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A catalogue of neuronal cell types has often been called a 'parts list' of the brain1, and regarded as a prerequisite for understanding brain function2,3. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision4,5. Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi)6-10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with 'boundary types' that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development.

Abstract Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Introduction: While traditionally a treatment for congenital deformities, limb-lengthening surgery has recently been utilized as a cosmetic solution for patients with less-than-desirable heights. Despite a growing rise in popularity, stature-lengthening surgery carries a host of social stigmas and ethical concerns. With the emergence of natural language processing artificial intelligence (NLP AI) models such as ChatGPT, patients interested in stature-lengthening surgery may turn to these chatbots for medical information instead of primary care providers. This study seeks to evaluate the quality and readability of NLP AI model responses to common questions regarding stature-lengthening surgery to ensure proper patient education and direction toward a licensed orthopedic surgeon. Materials and Methods: Eleven questions regarding limb-lengthening surgery were posed to ChatGPT version 3.5. All named authors reviewed the AI responses independently and utilized the following scoring systems to assess readability and quality: DISCERN, ChatGPT Response Accuracy Scoring (CRAS) developed by Mika et al., Flesch–Kincaid Reading Ease (FRES), and Flesch–Kincaid Grade Level (FKGL). Cohen’s kappa was utilized to determine the inter-rater reliability between each reviewer’s assigned DISCERN and CRAS scores. Results: The average DISCERN score across all independent reviewers was 55.2 ± 5.63, with an inter-rater reliability of 0.293, indicating good scores with fair agreement, respectively. The average CRAS score across all senior reviewers was 1.60 ± 0.63 with inter-rater reliability being 0.014, indicating none to slight agreement. The average FRES score was 14.8 ± 2.24, and the average FKGL score was 18.9 ± 11.0, indicating a required reading level of a college graduate. Conclusions: The results of our study show that NLP AI models provide generally high-quality responses to patient questions regarding stature-lengthening surgery. However, notable flaws were identified, including a high required education level for proper comprehension as well as an inability to cite source material used for each response.

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.

Abstract Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate classes exploit the same transporter’s mechanism. Any disclosure of plasticity in transporter mechanism when treated with different substrates becomes critical for developing general selectivity principles in membrane transport catalysis. Using extensive molecular dynamics simulations with an enhanced sampling approach, we select the Arabidopsis sugar transporter AtSWEET13 as a model system to identify the basis for glucose versus sucrose molecular recognition and transport. Here we find that AtSWEET13 chemical selectivity originates from a conserved substrate facial selectivity demonstrated when committing alternate access, despite mono-/di-saccharides experiencing differing degrees of conformational and positional freedom throughout other stages of transport. However, substrate interactions with structural hallmarks associated with known functional annotations can help reinforce selective preferences in molecular transport.

Abstract Background Individual and social characteristics are attributed to violent behavior in schools, yet environmental hazards may play an understudied role. Ambient air pollution has been linked to neurological dysfunction that inhibits decision-making and may result in violent behavior in adult populations. However, little is known on how air pollution may be associated with violent behaviors in children. Methods A cross-sectional ecologic study was designed to estimate the associations between air pollution (fine particulate matter, carbon monoxide, and nitrogen dioxide) with the occurrence of violent incidents and incidents involving a weapon among a cohort of children in Minnesota schools (2008–2012). Differences by urban and rural status of schools were also explored. Negative binomial regression models were developed to estimate incidence rate ratios (IRR) and incidence rate differences (IRD) to describe associations between air pollution and violent incidents in school settings. Results Our results indicate that the highest levels of carbon monoxide, nitrogen dioxide and fine particulate matter concentrations were associated with increased violent disciplinary incidents. Among the total student population, the 4th quartile of carbon monoxide exposure was associated with an IRD of 775.62 (95% CI 543.2, 1008.05) violent incidents per 100,000 students per school year compared to schools in the lowest quartile of exposure. Comparing the 4th to the 1st quartiles of exposure, nitrogen dioxide and fine particulate matter had an IRD of 629.16 (95% CI 384.87, 873.46), and 510.49 (95% CI 274.92, 746.05) violent incidents per 100,000 students per school year respectively. Schools in urban settings shared a larger burden of violent incidents associated with air pollution compared to rural schools. Conclusions Modifying environmental pollutants surrounding school environments, particularly for high exposure communities, may be a novel tool for reducing violence and subsequent injuries in schools.

Abstract Wolves are opportunistic generalists that can respond quickly to new and unique food sources. Wolves in some ecosystems will consume berries and other fruits when they are abundant and available; however, many aspects of this behavior remain unknown. In the Greater Voyageurs Ecosystem (GVE), Minnesota, USA, wolves consistently consume berries, particularly blueberries, when they are available. We deployed remote cameras in blueberry patches to record wolves foraging on berries over several years. We captured footage of wolves of all age classes, social statuses, and sex foraging on blueberries alone or with other wolves. Our observations indicate berry consumption by wolves is a widespread behavior in the GVE and likely in similar southern boreal ecosystems. We hope our work spurs researchers across wolf range to examine whether berry consumption by wolves is a widespread and ubiquitous behavior for wolves.

Social Network Analysis (SNA) is a statistical method used to analyze the social structure and interactions among individuals within a network. SNA is used extensively in a number of disciplines such as sociology, geography, and communications research. However, the use of SNA by practitioners and researchers in assessment and evaluation is much lower than their counterparts in other social science disciplines. One of the primary barriers to utilizing SNA in social science research is correctly formatting the data for use. The focus of this article is to provide researchers with a tool for restructuring long form data so that it can be used to conduct social network analyses and generate undirected sociograms.

Abstract American Samoa is experiencing rapid relative sea level rise due to increases in global sea level and significant post-2009 earthquake land subsidence, endangering homes and critical infrastructure. Wave and water-level observations collected over a fringing reef at Faga‘itua Bay, American Samoa, in 2017 reveal depth-limited shoreline sea-swell wave heights over the range of conditions sampled. Using field data to calibrate a one-dimensional, phase-resolving nonhydrostatic wave model (SWASH), we examine the influence of water level on wave heights over the reef for a range of current and future sea levels. Assuming a fixed reef bathymetry, model results predict rising sea levels will escalate nearshore extreme water levels that are dominated by an increase in nearshore sea-swell wave heights. Model results provide insight into how and at what reef depths rising sea levels reduce reef capacity to dissipate wave energy, compounding shoreline threats. This study aims to bring increased attention to the immediate threats to American Samoa’s way of life, and to demonstrate the utility of SWASH for extrapolating wave transformation to future sea level.

Abstract. Introduction:. Traditionally, stiff hypertrophic nonunions have been managed with open preparation of the nonunion site, which is then secured with internal fixation. Alternative surgical options are available including distraction osteogenesis with an external fixator. There is currently a limited amount of literature pertaining to the use of distraction osteogenesis in the management of hypertrophic nonunion. The aim of this systematic review was to collate and assess the effectiveness of distraction osteogenesis (DO) in the management of hypertrophic nonunions and to evaluate the complications that are commonly reported in the literature. Methods:. We searched for articles pertaining to the treatment of hypertrophic nonunion using distraction osteogenesis. Several electronic bibliographic databases and clinical trial registries were searched using the MeSH terms “hypertrophic non-union,” “distraction osteogenesis,” “stiff non-union,” and “External Fixation” in various combinations to return the maximal number of studies for review. We performed a systematic review and identified a total of 11 studies eligible for review. Results:. The review of the literature demonstrated that this technique is highly effective in achieving bony union with minimal complications. The most common complication is mild superficial pin site infections, usually managed with oral antibiotics and effective wound hygiene. Other complications reported were deep pin tract infections, broken hardware, and deformity recurrence due to collapse of regenerate bone. Conclusion:. The use of distraction osteogenesis with external fixator devices is an effective and safe method for producing bony union in hypertrophic nonunions. There were minimal associated complications.

Background A high minute ventilation/rate of carbon dioxide production (V̇E/V̇co2) slope during exercise is prognostic for cardiovascular death. Recent data indicate that adults with either controlled or untreated primary hypertension, but not those with uncontrolled hypertension, exhibit a higher V̇E/V̇co2 slope during exercise. However, the sample sizes were modest. Therefore, we used the Fitness Registry and the Importance of Exercise National Database to determine whether adults with hypertension, particularly those with controlled or untreated hypertension, exhibit higher V̇E/V̇co2 slopes compared with adults without hypertension. Methods and Results Using the Fitness Registry and the Importance of Exercise National Database, we isolated primary hypertension by excluding those with any disease other than hypertension or taking any medications other than antihypertension medications. We also excluded current smokers and those with obesity. The V̇E/V̇co2 slope was determined during a peak cycling exercise test. All data are presented as median [interquartile range]. We compared groups using linear regression adjusted for age, male/female, and body mass index. The characteristics of the entire sample (n=4109) were age, 42 [18] years; 48% women; body mass index, 26 [4] kg/m2. The V̇E/V̇co2 slope did not differ between adults with hypertension (n=1940; 24.7 [3.7]) compared with those without hypertension (n=2169; 24.9 [3.8]) (hypertension versus no hypertension, P=0.31; overall model: R2=0.07, F4,4104=73.0; P

Abstract With the diversity of lipid-protein interactions, any observed membrane protein dynamics or functions directly depend on the lipid bilayer selection. However, the implications of lipid bilayer choice are seldom considered unless characteristic lipid-protein interactions have been previously reported. Using molecular dynamics simulation, we characterize the effects of membrane embedding on plant aquaporin SoPIP2;1, which has no reported high-affinity lipid interactions. The regulatory impacts of a realistic lipid bilayer, and nine different homogeneous bilayers, on varying SoPIP2;1 dynamics are examined. We demonstrate that SoPIP2;1’s structure, thermodynamics, kinetics, and water transport are altered as a function of each membrane construct’s ensemble properties. Notably, the realistic bilayer provides stabilization of non-functional SoPIP2;1 metastable states. Hydrophobic mismatch and lipid order parameter calculations further explain how lipid ensemble properties manipulate SoPIP2;1 behavior. Our results illustrate the importance of careful bilayer selection when studying membrane proteins. To this end, we advise cautionary measures when performing membrane protein molecular dynamics simulations.

Abstract The human gastrointestinal microbiota and its unique metabolites regulate a diverse array of physiological processes with substantial implications for human health and performance. Chronic exercise training positively modulates the gut microbiota and its metabolic output. The benefits of chronic exercise for the gut microbiota may be influenced by acute changes in microbial community structure and function that follow a single exercise bout (i.e., acute exercise). Thus, an improved understanding of changes in the gut microbiota that occur with acute exercise could aid in the development of evidence‐based exercise training strategies to target the gut microbiota more effectively. In this review, we provide a comprehensive summary of the existing literature on the acute and very short‐term (

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.

Although higher education scholars have examined chaplaincy in college and university settings, we are not aware of any studies that have sought to examine chaplains who live and serve in residence halls. As such, we conducted a collective case study of three Protestant institutions with residential chaplain roles--Taylor University, Pepperdine University, and Baylor University. We present an overview of each institutional model employed for residential chaplains and provide comparative analysis. All of the models we analyzed utilized students as residential chaplains, provided joint residence life and spiritual life training, navigated tensions with other roles in the institution, and took advantage of institution-specific resources and contexts. However, these roles had slightly different foci, used students of different academic levels, and were compensated in different ways. In light of our findings, we believe institutions without residential chaplains should see potential options for incorporating such a role into their campus structure, and those who already have residential chaplains should continue thinking about the structure, strengths, and benefits of their current models.

Emotion recognition application programming interface (API) is a recent advancement in computing technology that synthesizes computer vision, machine-learning algorithms, deep-learning neural networks, and other information to detect and label human emotions. The strongest iterations of this technology are produced by technology giants with large, cloud infrastructure (i.e., Google, and Microsoft), bolstering high true positive rates. We review the current status of applications of emotion recognition API in psychological research and find that, despite evidence of spatial, age, and race bias effects, API is improving the accessibility of clinical and educational research. Specifically, emotion detection software can assist individuals with emotion-related deficits (e.g., Autism Spectrum Disorder, Attention Deficit-Hyperactivity Disorder, Alexithymia). API has been incorporated in various computer-assisted interventions for Autism, where it has been used to diagnose, train, and monitor emotional responses to one's environment. We identify AP's potential to enhance interventions in other emotional dysfunction populations and to address various professional needs. Future work should aim to address the bias limitations of API software and expand its utility in subfields of clinical, educational, neurocognitive, and industrial-organizational psychology.

"U.S. News and World Report's" "Best Law Schools" dominate the conversation on quality in legal education. Despite their popularity, the criteria used to rank schools often has little to do with the quality of the educational experience. If rankings are intended to demonstrate quality, then these measures should be related with other measures of collegiate quality, such as student engagement. This study investigated the relationship between law school rankings and student engagement using data from the Law School Survey of Student Engagement. Findings reveal no relationship between ranking and engagement, except for a small, positive relationship between ranking and satisfaction.