bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electroconvulsive Therapy for Treatment-Resistant Depression in a Patient With Wolff-Parkinson-White Syndrome
Authors: Gutiérrez-Alzate María Paula , López-Ospino Sebastián , Suárez-Chacón Andrea Marcela , Coral-Sánchez Gina Tatiana , Acero-González Ángela R. 
Published: February 2025

Abstract
Electroconvulsive therapy (ECT) has been recognized as an effective treatment option in severe major depression and treatment-resistant depression. However, its use has been associated with an initial increase in parasympathetic and subsequently sympathetic tone; this has relevance in the context of patients with arrhythmias or pre-excitation syndromes in which some adverse effects have been reported. We present the case of a young female with treatment-resistant depression and a history of Wolff Parkinson White Syndrome admitted for modified ECT. To date, there is no evidence of the anesthetic management of patients with pre-excitation syndromes who require ECT treatment. Therefore, doubts arose regarding the management prior to the procedure. After performing 12 modified ECT sessions an improvement in depressive symptoms was evidenced without any adverse event.
USP7 inhibition perturbs proteostasis and tumorigenesis in triple negative breast cancer
Authors: Kim Ahhyun , Gopalakrishnan Priya , Chen Claire C. , Umesh Nikita , Mordant Angie , Barker Natalie K. , Herring Laura E. , Suárez-Pizarro Marina , Kakati Rasha T. , Spanheimer Philip M. , Emanuele Michael J. , Benavente Claudia A. 
Published: February 2025

ABSTRACTThe deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7’s p53-independent roles in proliferation and tumorigenesis. Triple negative breast cancers frequently inactivate p53 and this disease subtype remains difficult to treat and in need of new therapeutic options. Our study reveals that USP7 is upregulated in TNBC patient tumors. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC models. To explore USP7’s role in p53-mutant TNBCs, we performed deep quantitative proteomics across TNBC cell lines, identifying shared USP7 targets involved in cell proliferation, genome stability, and proteostasis. Acute USP7 inactivation allowed us to infer proximally controlled proteins which are likely direct targets. Surprisingly, many of the proteins downregulated by USP7 inhibition are E3 ubiquitin ligases. Thus, a key USP7 function in TNBC is to antagonize the degradation of ubiquitinating enzymes, since these enzymes are often susceptible to auto-ubiquitination and degradation. Notably, we identified TOPORS, a dual ubiquitin- and SUMO-ligase, among novel USP7 substrates. TOPORS interacts with the BRCA1-A DNA damage repair complex suggesting a USP7-TOPORS-BRAC1-A axis that might further explain the continued proliferation of genomically unstable TNBCs. Collectively, these data nominate USP7 as a potential therapeutic in TNBC.
Factors associated with newly diagnosed ischemic stroke among people in Thailand: A population-based case-control study
Authors: Phasom Junjira , Ungcharoen Ratchadaporn , Pusuwan Pakorn , Phoosuwan Nitikorn 
Published: February 2025

AbstractBackgroundStroke is a leading cause of death and disability-adjusted life years globally. The incidence of stroke is increasing in Asia, with ischemic stroke accounting for approximately 80% of stroke cases in Thailand. Stroke often results in long-term disabilities, including impairments in speech, communication, and concentration.ObjectiveThis study aimed to investigate factors associated with newly diagnosed ischemic stroke.MethodsA matched case-control study was conducted, including 154 newly diagnosed ischemic stroke cases and 183 non-stroke individuals with type 2 diabetes mellitus (T2DM) as controls. Data were collected between February and September 2022 (post-COVID-19 period) using a structured questionnaire covering (1) socio-demographics, (2) lifestyle factors, (3) perceived social support, and (4) self-care management (SCM). Multivariable logistic regression models were employed to calculate adjusted odds ratios (aOR) with 95% confidence intervals (CI).ResultsMost participants were female (60.8%), Buddhists (92.9%), and agriculturists (66.5%), with a mean age of 58.9 (±9.9) years. Factors associated with ischemic stroke included male sex (aOR=3.533, 95%CI 1.732–7.206), Buddhism (aOR=3.529, 95%CI 1.107–11.250), sedentary occupation (aOR=5.785, 95%CI 2.613–12.807), and having T2DM for over 10 years (aOR=6.194, 95%CI 3.553–10.798). Protective factors included age ≥ 60 years (aOR=0.553, 95%CI 0.312–0.982) and moderate SCM levels (aOR=0.453, 95%CI 0.256–0.802).ConclusionProlonged T2DM and sedentary occupations significantly contribute to ischemic stroke incidence. Effective prevention programs, including lifestyle modifications and diabetes self-care management education, may help reduce the burden of ischemic stroke.
SEPSIS-INDUCED LIPID DROPLET ACCUMULATION ENHANCES ANTIBACTERIAL INNATE IMMUNITY
Authors: Pereira-Dutra Filipe S. , Santos Julia Cunha , Souza Ellen Kiarely , Savi Rodrigo Vieira , Souza Tamyris S. , Espinheira-Silva Hugo , Ferraro-Moreira Felipe , Iack Guilherme , Cunha-Fernandes Tamires , Igreja-Silva Tathiany , Palhinha Lohanna , Campos Mariana Macedo , Oliveira Douglas Mathias , Cardoso Vinicius Soares , Rajão Matheus A. , Teixeira Livia , Souza-Moreira Luciana , Costa Maria Fernanda Souza , Reis Patrícia Alves , Bozza Patrícia T. 
Published: February 2025

ABSTRACTLipid droplets (LDs) are lipid-rich organelles recognized as central players in lipid homeostasis, signaling, and inflammation. While their functions in inflammation are well-documented, the role of LDs in antibacterial immunity and infection resistance remains less understood. In this study, we investigated triglyceride synthesis and LD accumulation in the context of antibacterial innate immunity during sepsis. Our results show that LD accumulation is part of immunometabolic reprogramming inE. coli-infected macrophages. Pharmacological inhibition or genetic knockdown of DGAT1, a key enzyme in triglyceride synthesis, reduced LD formation, bacterial clearance, and pro-inflammatory responses (nitric oxide, PGE2, CCL2, IL-6, IFN-β). Notably, DGAT1 inhibition impaired the expression of several interferon-stimulated genes (ISGs), including viperin, iNOS, cathelicidin, and IGTP, inE. coli-infected macrophages. In a sepsis model, DGAT1 inhibition reduced sepsis-induced LD accumulation in peritoneal cells and decreased levels of CCL2, IFN-β, nitric oxide, and lipid mediators (PGE2, LTB4, and RvD1). Furthermore, DGAT1 inhibition accelerated sepsis-related mortality, coinciding with elevated bacterial loads in the peritoneum and bloodstream at 6 and 24 hours post-sepsis. Our results demonstrate that tryglicerides synthesis and LDs are critical regulators of infection resistance, contributing to both bacterial clearance and the coordination of a protective proinflammatory response during sepsis.
Systematic position of edible tropical oysters and first record of genusTalonostrea(Ostreidae) in the Myeik coastal area, Myanmar
Authors: Toyokawa Masaya , Yurimoto Tatsuya , Kang Bong Jung , Sultana Zakea , Aung Cherry 
Published: February 2025

ABSTRACTBelcher’s (Magallana belcheri) and hooded (Saccostrea cuccullata) oysters are edible species in Myeik, Myanmar. Belcher’s oyster is particularly desirable for aquaculture because of its high price and potential value as export products. Previous studies have noted a mismatch between oyster spat settlement patterns and the maturity of the species’ gonads, suggesting the possible settling of unintended oyster species in the Myeik coastal area. To address this issue, DNA barcoding was used to identify oyster species collected from the Myeik coast. Genetic analysis of mitochondrial DNA sequences from various sources of oysters sampled from mangrove roots, experimental cultivation rafts, and settled natural spat revealed an abundance of unidentified species of the genusTalonostreain addition to Belcher’s and hooded oysters. Therefore, this study suggested that collecting aquaculture target oysters from natural spat is inefficient because only a low percentage is found in coastal areas.
Altered endothelial mitochondrial Opa1-related fusion in mouse amplifies age-associated vascular and kidney damages
Authors: Turnaturi Carlotta , L’Hoste Loïck , Proux Coralyne , Grimaud Linda , Vessieres Emilie , Zorzano Antonio , Teissier Anne , Reynier Pascal , Sorrentino Raffaella , Lenaers Guy , Loufrani Laurent , Henrion Daniel 
Published: February 2025

AbstractBackgroundCardiovascular diseases are the major cause of death worldwide and their frequency increases with age in association with progressive kidney damages. Endothelial cells (ECs) are early affected in cardiovascular diseases. Although energy production in ECs involves glycolysis, endothelial mitochondria play a role in modulating cellular signalling. A reduction in fusion protein Opa1 level in ECs decreases the vascular response to flow and increased oxidative stress in perfused kidneys. Thus, we hypothesized that reduced Opa1 expression contributes to vascular aging.MethodsWe used male and female mice with ECs specific Opa1 knock-out (EC-Opa1), and littermate wild-type (EC-WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and Western-blot analysis.ResultsIn old EC-Opa1 mice blood urea was greater than in age-matched EC-WT mice and MRA showed hypercontractilty and reduced endothelium-dependent relaxation. In kidneys, the mitochondria fission protein Fis-1 and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were increase in old EC-Opa1 mice. The level of eNOS expression was greater in young EC-Opa1 mice and caveolin-1 expression greater in old EC-Opa1 mice. Moreover, in kidneys from EC-Opa1 old mice, NADPH-oxidase subunits gp91, p47 and p67 expression was greater than in age-matched EC-WT mice. No difference was observed between old and young EC-WT mice.ConclusionReduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney during aging.
Unusually high frequency of dengue cases with warning signs in patients with no history of previous dengue infection at the Santa Rosa Hospital in the city of Lima
Authors: Durand Solomon , Wong Nadia , Briceño Estefanía , Delgado Raquel , Sánchez Yolanda , Huamani Maria , Fabian Judith , Flores Jean , Contreras Pedro 
Published: February 2025

SummaryIntroductionIn2024, a dengue epidemic affected the city of Lima, a city of more than 10 million inhabitants, for the first time. The Santa Rosa hospital treated more than 5000 febrile patients between January and July 2024, identifying 1788 patients with dengue, 18.6% of them with warning signs or serious, despite being the first infection for them. In order to know the factors related to this unusually high frequency of cases with warning signs and severity in a group of patients who were infected for the first time, this study was developed.MethodologyThe epidemiological records were reviewed and contrasted with the information from the hospital’s emergency care records. The laboratory results were obtained from the laboratories of the hospital and reference in Lima.ResultsBetween January and July 2024, 5,862 febrile patients presented to the hospital emergency room, 1788 were considered cases of dengue. Nine cases (0.5%) were classified as severe dengue and 324 (18.1%) as dengue with warning signs. 4 died. 9.3% of patients over 65 years of age presented some warning or severity sign, while 6.4% of patients under 65 years of age presented warning signs (P 0.05). Only 2.5% (45/1788) responded that they had previously had dengue, but there was no difference between those who presented warning signs or severity.ConclusionsIn conclusion, the dengue epidemic in Lima reached a greater severity than expected despite being the first infection for the affected population, a new massive outbreak and the entry of a new serotype could further increase the severity of the cases.
Modeling Monkeypox Epidemics: Thresholds, Temporal Dynamics, and Waning Immunity from Smallpox Vaccination”
Authors: Yaga Samaila Jackson 
Published: February 2025

AbstractThis study investigates the dynamics of Monkeypox virus (MPXV) through a novel theoretical framework that extends classical epidemic threshold theory. The dual threshold theory is introduced, highlighting the interplay between the time-dependent basic reproduction number and the susceptible population density. Epidemic initiation is shown to occur when the time dependent reproductive number is greater than the threshold value of one and the susceptible population density at any time is greater than the critical threshold density of susceptibles. The model incorporates waning immunity from prior smallpox vaccination and immunity loss from previous MPXV infections, revealing complex epidemic behaviors such as oscillatory waves, prolonged outbreaks, and extended inter-epidemic periods under high transmission scenarios. Sensitivity analyses identify key drivers of epidemic initiation and progression, emphasizing the critical influence of waning immunity and zoonotic reservoirs. Public health implications underline the importance of targeted vaccination campaigns, rodent control, and continuous surveillance to reduce epidemic risks and prevent resurgence. This study provides actionable insights for managing MPXV outbreaks, while the dual threshold framework offers a robust theoretical foundation for understanding the dynamics of waning of vaccine cross immunity and zoonotic diseases.
Failing maternal-fetal tolerance in Systemic Lupus Erythematosus (FaMaLE): a prospective cohort study for finding the molecular mechanisms behind pregnancy complications
Authors: Dankers W. , van Ruitenbeek J.F. , Germe S.A. , Sanchez A.R. Parra , van Gaal M.F.H.M. , de Boer M.A. , van Baarsen L.G.M. , Bultink I.E.M. 
Published: February 2025

ABSTRACTIntroductionPregnant women with systemic lupus erythematosus (SLE) have an increased risk of maternal complications and adverse fetal outcomes. These include preeclampsia, preterm birth and fetal growth restriction. Interestingly, this increased risk persists in subsequent pregnancies, whereas it decreases in healthy women due to the development of maternal-fetal tolerance. As maternal-fetal tolerance is crucial for a healthy pregnancy, we hypothesize that its failure contributes to the increased risk of pregnancy complications in women with SLE. Therefore, we initiated the FaMaLE study to investigate the failure of maternal-fetal tolerance in pregnant women with SLE.Methods and analysisIn the FaMaLE study, healthy women and women with SLE are included in their first trimester of pregnancy (< 14 weeks gestational age (GA)) at Amsterdam UMC. Throughout the pregnancy, data on SLE disease progression, pregnancy course, and medication use are collected. Peripheral blood is collected once per trimester, within 48 hours before delivery and 5-12 weeks post-partum. In addition, the placenta is collected after delivery. Whole blood, peripheral blood mononuclear cells (PBMC) and placenta samples are freshly analyzed by flow cytometry to assess immune cell composition. The resulting data are analyzed in relation to SLE disease course, pregnancy course and pregnancy outcomes.Ethics and disseminationThe study has been approved by the Amsterdam UMC Medical Ethics Committee and all participating women will be asked to provide informed consent. The findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and via patient organizations.STRENGTHS AND WEAKNESSES-A unique prospective longitudinal study design, featuring the collection of serum, plasma and PBMC throughout and after pregnancy, alongside placental cells and biopsies from the same participants. This is complemented by detailed clinical data on SLE disease course and pregnancy course, and outcomes.-Fresh flow cytometry analyses allow immediate assessment of cell composition in blood and placenta, without freeze/thawing effects-The study does not include pre-pregnancy collection of serum, plasma and PBMC; however detailed clinical data are collected during this period.
Evaluating the economic and health impact of proactive genomic epidemiology in a hospital setting
Authors: Hertz Frederik Boetius , Nielsen Karen Leth , Strunin Dmytro , Erdmann Jelena , Jørgensen Martin Lucas , Bendixen Theiss , Srinathan Roshkan , Marvig Rasmus L. , Rasmussen Steen Christian , Rasmussen Asger Nellemann , Jensen Christian Salgaard , Knudsen Jenny Dahl , Häussler Susanne 
Published: February 2025

AbstractBackgroundGenomic epidemiology which combines whole genome sequencing (WGS) of bacterial isolates with patient movement data, promises improved detection, prevention, and management of infection transmission, enhancing patient safety and reducing healthcare costs. However, evidence on its cost-effectiveness and clinical utility remains limited, as initial studies were restricted to selected pathogens and based on extrapolated assumptions from partial WGS data.MethodsWe conducted a 28-month observational study at Rigshospitalet, a 1 200-bed tertiary hospital in Copenhagen. The study involved collecting patient movement and WGS data for clinical isolates of 19 bacterial species, regardless of their site of isolation, or antibiotic susceptibility profile. This included sequencing of 18 940 clinical isolates from 7 760 patients.FindingsWe found that 27·1 % of culture-positive hospitalized patients harboured a pathogen genetically related to another patient’s isolate. 69 % had an epidemiological link, indicating transmission between patients, withEnterococcus faeciumbeing the most prevalent. Notably, there were 2·2 times more transmissions of antibiotic-susceptible than resistant isolates. We estimated that prevention based on genomic epidemiology could potentially generate net savings of €1·25 million annually and avoid more than 750 disability adjusted life years (DALYs).InterpretationOur holistic, proactive genomic epidemiology approach reveals previously unexplored transmission landscapes. We discovered that transmission is widespread, varies significantly between species, and is not limited to resistant isolates. Our results highlight the potential for WGS-informed infection control, greater savings by including susceptible isolates, and an incremental cost-effectiveness ratio (ICER) classification by pathogen species.FundingNovo Nordisk Foundation, Beta.Health, Den Frie Forskningsfond
Context-dependent effects of microbial inoculation on sagebrush seedlings during drought stress
Authors: Heil Jacob A. , Geisler Mathew , Skinner Maddy , DeFehr Chadwick , Arogundade Adedotun , Finney Bruce , Bittleston Leonora S. 
Published: February 2025

SummaryThe leaf microbiome interacts with its plant host and can have critical positive and negative effects on plant health. However, the interactions between leaf microbiomes and host plants remain understudied, particularly in reference to context-dependency, e.g., during drought conditions. Plants naturally exist in environments with ever-changing weather and epiphytic foliar microbes are often exposed to extreme conditions. Little is known about how different environmental contexts can alter the effects of phyllosphere microbes on their plant hosts. In this study, we measured the response of seedlings to microbial inoculations and drought conditions. We usedArtemisia tridentatasubsp.tridentata(hereafter, sagebrush), a foundation species in the vast and critically threatened sagebrush steppe ecosystem. We grew sagebrush plants in growth chambers from sterile seed and after 6 months the seedlings were inoculated in one of four inoculation treatments: (1) no inoculant, (2) sterile water, (3) the microbes washed from the surface of the leaves (a whole natural community), and (4) the single species,Bacillus amyloliquefaciens. We then exposed the seedlings to two environmental treatments: regular watering and a tapered drought. We found context-dependent effects of inoculation on seedling health for both of our inoculation microbial treatments. For example, both inoculants had a negative effect on host plant photosynthesis, which was lessened drought conditions. Furthermore, seedlings inoculated withB. amyloliquefacienshad increased leaf nitrogen levels, and the highest survival under drought conditions. Our study shows that seedling health and survival can be influenced by leaf-associated microbes, and is dependent on environmental context.
A privileged ER compartment for post-translational heteromeric assembly of an ion channel
Authors: Kannan Sudharsan , Kasberg William , Ernandez Liliana R. , Audhya Anjon , Robertson Gail A. 
Published: February 2025

AbstractMechanisms underlying heterotypic subunit assembly of ion channels and other oligomeric assemblies are poorly understood. In the human heart, heteromeric assembly of two isoforms encoded by thehuman ether-à-go-go related gene(hERG) is essential for the normal function of cardiac IKrin ventricular repolarization, with loss of hERG1b contributing to arrhythmias associated with long QT-syndrome. While hERG1a homomers traffic efficiently to the plasma membrane, hERG1b homomers are retained in the endoplasmic reticulum (ER). When expressed together, the two subunits avidly associate during biogenesis. Seeking rules specifying heteromeric association, we characterized the fate of hERG1b proteins using confocal and superresolution imaging in fixed and live HeLa cells. We found hERG1b sequestered in punctate intracellular structures when expressed alone in HeLa cells. These puncta, driven by an N-terminal “RXR” ER retention signal and phase separation, are distinct from other membranous compartments and proteasomal degradation pathways. The puncta represent a privileged ER sub-compartment distinct from that of ER-retained, type 2 (hERG-based) LQTS mutant proteins, which were rapidly degraded by the proteasome. Introducing hERG1a to cells with preformed hERG1b puncta dissolved these puncta by rescuing extant hERG1b. Rescue occurs by association of fully translated hERG1b with 1a, a surprising finding given previous studies demonstrating cotranslational heteromeric association. We propose that sequestration limits potentially deleterious surface expression of hERG1b homomeric channels while preserving hERG1b for an alternative mode of heteromeric hERG1a/1b channel assembly post-translationally. These findings reveal a surprising versatility of biosynthetic pathways promoting heteromeric assembly.