bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversible inhibition of GluN2B-containing NMDA receptors with anin situred-shifted, photoswitchable antagonist
Authors: Geoffroy Chloé , Berraud-Pache Romain , Chéron Nicolas , McCort-Tranchepain Isabelle , Paoletti Pierre , Mony Laetitia 
Published: October 2023

AbstractNMDA receptors (NMDARs) are glutamate-gated ion channels playing a central role in synaptic transmission and plasticity. Dysregulation of NMDARs is linked to various neuropsychiatric disorders, emphasizing the need to understand the functional roles of individual NMDAR subtypes in the brain. GluN2B-containing NMDARs (GluN2B-NMDARs) are particularly important due to both pro-cognitive and pro-excitotoxic roles, although these functions remain under debate. Traditional pharmacological and genetic approaches have important shortcomings in terms of specificity and spatio-temporal resolution, limiting their use in native tissues. We therefore turned to optopharmacology, a technique based on the use of photosensitive ligands, whose activity can be reversibly tuned via illumination with different wavelengths. We developed OptoNAM-3, an azobenzene-based, photoswitchable negative allosteric modulator selective for GluN2B-NMDARs. OptoNAM-3 is a potent inhibitor of GluN2B-NMDARs in itstransconfiguration and inactive in itscisconfiguration. When bound to GluN2B-NMDARs, OptoNAM-3 displays remarkable red-shifting of its photoswitching properties that we attributed to geometric constraints imposed by the binding site onto the ligand azobenzene moiety. OptoNAM-3 allowed fast and reversible photomodulation of GluN2B-NMDAR activityin vitrousing either UV/green or blue/green light illumination cycles. OptoNAM-3 furthermore acted as a reversible, red-shiftedin vivophotomodulator of Xenopus tadpole locomotion. By enabling fast and reversible photocontrol of endogenous GluN2B-NMDARs within vivocompatible photochemical properties, OptoNAM-3 should advance our understanding of the role of this class of NMDARs in brain function and dysfunction.Significance statementThis article presents the development and characterization of a photoswitchable negative allosteric modulator (NAM) targeting GluN2B-containing NMDA receptors (GluN2B-NMDARs). Traditional GluN2B-selective NAMs suffer from slow kinetics and irreversible effects, limiting their use in native tissues. OptoNAM-3 emerged as a potent and selective inhibitor of GluN2B-NMDARs, exhibiting fast temporal resolution of action and reversibility bothin vitroandin vivo. OptoNAM-3 furthermore exhibited different spectral properties when in solution or bound to its target, thus behaving as anin situ“red-shifted” photodependent antagonist with improvedin vivocompatibility. This study therefore provides a valuable photoswitchable tool for precise control of NMDAR activity in native tissues. It furthermore reveals the importance of the protein environment on the spectral properties of photosensitive molecules.
Analysis of Social Determinants of Hypertension Outcomes among Asian Americans in Los Angeles
Authors: Yu Megan R. , Liu Haoyuan , Kung Madyllen , Tran Caitlyn , Mitra Shameek , Dang Preston , Woo Benjamin K. 
Published: October 2023

AbstractAsian Americans are a diverse and significant group within the United States and encompass a wide range of social demographics. Research on social determinants of hypertension within this population is limited, despite a notable burden of illness. Asian American attendees at health fairs held in Monterey Park and Rosemead, California in Los Angeles County were surveyed on various social demographics and screened for presence of hypertension outcomes. Logistic regression modeling was employed to determine major demographic contributors to the prevalence of prehypertensive or higher outcomes, ultimately finding that health fair location was a significant predictor (OR: 3.41; 95% CI: 1.54, 7.58; P-Value: 0.003). Further analysis of only attendees exhibiting prehypertensive or higher outcomes showed a significant distribution in the conditional distribution of education levels between Monterey Park and Rosemead attendees. Study findings uncover further areas for research into both Asian American and Chinese American populations and contribute to an overall gap in research within these demographic groups.
Socioeconomic inequalities in COVID-19 infection and vaccine uptake among children and adolescents in Catalonia, Spain
Authors: López-Sánchez Irene , Perramon Aida , Soriano-Arandes Antoni , Prats Clara , Duarte-Salles Talita , Raventós Berta , Roel Elena 
Published: October 2023

AbstractIMPORTANCEThe relationship between socioeconomic deprivation and COVID-19 infection and vaccination among children and adolescents remains unclear.OBJECTIVETo investigate the association between deprivation and COVID-19 vaccine uptake and infection among children and adolescents before and after the vaccination rollout in Catalonia, Spain.DESIGN AND SETTINGPopulation-based cohort study using primary care electronic health records from the Information System for Research in Primary Care. Individuals were followed 3 months before the start of the vaccination campaign in Spain and 3 months after the vaccination rollout among adolescents and children.PARTICIPANTSChildren (5-11 years) and adolescents (12-15 years) with at least 1 year of prior history observation available and without missing deprivation data.EXPOSUREDeprivation, assessed using an ecological socioeconomic deprivation index (SDI) score for census tract urban areas and categorized into quintiles.MAIN OUTCOMES AND MEASURESCOVID-19 infection and COVID-19 vaccination. For each outcome, we calculated cumulative incidence and crude Cox proportional-hazard models by SDI quintiles, and estimated hazard ratios (HRs) of COVID-19 infection and vaccine uptake relative to the least deprived quintile, Q1.RESULTSBefore COVID-19 vaccination rollout, 290,625 children and 179,685 adolescents were analyzed. Increased HR of deprivation was associated with a higher risk of COVID-19 infection in both children (Q5: 1.55 [95% CI, 1.47 - 1.63]) and adolescents (Q5: 1.36 [95% CI, 1.29 - 1.43]). After the rollout, this pattern changed among children, with lower risk of infection in more deprived areas (Q5: 0.62 [95% CI, 0.61 - 0.64]). Vaccine uptake was higher among adolescents (72.6%) than children (44.8%), but in both age groups, non-vaccination was more common among those living in more deprived areas (39.3% and 74.6% in Q1 vs. 26.5% and 66.9% in Q5 among children and adolescents, respectively).CONCLUSIONS AND RELEVANCEIn this cohort study, children and adolescents living in deprived areas were at higher risk of COVID-19 non-vaccination. Socioeconomic disparities in COVID-19 infection were also evident before vaccine rollout, with a higher infection risk in deprived areas across age groups. Our findings suggest that changes in the association between deprivation and infections among children after the vaccine rollout were likely due to testing disparities.
HIV prevalence and associated factors among adolescent boys and young men in South Africa, 2017
Authors: Makusha Tawanda , Mabaso Musawenkosi , Zungu Nompumelelo , Moyo Sizulu , Naidoo Inbarani , Jooste Sean , Mohapanele Karabo , Zuma Khangelani , Simbayi Leickness 
Published: October 2023

AbstractIntroductionIn South Africa, current epidemic control efforts include strategies to reach all young people and leave no one behind. Hence there is a need to track HIV among adolescent boys and young men (ABYM) to support these efforts. We examined HIV prevalence and associated factors among ABYM aged 15-24 years using the 2017 South African National HIV Prevalence, Incidence, Behaviour, and Communication Survey.MethodsThe cross-sectional survey used a multi-stage stratified cluster randomised sample. Descriptive statistics were used to characterise HIV prevalence among ABYM. Multivariate backward stepwise logistic regression was used to determine factors associated with HIV prevalence.ResultsA total of 4792 ABYM aged 15-24 years were interviewed of whom 4.01% [95% CI: 3.28-4.90] were HIV positive, translating to 255 366 ABYM living with HIV in the country in 2017. The odds of being HIV positive were significantly lower among ABYM with tertiary education level (AOR=0.06 [95% CI 0.01-0.50], p=0.009, employed (AOR=0.34 [95% CI: 0.14-0.81], p=0.015), and those who had tested and were aware of their HIV status (AOR=0.29 [95% CI: 0.10-0.83], p=0.015).ConclusionThese findings suggest that ABYM with low educational attainment and those unemployed need to be reached with sexual and reproductive health interventions, including the promotion of uptake of HIV testing and awareness for this population group.
The SHOW COVID-19 cohort: methods and rationale for examining the statewide impact of COVID-19 on the social determinants of health
Authors: Schultz Amy A. , Nelson-Bakkum Erin , Nikodemova Maria , Luongo Sarah , Barnet Jodi H , Walsh Matthew C. , Bersch Andrew , Cadmus-Bertram Lisa , Engelman Corinne D. , Lubsen Julia , Peppard Paul , Sethi Ajay , Malecki Kristen MC 
Published: October 2023

AbstractBackgroundNational and large city mortality and morbidity data emerged during the early years of the COVID-19 pandemic, yet statewide data to assess the impact COVID-19 had across urban and rural landscapes on subpopulations was lacking. The SHOW COVID-19 cohort was established to provide descriptive and longitudinal data to examine the influence the social determinants of health had on COVID-19 related outcomes.MethodsParticipants were recruited from the 5,742 adults in the Survey of the Health of Wisconsin (SHOW) cohort who were all residents of Wisconsin, United States when they joined the cohort between 2008-2019. Online surveys were administered at three timepoints during 2020-2021. Survey topics included COVID-19 exposure, testing and vaccination, COVID-19 impact on economic wellbeing, healthcare access, mental and emotional health, caregiving, diet, lifestyle behaviors, social cohesion, and resilience.ResultsA total of 2,304 adults completed at least one COVID-19 online survey, with n=1,090 completing all three survey timepoints. Non-Whites were 2-3 times more likely to report having had COVID-19 compared to Whites, females were more likely than males to experience disruptions in their employment, and those with children in the home were more likely to report moderate to high levels of stress compared to adults without children.ConclusionLongitudinal, statewide cohorts are important for investigating how the social determinants of health affect people’s lives, health, and well-being during the first years of a pandemic and offer insight into future pandemic preparation. The data are available for researchers and cohort is active for continued and future follow-up.Key MessagesMortality and morbidity data emerged during the early years of the COVID-19 pandemic at the national scale and in large cities, yet comprehensive social, cultural, and economic population-level data at the state level was lacking for identifying sub-population trends.COVID-19 disrupted lives and affected people differently based on socio-economic status, demographics, family dynamics, geography, health status, and employment.SHOW COVID-19 cohort is a unique non-clinical, non-hospital-based sample with pre-COVID-19 baseline survey data and biospecimen and three waves of COVID-19 data and specimen available to examine effects of COVID-19 on the social determinants of health.
Can diffuse reflectance spectroscopy identify shuntodynia in pediatric hydrocephalus patients?
Authors: Kline Olivia , Vishwanath Karthik , Colbrunn Boyd , Peachman Andrew , Zhang Jing , Vadivelu Sudhakar 
Published: October 2023

AbstractSignificanceShuntodynia is patient reported pain at the site of the implanted ventriculo-peritoneal (VP) shunt. Pediatric hydrocephalus requiring shunt placement is a chronic and prevalent standard of care treatment and requiring lifetime management. Shuntodynia is a subjective measure of shunt dysfunction. Quantitative, white-light tissue spectroscopy could be used to objectively identify this condition in the clinic.AimPediatric subjects were recruited for optical sensing during routine clinical follow-up visits, post VP shunt implantations. Acquired optical signals were translated into skin-hemodynamic signatures and were compared between subjects that reported shuntodynia vs. those that did not.ApproachDiffuse reflectance spectroscopy (DRS) measurements were collected between 450-700 nm using a single-channel fiber-optical probe from (N=35) patients. Multiple reflectance spectra were obtained by the attending physician from regions both proximal and distal to the VP shunt sites, and from a matched contralateral site for each subject. Acquired reflectance spectra were processed quantitatively into functional tissue optical endpoints. A two- way, repeated measures analysis of variance (ANOVA) was used to assess whether and which of the optical variables were statistically separable, across subjects with shuntodynia vs. those without.ResultsResults showed that vascular oxygen saturation was significantly lower in subjects reporting shuntodynia, when measured proximal to shunt sites. Subjects with shuntodynia also had lower total hemoglobin at the shunt site relative to distal sites. Both patient groups showed higher tissue scattering at the shunt sites in comparison to the contralateral sites.ConclusionsOptically derived hemodynamic variables were statistically significantly different in subjects presenting with shuntodynia relative to those without. DRS could provide a viable mode in routine bedside monitoring of subjects with VP shunts for clinical management and risk assessment of shuntodynia.
HAI-VECT(SCD): AI-Humanoid Enabled Virtual Clinical Trial for Sickle Cell Disease
Authors: Danter WR 
Published: October 2023

AbstractBackgroundSickle Cell Disease (SCD) remains a globally important disorder with limited therapeutic options. This study utilizes the advanced capabilities of the DeepNEU© platform v8.2 and aiHumanoid (Pat. Pend.) simulations to evaluate potential drug combinations for treating SCD, focusing on vaso-occlusive events (VOE) and associated secondary outcomes.MethodsUsing data from 25 virtual patients in each of six treatment groups, therapeutic responses to each treatment were investigated. The study evaluated the primary outcome of VOE and secondary outcomes, including HbA, HbF, Quality of Life (QoL), RBC hemolysis, and Pain. Treatment toxicities were also assessed across all dosage levels.ResultsThe combination of Endari (L-glutamine powder) plus Crizanlizumab (a P-selectin antibody) demonstrated superior efficacy, with significant improvements in primary and secondary endpoints. This regimen, along with Voxelotor (a hemoglobin S polymerization inhibitor) plus Crizanlizumab, showed promising reductions in VOE, RBC hemolysis, and enhanced QoL scores. Notably, these results align with existing literature emphasizing the benefits of combination therapies in SCD management. Furthermore, aiHumanoid simulations indicated that these treatment combinations present lower cumulative multi-organoid toxicity, potentially translating to better patient outcomes and reduced healthcare costs.ConclusionAI-driven virtual clinical trials offer an innovative approach in evaluating drug combinations, presenting a robust case for the efficacy of Endari plus Crizanlizumab in managing SCD. The results warrant further research and real-world trials, potentially reshaping clinical guidelines for SCD treatment.
Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother-child pairs
Authors: Leinonen Jaakko T. ,   FinnGen, Pirinen Matti , Tukiainen Taru 
Published: October 2023

AbstractEpidemiological studies have robustly linked lower birth weight to later-life disease risks. These observations may reflect the adverse impact of intrauterine growth restriction on a child’s health. However, causal evidence supporting such a mechanism in humans is largely lacking.Using Mendelian Randomization and 36,211 genotyped mother-child pairs from the FinnGen study, we assessed the relationship between intrauterine growth restriction and five common health outcomes (coronary heart disease (CHD), hypertension, statin use, type 2 diabetes and cancer). We proxied intrauterine growth restriction with polygenic scores for maternal effects on birth weight and took into account transmission of genetic variants between a mother and a child in the analyses.We find limited evidence for contribution of normal variation in maternally influenced intrauterine growth on later-life disease. Instead, we find support for genetic pleiotropy in the child genome linking birth weight to CHD and hypertension. Our study illustrates the opportunities that data from genotyped parent-child pairs from a population-based biobank provides for addressing causality of maternal influences.
Disease-specific prioritization of non-coding GWAS variants based on chromatin accessibility
Authors: Liang Qianqian , Abraham Abin , Capra John A , Kostka Dennis 
Published: October 2023

AbstractNon-protein-coding genetic variants are a major driver of the genetic risk for human disease; however, identifying which non-coding variants contribute to which diseases, and their mechanisms, remains challenging. In-silico variant prioritization methods quantify a variant’s severity in the context of having a phenotypic effect; but for most methods the specific phenotype and disease context of the prediction are poorly defined. For example, many commonly used methods provide a single organism-wide score for each variant, while other methods summarize a variant’s impact specifically in certain tissues and/or cell-types. Here we propose a complementary disease-specific variant prioritization scheme, which is motivated by the observation that the variants contributing to different diseases often operate through different biological mechanisms.We combine tissue/cell-type specific scores into disease-specific scores with a logistic regression approach and apply it to 25,000 non-coding variants spanning 111 diseases. We show that disease-specific aggregation of tissue/cell-type specific scores (GenoSkyline, Fit-Cons2, DNA accessibility) signifiantly improves the association of common non-coding genetic variants with disease (average precision: 0.151, baseline=0.09), compared with organism-wide scores (GenoCanyon, LINSIGHT, GWAVA, eigen, CADD; average precision: 0.129, base-line=0.09). Calculating disease similari-ties based on data-driven aggregation weights highlights meaningful disease groups (e.g., immune system related diseases and mental/behavioral disorders), and it provides information about tissues and cell-types that drive these similarities (e.g., lymphoblastoid T-cells for immune-system diseases). We also show that so-learned similarities are complementary to genetic similarities as quantified by genetic correlation. Overall, our aggregation approach demonstrates the strengths of disease-specific variant prioritization, leads to improvement in non-coding variant prioritization, and it enables interpretable models that link variants to disease via specific tissues and/or cell-types.
Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022
Authors: Moreira Rodrigo , Bastos Leonardo S , Carvalho Luiz Max , Freitas Laís Picinini , Pacheco Antonio G 
Published: October 2023

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood.MethodsThis study analyzed mortality data from Brazil’s mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models.ResultsBetween 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced.ConclusionThis study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic’s impact on mortality rates.
Partial elimination ofWolbachiain the Asian citrus psyllid,Diaphorina citri, increases phytopathogen acquisition and decreases fitness
Authors: Roldán Erik L. , Stelinski Lukasz , Pelz-Stelinski Kirsten S. 
Published: October 2023

AbstractWolbachiais a maternally inherited intracellular bacterium that infects a wide range of arthropods.Wolbachiacan have a significant impact on host biology and development, often due to its effects on reproduction. We investigatedWolbachiainfection in the Asian citrus psyllid,Diaphorina citri, which transmitsCandidatusLiberibacter asiaticus (CLas), the causal agent of citrus greening disease.D. citriare naturally infected withWolbachia; therefore, investigatingWolbachia-mediated effects onD. citrifitness andCLas transmission required artificial elimination of this endosymbiont with application of doxycycline. Doxycycline treatment of psyllids reducedWolbachiainfection by approximately 60% in both male and femaleD. citri; however, this reduction varied between generations of treated psyllids. Psyllids treated with doxycycline exhibited higherCLas acquisition as both adults and nymphs as compared with negative controls. In addition, doxycycline-treated psyllids exhibited decreased fitness as measured by reduced egg and nymph production as well as adult emergence as compared with controls lines whereWolbachiawas not manipulated. Our results indicate thatWolbachiabenefitsD. citriby improving fitness and potentially competes withCLas by interfering with phytopathogen acquisition. Targeted manipulation of endosymbionts in this phytopathogen vector may yield disease management tools.Importance of the studyThis study provides insights into the critical role ofWolbachiain the Asian citrus psyllid,Diaphorina citri, a known vector of the presumed causal agent of citrus greening disease. Our data indicate a beneficial role ofWolbachiainD. citri, whereby the bacteria greatly enhance overall fitness and affect sex ratio of the host but interfere with acquisition of the phytopathogen,CandidatusLiberibacter asiaticus (CLas). By artificially eliminatingWolbachiafrom psyllids, the study confirms its endosymbiotic role and opens potential avenues for development of disease control methods. Specifically, our data suggest that targeted manipulation of insect endosymbionts likeWolbachiamay potentially contribute new tools for management of this economically devastating and globally widespread disease of citrus.