bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia Caspase11 non‐canonical inflammasome drives fever
Authors: Yu Ping , Li Yuangeng , Fu Wenwen , Yu Xiaofeng , Sui Dayun , Xu Huali , Sun Weilun 
Published: June 2024

AbstractAimAnimals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high‐grade fever indicates poor clinical outcomes. Caspase11 (Casp11) is involved in many inflammatory diseases. Whether Casp11 leads to fever remains unclear. In this study, we investigate the role of the preoptic area of the hypothalamus (PO/AH) microglia Casp11 in fever.MethodsWe perform experiments using a rat model of LPS‐induced fever. We measure body temperature and explore the functions of peripheral macrophages and PO/AH microglia in fever signaling by ELISA, immunohistochemistry, immunofluorescence, flow cytometry, macrophage depletion, protein blotting, and RNA‐seq. Then, the effects of macrophages on microglia in a hyperthermic environment are observed in vitro. Finally, adeno‐associated viruses are used to knockdown or overexpress microglia Casp11 in PO/AH to determine the role of Casp11 in fever.ResultsWe find peripheral macrophages and PO/AH microglia play important roles in the process of fever, which is proved by macrophage and microglia depletion. By RNA‐seq analysis, we find Casp11 expression in PO/AH is significantly increased during fever. Co‐culture and conditioned‐culture simulate the induction of microglia Casp11 activation by macrophages in a non‐contact manner. Microglia Casp11 knockdown decreases body temperature, pyrogenic factors, and inflammasome, and vice versa.ConclusionWe report that Casp11 drives fever. Mechanistically, peripheral macrophages transmit immune signals via cytokines to microglia in PO/AH, which activate the Casp11 non‐canonical inflammasome. Our findings identify a novel player, the microglia Casp11, in the control of fever, providing an explanation for the transmission and amplification of fever immune signaling.
Continuing or stopping 5‐aminosalicylates in patients with inflammatory bowel disease on anti‐TNF therapy: A nationwide population‐based study
Authors: Seo Jeongkuk , Kim Seonok , Hong Seung Wook , Hwang Sung Wook , Park Sang Hyoung , Yang Dong‐Hoon , Byeon Jeong‐Sik , Myung Seung‐Jae , Yang Suk‐Kyun , Kim Ye‐Jee , Ye Byong Duk 
Published: June 2024

SummaryBackgroundThe impact of continuing or stopping 5‐aminosalicylates (5‐ASA) after commencing anti‐tumour necrosis factor (anti‐TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear.AimsTo compare the outcomes of patients with IBD who stopped or continued 5‐ASA after starting anti‐TNF therapy.MethodsWe analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5‐ASA within 90 days of anti‐TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD‐related hospitalisation, or intestinal surgery.ResultsAmong 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5‐ASA within 90 days of starting anti‐TNF therapy. During a median 4.3‐year follow‐up, discontinuation of 5‐ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93–1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5‐ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups.ConclusionsIn this nationwide population‐based study, discontinuing 5‐ASA after starting anti‐TNF therapy was not associated with an increased risk of adverse events in patients with IBD.
Estimating the prevalence of potential and actionable drug‐gene interactions in Irish primary care: A cross‐sectional study
Authors: Johnson L. , Youssef E. , O'Shea J. , Thornley T. , Gallagher J. , Ledwidge M. , Ryan C. 
Published: June 2024

AbstractAimsPharmacogenetics (PGx) is increasingly recognized as a strategy for medicines optimisation and prevention of adverse drug reactions. According to guidelines produced by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG), most medicines with drug‐gene interactions (DGIs) are prescribed in primary care. This study aimed to estimate the prevalence of potential and actionable DGIs involving all medicines dispensed in Irish primary care.MethodsDispensings of 46 drugs to General Medical Services (GMS) patients in the Health Service Executive Primary Care Reimbursement Service Irish pharmacy claims database from 01 January 2021 to 31 December 2021 were analysed to estimate the national prevalence of total dispensings and incidence of first‐time dispensings of drugs with potential DGIs according to the CPIC and/or DPWG guidelines. Phenotype frequency data from the UK Biobank and the CPIC were used to estimate the incidence of actionable DGIs.ResultsOne in five dispensings (12 443 637 of 62 754 498, 19.8%) were medicines with potential DGIs, 1 878 255 of these dispensed for the first time. On application of phenotype frequencies and linked guideline based therapeutic recommendations, 2 349 055 potential DGIs (18.9%) required action, such as monitoring and guarding against maximum dose, drug or dose change. One in five (369 700, 19.7%) first‐time dispensings required action, with 139 169 (7.4%) requiring a change in prescribing. Antidepressants, weak opioids and statins were most commonly identified as having actionable DGIs.ConclusionsThis study estimated a high prevalence of DGIs in primary care in Ireland, identifying the need and opportunity to optimize drug therapy through PGx testing.
An agent‐based model of consumer demand
Authors: Tsiatsios Georgios Alkis , Kollias Iraklis , Leventides John , Melas Evangelos 
Published: June 2024

AbstractThis paper studies an agent‐based model of consumer demand. Agents are heterogeneous with respect to their preferences and incomes. There are two basic ingredients in the model. The first ingredient is a metric that captures the degree of heterogeneity between agents. The second ingredient is a serial computer algorithm that is used in order to compute a terminal consumption bundle at which income is exhausted and overall utility is maximized. Agents are clustered into heterogeneous groups based on their preferences and incomes. We extract information about the evolution of consumer expenditure under different price regimes and the buildup of optimal demand for varying levels of income and preference parameter values. These features cannot be obtained in the classical framework of static utility maximization. Our agent‐based data‐driven methodology can be applied to any relevant data set and so provide a reliable model for forecasting demand given some agent characteristics.
Large‐scale deviations between realized and fundamental thermal niches in global seaweed distributions
Authors: Laeseke Philipp , Martínez Brezo D.‐C. , Bischof Kai 
Published: June 2024

AbstractAimClimate change has profound effects on species' distributions, and it is crucial to understand how well physiological limits correspond to distribution patterns to provide realistic estimations of future range shifts and/or extinctions. Seaweeds are foundation species of global coastal ecosystems, and sea surface temperature is a main predictor to explain their distributions and redistributions under global warming. We here test the hypothesis that, in contrast to other marine ectotherms, physiological knowledge of temperature niches is a weak predictor for seaweed distributions.LocationGlobal.Time PeriodPresent (1984–2019).TaxaSeaweeds.MethodsWe analysed the predictive power of physiological temperature limits to predict real‐world distributions in 126 globally distributed seaweed species with linear and generalized linear mixed models.ResultsIn 72% of the species, there was a difference of ≥|2|°C between the physiological and the realized thermal limits. Both, thermal underfilling (distributional thermal limits narrower than the physiological limits) and overfilling (distributional thermal limits wider than the physiological limits) were present. Thus, in only 28% of the species the physiological limits corresponded to the distributional limits. While heat‐tolerance is a significant predictor for upper distributional temperature limits, we found no relationship between cold‐tolerance and lower distributional temperature limits and the latter two seem to be independent.Main ConclusionsPhysiological thermal limits have limited predictive power for seaweed distributions and deviations may be large. Especially cold‐tolerances are a weak predictor, and forecasting of migrations under changing global conditions (e.g. towards the poles) will need special attention. This indicates that responses towards climate change might be highly variable between seaweed species and difficult to predict. Further, nearly 60% of the investigated species had populations which are close to or beyond their reported upper survival limits and are thus probably under threat of eradication by elevation of sea surface temperature.
The significance of local government in disaster management for international migrants: the case of Minoh City, Osaka Prefecture
Authors: Kobayashi Yasuko Hassall 
Published: June 2024

AbstractDisaster research predominantly focuses on citizens, not on migrants. This tilted spotlight needs to be readjusted, since many advanced countries around the world have become immigration countries, and safeguarding the lives of migrants at times of disaster has become an important and immediate policy issue. Hence, this research concentrates on disaster management to protect the lives of migrants in a disaster‐prone and de facto immigration country. The particular country and event in question are Japan and the northern Osaka earthquake of June 2018. More than 100 migrants who lived near the earthquake's epicentre rushed to an evacuation shelter managed by the local municipal government of Minoh City, Osaka Prefecture. While non‐governmental organisations attract more attention, this paper centres on a local government and demonstrates the key role that it can play in both bridging and building networks across different communities, and thus in safeguarding the lives of migrants at times of disaster.
Global and regional burden of vaccine‐induced thrombotic thrombocytopenia, 1969–2023: Comprehensive findings with critical analysis of the international pharmacovigilance database
Authors: Lee Sooji , Jo Hyesu , Woo Selin , Jeong Yi Deun , Lee Hayeon , Lee Kyeongmin , Lee Jinseok , Kim Hyeon Jin , Kang Jiseung , Jacob Louis , Smith Lee , Rahmati Masoud , López Sánchez Guillermo F. , Dragioti Elena , Son Yejun , Kim Soeun , Yeo Seung Geun , Park Jaeyu , Yon Dong Keon 
Published: June 2024

AbstractObjectiveThe scarcity of studies on vaccine‐induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine‐induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination.MethodsThis study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine‐induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine‐induced TTS across 156 countries.ResultsWe identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine‐induced TTS among 404 388 reports of all‐cause TTS. There has been a significant increase in reports of vaccine‐induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID‐19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75–3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07–2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78–2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50–2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50–1.86]; 0.73 [0.55]), adenovirus Type 5 vector‐based (Ad5‐vectored) COVID‐19 (1.64 [1.59–1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49–1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12–1.78]; 0.49 [0.11]). Concerning age and sex‐specific risks, reports of vaccine‐induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%).ConclusionA rise in vaccine‐induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5‐vectored COVID‐19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine‐induced TTS for preventive interventions and early diagnosis.
Industrial heterogeneity, governance structure and firm value
Authors: Amin Qazi Awais , Cumming Douglas 
Published: June 2024

AbstractWe examine the impact of corporate governance on firm value by using a unique research approach ‘sector‐wise analyses’ by employing a data set of listed firms in Taiwan. We investigate whether the unique dynamics of each industrial sector could differently affect internal corporate governance (CG) practice. In addition, we investigate the moderating effect of block ownership on the relationships between CG and firm value. Our results show that CG and firm value relationships significantly differ across industrial sectors and conclude that the CG model is not one‐size‐fits‐all for industrial sectors—while observed a significant impact of block ownership as a moderating variable.
Rubble persistence under ocean acidification threatened by accelerated bioerosion and lower‐density coral skeletons
Authors: Webb Alice E. , Palacio‐Castro Ana M. , Cooke Kenzie , Eaton Katherine R. , Chomitz Benjamin , Soderberg Nash , Chakraborty Morgan , Zagon Zachary , Boyd Albert , Kiel Patrick M. , DeMerlis Allyson , Perry Chris T. , Enochs Ian C. 
Published: June 2024

AbstractAs the balance between erosional and constructive processes on coral reefs tilts in favor of framework loss under human‐induced local and global change, many reef habitats worldwide degrade and flatten. The resultant generation of coral rubble and the beds they form can have lasting effects on reef communities and structural complexity, threatening the continuity of reef ecological functions and the services they provide. To comprehensively capture changing framework processes and predict their evolution in the context of climate change, heavily colonized rubble fragments were exposed to ocean acidification (OA) conditions for 55 days. Controlled diurnal pH oscillations were incorporated in the treatments to account for the known impact of diel carbonate chemistry fluctuations on calcification and dissolution response to OA. Scenarios included contemporary pH (8.05 ± 0.025 diel fluctuation), elevated OA (7.90 ± 0.025), and high OA (7.70 ± 0.025). We used a multifaceted approach, combining chemical flux analyses, mass alteration measurements, and computed tomography scanning images to measure total and chemical bioerosion, as well as chemically driven secondary calcification. Rates of net carbonate loss measured in the contemporary conditions (1.36 kg m−2 year−1) were high compared to literature and increased in OA scenarios (elevated: 1.84 kg m−2 year−1 and high: 1.59 kg m−2 year−1). The acceleration of these rates was driven by enhanced chemical dissolution and reduced secondary calcification. Further analysis revealed that the extent of these changes was contingent on the density of the coral skeleton, in which the micro‐ and macroborer communities reside. Findings indicated that increased mechanical bioerosion rates occurred in rubble with lower skeletal density, which is of note considering that corals form lower‐density skeletons under OA. These direct and indirect effects of OA on chemical and mechanical framework‐altering processes will influence the permanence of this crucial habitat, carrying implications for biodiversity and reef ecosystem function.
Changepoint Analysis of Natural Attenuation in Groundwater Improves Forecasts of Time to Attain Goal
Authors: Ferrey Mark L. , William Bouchard Raymond , Wilson John T. 
Published: June 2024

AbstractWhen a remedy is selected for groundwater contamination, the monitoring record is often evaluated to extract rate constants for attenuation of contaminants over time, and the rate constants are used to forecast a time when the concentrations will attain a clean‐up goal. These evaluations typically assume the rate constant does not change. Data from 11 monitoring wells at the former Twin Cities Army Ammunition Plant (TCAAP) were evaluated to test whether this assumption was valid for this site. A previous evaluation at this site (based on data from 1987 through 1999) extracted rate constants that would bring the concentrations of trichloroethylene (TCE) in the 11 wells to the maximum contaminant level (MCL) on or before 2013. By 2020, only four wells had reached the MCL. Piecewise linear regressions were used to model the relationship between time elapsed and concentration of TCE for each well, and to identify any changepoints in the rate of attenuation over time. Each well had at least one changepoint with different TCE attenuation rates on either side of the changepoints. The slope of the most recent segment after the last changepoint provides the best information to forecast concentrations in the future. For four of the wells, that forecast indicated that concentrations of TCE would never reach the MCL. Piecewise linear regression analysis proved to be a valuable tool to detect changes in rate constants, and to update forecasts of the time required for groundwater concentrations to reach a cleanup goal.
A role of epigenetic mechanisms in regulating female reproductive responses to temperature in a pest beetle
Authors: McCaw Beth A. , Leonard Aoife M. , Stevenson Tyler J. , Lancaster Lesley T. 
Published: June 2024

AbstractMany species are threatened by climate change and must rapidly respond to survive in changing environments. Epigenetic modifications, such as DNA methylation, can facilitate plastic responses by regulating gene expression in response to environmental cues. Understanding epigenetic responses is therefore essential for predicting species' ability to rapidly adapt in the context of global environmental change. Here, we investigated the functional significance of different methylation‐associated cellular processes on temperature‐dependent life history in seed beetles, Callosobruchus maculatus Fabricius 1775 (Coleoptera: Bruchidae). We assessed changes under thermal stress in (1) DNA methyltransferase (Dnmt1 and Dnmt2) expression levels, (2) genome‐wide methylation and (3) reproductive performance, with (2) and (3) following treatment with 3‐aminobenzamide (3AB) and zebularine (Zeb) over two generations. These drugs are well‐documented to alter DNA methylation across the tree of life. We found that Dnmt1 and Dnmt2 were expressed throughout the body in males and females, but were highly expressed in females compared with males and exhibited temperature dependence. However, whole‐genome methylation did not significantly vary with temperature, and only marginally or inconclusively with drug treatment. Both 3AB and Zeb led to profound temperature‐dependent shifts in female reproductive life history trade‐off allocation, often increasing fitness compared with control beetles. Mismatch between magnitude of treatment effects on DNA methylation versus life history effects suggest potential of 3AB and Zeb to alter reproductive trade‐offs via changes in DNA repair and recycling processes, rather than or in addition to (subtle) changes in DNA methylation. Together, our results suggest that epigenetic mechanisms relating to Dnmt expression, DNA repair and recycling pathways, and possibly DNA methylation, are strongly implicated in modulating insect life history trade‐offs in response to temperature change.
Impact of socioeconomic status on healthy immune responses in humans
Authors: Bertrand Anthony , Sugrue Jamie , Lou Tianai , Bourke Nollaig M , Quintana‐Murci Lluis , Saint‐André Violaine , O'Farrelly Cliona , Duffy Darragh ,   the Milieu Intérieur Consortium
Published: June 2024

AbstractIndividuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared with people with higher SES. Age, sex, host genetics, smoking and cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo‐rating system using socioeconomic features such as education, income and home ownership status to objectively rank SES in the 1000 donors. We observed sex‐specific SES associations, such as females with a low SES having a significantly higher frequency of CMV seropositivity compared with females with high SES, and males with a low SES having a significantly higher frequency of active smoking compared with males with a high SES. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES‐dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind SES effects on immune responses and ultimately disease.