Culture

Researchers at Rutgers Robert Wood Johnson Medical School are reporting the first instance of COVID-19 triggering a rare recurrence of potentially serious blood clots in people's arms.

The discovery, published in the journal Viruses, improves the understanding of how inflammation caused by COVID-19 can lead to upper extremity blood clots and how best to treat them. The case study is part of a larger Rutgers study of 1,000 hospitalized patients diagnosed with COVID-19 who were admitted and discharged between March and May 2020.

While there have been reports of lower extremity deep vein thrombosis following COVID-19, this is the first study in which COVID-19 triggered a recurrence in the upper arm of an active 85-year-old man who had a prior diagnosis of upper extremity blood clots.

"The patient presented to his primary care physician with complaints of swelling in his left arm and was sent to the hospital for further management where he was diagnosed with an upper arm blood clot and an asymptomatic COVID-19 infection," said Payal Parikh, an assistant professor of medicine at Rutgers Robert Wood Johnson Medical School, who led the study along with Martin Blaser, director of the Center for Advanced Biotechnology and Medicine and a professor at Rutgers Robert Wood Johnson Medical School. "While his oxygen levels were not diminished, he was hospitalized for the management of the upper extremity deep vein blood clot. Often, blood clots are preceded by chronic inflammatory conditions exacerbated by immobility, and rarely do they occur in patients who are otherwise healthy and active at baseline."

Most cases of deep vein thrombosis occur in the legs. Only about 10 percent of blood clots occur in the arms and of those cases only 9 percent recur.

"This is of concern since in 30 percent of these patients, the blood clot can travel to the lung and be possibly fatal," said Parikh. "Other disabling complications include persistent swelling, pain and arm fatigue."

The study suggests that clinicians should consider testing for deep vein thrombosis and COVID-19 in patients who present with complaints of unexplained swelling. People who test positive for COVID-19 should seek medical attention if they have declining oxygen levels, shortness of breath and any unexplained swelling.

"If you have been previously diagnosed with deep vein thrombosis or have chronic medical illness that predisposes you to blood clots, you have a higher risk for recurrence of a deep vein thrombus in the setting of a COVID-19 infection and thus, should be vigilant," said Parikh.

ATS 2021, New York, NY - The use of e-cigarettes is associated with wheezing and shortness of breath in young adults and adolescents, even in those who don't smoke cigarettes or marijuana, according to research presented at the ATS 2021 International Conference.

Alayna P. Tackett, PhD, assistant professor of preventive medicine, University of Southern California Keck School of Medicine, and colleagues conducted a web-based survey of 2,931 adolescents and young adults (average age: 18.9) with questions on the use of e-cigarettes, cigarettes and cannabis, along with self-reported asthma diagnosis and respiratory symptoms, over the previous 30 days. The survey was fielded between August 6 and 30, 2020 among a national convenience sample of youth and young adults aged 14-21 using Lucid™, a survey management company. Recruitment, data collection, and compensation were handled by Lucid and company partners. Statistical analyses were used by the researchers to examine possible relationships among these variables.

They found that, after controlling for age, gender and race/ethnicity, past 30-day e-cigarette use was associated with increased odds of self-reported asthma, wheezing and shortness of breath, compared with survey respondents who reported never using e-cigarettes. This relationship held true, even after statistically controlling for those who said they had ever used cigarettes or cannabis. After controlling for past 30-day cigarette and cannabis use, past 30-day e-cigarette use was no longer associated with asthma--but was still associated with shortness of breath and increased wheezing.

The prevalence of asthma, wheeze and shortness of breath was 24 percent, 13 percent and 20 percent, respectively. Among past 30-day e-cigarette users, 15 percent reported using cigarettes and 37 percent reported cannabis use.

"As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research," said Dr. Tackett. "This preliminary study highlights the need for more longitudinal studies and studies that incorporate objective assessments of respiratory health to further determine the specific respiratory risks from e-cigarettes. We also need to better understand the complex relationships between these products and whether multiple product use is associated with worse respiratory outcomes."

The number of adolescents and young adults who use e-cigarettes continues to increase, with estimates of 5.4 million new users in 2019. E-cigarettes are the most commonly used tobacco product in this age group, but researchers have found it difficult to disentangle the risk of asthma and related respiratory symptoms associated with e-cigarettes due to a high frequency of cigarette and cannabis smoking among e-cigarette users age 14-21.

"Wheeze and shortness of breath are just two indicators of many to assess respiratory health," said Dr. Tackett. "The respiratory system is complex and it may be that measuring respiratory health more frequently through such means as spirometry may help tell us more about the relationship between e-cigarette use, multiple product use and respiratory outcomes."

Dr. Tackett's team is currently conducting two follow-up studies that use objective measurement tools like handheld, home-based spirometry to examine adolescent and young adult reported respiratory symptoms. Those who exclusively use e-cigarettes as well as those who have never used them will be recruited to examine their differences and better understand the relationship between e-cigarette use and respiratory health.

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Session: TP68
Abstract Presentation Time: AVAILABLE ON-DEMAND

ATS 2021, New York, NY - Individuals with asthma who live in redlined neighborhoods have worse lung function than those in locales that excluded Black people and benefited from decades of inequitable wealth accumulation at the expense of Black communities in the United States, according to research presented at the ATS 2021 International Conference.

Alexander Schuyler, MD/PhD candidate, University of Pittsburgh School of Medicine, and Sally Wenzel, MD, director, Asthma & Environmental Lung Health Institute, University of Pittsburgh Medical Center, sought to examine the connection between residence in historically redlined communities and the impact on lung function and asthma outcomes. Redlining is a form of institutional racism and discriminatory mortgage lending practice enacted by the Home Owners' Loan Corporation in the New Deal era that resulted in racialized economic deprivation and segregation. These historically validated and geographically defined mechanisms contribute to current environmental inequities, and, as the authors propose, to worsening asthma outcomes in Black neighborhoods across the U.S.

"Lung health in Black people is impacted by converging legacies of institutional racism, including racist mortgage loaning practices like redlining, and associated environmental inequities," stated Mr. Schuyler. "Racist housing policies have had a long-term negative impact on diseases like asthma. In addition, the clinical and research convention of applying a race correction to lung function measurements may have accentuated these effects, underestimating the impact of racism and environmental inequities on lung health."

Race-based correction for spirometry was constructed in the 1840s by White supremacist physician and enslaver Samuel Cartwright, who used research to justify Black enslavement and to fabricate arguments that Black people were inferior to White people, including having lower lung function. These adjustments continue today, and are considered accepted medical practice. The authors state that the sickest Black patients with asthma may be undertreated because the results of their breathing tests are "adjusted" and may appear to have better lung function than they actually do.

To examine the impact of institutional racism on asthma outcomes, the researchers looked at the lung health of 326 Pittsburgh residents with asthma localized by zip code to determine if they lived in redlined neighborhoods. Patients were identified by the University of Pittsburgh Asthma and Environmental Lung Health Institute at UPMC's patient registry. Study participants were given spirometry lung function tests and questionnaires.

The researchers determined that residence in redlined neighborhoods was independently associated with lower forced expiratory volume (FEV1 -- the maximum amount of air a person can forcibly exhale in one second) after theoretical adjustment for several variables used to "normalize" lung function in research and clinical practice. Supporting these differences, they found that despite no difference in life-threatening asthma episodes, an increased prevalence of co-occurring diseases (co-morbidities) was present in asthmatic adults living in more redlined neighborhoods, independent of race.

"Race is a social construct," said Mr. Schuyler. "We propose that race-based corrections of spirometric values, a multiplicative scaling factor applied to height, age, and sex-adjusted FEV1 and FVC (forced vital capacity--maximum amount exhaled forcefully after breathing in deeply) values on the basis of race, should be abolished. Redlined neighborhoods experience persistently poor air quality, supporting a link with environmental inequality. The use of race-based corrections for spirometric values suggests that observed variations (if any) in lung function across racial groups are related to differential biology when, in fact, disproportionately higher exposure to pollution likely contributed to these differences."

He added, "Clinicians should not use spirometric values alone to make medical decisions, without including the clinical or socioenvironmental context."

The authors explained how spirometric values are adjusted for Black asthma patients: "The equations used to correct spirometric values are generated in reference to a White population. Thus, for this equation White people are artificially assigned a correction factor of 1, while Black people, Asian people, and other racial groups are assigned a correction factor of less than 1. Black people have a correction factor that is typically 85-90% of that used for the White population.

"Applying this correction factor to Black folks compresses the difference between the actual and 'predicted' values in liters to a higher degree than in White people, meaning, in those with severe disease, their lung function appears numerically better than it is. This could lead to clinical decisions to undertreat Black patients. In contrast, there is no recentering of the 'predicted' value in liters in White people. Lower than normal lung function in White people may promote earlier treatment, as they would have lower percent predicted values compared to 'otherwise identical' Black people. Everyone will benefit more if asthma care is driven by the best possible percent predicted values for all people, regardless of race."

Since submitting this ATS 2021 research abstract, Mr. Schuyler and Dr. Wenzel expanded their study to include 1,034 adults with asthma residing in Allegheny County, which includes Pittsburgh. "This gives us a much more detailed view and helps provide better context for each patient." They state that this expanded analysis has helped them determine that residence in redlined neighborhoods, in addition to lower FEV1, is associated with uncontrolled and/or severe asthma. Their additional research also found persistently poor air quality in redlined neighborhoods, linking it strongly with environmental inequity.

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Session: TP16

Abstract Presentation Time: Available On-Demand; 8 a.m. EDT, Friday, May 14, 2021

ATS 2021, New York, NY - While vaping is thought to be a safer alternative to smoking, teens and adults who use e-cigarettes have increased odds of developing asthma and having asthma attacks, according to research presented at the ATS 2021 International Conference.
T

eresa To, PhD, senior scientist in the Child Health Evaluative Sciences program at The Hospital for Sick Children (SickKids), and colleagues sought to determine whether youth and young adults who are current e-cigarette users have increased odds of self-reported asthma and had an asthma attack within the last 12 months.

The researchers used data collected from the 2015-2016 and 2017-2018 cycles of the Canadian Community Health Survey (CCHS), a cross-sectional survey that collects self-reported information about health status, health determinants, and behaviors. They found that 3 percent of survey participants reported e-cigarette use within the previous 30 days, which corresponds to 1 in 32 individuals using e-cigarettes during that time period. Approximately half of e-cigarette users also reported smoking cigarettes daily. One in 8 (13 percent) e-cigarette users had asthma and those with asthma had nearly 24 percent increased odds of having an asthma attack within 12 months.

"To curtail the adverse health effects of vaping we should raise the awareness of the potential harmful health effects of vaping, and develop and implement evidence-based strategies to prevent and reduce e-cigarette use, especially in youth," said Dr. To. "We should also provide means and support to help those who currently vape to quit."

The study included 17,190 individuals aged 12 years and above who participated in the CCHS, in which 3.1 percent reported e-cigarette use in the past 30 days. After making statistical adjustments for other variables that might affect results (confounders), e-cigarette users had 19 percent higher odds of having asthma. Current smokers had 20 percent higher odds of having asthma, while former smokers had 33 percent higher odds. Those who never smoked or used e-cigarettes did not have significant associations with asthma.

"Interestingly, our study found a significantly higher proportion of those who used e-cigarettes reported fair to poor mental health (15 percent) compared to those who did not vape (7 percent)," said Dr. To.

"In addition, those who used e-cigarettes had 60 percent higher odds of self-reported high levels of life stress compared to those who did not. While vaping may not cause stress, it appears that vape cravings may be triggered by stress and anxiety, making it harder for the e-cigarette user to quit. This may be particularly relevant during the pandemic when stress and anxiety are highly prevalent."

"Our findings suggest that e-cigarette use is a modifiable risk factor for asthma to be considered in the primary care of youth and young adults," she concluded.

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Session: TP91

Abstract Presentation Time: On Demand; 8 a.m. EDT, Friday, May 14, 2021

ATS 2021, New York, NY - Having genetic risk variants in the ABO gene might significantly increase the chances of developing COVID-19, and other genes may also increase COVID-19 risk, according to research presented at the ATS 2021 International Conference.

Much about COVID-19 remains a medical mystery, including whether certain genes place individuals at greater risk of contracting the SARS-CoV-2 virus, which causes COVID-19. Ana Hernandez Cordero, PhD, postdoctoral fellow with the Centre for Heart Lung Innovation, University of British Columbia, and colleagues used integrative genomics combined with proteomics to identify these genes.

Genomic research identifies specific genes that may play a role in biological processes such as the development of disease, while proteomics does the same for proteins. Researchers can get a fuller picture of disease processes by integrating tools to investigate both.

"DNA is a big, complex molecule and so, genetic associations alone cannot pinpoint the exact gene responsible for COVID-19," said Dr. Hernandez. "However, by combining COVID-19 genetic information with gene expression and proteomic datasets, we can figure out which genes are driving the relationship with COVID-19."

The researchers combined genetic information with an examination of lung gene expression to identify genetic variants that were controlling gene expression in the lung that were responsible for COVID-19. The researchers identified specific genes' markers that share their effects on gene expression and protein levels with COVID-19 susceptibility. For the analysis, they used bioinformatics to integrate: (1) a genomic dataset obtained from patients who were infected with SARS-CoV-2 as well as non-infected individuals (controls); (2) lung and blood tissue gene expression datasets from clinical populations (non-COVID-19); and (3) a proteome dataset obtained from blood donors (non-COVID-19).

By doing this, they found that several genes responsible for the immune system's response to COVID-19 are also involved in COVID-19 susceptibility. What they discovered was supported by the findings of previous research.

Looking for candidate genes in blood proteins, they were able to go one step further in connecting the effects of genes to susceptibility to COVID-19. Blood proteomics can also help identify markers in the blood that can be easily measured to indicate disease status, and potentially, to monitor the disease.

"By harnessing the power of genomic information, we identified genes that are related to COVID-19," said Dr. Hernandez. "In particular, we found that the ABO gene is a significant risk factor for COVID-19. Of particular note was the relationship between the blood group ABO and COVID-19 risk. We showed that the relationship is not just an association but causal."

In addition to the ABO gene, Dr. Hernandez and colleagues found that people carrying certain genetic variants for SLC6A20, ERMP1, FCER1G and CA11 have a significantly higher risk of contracting COVID-19. "These individuals should use extreme caution during the pandemic. These genes may also prove to be good markers for disease as well as potential drug targets."

Several of the genes identified in the researchers' analysis have already been linked with respiratory diseases. For example, ERMP1 has been linked to asthma. CA11 may also elevate COVID-19 risk for people with diabetes.

Genetic associations for COVID-19 and gene and protein expression were combined using integrative genomics (IG). IG aims to identify mechanisms (for example: gene expression levels) that connect the effects of the genetic code to a complex disease. These methods, although complex, are also fast and their outcomes can help researchers to prioritize candidate genes for in vitro (in the lab) and in vivo (in living organisms) testing.

Dr. Hernandez added, "Our research has progressed since the time that we first conducted this analysis. We have now identified even more interesting candidates for COVID-19 such as IL10RB, IFNAR2 and OAS1. These genes have been linked to severe COVID-19. Their role in the immune response to viral infections and mounting evidence suggest that these candidates and their role in COVID-19 should be further investigated."

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The mysteries of sexual attraction just became a little less mysterious - at least for moths. A team of six American and European research groups including Tufts University has discovered which gene expressed in the brain of the male European corn borer moth controls his preference for the sex pheromone produced by females. This complements a previous study on the gene expressed in the female pheromone gland that dictates the type of blend she emits to attract males. The study was reported today in Nature Communications.

The implications go beyond making a better dating app for bugs. Now scientists can begin to ask why mating signals and mating preferences change in the first place, which is a long-standing paradox since any change could reduce the ability of an organism to successfully mate. Knowledge of these two genes will provide a better understanding of how the pheromones of the 160,000 moth species have evolved.

Of course, one important role for mating preferences is to make sure you are not matching up with a completely different species. The signal sent by females must be preferred by males of the same species to ensure that like mates with like--a mechanism called assortative mating. The European corn borer is interesting because there are two types, called E and Z, with assortative mating within each type. Even though the two types can be mated to each other in captivity, E mostly mates with E, and Z with Z in the field. For this reason, the European corn borer has been used as a model for how one species can split into two, ever since the two pheromone types were first discovered 50 years ago.

"That means we now know - at the molecular level - how chemical matchmaking aids in the formation of new species. Similar genetic changes to pheromone preference could help explain how tens of thousands of other moth species remain separate," said Erik Dopman, professor of biology in the School of Arts and Sciences at Tufts and corresponding author of the study.

Different aspects of the research were conducted by the three co-first authors Fotini Koutroumpa of University of Amsterdam, Melanie Unbehend of the Max Planck Institute for Chemical Ecology, and Genevieve Kozak, a former post-doctoral scholar at Tufts University and now assistant professor at University of Massachusetts, Dartmouth. "Our study's success can be attributed to a team with a common vision and strong sense of humor that helped make the science worthwhile and fun," said Dopman.

One of the surprise discoveries made by the team was that while females may vary their signals in the blend of pheromones they produce, preference in the male is driven by a protein that changes their brain's neuronal circuitry underlying detection rather than affecting the receptors responsible for picking up the pheromones.

Preference for a particular cocktail of pheromones is determined by any of hundreds of variants found within the bab gene of the male. The relevant variants of bab are not in parts of the gene that code for a protein, but in parts that likely determine how much of the protein is produced, which in turn affects the neuronal circuits running from the antennae to the brain. The researchers were able to determine anatomical differences in the male, including the reach of olfactory sensory neurons into different parts of the moth brain, and link them to their attraction to E or Z females.

"This is the first moth species out of 160,000 in which female signalling and male preference genes have both been identified," said Astrid Groot of the University of Amsterdam, who also helped identify the gene controlling the pheromone difference in E and Z females. "That provides us with complete information on the evolution of mate choice and a way to measure how closely these choices are linked to evolving traits and populations."

The ability to predict mating could also help control reproduction in pest insects. The European corn borer is a significant pest for many agricultural crops in addition to corn. In the U.S., it costs nearly $2 billion each year to monitor and control. It is also the primary pest target for genetically modified "Bt corn" which expresses insecticidal proteins derived from the bacterium, Bacillus thuringiensis. While Bt corn remains an effective control of the corn borer moth in the U.S., corn borers in Nova Scotia are now evolving resistance to another variety of Bt corn.

"Our results can help to predict whether Bt resistance could spread from Nova Scotia to the Corn Belt of the U.S., or whether assortative mating could prevent or delay it", said co-author David Heckel at the Max Planck Institute for Chemical Ecology, who also studies how insects evolve resistance to Bt. "Bt corn has enabled a huge reduction in the use of chemical insecticides, and it should be a high priority to preserve its ecological benefits as long as possible."

The COVID-19 pandemic has been shown to have caused a significant strain on the healthcare system and resources in the United States. However, data regarding the impact of the virus on hip fractures, primarily seen in elderly patients, is lacking.

Researchers at Hospital for Special Surgery (HSS) sought to compare characteristics and outcomes of hip fracture patients admitted during the COVID-19 outbreak to patients admitted before the outbreak. They also examined characteristics and outcomes of hip fracture patients with and without the virus. Their findings were presented at the 2021 Spring American Society of Regional Anesthesia and Pain Medicine (ASRA) Annual Meeting.1

"Studying this topic is important because events that stress the healthcare system, like this pandemic, allow us to gain rare insights into what happens to medical care when resources become scarce," said principal investigator Stavros Memtsoudis, MD, PhD, MBA, an anesthesiologist at HSS.

Dr. Memtsoudis and colleagues compared patient and healthcare characteristics, COVID-19 diagnoses and outcomes for hip-fracture patients from March to April 2019 and March to April 2020. Observed outcomes included length of hospital stay, admission to an intensive care unit (ICU), use of mechanical ventilation, 30-day readmission, discharge disposition and postoperative complications.

The number of hip fracture cases during the COVID-19 surge decreased by 50% compared with the same time period during the previous year. "One of the major takeaways from this study was we saw that fractures were more commonly treated nonoperatively, and how outcomes differed," Dr. Memtsoudis noted. During the pandemic, hip fracture patients were discharged earlier and were less likely to be admitted to the ICU.

Other factors did not differ before and after COVID-19, including in-hospital mortality rate, 30-day readmission rate, use of mechanical ventilation, and complication rate.

Hip-fracture patients with COVID-19 stayed in the hospital longer, had higher rates of complications during surgery, increased rates of mortality, and more frequently received nonsurgical treatment.

These results show two main considerations for hospitals. As society begins to return to more normal activities, rates of hip fracture are likely to increase back to pre-COVID-19 levels. Hospitals should be prepared and have plans for treating hip fracture patients with COVID-19, as well as protecting non-COVID-19 patients from exposure.

Additionally, findings that demonstrate shorter length of stay in the hospital, less use of the ICU, and earlier home discharge did not compromise outcomes and deserve further study. This raises the question of whether the strategies of care for hip fracture patients used before the pandemic should be adjusted.

"These results should make us reevaluate our practice going forward to make sure we do not waste resources but also affirm interventions that truly are beneficial," Dr. Memtsoudis concluded.

Researchers at the University of Bristol found that plant eaters diversified quickly after mass extinctions to eat different kinds of plants, and the ones that were able to chew harsher materials, which reflected the drying conditions of the late Triassic, became the most successful. These tougher herbivores included some of the first dinosaurs.

Following the largest mass extinction of all time, the end-Permian mass extinction, ecosystems rebuilt from scratch during Triassic times, from 252-201 million years ago paving the way for new species, and many new kinds of plants and animals emerged. In a new study published in Nature Communications and led by Dr Suresh Singh of Bristol's School of Earth Sciences, fresh evidence has emerged of the complexity of the post-extinction recovery.

"I wanted to focus on the plant-eaters, including some of the first dinosaurs," says Dr Suresh Singh. "The main animals in any ecosystem tend to be the herbivores, and we found that they show remarkable evidence of specialisation in the turbulent times after the great mass extinction. In fact, the environmental shocks that killed so many species, such as global warming and acid rain, were still returning from time to time, but the survivors were set on exploring new diets."

"We were surprised to be able to identify definite specialisations among the herbivores," said Dr Tom Stubbs, a collaborator. "We call these groups, the ingestion generalists, prehension specialists, durophagous specialists, shearing pulpers, and heavy oral processors; these names reflect the power of their jaws, their teeth, and the kinds of plants they would likely have been eating."

"It might seem to be a speculative enterprise to identify the diets of animals that died over 200 million years ago," said Professor Emily Rayfield, who also co-led the project. "But we measured hundreds of fossil jaws and compared their shapes with living animals, and we estimated key functional values from the fossil jaws such as mechanical advantage and bite force, measuring the leverage of the jaws and how fast or forcefully they could shut."

Results were studied through the 80 million years following the mass extinction and including the diversification of the first plant-eating dinosaurs. "We were able to map the evolution of all the functional characters relating to feeding across the evolutionary tree and through time," said Dr Armin Elsler, collaborator. "We found to our surprise that, during this time, several new groups diversified as herbivores, and they seemed to take over their roles by pushing potential competitors aside, not necessarily by wiping them out."

The plants were also diversifying through the Triassic, and some of the evolution of herbivores relates to the availability of new kinds of plant food. "One key thing was the expansion of groups that were able to handle tough plant material, with powerful jaws for chopping and chomping," says Dr Singh. "This reflects the drying conditions especially in the Late Triassic, when many softer plant groups became less common, and dry-adapted conifers for example, spread worldwide. These changes combined with strictly enforced niche separation drove patterns of extinction as the generalist, hardy herbivores thrived, as other herbivores died out."

"This kind of macroecological analysis represents a huge amount of work," said Professor Mike Benton, who co-led the study. "But it sheds real light on key processes at an ecological level and helps explain why some groups died out and were replaced by others such as the first dinosaurs. We can be reasonably certain of the results because we have excellent data on the geological ages of the specimens, their relationships to each other, and the key features of their jaws and teeth that correspond to their ancient diets. What was once quite a speculative kind of project has now become much more analytical and testable."

While it has been said that the eyes are a window to the soul, a new study shows they could be a means for understanding diseases of the brain. According to new research by scientists at the UCSF Weill Institute for Neurosciences, retinal scans can detect key changes in blood vessels that may provide an early sign of Alzheimer's, while offering important insights into how one of the most common Alzheimer's risk genes contributes to the disease.

"The most prevalent genetic risk for Alzheimer's disease is a variant of the APOE gene, known as APOE4," said lead author Fanny Elahi, MD, PhD. "We still don't fully understand how this variant increases risk of brain degeneration, we just know that it does, and that this risk is modified by sex, race, and lifestyle. "Our research provides new insights into how APOE4 impacts blood vessels and may provide a path forward for early detection of neurodegenerative disease."

Studies in mice have explored the effect of APOE4 on capillaries in the brain. Elahi, an assistant professor of neurology and member of the UCSF Memory and Aging Center (MAC), has long suspected these tiny blood vessels may play a significant role in Alzheimer's disease, since they deliver nutrients and oxygen, carry away waste, and police immune system responses through the protective shield known as the blood-brain barrier. Damage to these blood vessels could cause a host of problems, she says, including the protein buildup and cognitive decline seen in individuals affected by Alzheimer's disease.

Because the technology does not exist to visualize individual capillaries in living people's brains, Elahi and colleagues turned to the eye. In the new study, which published May 11, 2021, in the journal Alzheimer's and Dementia: Diagnosis, Assessment & Disease Monitoring, Elahi and her team have shown that APOE4-associated capillary changes can be detected in humans through an easy, comfortable eye scan. As a light-penetrating tissue that shares biology with the brain, the retina, researchers believe, may help determine what APOE4 variants may be doing to similar capillaries inside the brain, even in those without dementia.

The team - which includes Ari Green, MD, a neuro-ophthalmologist, professor, and director of the UCSF Neurodiagnostics Center, and Amir Kashani, MD, PhD, associate professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute - used an advanced retinal imaging technique known as optical coherence tomography angiography (OCTA) to peer into the eyes of aging people with and without APOE4 mutations to evaluate the smallest blood vessels at the back of the eye.

The team leveraged the well-characterized cohorts of people enrolled in ongoing studies of brain aging and neurodegenerative disease at the MAC. By adding OCTA scans to existing MRI and PET scan data, they gain comparative insights without putting volunteer participants through additional discomfort. "That's the beauty of this technique," Elahi said. "It's very easy, noninvasive and participant-friendly."

Analyzing the retinal scans, the researchers found reduced capillary density in APOE4 carriers, an effect that increased with participant age. To test whether those scans accurately reflected what was happening in the brain, the team then compared the abnormalities seen in OCTA scans of retinal capillaries to measurements of brain perfusion, or the flow of blood through the brain, as measured via MRI. They found that people with higher retinal capillary density also had greater blood flow in the brain.

Finally, the team looked to participants with prior PET scans of beta-amyloid, the protein associated with Alzheimer's disease, to see how their retinal capillary measurements related to the burden of amyloid plaques in the brain, which is the major focus of Alzheimer's disease diagnosis, research and treatment to date. They found that capillary density did not differ between groups with and without amyloid plaques, nor did it vary along with amyloid burden. According to Elahi, that independence suggests that capillary abnormalities are unlikely to be driven by amyloid pathology, or that their relation may at most be indirect.

"This is the first time that we have demonstrated in living, asymptomatic humans that the smallest blood vessels are affected in APOE4 gene carriers," said Elahi. That's important, she added, because it suggests that the increased risk of brain degeneration and Alzheimer's disease in APOE4 carriers may be through its effect on blood vessels.

Elahi and her colleagues plan to follow their study participants to better understand blood vessel dysfunction at a molecular level. That work could help detect the onset of Alzheimer's disease before significant damage occurs to the brain and identify new vascular targets for early treatment.

"This is just the beginning," Elahi said. "But the implications for early detection and possible intervention can be significant in combatting Alzheimer's disease and other neurodegenerative disorders. It's much harder to regenerate neurons than to stop their degeneration from happening in the first place. Similar to cancer, early detection can save lives,"

Plants have evolved unique immunity mechanisms that they can activate upon detecting the presence of a pathogen. Interestingly, the presence of some nonpathogenic microorganisms can also prompt a plant to activate its systemic immunity mechanisms, and some studies have shown that pretreating agricultural crops with such "immunity-activating" nonpathogenic microorganisms can leave the crops better prepared to fight off infections from pathogenic microorganisms. In effect, this means that immunity-activating nonpathogenic microorganisms can function like vaccines for plants, providing a low-risk stimulus for the plant's immune system that prepares it for dealing with genuine threats. These are exciting findings for crop scientists because they suggest the possibility of using such pretreatment as a form of biological pest control that would reduce the need for agricultural pesticides.

However, before pretreatment with nonpathogenic microorganisms can become a standard agricultural technology, scientists need a way to screen microorganisms for the ability to stimulate plant immune systems without harming the plants. There is currently no simple method for evaluating the ability of microorganisms to activate plant immune systems. Conventional methods involve the use of whole plants and microorganisms, and this inevitably makes conventional screening a time-consuming and expensive affair. To address this problem, Associate Professor Toshiki Furuya and Professor Kazuyuki Kuchitsu of Tokyo University of Science and their colleagues decided to develop a screening strategy involving cultured plant cells. A description of their method appears in a paper recently published in Scientific Reports.

The first step in this screening strategy involves incubating the candidate microorganism together with BY-2 cells, which are tobacco plant cells known for their rapid and stable growth rates. The next step is to treat the BY-2 cells with cryptogein, which is a protein secreted by fungus-like pathogenic microorganisms that can elicit immune responses from tobacco plants. A key part of the cryptogein-induced immune responses is the production of a class of chemicals called reactive oxygen species (ROS), and scientists can easily measure cryptogein-induced ROS production and use it as a metric for evaluating the effects of the nonpathogenic microorganisms. To put it simply, an effective pretreatment agent will increase the BY-2 cells' ROS production levels (i.e., cause the cells to exhibit stronger immune system activation) in response to cryptogein exposure.

To test the practicability of their screening strategy, Dr. Furuya and his colleagues used the strategy on 29 bacterial strains isolated from the interior of the Japanese mustard spinach plant (Brassica rapa var. perviridis), and they found that 8 strains boosted cryptogein-induced ROS production. They then further tested those 8 strains by applying them to the root tips of seedlings from the Arabidopsis genus, which contains species commonly used as model organisms for studies of plant biology. Interestingly, 2 of the 8 tested strains induced whole-plant resistance to bacterial pathogens.

Based on the proof-of-concept findings concerning those 2 bacterial strains, Dr. Furuya proudly notes that his team's screening method "can streamline the acquisition of microorganisms that activate the immune system of plants." When asked how he envisions the screening method affecting agricultural practices, he explains that he expects his team's screening system "to be a technology that contributes to the practical application and spread of microbial alternatives to chemical pesticides."

In time, the novel screening method developed by Dr. Furuya and team may make it significantly easier for crop scientists create greener agricultural methods that rely on the defense mechanisms that plants themselves have evolved over millions of years.

Ishikawa, Japan - Today, many well-studied materials in various fields, such as electronics and catalysis, are close to reaching their practical limits. To further improve upon modern technology and outperform state-of-the-art devices, researchers looking for new functional materials have to push the boundaries and explore more extreme cases. A clear example of this is the study of low-dimensional materials, such as monoatomic layers (2D materials) and monoatomic chains (1D materials).

It has been proved time and time again that low-dimensional materials exhibit exotic properties that are absent in their 3D bulk counterparts. For example, monoatomic chains of metals like gold and platinum (Pt) can exhibit the contribution of certain quantum phenomena, such as magnetic order or thermal transport, in ways that could find practical applications. However, it is very difficult to experimentally observe what goes on in monoatomic chains composed of five or less atoms, and the mechanical properties of single-atom bonds remain elusive.

To tackle this issue, a research group lead by Professor Yoshifumi Oshima from Japan Advanced Institute of Science and Technology (JAIST), Japan, is pioneering a novel and promising technique to measure the strength of individual atomic bonds. Their latest study, which was published in Nano Letters and showcased their strategy, involved researchers from JAIST (Dr. Zhang, Dr. Ishizuka, Prof. Tomitori, Prof. Maezono and Prof. Hongo), as well as Prof. Arai from Kanazawa University and Prof. Tosatti from the International School for Advanced Studies (SISSA) and The Abdus Salam International Centre for Theoretical Physics (ICTP).

This new technique, which Oshima named the "microscopic nanomechanics measurement method," combines transmission electron microscopy (TEM) with a quartz length-extension resonator (LER). TEM is a widely used imaging technique with incredibly high spatial resolution--enough to make out individual atoms--whereas the LER is a device that can oscillate at incredibly small amplitudes of a few ten trillionths of a meter and serves as a force sensor.

The researchers devised an experimental setup in which a small Pt juncture was stretched to its absolute breaking point, that is, when the two pieces of Pt were linked by a monoatomic chain of two to five atoms. By carefully aligning the pieces in the TEM, they observed the formation and breaking of the monoatomic Pt chains in real time. Moreover, using the quartz LER, they measured the conductance across the chain and its stiffness, from which the strength of individual Pt bonds was calculated with success. "We found the bond strength of 25 N/m in the monoatomic Pt chains to be remarkably high, especially compared to the 20 N/m normally found in bulk Pt crystals," comments Zhang. ""Moreover, these single-atom bonds could be stretched about 24% of their regular distance, in stark contrast to the 5% that bonds between Pt atoms in bulk can be stretched," he adds.

The results of the study showcase the potential of this novel technique to probe monoatomic chain bonds, which could lead to a better understanding of the interfaces or surfaces of low-dimensional materials. "Our method could greatly contribute to the design of advanced materials and catalysts as well as shed light on nanoscale phenomena in terms of surface or interface nanomechanics," highlights Oshima. In turn, more sophisticated materials and a better understanding of their surface properties will undoubtedly advance the fields of electronics, chemistry, and nanotechnology, paving the way to innovative and hopefully sustainable designs.

It's very likely that the expression "hanging by a thread" will soon get a more positive meaning in nanomaterials science!

An international research team analyzed a database of more than 1000 supernova explosions and found that models for the expansion of the Universe best match the data when a new time dependent variation is introduced. If proven correct with future, higher-quality data from the Subaru Telescope and other observatories, these results could indicate still unknown physics working on the cosmic scale.

Edwin Hubble's observations over 90 years ago showing the expansion of the Universe remain a cornerstone of modern astrophysics. But when you get into the details of calculating how fast the Universe was expanding at different times in its history, scientists have difficulty getting theoretical models to match observations.

To solve this problem, a team led by Maria Dainotti (Assistant Professor at the National Astronomical Observatory of Japan and the Graduate University for Advanced Studies, SOKENDAI in Japan and an affiliated scientist at the Space Science Institute in the U.S.A.) analyzed a catalog of 1048 supernovae which exploded at different times in the history of the Universe. The team found that the theoretical models can be made to match the observations if one of the constants used in the equations, appropriately called the Hubble constant, is allowed to vary with time.

There are several possible explanations for this apparent change in the Hubble constant. A likely but boring possibility is that observational biases exist in the data sample. To help correct for potential biases, astronomers are using Hyper Suprime-Cam on the Subaru Telescope to observe fainter supernovae over a wide area. Data from this instrument will increase the sample of observed supernovae in the early Universe and reduce the uncertainty in the data.

But if the current results hold-up under further investigation, if the Hubble constant is in fact changing, that opens the question of what is driving the change. Answering that question could require a new, or at least modified, version of astrophysics.

These results will appear as M.G. Dainotti et al. "On the Hubble Constant Tension in the SNe Ia Pantheon Sample" in the Astrophysical Journal on May 17, 2021.

The protein made by the ASH1L gene plays a key role in the development of acute leukemia, along with other diseases. The ASH1L protein, however, has been challenging to target therapeutically.

Now a team of researchers led by Jolanta Grembecka, Ph.D., and Tomasz Cierpicki, Ph.D., from the University of Michigan has developed first-in-class small molecules to inhibit ASH1L's SET domain -- preventing critical molecular interactions in the development and progression of leukemia.

The team's findings, which used fragment-based screening, followed by medicinal chemistry and a structure-based design, appear in Nature Communications.

In mouse models of mixed lineage leukemia, the lead compound, known as AS-99, successfully reduced leukemia progression.

"This work points to a new, exiting avenue to develop new therapeutic agents against acute leukemia, as well as providing a new approach to further study the biological functions of ASH1L and its role in the development of the disease," says Grembecka, associate professor of pathology at Michigan Medicine and co-director of the developmental therapeutics program at the U-M Rogel Cancer Center.

The study was a close collaboration between her lab and the lab of co-senior author Cierpicki, an associate professor of biophysics and pathology.

Bethesda, MD (May 14, 2021) -- Despite the fact that certain racial and ethnic minorities get pancreatic cancer more often, are diagnosed at a younger age and die sooner, clinical trials fail to include representative proportions of non-White patients at every phase of study, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2021.

"We see disparities in representation across all kinds of clinical trials, so we were not surprised to see that it also occurs in pancreatic cancer trials. But hopefully we can make a change in that arena in the future," said Kelly Herremans, MD, lead researcher on the study and surgical research fellow at the University of Florida College of Medicine, Gainesville.

Researchers analyzed data from 8,429 participants in 207 clinical trials in the U.S. for treatments for pancreatic ductal adenocarcinoma on ClinicalTrials.gov, a national registry of clinical trial data. Gender was reported in 99 percent of the trials, while race and ethnicity were reported in 49.3 percent and 34.7 percent of trials, respectively.

Minorities were substantially underrepresented in trials:

Black patients represented 8.2 percent of trial participants vs. 12.4 percent of the U.S. incident cases.

Hispanic patients represented 6 percent of trial participants compared to 8.5 percent of the U.S. incident cases.

Asian or Pacific Islander patients represented 2.4 percent of trial participants vs. 3.3 percent of the U.S. incident cases.

American Indians and Alaska Native patients represented 0.3 percent of trial participants compared to 0.4 percent of the U.S. incident cases.

White patients were overrepresented, making up 84.7 percent of the total trial participants, while they account for 82.3 percent of the total U.S. incident cases. In all, 54.8 percent of trial participants were male, and 45.2 percent female.

Pancreatic ductal adenocarcinoma is particularly deadly, with an estimated 5-year survival rate of only 9 percent. Diversity is important for clinical trials because previous research has shown racial differences in tumor biology, Dr. Herremans said. For example, Black patients have different rates of both somatic and germline mutations when compared to other racial subgroups, which means they may respond differently to treatment.

"We are treating everybody as if they were the same and their tumors would react the same to treatments, but it's important to look at the ancestral differences of tumor biology and therapeutic response," Dr. Herremans said.

Lack of diversity in clinical trials is often attributed to reluctance to participate due to historic wrongs such as the infamous 1932 Tuskegee Syphilis Study that left Black men untreated for many years to study the long-term impact of syphilis. But research has shown that Black patients are just as willing as White patients to be part of a clinical trial, Dr. Herremans said.

Lack of representation may be a result of systemic racism, provider biases that interfere with recruitment as well as study inclusion criteria, which can create impediments to enrollment, such as turning away patients with obesity and diabetes, which have increased prevalence in minority populations.

"It is multifaceted, and regulations have been put in place that have tried to combat this problem, but over the last 15 years, we really haven't made much headway," Dr. Herremans said.

DDW Presentation Details

Dr. Herremans will present data from the study, "Trials and tribulations: Diversity and inclusion in pancreatic ductal adenocarcinoma clinical trials," abstract 901, on Sunday, May 23, at 6 p.m. EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

Researchers from Monash University, Queensland University of Technology, and Capital University of Economics and Business published a new paper in the Journal of Marketing that examines the effects of imaginative product displays in retail stores on customers' purchase behavior.

The study, forthcoming in the Journal of Marketing, is titled "Gimmicky or Effective? The Effects of Imaginative Displays on Customers' Purchase Behavior" and is authored by Hean Tat Keh, Di Wang, and Li Yan.

Imaginative displays are constructed using multiple units of the same product in a novel, yet aesthetically appealing, form. Results from six studies show that, relative to standard displays (i.e., non-novel and neutral aesthetics), imaginative displays can increase customers' purchase intention, actual purchases, product sales, and ROI.

Importantly, the effects of imaginative displays can be explained by the dual mechanisms of affect-based arousal and cognition-based inferred benefits. That is, an imaginative display increases customer arousal and a themed imaginative display leads customers to infer benefits from the display, which increases their purchase behavior. Moreover, the researchers identify a theoretically meaningful and managerially relevant moderator--congruence between display form and perceived product benefit, which can enhance or attenuate the core effects.

There are three major takeaways:

First, an imaginative display represents a cost-effective way to enhance customers' purchase behavior and increase product sales and ROI. This effect applies to both familiar and less familiar brands.

Second, effective imaginative displays have to be both novel and aesthetically appealing, which highlights the overlooked aesthetic element in innovative design.

Third, the inferred benefits of imaginative displays are context-dependent. For a themed imaginative display (i.e., has a particular shape mimicking an object), the retailer should ensure that the display form is congruent with the perceived product benefit to increase purchase behavior. Incongruence between display form and product benefit would backfire.

The authors observe that "Our findings not only explain why some retailers utilize 'gimmicky' imaginative displays, but also provide evidence on the processes and boundary conditions of these displays to favorably influence customers' purchase behavior and increase product sales at relatively low costs."