A diffusion MRI tractography atlas for concurrent white matter mapping across Eastern and Western populations.

The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

Engaging With Health Consumers in Scientific Conferences-As Partners not Bystanders.

INTRODUCTION: It is now widely recognised that engaging consumers in research activities can enhance the quality, equity and relevance of the research. Much of the commentary about consumer engagement in research focuses on research processes and implementation, rather than dissemination in conference settings. This article offers reflections and learnings from consumers, researchers and conference organisers on the 12th Health Services Research Conference, a biennial conference hosted by the Health Services Research Association of Australia and New Zealand (HSRAANZ). METHOD: We were awarded funds via a competitive application process by Bellberry Limited, a national not-for-profit agency with a focus on improving research quality, to incorporate consumer engagement strategies in conference processes and evaluate their impact. FINDINGS: Strategies included consumer scholarships, a buddy system, designated quiet space and consumer session co-chairs; the reflections explored in this paper were collected in the funded, independent evaluation. Our insights suggest a need for more structured consumer involvement in conference planning and design, as well as the development of specific engagement strategies. CONCLUSION: To move toward active partnership in scientific conference settings, our experience reinforces the need to engage consumers as members in designing and conducting research and in presenting research and planning conference content and processes. PUBLIC CONTRIBUTION: Consumer engagement in research dissemination at conferences is the focus of this viewpoint article. Consumers were involved in the conception of this article and have contributed to authorship at all stages of revisions and edits.

Navigation-Based Telehealth Informed Decision-Making for Prostate Cancer Screening in Black Men.

The rapid increase in telehealth has the potential to bring informed decision-making for prostate cancer screening (PCS) at the population level to high-risk individuals. We utilized a global technology platform of electronic health records data repositories (TriNetX) to determine its utility for Navigator-guided decision-making aid for PCS in Black men ages 45-79 years with no history of prostate cancer and PSA testing. Patients from Pennsylvania were invited to participate in a telehealth-delivered informed decision-making session for PCS. Focus groups, social learning theory, visual diagrams, and quantitative data on PCS risks and benefits were used to develop the content of the sessions, which included numerical discussions of risks vs. benefits in Black men. Participants completed several surveys, including baseline demographic and numeracy questionnaires, a one-on-one telehealth session with a trained Navigator, post-Navigation surveys, and an optional follow-up session with a urologist. Eighty-seven participants were consented and recruited. Although the mean numeracy score was only 1.9 out of 6, more than 90% rated as good or excellent that the sessions aided their PCS decision-making skills. This study indicates that Navigation by telehealth offers the ability to assist in informed decision-making for PCS at the population level.

TractoSCR: a novel supervised contrastive regression framework for prediction of neurocognitive measures using multi-site harmonized diffusion MRI tractography.

Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain's structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely TractoSCR, that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e., neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8,735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR obtains significantly higher accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities. Our code will be available at: https://github.com/SlicerDMRI/TractoSCR.

Probing the Electrostatic Effects of H-Ras Tyrosine 32 Mutations on Intrinsic GTP Hydrolysis Using Vibrational Stark Effect Spectroscopy of a Thiocyanate Probe.

The wildtype H-Ras protein functions as a molecular switch in a variety of cell signaling pathways, and mutations to key residues result in a constitutively active oncoprotein. However, there is some debate regarding the mechanism of the intrinsic GTPase activity of H-Ras. It has been hypothesized that ordered water molecules are coordinated at the active site by Q61, a highly transforming amino acid site, and Y32, a position that has not previously been investigated. Here, we examine the electrostatic contribution of the Y32 position to GTP hydrolysis by comparing the rate of GTP hydrolysis of Y32X mutants to the vibrational energy shift of each mutation measured by a nearby thiocyanate vibrational probe to estimate changes in the electrostatic environment caused by changes at the Y32 position. We further compared vibrational energy shifts for each mutation to the hydration potential of the respective side chain and demonstrated that Y32 is less critical for recruiting water molecules into the active site to promote hydrolysis than Q61. Our results show a clear interplay between a steric contribution from Y32 and an electrostatic contribution from Q61 that are both critical for intrinsic GTP hydrolysis.

Psychometric properties of the Perth emotional labour scale: Preliminary support for a new measure with theoretical implications.

Emotional labour is the process by which people regulate emotions congruently with occupational requirements. Research consistently links emotional labour to greater levels of burnout. However, we argue this literature is potentially confounded by measurement error. We sought to validate an English adaptation of a recent emotional labour measure that addresses measurement error concerns in an under-researched sample at risk of burnout-psychologists providing psychotherapy. We termed this measure the Perth Emotional Labour Scale (PELS) which is based upon Andela and colleagues' (2015) original measure. Additionally, we explored what factors of emotional labour contributed most to burnout in this group. We recruited 418 psychologists (81.58% female, 17.46% male, 0.96% non-binary) across Australia (N = 362, 86.60%) and New Zealand (N = 56, 13.40%). Factor analyses and correlational analyses examined the PELS' reliability and validity. Hierarchical multiple regression analysis explored whether each component of emotional labour contributed unique variance to emotional exhaustion (EE). Preliminary support for the PELS' psychometric properties was found and emotional dissonance was found to be the only emotional labour factor that uniquely contributed to EE. We demonstrate preliminary psychometric support for the PELS but recommend further development and argue our findings have unique implications for research and practice.

Human B Cell Receptor Repertoire Sequencing.

Next-generation sequencing has the potential to uncover the complex nature of B cell immunity by revealing the full complexity of B cell receptor (BCR) repertoires in health and disease. However, there are drawbacks which can compromise the validity of the repertoire analysis caused by quantitative bias and accumulation of sequencing errors during the library preparation and sequencing. Here, we provide an optimized protocol designed to minimize bias for reproducible and accurate preparation of human BCR repertoire libraries for high-throughput sequencing.

Fetal alcohol spectrum disorder resources for health professionals: a scoping review.

OBJECTIVES: This scoping review aimed to identify and critically appraise resources for health professionals to identify, diagnose, refer, and support individuals with fetal alcohol spectrum disorder (FASD)-including the extent to which the resources are appropriate for use in communities with First Nations Peoples. METHOD: Seven peer-reviewed databases (April 2022) and 14 grey literature websites (August 2022) were searched. The reference lists of all sources that underwent full-text review were handsearched, and FASD experts were consulted for additional sources. Resources were assessed using the Appraisal of Guidelines for REsearch and Evaluation II instrument and an adapted version of the National Health and Medical Research Council FORM Framework and iCAHE Guideline Quality Checklist. RESULTS: A total of 41 resources underwent data extraction and critical appraisal, as screening and/or diagnosis guidelines were excluded because they are covered in other reviews. Most were recently published or updated (n=24), developed in the USA (n=15, 36.6%) or Australia (n=12, 29.3%) and assisted with FASD patient referral or support (n=40). Most management guidelines scored 76%-100% on overall quality assessment (n=5/9) and were recommended for use in the Australian context with modifications (n=7/9). Most of the guides (n=15/22) and factsheets (n=7/10) received a 'good' overall score. Few (n=3/41) resources were explicitly designed for or with input from First Nations Australians. CONCLUSION: High-quality resources are available to support health professionals providing referrals and support to individuals with FASD, including language guides. Resources should be codesigned with people living with FASD to capture and integrate their knowledge and preferences.

Self-Reporting Conjugated Polymer Nanoparticles for Superoxide Generation and Detection.

Conjugated polymer nanoparticles (CPNs or Pdots) have become increasingly popular fluorophores for multimodal applications that combine imaging with phototherapeutic effects. Reports of CPNs in photodynamic therapy applications typically focus on their ability to generate singlet oxygen. Alternatively, CPN excited states can interact with oxygen to form superoxide radical anion and a CPN-based hole polaron, both of which can have deleterious effects on fluorescence properties. Here, we demonstrate that CPNs prepared from the common conjugated polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1',3}-thiadiazole)] (PFBT, also known as F8BT) generate superoxide upon irradiation. We use the same CPNs to detect superoxide by doping them with a superoxide-responsive hydrocyanine dye developed by Murthy and co-workers. Superoxide induces off-to-on fluorescence switching by converting quenching hydrocyanine dyes to fluorescent cyanine dyes that act as fluorescence resonance energy transfer (FRET) acceptors for PFBT chromophores. Amplified FRET from the multichromophoric CPNs yields fluorescence signal intensities that are nearly 50 times greater than when the dye is excited directly or over 100 times greater when signal readout is from the CPN channel. The dye loading level governs the maximum amount of superoxide that induces a change in fluorescence properties and also influences the rate of superoxide generation by furnishing competitive excited state deactivation pathways. These results suggest that CPNs can be used to deliver superoxide in applications in which it is desirable and provide a caution for fluorescence-based CPN applications in which superoxide can damage fluorophores.

OpenTn5: Open-Source Resource for Robust and Scalable Tn5 Transposase Purification and Characterization.

Tagmentation combines DNA fragmentation and sequencing adapter addition by leveraging the transposition activity of the bacterial cut-and-paste Tn5 transposase, to enable efficient sequencing library preparation. Here we present an open-source protocol for the generation of multi-purpose hyperactive Tn5 transposase, including its benchmarking in CUT&Tag, bulk and single-cell ATAC-seq. The OpenTn5 protocol yields multi-milligram quantities of pG-Tn5E54K, L372P protein per liter of E. coli culture, sufficient for thousands of tagmentation reactions and the enzyme retains activity in storage for more than a year.

Plate-Based High-Throughput Fluorescence Assay for Assessing Enveloped Virus Integrity.

Viruses are a considerable threat to global health and place major burdens on economies worldwide. Manufactured viruses are also being widely used as delivery agents to treat (gene therapies) or prevent diseases (vaccines). Therefore, it is vital to study and fully understand the infectious state of viruses. Current techniques used to study viruses are often slow or nonexistent, making the development of new techniques of paramount importance. Here we present a high-throughput and robust, cell-free plate-based assay (FAIRY: Fluorescence Assay for vIRal IntegritY), capable of differentiating intact from nonintact enveloped viruses, i.e, infectious from noninfectious. Using a thiazole orange-terminated polymer, a 99% increase in fluorescence was observed between treated (heat or virucide) and nontreated. The FAIRY assay allowed for the rapid determination of the infectivity of a range of enveloped viruses, highlighting its potential as a valuable tool for the study of viruses and interventions against them.

Immune gene regulation is associated with age and environmental adversity in a nonhuman primate.

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.

A Protocol for Using Point-of-Care Ultrasound as an Adjunct in Pediatric Cardiac Arrest: Pediatric Ultrasound for Life-Supporting Efforts.

ABSTRACT: Pediatric cardiac arrest is a rare but time-critical event that poses significant challenges to health care providers. Initiation of point-of-care ultrasound (POCUS) early in resuscitation can help optimize the location of chest compressions, identify inadequate compressions, evaluate for sonographic pulse, and help direct management. Although several algorithms currently exist to incorporate POCUS into adult cardiac arrest, none, to our knowledge, currently exist for the pediatric population. We propose a novel protocol for POCUS use as an adjunct to existing standard-of-care measures in pediatric cardiac arrest, which we call the Pediatric Ultrasound for Life-Supporting Efforts protocol.

Leadership Perspectives on Nursing Home Operations From Crisis to Control: A Mixed Methods Study.

OBJECTIVES: Nursing home (NH) leaders remain challenged to deliver quality care, despite the COVID-19 transition to an endemic phase. This study describes NH leadership perspectives on preparing and maintaining quality care during times of diminishing resources as experienced through the COVID-19 pandemic to gain insight on how best to support NHs moving forward. DESIGN: This was a cross-sectional, parallel convergent mixed methods study. SETTING AND PARTICIPANTS: This study reports quantitative data from 5001 NHs across 12 states along with qualitative data from a subsample of NH leaders (N = 15). METHODS: Publicly reported survey data were analyzed using descriptive statistics. Individual in-depth interviews with NH leaders conducted at 12-month follow-up were analyzed using inductive thematic coding organized by a guiding framework. Data were integrated using convergent analysis and a joint display. RESULTS: NH leaders (licensed administrators, clinical directors, and managers) reported resident and staff infection rates, and access to resources (such as personal protective equipment and testing supplies) that aligned with national trends. Leaders described their NHs (N = 14; 43% rural; 71% not for profit) to be in varied states of operational readiness (standard, contingency, crisis) to support quality infection prevention and control (IPC) at the transition to the endemic COVID-19 phase. Leadership reported continued challenges in addressing resident and staff vaccinations, securing testing supplies, obtaining financial resources to maintain acceptable levels of personal protective equipment, continued staffing shortages, and issues in implementing isolation practices in current facilities. CONCLUSION AND IMPLICATIONS: NH leaders continue to struggle delivering quality IPC care post-pandemic and require focused support in several areas. Clinical practice guidelines should include IPC practices to prevent the infection and spread of any COVID-19 variant in this endemic phase. Policies should support continued reporting of IPC-related metrics and adequate funding to account for the long-term financial burden NHs face.

Community health worker training on older adults: A qualitative needs assessment.

BACKGROUND: Community health workers (CHWs) are frontline public health personnel who serve as liaisons between vulnerable patient populations and the healthcare system. They are instrumental in health promotion and education for urban-dwelling older adults. However, no research exists on training that CHWs receive on age-friendly health care. This article explores CHW education on the 4Ms of an Age-Friendly Health System and identifies areas where additional training may be necessary. METHODS: As part of a two-pronged qualitative needs assessment, four focus groups were held with a total of 17 CHWs and semistructured interviews were conducted with 10 clinicians, including both healthcare providers and social workers. Focus group and interview transcripts were then analyzed for major themes in Dedoose, a qualitative coding software. RESULTS: Clinicians most often identified Mentation and Mobility as areas where CHWs can have the greatest impact. Correspondingly, CHWs felt under-equipped to assist patients in these areas and expressed strong interest in additional training. In general, CHWs and clinicians agreed that Medications and What Matters do not fall under CHW scope of practice. CONCLUSIONS: Our findings confirm the critical role that CHWs can play in promoting the health and well-being of urban-dwelling older adults. However, we also demonstrate that many CHWs lack adequate training in age-friendly care. To meet the social and medical needs of a rapidly aging US population, there is a pertinent need to develop a novel community health worker training curriculum on Mentation and Mobility.

Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries.

Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.

Effects of acute hypoxia exposure and acclimation on the thermal tolerance of an imperiled Canadian minnow.

Elevated water temperatures and low dissolved oxygen (hypoxia) are pervasive stressors in aquatic systems that can be exacerbated by climate change and anthropogenic activities, and there is growing interest in their interactive effects. To explore this interaction, we quantified the effects of acute and long-term hypoxia exposure on the critical thermal maximum (CTmax) of Redside Dace (Clinostomus elongatus), a small-bodied freshwater minnow with sparse populations in the Great Lakes Basin of Canada and designated as Endangered under Canada's Species at Risk Act. Fish were held at 18°C and acclimated to four levels of dissolved oxygen (>90%, 60%, 40%, and 20% air saturation). CTmax was measured after 2 and 10 weeks of acclimation and after 3.5 weeks of reoxygenation, and agitation behavior was quantified during CTmax trials. Aquatic surface respiration behavior was also quantified at 14 weeks of acclimation to oxygen treatments. Acute hypoxia exposure decreased CTmax in fish acclimated to normoxia (>90% air saturation), but acclimation to hypoxia reduced this effect. There was no effect of acclimation oxygen level on CTmax when measured in normoxia, and there was no effect of exposure time to hypoxia on CTmax. Residual effects of hypoxia acclimation on CTmax were not seen after reoxygenation. Agitation behavior varied greatly among individuals and was not affected by oxygen conditions. Fish performed aquatic surface respiration with low frequency, but performed it earlier when acclimated to higher levels of oxygen. Overall, this work sheds light on the vulnerability of fish experiencing acute hypoxia and heat waves concurrently.

Contemporary Patterns of Financial Toxicity Among Patients With Rheumatologic Disease in the United States.

BACKGROUND/OBJECTIVE: Rheumatologic diseases encompass a group of disabling conditions that often require expensive clinical treatments and limit an individual's ability to work and maintain a steady income. The purpose of this study was to evaluate contemporary patterns of financial toxicity among patients with rheumatologic disease and assess for any associated demographic factors. METHODS: The cross-sectional National Health Interview Survey was queried from 2013 to 2018 for patients with rheumatologic disease. Patient demographics and self-reported financial metrics were collected or calculated including financial hardship from medical bills, financial distress, food insecurity, and cost-related medication (CRM) nonadherence. Multivariable logistic regressions were used to assess for factors associated with increased financial hardship. RESULTS: During the study period, 20.2% of 41,502 patients with rheumatologic disease faced some degree of financial hardship due to medical bills, 55.0% of whom could not pay those bills. Rheumatologic disease was associated with higher odds of financial hardship from medical bills (adjusted odds ratio, 1.29; 95% confidence interval, 1.22-1.36; p < 0.001) with similar trends for patients suffering from financial distress, food insecurity, and CRM nonadherence (p < 0.001 for all). Financial hardship among patients with rheumatologic disease was associated with being younger, male, Black, and uninsured (p < 0.001 for all). CONCLUSION: In this nationally representative study, we found that a substantial proportion of adults with rheumatologic disease in the United States struggled with paying their medical bills and suffered from food insecurity and CRM nonadherence. National health care efforts and guided public policy should be pursued to help ease the burden of financial hardship for these patients.

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.

Prolonged Grief Disorder, but Not Death From COVID-19, Elicits Public Stigma: A Vignette-Based Experiment.

We investigated the effects of cause of death (COVID-19 with an underlying medical condition vs. without) and prolonged grief disorder status (PGD present or absent) on participants' reported public stigma towards the bereaved. Participants (N = 304, 66% women; Mage = 39.39 years) were randomly assigned to read one of four vignettes describing a bereaved man. Participants completed stigma measures assessing negative attributions, desired social distance, and emotional reactions. Participants reported significantly stronger stigmatizing responses towards an individual with PGD (vs. without PGD) across all stigma measures. There was no significant difference in stigma based on cause of death; however, stigma was reported regardless of cause of death. There was no significant interaction between cause of death and PGD on stigma. This study supports the robust finding of public stigma being reported toward an individual with PGD, suggesting these individuals are at risk of public stigma and not receiving adequate bereavement support.