bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered resting-state functional connectivity in hiPSC-derived neuronal networks from schizophrenia patients
Authors: Puvogel Sofía , Blanchard Kris , Casas Bárbara S. , Miller Robyn , Garrido Delia , Sanhueza Magdalena , Palma Verónica 
Published: August 2021

ABSTRACTSchizophrenia (SZ) is a complex mental disease thought to arise from abnormal neurodevelopment, characterized by an altered reality perception and widely associated with brain connectivity anomalies. Previous work has shown disrupted resting-state brain functional connectivity (FC) in SZ patients. We used Human Induced Pluripotent Stem Cells (hiPSC)-derived neuronal cultures to study SZ’s neural communicational dynamics during early development. We conducted gene and protein expression profiling, calcium imaging and mathematical modeling to evaluate FC. Along the neurodifferentiation process, SZ networks displayed altered expression of genes related to synaptic function, cell migration and cytoskeleton organization, suggesting alterations in excitatory/inhibitory balance. Resting-state FC in neuronal networks derived from healthy controls (HC) and SZ patients emerged as a dynamic phenomenon exhibiting “hub-states”, which are connectivity configurations reoccurring in time. Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub-states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our observations at a single cell resolution may reflect intrinsic dynamical principles ruling brain activity at rest and highlight the relevance of identifying multiscale connectivity properties between functional brain units. We propose that FC alterations in SZ patients are a consequence of an abnormal early development of synaptic communication dynamics, compromising network’s ability for rapid and efficient reorganization of neuronal activity patterns. Remarkably, these findings mirror resting-state brain FC in SZ patients, laying the groundwork for future studies among such different spatiotemporal domains, as are brains and neurons, in both health and disease.
Behavioural barriers to COVID-19 testing in Australia: Two national surveys to identify barriers and estimate prevalence by health literacy level
Authors: Bonner Carissa , Batcup Carys , Ayre Julie , Pickles Kristen , Cvejic Erin , Copp Tessa , Cornell Samuel , Dodd Rachael , Isautier Jennifer , Nickel Brooke , McCaffery Kirsten 
Published: August 2021

ABSTRACTBackgroundCOVID-19 testing and contact tracing has been crucial in Australia’s prevention strategy. However, testing for COVID-19 is far from optimal, and behavioural barriers are unknown. Study 1 aimed to identify the range of barriers to testing. Study 2 aimed to estimate prevalence in a nationally relevant sample to target interventions.MethodsStudy 1: National longitudinal COVID-19 survey from April-November 2020. Testing barriers were included in the June survey (n=1369). Open responses were coded using the COM-B framework (capability-opportunity-motivation). Study 2: Barriers from Study 1 were presented to a new nationally representative sample in November to estimate prevalence (n=2869). Barrier prevalence was analysed by health literacy level using Chi square tests.ResultsStudy 1: 49% strongly agreed to get tested for symptoms, and 69% would self-isolate. Concern about pain was the top barrier from a provided list (11%), but 32 additional barriers were identified from open responses and coded to the COM-B framework. Study 2: The most prevalent barriers were motivation issues (e.g. don’t believe symptoms are COVID-19: 28%, few local cases: 18%). Capability issues were also common (e.g. not sure symptoms are bad enough: 19%, not sure whether symptoms need testing: 15%). Many barriers were more prevalent amongst people with low compared to high health literacy, including motivation (preference to self isolate: 21% vs 12%, pain: 15% vs 9%) and capability (not sure symptom needs testing: 12% vs 8%, not sure how to test:11% vs 4%).ConclusionEven in a health system with free and widespread access to COVID-19 testing, motivation and capability barriers were prevalent issues, particularly for people with lower health literacy. This study highlights the important of diagnosing behaviour barriers to target public health interventions for COVID-19 and future pandemics.
Racial discrimination, low trust in the health system, and COVID-19 vaccine uptake: a longitudinal observational study of 633 UK adults from ethnic minority groups
Authors: Paul Elise , Fancourt Daisy , Razai Mohammad 
Published: August 2021

AbstractObjectiveTo examine whether racial/ethnic discrimination predicts future COVID-19 vaccine refusal, and whether this association is explained by trust in government and the health system.DesignLongitudinal observational study of racial/ethnic discrimination occurring since the start of the first lockdown (measured in July 2020) and later COVID-19 vaccine status.SettingUK (England, Scotland, Wales, and Northern Ireland)Participants633 adults belonging to ethnic minority groups who took part in the UCL COVID-19 Social Study.Main outcome measureCOVID-19 vaccine refusal (vs accepted/waiting/had at least one dose) between 23 December 2020 and 14 June 2021.ResultsNearly one in ten (6.7%) who had refused a COVID-19 vaccine had experienced racial/ethnic discrimination in a medical setting since the start of the pandemic and had experienced twice as many incidents of racial/ethnic discrimination than those who had accepted the vaccine. Structural equation modelling results indicated a nearly 4-fold (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.4 to 10.9) total effect of racial/ethnic discrimination on refusing the vaccine was which was mediated by low trust in the health system to handle the pandemic (OR = 2.5, 95% CI = 1.1 to 5.4). Analyses adjusted for a range of demographic and COVID-19 related factors.ConclusionsFindings underscore the importance of addressing racial/ethnic discrimination and the role the National Health Service in regaining trust from ethnic minority groups to increase COVID-19 vaccine uptake amongst ethnic minority adults.
A Learning Health System Approach to the COVID-19 Pandemic: System-Wide Changes in Clinical Practice and 30-Day Mortality Among Hospitalized Patients
Authors: McCreary Erin K. , Kip Kevin E. , Bariola J. Ryan , Schmidhofer Mark , Minnier Tami , Mayak Katelyn , Albin Debbie , Daley Jessica , Linstrum Kelsey , Hernandez Erik , Sackrowitz Rachel , Hughes Kailey , Horvat Christopher , Snyder Graham M. , McVerry Bryan J. , Yealy Donald M. , Huang David T. , Angus Derek C. , Marroquin Oscar C. 
Published: August 2021

ABSTRACTIntroductionRapid, continuous implementation of credible scientific findings and regulatory approvals is often slow in large, diverse health systems. The COVID-19 pandemic created a new threat to this common “slow to learn and adapt” model in healthcare. We describe how UPMC committed to a rapid learning health system (LHS) model to respond to the COVID-19 pandemic.MethodsAn observational cohort study was conducted among 11,429 hospitalized patients from 22 hospitals (PA, NY) with a primary diagnosis of COVID-19 infection (March 19, 2020 – June 6, 2021). Sociodemographic and clinical data were captured from UPMC electronic medical record (EMR) systems. Patients were grouped into four time-defined patient “waves” based on nadir of daily hospital admissions, with wave 3 (September 20, 2020 – March 10, 2021) split at its zenith due to high volume with steep acceleration and deceleration. Outcomes included changes in clinical practice (e.g., use of corticosteroids, antivirals, and other therapies) in relation to timing of internal system analyses, scientific publications, and regulatory approvals, along with 30-day rate of mortality over time.ResultsMean (SD) daily number of hospital admissions was 26 (28) with a maximum 7-day moving average of 107 patients. System-wide implementation of the use of dexamethasone, remdesivir, and tocilizumab occurred within days of release of corresponding seminal publications and regulatory actions. After adjustment for differences in patient clinical profiles over time, each month of hospital admission was associated with an estimated 5% lower odds of 30-day mortality (adjusted OR = 0.95, 95% confidence interval: 0.92 – 0.97, p < .001).ConclusionsIn our large LHS, near real-time changes in clinical management of COVID-19 patients happened promptly as scientific publications and regulatory approvals occurred throughout the pandemic. Alongside these changes, patients with COVID-19 experienced lower adjusted 30-day mortality following hospital admission over time.
Assessing the impact of community-based interventions on hypertension and diabetes management in three Minnesota communities: findings from the prospective evaluation of US HealthRise programs
Authors: Fullman Nancy , Cowling Krycia , Flor Luisa S , Wilson Shelley , Bhatt Paurvi , Bryant Miranda F , Camarda Joseph N , Colombara Danny V , Daly Jessica , Gabert Rose K , Harris Katie Panhorst , Johanns Casey K , Mandile Charlie , Marshall Susan , McNellan Claire R , Mulakaluri Vasudha , Phillips Bryan K , Reitsma Marissa B , Sadighi Naomi , Tamene Tsega , Thomson Blake , Wollum Alexandra , Gakidou Emmanuela 
Published: August 2021

AbstractBackgroundCommunity-based health interventions are increasingly viewed as models of care that can bridge healthcare gaps experienced by underserved communities in the United States (US). With this study, we sought to assess the impact of such interventions, as implemented through the US HealthRise program, on hypertension and diabetes among underserved communities in Hennepin, Ramsey, and Rice Counties, Minnesota.Methods and findingsHealthRise patient data from June 2016 to October 2018 were assessed relative to comparison patients in a difference-in-difference analysis, quantifying program impact on reducing systolic blood pressure (SBP) and hemoglobin A1c, as well as meeting clinical targets (< 140 mmHg for hypertension, < 8% Al1c for diabetes), beyond routine care. For hypertension, HealthRise participation was associated with SBP reductions in Rice (6.9 mmHg [95% confidence interval: 0.9–12.9]) and higher clinical target achievement in Hennepin (27.3 percentage-points [9.8–44.9]) and Rice (17.1 percentage-points [0.9 to 33.3]). For diabetes, HealthRise was associated with A1c decreases in Ramsey (1.3 [0.4–2.2]). Qualitative data showed the value of home visits alongside clinic-based services; however, challenges remained, including community health worker retention and program sustainability.ConclusionsHealthRise participation had positive effects on improving hypertension and diabetes outcomes at some sites. While community-based health programs can help bridge healthcare gaps, they alone cannot fully address structural inequalities experienced by many underserved communities.
Socioeconomic and comorbid factors affecting mortality and length of stay in COVID-19
Authors: Delora Adam V. , Mills Ashlynn , Jacobson David , Cornett Brendon , Peacock W. Frank , Datta Anita , Jenks Shane 
Published: August 2021

AbstractBackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic exposed and exacerbated health disparities between socioeconomic groups. Our purpose was to determine which disparities are most prevalent and their impact on length of stay (LoS) and in hospital mortality in patients diagnosed with Covid-19.MethodsDe-Identified data for patients who tested positive for COVID-19 was abstracted from the HCA enterprise database. Data was binned into summary tables. A negative binomial regression with LoS as the dependent variable and a logistic regression of in-hospital mortality data, using age, insurance status, sex, comorbidities as the dependent variables, were performed.ResultsFrom March 1, 2020 to August 23, 2020, of 111,849 covid testing patient records, excluding those with missing data (n=7), without confirmed COVID-19 (n=27,225), and those from a carceral environment (n=1,861), left 84,624 eligible patients. Compared to the US population, the covid cohort had more black patients (23.17% vs 13.4%). Compared to the white cohort, the black cohort had higher private insurance rates (28.52% vs. 23.68%), shorter LoS (IRR=0.97 CI=0.95-0.99, P<0.01) and lower adjusted mortality (OR 0.81, 95% CI 0.75-0.97). Increasing age was associated with increased mortality and LoS. Patients with Medicare or Medicaid had longer LoS (IRR=1.07, 95% CI=1.04-1.09) and higher adjusted mortality rates (OR=1.11, 95% CI=1-1.23) than those with private insuranceConclusionConclusions We found that when blacks have higher rates of private insurance, they have shorter hospitalizations and lower mortality than whites, when diagnosed with Covid-19. Some other psychiatric and medical conditions also significantly impacted outcomes in patients with Covid-19.Key PointsQuestionWhich social determinants of health and comorbidities are most prevalent and their impact on length of stay and in-hospital mortality in patients diagnosed with Covid-19?FindingsIn this retrospective cohort of 84,624 with the black cohort having higher private insurance rates (28.52% vs. 23.68%), there was shorter LoS (IRR=0.97 CI=0.95-0.99, P<0.01) and lower adjusted mortality (OR 0.81, 95% CI 0.75-0.97). Age and several other medical and psychiatric comorbidities were also found to correlate with length of stay and mortality.MeaningThe genetics of race is not important in predicting mortality and length of stay in COVID-19 patients, but age, comorbidities, and insurance status appear to have a significant difference in mortality and length of stay.
Predicting and measuring decision rules for social recognition in a Neotropical frog
Authors: Tumulty James P. , Fouilloux Chloe A. , Vallejos Johana Goyes , Bee Mark A. 
Published: August 2021

AbstractMany animals use signals, such as vocalizations, to recognize familiar individuals. However, animals risk making recognition mistakes because the signal properties of different individuals often overlap due to within-individual variation in signal production. To understand the relationship between signal variation and decision rules for social recognition, we studied male golden rocket frogs, which recognize the calls of territory neighbors and respond less aggressively to a neighbor’s calls than to the calls of strangers. We quantified patterns of individual variation in acoustic properties of calls and predicted optimal discrimination thresholds using a signal detection theory model of receiver utility that incorporated signal variation, the payoffs of correct and incorrect decisions, and the rates of encounters with neighbors and strangers. We then experimentally determined thresholds for discriminating between neighbors and strangers using a habituation-discrimination experiment with territorial males in the field. Males required a threshold difference between 9% and 12% to discriminate between calls differing in temporal properties; this threshold matched those predicted by a signal detection theory model under ecologically realistic assumptions of infrequent encounters with strangers and relatively costly missed detections of strangers. We demonstrate empirically that receivers group continuous variation in vocalizations into discrete social categories and show that signal detection theory can be applied to investigate evolved decision rules.
Transcriptomic mapping of the inter-individual variability of cellular stress response activation in primary human hepatocytes
Authors: Niemeijer Marije , Wiecek Witold , Huppelschoten Suzanna , Bouwman Peter , Baze Audrey , Parmentier Céline , Richert Lysiane , Paules Richard S. , Bois Frederic Y. , van de Water Bob 
Published: August 2021

AbstractBackground & AimsOne of the early key events of drug-induced liver injury (DILI) is the activation of adaptive stress responses, a cellular mechanism to overcome stress. Given the diversity of DILI outcomes and lack in understanding of population variability, we mapped the inter-individual variability in stress response activation to improve DILI prediction.Approach & ResultsHigh-throughput transcriptome analysis of over 8,000 samples was performed in primary human hepatocytes of 50 individuals upon 8 to 24 h exposure to broad concentration ranges of stress inducers: tunicamycin to induce the unfolded protein response (UPR), diethyl maleate for the oxidative stress response, cisplatin for the DNA damage response and TNFα for NF-κB signalling. This allowed investigation of the inter-individual variability in concentration-dependent stress response activation, where the average of benchmark concentrations (BMCs) had a maximum difference of 864, 13, 13 and 259-fold between different hepatocytes for UPR, oxidative stress, DNA damage and NF-κB signalling-related genes, respectively. Hepatocytes from patients with liver disease resulted in less stress response activation. Using a population mixed-effect framework, the distribution of BMCs and maximum fold change were modelled, allowing simulation of smaller or larger PHH panel sizes. Small panel sizes systematically under-estimated the variance and resulted in low probabilities in estimating the correct variance for the human population. Moreover, estimated toxicodynamic variability factors were up to 2-fold higher than the standard uncertainty factor of 101/2 to account for population variability during risk assessment, exemplifying the need of data-driven variability factors.ConclusionsOverall, by combining high-throughput transcriptome analysis and population modelling, improved understanding of variability in stress response activation across the human population could be established, thereby contributing towards improved prediction of DILI.
Spatial phylogenetics of Japanese ferns: Patterns, processes, and implications for conservation
Authors: Nitta Joel H. , Mishler Brent D. , Iwasaki Wataru , Ebihara Atsushi 
Published: August 2021

AbstractPremiseBiodiversity is often only measured with species richness. However, this ignores evolutionary history and is not sufficient for making conservation decisions. Here, we characterize multiple facets and drivers of biodiversity to understand how these relate to bioregions and conservation status in the ferns of Japan.MethodsWe compiled a community dataset of 1,239 20 km × 20 km grid-cells including 672 taxa based on > 300,000 specimen records. We combined this with a phylogeny and functional traits to analyze taxonomic, phylogenetic, and functional diversity, and modeled biodiversity metrics in response to environmental factors and reproductive mode. Hierarchical clustering was used to delimit bioregions. Conservation status and threats were assessed by comparing the overlap of significantly diverse grid-cells with conservation zones and range maps of native Japanese deer.ResultsTaxonomic richness was highest at mid-latitudes. Phylogenetic and functional diversity and phylogenetic endemism were highest in small southern islands. Relative phylogenetic and functional diversity were high at high and low latitudes, and low at mid-latitudes. Grid-cells were grouped into three (phylogenetic) or four (taxonomic) major bioregions. Temperature and apomixis were identified as drivers of biodiversity patterns. Conservation status was generally high for grid-cells with significantly high biodiversity, but the threat due to herbivory by deer was greater for taxonomic richness than other metrics.ConclusionsOur integrative approach reveals previously undetected patterns and drivers of biodiversity in the ferns of Japan. Future conservation efforts should recognize that threats can vary by biodiversity metric and consider multiple multiple metrics when establishing conservation priorities.
Goal-Dependent Hippocampal Representations Facilitate Self-Control
Authors: Edelson Micah G. , Hare Todd A. 
Published: August 2021

AbstractMnemonic influences on decision-making processes are important for linking past experiences and simulations of the future with current goals. The ways in which mnemonic information is represented may be especially critical in situations where one needs to overcome past rewarding experiences and exert self-control. We propose that self-control success or failure may depend on how information is retrieved from memory and how effectively this memory retrieval process can be modified to achieve a specific goal. We test our hypothesis using representational similarity analyses of human neuroimaging data during a dietary self-control task in which individuals must overcome taste temptations to choose healthy foods. We find that self-control is indeed associated with the way individuals represent taste information in the brain and how taste representations adapt to align with different goals. These results provide new insights into the processes leading to self-control success and indicate the need to update the classical view of self-control to continue to advance our understanding of its behavioral and neural underpinnings.
NKG2D signaling regulates IL-17A-producing γδT cells to promote cancer progression
Authors: Curio Sophie , Edwards Sarah C. , Suzuki Toshiyasu , McGovern Jenny , Triulzi Chiara , Yoshida Nagisa , Jonsson Gustav , Glauner Teresa , Rami Damiano , Purcell Rachel Violet , Coffelt Seth B. , Guerra Nadia 
Published: August 2021

AbstractγδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance and homeostasis. γδT cell activation is mediated by the T cell receptor composed of γ and δ chains, as well as activating receptors for stress-induced ligands, such as NKG2D. Contrary to the well-established anti-tumor function of γδT cells, recent studies have shown that γδT cells can promote tumor development in certain contexts. However, the mechanisms leading to this diseasepromoting role remain poorly understood. Here, we show that mice lacking γδT cells survive longer in a mouse model of intestinal cancer, further supporting their pro-tumoral role. In a surprising conceptual twist, we found that these pro-tumor γδT cells are regulated by NKG2D signaling, a receptor normally associated with cancer cell killing. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduces the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increases the frequency of γδT cells. Together, these data support the hypothesis that in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.