Predicting the future of our oceans-Evaluating genomic forecasting approaches in marine species.

Climate change is restructuring biodiversity on multiple scales and there is a pressing need to understand the downstream ecological and genomic consequences of this change. Recent advancements in the field of eco-evolutionary genomics have sought to include evolutionary processes in forecasting species' responses to climate change (e.g., genomic offset), but to date, much of this work has focused on terrestrial species. Coastal and offshore species, and the fisheries they support, may be even more vulnerable to climate change than their terrestrial counterparts, warranting a critical appraisal of these approaches in marine systems. First, we synthesize knowledge about the genomic basis of adaptation in marine species, and then we discuss the few examples where genomic forecasting has been applied in marine systems. Next, we identify the key challenges in validating genomic offset estimates in marine species, and we advocate for the inclusion of historical sampling data and hindcasting in the validation phase. Lastly, we describe a workflow to guide marine managers in incorporating these predictions into the decision-making process.

Fear of a Black Neighborhood: Anti-Black Racism and the Health of White Americans.

Does anti-Black racism harm White Americans? We advance hypotheses that address this question within the neighborhood context. Hypotheses are tested with neighborhood and survey data from a probability sample of White residents of Nashville, Tennessee. We find that regardless of neighborhood crime rates or socioeconomic compositions, Whites report heightened perceptions of crime and danger in their neighborhoods as the proportion of Black residents increases. Perceived neighborhood danger, in turn, predicts increased symptoms of psychophysiological distress. When stratified by socioeconomic status (SES), however, low-SES Whites also report perceptions of higher status when living near more Black neighbors, which entirely offsets their distress. We conclude that although anti-Black racism can ironically harm the health of White Americans, compensatory racist ideologies can also offset these harms, particularly for lower-status Whites. We situate our findings within broader discussions of anti-Black racism, residential segregation, and psychiatric disorders commonly observed among White Americans.

Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant With Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used for critically ill candidates with excellent outcomes, but data on this strategy in older recipients remain limited. We compared outcomes of no BTT, mechanical ventilation (MV)-only BTT, and ECMO BTT in recipients of greater than or equal to 65 years. Lung-only recipients of greater than or equal to 65 years in the United Network for Organ Sharing database between 2008 and 2022 were included and stratified by bridging strategy. Of the 9,936 transplants included, 226 (2.3%) were MV-only BTT and 159 (1.6%) were ECMO BTT. Extracorporeal membrane oxygenation BTT recipients were more likely to have restrictive disease pathology, had higher median lung allocation score, and spent fewer days on the waitlist (all p < 0.001). Compared to no-BTT recipients, ECMO BTT recipients were more likely to be intubated or on ECMO at 72 hours posttransplant and had longer hospital lengths of stay (all p < 0.001). Extracorporeal membrane oxygenation BTT recipients had increased risk of 3 years mortality compared to both no-BTT (adjusted hazard ratio [aHR] = 1.48 [95% confidence interval {CI}: 1.14-1.91], p = 0.003) and MV-only recipients (aHR = 1.50 [95% CI: 1.08-2.07], p = 0.02). Overall, we found that ECMO BTT in older recipients is associated with inferior posttransplant outcomes compared to MV-only or no BTT, but over half of recipients remained alive at 3 years posttransplant.

Phylogenetic and Protein Structure Analyses Provide Insight into the Evolution and Diversification of the CD36 Domain "Apex" among Scavenger Receptor Class B Proteins across Eukarya.

The cluster of differentiation 36 (CD36) domain defines the characteristic ectodomain associated with class B scavenger receptor (SR-B) proteins. In bilaterians, SR-Bs play critical roles in diverse biological processes including innate immunity functions such as pathogen recognition and apoptotic cell clearance, as well as metabolic sensing associated with fatty acid uptake and cholesterol transport. Although previous studies suggest this protein family is ancient, SR-B diversity across Eukarya has not been robustly characterized. We analyzed SR-B homologs identified from the genomes and transcriptomes of 165 diverse eukaryotic species. The presence of highly conserved amino acid motifs across major eukaryotic supergroups supports the presence of a SR-B homolog in the last eukaryotic common ancestor. Our comparative analyses of SR-B protein structure identify the retention of a canonical asymmetric beta barrel tertiary structure within the CD36 ectodomain across Eukarya. We also identify multiple instances of independent lineage-specific sequence expansions in the apex region of the CD36 ectodomain-a region functionally associated with ligand-sensing. We hypothesize that a combination of both sequence expansion and structural variation in the CD36 apex region may reflect the evolution of SR-B ligand-sensing specificity between diverse eukaryotic clades.

Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comprise a spectrum of neurodegenerative diseases linked to TDP-43 proteinopathy, which at the cellular level, is characterized by loss of nuclear TDP-43 and accumulation of cytoplasmic TDP-43 inclusions that ultimately cause RNA processing defects including dysregulation of splicing, mRNA transport and translation. Complementing our previous work in motor neurons, here we report a novel model of TDP-43 proteinopathy based on overexpression of TDP-43 in a subset of Drosophila Kenyon cells of the mushroom body (MB), a circuit with structural characteristics reminiscent of vertebrate cortical networks. This model recapitulates several aspects of dementia-relevant pathological features including age-dependent neuronal loss, nuclear depletion and cytoplasmic accumulation of TDP-43, and behavioral deficits in working memory and sleep that occur prior to axonal degeneration. RNA immunoprecipitations identify several candidate mRNA targets of TDP-43 in MBs, some of which are unique to the MB circuit and others that are shared with motor neurons. Among the latter is the glypican Dally-like-protein (Dlp), which exhibits significant TDP-43 associated reduction in expression during aging. Using genetic interactions we show that overexpression of Dlp in MBs mitigates TDP-43 dependent working memory deficits, conistent with Dlp acting as a mediator of TDP-43 toxicity. Substantiating our findings in the fly model, we find that the expression of GPC6 mRNA, a human ortholog of dlp, is specifically altered in neurons exhibiting the molecular signature of TDP-43 pathology in FTD patient brains. These findings suggest that circuit-specific Drosophila models provide a platform for uncovering shared or disease-specific molecular mechanisms and vulnerabilities across the spectrum of TDP-43 proteinopathies.

Is Irreligion a Risk Factor for Suicidality? Findings from the Nashville Stress and Health Study.

Suicide is a public health problem and one of the leading causes of death in the United States. Research exploring the linkages between religion and spirituality has received intermittent attention. Data was derived from the Nashville Stress and Health Study (2011-2014), a cross-sectional probability survey of black and white adults from Davidson County, Tennessee (n = 1252). Results indicate that those with no perceived belief in divine control had a higher likelihood of suicidality. This study provides a fresh perspective on the links between religious factors and suicidality by (a) considering multiple religious and spiritual domains and (b) focusing on the association between irreligion and suicidality.

System Configuration Evaluation for a Province-Wide Clinical Information System Using the eSafety Checklist.

BACKGROUND: According to Digital Health Canada 2013 eSafety Guidelines, an estimated one-third of patient safety incidents following implementation of clinical information systems (CISs) are technology-related. An eSafety checklist was previously developed to improve CIS safety by providing a comprehensive listing of system-agnostic, evidence-based configuration recommendations. OBJECTIVES: We sought to use the checklist to support safe initial configuration of a provincial system-wide CIS (Alberta, Canada), referred to as Connect Care. METHODS: The checklist was applied to 13 Connect Care modules in three successive phases. First, the checklist was adapted to an abbreviated high-priority version. Second, demonstrations of each module were recorded. Finally, independent evaluation of each recording was conducted by two eSafety evaluators using the abbreviated eSafety checklist. RESULTS: All modules achieved greater than 72% compliance, with an average of 84%. Overall, 273 opportunities for improvement were identified, with four major areas or themes emerging: (1) inconsistent date and time, (2) unclear patient identification, (3) ineffective alert system, and (4) insufficient decision support. These opportunities were forwarded to the appropriate build teams for review and implementation. CONCLUSION: This work is the first to utilize the eSafety checklist in a real-world CIS, which will become one of the largest in Canada. The checklist has shown clinical applicability in identifying gaps in CIS configuration and should be considered for use in future and pre-existing CISs.

Effect of Soil Temperature on Reproduction of Root-knot Nematodes in Flue-cured Tobacco with Homozygous Rk1 and/or Rk2 Resistance Genes.

Most commercial flue-cured tobacco cultivars contain the Rk1 resistance gene, which provides resistance to races 1 and 3 of Meloidogyne incognita and race 1 of M. arenaria. A number of cultivars now possess a second root-knot resistance gene, Rk2. High soil temperatures have been associated with a breakdown of root-knot resistance genes in a number of crops. Three greenhouse trials were performed from 2014 to 2015 investigate the effect of high soil temperature on the efficacy of Rk1 and/or Rk2 genes in reducing parasitism by a population of M. incognita race 3. Trials were arranged in randomized complete block design in open-top growth chambers set at 25°, 30°, and 35°C. Plants were inoculated with 3,000 eggs and data were collected 35 days post-inoculation. Galling, numbers of egg masses and eggs, and reproductive index were compared across cultivar entries. Nematode reproduction was reduced at 25°C and 30°C on entries possessing Rk1 and Rk1Rk2 compared to the susceptible entry and the entry possessing only Rk2. However, there were often no significant differences in reproduction at 35°C between entries with Rk1 and/or Rk2 compared to the susceptible control, indicating an increase of root-knot nematode parasitism on resistant entries at higher temperatures. Although seasonal differences in nematode reproduction were observed among experiments, relative differences among tobacco genotypes remained generally consistent.

The Direct Conversion of Esters to Ketones Enabled by a Traceless Activating Group.

We report here the design and development of a method for the single-step conversion of esters to ketones with simple reagents. The selective transformation of esters to ketones, rather than tertiary alcohols, is made possible by the use of a transient sulfinate group on the nucleophile that activates the adjacent carbon toward deprotonation to form a carbanion that adds to the ester, followed by a second deprotonation to prevent further addition. The resulting dianion undergoes spontaneous fragmentation of the SO2 group upon quenching with water to reveal the ketone product.

Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

Impact of Disease Activity and Inflammatory Bowel Disease Subtype on Quality of Life in Preconception and Pregnant Patients.

BACKGROUND: Inflammatory bowel disease (IBD) and pregnancy both impact health-related quality of life (HRQoL). However, little is known about IBD-related HRQoL around pregnancy. AIMS: To assess the trajectory and predictors of HRQoL in preconception and pregnant patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Preconception and pregnant patients with IBD were followed prospectively from preconception to twelve months postpartum at a tertiary referral centre. Participants completed the Short IBD Questionnaire (SIBDQ) and were assessed for clinical disease activity (modified Harvey Bradshaw Index or partial Mayo score) and objective disease activity (C-reactive protein [CRP], fecal calprotectin [FCP]). RESULTS: A total of 61 patients with IBD (25 CD, 36 UC) were included. During preconception, patients with UC had higher SIBDQ bowel and social sub-scores than those with CD, but this reversed during postpartum. Patients with CD but not UC developed a significant, sustained improvement in SIBDQ upon becoming pregnant, which persisted into 12 months postpartum. In a multivariable linear regression model, clinical disease activity negatively predicted SIBDQ at every pregnancy timepoint and up to 12 months postpartum. SIBDQ was significantly lower in patients with CRP ≥ 8.0 mg/L during trimester 1 (T1), but not later in pregnancy. SIBDQ bowel sub-scores were significantly lower in patients with FCP ≥ 250 mg/kg at T2, T3, and 6 months postpartum. CONCLUSIONS: Clinical disease activity is a consistent negative predictor of HRQoL from conception to 12 months postpartum. Patients with UC experience better preconception HRQoL but suffer worse postpartum HRQoL than those with CD.

Is it the Sermon or the Choir? Pastoral Support, Congregant Support, and Worshiper Mental Health.

Background: Although religious involvement tends to be associated with improved mental health, additional work is needed to identify the specific aspects of religious practice that are associated with positive mental health outcomes. Our study advances the literature by investigating how two unique forms of religious social support are associated with mental health. Purpose: We explore whether support received in religious settings from fellow congregants or religious leaders is associated with participants' mental health. We address questions that are not only of interest to religion scholars, but that may also inform religious leaders and others whose work involves understanding connections between religious factors and psychological outcomes within religious communities. Methods: We test several hypotheses using original data from the "Mental Health in Congregations Study (2017-2019)", a survey of Christian and Jewish congregants from South Texas and the Washington DC area (N = 1882). Surveys were collected using both paper and online surveys and included an extensive battery of religious and mental health measures. Results: Congregant support has more robust direct associations with mental health outcomes than faith leader support. Increased congregant support is significantly associated (p < 0.001) with fewer symptoms of psychological distress (ß = - 0.168), anxiety (ß = - 0.159), and anger (ß = - 0.190), as well as greater life satisfaction (ß = 0.269) and optimism (ß = 0.283). However, faith leader support moderates these associations such that congregant support is associated with better mental health only in cases where faith leader support is also high. When leader support is low, congregant support and mental health are not associated. Conclusions and Implications: At the conceptual level, our study adds to an extensive literature on the relationship between religious social support and mental health. Additionally, our work may provide important insights to religious leadership in terms of communications strategies, services, and resources that might enhance overall congregant mental health and well-being.

Skin Tone and the Health Returns to Higher Status.

This study addresses two questions. First, why do Black Americans exhibit worse health outcomes than White Americans even at higher levels of socioeconomic status (SES)? Second, are diminished health returns to higher status concentrated among Black Americans with darker skin color? Novel hypotheses are tested with biosocial panel data from Add Health, a nationally representative cohort of Black and White adolescents who have transitioned to adulthood. We find that White and light-skin Black respondents report improved health after achieving higher SES, on average, while their darker-skin Black peers report declining health. These patterns persist regardless of controls for adolescent health status and unmeasured between-person heterogeneity. Moreover, increased inflammation tied to unfair treatment and perceptions of lower status helps to account for patterns of diminished health returns for dark-skin Black groups. Our study is the first to document skin tone heterogeneity in diminished health returns and one of few studies to identify life course stress processes underlying such disparities. We consider additional processes that could be examined in future studies, as well as the broader health and policy implications of our findings.

Checklist for Improving Patient Communication on Bladder Preservation Options: The Patient Advocate Perspective.

Trimodal therapy (TMT) - maximal transurethral resection of bladder tumour followed by chemotherapy and radiation - is an effective treatment for some patients diagnosed with muscle-invasive bladder cancer. Yet eligible patients are not always offered this option or are unclear that this option is (or was) appropriate, desirable and available to them. Communication challenges are a critical barrier to delivering the high-quality care and shared decision-making that bladder cancer patients seek. Leveraging patient and clinician feedback, a checklist was created and is proposed that proactively addresses patients' concerns and questions and ensures that patients are well-informed about TMT. By using the checklist, members of multidisciplinary bladder cancer medical teams can ensure that patients are well-informed about TMT and are confident that TMT has been appropriately and jointly explored as a treatment option. The checklist can reduce communication challenges and frustrations and ensure that, through shared decision-making, patients have chosen their most appropriate treatment.

"Moving on Up? Neighborhood Status and Racism-Related Distress among Black Americans".

At all levels of socioeconomic status, Black Americans can expect to live shorter and sicker lives than their White counterparts. This study advances the perspective that anti-Black stigma from Whites precludes Blacks from reaping the full health rewards of higher status, particularly within the context of neighborhoods. To test this hypothesis, I merge census data with rich survey and biomarker data from the Nashville Stress and Health Study, a representative sample of Black and White adults from Davidson County, Tennessee (n = 1,252). Initially, I find that Blacks who reside in higher-status and mostly White communities exhibit lower levels of neuroendocrine stress hormones, relative to their peers living in disadvantaged Black neighborhoods. But Blacks in higher-status areas also report more perceived discrimination. In turn, perceived discrimination is associated with chronic bodily pain, as well as elevated stress hormones and blood pressure tied to high goal-striving stress, or fears of being blocked from reaching life goals. After accounting for racism-related stressors, Blacks exhibit comparable levels of physiological distress regardless of neighborhood context. The inverse is true for Whites, who report fewer stressors in higher-status neighborhoods, and less physiological distress than Blacks overall. Findings are discussed within the context of social evolutionary theories of the human brain and are dovetailed with broader racial health disparities in the United States.

Dysregulation of Translation in TDP-43 Proteinopathies: Deficits in the RNA Supply Chain and Local Protein Production.

Local control of gene expression provides critical mechanisms for regulating development, maintenance and plasticity in the nervous system. Among the strategies known to govern gene expression locally, mRNA transport and translation have emerged as essential for a neuron's ability to navigate developmental cues, and to establish, strengthen and remove synaptic connections throughout lifespan. Substantiating the role of RNA processing in the nervous system, several RNA binding proteins have been implicated in both developmental and age dependent neurodegenerative disorders. Of these, TDP-43 is an RNA binding protein that has emerged as a common denominator in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and related disorders due to the identification of causative mutations altering its function and its accumulation in cytoplasmic aggregates observed in a significant fraction of ALS/FTD cases, regardless of etiology. TDP-43 is involved in multiple aspects of RNA processing including splicing, transport and translation. Given that one of the early events in disease pathogenesis is mislocalization from the nucleus to the cytoplasm, several studies have focused on elucidating the pathogenic role of TDP-43 in cytoplasmic translation. Here we review recent findings describing TDP-43 translational targets and potential mechanisms of translation dysregulation in TDP-43 proteinopathies across multiple experimental models including cultured cells, flies, mice and patient derived neurons.

Artificial intelligence enabled automated diagnosis and grading of ulcerative colitis endoscopy images.

Endoscopic evaluation to reliably grade disease activity, detect complications including cancer and verification of mucosal healing are paramount in the care of patients with ulcerative colitis (UC); but this evaluation is hampered by substantial intra- and interobserver variability. Recently, artificial intelligence methodologies have been proposed to facilitate more objective, reproducible endoscopic assessment. In a first step, we compared how well several deep learning convolutional neural network architectures (CNNs) applied to a diverse subset of 8000 labeled endoscopic still images derived from HyperKvasir, the largest multi-class image and video dataset from the gastrointestinal tract available today. The HyperKvasir dataset includes 110,079 images and 374 videos and could (1) accurately distinguish UC from non-UC pathologies, and (2) inform the Mayo score of endoscopic disease severity. We grouped 851 UC images labeled with a Mayo score of 0-3, into an inactive/mild (236) and moderate/severe (604) dichotomy. Weights were initialized with ImageNet, and Grid Search was used to identify the best hyperparameters using fivefold cross-validation. The best accuracy (87.50%) and Area Under the Curve (AUC) (0.90) was achieved using the DenseNet121 architecture, compared to 72.02% and 0.50 by predicting the majority class ('no skill' model). Finally, we used Gradient-weighted Class Activation Maps (Grad-CAM) to improve visual interpretation of the model and take an explainable artificial intelligence approach (XAI).

Reproduction of Meloidogyne arenaria race 2 on flue-cured tobacco with putative resistance derived from Nicotiana repanda.

Chemical controls for root-knot nematodes are increasingly restricted due to environmental and human health concerns. Host resistance to these nematodes is key to flue-cured tobacco production in Virginia. Resistance to Meloidogyne incognita races 1 and 3, and race 1 of M. arenaria is imparted by the gene Rk1, which is widely available in commercial flue-cured tobacco. Rk2 imparts increased resistance to M. javanica when stacked with Rk1 and is becoming commercially available. The efficacy of Rk2 against M. arenaria race 2, which is increasingly prevalent in Virginia, is unclear. Greenhouse trials were conducted in 2017 to determine how potential resistance derived from N. repanda compares to the root-knot nematode resistance afforded by Rk1 and Rk2. Trials were arranged in a completely randomized block design and included an entry with traits derived from N. repanda, a susceptible entry and entries possessing Rk1 and/or Rk2. Data collected after 60 days included percent root galling, egg mass counts, and egg counts. Root galling and reproduction were significantly lower on the entry possessing traits derived from N. repanda relative to other entries, suggesting that the N. repanda species may hold a novel source of root-knot nematode resistance for commercial flue-cured tobacco cultivars.