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Abstract Bermudagrass (Cynodon dactylon (L.) Pers.) is one of the primary perennial forages in the southeastern USA. Newer hybrid cultivars have superior production and nutritive value compared to common ecotypes. However, there are many challenges facing bermudagrass production in the region. First, the bermudagrass stem maggot (BSM; Atherigona reversura Villeneuve) has severely damaged bermudagrass throughout the region. Strategically timed pyrethroid applications significantly reduce adult BSM populations, but efforts are needed to develop integrated pest management plans. Second, an increasing number of producers are noting challenges with green‐up following winter dormancy. This may be attributed to disease, unbalanced soil fertility, and weed pressure. Perhaps one of the most limiting factors for continued production is the deficit of sprigs and trained personnel to sprig hybrid bermudagrasses. This research is critically important as the need for cold‐tolerant bermudagrass is increasing as tall fescue (Lolium arundinaceum (Schreb.) S. J. Darbyshire) is declining due to changes in temperature and precipitation throughout the northern parts of the region. Plant breeders are investigating hybrid bermudagrass at latitudes >35° with respect to freeze or cold tolerance. Despite the many challenges facing hybrid bermudagrass in the southeastern USA, researchers are working to ensure its persistence, productivity, and availability for the future.

Introduction: Nasopharyngeal carcinoma (NPC) is a rare disease and most studies have therefore been conducted in endemic areas. The aim of this study was to describe epidemiology and treatment outcomes of NPC in a population-based, non-endemic setting. Material and methods: Patients with NPC diagnosed in Denmark from 2000 to 2018 were identified in the Danish Head and Neck Cancer Study Group (DAHANCA) database. Clinical records were reviewed to obtain missing data and confirm outcome, histological subtypes, Epstein-Barr virus (EBV)-status, prognostic factors, and treatment. Results: NPC was identified in 394 patients corresponding to age-standardized incidence rates of 0.5 and 0.2 per 100,000 in men and women, respectively. The 5-year overall (OS) and disease-specific survival (DSS) were 56 and 66%. In multivariate analysis, stage, smoking, and histology affected both OS and DSS, as patients with undifferentiated carcinomas had superior outcomes. Tumor EBV-status was determined in 221 patients, of whom 160 (72%) tested positive. EBV-positivity was associated with an improved OS in univariate analysis, but not after adjustment for relevant clinical factors. Interpretation: NPC is a rare malignancy in Denmark, and three in four patients have EBV-associated tumors. Tumor histology, smoking status, and stage, but not EBV-status, had independent prognostic impact on survival.

IntroductionThe COVID-19 pandemic led to major disruptions in the lives of university students, which is a population that is already at a greater risk of mental health concerns. Little is known about how the pandemic impacted distress and mental health services utilization among university students across the United States.MethodsUsing survey data from the National College Health Assessment, both before the COVID-19 pandemic (pre-March 2020, n = 88,986) and during the pandemic (Spring 2021, n = 96,489), the present study examined mental health symptoms and utilization of mental health services among undergraduate students attending four-year universities in the United States.ResultsThere were notable increases in measures of psychological distress and reductions in well-being from before the pandemic to during the pandemic. However, overall utilization rates of mental health services slightly decreased from pre-pandemic to during the pandemic. Predictors of severe psychological distress included those who experienced loneliness, COVID-19 related stressors, and loss of a loved one from COVID-19. COVID-related stressors and loneliness were associated with higher utilization rates of mental health services, while well-being and resilience were associated with lower utilization rates.DiscussionAnalyses revealed that several demographic groups were at an elevated risk for severe psychological distress, including non-binary, female, and sexual minority students, and especially those who identify as both non-binary and non-heterosexual. Results indicated that students of color, especially female students of color, were less likely to receive mental health services. Future research is needed to increase our understanding of the barriers to mental health service use among high-risk university students.

Abstract The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.

Here we replicate previous work on the fear of being single (FBS), personality, attachment, and relationship-contingent self-esteem, and also examine whether those with high FBS attempt to initiate romantic relationships more frequently and are more motivated by continued romantic attraction to remain friends with ex-partners than others. In line with prior work, FBS was positively associated with anxious attachment, relationship-contingent self-esteem, and emotionality. FBS was negatively associated with relationship initiation behaviors. Similarly, single men were more likely to attempt to initiate a romantic relationship with an opposite-sex friend than were single women, particularly if they were low in FBS. Although FBS was not associated with whether or not an individual remains friends with ex-partners, there was an association between FBS and continued romantic attraction as a motivator behind these friendships.

Abstract Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5–15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Abstract Background Childhood traumatic experiences may result in post-traumatic stress disorder. Although pediatricians are encouraged to address these traumas in clinical encounters, measures of childhood traumatic stress have not been adopted by primary care clinicians. In this study, we describe the feasibility and potential utility of the UCLA Brief Screen, a validated screener for childhood traumatic stress symptoms, in pediatric primary care clinics. Methods Children 6–17 years of age presenting for routine well-child care in community-based pediatric clinics were eligible for traumatic stress screening. We described the feasibility and acceptability of screening based on screener adoption by eligible pediatric clinicians. We assessed the potential utility of screening based on prevalence and distribution of potentially traumatic events and traumatic stress symptoms in this general pediatric population. Finally, we compared results of the UCLA Brief Screen with those of the Patient Health Questionnaire-A to evaluate associations between symptoms of traumatic stress, depression, and suicidality among adolescents in this community setting. Results 14/18 (77.8%) pediatric clinicians in two clinics offered an adapted UCLA Brief Screen during 2359/4959 (47.6%) eligible well-child checks over 14 months. 1472/2359 (62.4%) of offered screeners were completed, returned, and scored. One-third (32.5%) of completed screeners captured a potentially traumatic event experience described by either children or caregivers. Moderate to severe traumatic stress symptoms were identified in 10.7% and 5.2% of patients, respectively. Concurrent depression screening revealed that 68.3% of adolescents with depressive symptoms reported a potentially traumatic event (PTE) and 80.5% had concurrent traumatic stress symptoms. Adolescents reporting a PTE were 3.5 times more likely to report thoughts of suicide or self-harm than those without this history. Conclusions Results from this pilot study suggest that traumatic stress screening in the pediatric primary care setting may be feasible and may identify and classify mental health symptoms missed with current screening practices for depression. The prevalence of PTEs and traumatic stress symptoms associated with PTEs support the potential utility of a standardized screening in early identification of and response to children with clinically important symptoms of childhood traumatic stress. Future research should evaluate meaningful clinical outcomes associated with traumatic stress screening.

As climate change intensifies, Inuvialuit in Canada's Western Arctic are facing a rapidly changing environment and associated impacts on human health, safety, and food security. Learning to cope with these changes requires context-based and current information that can inform subsistence activities and environmental management, and no one is better positioned to acquire this information than Inuvialuit themselves. This paper presents findings from in-depth interviews conducted in 2012 with six knowledge holders and seasonal residents of Kendall Island (Ukiivik in Uummarmiutun), a traditional whaling camp situated along the Beaufort Sea coast bordering the Okeevik Tarium Niryutait Marine Protected Area. A transdisciplinary and Inuvialuit-led effort, this research documents observations of change at this culturally important site and explores how residents are adapting to changing conditions. Interview transcripts were analyzed using iterative rounds of qualitative coding in NVivo software. Findings reveal pervasive social and environmental change on Kendall Island and in adjacent harvesting areas and highlight how changing conditions are affecting residents’ lives. This study identifies benchmarks upon which to compare and evaluate subsequent changes at this site and documents Inuvialuit knowledge and perspectives that can inform local-scale environmental monitoring, management, and climate change adaptation planning.

Cytogenetic bands reflect genomic organization in large blocks of DNA with similar properties. Because banding patterns are invariant, this organization may often be assumed unimportant for genome regulation. Results here challenge that view. Findings here suggest cytogenetic bands reflect a visible framework upon which regulated genome architecture is built. Given Alu and L1 densities differ in cytogenetic bands, we examined their distribution after X-chromosome inactivation or formation of senescent-associated heterochromatin foci (SAHFs). Alu-rich regions remain outside both SAHFs and the Barr Body (BB), affirming that the BB is not the whole chromosome but a condensed, L1-rich core. Hi-C analysis of senescent cells demonstrates large (~10 Mb) G-bands remodel as a contiguous unit, gaining distal intrachromosomal interactions as syntenic G-bands coalesce into SAHFs. Striking peaks of Alu within R-bands strongly resist condensation. Thus, large-scale segmental genome architectur relates to dark versus light cytogenetic bands and Alu-peaks, implicating both in chromatin regulation.

Arctic populations are amongst the highest exposed populations to long-range transported contaminants globally, with the main exposure pathway being through the diet. Dietary advice is an important immediate means to address potential exposure and help minimize adverse health effects. The objective of this work is to enable easier access to dietary advice and communication guidance on contaminants with a focus on the Arctic. This manuscript is part of a special issue summarizing the Arctic Monitoring and Assessment Programme’s Assessment 2021: Human Health in the Arctic. The information was derived with internet searches, and by contacting relevant experts directly. Results include risk communication efforts in European Arctic countries, effectiveness evaluation studies for several Arctic countries, experience of social media use, and the advantages and challenges of using social media in risk communication. We found that current risk communication activities in most Arctic countries emphasize the importance of a nutritious diet. Contaminant-related restrictions are mostly based on mercury; a limited amount of dietary advice is based on other contaminants. While more information on effectiveness evaluation was available, specific information, particularly from Arctic countries other than Canada, is still very limited.

Immune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden. We find that the risk of ICI-induced CRS – defined as fever, negative microbiological findings and absence of other probable causes within 30 days after ICI treatment – is approximately 1%, higher than previously reported. ICI-induced CRS was often mild and rechallenge with ICIs after mild CRS was generally safe. However, two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein (CRP) and procalcitonin were not discriminative of fatal CRS, our data suggest that the quick Sequential Organ Failure Assessment (qSOFA) score might identify high-risk patients. These data provide a framework for CRS risk assessment and motivate multicenter studies to improve early CRS diagnosis.

Objective: The purpose of this study was to investigate the effects of different exercise intensities on postprandial lipemia (PHTG) and insulin resistance in healthy individuals. Methods: Participants were 10 adult males with normal fasting triglyceride (TG) concentrations (age = 34 ± 2.8 y, body mass = 72.9 ± 2.4 kg, fasting plasma TG = 1.36 ± 0.18 mmol/l, VO2max = 43.7 ± 3.0 ml/kg/min, fasting glucose = 5.2 ± 0.2 mmol/l and fasting Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR) = 1.7 ± 0.3). In this study, each participant performed a control trial (Ctr, no exercise), and 3 exercise trials at 40 % (40%T), 60 % (60%T), and 70 % (70%T) of their VO2max. In the exercise trials, participant jogged on a treadmill for 1 h at a designated intensity. A fat-rich meal was consumed by each participant 12 h after exercise. Blood samples were taken at 0 h (before the meal), and 2 h, 4 h, 6 h, 8 h, and 24 h after the meal. The plasma TG, area score under TG concentration curve over an 8 h-period (TG tAUC) after the meal, and HOMA2-IR were analyzed. Results: Our results showed that at 2 h, 4 h, and 6 h after the meal, TG in all exercise trials were lower than Ctr (p

This essay is adapted from a keynote address offered at Societas Homiletica in Budapest, Hungary (August 2022). It frames preaching in shifting social contexts as a practice of theologically ethical meaning-making—supported by accountability to lived experiences, practical wisdom and decision making, and imaginations grounded in boldness and humility. The essay argues that pedagogical strategies in support of these practices prioritize the possibilities that emerge in the constraints of learning contexts. Teaching within the mass crisis of a global pandemic is offered as a case study in the connected outcomes afforded in reassessing one’s presuppositions in both pedagogy and preaching.

Background: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001–2021. Method: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen–Johansen estimators and assessed associated risk factors using Cox regression. Results: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001–2010 and 2.5% during 2011–2021 (p = 0.20). During 2011–2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. Interpretation: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

ABSTRACT: The effects of high oleic oil full-fat (HO-FF) soybean meal (SBM) on broiler meat quality could lead to value-added food products. This experiment evaluated the effects of dietary normal oleic extruded expelled (NO-EE), normal oleic full-fat (NO-FF), or HO-FF SBM on live performance, carcass and parts yield, and breast fatty acid composition. Diets were formulated to be isoenergetic and isonitrogenous. A total of 540 Ross-708 male broilers were raised on floor pens with 18 broilers/pen and 10 replicates/treatment. Data were analyzed in a completely randomized design. Chickens were fed with a starter (0–14 d), grower (15–35 d), or a finisher diet (36–47 d) up to 47 d. Chickens were weighed at 7, 14, 35, and 47 d. At 48 d, 4 broilers per pen were processed. Breast samples were collected and evaluated for quality and fatty acid content. Broilers fed diets with NO-EE were heavier (P < 0.05) than chickens fed diets with full-fat SBM (NO-FF and HO-FF) at d 7, 14, 35 while feed conversion ratio (FCR) of NO-EE was best (P < 0.05) at 7 and 47 d. Carcass yield was also higher for broilers fed NO-EE than the other treatments. Diet did not affect parts yield, breast meat color, cooking, drip loss, white stripping, or SM quality parameters. More breast fillets without wooden breast (score 1) were observed (P < 0.05) for NO-FF than the other 2 treatments. The breast meat fatty acid profile (g fatty acid/100 g of all fatty acids) was significantly affected (P < 0.001) by diet. Broilers fed the HO-FF SBM diet had 54 to 86% more oleic acid, 72.5% to 2.2 times less linoleic acid, and reduced stearic and palmitic acid levels in the breast meat than NO-FF and NO-EE. In conclusion, feeding HO-FF to broilers enriched the oleic acid content of their breast meat while reducing the saturated fatty acid content relative to the NO-FF and NO-EE treatment groups.

Abstract Objective The aim was to develop and test a novel screen of adult ADHD, with a specific focus on clinical use. We designed a series of three studies to accomplish this aim. Method Study One (n = 155) and Study Two (n = 591) collected data via surveys to conduct exploratory and confirmatory factor analyses, respectively. Study Three analyzed the scale’s psychometrics in a clinical sample (n = 151). Results Study One and Study Two identified a 10-item scale with a two-factor structure. Study Three found good discriminant validity, sensitivity = 80.0%, specificity = 80.2%, and convergent validity with both the Brown Executive Function/Attention Scales, r (131) = .76, p

Background: The ongoing COVID-19 pandemic has seen the emergence of numerous novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, we compared the efficacy of three different forms of immunization against the wild-type, delta, and omicron variants of the virus: two doses of the BNT or AZ vaccine (BNT/BNT or AZ/AZ) as homologous vaccination, three doses of AZ/AZ/BNT as heterologous vaccination, and naturally occurring immunization in severe COVID-19 cases. Methods: We collected serum samples from vaccine recipients (67 receiving BNT/BNT, 111 receiving AZ/AZ, and 18 receiving AZ/AZ/BNT) and 46 patients who were admitted to the hospital with severe COVID-19. Blood samples were taken one month after the last injection and the efficacy of the vaccination was determined using the surrogate virus neutralization test (sVNT), with a positive result defined as an inhibition rate of over 30%. Serum samples from COVID-19 patients were taken at various points during their hospitalization and tested for inhibition rates. Results: Our results indicated that there was no notable difference in the levels of neutralizing antibodies (nAb) in vaccine recipients and patients against the wild-type and delta variants. However, when it came to the omicron variant, the vaccine recipients had significantly lower nAb titers. Among the vaccine recipients, those who received a booster dose of BNT after their first two doses of AZ (AZ/AZ/BNT) demonstrated the highest level of protection against the omicron variant at 44.4%, followed closely by the COVID-19 patients. In analyzing the serial samples taken from hospitalized COVID-19 patients, we observed that their inhibition rates against the wild-type and delta variants improved over time, while the inhibition rate against the omicron variant decreased. Conclusion: In conclusion, our findings suggest that heterologous booster vaccination after primary vaccination produces higher nAb titers and provides a higher level of protection against the omicron variant compared to primary vaccination alone. This protective effect was similar to that observed in patients with severe COVID-19.

Societal Impact Statement Humans are dependent upon plants for oxygen, food, textiles, and medicines. Climate change and deforestation represent serious threats to our planet, causing significant disruptions to our ability to access and utilize these plant resources; this makes a botanically literate workforce and plant science careers more important than ever. Unfortunately, the current state of botanical career opportunities and training programs in the United States remains unclear. This study focuses on the current employment trends of government and private sector botanists and what skills future plant scientists will need to be successful in these careers. Summary Plant science plays a crucial role in our society and in ongoing efforts to address many global challenges, including food insecurity and climate change. Yet, despite a predicted increase in plant science career opportunities in the United States, the botanical career landscape outside of academia is not well understood. To further our understanding of the training required for non‐academic botanical careers, the botanical sub‐disciplines used on the job, and career challenges faced by plant scientists, we surveyed 61 scientists working in government and 59 scientists working in the private sector in the United States. In both career sectors, > 80% of survey participants reported recent hires at the bachelor's degree level. New personnel with master's degrees were more commonly reported in the government sector (95%) than in the private sector (69%). Most plant scientists working in government reported a focus on plant ecology and resource management. By contrast, most industry/non‐profit work involved horticulture and biotechnology, with some specific skills spanning both sectors. Notably, one prediction made nearly a decade ago appears to be manifesting: plant scientists seem to be retiring more quickly than they are being replaced. Survey respondents reported that attempts to hire full‐time staff are met with obstacles, including insufficient funding. Plant science professionals in both career sectors emphasized their routine use of botanical skills developed as students, highlighting the need for effective training at the undergraduate level. We discuss the implications of these findings and present several recommendations for preparing future generations of plant scientists and increasing the scientific community's botanical capacity.

Societal Impact Statement Botanical careers are more important than ever, given that environmental challenges such as climate change and deforestation threaten plants daily and because plants contribute to solutions to these problems. Plants act as our sources of food, medicine, textiles, and oxygen, which means finding ways to mitigate these environmental challenges is crucial. Despite this, little is known about what career opportunities exist for botanists outside of academia and how well academia is training graduate students for these careers. This study centers on the current state of academic botanical careers and how well students completing post‐baccalaureate degrees (herein referred to as graduate students) are being prepared to fill careers within the botanical workforce. Summary Plant science plays a crucial role in our society and in ongoing efforts to address many global challenges, including food insecurity and climate change. Despite a predicted increase in botanical career opportunities, little is known about how well academia is training graduate students for careers outside of academia. To further our understanding of the current state of academic training for botanical careers, we surveyed 85 faculty and 40 graduate students working in academia in the plant sciences in the United States. We found that the top challenges to university professors in academia are lack of support staff and funding, whereas students completing their post‐baccalaureate degrees cited finances and lack of supportive mentoring as their top challenges. Despite the fact that most graduate students surveyed wanted a career at a research‐intensive university, many botanists in academia are retiring without being replaced by more botanists. Faculty expertise is also misaligned with needs from industry and government employers, causing challenges to training graduate students for these careers outside of academia. Although our data point to a lack of career opportunities within academia, we also note that current graduate student education still emphasizes such careers and is not properly preparing graduate students for the careers they are more likely to obtain within the private and government sectors. We discuss the implications of these findings and present several recommendations for preparing future generations of plant scientists for more realistic career trajectories.

Abstract Background Migration enables organisms to access resources in separate regions that have predictable but asynchronous spatiotemporal variability in habitat quality. The classical migration syndrome is defined by key traits including directionally persistent long-distance movements during which maintenance activities are suppressed. But recently, seasonal round-trip movements have frequently been considered to constitute migration irrespective of the traits required to meet this movement type, conflating common outcomes with common traits required for a mechanistic understanding of long-distance movements. We aimed to test whether a cetacean ceases foraging during so-called migratory movements, conforming to a trait that defines classical migration. Methods We used location and dive data collected by satellite tags deployed on beluga whales (Delphinapterus leucas) from the Eastern Beaufort Sea population, which undertake long-distance directed movements between summer and winter areas. To identify phases of directionally persistent travel, behavioural states (area-restricted search, ARS; or Transit) were decoded using a hidden-Markov model, based on step length and turning angle. Established dive profiles were then used as a proxy for foraging, to test the hypothesis that belugas cease foraging during these long-distance transiting movements, i.e., they suppress maintenance activities. Results Belugas principally made directed horizontal movements when moving between summer and winter residency areas, remaining in a Transit state for an average of 75.4% (range = 58.5–87.2%) of the time. All individuals, however, exhibited persistent foraging during Transit movements (75.8% of hours decoded as the Transit state had ≥ 1 foraging dive). These data indicate that belugas actively search for and/or respond to resources during these long-distance movements that are typically called a migration. Conclusions The long-distance movements of belugas do not conform to the traits defining the classical migration syndrome, but instead have characteristics of both migratory and nomadic behaviour, which may prove adaptive in the face of unpredictable environmental change. Such patterns are likely present in other cetaceans that have been labeled as migratory. Examination of not only horizontal movement state, but also the vertical behaviour of aquatic animals during directed movements is essential for identifying whether a species exhibits traits of the classical migration syndrome or another long-distance movement strategy, enabling improved ecological inference.

Abstract Background Pregnant women and children living with HIV in Kenya achieve viral suppression (VS) at lower rates than other adults. While many factors contribute to these low rates, the acquisition and development of HIV drug resistance mutations (DRMs) are a contributing factor. Recognizing the significance of DRMs in treatment decisions, resource-limited settings are scaling up national DRM testing programs. From provider and patient perspectives, however, optimal ways to operationalize and scale-up DRM testing in such settings remain unclear. Methods Our mixed methods study evaluates the attitudes towards, facilitators to, and barriers to DRM testing approaches among children and pregnant women on antiretroviral therapy (ART) in five HIV treatment facilities in Kenya. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with adolescents, caregivers, pregnant women newly initiating ART or with a high viral load, and providers, laboratory/facility leadership, and policy makers. Our KII guides covered the following domains: (1) DRM testing experiences in routine care and through our intervention and (2) barriers and facilitators to routine and point-of-care DRM testing scale-up. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. Results The following themes emerged from our analysis: (1) DRM testing and counseling were valuable to clinical decision-making and reassuring to patients, with timely results allowing providers to change patient ART regimens faster; (2) providers and policymakers desired an amended and potentially decentralized DRM testing process that incorporates quicker sample-to-results turn-around-time, less burdensome procedures, and greater patient and provider “empowerment” to increase comfort with testing protocols; (3) facility-level delays, deriving from overworked facilities and sample tracking difficulties, were highlighted as areas for improvement. Conclusions DRM testing has the potential to considerably improve patient health outcomes. Key informants recognized several obstacles to implementation and desired a more simplified, time-efficient, and potentially decentralized DRM testing process that builds provider comfort and confidence with DRM testing protocols. Further investigating the implementation, endurance, and effectiveness of DRM testing training is critical to addressing the barriers and areas of improvement highlighted in our study. Trial Registration NCT03820323.

Abstract Background Racial and ethnic minoritized groups are disproportionately at risk for Alzheimer’s Disease (AD), but are not sufficiently recruited in AD neuroimaging research in the United States. This is important as sample composition impacts generalizability of findings, biomarker cutoffs, and treatment effects. No studies have quantified the breadth of race/ethnicity representation in the AD literature. Methods This review identified median race/ethnicity composition of AD neuroimaging US-based research samples available as free full-text articles on PubMed. Two types of published studies were analyzed: studies that directly report race/ethnicity data (i.e., direct studies), and studies that do not report race/ethnicity but used data from a cohort study/database that does report this information (i.e., indirect studies). Results Direct studies (n = 719) have median representation of 88.9% white or 87.4% Non-Hispanic white, 7.3% Black/African American, and 3.4% Hispanic/Latino ethnicity, with 0% Asian American, Native Hawaiian/Pacific Islander, and American Indian/Alaska Native, Multiracial, and Other Race participants. Cohort studies/databases (n = 44) from which indirect studies (n = 1745) derived are more diverse, with median representation of 84.2% white, 83.7% Non-Hispanic white, 11.6% Black/African American, 4.7% Hispanic/Latino, and 1.75% Asian American participants. Notably, 94% of indirect studies derive from just 10 cohort studies/databases. Comparisons of two time periods using a median split for publication year, 1994–2017 and 2018–2022, indicate that sample diversity has improved recently, particularly for Black/African American participants (3.39% from 1994–2017 and 8.29% from 2018-2022). Conclusions There is still underrepresentation of all minoritized groups relative to Census data, especially for Hispanic/Latino and Asian American individuals. The AD neuroimaging literature will benefit from increased representative recruitment of ethnic/racial minorities. More transparent reporting of race/ethnicity data is needed.

The prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer’s Disease Research Center Minority Aging Research Study (MARS) and African American Clinical Core (AACORE). We assessed baseline DCTclock scores in 646 participants (baseline median age = 78.0 ± 6.4, median years of education = 14.0 ± 3.2, 78% female) and found significantly lower baseline DCTclock scores in those who received a dementia diagnosis within 3 years. We also found that 16.4% of participants with a baseline DCTclock score less than 60 were significantly more likely to develop dementia in 5 years vs. those with the highest DCTclock scores (75–100). This research demonstrates the DCTclock’s ability to estimate the 5-year risk of developing dementia in an African American population. Early detection of elevated dementia risk using the DCTclock could provide patients, caregivers, and clinicians opportunities to plan and intervene early to improve cognitive health trajectories. Early detection of dementia risk can also enhance participant selection in clinical trials while reducing screening costs.

Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19.

Koch and Brown et al. led a collaborative and comprehensive synthesis that shows the transfer of ice algal carbon is widespread throughout the Arctic marine food web and contributes to supporting organisms throughout the dark winter months

Abstract Introduction Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized laboratory systems faces many barriers. We aimed to determine the impact of point‐of‐care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy. Methods We conducted a pre/post‐intervention prospective cohort study among 820 pregnant women accessing HIV care at five public‐sector facilities in western Kenya from 2019 to 2022. The pre‐intervention or “control” group consisted of standard‐of‐care (SOC) centralized VL testing every 6 months and the post‐intervention or “intervention” group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS. Results At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS (aRR 1.00, 95% confidence interval [CI] 0.98, 1.02). When assessing VS using a threshold of 1000 copies/ml) who underwent successful DRM testing in the intervention group, all (46/46, 100%) had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day (IQR 1, 4) for POC VL in the intervention group and 7 days (IQR 5, 9) for SOC VL in the control group. Sustained VS throughout follow‐up was similar between groups with either POC or SOC VL testing (90−91% for

Summary: SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection.The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73–0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48–0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30–0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Abstract Background Bermudagrass (Cynodon spp.) is one of the most common perennial warm‐season forages grown in the Southeastern United States. The incorporation of alfalfa (Medicago sativa) into bermudagrass pastures could serve as an alternative source of nitrogen (N) while also improving the nutritive value of the forage base. Methods A 2‐year grazing evaluation arranged in a randomized complete block design was conducted from May to September 2018 (Year 1) and May–August 2019 (Year 2) in Tifton, GA, USA. The objective was to compare the production of alfalfa–bermudagrass mixed pastures (BGA) with bermudagrass monoculture pastures with (BGN) or without (BG) the application of synthetic nitrogen on forage production and stocker cattle performance. Results Differences were observed for average daily gain (p = 0.10), gain per hectare (p = 0.02) and stocking rate (p = 0.01), in that BGA was greatest compared to BGN and BG, which did not differ from each other. Furthermore, BGA had increased forage crude protein (p = 0.01) and total digestible nutrients (p = 0.01) compared to BGN and BG. Finally, BGA provided the greatest economic return per hectare compared to BG or BGN. Conclusions These data illustrate improved animal performance and forage nutritive value using alfalfa–bermudagrass systems and offer a viable option for producers seeking alternatives to synthetic N sources for bermudagrass pastures in the Southeastern United States.

Abstract Background Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed. Methods We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. Results Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing’s faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders. Conclusion The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs. Trial registration NCT03820323, 29/01/2019

Arctic ecosystems are at risk to climate impacts, challenging existing conservation measures such as protected areas. This study aims to describe the ecological dynamics of the Canadian Beaufort Sea Shelf (BSS) ecosystem and the Tarium Niryutait Marine Protected Area (TNMPA) under historical changes in sea surface temperature and sea ice extent. Using Ecopath with Ecosim, we compared the status of the BSS between two time periods, 1970–1974 and 2008–2012, and against four ecosystem models (Eastern Chukchi Sea, Barents Sea, Eastern Bering Sea, Gulf of Alaska) to inform the relative long-term health and status of Arctic marine ecosystems. We find that relative to the comparable ecosystems, the BSS had a greater proportion of biomass from pelagic primary and secondary producers, and limited production from higher trophic levels. Estimates of trophic structure indices for the BSS indicate temporal ecosystem stability, and no loss in diversity. While beluga whales are a focus of the TNMPA management plan, they are not considered a key component of the modeled food web. Rather, Arctic and polar cods (main beluga prey group), arthropods, large copepods, micro-zooplankton, and herring and smelt, were identified as keystone species and warrant attention as proxies for both beluga whales and ecosystem health.

During summer, the Eastern Beaufort Sea beluga whale (Delphinapterus leucas (Pallas, 1776)) population aggregates in the waters of the Mackenzie Estuary and Tarium Niryutait Marine Protected Area (TNMPA). Guided by local communities’ priorities, this study aimed to better understand beluga summer habitat selection and to examine whether shifts in beluga distribution are expected under a changing climate. We used a resource selection function (RSF) based on aerial survey data and satellite remote sensing images to estimate the likelihood of beluga presence as a function of environmental conditions. The RSF revealed that belugas selected warm and turbid waters, with suspended particulate matter concentrations and sea surface temperatures ranging above average estuarine values. These specific conditions support hypotheses on the ecological roles of estuaries for belugas such as providing a thermal advantage for their calves or for beluga epidermal moulting. Using a diachronic analysis, we found a distribution shift towards coastal and inshore waters, areas already experiencing effects of climate change. Thus, the current distribution may reflect beluga responses to a changing climate, selecting warmer and more turbid areas. Our finding provides insight into current and evolving beluga habitat and habitat selection under a changing climate, which may help inform beluga management in the TNMPA.

Abstract Background The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations – assessed via the 2018 WCRF/AICR Score – was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS). Methods The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with additional follow-up in DPPOS for 11 years (mean: 15 years total). 2018 WCRF/AICR Scores included seven components: body weight, physical activity, plant-based foods, fast foods, red and processed meat, sugar-sweetened beverages, and alcohol; the optional breastfeeding component was excluded. Scores ranged 0-7 points (with greater scores indicating greater alignment with the recommendations) and were estimated at years 0, 1, 5, 6, 9, and 15 (N=3,147). Fasting glucose and HbA1c were measured every six months and oral glucose tolerance tests were performed annually. Adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were used to examine the association of both Score changes from years 0-1 and time-dependent Score changes on diabetes risk through DPP and year 15. Results Scores improved within all groups over 15 years (p

IntroductionVariation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers.MethodsPBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created.Results67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)].ConclusionDifferences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.

Summary: Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT1A) receptors in Agouti-related peptide (AgRP) neurons contribute to the integrative control of RMR, and deletion of AT1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT1A and Gαi, or stimulation via Ang-II type 2 (AT2) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT1A-inhibited AgRP neurons undergo a spontaneous G-protein “signal switch,” whereby AT1A stop inhibiting the cell via Gαi and instead begin stimulating the cell via Gαq. DREADD-mediated activation of Gαi, but not Gαq, in AT1A-expressing AgRP cells stimulates RMR in lean and obese mice. Thus, loss of AT1A-Gαi coupling within the AT1A-expressing AgRP neuron subtype represents a molecular mechanism contributing to RMR adaptation.

Summary: XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2–4 h, barely visible transcripts populate the large “sparse zone” surrounding the smaller “dense zone”; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for H2AK119ub and CIZ1, a matrix protein. H3K27me3 appears hours later in the dense zone, which enlarges with chromosome condensation. Genes examined are silenced after compaction of the RNA/DNA territory. Insights into this come from the findings that the A-repeat alone can silence genes and rapidly, but only where dense RNA supports sustained histone deacetylation. We propose that sparse XIST RNA quickly impacts architectural elements to condense the largely non-coding chromosome, coalescing RNA density that facilitates an unstable, A-repeat-dependent step required for gene silencing.

The onset of the COVID-19 pandemic triggered a rapid scale-up in the use of genomic surveillance as a pandemic preparedness and response tool. As a result, the number of countries with in-country SARS-CoV-2 genomic sequencing capability increased by 40% from February 2021 to July 2022. The Global Genomic Surveillance Strategy for Pathogens with Pandemic and Epidemic Potential 2022–2032 was launched by the World Health Organization (WHO) in March 2022 to bring greater coherence to ongoing work to strengthen genomic surveillance. This paper describes how WHO’s tailored regional approaches contribute to expanding and further institutionalizing the use of genomic surveillance to guide pandemic preparedness and response measures as part of a harmonized global undertaking. Challenges to achieving this vision include difficulties obtaining sequencing equipment and supplies, shortages of skilled staff, and obstacles to maximizing the utility of genomic data to inform risk assessment and public health action. WHO is helping to overcome these challenges in collaboration with partners. Through its global headquarters, six regional offices, and 153 country offices, WHO is providing support for country-driven efforts to strengthen genomic surveillance in its 194 Member States, with activities reflecting regional specificities. WHO’s regional offices serve as platforms for those countries in their respective regions to share resources and knowledge, engage stakeholders in ways that reflect national and regional priorities, and develop regionally aligned approaches to implementing and sustaining genomic surveillance within public health systems.

We present a minimal construction using leptonic portal matter that addresses the muon g−2 anomaly. While the chiral enhancement mechanism is reminiscent of that of fermiophobic Z′ gauge models, the parameter space motivated by the kinetic mixing/vector portal dark matter model paradigm is vastly different and can be readily explored in current and forthcoming experiments.

Abstract Machine learning analyses were performed on graph theory (GT) metrics extracted from brain functional and morphological data from temporal lobe epilepsy (TLE) patients in order to identify intrinsic network phenotypes and characterize their clinical significance. Participants were 97 TLE and 36 healthy controls from the Epilepsy Connectome Project. Each imaging modality (i.e., Resting-state functional Magnetic Resonance Imaging (RS-fMRI), and structural MRI) rendered 2 clusters: one comparable to controls and one deviating from controls. Participants were minimally overlapping across the identified clusters, suggesting that an abnormal functional GT phenotype did not necessarily mean an abnormal morphological GT phenotype for the same subject. Morphological clusters were associated with a significant difference in the estimated lifetime number of generalized tonic–clonic seizures and functional cluster membership was associated with age. Furthermore, controls exhibited significant correlations between functional GT metrics and cognition, while for TLE participants morphological GT metrics were linked to cognition, suggesting a dissociation between higher cognitive abilities and GT-derived network measures. Overall, these findings demonstrate the existence of clinically meaningful minimally overlapping phenotypes of morphological and functional GT networks. Functional network properties may underlie variance in cognition in healthy brains, but in the pathological state of epilepsy the cognitive limits might be primarily related to structural cerebral network properties.

Abstract SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associated with mild or moderate symptoms were already robust and included severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity was marked by upregulation of classical antiviral pathways, including those regulating IRF1 and IRF7, whereas in moderate disease, these classical antiviral signals diminished, suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.

Abstract Background Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy. Methods Human osteochondral explants were harvested from normal (Collins grade 0–1) ankle talocrural joints of human donors (2 female, 5 male, ages 23–70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2–3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed. Results Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses. Conclusions Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.

A common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT1R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological and pathophysiological significance of distinct subtypes of neuronal and glial cell types.

IntroductionDespite known health disparities in cognitive aging, a comprehensive rationale for the increased burden in older minoritized populations including non-Latino Black and Latino adults has yet to be elucidated. While most work has focused on person-specific risk, studies are increasingly assessing neighborhood-level risk. We evaluated multiple aspects of the environmental milieu that may be critical when considering vulnerability to adverse health outcomes.MethodsWe investigated associations between a Census-tract derived Social Vulnerability Index (SVI) and level of and change in cognitive and motor functioning in 780 older adults (590 non-Latino Black adults, ∼73 years old at baseline; 190 Latinos, ∼70 years old baseline). Total SVI scores (higher = greater neighborhood-level vulnerability) were combined with annual evaluations of cognitive and motor functioning (follow-up ranged from 2 to 18 years). Demographically-adjusted mixed linear regression models tested for associations between SVI and cognitive and motor outcomes in analyses stratified by ethno-racial group.ResultsFor non-Latino Black participants, higher SVI scores were associated with lower levels of global cognitive and motor functioning-specifically, episodic memory, motor dexterity and gait-as well as longitudinal change in visuospatial abilities and hand strength. For Latinos, higher SVI scores were associated with lower levels of global motor functioning only-specifically, motor dexterity; there were no significant associations between SVI and change in motor functioning.DiscussionNeighborhood-level social vulnerability is associated with cognitive and motor functioning in non-Latino Black and Latino older adults, although associations appear to contribute to level more so than longitudinal change.