Culture

What The Study Did: This observational study looked at whether race and socioeconomic factors were associated with children enrolled in national clinical trials receiving high-cost proton radiotherapy for treatment of cancer.

Authors: Daphne A. Haas-Kogan, M.D., of the Dana-Farber Cancer Institute in Boston, is the corresponding author.

 To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoncol.2020.2259)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Non-white Americans, especially Asian Americans, are at disproportionately higher risk for gastric cancer compared to non-Hispanic white Americans. A new study breaks down this risk according to specific ethnicities and locations within the stomach.

The study published Aug. 6 in Gastroenterology analyzed California Cancer Registry data for the seven largest Asian American populations (Chinese, Japanese, Korean, Filipino, Vietnamese, South Asian and Southeast Asian) as well as for non-Hispanic whites, non-Hispanic blacks and Hispanic populations.

The population-based study revealed that non-white race and ethnic groups had a several-fold higher risk of developing stomach cancer in the main area of the stomach (noncardia gastric cancer) compared to the non-Hispanic white population. This risk was most striking among Korean Americans age 50 and older, who demonstrated a 12-fold to 14.5-fold higher risk compared to non-Hispanic whites. This is the most common location for stomach cancer to develop. However, Asian Americans -- with the exception of Japanese American men -- had a lower risk than non-Hispanic whites of developing gastric cancer in the upper portion of the stomach where it joins the esophagus (cardia gastric cancer).

"We specifically chose to analyze individuals age 50 years and older since this is the age group for whom average-risk colorectal cancer screening and high-risk esophageal cancer screening is recommended," said Shailja Shah, MD, MPH, assistant professor of Medicine, the study's lead author and corresponding author.

"Unfortunately, even though certain ethnic groups have rates of gastric cancer that even exceed colorectal cancer, and even though gastric cancer is more common than esophageal cancer, screening for gastric cancer does not yet occur in the United States among high-risk groups. We are hopeful that the findings of this study will break the inertia surrounding gastric cancer screening"

The research sets the stage for developing targeted risk reduction programs for gastric cancer in the United States. Shah and colleagues recently published two studies demonstrating that gastric cancer screening starting at age 50 old in non-white race and ethnic groups is cost-effective. Shah was also one of the lead members of the American Gastroenterology Association's Technical Review team on gastric intestinal metaplasia (gastric precancer) surveillance for early gastric cancer detection. Shah's research is set on developing a strong foundation of evidence to establish screening guidelines for gastric cancer in the United States, where the number of people at risk for the cancer is increasing as the nation's population becomes more diverse.

Worldwide, gastric cancer is the fifth most common cancer and third leading cause of cancer-related death. In the United States, gastric cancer ranks 15th among cancers, but it afflicts population groups disproportionately.

The study in Gastroenterology revealed that for gastric cancer in the main area of the stomach, the incidence rate for Korean Americans was 49 cases per 100,000 people, 23.9 for Vietnamese Americans, 21.1 for Southeast Asian Americans (Cambodian, Laotian, Hmong and Thai), 19.2 for Japanese Americans, 17.6 for Chinese Americans, 14.0 for Hispanic Americans, 11.2 for non-Hispanic black Americans, 7.75 for South Asian Americans, 6.69 for Filipino Americans and 3.7 for non-Hispanic white Americans.

Men had significantly higher rates of gastric cancer compared to women. For instance, the rate for gastric cancer in the main area of the stomach was 70.0 per 100,000 for Korean American men compared to 33.5 for Korean American women.

"The immediate need for gastric cancer prevention and early detection efforts in the U.S. is amplified when considering that the pool of at-risk individuals is only expected to grow, with non-Hispanic whites now considered the minority population in 35 of the 50 largest cities and projections that non-Hispanic whites will no longer be the overall majority population by 2065," Shah said.

Its neck was three times as long as its torso, but had only 13 extremely elongated vertebrae: Tanystropheus, a bizarre giraffe-necked reptile which lived 242 million years ago, is a paleontological absurdity. A new study led by the University of Zurich has now shown that the creature lived in water and was surprisingly adaptable.

For over 150 years, paleontologists have puzzled over Tanystropheus, its strangely long neck and whether it lived mostly underwater or on land. An international team led by the University of Zurich has now reconstructed its skull in unprecedented detail using synchrotron radiation micro-computed tomography (SRμCT), an extremely powerful form of CT scanning. In addition to revealing crucial aspects of its lifestyle, this also shows that Tanystropheus had evolved into two different species.

Underwater ambush predator

The researchers were able to reconstruct an almost complete 3D skull from a severely crushed fossil. The reconstruction reveals that the skull of Tanystropheus has several very clear adaptations for life in water. The nostrils are located on the top of the snout, much like in modern crocodilians, and the teeth are long and curved, perfectly adapted for catching slippery prey like fish and squid. However, the lack of visible adaptations for swimming in the limbs and tail also means that Tanystropheus was not a particularly efficient swimmer. "It likely hunted by stealthily approaching its prey in murky water using its small head and very long neck to remain hidden," says lead author and UZH paleontologist Stephan Spiekman.

Two species living together

Tanystropheus remains have mainly been found at Monte San Giorgio on the border between Switzerland and Italy, a place so unique for its Triassic fossils that it has been declared a UNESCO World Heritage Site. Two types of Tanystropheus fossils are known from this location, one small and one large. Until now, these were believed to be the juveniles and adults of the same species.

However, the current study disproves this assumption. The reconstructed skull, belonging to a large specimen, is very different from the already known smaller skulls, particularly when it comes to its dentition. In order to see whether the small fossils actually belonged to young animals, the researchers looked at cross sections of limb bones from the smaller type of Tanystropheus. They found many growth rings which form when bone growth is drastically slowed down. "The number and distribution of the growth rings tells us that these smaller types were not young animals, as previously considered, but mature ones," says last author Torsten Scheyer. "This means that the small fossils belonged to a separate, smaller species of Tanystropheus."

Specialists in different food sources

According to Spiekman, these two closely related species had evolved to use different food sources in the same environment: "The small species likely fed on small shelled animals, like shrimp, in contrast to the large species which ate fish and squid." For the researchers, this is a really remarkable finding: "We expected the bizarre neck of Tanystropheus to be specialized for a single task, like the neck of a giraffe. But actually, it allowed for several lifestyles."

ANN ARBOR, Michigan -- When COVID-19 struck, health care pivoted hard. Any unnecessary procedures or appointments were postponed. For people with cancer, that pivot was particularly shattering.

"COVID-19 changed the face of health care in the United States virtually overnight. Oncologists were discussing with their patients whether the benefit of coming in for treatment outweighed the risk of being exposed to the virus in the health care setting," says Laila A. Gharzai, M.D., LLM, a radiation oncology resident at Michigan Medicine.

"It was a challenging shift for physicians, and we personally wanted some help navigating these conversations," she says.

In response, Gharzai and colleagues interviewed eight physicians to identify specific communication challenges related to COVID-19 and surveyed 48 patients to get their perspective.

They identified three core communication strategies and applied them to eight specific scenarios impacting patients, including concerns around risk of COVID-19, delays in testing or treatment, changes to treatment and follow-up care. Informed by the communication strategies, the team created examples of language that oncologists could use to respond to patients empathetically. Their results are published in JAMA Oncology.

"What impacted me most was hearing just how tough these conversations were. As oncologists, we are used to having tough conversations with our patients. COVID-related conversations took this to a whole other level, by incorporating a new challenge of having to view all of our decisions with a public health lens. This guide was important to give providers a quick resource when they needed it most," Gharzai says.

Patients' concerns ranged from their risk of getting coronavirus to fears that a delayed test could miss a growing cancer. Many patients felt they were being punished or ignored, as if their health needs were less important. And while the decisions were all made with a view toward keeping patients safe from the greater threat of COVID-19, cancer is not used to taking a backseat.

"Patients are understandably emotional when they receive a cancer diagnosis, even under normal circumstances. This emotional response was amplified by the stress of changes due to the pandemic," says Reshma Jagsi, M.D., D.Phil, Newman Family Professor and deputy chair of radiation oncology at Michigan Medicine and senior author on the paper.

"The practical language in the guide really helped me to reassure patients that I recognized their very appropriate emotions, that I care deeply about them, and that I was going to try to help," she says.

The team published their guidelines online in April, when COVID-19 was peaking in Michigan. It remains available to providers.

CAMBRIDGE, MA -- Several thousand strains of bacteria live in the human gut. Some of these are associated with disease, while others have beneficial effects on human health. Figuring out the precise role of each of these bacteria can be difficult, because many of them can't be grown in lab studies using human tissue.

This difficulty is especially pronounced for species that cannot live in oxygen-rich environments. However, MIT biological and mechanical engineers have now designed a specialized device in which they can grow those oxygen-intolerant bacteria in tissue that replicates the lining of the colon, allowing them to survive for up to four days.

"We thought it was really important to contribute a tool to the community that could be used for this extreme case," says Linda Griffith, the School of Engineering Professor of Teaching Innovation in MIT's Department of Biological Engineering. "We showed that you can grow these very fastidious organisms, and we were able to study the effects they have on the human colon."

Using this system, the researchers showed that they could grow a strain of bacteria called Faecalibacterium prausnitzii, which lives in the human gut and protects against inflammation. They also showed that these bacteria, which are often diminished in patients with Crohn's disease, appear to exert many of their protective effects through the release of a fatty acid called butyrate.

Griffith and David Trumper, an MIT professor of mechanical engineering, are the senior authors of the study, which appears today in the journal Med. MIT postdocs Jianbo Zhang and Yu-Ja Huang are the lead authors of the paper.

Oxygen sensitivity

The human gut's complex microbiome environment is difficult to model using animals such as mice, in part because mice eat a very different diet from humans, Griffith says.

"We've learned a huge amount from mice and other animal models, but there are a lot of differences, especially when it comes to the gut microbiome," she says.

Most of the bacteria that live in the human gut are anaerobic, meaning that they do not require oxygen to survive. Some of these bacteria can tolerate low levels of oxygen, while others, such as F. prausnitzii, cannot survive oxygen exposure, which makes it difficult to study them in a laboratory. Some researchers have designed devices in which they can grow human colon cells along with bacteria that tolerate low levels of oxygen, but these don't work well for F. prausnitzii and other highly oxygen-intolerant microbes.

To overcome this, the MIT team designed a device that allows them to precisely control oxygen levels in each part of the system. Their device contains a channel that is coated with cells from the human mucosal barrier of the colon. Below these cells, nutrients are pumped in to keep the cells alive. This bottom layer is oxygen-rich, but the concentration of oxygen decreases toward the top of the mucosal cell layer, similarly to what happens in the interior of the human colon.

Just as they do in the human colon, the barrier cells in the channel secrete a dense layer of mucus. The MIT team showed that F. prausnitzii can form clouds of cells in the outer layer of this mucus and survive there for up to four days, in an environment that is kept oxygen-free by fluid flowing across it. This fluid also contains nutrients for the microbes.

Using this system, the researchers were able to show that F. prausnitzii does influence cell pathways involved in inflammation. They observed that the bacteria produce a short-chain fatty acid called butyrate, which has previously been shown to reduce inflammation. After butyrate levels went up, the mucosal cells showed a reduction in the activity of a pathway called NF kappa B. This reduction calms inflammation.

"Overall, this pathway has been reduced, which is really similar to what people have seen in humans," Zhang says. "It seems that the bacteria are desensitizing the mammalian cells to not overreact to the dangers in the outside environment, so the inflammation status is being calmed down by the bacteria."

Patients with Crohn's disease often have reduced levels of F. prausnitzii, and the lack of those bacteria is hypothesized to contribute to the overactive inflammation seen in those patients.

When the researchers added butyrate to the system, without bacteria, it did not generate all of the effects that they saw when the bacteria were present. This suggests that some of the bacteria's effects may be exerted through other mechanisms, which the researchers hope to further investigate.

Microbes and disease

The researchers also plan to use their system to study what happens when they add other species of bacteria that are believed to play a role in Crohn's disease, to try to further explore the effects of each species.

They are also planning a study, working with Alessio Fasano, the division chief of pediatric gastroenterology and nutrition at Massachusetts General Hospital, to grow mucosal tissue from patients with celiac disease and other gastrointestinal disorders. This tissue could then be used to study microbe-induced inflammation in cells with different genetic backgrounds.

"We are hoping to get new data that will show how the microbes and the inflammation work with the genetic background of the host, to see if there could be people who have a genetic susceptibility to having microbes interfere with the mucosal barrier a little more than other people," Griffith says.

She also hopes to use the device to study other types of mucosal barriers, including those of the female reproductive tract, such as the cervix and the endometrium.

CHICAGO: A new breast cancer study brings reassuring findings for women with early-stage breast cancer who were forced to delay their cancer operations because of the Coronavirus Disease 2019 (COVID-19) pandemic. A longer time from diagnosis to surgical treatment does not lower overall survival of women with early-stage breast cancer who underwent delayed operations before the pandemic, according to the study results, which are published as an "article in press" on the Journal of the American College of Surgeons website in advance of print.

The researchers also found no survival decrease with operative delays in women with estrogen-sensitive, early-stage breast cancer who received neoadjuvant endocrine therapy (NET). NET is preoperative hormone treatment with anti-estrogen drugs such as tamoxifen or aromatase inhibitors.

Patients with estrogen receptor (ER)-positive breast cancer, whose cancer is fueled by estrogen, typically receive anti-estrogen therapy after surgical removal of the tumor or breast. However, endocrine therapy was recommended nationwide as the initial treatment of ER-positive breast cancer during pandemic-related surgical delays, said lead study author Christina Minami, MD, MS, an associate surgeon at Brigham and Women's Hospital, Boston.

"Usually we take these patients with very small tumors directly to surgery, so it is a big change in practice to first put those patients on tamoxifen or an aromatase inhibitor," Dr. Minami said. "What we can say from our findings is that despite the delay in surgical therapy, because you were on neoadjuvant endocrine therapy, we do not think that your survival will at all be impacted."

The study included data from nearly 379,000 patients in two groups. One group had ductal carcinoma in situ (DCIS), the earliest form of breast cancer, also called stage 0 or noninvasive. The other group had small invasive tumors--stage I and limited stage II--that had not spread to nearby lymph nodes and were ER-positive.

Surgical intervention delays due to COVID-19

These groups, Dr. Minami said, represent most breast cancer patients who needed to postpone their nonurgent operations early in the COVID-19 outbreak according to the surgical prioritization recommendations of the COVID-19 Pandemic Breast Cancer Consortium. In March, the Consortium recommended NET for patients with ER-positive DICS and ER-positive, invasive early-stage breast cancer while they waited for their operations.1 At that time, the Consortium included the American Society of Breast Surgeons, National Accreditation Program for Breast Centers, National Comprehensive Cancer Network, American College of Surgeons Commission on Cancer, and American College of Radiology.

To better understand the ramifications of these surgical delay tactics, the researchers conducted this study using the National Cancer Database and analyzed data for 378,839 patients with early-stage breast cancer treated from 2010 to 2016. Cosponsored by the ACS and the American Cancer Society, this database includes information on more than 70 percent of newly diagnosed cancer cases in the United States and is the largest cancer registry of its kind.

The researchers evaluated whether longer time to surgical treatment up to one year after diagnosis had an association with final pathologic staging of the cancer or with five-year overall survival.

Increased "upstaging"

In women with invasive early-stage breast cancer, a longer time to the initial cancer operation showed no association with pathologic upstaging, the researchers reported. Upstaging is a change to a higher cancer stage based on surgical and pathologic findings, compared with the clinical stage--what a surgeon determined from physical examination and imaging results.

Women with ER-positive DCIS, however, had a slightly increased odds of pathologic upstaging with a surgical delay exceeding 60 days, the researchers reported. Patients whose DCIS was ER-negative (not estrogen-fueled) had a higher risk of upstaging only if they underwent an operation more than 120 days after diagnosis; they had an odds of 1.36 to 1 compared with patients who underwent surgical treatment within the first 60 days, according to the article.

This increase in upstaging among DCIS patients had no impact on their overall survival, Dr. Minami said.

She stressed, however, that the patient population in their study differs from the patients who received NET during the pandemic. Before the pandemic, NET was not in wide use for U.S. patients with early-stage, ER-positive breast cancer.2 Study participants who received NET from 2010 to 2016 did so for specific reasons, such as older age and coexisting illnesses, whereas in the pandemic, NET recipients were "almost an unselected population," Dr. Minami explained.

She added that although the researchers used "the best data currently available to study the possible outcomes of oncologic surgical delays," determination of the actual impact of COVID-19-related surgical delays requires study in patients treated during this time.

Despite this study limitation, senior study author Elizabeth Mittendorf, MD, PhD, FACS, professor of surgery at Brigham and Women's Hospital, said she has found the study findings helpful to share with her patients who experienced surgical delays.

"We can tell our patients they can still expect an excellent prognosis from their early-stage hormone receptor-positive cancer and that their excellent prognosis is not negatively impacted by this delay they have experienced," Dr. Mittendorf said.

Ants are the most successful social insects and play an important role in modern terrestrial ecosystems. The origin and early evolution of ants have attracted lots of attention.

Among the earliest fossil ants known, haidomyrmecine "hell ants" from Cretaceous amber reveal an ancient and dramatic early burst radiation of adaptive forms.

Hell ants possessed bizarre scythe-like mouthparts along with a striking array of horn-like cephalic projections. But how did this type of ant evolve? This question was long a mystery.

Now, however, an international research team co-led by Prof. WANG Bo from the Nanjing Institute of Geology and Palaeontology (NIGPAS) of the Chinese Academy of Sciences has confirmed the special trap-jaw predation mechanism of hell ants, providing new insights into their evolution.

The study was published in Current Biology on August 6.

The research team conducted morphological and anatomical analysis of the heads of all hell ants in the amber specimens, in combination with a special predator specimen, and confirmed the "trap-jaw" predation mechanism adopted by hell ants from their morphological and functional aspects.

The scientists reported an instance of fossilized predation that provides direct evidence for the function of dorsoventrally expanded mandibles and elaborate horns.

Their findings confirmed the hypothesis that hell ants captured other arthropods between mandible and horn in a manner that could only be achieved by articulating their mouthparts in an axial plane perpendicular to that of modern ants.

The head capsule and mandibles of hell ants are uniquely integrated as a consequence of this predatory mode and covary across species, while no evidence has been found of such modular integration in extant ant groups.

The results of this study suggest an extinct early burst adaptive radiation into morphospace that was unoccupied by any living taxon. This radiation was triggered by an innovation in mouthpart movement and subsequent modular covariation between mandible and horn.

The new results also suggest that hell ant cephalic integration - analogous to the vertebrate skull - triggered a pathway for an ancient adaptive radiation and expansion into morphospace unoccupied by any living taxon.

Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition. Experts from Charité - Universitätsmedizin Berlin, the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF), along with colleagues from a nationwide research network, present these findings in the scientific journal Cell.

Most patients infected with the coronavirus SARS-CoV-2 show mild or even no symptoms. However, 10 to 20 percent of those affected develop pneumonia during the course of COVID-19 disease, some of them with life-threatening effects. "There is still not very much known about the causes of these severe courses of the disease. The high inflammation levels measured in those affected actually indicate a strong immune response. Clinical findings, however, rather tend to indicate an ineffective immune response. This is a contradiction," says Joachim Schultze, professor at the University of Bonn and research group leader at the DZNE. "We therefore assume that although immune cells are produced in large quantities, their function is defective. That is why we examined the blood of patients with varying degrees of COVID-19 severity," explains Leif Erik Sander, Professor of Infection Immunology and Senior Physician Charité's Medical Department, Division of Infectious Diseases and Respiratory Medicine.

High-precision methods

The study was carried out within the framework of a nationwide consortium - the "German COVID-19 OMICS Initiative" (DeCOI) - resulting in the analysis and interpretation of the data being spread across various teams and sites. Joachim Schultze was significantly involved in coordinating the project. The blood samples came from a total of 53 men and women with COVID-19 from Berlin and Bonn, whose course of disease was classified as mild or severe according to the World Health Organization classification. Blood samples from patients with other viral respiratory tract infections as well as from healthy individuals served as important controls.

The investigations involved the use of single-cell OMICs technologies, a collective term for modern laboratory methods that can be used to determine, for example, the gene activity and the amount of proteins on the level of single, individual cells - thus with very high resolution. Using this data, the scientists characterized the properties of immune cells circulating in the blood - so-called white blood cells. "By applying bioinformatics methods on this extremely comprehensive data collection of the gene activity of each individual cell, we could gain a comprehensive insight of the ongoing processes in the white blood cells," explains Yang Li, Professor at the Centre for Individualised Infection Medicine (CiiM) and Helmholtz Centre for Infection Research (HZI) in Hannover. "In combination with the observation of important proteins on the surface of immune cells, we were able to decipher the changes in the immune system of patients with COVID-19," adds Birgit Sawitzki, Professor at the Institute of Medical Immunology on Campus Virchow-Klinikum.

"Immature" cells

The human immune system comprises a broad arsenal of cells and other defense mechanisms that interact with each other. In the current study, the focus was on so-called myeloid cells, which include neutrophils and monocytes. These are immune cells that are at the very front of the immune response chain, i.e. they are mobilized at a very early stage to defend against infections. They also influence the later formation of antibodies and other cells that contribute to immunity. This gives the myeloid cells a key position.

"With the so-called neutrophils and the monocytes we have found that these immune cells are activated, i.e. ready to defend the patient against COVID-19 in the case of mild disease courses. They are also programmed to activate the rest of the immune system. This ultimately leads to an effective immune response against the virus," explains Antoine-Emmanuel Saliba, head of a research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg.

But the situation is different in severe cases of COVID-19, explains Sawitzki: "Here, neutrophils and monocytes are only partially activated and they do not function properly. We find considerably more immature cells that have a rather inhibitory effect on the immune response." Sander adds: "The phenomenon can also be observed in other severe infections, although the reason for this is unclear. Many indications suggest that the immune system stands in its own way during severe courses of COVID-19. This could possibly lead to an insufficient immune response against the corona virus, with a simultaneous severe inflammation in the lung tissue."

Approaches to therapy?

The current findings could point to new therapeutic options, says Anna Aschenbrenner from the LIMES Institute at the University of Bonn: "Our data suggest that in severe cases of COVID-19, strategies should be considered that go beyond the treatment of other viral diseases." The Bonn researcher says that in the case of viral infections one does not actually want to suppress the immune system. "If, however, there are too many dysfunctional immune cells, as our study shows, then one would very much like to suppress or reprogram such cells." Jacob Nattermann, Professor at the Medical Clinic I of the University Hospital Bonn and head of a research group at the DZIF, further explains: "Drugs that act on the immune system might be able to help. But this is a delicate balancing act. After all, it's not a matter of shutting down the immune system completely, but only those cells that slow down themselves, so to speak. In this case these are the immature cells. Possibly we can learn from cancer research. There is experience with therapies that target these cells."

Nationwide team effort

In view of the many people involved, Schultze emphasizes the cooperation within the research consortium: "As far as we know, this study is one of the most comprehensive studies to date on the immune response in COVID-19 based on single cell data. The parallel analysis of two independent patient cohorts is one of the strengths of our study. We analyzed patient cohorts from two different sites using different methods and were thus able to validate our findings directly. This is only possible if research data is openly shared and cooperation is based on trust. This is extremely important, especially in the current crisis situation."

Despite our broad understanding of the different brain regions activated during rapid-eye-movement sleep, little is known about what this activity serves for. Researchers at the University of Bern and the Inselspital have now discovered that the activation of neurons in the hypothalamus during REM sleep regulates eating behaviour: suppressing this activity in mice decreases appetite.

While we are asleep, we transition between different phases of sleep each of which may contribute differently to us feeling rested. During (rapid eye movement) REM sleep, a peculiar sleep stage also called paradoxical sleep during which most dreaming occurs, specific brain circuits show very high electrical activity, yet the function of this sleep-specific activity remains unclear.

Among the brain regions that show strong activation during REM sleep are areas that regulate memory functions or emotion, for instance. The lateral hypothalamus, a tiny, evolutionarily well conserved brain structure in all mammals also shows high activity during REM sleep. In the awake animals, neurons from this brain region orchestrate appetite and the consumption of food and they are involved in the regulation of motivated behaviours and addiction.

In a new study, researchers headed by Prof. Dr. Antoine Adamantidis at the University of Bern set out to investigate the function of the activity of hypothalamic neurons in mice during REM sleep. They aimed at better understanding how neural activation during REM sleep influences our day-to-day behaviour. They discovered that suppressing the activity of these neurons decreases the amount of food the mice consume. "This suggests that REM sleep is necessary to stabilize food intake", says Adamantidis. The results of this study have been published in the journal Proceedings of the National Academy of Sciences (PNAS).

Long-lasting effect on neuronal activity and feeding behavior

The researcher discovered that specific activity patterns of neurons in the lateral hypothalamus that usually signal eating in the awake mouse are also present when the animals were in the stage of REM sleep. To assess the importance of these activity patterns during REM sleep the research group used a technique called optogenetics, with which they used light pulses to precisely shut down the activity of hypothalamic neurons during REM sleep. As a result, the researchers found that the activity patterns for eating were modified and that the animals consumed less food.

"We were surprised how strongly and persistently our intervention affected the neural activity in the lateral hypothalamus and the behaviour of the mice", says Lukas Oesch, the first author of the study. He adds: "The modification in the activity patterns was still measurable after four days of regular sleep." These findings suggest that electrical activity in hypothalamic circuits during REM sleep are highly plastic and essential to maintain a stable feeding behaviour in mammals.

It is a question of quality

These findings point out that sleep quantity alone is not solely required for our well-being, but that sleep quality plays a major role in particular to maintain appropriate eating behaviour. "This is of particular relevance in our society where not only sleep quantity decreases but where sleep quality is dramatically affected by shift work, late night screen exposure or social jet-lag in adolescents", explains Adamantidis.

The discovered link between the activity of the neurons during REM sleep and eating behaviour may help developing new therapeutical approaches to treat eating disorders. It might also be relevant for motivation and addiction. "However, this relationship might depend on the precise circuitry, the sleep stage and other factors yet to be uncovered", adds Adamantidis.

Rhythms produced by the brain can reliably be used to predict how sensitive we are to pain, new research shows.

The living brain is constantly producing regular rhythmic patterns of activity, which can be compared to musical notes. Scientists at the University of Birmingham in the UK, and the University of Maryland School of Dentistry in the US, have successfully demonstrated that one particularly prevalent pattern of brain activity, called alpha waves, strongly relates to the body's susceptibility or resilience to pain.

Alpha waves oscillate between 8-14 Hz, with the peak frequency varying across individuals. The researchers demonstrated how a measurement of an individual's alpha wave frequency can be used as a reliable pain indicator.

The study, led by graduate student Andrew Furman and published in the journal Cerebral Cortex, suggests that these alpha waves could be used to help clinicians understand how susceptible a patient to experience severe pain post-surgery.

Dr David Seminowicz of the University of Maryland School of Dentistry is co-author of the study. He explains: "Understanding a patient's pain sensitivity could be really important in, for example, deciding whether an elective procedure is the best option or planning post-surgery rehabilitation. Pain management drugs or techniques such as mindfulness meditation can also be used before surgery to help minimise pain."

Dr Ali Mazaheri, from the University of Birmingham's School of Psychology and Centre for Human Brain Health and also co-author of the study, adds: "Severe pain following surgery is often also a good indicator of whether or not a patient is likely to go on to develop chronic pain. Understanding whether or not a person is at high risk of developing these symptoms will help patients and clinicians make better informed choices about the best course of treatment."

Alpha waves are just one type of electrical activity going on continually in our brains. They're thought to be most present when a person is awake, but maybe idle. In our sensory systems, their presence signals that a particular part of the system has 'closed down' for processing. When the waves are reduced, that system is ready to start working again.

For most people these oscillations occur continuously in the brain at frequencies of between 8-14Hz. Previous research carried out by the group showed that people with alpha waves occurring at the higher end of this scale were more resilient to pain, while those at the lower end were more susceptible.

In this experiment, the team wanted to find out whether, by taking an initial measurement of the subject's alpha waves, it was possible to predict their reaction to pain.

The researchers tested 61 healthy participants, both men and women, aged between 21 and 42. Alpha waves were measured in each participant using electroencephalography (EEG) and then participants were each exposed to two different pain episodes. In the first of these a cream containing capsaicin - the active ingredient in chilli peppers - was applied to produce sensitised skin; in the second participants underwent repeated applications of heat. After eight weeks, the subjects returned to repeat the experiment.

The results showed that measuring alpha waves did give a reliable indication of a person's susceptibility or resilience to pain. These results were reliable both in the initial assessment and in the eight-week follow up.

In Birmingham, these principles are already being tested in partnership with clinicians at the Heartlands and Queen Elizabeth Hospitals. Dr Mazaheri is leading a study investigating the use of alpha waves and the pain experience of lung cancer patients undergoing lung biopsies.

"We know that lung surgery is a particularly painful procedure, with between 40 and 60 per cent of patients going on to develop debilitating pain after surgery," explains Dr Mazaheri. "By predicting which patients are likely to develop this pain, we can start to explore other options, such as radiotherapy, or make sure that intensive rehabilitation programmes are in place to support those patients through recovery."

The team is currently actively seeking funding to continue this work.

Researchers have identified a pattern of longer-term symptoms likely to be experienced by people who were hospitalised with the COVID-19 infection.

They include fatigue, breathlessness, psychological distress - including problems with concentration and memory - and a general decline in quality of life.

Some patients, particularly those who had been in intensive care, had symptoms associated with cases of PTSD (post-traumatic stress disorder).

The findings provide the first detailed insight into problems facing patients recovering from COVID-19 in the UK.

Dr Manoj Sivan, Associate Clinical Professor at the University of Leeds and a Consultant in Rehabilitation Medicine at Leeds General Infirmary, supervised the research project. He said: "COVID-19 is a new illness and we have very little information on longer term problems in individuals after discharge from hospital."

"The emerging evidence is that for some, the road to recovery may take months and it is vital specialist rehabilitation is on hand to support them. This research gives an important insight into patient needs, and that will help shape services in the community."

The findings - Post-discharge symptoms and rehabilitation needs in survivors of COVID-19 infection: a cross-sectional evaluation - have been published in the Journal of Medical Virology.

Dr Stephen Halpin, Senior Research Fellow at the University of Leeds and Consultant with Leeds Teachings Hospitals NHS Trust, said: "This research follows our previous work of predicting COVID-19 patients' long-term needs based on previous coronavirus outbreaks of SARS in 2002 and MERS in 2012. The health problems are similar but on a larger scale given the number of people affected."

The research team - involving multidisciplinary specialists from the University of Leeds, Leeds Teaching Hospitals NHS Trust, Leeds Community Healthcare NHS Trust and Leeds Beckett University - followed 100 people recovering from COVID-19, four-to-eight weeks after being discharged from hospital in Leeds.

The COVID-19 survivors were divided into two groups: those who had become critically ill and needed intensive care - 32 people were in this category; and those who were treated on a ward without needing intensive care - 68 people were in this category.

Patients were contacted by a member of the hospital's rehabilitation team and asked a series of questions about their recovery and symptoms they were still experiencing.

Results

The most prevalent symptom was fatigue. More than 60 percent of people who had been treated on a ward reported fatigue, and one-third of them described it as moderate or severe. For patients who had been in intensive care, 72 percent reported fatigue. Of those, more than half said it was moderate or severe.

The second most common symptom was breathlessness. People in both groups said they had feelings of breathlessness which had not existed before they contracted COVID-19. This was higher in the group that had been the most ill, the intensive care group versus those who had been treated in a ward - 65.6 percent versus 42.6 percent.

The third most prevalent symptoms were neuropsychological. The research survey found that almost one quarter of the people who had been on a ward and just under a half of the people who had been in intensive care had some of the symptoms of PTSD.

Writing in the paper, the researchers said: "PTSD symptoms are a well-recognised component of post- intensive care unit syndrome caused by a variety of factors including fear of dying, invasive treatment, pain, delirium, inability to communicate, weakness, immobility, and sensory problems and sleep deprivation."

More than two-thirds (68.8 percent) of patients in the intensive care group and just under half (45.6 percent) of the other group said their overall quality of life had deteriorated.

The researchers say the rehabilitation needs of patients who did not require hospital care need to be further investigated and they are working on understanding this in future research.

BOSTON (Aug. 6, 2020)--Researchers at Tufts University School of Medicine and Tufts Graduate School of Biomedical Sciences have discovered neural mechanisms in mice specific to females that can shift estrogen from playing a protective role in glucose metabolism to one that is disruptive. The authors of the study, published online in the Proceedings of the National Academies of Sciences (PNAS), hypothesize that the metabolic "switch" mediated by estrogen may provide clues to the increased risk of insulin resistance and diabetes among post-menopausal women.

The study focused on a region of the brain called the ventromedial hypothalamus (VMH) and found that the removal of the metabotropic glutamate receptor 5 (mGluR5) in that area caused estrogen to reduce the activity of neurons important for glycemic control, leading to insulin resistance and glucose intolerance. These effects were opposite to the increased neuronal activity and enhanced glucose metabolism observed in mice with the receptor following estrogen delivery. The paradoxical outcome on glucose metabolism was seen in female, but not male, mice.

Prior research by others had indicated that the VMH region of the brain plays a role in managing appropriate levels of glucose production in the liver and utilization of circulating glucose by cells and tissues. Within the VMH, steroidogenic factor 1 (SF1) neurons are responsible for helping to regulate glucose as well as lipid levels, e.g. cholesterol and triglycerides. However, less was known about exactly how the VMH regulates glucose metabolism. Similarly, while the beneficial effects of estrogen have long been recognized, the mechanisms driving these effects remain poorly understood.

mGluR5 is highly expressed in the VMH and is known to regulate neuron activity in other parts of the brain. When the researchers knocked out the expression of mGluR5 specifically in the VMH using gene editing methods, they observed a reduction of SF1 neuron activity and a disruption of normal glucose regulation, but only in the female mice.

Knocking out mGluR5 in male mice did not have these effects and their glucose metabolism remained normal.

Noting different effects on glucose metabolism between male and female mice, the researchers examined the potential involvement of sex hormones. They discovered that estrogen, which normally promotes metabolic health in females, supports glycemic control only when mGluR5 is present in the VMH. Without mGluR5, estrogen actually suppresses the neurons responsible for regulating glucose - it becomes a metabolic liability.

"Our findings show that the glutamate receptor is essential for the effects of estrogen regulating proper glucose levels and utilization in females, whereas it does not appear to play that regulatory role in males. This could give us insight into many of the differences between men and women in their risk of diabetes and disease progression throughout life," said senior author Maribel Rios, researcher in neuroscience at Tufts School of Medicine and a member of the neuroscience and cell, molecular and developmental biology program faculties at Tufts Graduate School of Biomedical Sciences.

(Jena, Germany) The periodic system contains 118 chemical elements. However, only a few of them, such as hydrogen, carbon, nitrogen, oxygen and silicon, are of major importance in our daily lives. But things become really exciting from a chemical point of view when less well-known elements are involved. An international research group from Germany and Finland discovered astonishing and beautiful molecular structures when, instead of oxygen or sulphur, they used the element tellurium, which has a different weight, in ring-shaped hydrocarbon molecules. These compounds are distinguished by the fact that they are arranged in the crystal to form highly symmetrical tubes that interact with each other via the tellurium atoms.

Molecular rings are arranged into tubes

The semiconductor tellurium has similar chemical properties to the 'related' elements sulphur and selenium. It is therefore not surprising that the ring-shaped hydrocarbons, into which the team specifically incorporated tellurium atoms, also behave similarly to the corresponding known compounds that contain sulphur or selenium - at least when they are dissolved. Tellurium nevertheless occupies a special position.

"Something special happens when these substances form crystals," says Prof. Wolfgang Weigand of Friedrich Schiller University Jena, one of the two corresponding authors of the current publication on this topic. "Virtually infinitely long tubes are then formed, in which the ring-shaped molecules are held together by the tellurium atoms. This happens due to an unusually strong intermolecular interaction. As a result, very interesting structures are created, which we can observe here." Similar structures are already known in chemistry, for example those called metal-organic frameworks. "In contrast to those, however, our compounds are not coordination polymers," explains Weigand. "Therefore, they behave differently. This can be seen, for example, in the fact that they only make these supramolecular forms as crystals and not when they are dissolved." However, initial experimental findings show that atmospheric oxygen can oxidise the tellurium atoms and then link them together to form stacked compounds.

A new way to store gas?

The German-Finnish research team has discovered that, due to their special cavities, these tellurium compounds in solid form have an extremely large surface area of nearly 1000 square metres per gram - or around two-and-a-half basketball courts. "It is in principle conceivable that gases, such as carbon dioxide, could be captured in these cavities," says Wolfgang Weigand. "However, it was important to us first of all to explore and study these exciting compounds." Further research is needed before practical applications could become possible.

"This research would not have been possible without the EU's Erasmus Programme," adds Jena chemist Weigand. "The idea for this work originally came from my former doctoral candidate, Dr Tobias Niksch, in Jena, and through a stay as a visiting scientist at the University of Oulu in Finland by my former Master's student, Marko Rodewald, in the group led by Prof. Risto Laitinen. We have had a very good relationship with the university for 15 years and we have frequently published research results together. And the theoretical calculations in this paper were done by one of Risto Laitinen's former doctoral candidates, who is now doing research at the University of Jyväskylä in Finland. This paper therefore shows how important exchanges and networking are for scientific progress. I'm already looking forward to doing further research on these interesting structures with our Finnish colleagues."

Beginning in March, as COVID-19 cases surged in various states in the U.S., the COVID-19 Pandemic Breast Cancer Consortium released recommendations that operations for ductal carcinoma in situ (DCIS) be deferred due to the pandemic. DCIS, which goes by many names including "stage 0" breast cancer, is a non-invasive form of cancer that begins in the milk ducts and is generally surgically excised. In approximately one in five cases, surgeons may find evidence of invasive cancer during surgery. During the pandemic, patients and clinicians expressed concern about what surgical delays might mean for patients' outcomes. A new study led by, investigators from Brigham and Women's Hospital, of more than 378,000 patients who were diagnosed with very early stage breast cancer between 2010 and 2016 offers new data and insights to help address these unknowns. The research team found that while increased time to surgery was associated with a small increase in pathological upstaging in DCIS patients, it did not impact overall survival. Results are published in the Journal of the American College of Surgeons.

"The most pressing question today is what will surgical delays due to the pandemic mean for patient outcomes, and the reality is that we will only have the answers years from now," said lead author Christina Minami, MD, MS, a surgeon in the Division of Breast Surgery at the Brigham. "In the meantime, these data should provide some reassurance and encouragement -- they don't indicate that outcomes will be changed dramatically. But we do encourage patients to follow up with their surgeons on a care plan as COVID-19 surges grow or subside locally."

Minami and colleagues leveraged data from the National Cancer Database for patients, which captures approximately 70 percent of newly diagnosed cancer in the U.S. All patients diagnosed January 1, 2010 to December 31, 2016 who underwent breast cancer surgery were identified. The team focused on patients with DCIS or early-stage (cT1-2N0) ER+ disease, an early form of breast cancer that may be susceptible to hormone therapy drugs.

More than 98 percent of patients with DCIS underwent surgery within three months. Among those who delayed surgery 60 days or longer, there was no significant difference in overall survival but there was a slight increase in upstaging. In patients with cT1-2N0 disease who were placed on neoadjuvant endocrine therapy -- a hormone therapy -- increased time to surgery did not impact stage or overall survival.

The authors note that extrapolating from the historical data to determine what this means for patients whose surgery has been delayed during the pandemic is challenging. Those who delayed surgery during the study period were a highly selective group -- they may not be representative of the wide swath of patients whose surgery was delayed due to the pandemic. In addition, the research team was only able to look at outcomes of three to four years -- understanding the longer-term effects of surgical delays may provide more meaningful insights for patients and clinicians.

"Anxiety for both surgeons and patients alike stems from the unknown -- what does a delay in surgery mean for our patients?" said Minami. "We sought to help address questions about outcomes. Ideally, we'd like to have randomized, controlled studies, but under the circumstances, we needed to take the more unconventional approach by looking at retrospective data."

Philadelphia and Newark, N.J. August 6, 2020 - A team of researchers from New Jersey Institute of Technology (NJIT) and Children's Hospital of Philadelphia (CHOP) have developed an algorithm through machine learning that helps predict sites of DNA methylation - a process that can change the activity of DNA without changing its overall structure - and could identify disease-causing mechanisms that would otherwise be missed by conventional screening methods.

The paper was published online this week by the journal Nature Machine Intelligence.

DNA methylation is involved in many key cellular processes and an important component in gene expression. Likewise, errors in methylation can be linked to a variety of human diseases. While genomic sequencing tools are effective at pinpointing polymorphisms that may cause a disease, those same methods are unable to capture the effects of methylation because the individual genes still look the same. Specifically, there has been considerable effort to study DNA methylation on N6-adenine (6mA) in eukaryotic cells, which include human cells, but while genomic data is available, the role of methylation in these cells remains elusive.

"Previously, methods that had been developed to identify these methylation sites in the genome were very conservative and could only look at certain nucleotide lengths at a given time, so a large number of methylation sites were missed," said Hakon Hakonarson, MD, PhD, Director of the Center for Applied Genomics (CAG) at CHOP and one of the senior co-authors of the study. "We needed to develop a better way of identifying and predicting methylation sites with a tool that could identify these motifs throughout the genome that may have a robust functional impact and are potentially disease causing."

In order to address this issue plaguing the research community, CAG and its partners at NJIT turned to deep learning. Zhi Wei, PhD, a professor of computer science at NJIT and a senior co-author of the study, worked with Hakonarson and his team to develop a deep learning algorithm that could predict where these sites of methylation happened, which would then help researchers determine the effect they might have on certain nearby genes.

Wei calls his software Deep6mA. To predict where these methylation sites might be found, Wei led the development of a neural network, which is a machine learning model that attempts to learn in similar ways to a brain. Neural networks have been utilized in cellular research before, but this is its first application to studyDNA methylation sites on natural multicellular organisms.

Wei cited four advantages of the new method: automation of the sequence feature representation of different levels of detail; integration of a broad spectrum of methylation sequences flanking genes of interest; enabling of the potential visualization of inherent sequence motifs for interpretation; and facilitation of model development and prediction in large-scale genomic data.

The study team applied this algorithm to three different types of representative organisms: A. thaliana, D. melanogaster, and E.coli, the first two being eukaryotic. Deep6mA was able to identify 6mA methylation sites down to the resolution of a single nucleotide, or basic unit of DNA. Even in this initial confirmation study, the researchers were able to visualize regulatory patterns that they had been unable to observe using previously existing methods.

"One limitation is that our proposed prediction is purely based on sequence information," Wei said in his discussion statement of the study. "Whether a candidate is a 6mA site or not will also depend on many other factors. Methylation, including 6mA, is a dynamic process, which will change with cellular context. In the future, we would like to take other factors into consideration [such as] gene expression. We hope to predict 6mA across cellular context by integrating other data."

"We already know that a number of genes have a disease-causing mechanism brought about by methylation, and while this study was not done in human cells, the eukaryotic cell models were very comparable," Hakonarson said. "Genomic scientists looking to translate their findings into clinical applications would find this tool very useful, and the level of precision could eventually lead to the discovery of specific cells or targets that are candidates for therapeutic intervention."