bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic liability to insomnia and substance use disorders in patients with bipolar disorder
Authors: Melhuish Beaupre Lindsay M. , Coombes Brandon , Batzler Anthony , Sanchez-Ruiz Jorge A. , Kolla Bhanu Prakash , Romo-Nava Francisco , Pazdernik Vanessa , Jenkins Gregory , Waller T. Cameron , Skime Michelle , McElroy Susan , Frye Mark , Biernacka Joanna M. 
Published: September 2024

AbstractBackgroundInsomnia and substance use disorders (SUD) are common comorbidities of bipolar disorder (BD). Genome-wide association studies (GWAS) have uncovered shared genetic contributions to insomnia and BD as well as SUDs and BD. Using electronic health record (EHR) derived phenotypes (phecodes) and questionnaire data, the authors examined the relationship between insomnia genetic liability and SUDs in BD.Methods40,839 participants from the Mayo Clinic Bipolar Disorder Biobank (BD Biobank; n=774) and Mayo Clinic Biobank (n=485 BD cases, n=39,580 controls) were included in the phecode analyses [insomnia, SUD, alcohol use disorder (AUD) and tobacco use disorder (TUD)]. 1789 cases were included in analyses of the BD Biobank questionnaire data, which included information on BD subtype and various SUDs. Logistic regression was used to test for associations between insomnia polygenic risk scores (PRS) and insomnia and SUD phenotypes in BD cases and controls.ResultsInsomnia PRS was associated with the insomnia phecode in controls (OR=1.19, p=9.64e-33) but not in BD cases (OR=1, p=0.95). Associations between insomnia PRS and SUD phecodes were significant in BD cases and controls with the effect of the association between insomnia PRS and SUD being stronger in BD cases (interaction p=0.024). In the BD Biobank, the insomnia PRS was associated with increased odds of AUD (OR=1.19, p=4.26e-04), TUD (OR=1.21, p=1.25e-05) and cannabis use disorder (OR=1.16, p=4.19e-03).ConclusionThe effect of genetic predisposition to insomnia on SUD may be stronger in BD cases than controls. This could have clinical treatment implications for individuals with BD and comorbid SUD.
Clonal Hematopoiesis and the Risk for Rheumatoid Arthritis
Authors: Corty Robert , Heimlich J. Brett , Pershad Yash , Sharber Brian , Vlasschaert Caitlyn , Ormseth Michelle , Stein C. Michael , Bick Alexander 
Published: September 2024

AbstractObjectiveRheumatoid arthritis (RA) is a systemic autoimmune disease with complex pathogenesis involving the innate and adaptive immune system. Clonal hematopoiesis of indeterminate potential (CHIP) is defined by clonal proliferation of one hematopoietic stem cell and is typically asymptomatic. Both are common among older adults. CHIP is associated with multiple autoimmune diseases, but has not been thoroughly evaluated for its relationship with RA.MethodsWe examined three large biobanks where CHIP status of participants has been determined from whole genome sequencing data. We ascertained cases of RA, seropositive RA (SPRA), and seronegative RA (SNRA) using established methods and used survival analysis to test whether CHIP status was predictive of incident disease. We combined the results of the three biobank studies using random effects meta-analysis. For validation, we performed deep, targeted sequencing of CHIP-causing genes in an established clinical cohort of 132 RA cases, 56 controls, and 544 external controls. We compared the rates of CHIP between cases and controls using logistic linear regression.ResultsIn the UKBiobank and in meta-analysis, the presence of a large CHIP clone was associated with an increased risk for SPRA (HR = 2.57 with CI [1.46, 4.52] and p = 0.001) and RA (HR = 1.43 with CI [1.16, 1.75] and p = 7 × 10−4). Medium CHIP clones were associated with smaller increases in risk for SPRA and RA, and small CHIP clones carried no increased risk of any outcome. There were no associations detected between SNRA and CHIP of any size. In the clinical RA cohort, cases were more likely to have CHIP than controls after correcting for age, age2, and sex (OR: 2.08, HR [1.09, 3.83], p = 0.02).ConclusionIn a meta-analysis combing data from three large biobanks, large CHIP clones were associated with an increased risk for incident SPRA and, to a lesser extent, increased risk for RA. Validating this biobank-based finding, in a well-phenotyped clinical cohort, cases had higher rates of CHIP than age-matched controls. The mechanism by which CHIP drives the increased risk for SPRA is not known, but if it were discovered, could inform early intervention for patients with CHIP to prevent RA or personalized therapy for patients with RA based on CHIP status.
A one-step protocol to generate impermeable fluorescent HaloTag substrates forin situlive cell application and super-resolution imaging
Authors: Roßmann Kilian , Sun Siqi , Olesen Christina Holmboe , Kowald Maria , Tapp Eleni , Pabst Ulrich , Bieck Marie , Birke Ramona , Shields Brenda C. , Jeong PyeongHwa , Hong Jiyong , Tadross Michael R. , Levitz Joshua , Lehmann Martin , Lipstein Noa , Broichhagen Johannes 
Published: September 2024

ABSTRACTCommunication between cells is largely orchestrated by proteins on the cell surface, which allow information transfer across the cell membrane. Super-resolution and single-molecule visualization of these proteins can be achieved by genetically grafting HTP (HaloTag Protein) into the protein of interest followed by brief incubation of cells with a dye-HTL (dye-linked HaloTag Ligand). This approach allows for use of cutting-edge fluorophores optimized for specific optical techniques or a cell-impermeable dye-HTL to selectively label surface proteins without labeling intracellular copies. However, these two goals often conflict, as many high-performing dyes exhibit membrane permeability. Traditional methods to eliminate cell permeability face synthetic bottlenecks and risk altering photophysical properties. Here we report that dye-HTL reagents can be made cell-impermeable by inserting a charged sulfonate directly into the HTL, leaving the dye moiety unperturbed. This simple, one-step method requires no purification and is compatible with both the original HTL and second-generation HTL.2, the latter offering accelerated labeling. We validate such compounds, termed dye-SHTL (‘dye shuttle’) conjugates, in live cells via widefield microscopy, demonstrating exclusive membrane staining of extracellular HTP fusion proteins. In transduced primary hippocampal neurons, we label mGluR2, a neuromodulatory G protein-coupled receptor (GPCR), with dyes optimized for stimulated emission by depletion (STED) super-resolution microscopy, allowing unprecedented accuracy in distinguishing surface and receptors from those in internal compartments of the presynaptic terminal, important in neural communication. This approach offers broad utility for surface-specific protein labelling.
Unraveling the GM1specificity of Galectin-1 binding to lipid membranes
Authors: Scollo Federica , Kulig Waldemar , Nicita Gabriele , Ludwig Anna-K. , Ricardo Joana C. , Zito Valeria , Kapusta Peter , Vattulainen Ilpo , Cebecauer Marek , Gabius Hans-Joachim , Kaltner Herbert , Maccarrone Giuseppe , Hof Martin 
Published: September 2024

AbstractGalectin-1 (Gal-1) is a galactose-binding protein involved in various cellular functions. Gal-1’s activity has been suggested to be connected to two molecular concepts, which are however lacking experimental proof: a) enhanced binding affinity of Gal-1 towards membranes containing monosialotetrahexosylganglioside (GM1) over disialoganglioside GD1a and b) cross-linking of GM1’s by homodimers of Gal-1. We provide evidence about the specificity and the nature of Gal-1 interaction with model membranes containing GM1or GD1a, employing a broad panel of fluorescence-based and label-free experimental techniques, complemented by atomistic biomolecular simulations. Our study demonstrates that Gal-1 binds indeed specifically to GM1, and not to GD1a, when embedded in membranes over a wide range of concentrations (i.e., 30 nM to 10 μM). The apparent binding constant is about tens of micromoles. On the other hand, no evidence of Gal-1/GM1cross-linking was observed. Our findings suggest that cross-linking does not result from sole interactions between GM1and Gal-1, indicating that in a physiological context, additional triggers are needed, which shift the GM1/Gal-1 equilibria towards the membrane-bound homodimeric Gal-1.Abstract Figure
The health, wellbeing and health service use of women attempting or planning pregnancy: a nationwide cross-sectional survey of Australian women
Authors: Steel Amie , Schoenaker Danielle , Harnett Joanna , Adams Jon 
Published: September 2024

AbstractBackgroundHealth and wellbeing during the preconception period influence maternal and child health outcomes. We describe the sociodemographic and health characteristics of Australian women currently attempting pregnancy or planning to conceive in the next 12 months, compared with other women of reproductive age, to identify opportunities for preconception care.MethodsA sub-analysis of survey data obtained in 2022 that included 874 responses from females aged 18-49 years was conducted. Socio-demographic characteristics, health and wellbeing status, and health service utilization data were described according to pregnancy intention.ResultsOf 874 women, 64 (7.4%) reported currently attempting pregnancy and 45 (5.2%) reported planning to become pregnant in the next 12 months. Both groups of women were commonly married or in a de facto relationship. Women who were planning to become pregnant were more commonly aged 25-34 years (71.1%) compared to 18 to 24 years (20.0%) or aged 35 years or older (8.9%). They were also more likely to consult a chiropractor (OR 1.5). Women currently attempting pregnancy were less likely to not be in the paid workforce (OR 0.34) compared to working full time. They were also less likely to be using prescription-only pharmaceuticals (OR 0.30) and more likely to be consulting a Traditional Chinese medicine practitioner (OR 2.66) or a dietician (OR 2.11).ConclusionThe findings of this study can be used for informing health service planning and policy that takes a whole-of-health-system approach when designing preconception health primary care interventions.
Impact of 10-valent pneumococcal conjugate vaccine on the epidemiology of otitis media with otorrhea among Bangladeshi children
Authors: Naziat Hakka , Rahman Md Hafizur , Das Rajib C , Islam Maksuda , Saha Shampa , Hussain Md. Manzoor , Sattar Asif , Uddin Mohammad J , Alam Md. Jahangir , Whitney Cynthia G. , Saha Senjuti , Hooda Yogesh , Saha Samir K 
Published: September 2024

ABSTRACTIn 2015, Bangladesh introduced the ten-valent pneumococcal conjugate vaccine (PCV10). This study evaluates the impact of PCV10 on pneumococcal otitis media (OM), a prevalent middle ear infection amongst children in low-and-middle income countries, including Bangladesh. We analyzed ear swabs from OM cases with otorrhea collected at the largest pediatric hospital in Dhaka, Bangladesh from April 2014 to March 2019. The study involved identifying pathogens and conducting pneumococcal serotyping using the Quellung reaction.Four years post PCV10 introduction, the rate of detection of pneumococcus among otorrhea cases decreased from 18.4% (164/892) in 2014-15 to 15.6% (581/3735) in 2018-19, reflecting a 15.4% reduction. Notably, vaccine serotypes (VTs) demonstrated a significant decline throughout the post-PCV years, with a 44.1% reduction compared to the pre-PCV period. Specific VTs like 14, 6B and 19F exhibited significant reductions of 60.2%, 57.5% and 42.9% respectively. Conversely, non-vaccine serotypes (NVTs) showed non-significant increase of 8.6%; specifically serotype 35B showed a 70.1% increase. Administration of two or three doses of PCV10 provided 84.4% protection against OM cases caused by serotypes covered by PCV10.This is the first report from South Asia assessing PCV’s impact on pneumococcal OM. It demonstrates a 15.4% reduction in pneumococcal isolation over four years and over 80% efficacy of PCV10 in preventing vaccine type pneumococcal OM cases. While some vaccine serotypes decreased significantly, the impact of PCV10 on overall pneumococcal OM cases was dampened by increasing isolation of non-vaccine serotypes.
BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability
Authors: Longo Michael A. , Ahmed Syed Moiz , Chen Yue , Tsai Chi-Lin , Namjoshi Sarita , Wang Xiaoyan , Perera Rajika L. , Arvai Andy , Lee Miyoung , Kong Li Ren , Engl Wilfried , Shyuan Woei , Zhao Ziqing Winston , Venkitaraman Ashok R. , Tainer John A. , Schlacher Katharina 
Published: September 2024

SUMMARYTumor suppressor protein BRCA2 acts with RAD51 in replication-fork protection (FP) and homology-directed DNA break repair (HDR). Critical for cancer etiology and therapy resistance, BRCA2 C-terminus was thought to stabilize RAD51-filaments after they assemble on single-stranded (ss)DNA. Here we determined the detailed crystal structure for BRCA2 C-terminal interaction-domain (TR2i) with ATP-bound RAD51 prior to DNA binding. In contrast to recombinogenic RAD51-filaments comprising extended ATP-bound RAD51 dimers, TR2i unexpectedly reshapes ATP-RAD51 into a unique dimer conformation accommodating double-stranded B-DNA binding unsuited for HDR initiation. Structural, biochemical, and molecular results with interface-guided mutations uncover TR2i’s FP mechanism. Proline-driven secondary-structure stabilizes residue triads and spans the RAD51 dimer engaging pivotal interactions of RAD51 M210 and BRCA2 S3291/P3292, the cyclin-dependent kinase (CDK) phosphorylation site that toggles between FP during S-phase and HDR in G2. TR2i evidently acts as an allosteric clamp switching RAD51 from ssDNA to double-stranded and B-DNA binding enforcing FP over HDR.
Prospects of HIV elimination among men who have sex with men: a systematic review of modeling studies
Authors: Roberts Jacob Aiden , Teslya Alexandra , Kretzschmar Mirjam E. , van de Wijgert Janneke H.H.M. , Rozhnova Ganna 
Published: September 2024

AbstractBackgroundDespite advances in HIV treatment and prevention, men who have sex with men (MSM) remain disproportionately affected by HIV worldwide. This systematic review summarizes the results of mathematical modeling studies that evaluated whether interventions might eliminate HIV in MSM populations by geographical setting, type of intervention(s), elimination definition, and model characteristics.MethodsWe searched Embase and PubMed for modeling studies published between July 1, 2016 and August 7, 2023. Studies were included if they used a dynamic model to assess the impact of interventions on HIV transmission among MSM. Data were extracted on article information, study population, interventions, elimination definitions, model type, model structure, and calibration. The studies were critically appraised by evaluating the comprehensiveness of their models in addressing elimination.FindingsOf the 2,732 identified records, 80 studies were included. MSM populations in only five of the eight Joint United Nations Programme on HIV/AIDS (UNAIDS) regions were modeled, with over half of the models considering MSM in the USA. Complex agent-based models were the most common overall, while simpler compartmental models predominated outside Western and Central Europe and North America. Thirty-five of the 80 studies defined elimination as reductions or thresholds in HIV incidence or prevalence, a reproduction number below one, or the elimination of racial disparities. Elimination was achieved in 32 out of 44 modeled scenarios, but the authors of only six of these 32 scenarios thought the interventions required to achieve elimination were feasible. The six feasible elimination scenarios were reported in compartmental models for few countries in Western Europe and Asia. Models in which elimination was achieved most commonly used a combination of interventions that included pre-exposure prophylaxis (PrEP) and/or test-and-treat, except in Africa, where PrEP was not included.InterpretationModeling efforts to understand HIV elimination prospects among MSM outside Western and Central Europe and North America should be intensified. Various definitions of elimination reflect perspectives from both modeling and public health. To enhance study comparability and for models to contribute effectively to public health policy, the use of an elimination definition based on an incidence threshold would be the most valuable. Furthermore, by identifying gaps in current studies, we recommend novel research directions for modeling to inform a coordinated global response for HIV elimination among MSM.FundingAidsfonds, EU.
Comparative pan-genomics reveals divergent adaptations in clinically-relevant members of theFusarium solanispecies complex
Authors: Brassington Phillip J.T. , Fabre Maria Laura , Zimmermann Anna , Perrier Marion , Martin Ronny , Kurzai Oliver , Barber Amelia E. 
Published: September 2024

AbstractTheFusarium solanispecies complex are a group of dual-kingdom fungal pathogens capable of causing devastating disease on a wide range of host plants and life-threatening infections in humans that are difficult to treat. In this study, we generate highly contiguous genomes for three clinical isolates ofFusarium keratoplasticumand three clinical isolates ofFusarium petroliphilumand compare them with other genomes of the FSSC from plant and animal sources. We find that human pathogenicity is polyphyletic within the FSSC, including inF. keratoplasticum. Pan-genome analysis revealed a high degree of gene presence-absence in the complex, with only 41% of genes (11,079/27,068) found in all samples and the presence of accessory chromosomes encoding isolate- and species-specific genes. We also defined conserved long non-coding RNAs (lncRNAs) betweenF. keratoplasticumandF. petroliphilum,revealing that they show a similar low degree of presence-absence variation. Secondary metabolite analysis revealed a conserved core set of biosynthetic gene clusters across the FSSC, as well as a unique cluster potentially linked to keratitis. Transcriptomic analysis under stress conditions showed minimal differential gene expression, indicating that bothF. keratoplasticumandF. petroliphilumare well adapted to human infection-relevant conditions. This study provides valuable insights into the evolutionary dynamics, genomic architecture, and potential pathogenicity mechanisms of the FSSC, with implications for understanding multi-kingdom virulence, of increasing relevance as climate change potentially increases the number of fungal species that can grow at human temperatures.
Investigating customers’ purchase intentions for electric vehicles with linkage of theory of reasoned action and self-image congruence
Authors: Rahma Baher , Kramberger Tomaž , Barakat Mahmoud , Ali Ahmed Hussein 
Published: September 2024

PurposeIn recent years, the global focus has increasingly shifted toward the adoption of electric vehicles (EVs) due to growing concerns about environmental sustainability and the imperative of reducing greenhouse gas emissions. The transportation sector, a significant contributor to air pollution and climate change, faces increasing pressure to embrace EVs as a solution. However, the resistance exhibited by customers toward adopting new technology poses a substantial obstacle to the widespread adoption of EVs. Drawing on the link between theory of reasoned action (TRA) and self-congruity theory, this research aims to determine the factors that affect the customer intention toward EV.Design/methodology/approachThe research conducts a questionnaire collecting 950 respondents from the Egyptian market. The research used primary quantitative data from online and self-administered questionnaires.FindingsThe findings indicated that green trust, price sensitivity and reliability have a positive impact on customer’s intention. However, self-image congruence was not affecting customer intention. For the moderating role of financial self-efficacy, it is affecting the relationship between price sensitivity and customer’s purchase intentions toward EV.Research limitations/implicationsThis research will expand the theory by conceptualizing its abstract notions through research variables and implementing them in the Egyptian market. Furthermore, it links the two distinct theories. This knowledge can be utilized by policymakers and stakeholders to expedite the adoption of EVs in the Egyptian market.Originality/valueThis study presents a conceptual framework for managers and policymakers about the factors that affect the customer to buy EVs, since the international organizations emphasize eco-friendly transportation systems.
Tripartite evolutionary game analysis of government reward and punishment mechanisms and agricultural resilience under a dual carbon context
Authors: Zhou Xiaoli , Han Mingyang 
Published: September 2024

PurposeUnder the “dual carbon” framework, the article explores the equilibrium points among the government, agricultural enterprises and village committees, and uses sensitivity analysis to reveal the dynamic factors affecting these stakeholders, thereby proposing methods to enhance agricultural disaster resilience.Design/methodology/approachThe article uses MATLAB to construct a game model for the three parties with interests: agribusiness, government and village council. It examines the stability of strategies among these entities. Through graphical simulation, the paper analyzes the sensitivity of agricultural enterprises carbon emissions and village committees’ rent-seeking behaviors in the decision-making process, focusing on significant factors such as government carbon tax and regulatory policies.FindingsA single government reward and punishment mechanism is insufficient to influence the strategic choices of enterprises and village committees. The cost of rent-seeking does not affect the strategic choices of enterprises and village committees. A key factor influencing whether the village committee engages in rent-seeking is the level of labor income of the village committee as an “intermediary”.Originality/valueThis paper focuses on the dynamic game between three stakeholders (the government, agricultural enterprises and village committees), seeking dynamic equilibrium and conducting sensitivity analysis through visualization to provide the government with optimal policy recommendations.