Culture

A study of 1,095 patients hospitalized with COVID-19 discovered that two easily measurable signs of health - respiration rate and blood-oxygen saturation - are distinctly predictive of higher mortality. Notably, the authors said, anyone who receives a positive COVID-19 screening test can easily monitor for these two signs at home.

This context is lacking in current guidance from the Centers for Disease Control and Prevention, which tells people with COVID-19 to seek medical attention when they experience overt symptoms such as "trouble breathing" and "persistent pain or pressure in the chest" - indications that may be absent even when respiration and blood oxygen have reached dangerous levels, the authors say.

"These findings apply to the lived experience of the majority of patients with COVID-19: being at home, feeling anxious, wondering how to know whether their illness will progress and wondering when it makes sense to go to the hospital," said Dr. Neal Chatterjee of the University of Washington School of Medicine.

Chatterjee and fellow cardiologist Dr. Nona Sotoodehnia were co-lead authors of the paper, which was to be published May 24 in the journal Influenza and Other Respiratory Viruses.

They said the findings suggest that, for some people with COVID-19, by the time they feel bad enough to come to the hospital, a window for early medical intervention might have passed.

"Initially, most patients with COVID don't have difficulty breathing. They can have quite low oxygen saturation and still be asymptomatic," said Sotoodehnia. "If patients follow the current guidance, because they may not get short of breath until their blood oxygen is quite low, then we are missing a chance to intervene early with life-saving treatment."

The researchers examined the cases of 1,095 patients age 18 and older who were admitted with COVID-19 to UW Medicine hospitals in Seattle or to Rush University Medical Center in Chicago. The study span was March 1 to June 8, 2020. The lone exclusions were people who chose "comfort measures only" at time of their admission.

While patients frequently had hypoxemia (low blood-oxygen saturation; 91% or below for this study) or tachypnea (fast, shallow breathing; 23 breaths per minute for this study), few reported feeling short of breath or coughing regardless of blood oxygen.

The study's primary measure was all-cause in-hospital mortality. Overall, 197 patients died in the hospital. Compared to those admitted with normal blood oxygen, hypoxemic patients had a mortality risk 1.8 to 4.0 times greater, depending on the patient's blood oxygen levels. Similarly, compared to patients admitted with normal respiratory rates, those with tachypnea had a mortality risk 1.9 to 3.2 times greater. By contrast, other clinical signs at admission, including temperature, heart rate and blood pressure, were not associated with mortality.

Nearly all patients with hypoxemia and tachypnea required supplemental oxygen, which, when paired with inflammation-reducing glucocorticoids, can effectively treat acute cases of COVID-19.

"We give supplemental oxygen to patients to maintain blood oxygen saturation of 92% to 96%. It's important to note that only patients on supplemental oxygen benefit from the life-saving effects of glucocorticoids," Sotoodehnia said. "On average our hypoxemic patients had an oxygen saturation of 91% when they came into the hospital, so a huge number of them were already well below where we would've administered life-saving measures. For them, that care was delayed."

The findings have relevance for family-medicine practitioners and virtual-care providers, who typically are first-line clinical contacts for people who have received a positive COVID-19 test result and want to monitor meaningful symptoms.

"We recommend that the CDC and [World Health Organization] consider recasting their guidelines to account for this population of asymptomatic people who actually merit hospital admission and care," Chatterjee said. "But people don't walk around knowing WHO and CDC guidelines; we get this guidance from our physicians and news stories."

Sotoodehnia recommended that people with positive COVID-19 test results, particularly those at higher risk of adverse outcomes due to advanced age or obesity, buy or borrow a pulse oximeter and monitor for blood-oxygen below 92%. The clip-like devices fit over a fingertip and can be purchased for under $20.

"An even simpler measure is respiratory rate - how many breaths you take in a minute. Ask a friend or family member to monitor you for a minute while you're not paying attention to your breathing, and if you hit 23 breaths per minute, you should contact your physician," she said.

Oncotarget published "Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens" which reported that the current study examines urine samples from 66 subjects, comprising of 31 Urology clinic controls and 35 bladder cancer patients, using a Luminex based screening platform.

ELISA validation was carried out for the top 4 prospective urine biomarkers using an independent cohort of 20 Urology clinic controls and 60 bladder cancer subjects.

Eight of these urine proteins were able to differentiate BC from control urine with ROC AUC values exceeding 0.70 at p

These Oncotarget findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer.

These Oncotarget findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer.

Urine IL-8 not only distinguishes bladder cancer from controls, it also discriminates high grade from low grade disease, and the successive clinical stages of bladder cancer.

Dr. Chandra Mohan from The University of Houston said, "Bladder cancer (BC) is the sixth most common cancer diagnosis in the United States and is over four times more common in men than women."

Urine biomarkers could potentially provide preliminary confirmation of low-grade BC before invasive procedures are performed and facilitate surveillance of BC, as reviewed.

The present study implements a Luminex based screening platform with a cytokine/chemokine panel that simultaneously interrogates 16 urine biomarkers, followed by ELISA validation of 4 prospective urine biomarkers.

Of the 16 proteins screened by Luminex, 12 were within the detectable range and among these, 10 urine biomarkers showed significant elevation in BC compared to the controls.

ELISA validation for these 4 urine biomarkers was carried out using an independent cohort of 20 urology clinic controls and 60 BC subjects.

Of these 4 proteins, IL-8 displayed the highest significance in discriminating between controls and BC patients and discriminating highly advanced stages/grades of BC from less advanced stages/grades of BC.

The Mohan Research Team concluded in their Oncotarget Research Output that these studies indicate that urine IL-1α, IL-1ra, and IL-8 are potential biomarkers of BC, two of which re-affirm previous reports.

These studies shed additional light on the potential utility of these markers, since some of them also exhibit the ability to discriminate T1 and/or T2-T4 from Ta BC, as well as high grade from low grade BC.

Looking forward, systematic studies in larger patient cohorts are warranted to establish the specific clinical contexts in which these markers may be used, including the following: for initial diagnosis of BC, for surveillance of tumor recurrence, and/or for assessing treatment response following BCG therapy or other therapeutic modalities.

Finally, these newer urine biomarkers need to be compared against the performance of current yardsticks such as the Bladderchek and UroVysion FISH assay.

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27941

Full text - https://www.oncotarget.com/article/27941/text/

Correspondence to - Chandra Mohan - cmohan@central.uh.edu

Keywords -
urothelial,
proteomics,
targeted screens,
interleukins,
inflammation

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

Journal

Oncotarget

DOI

10.18632/oncotarget.27941

Oncotarget published "Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas" which reported that herein the authors evaluate expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with potential ties to both pathways, in sarcomas of different histological types.

Immunohistochemical staining of a tissue microarray including 163 sarcomas and correlation with clinical data showed that elevated YAP and TAZ independently predict worse overall and progression-free survival, respectively.

In the absence of p53 expression, combined TAZ and YAP expression adversely affect overall, progression free, and metastasis free survival more than TAZ or YAP activation alone.

RABL6A independently predicted shorter time to metastasis and was positively correlated with p53, MDM2 and YAP expression, supporting a possible functional relationship between the biomarkers.

Network analysis further showed that TAZ is positively correlated with MDM2 expression.

Dr. Munir R. Tanas from The University of Iowa said, "Sarcomas are difficult to treat malignant mesenchymal neoplasms arising in bone or soft tissue."

In epithelioid hemangioendothelioma, a vascular sarcoma, a WWTR1-CAMTA1 gene fusion encodes a constitutively activated form of TAZ that activates a TAZ-like transcriptional program.

Alterations of the p53 pathway are among the most frequent aberrations observed in human cancers, including sarcomas.

Among the most common type of tumors noted in individuals with LFS are sarcomas, specifically soft tissue sarcomas and osteosarcomas.

As such, the amplification of the MDM2 gene region in several sarcomas including well-differentiated liposarcoma/dedifferentiated liposarcoma, parosteal and low-grade central osteosarcoma, and intimal sarcomas represents an effective mechanism of p53 inactivation.

RABL6A is a newly recognized oncoprotein that has been implicated in various human cancers, including pancreatic neuroendocrine tumors, breast cancer, colon cancer, non-small cell lung cancer, pancreatic ductal adenocarcinomas and osteosarcoma.

The Tanas Research Team concluded in their Oncotarget Research Output, "We expect that combination therapies targeting this network will be most effective in the treatment of sarcomas. Furthermore, there is a need to further validate these RABL6A/YAP/p53 and TAZ/MDM2 expression signatures in larger numbers of different histological types of sarcoma to determine if it differentially predicts prognosis or response to therapy within individual subsets of these sarcomas. We anticipate these above efforts will lead to a more effective, tailored approach for these cancers for which few effective medical therapies are currently available."

For the first time, researchers have observed plasma jets interacting with magnetic fields in a massive galaxy cluster 600 million light years away, thanks to the help of radio telescopes and supercomputer simulations. The findings, published in the journal Nature, can help clarify how such galaxy clusters evolve.

Galaxy clusters can contain up to thousands of galaxies bound together by gravity. Abell 3376 is a huge cluster forming as a result of a violent collision between two sub-clusters of galaxies. Very little is known about the magnetic fields that exist within this and similar galaxy clusters.

"It is generally difficult to directly examine the structure of intracluster magnetic fields," says Nagoya University astrophysicist Tsutomu Takeuchi, who was involved in the research. "Our results clearly demonstrate how long-wavelength radio observations can help explore this interaction."

An international team of scientists have been using the MeerKAT radio telescope in the Northern Cape of South Africa to learn more about Abell 3376's huge magnetic fields. One of the telescope's very high-resolution images revealed something unexpected: plasma jets emitted by a supermassive black hole in the cluster bend to form a unique T-shape as they extend outwards for distances as far as 326,156 light years away. The black hole is in galaxy MRC 0600-399, which is near the centre of Abell 3376.

The team combined their MeerKAT radio telescope data with X-ray data from the European Space Agency's space telescope XXM-Newton to find that the plasma jet bend occurs at the boundary of the subcluster in which MRC 0600-399 exists.

"This told us that the plasma jets from MRC 0600-399 were interacting with something in the heated gas, called the intracluster medium, that exists between the galaxies within Abell 3376," explains Takeuchi.

To figure out what was happening, the team conducted 3D 'magnetohydrodynamic' simulations using the world's most powerful supercomputer in the field of astronomical calculations, ATERUI II, located at the National Astronomical Observatory of Japan.

The simulations showed that the jet streams emitted by MRC 0600-399's black hole eventually reach and interact with magnetic fields at the border of the galaxy subcluster. The jet stream compresses the magnetic field lines and moves along them, forming the characteristic T-shape.

"This is the first discovery of an interaction between cluster galaxy plasma jets and intracluster magnetic fields," says Takeuchi.

An international team has just begun construction of what is planned to be the world's largest radio telescope, called the Square Kilometre Array (SKA).

"New facilities like the SKA are expected to reveal the roles and origins of cosmic magnetism and even to help us understand how the universe evolved," says Takeuchi. "Our study is a good example of the power of radio observation, one of the last frontiers in astronomy."

Bethesda, MD (May 23, 2021) -- Patients' irritable bowel syndrome (IBS) symptoms unexpectedly improved when they were under COVID-19 stay-at-home orders, reaffirming the gut-brain connection in functional gastrointestinal disorders, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2021.

"One of our main hypotheses was that these patients were going to be worse because of pressure and stress due to COVID-19," said Juan Pablo Stefanolo, MD, a lead author on the study and a physician with the Neurogastroenterology and Motility section, Hospital de Clínicas José de San Martín, Buenos Aires University, Argentina. "We think the results have something to do with people staying at home. They were not exposed to outside stress, and at home they were able to avoid food triggers."

Pandemic lockdown orders in Argentina created a unique opportunity for researchers to study the impact of pandemic stressors and reduced social interaction on 129 IBS patients whose pre-pandemic data had already been collected through an earlier research project. The patients were re-assessed during the lockdown with the same online survey that included multiple validated measures of IBS severity, anxiety and depression, along with questions about co-occurring illnesses, including heartburn, regurgitation, indigestion, chronic fatigue, fibromyalgia and nonmigraine headaches.

During the lockdown in Argentina -- one of the longest lockdowns in the world -- the number of patients experiencing severe IBS fell sharply from 65 to 39. The mean Irritable Bowel Syndrome Severity Scale score for the group also fell 66 points, from 278 to 212 on a 500-point scale. IBS symptoms of pain, distention, stool consistency, anxiety, somatization, fibromyalgia and chronic fatigue symptoms all improved during the lockdown.

Patients with functional gastrointestinal disorders experience symptoms even though no structural or biochemical abnormalities are present. The gut-brain connection refers to the role of stress and psychological difficulties in triggering debilitating gut-related symptoms. Headache, heartburn and regurgitation -- all outside the category of functional disorders -- became worse during the study, likely due to the increase in weight that nearly 60 percent of patients reported.

"Our results reinforce the concept that IBS, or functional gastrointestinal disorders, have a connection to psychosocial factors, as well as food and other factors," Dr. Stefanolo said. "The gut-brain axis has a lot of facets."

"If you build it, they will come," so says the idiom but it's the storytellers, knowledge-makers and an "agentic" or open-minded population who help create great entrepreneurial cities.

A new research study, conducted by QUT, RMIT and the University of Indiana, analysed data from 362 American cities with a focus on human agency, entrepreneurial spirit, and economic growth.

The study, based on geographic psychological profiles of millions of people based in the US, found people and an empowered city life matter in shaping urban vitality.

The research points to San Francisco and Austin as the zip codes that drive the highest-impact entrepreneurship conducive to economic growth. Other cities scoring high included New York, Los Angeles, Dallas, Miami, San Jose, Riverside, Sacramento and Tampa.

Professor Martin Obschonka, Director of QUT's Australian Centre for Entrepreneurship Research and a joint author of the research, said the findings needed to be tested in other areas like Australia.

"Our study describes an ideal and what cities should strive for," Professor Obschonka said. "Future research could provide a more nuanced picture on how local populations with their unique psychological makeup interact with a structural city environment."

The researchers acknowledge a "people-focused view" on great entrepreneurial cities builds on the work by influential author, theorist, journalist, and activist Jane Jacobs who wrote the book The Death and Life of Great American Cities.

The 1961 publication spearheaded a movement against a four-lane road through New York's Greenwich Village dismissing the scientific rationalism of urban planning and coining metaphoric concepts such as the "ballet of sidewalk" and "eyes on street".

The new study, published in Research Policy, tests and extends Jane Jacob's theory by revealing best performing cities in terms of growth-oriented entrepreneurship are those that empower open and agentic people.

"They are empowered by a physical and industrial city landscape that enables them to act in more innovative and entrepreneurial ways," Professor Obschonka said.

Professor Martin Obschonka said most empirical research addressing the economic performance of cities focus on the physical and industrial structures of cities, underestimating the role of people.

"The core message and spirit of Jane Jacobs has been overlooked," he said.

"The most compelling finding of our study suggests that a strong open orientation of people in cities, designed to be dense and diverse, results in high impact entrepreneurship with start-ups that have the potential to grow significantly," he said.

Professor Obschonka said by building a psychological profile of a city, a model was developed to identify geographic personality traits.

He said regions that demonstrated agentic tendencies, whereby people are more open-minded, learning-oriented, and creative acted in more innovative and entrepreneurial ways.

"One secret of great entrepreneurial cities seems to be that open-minded people are empowered by a city environment, bringing many similarly open-minded people together in dense and diverse places to interact, share new ideas and knowledge and inspire creativity," he said.

"Empowering people liberates their imaginations and not only is the human spirit lifted through interactions among people in a city, but the flow of new ideas inspires vital new innovations."

Professor Obschonka said the study also has major implications for entrepreneurial ecosystems and cities, including those in Australia.

"It's not only about promoting diversity of people but diversity of economic activities within sectors with cities to help create a fertile environment for sharing knowledge," Professor Obschonka said.

"Cities and regions can promote a local open psychological orientation to stimulate growth in innovation processes."

Feeling anxious can direct our attention and memory toward supernatural beings such as gods, a University of Otago study has found.

Lead author Dr Thomas Swan, of the Department of Psychology, says the research may help explain how religious beliefs are formed.

For the study, published in the International Journal for the Psychology of Religion, 972 participants completed an online recall test to determine if a bias to recall supernatural agents was stronger in anxious people, rather than non-anxious people.

Those who felt anxious were more likely to remember beings with supernatural abilities than beings without.

"Anxiety is an emotion that evolved to make us pay greater attention to potential threats, so when we feel anxious, a god that can read our thoughts and punish us for them, or flood the Earth, is going to be memorable," he says.

Previous research has shown anxiety can lead to greater levels of religious belief, with the explanation being that belief provides comfort. However, this so-called 'comfort theory' has problems: why are there punishing gods and hellish afterlives when these are far from comforting?

Dr Swan believes the theory also fails to address what comes between feeling anxious and becoming a believer. This research suggests the first step involves the cognitive effects of anxiety, which cause people to attend to and recall threats.

"In our previous research, we found that supernatural beings are perceived as potentially threatening because they have abilities that defy our expectations about the world. The present research confirms that the cognitive effects of anxiety also extend to the threat that is afforded by supernatural beings.

"Ironically then, our research suggests comfort theory has it somewhat backwards: anxious people are attracted, at least initially, to the scary traits of gods, which may explain why so many gods have scary features. Comfort, we suspect, comes later when some people transform their view of the god into something more palatable that they are happier believing," he says.

The research also suggests other supernatural concepts - such as ghosts, psychics, and astrology - will be digested in the same way because of how they alarmingly defy our expectations about what is possible.

Dr Swan hopes the research prompts people to develop a greater understanding of how their emotional states affect the information they look at and remember, particularly religious information.

"We should all be mindful of how we came to believe the things we do, especially those with anxiety disorders who feel anxious much of the time - they should be mindful of what they are attracted to and why. If they find themselves reading fantasy novels, that may be harmless. If they find themselves joining a cult, then it's time for some reflection. The same goes for people without disorders who are just in anxious situations, such as sitting in a hospital bed or suffering financial troubles."

On the flipside, he hopes religious groups pay more attention to people's mental states.

"They should be providing care but also giving people time to overcome their troubles before integrating them into a highly religious system of beliefs and practices. If they are still willing to join the religion when the turmoil is over, that might be a more ethical moment."

Free access to essential medicines increases patient adherence to taking medication by 35 per cent and reduces total health spending by an average of over $1,000 per patient per year, according to a two-year study that tested the effects of providing patients with free and convenient access to a carefully selected set of medications.

The findings, published May 21 in PLOS Medicine, come as advocates urge Canada to carve a path toward single-payer, public pharmacare. Canada is the only country with universal healthcare that does not have a universal pharmacare program.

A group of researchers led by St. Michael's Hospital of Unity Health Toronto recruited a total of 786 patients across nine primary care sites in Ontario who reported cost-related non-adherence to medications. Most of the study participants were recruited from St. Michael's Department of Family and Community Medicine and others were recruited from three rural sites. Participants were randomized into two groups - half received free medications via mail, the other half had their usual access to medications.

Two years into the study, adherence to all appropriate prescribed medicines was 35 per cent higher in the free distribution group compared with the group that had usual access to medications. Free distribution of medication also showed to reduce healthcare costs, including hospitalization, by an average of $1,222 per patient per year.

"The cost savings are substantial, but they are less important than people simply being able to afford taking lifesaving medications," said Dr. Nav Persaud, a scientist at the Li Ka Shing Knowledge Institute of St. Michael's and lead author of the study.

"This is the first study of providing people with free access to a comprehensive set of medicines, and hopefully it will be the last one needed before policy changes," said Dr. Persaud, who is also a family physician at St. Michael's Hospital.

In June 2019, the Advisory Council on the Implementation of National Pharmacare recommended a universal, single-payer, public pharmacare, estimating such a program would save Canada an estimated $5 billion per year. The report cited a list of medicines like the one used in the CLEAN Meds study as "a starting point" for determining which drugs all Canadians should have free access to.

The CLEAN Meds Trial focused on 128 essential medicines, adapted from the WHO Model List of Essential Medicines and removed treatments not needed in Canada. The medicines in the study included treatments for acute conditions, such as antibiotics and pain relievers, as well as chronic conditions, such as antipsychotics and HIV-AIDS medications.

The paper is the final result of the CLEAN Meds Trial. Preliminary results of the trial after one year of free medication indicated improved adherence, improvements in some health outcomes, and that free distribution of essential medicines led to a 160 per cent increase in the likelihood of participants being able to make ends meet.

What The Study Did: Oregon's Reproductive Health Equity Act ensured coverage for family planning (abortion and contraception) using state funds for all low-income state residents regardless of citizenship status. Researchers in this study describe the first two years of abortion services covered and the distances traveled by women to receive care.

Authors: Maria I. Rodriguez, M.D., M.P.H., of Oregon Health & Science University in Portland, 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/jamahealthforum.2021.0402)

Editor's Note: The article includes conflict of interest 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.

What The Study Did: Variation in SARS-CoV-2 infection risk and socioeconomic disadvantage among a Mayan-Latinx population in Fruitvale, California, was examined in this study.

Authors: Paul Wesson, Ph.D., of the University of California, San Francisco, 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/jamanetworkopen.2021.10789)

Editor's Note: The article includes conflict 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.

Papers in leading psychology, economic and science journals that fail to replicate and therefore are less likely to be true are often the most cited papers in academic research, according to a new study by the University of California San Diego's Rady School of Management.

Published in Science Advances, the paper explores the ongoing "replication crisis" in which researchers have discovered that many findings in the fields of social sciences and medicine don't hold up when other researchers try to repeat the experiments.

The paper reveals that findings from studies that cannot be verified when the experiments are repeated have a bigger influence over time. The unreliable research tends to be cited as if the results were true long after the publication failed to replicate.

"We also know that experts can predict well which papers will be replicated," write the authors Marta Serra-Garcia, assistant professor of economics and strategy at the Rady School and Uri Gneezy, professor of behavioral economics also at the Rady School. "Given this prediction, we ask 'why are non-replicable papers accepted for publication in the first place?'"

Their possible answer is that review teams of academic journals face a trade-off. When the results are more "interesting," they apply lower standards regarding their reproducibility.

The link between interesting findings and nonreplicable research also can explain why it is cited at a much higher rate--the authors found that papers that successfully replicate are cited 153 times less than those that failed.

"Interesting or appealing findings are also covered more by media or shared on platforms like Twitter, generating a lot of attention, but that does not make them true," Gneezy said.

Serra-Garcia and Gneezy analyzed data from three influential replication projects which tried to systematically replicate the findings in top psychology, economic and general science journals (Nature and Science). In psychology, only 39 percent of the 100 experiments successfully replicated. In economics, 61 percent of the 18 studies replicated as did 62 percent of the 21 studies published in Nature/Science.

With the findings from these three replication projects, the authors used Google Scholar to test whether papers that failed to replicate are cited significantly more often than those that were successfully replicated, both before and after the replication projects were published. The largest gap was in papers published in Nature/Science: non-replicable papers were cited 300 times more than replicable ones.

When the authors took into account several characteristics of the studies replicated--such as the number of authors, the rate of male authors, the details of the experiment (location, language and online implementation) and the field in which the paper was published--the relationship between replicability and citations was unchanged.

They also show the impact of such citations grows over time. Yearly citation counts reveal a pronounced gap between papers that replicated and those that did not. On average, papers that failed to replicate are cited 16 times more per year. This gap remains even after the replication project is published.

"Remarkably, only 12 percent of post-replication citations of non-replicable findings acknowledge the replication failure," the authors write.

The influence of an inaccurate paper published in a prestigious journal can have repercussions for decades. For example, the study Andrew Wakefield published in The Lancet in 1998 turned tens of thousands of parents around the world against the measles, mumps and rubella vaccine because of an implied link between vaccinations and autism. The incorrect findings were retracted by The Lancet 12 years later, but the claims that autism is linked to vaccines continue.

The authors added that journals may feel pressure to publish interesting findings, and so do academics. For example, in promotion decisions, most academic institutions use citations as an important metric in the decision of whether to promote a faculty member.

This may be the source of the "replication crisis," first discovered the early 2010s.

"We hope our research encourages readers to be cautious if they read something that is interesting and appealing," Serra-Garcia said. "Whenever researchers cite work that is more interesting or has been cited a lot, we hope they will check if replication data is available and what those findings suggest."

Gneezy added, "We care about the field and producing quality research and we want to it to be true."

What The Study Did: This observational study found no association between long-term dietary intake of gluten and cognitive function among a large group of middle-age women without celiac disease.

Authors: Andrew T. Chan, M.D., M.P.H., of Massachusetts General Hospital and Harvard Medical School 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/jamanetworkopen.2021.13020)

Editor's Note: The article includes conflict 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.

#  #  #

Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2021.13020?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=052121

About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

Irvine, Calif. - A record of medicine utilization patterns assembled by an interdisciplinary team of researchers at the University of California, Irvine and the UC San Diego School of Medicine reveals the thought, care and scientific rigor clinicians at UC Health medical centers applied in their treatment of patients with COVID-19 in 2020.

For a study published today in Journal of the American Medical Association Network Open, the investigators examined data on the usage rates of 10 different medicines and medicine categories to map how drugs were used on people hospitalized with the viral infection.

The authors got their data from the University of California COVID Research Data Set and tracked 22,896 patients admitted to UC Health medical centers in Davis, Irvine, Los Angeles, San Diego and San Francisco between March 10 and Dec. 31, 2020.

"The home run of this paper is really in the figures built from the UC CORDS database," said lead author Jonathan Watanabe, UCI professor of clinical pharmacy. "You can clearly see how usage of certain medicines grew or declined over the course of the pandemic and how those movements were tied to evidence-based decisions being made by UC healthcare providers in real time. You can monitor the evolution in how we treat our sickest patients."

A stark example can be seen in the shift in acceptance of the antimicrobial medication hydroxychloroquine, which was the subject of public discussion in White House briefings and substantial media attention. In the early stages of the pandemic, the drug was given to more than 40 percent of patients, but by June, usage was below 5 percent. Usage of another drug in that class, azithromycin, fell from 40 to 30 percent in that same timeframe.

"There were some studies conducted in the early part of the pandemic that were not particularly well-designed and were limited in size that appeared to show hydroxychloroquine to be useful," said Watanabe, who's also UCI's founding associate dean of pharmacy assessment and quality in UCI's School of Pharmacy & Pharmaceutical Sciences. "We saw high uptake of the drug early on, but then it just cratered, because as time progressed and more high-quality trials came in, it was shown to be not effective."

The opposite can be seen with dexamethasone, which increased from being administered to 1.4 percent of patients per day on March 31 to 67.5 percent by the end of December. The inexpensive, generic corticosteroid was found to be effective in large trials in hospitalized patients in the U.K., according to Watanabe.

"At first glance, a lot of people might say you wouldn't want to use a corticosteroid that, theoretically, could reduce the immune response in a COVID patient," he said. "But the trials really demonstrated that the knee-jerk mechanism of action-response was not correct in this case: The anti-inflammatory effect of the drug to tame cytokine storms was evidently more important than any blunting of the immune response."

Remdesivir use grew 12-fold, from 4.9 percent on June 1 to 62.5 percent on Dec. 31. Watanabe said one possible explanation for this is that the medication was only available in conjunction with trials in the UC system in the early part of the pandemic and was more widely distributed as time went on.

Enoxaparin, used to both treat and prevent thrombosis, also proved effective against COVID-19, of which blood clots are a common symptom. The drug remained above 50 percent in usage throughout 2020.

"We tend to put hospitalized patients in general on an anticoagulant to reduce the risk of clots, which can happen because they may be lying in place immobile for long stretches," Watanabe said. "But then we started to notice thrombophilia in COVID patients, so enoxaparin and heparin both became very important not just as prophylaxis but as treatments."

He noted that the utilization numbers in the paper show how physicians and other healthcare professionals responded to evidence and their own observations effectively in real time and that such information is important for clinicians to know for future planning purposes in terms of both treatment decision-making and ensuring a robust supply of proven drugs.

"This JAMA study is a thoughtful chronicle of the steps doctors, nurses and staff at UC Health medical centers took to help patients with a potentially life-threatening disease," said Jan Hirsch, founding dean of UCI's School of Pharmacy & Pharmaceutical Sciences. "In the beginning, not a lot was known about the right course of treatment for COVID-19, but our people learned fast and responded to evidence about what was effective on a daily and sometimes even more frequent basis."

Micropollutants such as steroid hormones contaminate drinking water worldwide and pose a significant threat to human health and the environment even in smallest quantities. Until now, easily scalable water treatment technologies that remove them efficiently and sustainably have been lacking. Scientists at the Karlsruhe Institute of Technology (KIT) developed a new chemical process for removing hormones. It takes advantage of the mechanisms of photocatalysis and transforms the pollutants into potentially safe oxidation products. The team reports on this in the scientific journal Applied Catalysis B: Environmental.

Organic pollutants such as pharmaceuticals, pesticides, and hormones - even at nanoscale concentrations - contaminate drinking water in a way that poses significant risks to humans, animals, and the environment. In particular, the steroid hormones estrone, estradiol, progesterone, and testosterone can cause biological damage in humans and wildlife. The European Union has therefore set strict minimum quality standards for safe and clean drinking water, which must also be taken into account in the development of new technologies for water treatment. "The challenge for science is to develop more sensitive methods to target the hormone molecules," says Professor Andrea Iris Schäfer, Head of the Institute for Advanced Membrane Technology (IAMT) at KIT. The main problem is that steroid hormones are very hard to detect in water. "There is one hormone molecule for every quintillion water molecules. This is an extremely low concentration," explains the expert.

Detecting - and Removing - Micropollutants

With conventional water treatment technologies, wastewater treatment plants can neither find nor remove micropollutants. Researchers at the IAMT and the KIT Institute of Microstructure Technology (IMT) are therefore working on new methods to not only detect and measure micropollutants, but also remove them. A new, photocatalytic process proves to be promising. The scientists coated a commercially available large-pore polymer membrane with Pd(II)-porphyrin, a palladium-containing, light-sensitive molecule that can absorb visible radiation. Exposure to radiation with simulated sunlight initiates a chemical process that produces so-called singlet oxygen, a highly reactive oxygen species. The singlet oxygen specifically "attacks" the hormone molecules and converts them into potentially safe oxidation products. "It is crucial that we coat the surface of each pore with the photosensitizer molecule, increasing the surface area of attack," explains Roman Lyubimenko, a scientist at IAMT and IMT.

Significant Reduction of the Estradiol Concentration

The chemical decomposition of steroid hormones and the filtration of other micropollutants can be realized in a single module. With this process, filtering of 60 to 600 liters of water per square meter of membrane is possible in one hour. The scientists were able to reduce the concentration of estradiol, the most biologically active steroid hormone, by 98 percent from 100 to 2 nanograms per liter. "This means that we are already very close to the EU target value of one nanogram per liter," emphasizes Schäfer. The next goal of the research team is to further optimize the photocatalytic process and transfer it to a larger scale. Open issues are to find out how much light intensity and how much porphyrin will be needed and whether the costly palladium from the platinum group of metals can be replaced by other metals. (sur)

The findings of a clinical trial by Trinity College Dublin researchers of treatment for atopic dermatitis have been published today in The Lancet journal (Friday, 21st May, 2021). Results of the clinical trial at the School of Medicine, Trinity College and St James's Hospital, Dublin have shown the drug upadacitinib to be the most effective treatment to date for this chronic, relapsing inflammatory condition. The research is vital as there is an unmet need which exists for therapies that provide remission of symptoms in moderate-to-severe atopic dermatitis.

The publication reports efficacy and safety results of upadacitinib compared with placebo for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents. This pivotal Global Phase 3 study involved 1,600 patients and took place over the last two years at The Wellcome Trust/Health Research Board Clinical Research Facility at St James's Hospital.

Atopic dermatitis is a chronic, relapsing inflammatory condition characterised by a cycle of intense itching and scratching leading to cracked, scaly, oozing skin. It affects up to an estimated 10 percent of adults and 25 percent of children. Between 20 and 46 percent of adults with atopic dermatitis have moderate to severe disease. The range of symptoms pose significant physical, psychological and economic burden on individuals impacted by the disease.

Results show upadacitinib to so far be the most effective treatment for atopic dermatitis in clinical trials. The magnitude and breadth of the treatment effect versus placebo across multifaceted aspects of atopic dermatitis provides evidence that a targeted therapy blocking multiple inflammatory pathways could help to address the substantial unmet needs in the treatment of moderate-to-severe atopic dermatitis.

These pivotal findings could potentially transform the treatment goals and standards of care for patients with moderate-to-severe atopic dermatitis.

Professor Alan Irvine, School of Medicine, Trinity College and Principal Investigator said:

"Atopic dermatitis is a common inflammatory skin disease which, when severe, has a very significant impact on quality of life. These results are hugely encouraging and will hopefully offer an additional treatment option for patients very soon. The success of this clinical trial also shows the value of investment in our Trinity research facility at St James's Hospital, meaning Irish patients have access to advanced therapies and Irish medical and nursing trainees gain valuable research skills. "