Culture

The fast-growing cancer incidence and mortality worldwide have raised great challenges for the currently available anticancer options, which warrants the development of new therapeutic modalities based on novel antitumor mechanisms. Ferroptosis, a recently discovered form of non-apoptotic cell death, is one such candidate and has already demonstrated immense potential in clinical oncology as it provides alternative therapeutic opportunities for the management of treatment-resistant tumors. In a research study published on Science Advances, lead author Prof. Shu-Hong Yu from the University of Science and Technology of China and his collaborator Prof. Zhong Luo in Chongqing University reported a novel strategy to induce ferroptosis in target cancer cells and further amplify the ferroptotic damage for efficient tumor therapy. The nanoformulation was designed to be exclusively activated in the tumor microenvironment, which has demonstrated potent inhibition effect against multiple types of tumors while sparing healthy cells and tissues.

"Overloading tumor cells with ferrous ions could readily initiate the ferroptotic death cascade, and the complexed doxorubicin may further amplify the ferroptotic damage by providing additional reactive oxygen species to sustain the lipid peroxidation." Says Prof. Shu-Hong Yu, head of the research group in the University of Science and Technology of China. "The benefit of coordinating Fe2+ ions with doxorubicin is manifold. It could not only enhance the stability of Fe2+ ions in biological environment, but also facilitate the subsequent lipid peroxidation process to promote ferroptosis. Moreover, doxorubicin is an FDA-approved anticancer drug capable of inhibiting the topoisomerase 2 in tumor cells to prevent DNA replication, leading to complementary ferroptosis/apoptosis effect against a broad spectrum of tumor indications." Says Prof. Luo, head of the research group in Chongqing University.

The underlying molecular mechanism for the synergy between Fe2+ and doxorubicin is that doxorubicin could generate high level of intracellular ROS by activating the intracellular NADPH oxidase 4 (NOX4) in tumor cells, which may supply H2O2 to sustain the Fe2+-catalyzed lipid peroxidation.

Prof. Shu-Hong Yu also commented on one of the major challenges for the tumor targeted delivery of the Fe2+-doxorubicin complex. "The coordination complex is rapidly dissociated into free Fe2+ and doxorubicin under acidic conditions. However, both species must interact with intracellular components to take effect, necessitating further refinement of the drug delivery process."

Inspired by the recent advances in self-assembly technology, researchers from the two groups developed an intricate self-assembly-based nanoplatform for the tumor-targeted cytosolic delivery of the Fe2+-doxorubicin complex. The Fe2+-doxorubicin complex were efficiently encapsulated into amorphous calcium carbonate nanospheres in a simple one-step co-condensation process, and the surface of the drug-loaded amorphous calcium nanoparticles was modified with polyamidoamine (PAMAM) dendrimer-based tumor-microenvironment-activatable multifunctional ligands, which would remain bioinert during circulation but switch to a tumor-affinitive state upon entering the matrix metalloproteinase-2 (MMP-2)-rich tumor microenvironment. Thanks to the acid sensitivity of the amorphous calcium carbonate contents, the nanoparticle could be readily degraded in the acidic tumor lysosomes to release the Fe2+-doxorubicin complex, which could be further reverted into free doxorubicin and Fe2+ through the protonation-induced dissociation. Meanwhile, the PAMAM dendrimers could disrupt the lysosomal membrane via "proton sponge" effect and release doxorubicin and Fe2+ to the cytosol, where the H2O2 produced during doxorubicin metabolism could stimulate the ferroptotic toxicity of Fe2+ ions to tumor cells.

"We two groups have been collaborating closely on the synthesis and functionalization of biocompatible inorganic nanomaterials." Says Prof. Zhong Luo, head of the research group in Chongqing University. "Amorphous calcium carbonate nanoparticle is a very promising inorganic nanomaterial for biomedical applications. It's easy to synthesize and has tunable drug loading capability. It could also be rapidly degraded in human body and the degradation products are all non-toxic."

Dr. Menghuan Li, a senior scientist in Prof. Zhong Luo's research group, says that the nanoplatform is also a good example of repurposing old drugs for new applications. "This would greatly benefit the clinical translation of the reported nanoformulation." Says Dr. Menghuan Li.

In the future, Prof. Shu-Hong Yu and Prof. Zhong Luo hope to further simplify the synthesis procedures of the amorphous calcium carbonate-based nanoplatform and thoroughly investigate their efficacy and safety in a clinically relevant context. "This system may open up new avenues for treatment against tumors that are resistant to conventional therapies." Says Prof. Shu-Hong Yu.

New USC research reveals how APOE4, a genetic culprit for Alzheimer's disease, triggers leaks in the brain's plumbing system, allowing toxic substances to seep into the brain areas responsible for memory encoding and other cognitive functions.

The damage is linked to future problems in learning and memory, even when the disease's signature sticky plaques have not appeared. The findings suggest that the smallest blood vessels in the brain, which form the blood-brain barrier, might be a potential target for early treatment.

The study appears today in Nature.

"This study sheds light on a new way of looking at this disease and possibly treatment in people with the APOE4 gene, looking at blood vessels and improving their function to potentially slow down or arrest cognitive decline," said senior author Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. "Severe damage to vascular cells called pericytes was linked to more severe cognitive problems in APOE4 carriers. APOE4 seems to speed up breakdown of the blood-brain barrier by activating an inflammatory pathway in blood vessels, which is associated with pericyte injury."

Scientists have long known that the APOE4 gene - which occurs in up to 14 percent of the population - increases the probability of developing Alzheimer's disease. Until now, it's been unclear how different pathologies determine the course of the disease in its early stages, or what underlying mechanisms lead to cognitive decline in APOE4 carriers.

Zlokovic's previous research shows that people who develop early memory problems also experience the most leakage in their brain's blood vessels - independent of amyloid plaque or tau, two common contributors to Alzheimer's. The leakage starts when cells called pericytes, which line the walls of blood vessels in the brain and maintain blood-brain barrier integrity, are damaged. These injured pericytes can be detected with a unique biomarker, developed by Zlokovic's lab in 2015, which shows up in cerebrospinal fluid.

For this study, scientists used standard memory tests to check the participants' cognitive abilities and their neuropsychological performance. They also used advanced neuroimaging and employed the biomarker that indicates damage to the brain's blood vessels.

In participants who had the APOE4 gene, researchers found damaged capillaries in the brain's memory center, the hippocampus and medial temporal lobe. The damage correlated with increased levels of a protein that causes inflammation, cyclophilin A - an early sign of the disease in people already at higher risk of developing Alzheimer's.

Zlokovic, who became director of the Zilkha Neurogenetic Institute in 2012, pioneered the concept that a breakdown in the blood-brain barrier contributes to cognitive impairment and dementia. The Zilkha Neurogenetic Institute opened at Keck School of Medicine in 2003 with a $20 million donation from Los Angeles businessman Selim Zilkha, who later contributed $10 million more to the effort.

Neurobiologists at KU Leuven have discovered how the signalling molecule Neuromedin U plays a crucial role in our learning process. The protein allows the brain to recall negative memories and, as such, learn from the past. The findings of their study on roundworms have been published in the journal Nature Communications.

If a certain type of food or drink has made you ill in the past, you will avoid it on future occasions. Similarly, you will avoid an uncomfortable situation that made you anxious before. This learning process, which is based on unpleasant or negative memories, is extremely important. It has fascinated researchers for years, but the molecular basis remains incompletely understood.

A new study carried out by the Division of Animal Physiology and Neurobiology of KU Leuven now sheds new light on the matter. The researchers studied the roundworm C. elegans and found that the protein Neuromedin U plays a key role in recalling negative memories. It acts as a signalling molecule allowing the neurons to communicate with each other.

Roundworms as a model organism

"The communication between brain cells is surprisingly similar between worms and humans", explains Professor Isabel Beets. "While C. elegans worms only have about 300 neurons, their brains produce many signalling molecules that are similar to those in the human brain. So, by studying C. elegans we can also learn more about the human brain."

Moreover, the worm is able to learn from past experiences, says Professor Beets. "Worms are intrinsically drawn to salt because they associate it with the presence of food. However, if they come into contact with salt when there is no food present, this results in a negative association. In other words, the worm will prefer to avoid salt."

Recalling negative memories

Inactivating the gene responsible for Neuromedin U changes the worms' behaviour, says doctoral student Jan Watteyne, lead author of the study. "We found that the protein plays a very specific role in the learning process: it ensures that the worm is able to learn from past experiences. If the worm encounters a salty environment without food, it will avoid the salt on future occasions. However, if we temporarily block Neuromedin U, the worm forgets this first experience and will be drawn to the salt again. This means that the protein doesn't help to make the association, but it does help to recall it."

"It's clear that the signalling molecule Neuromedin U plays a crucial role in learning and memory, and more specifically the retrieval of negative memories. This leads us to suspect that other similar molecules, so-called neuropeptides, also perform these specific functions."

Starting point

"Our findings in worms are a good starting point for further research into the cognitive functions of other animals. We know that Neuromedin U is also found in many other organisms and in the human brain", says Professor Liliane Schoofs. "A good knowledge of these basic mechanisms is, therefore, crucial to better understand the complex processes in the human brain."

LOUISVILLE, Ky. - Several years ago, Guillermo Rougier, Ph.D., professor in the Department of Anatomical Sciences and Neurobiology at the University of Louisville, was approached by David Krause, Ph.D., curator at the Denver Museum of Nature & Science, to help identify a complete, 3-D fossil he had discovered on Madagascar.

"When Dr. Krause showed it to me in a scientific meeting and asked me for my opinion, I said I had never seen anything like this," Rougier recalled. "This mammal has teeth for which we have no parallel."

Krause and a team of paleontologists discovered the fossil during an expedition in Madagascar and spent more than a decade working to determine where it falls in the long history of mammalian evolution and what it tells us about geography and changes in global fauna over time.

Rougier, a paleontologist who specializes in the study of the skull and teeth of ancient mammals, was intrigued and joined the international team of researchers to thoroughly analyze the fossil. Their analysis was published today in the journal Nature.

The fossil is remarkably complete, an extremely rare find for ancient mammals that lived alongside the dinosaurs. Rougier described the creature as very roughly resembling a beaver or a small capybara.

"First, it is surprising how complete it is," Rougier said. "Second, this fossil is preserved in three dimensions. When you have an animal that dies and is preserved in the rocks, the weight of the rocks on top of it flattens it out. Often it looks like a steam roller ran over it. So you might have a complete skeleton but it will be the thickness of a piece of paper - all splat out. This animal was preserved in 3-D so this gives us a wealth of detail that we very rarely have in other specimens."

The research team named the creature Adalatherium, which is translated from the Malagasy and Greek languages and means "crazy beast," a nod to its bizarre characteristics. They placed it among gondwanatherians, a poorly known group of mammals found in various locations in the Southern Hemisphere. Rougier used the teeth and skull of the animal to figure out how to relate it to other mammals that were living at the time and afterward.

"Teeth in mammals reflect their ancestry, diet and environment. In the case of Adalatherium, the morphology is so peculiar that it is hard to use the characters we normally use to establish family relationships," Rougier said. "Mammalian systematics and evolution rest heavily on dental morphology, so when you do not have teeth - or they are so strange that you do not know what to do with them (think of anteaters, whales, armadillos and pangolins) - we have a problem."

Rougier was part of the expeditions in which the first gondwanatherians were discovered in his native Argentina in the 1980s, but relatively few specimens of the group have been found since then. That makes this unusually complete discovery in Madgascar exceptionally useful in forming a more accurate picture of the enigmatic group.

Madagascar, an island off the coast of Africa, is known for unique animal species that developed in isolation over millions of years. The island broke off from India and over a period of 100 million years moved toward Africa, yet never quite arrived, allowing the animals to evolve distinctly from the larger continents.

"Adalatherium is a product of this time of isolation when Madagascar was an island, detached from India and shifting towards Africa, but before there was any African influence. So it was basically an experiment, an example of what we call island biogeography or island evolution," Rougier explained.

"Long isolated places produce very unique results in biology," Rougier said. "These fossils keep reminding us of the unexpected forms and shapes that evolution can take over long periods of time in an isolated place. Adalatherium is an animal for which we don't have any real parallels."

Although the discovery of Adalatherium is a breakthrough in understanding the gondwanatherians, there still is a great deal the scientists do not know about the animals of this time and place.

"Adalatherium is just one piece, but an important piece, in a very large puzzle on early mammalian evolution in the Southern Hemisphere," Krause said. "Unfortunately, most of the pieces are still missing."

An international research team led by the University of Hong Kong (HKU) developed a new method to accurately track the spread of COVID-19 using population flow data, and establishing a new risk assessment model to identify high-risk locales of COVID-19 at an early stage, which serves as a valuable toolkit to public health experts and policy makers in implementing infectious disease control during new outbreaks. The study findings have been published in the journal Nature today (April 29).

Dr. Jayson Jia, Associate Professor of Marketing at the Faculty of Business and Economics of HKU and lead author of the study, and his co-authors used nation-wide data provided by a major national carrier in China to track population movement out of Wuhan between 1 January and 24 January 2020, a period covering the annual Chunyun mass migration before the Chinese Lunar New Year to a lockdown of the city to contain the virus. The movement of over 11 million people travelling through Wuhan to 296 prefectures in 31 provinces and regions in China were tracked.

Differing from usual epidemiological models that rely on historical data or assumptions, the team used real-time data about actual movements focusing on aggregate population flow rather than individual tracking. The data include any mobile phone user who had spent at least 2 hours in Wuhan during the study period. Locations were detected once users had their phones on. As only aggregate data was used and no individual data was used, there was no threat to consumer privacy.

Combining the population flow data with the number and location of COVID-19 confirmed cases up to 19 February 2020 in China, Dr Jia's team showed that the relative quantity of human movement from the disease epicentre, in this case, Wuhan, directly predicted the relative frequency and geographic distribution of the number of COVID-19 cases across China. The researchers found that their model can explain 96% of the distribution and intensity of the spread of COVID-19 across China statistically.

The research team then used this empirical relationship to build a new risk detection toolkit. Leveraging on the population flow data, the researchers created an "expected growth pattern" based on the number of people arriving from the risk source, i.e. the disease epicentre. The team thereby developed a new risk model by contrasting expected growth of cases against the actual number of confirmed cases for each city in China, the difference being the "community transmission risk".

"The risk index we create is based on the following logic: If there are more reported cases than the model expected, there is a higher risk of community spread. If there are fewer reported cases than the model expected, it means that the city's preventive measures are particularly effective or it can indicate that further investigation by central authorities is needed to eliminate possible risks from inaccurate measurement," explained Dr Jia.

"What is innovative about our approach is that we use misprediction to assess the level of community risk. Our model accurately tells us how many cases we should expect given travel data. We contrast this against the confirmed cases using the logic that what cannot be explained by imported cases and primary transmissions should be community spread. " He added.

The approach is advantageous because it requires no assumptions or knowledge of how or why the virus spreads, is robust to data reporting inaccuracies, and only requires knowledge of relative distribution of human movement. It can be used by policy makers in any nation with available data to make rapid and accurate risk assessments and to plan allocation of limited resources ahead of ongoing disease outbreaks.

"Our research indicates that geographic flow of people outperforms other measures such as population size, wealth or distance from the risk source to indicate the gravity of an outbreak." said Dr Jia.

Dr Jia is currently exploring with fellow researchers the feasibility of applying this toolkit to other countries, and extending it to situations where there are multiple COVID-19 epicentres. The team is working with other national telecom carriers and seeking additional data partners.

CATONSVILLE, MD, April 29, 2020 - Job performance has long been understood to be the primary equalizing factor affecting promotions for men and women in the workplace, but research shows, women don't gain as much from the same performance improvements as men do. New research in the INFORMS journal Information Systems Research shows training plays an important part in promotions for women in the field of information technology.

"Women are more likely to be credited less for their performance improvements because of inherent biases against women in tech jobs, which may lead to management attributing performance improvements to luck or other factors rather than ability," said Nishtha Langer, one of the authors from Rensselaer Polytechnic Institute.

Women make up 57% of the U.S. labor market and 23% of computer and information technology careers. The study, "Onwards and Upwards? An Empirical Investigation of Gender and Promotions in IT Services," conducted by Langer, Ram Gopal of the Southern University of Science and Technology and Ravi Bapna of the University of Minnesota, found that women are more likely to be promoted than men, but not merely based off of performance improvements or work experience gains. Instead, oftentimes the promotion is based off training opportunities they have been involved in.

The researchers looked at data from a leading IT firm in India consisting of records of more than 7,000 employees from 2002-2007. It showed women benefit disproportionately more from training in increasing their chances of promotion but may be penalized for better performance in that their promotion likelihood is lower compared to men

"Women may see training as a credible signaling mechanism to let senior management know they are investing in themselves and are able to take on more senior roles," said Langer, a professor with the Lally School of Management at Rensselaer. "We believe training allows them to circumvent any social and structural biases that may have otherwise prevented their chances of promotions."

The researchers explain these findings by suggesting women may be more opportunistic when it comes to enrolling for courses because it can ensure faster promotions, or they may imbibe knowledge more effectively and are more adept at translating knowledge gains into promotability.

TROY, N.Y. -- Women are underrepresented in leadership positions throughout the information technology industry. While more and more women are earning degrees in science, technology, engineering, and math -- or STEM -- fields, they don't necessarily pursue careers in IT, because they don't see opportunities for growth.

New research from the Lally School of Management at Rensselaer Polytechnic Institute published in Information Systems Research examines how gender affects the likelihood of promotions in the context of the IT industry.

Using a five-year dataset of the promotions, demographics, performance, and training records of more than 7,000 employees at a leading IT services firm in India, Nishtha Langer, an assistant professor of business analytics at Rensselaer, determined that gender is a strong predictor of promotion.

"Contrary to our theoretical expectations, we find that women were more likely to be promoted," Langer said.

Learn more about Langer's research in this video.

Little prior research has examined archival data to understand the interplay of gender, performance, and training affects promotions in the IT industry to this extent. Even as IT firms embrace fairer organizational policies and egalitarian work environments, the study finds that that subtle discrimination against women in IT continues to exist. However, the study also points out effective strategies women in IT can use to forge ahead in their chosen career paths.

Langer conjectures that women are likely promoted more often because they are considered more helpful and trustworthy compared to men, and because -- as a result of disparities in pay -- they are often a lower-cost option.

However, when it comes to promotions based solely on performance improvements, Langer said her findings were less encouraging for women.

"Beyond all this good news for women in IT, men continue to show a higher likelihood of promotion from performance improvements," Langer said. "So, to me, that speaks to a more subtle form of discrimination compared to more overt forms of discrimination."

A more effective tool for women to signal their preparedness for promotion, Langer said, is to take training courses. They are more likely to be promoted than men who take the same training. According to the research, women may be more opportunistic when it comes to enrolling for courses that ensure faster promotions. They may also be more adept at translating knowledge gains into promotability.

Although Langer's study focuses on IT labor markets, she said her findings are generalizable to women in other male-dominated industries, particularly those in STEM areas.

Individuals with social anxiety disorder have markedly different personality traits than others. Emotional instability and introversion are hallmarks, according to a new study from Uppsala University published in PLOS ONE.

"Social anxiety disorder seems to be a problem that is strongly intertwined with personality, but at the same time it shows great variation," says Professor Tomas Furmark from the Department of Psychology at Uppsala University, who led the study.

Researchers have long been looking for the connection between personality factors and the risk of developing psychiatric illnesses. In psychological science, personality is typically described using five well-established dimensions: neuroticism, also known as emotional instability; extraversion, which deals with how outgoing a person is; openness; agreeableness; and conscientiousness - the 'Big Five'.

A study from Uppsala University, now published in PLOS ONE, shows that personality is strongly intertwined with the diagnosis of social anxiety disorder, also called social phobia.

The study involved 265 individuals with the diagnosis. They filled out comprehensive personality instruments, including the revised NEO Personality Inventory (NEO-PI-R) and the Karolinska Scales of Personality (KSP). They were also compared with healthy control subjects and Swedish norm data. The results showed that individuals with social anxiety disorder had markedly different personality traits, in particular, high neuroticism and introversion, in other words, a tendency to be emotionally unstable and inward turning.

At the same time, the study showed that there was a great deal of variation in personality traits among the socially anxious individuals. Three personality groups could be distinguished, based on cluster analysis of the Big Five personality dimensions.

The first group, with prototypical social anxiety, was both highly anxious and introverted - which may be seen as the typical form of social anxiety disorder. However, these individuals accounted for only one-third (33 per cent) of the total patient sample.

Individuals in the second group (29 per cent), with introvert-conscientious social anxiety, were very introverted but more moderately anxious and also had high levels of conscientiousness.

Individuals in the third and largest group (38 per cent), with unstable-open social anxiety disorder, were anxious while having almost normal levels of extraversion. Comparisons with norm data also showed that these individuals scored high on the personality trait openness.

"It is possible that the causes of social anxiety differ for the three groups, for example, with regard to abnormalities in brain neurotransmitter levels and genetic factors. It may also be that different treatment efforts are needed for the different types of social anxiety disorder, but further studies are needed to clarify this," says Furmark.

SALT LAKE CITY - To replace aging and worn cells, the body primarily uses a process called mitosis, in which one cell divides into two. When a cell is ready to divide, it duplicates its DNA so a complete copy is available for each of the daughter cells. In this process, the DNA pieces, or chromosomes, must be precisely apportioned into the daughter cells. If one cell has an incomplete copy of the DNA or if the DNA becomes damaged, genetic disorders and diseases such as cancer can result.

For cell division to occur, the two sets of DNA must be localized to opposite sides of the cell. First, the compartment that normally contains the DNA, the nucleus, disassembles its protective coating. Then the chromosomes are separated by an apparatus of fibers. A new nucleus forms around each DNA set. Finally, the cell splits into two, each with its own re-formed nuclear compartment inside.

Scientists at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) and collaborators at the University of California, San Francisco (UCSF) published research in the journal Nature extending our understanding of the intricate process of cell division. They discovered the protein LEM2 has two important functions during cell division. First, LEM2 creates seals in the protective coating of forming nuclei that keep the two sets of DNA shielded from damage. Second, LEM2 recruits factors that disassemble the apparatus of fibers responsible for separating the DNA sets. HCI's Katharine Ullman, PhD, and UCSF's Adam Frost, PhD, collaborated over the last six years on this work.

To visualize LEM2's role in mitosis, the Ullman Lab used colored fluorescent markers to label the different components: LEM2, the fibers, and the DNA. This process allowed the team to film LEM2--from when it first associates with intact fibers until the time of their disassembly. They observed LEM2 proteins concentrating and forming a gel-like seal with other proteins (ESCRTs) at holes where fibers traverse the protective coat of the nucleus. This LEM2 "O-ring" effectively sealed off the re-forming nuclear coat, safeguarding each set of DNA from material surrounding the nucleus.

"Using our imaging methods, we were able to see a process that only occurs over the course of about five minutes during cell division, something that would have been very difficult to study otherwise," said Dollie LaJoie, PhD, a researcher in Ullman's research group and a co-author on the study.

"This work was strengthened by the fact that both teams worked on this project using different approaches to better explain the role of LEM2," Ullman said. "My research group focused on this process in live cells while Frost's research group worked to understand more about the protein itself."

The authors note that this novel type of gel-like separation may prove important for other critical cell functions that LEM2 participates in, including higher-level DNA organization.

The authors also showed that disruptions to LEM2 as it assembles the nucleus resulted in DNA damage--which jeopardizes normal cell function.

"This work opens a door to identifying new pathways for DNA to be damaged, which in some cases may contribute to the development of cancer," said Ullman.

Moving forward, the Ullman and Frost Labs will build on this work by investigating the connection between improper nucleus formation and DNA damage. They will examine how cancer cells may lack the proper regulation of both nuclear assembly and nuclear repair.

(Boston)--In an effort to mitigate the spread of COVID-19 and to optimize allocation of healthcare resources, researchers are improving ways to treat patients with acute large vessel occlusion strokes in a safe manner that also better protects health care workers.

Developed by a team from the Society of Vascular & Interventional Neurology (SVIN) and led by a Boston University School of Medicine (BUSM) researcher, the new guidance statement is divided into four phases: pre-hospital to the emergency department, pre-thrombectomy procedure, thrombectomy intra-procedure and post-reperfusion therapy.

"Every opportunity and detail to recalibrate our acute neurological workflow to protect our frontline health care workers, our families, our colleagues and our patients should be sought, implemented and adapted to a resource-constrained environment," explained corresponding author Thanh Nguyen, MD, professor of neurology, neurosurgery and radiology at BUSM and director of the neuroendovascular service at Boston Medical Center.

Among the recommendations:

Screen every acute stroke patient for COVID-19 adhering to local EMS, emergency department (ED) protocols.

Use of remote tele-stroke technology to obtain history and perform neurological examination, post reperfusion monitoring, if available.

Minimize the number of people at an acute stroke or thrombectomy code: one person in protective equipment with patient, another at computer/phone to help coordinate care.

Consider low-dose chest computerized tomography (CT) as the same time as head CT/CTA to facilitate COVID-19 diagnosis.

Implement a "direct to the angiography suite" approach for stable transferred patients with stroke symptoms onset within 24 hours to minimize exposure to ED and CT personnel.

Consider conscious sedation as first-line to protect anesthesiologists from exposure, and to protect patients from unnecessary intubation as well as conserving mechanical ventilator resources.

If patients exhibit pulmonary symptoms, lower threshold to intubate patients in a controlled manner in a negative pressure room.

Defer any tests that won't change management until the patient has ruled out for COVID-19.

Consider repatriation of select patients back to primary stroke centers to recover after thrombectomy for hospitals overwhelmed with critical care or intensive care unit bed shortages. This can help maintain thrombectomy access.

According to the researchers, these new workflow applications are based on shared best practices, consensus among academic and non-academic practicing vascular and interventional neurologists and literature review, and could be adapted to the available resources of a local institution.

"The acute stroke patient is a vulnerable group to address because these patients often come emergently from the community with little information. Radical changes are necessary to optimize the safety of the providing team and our patients, limit unnecessary tests, conserve personal protective equipment (PPE) resources and mechanical ventilator usage," added David Liebeskind, MD, director of the UCLA Comprehensive Stroke Center and SVIN president.

Nguyen believes it is incumbent upon all of us to protect each other so that we are not unknowingly exposed or spread to our most vulnerable patients, while at the same time, providing optimal care, patient safety, and access to treatment for stroke patients. This guidance statement pertains to current practice and can change as new evidence arises.

This guidance statement appears online in the journal Stroke.

Researchers from Tilburg University in the Netherlands and the University of Cologne in Germany published a new paper in the Journal of Marketing that explains which factors influence media coverage of CSI events.

The study forthcoming in the Journal of Marketing is titled "When Does Corporate Social Irresponsibility Become News? Evidence from More than 1,000 Brand Transgressions Across Five Countries" and is authored by Samuel Stäbler and Marc Fischer.

Consumers beware! Media outlets do not report corporate misconduct, such as environmental offences, corruption, or violations of societal standards around human rights or employee working conditions, consistently and independently. Instead, media are often influenced by their own interests, including advertising revenues paid by offending companies.

Cases of corporate misconduct, often called Corporate Social Irresponsibility or CSI, are usually newsworthy events with high news value for the media. This study examined media coverage of 1,054 CSI events in 77 leading media outlets from five countries (USA, Mexico, Germany, Great Britain, and France). Results show that media reporting is not impartial. Overall, the online and offline newspapers and magazines studied most frequently report on the ethical misconduct of popular companies with well-known brands as well as misconduct by foreign companies, which are reported 39% and 80% more frequently, respectively. Also, liberal media report more frequently on CSI than conservative media.

Importantly, if these media have close advertising partnerships with a company, media report significantly less often on its CSI events. In fact, the probability of reporting falls by 45% to a level as low as 9.5%.

Unfortunately, the media seem to be unaware of this distortion. Interviews with editors of leading media in Germany uncovered the view that neither advertising revenues nor the political orientation of the newspaper influenced reporting. Our large-scale study shows the opposite.

As might be expected, these reporting patterns have important economic consequences for companies. According to the study, the average financial loss on the U.S. stock exchange due to a CSI event amounts to $321 million if four or more U.S. media report on the event.

When coverage is not based on the newsworthiness of the event, but on the popularity of the brand and whether it involves a foreign company, these economic consequences are unfairly distributed. Worse yet, if news media do not cover CSI events for their advertising partners, media coverage is compromised by a conflict of interest. Stäbler remarked, "The media fulfill an important role in democratic societies in that they contribute to the formation of public opinions. Consumers have the right to be informed about potential firm misbehavior in a transparent and balanced manner. Our study shows that media coverage varies significantly when it comes to reporting about a CSI event."

The media ideally fulfill an important role in democratic societies in that they contribute to the formation of public opinions. Consumers have the right to be informed about potential firm misbehavior in a transparent and balanced manner. Fischer added, "Our results call into question the self-proclaimed independence of the media. Among other things, it was astonishing how much more frequently the misconduct of foreign companies is reported, while in comparison, domestic companies are less frequently the subject of CSI reporting. The media exert a great deal of pressure and demand compliance with the highest ethical standards and social norms from public figures and companies. Our research on CSI reporting shows that media companies themselves do not always adhere to the high ethical standards they demand of others."

Researchers at Baylor College of Medicine, the University of South Carolina and other institutions have identified tobacco smoking as a potential risk factor for infection of the COVID-19 virus.

Co-corresponding authors Dr. Christopher I. Amos, director of the Institute of Clinical and Translational Research at Baylor, Dr. Guoshuai Cai, assistant professor at the University of South Carolina, and their colleagues analyzed datasets of the RNA expressed by various types of lung tissue, comparing current and former smokers and non-smokers.

They looked at the expression of ACE2, the molecule in the respiratory tract that the COVID-19 virus uses to attach to and infect human cells. They also looked at the expression of FURIN and TMPRSS2, human enzymes known to facilitate COVID-19 virus infection.

The researchers report in the American Journal of Respiratory and Critical Care Medicine a 25 percent increase in the expression of ACE2 in lung tissues from ever-smokers, people who have smoked at least 100 cigarettes during their lives, when compared with nonsmokers. Smoking also increased the presence of FURIN, but to a lower extent compared to ACE2. TMRPSS2 expression in lungs was not associated with smoking. They also found that smoking remodeled the gene expression of cells in the lungs so that the ACE2 gene was more highly expressed in goblet cells, cells that secrete mucus in order to protect the mucous membranes in the lungs.

The significant smoking effect on ACE2 pulmonary expression identified in this study indicates not only an increase in the entry points for the COVID-19 virus but also may suggest an increased risk for viral binding and entry of the virus in the lungs of smokers. The findings provide valuable information for identifying potentially susceptible populations.

"We hypothesized that the worse outcomes of COVID-19 infections in regions of the world with high levels of cigarette smoking may reflect host factors," Amos said. "Studies of COVID-19 patients would help resolve the influence of smoking on COVID-19 outcomes."

New Rochelle, NY, April 29, 2020--Researchers have reported a significant and positive relationship between the amount of virus present in a throat swab sample and the severity of COVID disease. The higher the relative viral load in the sample, the greater the organ damage, and the longer it would take for the viral RNA count to turn negative, according to the results published in Viral Immunology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Viral Immunology website through May 30, 2020.

In "Correlation Between Relative Nasopharyngeal Virus RNA Load and Lymphocyte Count Disease Severity in Patients with COVID-19" Wei Zhang and coauthors from The First Affiliated Hospital of Nanchang University (Jiangxi, China), collected nasopharyngeal samples from patients with mild and severe COVID-19. They measured the level of viral RNA in the sample, also known as the viral load. Viral load correlated positively with the severity of disease symptoms and with increased inflammatory factors. There was a negative correlation between SARS-CoV-2 viral load and lymphocytes, such as CD4+ and CD8+T lymphocytes, which fight infection.

David L. Woodland, PhD, Editor-in Chief of Viral Immunology and Adjunct Member of the Trudeau Institute in Saranac Lake, NY, states: "We currently have only a limited understanding of why some patients with the SARS-CoV-2 virus develop severe, life-threatening symptoms, whereas others do not. In this paper, Zhang and colleagues present data correlating viral loads in the nasopharynx with disease severity and progression. These important findings potentially offer medical professionals with crucial information when deciding on treatment options for COVID-19 patients."

As the COVID-19 curve shows signs of flattening in the U.S. and elsewhere, public health officials are trying to grasp just how many people have been infected. Now, a proof-of-concept study in ACS' Analytical Chemistry describes a quick, sensitive test for antibodies against the coronavirus in human blood. The test could help doctors track a person's exposure to the disease, as well as confirm suspected COVID-19 cases that tested negative by other methods.

Because COVID-19 symptoms range from mild to severe, with some people apparently having no symptoms, the number of people who have been infected with the SARS-CoV-2 virus at some point is likely much higher than the number of confirmed cases. As U.S. states begin to ease lockdown restrictions, widespread testing of the general population will be important to identify people at early stages of disease, or people who lack symptoms but can still infect others. Also, although more research needs to be done, it is possible that people with antibodies to the virus could be immune to future COVID-19 outbreaks. To help identify people with current or past exposure to SARS-CoV-2, Lei Yu, Yingsong Wu, Guanfeng Lin and colleagues wanted to develop a fast, sensitive antibody test.

The researchers based their test on a technique called a lateral flow immunoassay (LFA); a home pregnancy test is an example of this kind of assay. They attached a viral coat protein to a specific region on a strip of nitrocellulose, and then added human serum. The serum flowed from one end of the strip to the other, and any antibodies against the viral protein bound to that region on the strip. Then, the team detected the anti-SARS-CoV-2 antibodies with a fluorescently labeled antibody. This fluorescence-based detection is much more sensitive than some other LFAs, such as pregnancy tests, that can be read by the naked eye. The researchers tested the new assay on seven serum samples from COVID-19 patients and 12 samples from people who had tested negative for the disease by reverse transcriptase-polymerase chain reaction (RT-PCR), a common diagnostic test that occasionally fails to detect positive cases. The new assay correctly diagnosed all seven samples as positive -- as well as an additional "negative" case that had suspicious clinical symptoms -- in only 10 minutes per sample. The immunoassay could be helpful in confirming negative diagnoses, monitoring a patient's recovery, studying past exposures, and identifying recovered individuals with high levels of antibodies as potential convalescent plasma donors, the researchers say.

Each year, researchers from around the world visit the Department of Energy's SLAC National Accelerator Laboratory to conduct hundreds of experiments in chemistry, materials science, biology and energy research at the Linac Coherent Light Source (LCLS) X-ray laser. LCLS creates ultrabright X-rays from high-energy beams of electrons produced in a giant linear particle accelerator.

Experiments at LCLS run around the clock, in two 12-hour shifts per day. At the start of each shift, operators must tweak the accelerator's performance to prepare the X-ray beam for the next experiment. Sometimes, additional tweaking is needed during a shift as well. In the past, operators have spent hundreds of hours each year on this task, called accelerator tuning.

Now, SLAC researchers have developed a new tool, using machine learning, that may make part of the tuning process five times faster compared to previous methods. They described the method in Physical Review Letters on March 25.

Tuning the beam

Producing LCLS's powerful X-ray beam starts with the preparation of a high-quality electron beam. Some of the electrons' energy then gets converted into X-ray light inside special magnets. The properties of the electron beam, which needs to be dense and tightly focused, are a critical factor in how good the X-ray beam will be.

"Even a small difference in the density of the electron beam can have a huge difference in the amount of X-rays you get out at the end," says Daniel Ratner, head of SLAC's machine learning initiative and a member of the team that developed the new technique.

The accelerator uses a series of 24 special magnets, called quadrupole magnets, to focus the electron beam similarly to how glass lenses focus light. Traditionally, human operators carefully turned knobs to adjust individual magnets between shifts to make sure the accelerator was producing the X-ray beam needed for a particular experiment. This process took up a lot of the operators' time - time they could spend on other important tasks that improve the beam for experiments.

A few years ago, LCLS operators adopted a computer algorithm that automated and sped up this magnet tuning. However, it came with its own disadvantages. It aimed at improving the X-ray beam by making random adjustments to the magnets' strengths. But unlike human operators, this algorithm had no prior knowledge of the accelerator's structure and couldn't make educated guesses in its tuning that might have ultimately led to even better results.

This is why SLAC researchers decided to develop a new algorithm that combines machine learning - "smart" computer programs that learn how to get better over time - with knowledge about the physics of the accelerator.

"The machine learning approach is trying to tie this all together to give operators better tools so that they can focus on other important problems," says Joseph Duris, a SLAC scientist who led the new study.

A better beam, faster

The new approach uses a technique called a Gaussian process, which predicts the effect a particular accelerator adjustment has on the quality of the X-ray beam. It also generates uncertainties for its predictions. The algorithm then decides which adjustments to try for the biggest improvements.

For example, it may decide to try a dramatic adjustment whose outcome is very uncertain but could lead to a big payoff. That means this new, adventurous algorithm has a better chance than the previous algorithm of making the tweaks needed to create the best possible X-ray beam.

The SLAC researchers also used data from previous LCLS operations to teach the algorithm which magnet strengths have typically led to brighter X-rays, giving the algorithm a way of making educated guesses about the adjustments it should try. This equips the algorithm with knowledge and expertise that human operators naturally have, and that the previous algorithm lacked.

"We can rely on that physics knowledge, that institutional knowledge, in order to improve the predictions," Duris says.

Insights into the magnets' relationships to each other also improved the technique. The quadrupole magnets work in pairs, and to increase their focusing power, the strength of one magnet in a pair must be increased while the other's is decreased.

With the new process, tuning the quadrupole magnets has become about three to five times faster, the researchers estimate. It also tends to produce higher-intensity beams than the previously used algorithm.

"Our ability to increase our tuning efficiency is really, really critical to being able to deliver a beam faster and with better quality to people who are coming from all over the world to run experiments," says Jane Shtalenkova, an accelerator operator at SLAC who worked with Duris, Ratner and others to develop the new tool.

Beyond LCLS

The same method can be extended to tune other electron or X-ray beam properties that scientists may want to optimize for their experiments. For example, researchers could apply the technique to maximize the signal they get out of their sample after it's hit by LCLS's X-ray beam.

This flexibility also makes the new algorithm useful for other facilities.

"The nice thing about this machine learning algorithm is that you can do tech transfer relatively easily," says Adi Hanuka, a SLAC scientist who has been testing the technique at three other accelerators: SPEAR3, the accelerator ring powering SLAC's Stanford Synchrotron Radiation Lightsource (SSRL); PEGASUS at the University of California, Los Angeles; and the Advanced Photon Source (APS) at DOE's Argonne National Laboratory.

"This tool now exists in several labs," Hanuka says. "Hopefully, we'll be integrating it into even more labs soon."