bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Analysis on the Impact of Childhood Adversity, Anxiety, and C-Reactive Protein on Adult Chronic Pain in the Midlife in the United States (MIDUS) Study
Authors: Dalechek Danielle E. , Caes Line , McIntosh Gwenne , Whittaker Anna C. 
Published: December 2024

ABSTRACT

Objective
This study used the Midlife-Development in the United States (MIDUS) dataset to a) examine relationships between reported childhood adversity (CA), anxiety, and pain; b) assess associations between CAs, anxiety, C-reactive protein (CRP) levels, and pain; and c) explore how CAs, anxiety, and CRP are associated with pain medication consumption.

Methods
Data were from Project-4 of MIDUS-II (n = 1225), which utilized Project-1 demographics and supplemental chart review. For objectives 1–2, structural equational modeling (SEM) followed by general linear modeling (GLM) regression was conducted. For objective 3, all variables from the objective 1–2 dataset were used as possible independent variables for the exploratory regression.

Results
For objectives 1–2, CRP was significantly correlated with anxiety, emotional abuse, physical neglect, and chronic pain (n = 1173). The SEM (n = 1173) indicated that CAs, anxiety, and CRP all played a role in predicting chronic pain. Regression results (n = 1173) indicated that gender, total income, and highest education were significant predictors of chronic pain. Significant interactions to explain chronic pain included physical abuse/emotional neglect, emotional abuse/physical abuse, physical abuse/minimization, physical neglect/education, CRP/income, and CRP/education. For objective 3 (n = 600), there were no significant main effects, but a large variety of interactions contributed to predicting pain medication consumption. CAs interacting significantly to explain this included emotional abuse/physical abuse, physical abuse/emotional neglect, physical abuse/minimization, and sexual abuse/minimization. There were also significant interactions between CRP/income and CRP/education.

Conclusions
Based on a large US sample, sociodemographics played a meaningful role in predicting chronic pain in adults, and CRP was significantly correlated with anxiety, emotional abuse, physical neglect, multiple sociodemographic variables, and chronic pain. The influence of CAs on predicting long-term medication use for chronic pain was complex and warrants further study.
Registered Reports in Biopsychosocial Science and Medicine: To Infinity and Beyond
Authors: O’Connor Daryl B. 
Published: December 2024

Abstract
In April 2023, Psychosomatic Medicine, now renamed Biopsychosocial Science and Medicine, introduced registered reports as a new article format. Registered reports are a type of scientific article in which the research methods and proposed analyses are preregistered and peer-reviewed before the data are collected or analyzed. We were excited to be joining a growing number of journals internationally to offer this format and to be aligning with the Behavioral Medicine Research Council’s statement on open science, recognizing the value of publishing registered reports in our field. Recent work has shown that there is a 2-year lag between journals adopting registered reports and publishing their first registered report. Therefore, right in line with this timetable, we are delighted to be publishing our first full registered report article in this first issue that bears the Journal’s new name. This article is noteworthy for several reasons, not least because the findings make an important scientific contribution to the broader early life adversity literature but also because the article applies the registered report format to secondary data analyses. We hope that you, our readership, feel inspired to give the registered report approach a chance, whether it is for primary or secondary data collection approaches, and that you send your first, or next Stage 1 registered report to Biopsychosocial Science and Medicine.
A Framework for the Analysis of Communication Errors in Health Care
Authors: Bender John A. , Thiyagarajan Sreedevi , Morrish Wendy , Mims Maisha , Yackel Edward E. 
Published: December 2024

Objectives:
The goal of this study was to develop a systematic method to identify and classify different types of communication failures leading to patient safety events. We aimed to develop a taxonomy code sheet for identifying communication errors and provide a framework tool to classify the communication error types.

Methods:
This observational study used the Delphi method to develop a taxonomy code sheet for identifying communication errors reported in the Veterans Health Administration patient safety databases between April 2018 and March 2021. We also used Natural Language Processing to create a framework tool to classify the 9 types of communication errors using this taxonomy. Finally, analysis was done to identify affected clinical locations.

Results:
We identified 9 types of communication failures that impacted clinical outcomes using the taxonomy code sheet developed. The top 3 errors were related to nonadherence to facility standard operating procedures (993, 37.6%), followed by written errors (e.g., unclear documentation or not using plain language) (587, 22.3%) and no communication (347, 13.2%). The remaining categories of communication types are electronic (253, 9.6%), verbal (205, 7.8%), hand-off (124, 4.7%), visual (76, 2.9%), listening (41, 1.6%), and nonverbal (12, 0.5%). A cognitive aide was developed to demonstrate the step-by-step method for using the framework tool to classify the communication errors.

Conclusions:
The cognitive aide and the framework tool developed in this study can be used in any healthcare setting to identify and classify communication failures and mitigate potential risks contributing to safety events.
Uptake of HIV Preexposure Prophylaxis Among Medicare Beneficiaries — United States, 2014-2021
Authors: Huang Ya-Lin A. , Chang Man-Huei , Zhu Weiming , Hoover Karen W. 
Published: December 2024

Background:
Previous studies have estimated preexposure prophylaxis (PrEP) use among persons with commercial health insurance and Medicaid. However, data are lacking regarding PrEP use among those with Medicare.

Methods:
Using a previously developed algorithm, we estimated the number of Medicare beneficiaries (MBs) with fee-for-service (FFS) claims who were prescribed PrEP from 2014 to 2021. The analysis was stratified by age, sex, and race/ethnicity. We also examined trends in PrEP prevalence by U.S. state and demographic characteristics during 2014-2021.

Results:
The number of Medicare PrEP users increased 11-fold, from 388 in 2014 to 4,685 in 2021. MBs prescribed PrEP were predominantly younger men, White persons, residing in the South or West regions, living with a disability, and dually eligible for both Medicare and Medicaid. The prevalence of PrEP prescriptions among MBs increased 12-fold, from 9.7 per million in 2014 to to 120.0 per million in 2021. Black/African American persons had the highest prevalence of PrEP use, followed by Hispanic/Latino and White persons in 2021. The District of Columbia had the highest prevalence of PrEP use compared with other U.S. states in 2021. Significant increasing trends in PrEP use were observed across sex, age groups, and race/ethnicity.

Conclusions:
Disparities in PrEP uptake existed across MB demographic subgroups from 2014 to 2021. Public health interventions are needed to increase PrEP access and utilization, particularly among women, younger MBs, Black persons, and Hispanic persons, including those with Medicare. Strategies and policies to expand PrEP use are essential for optimal HIV prevention in the United States.
Strategies for robust, accurate, and generalizable benchmarking of drug discovery platforms
Authors: Van Norden Melissa , Mangione William , Falls Zackary , Samudrala Ram 
Published: December 2024

AbstractBenchmarking is an important step in the improvement, assessment, and comparison of the performance of drug discovery platforms and technologies. We revised the existing benchmarking protocols in our Computational Analysis of Novel Drug Opportunities (CANDO) multiscale therapeutic discovery platform to improve utility and performance. We optimized multiple parameters used in drug candidate prediction and assessment with these updated benchmarking protocols. CANDO ranked 7.4% of known drugs in the top 10 compounds for their respective diseases/indications based on drug-indication associations/mappings obtained from the Comparative Toxicogenomics Database (CTD) using these optimized parameters. This increased to 12.1% when drug-indication mappings were obtained from the Therapeutic Targets Database. Performance on an indication was weakly correlated (Spearman correlation coefficient>0.3) with indication size (number of drugs associated with an indication) and moderately correlated (correlation coefficient>0.5) with compound chemical similarity. There was also moderate correlation between our new and original benchmarking protocols when assessing performance per indication using each protocol. Benchmarking results were also dependent on the source of the drug-indication mapping used: a higher proportion of indication-associated drugs were recalled in the top 100 compounds when using the Therapeutic Targets Database (TTD), which only includes FDA-approved drug-indication associations (in contrast to the CTD, which includes associations drawn from the literature). We also created compbench, a publicly available head-to-head benchmarking protocol that allows consistent assessment and comparison of different drug discovery platforms. Using this protocol, we compared two pipelines for drug repurposing within CANDO; our primary pipeline outperformed another similarity-based pipeline still in development that clusters signatures based on their associated Gene Ontology terms. Our study sets a precedent for the complete, comprehensive, and comparable benchmarking of drug discovery platforms, resulting in more accurate drug candidate predictions.
Knock-inKcnh2Rabbit Model of Long QT Syndrome Type-2, Epilepsy, and Sudden Death
Authors: Singh Veronica , Wagner Kyle T. , Williams Laura G. , Ryan Justin M. , Keller Katherine R. , Mohnkern Jonathan D. , Gardner Robert S. , Dang Louis T. , Ziobro Julie M. , Wojcikiewicz Richard J. H. , Tucker Nathan R. , Auerbach David S. 
Published: December 2024

AbstractBackgroundLong QT Syndrome Type-2 (LQT2) is due to loss-of-functionKCNH2variants.KCNH2encodes Kv11.1 that forms a delayed-rectifier potassium channel in the brain and heart. LQT2 is associated with arrhythmias, seizures, sudden cardiac death, and sudden unexpected death in epilepsy (SUDEP). The goal of the study is to develop a translational model that reproduces the neuro-cardiac electrical abnormalities and sudden death seen in people with LQT2.MethodsWe generated the first knock-in rabbit model of LQT2 (Kcnh2(+/7bp-del)), due to a 7 base-pair (7bp) deletion in the pore domain of the endogenous rabbitKcnh2gene.ResultsMutantKcnh2is expressed in the heart and brain and constitutes 11% of totalKcnh2inKcnh2(+/7bp-del)rabbits. TotalKcnh2, WTKcnh2, and WT Kv11.1 expression is lower inKcnh2(+/7bp-del)vs. WT rabbits.Kcnh2(+/7bp-del)rabbits exhibit prolonged cardiac ventricular repolarization (QTc, JTec, JTpc). There is an increased prevalence of spontaneous epileptiform activity and clinical seizures inKcnh2(+/7bp-del)(7 of 37 rabbits) vs. WT rabbits (1:68 rabbits,p<0.003). 18.9% ofKcnh2(+/7bp-del)vs. 1.5% of WT rabbits died suddenly and spontaneously (p<0.003). We recorded 2 spontaneous lethal events inKcnh2(+/7bp-del)rabbits: (1) sudden cardiac death and (2) seizure-mediated sudden death due to generalized tonic-clonic seizures, post-ictal generalized EEG suppression, bradycardia, ECG-T-wave inversion, focal cardiac activity, and asystole/death.ConclusionsWe developed the first genetic rabbit model of LQT2 that reproduces the cardiac and epileptic phenotypes seen in people with LQT2.Kcnh2(+/7bp-del)rabbits provide a valuable tool for future mechanistic studies, development of neurotherapeutics, and cardiac-safety testing.
Collaterals influence oxygen metabolism on admission MRI in acute ischemic stroke
Authors: Patural Paul , Bani-Sadr Alexandre , Riva Roberto , Frindel Carole , de Bourguignon Charles , Hermier Marc , Gamondes Delphine , Jupin-Delevaux Emilien , Derex Laurent , Cho Tae-Hee , Mechtouff Laura , Nighoghossian Norbert , Berthezene Yves 
Published: December 2024

AbstractIntroductionThis study aimed to correlate cerebral collateral status and MRI-derived oxygen metabolism at admission in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy.MethodsThe HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological an Imaging markerS of CardiovascUlar Outcomes in Stroke; NCT: 03149705), a single-center observational study, enrolled AIS patients for thrombectomy following MRI triage due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. Dynamic-Susceptibility Contrast perfusion (DSC perfusion), Diffusion-Weighted Imaging (DWI) and penumbral volume (Tmax ≥ 6 secs) were post-processed to generate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) maps within DWI and penumbral anomalies, compared to contralateral areas. Collateral status, assessed via pretreatment digital subtraction angiography, was categorized as poor (0–2) or good (3–4) based on ASITN/SIR collateral grading system score from Higashida.ResultsBetween October 2016 and October 2022, 321 participants were enrolled in the cohort. Of these, 184 (57.3%) were excluded due to missing admission DSC perfusion MRI in 61 patients and artifacts precluding collateral status evaluation on DSA. A total of 137 patients were included (mean age 71 years; 56.2% male). The median National Institutes of Health Stroke Scale (NIHSS) score was 15 (interquartile range [IQR]: 8.0–18.0), and the median time from symptom onset to admission was 96.0 minutes ([IQR]: 78.0–137.0). Patients with good collaterals (78) exhibited a smaller baseline infarct core (median 9.83 mL; (P<0.0001) less impairment cerebral blood flow (CBF) within the DWI lesion (median -65.89%; (P<0.0001), and less severe decrease CMRO2 within the ischemic penumbra (median -17.29%; (P=0.03). Good collaterals were independently associated with a smaller baseline infarct core volume and less decrease in CMRO2 within the ischemic penumbra (respectively OR = 0.94; 95% CI: [0.92; 0.96]; (P<0.0001), and (OR = 1.30; 95% CI: [1.06; 1.82]; P=0.001).ConclusionGood collaterals are associated with a smaller infarct core and better CMRO2 within the ischemic penumbra.
FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses
Authors: Kim Choah , Gabriel Katlyn R. , Boone Dylan , Brown Matthew R. , Oppenheimer Katherine , Kost-Alimova Maria , Pablo Juan Lorenzo B. , Greka Anna 
Published: December 2024

AbstractExposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity. The screen revealed peroxisomal proteins, especially those that impact ether lipid synthesis, as important regulators of lipotoxicity. We identified Fas-associated factor family member 2 (FAF2) as a critical bifunctional co-regulator of peroxisomal and fatty acid biology. We further uncovered a new biological function for the ubiquitin-regulatory X (UBX) and UAS thioredoxin-like domains of FAF2, demonstrating their requirement for peroxisomal protein abundance and SFA-induced cellular stress. Our work highlights the role of FAF2 in regulating peroxisomal abundance and function, and the peroxisome as a key organelle in the cellular response to SFAs.
Thermal selection shifts genetic diversity and performance in blue mussel juveniles
Authors: Nascimento-Schulze Jennifer C. , Vajedsamiei Jahangir , Bean Tim P , Frankholz Lisa , Brennan Reid S. , Melzner Frank , Ellis Robert P 
Published: December 2024

AbstractMussels from the genus Mytilus, key inhabitants of the benthos, are important for the aquaculture industry and one of the most sustainable sources of animal protein available. Species within theMytilus eduliscomplex (M. edulis, M. galloprovincialisandM. trossulus) are commonly found in temperate regions globally and can easily hybridise whenever their geographic distributions overlap. In the Baltic Sea, populations are formed byM. edulisandM. trossulushybrids with low levels ofM. galloprovincialisintrogression. Given the economic and ecological relevance of mussels, this study aimed to investigate mechanisms through which their resilience towards global warming may be fast-tracked. For this, we developed two cohorts of juvenile mussels (i.e. recently settled animals) from the Baltic Sea (Kiel, Germany), one exposed to an extreme heat event early in life and one naïve to this stressor. Both cohorts were then exposed to experimental temperatures at the proposed upper thermal limit for this population, 21°C to 26°C, with animal performance measured after 25 days. We then assessed the impacts of thermal stress on the genetic composition of each cohort by genotyping 50 individuals using the blue mussel 60K SNP-array. We observed a significant increase inM. edulisgenotypes together with a decrease inM. trossulusin the S cohort in comparison with NS juveniles. We also found that exposure to high temperature has an effect on the performance of mussel cohorts, reducing dry tissue weight of the selected individuals. Results from this study provide relevant insights on how selection through thermal stress impacts performance and genetic composition of blue mussel juveniles, with key implications for understanding and managing mussel populations under future warming scenarios.
NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress
Authors: Amnekar Ramchandra V , Dite Toby , Lis Pawel , Bell Sebastian , Brown Fiona , Johnson Clare , Wilkinson Stuart , Raggett Samantha , Dorward Mark , Wightman Mel , Macartney Thomas , Soares Renata F , Lamoliatte Frederic , Alessi Dario R 
Published: December 2024

AbstractWNK family kinases are regulated by osmotic stress and control ion homeostasis by activating SPAK and OXSR1 kinases. Using a proximity ligation approach, we found that osmotic stress promotes the association of WNK1 with the NRBP1 pseudokinase and TSC22D2/4 adaptor proteins, results that are confirmed by immunoprecipitation and mass spectrometry and immunoblotting studies. NRBP1 pseudokinase is closely related to WNK isoforms and contains a RΦ-motif binding conserved C-terminal (CCT) domain, similar to the CCT domains in WNKs, SPAK and OXSR1. Knockdown or knock-out of NRBP1 markedly inhibited sorbitol-induced activation of WNK1 and downstream components. We demonstrate recombinant NRBP1 can directly induce the activation of WNK4in vitro. AlphaFold-3 modelling predicts that WNK1, SPAK, NRBP1, and TSC22D4 form a complex, in which two TSC22D4 RΦ-motifs interact with the CCTL1 domain of WNK1 and the CCT domain of NRBP1. Our data indicates NRBP1 functions as an upstream activator of the WNK pathway.TeaserNRBP1 functions as a scaffolding component regulating the assembly of a multi-subunit complex, required for the activation of the WNK Lysine Deficient Protein Kinase family in response to osmotic stress.Graphical Abstract
Neighborhood Deprivation, Genetic Predisposition, and Life Satisfaction: Evidence from the German Twin Family Panel
Authors: Harerimana Nadia V. , Liu Yixuan , Ruks Mirko 
Published: December 2024

AbstractBoth genes and the neighborhood are important for life satisfaction; however, there is little research on gene-environment interactions (GxE) that examines how the effect of genetic endowments varies as a function of the environmental context with life satisfaction as the outcome. This study investigated how neighborhood deprivation moderates the effects of genetic predisposition on life satisfaction. Using data from the German Twin Family Panel (TwinLife), we identified 760 dizygotic (DZ) twins and employed twin fixed-effect models to assess the GxE effects on life satisfaction. The findings reveal that the polygenic score (PGS) for subjective well-being is positively associated with life satisfaction. The effect of PGS for subjective well-being on life satisfaction is strongest for individuals living in moderately deprived areas, while it is weaker for those living in highly deprived and less deprived areas. Thus, there are signs of compensation in less deprived areas and, particularly, diathesis-stress/triggering in highly deprived areas.
Outcome-Driven Microscopy: Closed-Loop Optogenetic Control of Cell Biology
Authors: Passmore Josiah B. , Rates Alfredo , Schröder Jakob , van Laarhoven Menno T. P. , Hellebrekers Vincent J. W. , van Hoef Henrik G. , Geurts Antonius J. M. , van Straaten Wendy , Nijenhuis Wilco , Berger Florian , Smith Carlas S. , Smal Ihor , Kapitein Lukas C. 
Published: December 2024

ABSTRACTSmart microscopy is transforming biological imaging by integrating real-time analysis with adaptive acquisition to enhance imaging efficiency. Whereas many emerging implementations are event-driven and focus on on-demand data acquisition to reduce phototoxicity, we here present ‘outcome-driven’ microscopy, which combines smart microscopy with optogenetics to achieve subcellular spatiotemporal control of biology to predefined outcomes. We validate this approach using light-based control of cell migration and nucleocytoplasmic transport, and demonstrate unprecedented spatiotemporal control over cellular behaviour.