bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of pre-existing coronavirus antibodies on SARS-CoV-2 infection outcomes in exposed household members
Authors: Westerhof Ilse , Sikkema Reina , Rozhnova Ganna , van Beek Janko , Koopmans Marion , Bruijning-Verhagen Patricia 
Published: August 2024

AbstractBackground/RationaleWe investigated the effect of pre-existing antibodies against SARS-CoV-2 and seasonal human coronaviruses on infection outcomes in Omicron BA1/2 exposed household members from January to March 2022.MethodsData from a prospective household study in the Netherlands were used including 63 households with 195 household members exposed to a SARS-CoV-2 Omicron BA1/2 index case. The protocol included repeated nose-throat swab and saliva RT-PCR testing, paired serology, and self-reported daily symptom scoring by household members. Infection outcomes included the occurrence of secondary infections, symptom severity, and CT-value trajectories. We studied the effect of baseline binding antibody levels for SARS-CoVs and seasonal coronaviruses (hCoV) NL63, 229E, HKU1 and OC43 spike protein, on SARS-CoV-2 infection outcomes.Results132 of 195 (68%) exposed household members developed a SARS-CoV-2 infection. Among exposed household members, higher levels of SARS-CoV-2 and beta hCoV antibodies (HKU1 and OC43) at baseline, were associated with a reduced risk of secondary infection (adjusted Odds ratio 0.61; 95% Confidence interval 0.44-0.84 and aOR 0.72; 95%CI 0.56-0.92, respectively). No significant differences between antibody levels and symptom burden or CT-value trajectories were observed.ConclusionsOur study suggests that prior SARS-CoV-2 and beta hCoV antibodies provide some protection against Omicron BA.1/BA.2 infection, while effects on symptom burden or CT-value could not be demonstrated. The results highlight the relatively limited, but not negligible role of cross-protective antibodies, especially when facing immune escape variants of SARS-CoV-2.
Gene expression-based identification of prognostic markers in lung adenocarcinoma
Authors: Salomonsson Annette , Ehinger Daniel , Jönsson Mats , Botling Johan , Micke Patrick , Brunnström Hans , Staaf Johan , Planck Maria 
Published: August 2024

AbstractIntroductionMany studies have aimed at identifying additional prognostic tools to guide treatment choices and patient surveillance in lung cancer by assessing the expression of individual proteins through immunohistochemistry (IHC) or, more recently, through gene expression-based signatures. As a proof-of-concept, we used a multi-cohort, gene expression-based discovery and validation strategy to identify genes with prognostic potential in lung adenocarcinoma. The clinical applicability of this strategy was further assessed by evaluating a selection of the markers by IHC.Materials and MethodsPublicly available gene expression data sets from six microarray-based studies were divided into four discovery and two validation data sets. First, genes associated with overall survival (OS) in all four discovery data sets were identified. The prognostic potential of each identified gene was then assessed in the two validation data sets, and genes associated with OS in both data sets were considered as potential prognostic markers. Finally, IHC for selected potential prognostic markers was performed in two independent and clinically well-characterized lung cancer cohorts.Results and ConclusionsThe gene expression-based strategy identified 19 genes with correlation to OS in all six data sets. Out of these genes, we selected Ki67, MCM4 and TYMS for further assessment with IHC. Although an independent prognostic ability of the selected markers could not be confirmed by IHC, this proof-of-concept study demonstrates that by employing a gene expression-based discovery and validation strategy, potential prognostic markers can be identified and further assessed by a technique universally applicable in the clinical practice. The concept of studying potential prognostic markers through gene expression-based strategies, with a subsequent evaluation of the clinical utility, warrants further exploration.
Genetic analysis of asymptomatic antinuclear antibody production
Authors: Hocaoglu Mehmet , Casares-Marfil Desiré , Sawalha Amr H. 
Published: August 2024

AbstractObjectiveAntinuclear antibodies (ANA) are detected in up to 14% of the population and the majority of individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity in the population is limited. In this study, we aimed to perform a multi-ancestry genome-wide association study (GWAS) of asymptomatic ANA positivity.MethodsAsymptomatic ANA positive and negative individuals from the All of Us Research Program were included in this study, selecting those with an ANA test by immunofluorescence and no evidence of autoimmune disease. Imputation was performed and a multi-ancestry meta-analysis including approximately 6 million single-nucleotide polymorphisms (SNPs) was conducted. Genome-wide SNP based heritability was estimated using the GCTA software. A cumulative genetic risk score for lupus was constructed using previously reported genome-wide significant loci.Results1,955 asymptomatic ANA positive and 3,634 asymptomatic ANA negative individuals were included across three genetic ancestries. The multi-ancestry meta-analysis revealed SNPs with a suggestive association (p-value < 1×10−5) across 8 different loci, but no genome-wide significant loci were identified. A gene variant upstream ofHLA-DQB1(rs17211748,P= 1.4×10-6, OR = 0.82, 95% CI 0.76-0.89) showed the most significant association. The heritability of asymptomatic ANA positivity was estimated to be 24.9%. Asymptomatic ANA positive individuals did not exhibit increased cumulative genetic risk for lupus compared to ANA negative individuals.ConclusionANA production is not associated with significant genetic risk and is primarily determined by non-genetic, likely environmental, factors.
Empathy in psychotherapy: subjective ratings versus remote biosensing of interpersonal heart rate synchrony as outcome predictors
Authors: Gernert Clara C. , Falkai Peter , Falter-Wagner Christine M. 
Published: August 2024

AbstractIn addition to understanding empathy in an affective and cognitive dimension, the physiological domain plays a crucial role, especially in the emotional dynamics of interpersonal interactions during psychotherapy. Within the complex bio-psycho-social system of cognitive behavioural therapy language, cognition, emotion and physiological states of both, client and therapist, intertwine through interaction dynamics. The current study aimed to explore interpersonal physiological dynamics during psychotherapy sessions as an objective biomarker for predicting therapy outcome. In a follow-up assessment design, involving 25 client-psychotherapist dyads, wearable sensors monitored individual’s heart rate, while video cameras recorded movement behaviour during regular cognitive behavioural therapy sessions. Post-session reports and symptom questionnaires were collected from both, clients and therapists, after each session. Results showed that synchrony in head movement and heart rate emerged during psychotherapy sessions. Notably, heart rate synchrony from the initial session predicted changes in patients’ self-rated global severity index over time. The objective predictor, heart rate synchrony, emerged as particularly robust, surpassing patients’ subjective ratings of affiliation in explaining a higher variance of the therapy outcome variable. These findings highlight the potential shown by remote biomarker sensing of interpersonal dynamics for the prediction of psychotherapeutic effectiveness.
Fat burning capacity in a mixed macronutrient meal protocol does not reflect metabolic flexibility in women who are overweight or obese
Authors: Ahern Mary M. , Artegoitia Virginia M. , Bosviel Rémy , Newman John W. , Keim Nancy L. , Krishnan Sridevi 
Published: August 2024

AbstractIntroductionMetabolic flexibility, the ability to switch from glucose to fat as a fuel source, is considered a marker of metabolic health. Higher fat oxidation is often associated with greater flexibility and insulin sensitivity, while lower fat oxidation is linked to metabolic inflexibility and insulin resistance. However, our study challenges the universal validity of this relationship, uncovering a more nuanced understanding of the complex interplay between fuel source switching and fat oxidation, especially in the presence of insulin resistance.MethodsIn an 8-week controlled feeding intervention, overweight to obese women with insulin resistance (as defined by McAuley’s index) were randomized to consume either a diet based on the Dietary Guidelines for Americans 2010 (DGA) or a ‘Typical’ American Diet (TAD), n = 22 each. Participants were given a high-fat mixed macronutrient challenge test (MMCT) (60% fat, 28% carbohydrates, and 12% protein) at weeks 0, 2, and 8. Plasma lipids, metabolome, and lipidome were measured at 0, 0.5, 3, and 6h postprandial (PP); substrate oxidation measures were also recorded at 0,1 3, and 6h PP. Metabolic flexibility was evaluated as the change in fat oxidation from fasting to PP. Mixed model and multivariate analyses were used to evaluate the effect of diet on these outcomes, and to identify variables of interest to metabolic flexibility.ResultsIntervention diets (DGA and TAD) did not differentially affect substrate oxidation or metabolic flexibility, and equivalence tests indicated that groups could be combined for subsequent analyses. Participants were classified into three groups based on the % of consumed MMCT fat was oxidized in the 6h post meal period at weeks 0, 2 and 8. Low fat burners (LB, n = 6, burned <30% of fat in MMCT) and high fat burners (HB, n = 7, burned > 40% of fat in MMCT) at all weeks. Compared to LB, HB group had higher fat mass, total mass, lean mass, BMI, lower HDLc and lower RER (p < 0.05), but not different % body fat or % lean mass. During week 0, at 1h PP, LB had an increase in % fat oxidation change from 0h compared to HB (p<0.05), suggesting higher metabolic flexibility. This difference disappeared later in the PP phase, and we did not detect this beyond week 0. Partial least squares discriminant analysis (PLSDA (regular and repeated measures (sPLSDA)) models identified that LB group, in the late PP phase, was associated with higher rates of disappearance of acylcarnitines (AC) and lysophosphatidylcholines (LPC) from plasma (Q2: 0.20, R2X: 0.177, R2Y: 0.716).ConclusionIn women with insulin resistance, a high fat burning capacity does not imply high metabolic flexibility, and not all women with insulin resistance are metabolically inflexible. LPCs and ACs are promising biomarkers of metabolic flexibility.
SAHVAI-3D and 4D: A New, Automated Subarachnoid Hemorrhage Volumetric Artificial Intelligence (SAHVAI) Measurement Approach Using Non-Contrast Head CT Scans
Authors: Wirtz Melina , Salman Saif , Wei Yujia , Patel Vishal , Sharma Rohan , Gupta Vikash , Gu Qiangqiang , Dherin Benoit , Reddy Sanjana , Tawk Rabih , Erickson Bradley J , Freeman William David 
Published: August 2024

AbstractObjectivesTo automate subarachnoid hemorrhage volume (SAHV) calculation (SAHVAI-SAHV ArtificialIntelligence)and create 3D volumetric images (SAHVAI-3D) using non-contrast head CT (NCCT) imaging data in aneurysmal subarachnoid hemorrhage (SAH) patients. We also defined SAHVAI-4D, representing SAHV over time. The aim was to compare automated SAHVAI volumes to manual SAHV methods and computation times, explore these imaging biomarkers’ potential in identifying at-risk brain regions for delayed cerebral ischemia (DCI), and explore potential insights in future neurotherapeutic interventions for SAH patient recovery.MethodsA training set of 10 consecutive aneurysmal SAH cases was used to manually compute SAHV, SAHVAI-3D, and SAHVAI-4D, involving 92 non-contrast CT scans (182 slices each). The SAHVAI deep learning (DL) algorithm generated automated SAHV values in cubic centimeters (cc). For both SAHVAI and manual evaluations, a 3D SAH brain map was created for each patient. Blood volumetric outputs were analyzed and compared to neurological outcomes at discharge, including DCI events, symptomatic vasospasm (sVSP), and areas with the thickest SAH blood concentration.ResultsSAHVAI quantified SAH blood volume (SAHV) in average of 6.7 seconds per scan, significantly faster than the manual method, which took over 60 minutes per scan (Fisher’s exact test, P value <0.001). SAHVAI demonstrated an accuracy of 99.8%, a Dice score of 0.701, a false positive rate of 0.0005, and a negative predictive value of 0.999. The mean absolute error between SAHVAI and manual methods was 5.67 ml. The SAHVAI-3D brain map and total SAHV at admission were strongly associated with neurological outcomes, inversely with Glasgow coma scale (R2=0.23, p=0.017) and directly with length of hospital stay (R2=0.175, p=0.004), especially in regions with dense blood concentration.ConclusionSAHVAI-3D and SAHVAI-4D brain mapping techniques represent innovative imaging biomarkers for SAH. These advancements enable rapid evaluation and targeted interventions, potentially improving patient care in SAH management.
Exploring associations between estrogen and gene candidates identified by coronary artery disease genome-wide association studies
Authors: Aminbakhsh Ava P. , Théberge Emilie T. , Burden Elizabeth , Kalenga Adejumo Cindy , Lehman Anna , Sedlak Tara L. 
Published: August 2024

AbstractIntroductionCoronary artery disease (CAD) is the leading cause of death around the world, with well-described epidemiological sex and gender differences in prevalence, pathophysiology and management outcomes. It has been hypothesized that sex steroids, like estrogen, may contribute to these sex differences. There is a relatively large genetic component to developing CAD, with heritability estimates ranging between 40-60%. In the last two decades, the computational methods, capabilities and scalability of genome-wide association studies (GWAS) have contributed substantially to advancing the understanding of which genetic candidates contribute to CAD. The aim of this study was to determine if genes discovered in CAD GWASs are affected by estrogen by means of direct modulation or indirect down-stream targets.MethodsA scoping review of the literature was conducted using MEDLINE and EMBASE through to April 24, 2024, for studies synonymous to an atherosclerotic coronary artery disease phenotype, and a genome-wide association study (GWAS) design. Analysis was limited to candidate genes with corresponding single nucleotide polymorphisms (SNPs) surpassing genome-wide significance and had been mapped to genes by study authors. The number of studies that conducted sex-stratified analyses with significant genes were quantified. A literature search of the final gene lists was done to examine any evidence suggesting estrogen may modulate the genes and/or gene products.ResultsThere were 60 eligible CAD GWAS studies meeting inclusion criteria for data extraction. Of these 60, only 36 had genome-wide significant SNPs reported, and only 3 of these had significant SNPs from sex-stratified analyses mapped to genes. From these 36 studies, a total of 61 genes were curated, of which 26 genes (43%) were found to have modulation by estrogen. All 26 were discovered in studies that adjusted for sex. 12/26 genes were also discovered in studies that conducted sex-stratified analyses. 12/26 genes were classified as having a role in lipid synthesis, metabolism and/or lipoprotein mechanisms, while 11/26 were classified as having a role in vascular integrity, and 3/26 were classified as having a role in thrombosis.DiscussionThis study provides further evidence of the relationship between estrogen, genetic risk and the development of CAD. More sex-stratified research will need to be conducted to further characterize estrogen’s relation to sex differences in the pathology and progression of CAD.
Questionable practices in data and code sharing policy in high-profile medical journal and research
Authors: Li Wei , Liu Xuerong , Zhang Qianyu , Shi Liping , Zhang Jing-Xuan , Zhang Xiaolin , Luan Jia , Li Yue , Xu Ting , Zhang Rong , Han Xiaodi , Lei Jingyu , Wang Xueqian , Wang Yaozhi , Lan Hai , Chen Xiaohan , Wu Yi , Wu Yan , Xia Lei , Liao Haiping , Shen Chang , Yu Yang , Xu Xinyu , Deng Chao , Liu Pei , Feng Zhengzhi , Huang Chun-Ji , Chen Zhiyi 
Published: August 2024

AbstractBackgroundThe spurious and unavailable data/code sharing actions are crashing open medical sciences. In this study, we aimed to illustrate how high-profile medical journals are practically carried out their sharing policies and what questionable practices regarding data/code sharing are conducted by authors.MethodsIn this study, we appraised the policy on data/code availability of high-profile medical journals ranked at Q1 according to Clarivate Journal Citation Report (JCR 2021). Furthermore, we recruited post-publications published by four leading medical journals (i.e., The BMJ, JAMA, NEJM and The Lancet) from the issuing of data/code availability policy to December 2022 for the questionable practices in data/code sharing. The appraisal of papers was conducted by the Data/code Availability Statement Practice Evaluation Tool (DANCE), developed by systematically integrating mainstreaming open data/code guidelines.FindingsWe found that less than one-tenth journals (9.1%) mandated authors to share data/code, with an available statement. Among these journals, 70.6% (61.2%) did not consider censoring (restricting) spurious/invalid data/code sharing in publications. Furthermore, though journal impact factor could predict policy stringency on “offering availability statements” (p< .001), it failed to predict ones in “sharing data/code” (p= .73). For publications, even in leading medical journals (i.e., The BMJ, JAMA, NEJM and The Lancet), only 0.5% of the papers (16/3,191) fully complied with their public sharing statements for reaching reproducibility. Lack of availability statement, declining data/code sharing without reasons, and invalid repositories were leading questionable practices conducted by authors.InterpretationWe clarified specific questionable actions of implementing and practicing the sharing policy both in journal and papers, which should be addressed not only by the supportive publication ecosystem but also by crediting authors for taking responsibility and maintaining scientific integrity in data/code sharing.FundingNo funding.
Expression of IL-1R2 by T follicular regulatory cells prevents the exacerbation of allergy by blocking their IL-1-dependent proliferation
Authors: Engeroff Paul , Belbezier Aude , Vaineau Romain , Fourcade Gwladys , Lujan Hugo D , Bellier Bertrand , Graff-Dubois Stephanie , Klatzmann David 
Published: August 2024

ABSTRACTThe antibody response is regulated by follicular T helper (Tfh) and regulatory (Tfr) cells that control the germinal center (GC) reaction. Recent research has shown that Tfh/Tfr have a unique pattern of IL-1 receptor expression. We investigated the mechanisms by which this IL-1 axis in GCs could regulate the allergic response.To study this, we generated CD4creIL-1R1loxmice, specifically lacking IL-1R1 expression in T cells and FoxP3creIL-1R2loxmice, specifically lacking IL-1R2 expression in Tfr cells. The conditional knockout mice were compared to their respective control mice in a model of ovalbumin (OVA) sensitization and anaphylaxis, and a phenotypic and functional characterization of humoral and cellular responses was performed.While CD4creIL-1R1loxmice showed little phenotypic changes, FoxP3creIL-1R2loxmice were highly susceptible to allergic anaphylaxis and generated an increase in IgE responses that promoted basophil degranulation. Additionally, FoxP3creIL-1R2loxmice displayed significantly reduced OVA-specific IgG responses, limiting their ability to control allergy via the inhibitory IgG receptor FcγRIIb. Although FoxP3creIL-1R2loxmice showed an overall increase in splenic T and B cell numbers, they were unable to efficiently generate proliferating GC B cells. Uponex vivoIL-1β and/or OVA re-stimulation, we observed a striking IL-1R1-dependent activation and proliferation of Tfr cells in FoxP3creIL-1R2loxsplenocytes, that was neither observed in Tregs nor in Tfh. At the same time, B cell proliferation upon re-stimulation was suppressed.These findings suggest that IL-1R2 expression on Tfr cells prevents allergy by limiting excessive Tfr activation and suppressing the IgG/IgE ratio.
Phase separation promotes Atg8 lipidation for autophagy progression
Authors: Fujioka Yuko , Tsuji Takuma , Kotani Tetsuya , Kumeta Hiroyuki , Kakuta Chika , Fujimoto Toyoshi , Nakatogawa Hitoshi , Noda Nobuo N. 
Published: August 2024

SUMMARYUpon starvation, the autophagy-initiating Atg1 complex undergoes phase separation to organize the pre-autophagosomal structure (PAS) in yeast, from which autophagosome formation is considered to proceed. However, the physiological roles of the PAS as a liquid droplet remain unclear. Here we show that core Atg proteins are recruited into early PAS droplets that are formed by phase separation of the Atg1 complex with different efficiencies in vitro. The Atg12–Atg5–Atg16 E3 ligase complex for Atg8 lipidation is the most efficiently condensed in the droplets via specific Atg12–Atg17 interaction, which is also important for the PAS targeting of the E3 complex in vivo. In vitro reconstitution experiments reveal that E3-enriched early PAS droplets promote Atg8 lipidation and incorporate Atg8-coated vesicles to the interior, thereby protecting them from Atg4-mediated delipidation. These data suggest that the PAS utilizes its liquid-like property to function as an efficient production site for lipidated Atg8 and pool membrane seeds to drive autophagosome formation.