied among studies using wheel running, making it difficult to determine how much exercise would be necessary to see these positive effects in humans."

To address this, the researchers examined behavioral and neurological function in mice that had been exposed to phencyclidine (PCP) hydrochloride during perinatal development, which is a common model of schizophrenia. The mice were then exposed to 4 weeks of low-intensity exercise during adolescence, and tested to see whether they exhibited abnormal behaviors and associated neurological abnormalities.

"The results were surprising," explains senior author Professor Hideaki Soya. "Our finding that low-intensity exercise could prevent abnormal behaviors indicates that exercise may directly contribute to the prevention of schizophrenia."

This has important implications for the potential neuropathology of schizophrenia, especially given that the low-intensity exercise recovered changes in neural signaling associated with the expected behavioral abnormalities.

"Our findings indicate that mild exercise habits during development could have a powerful preventative effect in individuals who are genetically predisposed to schizophrenia. As such, exercise could be a particularly important consideration for individuals who are at risk for developing the condition," says Professor Soya.

Mild exercise during development could prevent schizophrenia by masking or improving neurodevelopmental abnormalities present due to genetic inheritance. Specialized exercise programs for individuals who are at risk may be successful in preventing the development of schizophrenia, with serious implications for the quality of life in these individuals.

How a very "sociable" protein can hold clues about Alzheimer's origin

An international team of scientists led by the ESRF, the European Synchrotron, have found how the ECSIT protein dictates the behaviour of proteins linked to the energy activity in mitochondria, which is largely affected in Alzheimer's disease. Their results are published today in Angewandte Chemie.

The origin of the most prevalent form of Alzheimer's disease, which accounts for 95% of cases, is still not clear despite decades of scientific studies. "Before understanding the pathology, we need to understand the biology", explains Montse Soler López, scientist leading research on Alzheimer's disease at the ESRF. "The only thing we are sure about is that the most common form of Alzheimer's is linked with ageing", she asserts.

So researchers have been focusing on parts of the body that degrade dramatically with age. Neurons, for example, are long-lived cells, meaning that they don't renew themselves like other cells do. Neurons lodge mitochondria, which are so-called the "powerhouse of cell" because of their active role generating energy in the body. With time, mitochondria suffer oxidative stress and this leads to their malfunction. It has been recently discovered that people with Alzheimer's may have an accumulation of amyloids inside mitochondria (previously it was thought amyloids were only outside the neurons). Montse Soler López is trying to find whether there is a link between mitochondrial dysfunction, presence of amyloids and early disease symptoms. "We believe that malfunctioning of the mitochondria can take place 20 years before the person shows symptoms of the disease".

The team at the ESRF joined forces with scientists at the Institut de Biologie Structurale (CNRS, CEA, Université Grenoble Alpes), Grenoble Institut des Neurosciences and the European Molecular Biology Laboratory (EMBL) to study the proteins involved in the respiratory complex that allows mitochondria to generate energy. The way mitochondria work is the following: first, "helper" complexes create respiratory complexes, which subsequently create energy in the form of ATP. Soler López and her team focused on a protein called ECSIT, which is key in the immune system and appears to "socialise" or interact with many proteins.

Using the ESRF cryo-electron microscope and Small Angle X-ray Scattering at the ESRF's beamline BM29, the researchers managed to decipher the role of ECSIT in mitochondrial activity. "We've found that ECSIT plays a major role in assembling the 'helper' complex, which will assemble the respiratory complex 1, the biggest complex of the respiratory chain in the mitochondria. In the 'helper' complex there are several proteins, and we've discovered that ECSIT regulates the function of the proteins so that they do the job they are required to do", explains Soler López.

One of these proteins is ACAD9. This is a protein that can work to oxidise fatty acids or to assemble the respiratory complex. Soler López and her colleagues found that ECSIT shuts down the oxidizing function so that the protein can focus on assembling the respiratory complex. "If ECSIT didn't take action, it would be a mess, with proteins doing several things at the same time, so ECSIT is actually crucial in the whole respiratory complex and hence, in mitochondrial activity", she adds.

They also found that ECSIT is very sensitive to amyloids presence. "We think that when the amyloids start appearing in the mitochondria, ECSIT goes into overdrive, pushing the respiration mechanism to protect the mitochondria from the damaging invasion. If the mechanism is not well controlled it can become destructive and end up destroying the neuron. But we are still investigating this, it is the next step in our research", concludes Soler López.

Tsukuba, Japan - The body plan of an organism, crafted over millennia of evolutionary trial and error, is so exquisitely fine-tuned that even a subtle deviation can be detrimental to individual survival and reproductive success. Now, researchers at the University of Tsukuba have elucidated the workings of an enzyme, lysine demethylase 7a (kdm7a), that facilitates appropriate development of the mouse embryo from tip to tail, 'according to plan' by modulating expression of Hox genes. As these genes, master regulators of embryonal morphogenesis, have been highly conserved over evolution, the findings apply in varying degree to lower species and to all vertebrates, us included.

It is an astounding fact that the unicellular zygote formed at fertilization contains all the information needed for development into a multicellular organism of immense complexity organized in well-ordered symmetry. How these data are encrypted and decoded is an escalating mystery as emerging answers only unearth further questions. Hox genes allocate regions along the head-tail axis of the developing embryo for development of appropriate structures; in vertebrates they specify the numbers and sequential shapes of the spinal bones.

Some histone-modifying enzymes have been implicated in normal morphogenesis as well as in disease. Using CRISPR-Cas9 gene editing technology, the research team first developed knockout mice (Kdm7a?/?) by introducing frameshift mutation. As a result, they obtained mice carrying the mutations for truncated Kdm7a proteins lacking demethylase activity.

The researchers analyzed postnatal skeletal preparations of both wild-type and Kdm7a-/-mice. Dr Yasuharu Kanki, senior author, describes the findings. "As expected, all wild-type mice showed a normal axial skeleton. Interestingly, all Kdm7a?/? mice and some heterozygous mutants exhibited vertebral transformation; some vertebrae assumed the characteristics and appendages of their anterior neighbors."

The researchers next used RNA sequencing to examine the expression of Hox genes during embryogenesis. Their findings support a functional role of Kdm7a-mediated transcriptional control, especially of the posteriorly situated Hox genes, and suggest that regulation of the repressive histone mark H3K9me2 might be involved.

"Our data help explain morphogenesis along the anterior/posterior axis in the mouse embryo and, by extension, in all vertebrates including humans," says Dr Kanki. "Deciphering the interplay of various genetic and epigenetic determinants of embryonal morphogenesis as well as the underlying molecular mechanisms increases our knowledge of evolutionary developmental biology and may help in the understanding of disease."