bluuebunny/crossref_metadata_2025_split huggingface dataset:
Storm‐Time Very‐Near‐Earth Magnetotail Reconnection: A Statistical Perspective
Authors: Beyene F. , Angelopoulos V. 
Published: April 2024

AbstractThe ring current, an equatorial near‐Earth current, fluctuates in response to solar wind plasma interactions with Earth's magnetosphere. Despite extensive research on storm‐time ring current energization, direct evidence of the energy transport into the inner‐magnetosphere that powers this current remains scarce. Recent observations revealing that very‐near‐Earth reconnection (VNERX, occurring at geocentric distance <14 RE) can occur during storms suggest that such reconnection could play an important role in ring current development. Here we address how common VNERX is. We use inner‐magnetosphere and plasma sheet observations from the Time History of Events and Macroscale Interactions during Substorms (THEMIS) satellites spanning 13 years. During this period, THEMIS observed 512 storms and 7 VNERX events. All VNERX events occurred during storm main‐phase at or near the pre‐midnight sector (None were observed during storm recovery‐phase.). The events occurred within 1 RE of the modeled neutral sheet, suggesting that VNERX events are elusive because they lie near the neutral sheet. Since THEMIS spent 5,253 hr within 1 RE of the modeled neutral sheet during storm main‐phase, the inferred observational VNERX occurrence rate is 1.3 per 1,000 hr of storm main‐phase. This rate is lower than published ion‐diffusion‐region occurrence rates seen in the near‐Earth plasma sheet during non‐storm times (likely substorms). These results suggest that while VNERX events might be significant for the storm‐time ring current's initial buildup (during storm main‐phase), other transport mechanisms, like enhanced global convection, may be responsible for maintaining the strength of the ring current during storm recovery‐phase.
Enhanced response of soil respiration to experimental warming upon thermokarst formation
Authors: Wang Guanqin , Peng Yunfeng , Chen Leiyi , Abbott Benjamin W. , Ciais Philippe , Kang Luyao , Liu Yang , Li Qinlu , Peñuelas Josep , Qin Shuqi , Smith Pete , Song Yutong , Strauss Jens , Wang Jun , Wei Bin , Yu Jianchun , Zhang Dianye , Yang Yuanhe 
Published: April 2024

AbstractAs global temperatures continue to rise, a key uncertainty of terrestrial carbon (C)–climate feedback is the rate of C loss upon abrupt permafrost thaw. This type of thawing—termed thermokarst—may in turn accelerate or dampen the response of microbial degradation of soil organic matter and carbon dioxide (CO2) release to climate warming. However, such impacts have not yet been explored in experimental studies. Here, by experimentally warming three thermo-erosion gullies in an upland thermokarst site combined with incubating soils from five additional thermokarst-impacted sites on the Tibetan Plateau, we investigate how warming responses of soil CO2 release would change upon upland thermokarst formation. Our results show that warming-induced increase in soil CO2 release is ~5.5 times higher in thermokarst features than the adjacent non-thermokarst landforms. This larger warming response is associated with the lower substrate quality and higher abundance of microbial functional genes for recalcitrant C degradation in thermokarst-affected soils. Taken together, our study provides experimental evidence that warming-associated soil CO2 loss becomes stronger upon abrupt permafrost thaw, which could exacerbate the positive soil C–climate feedback in permafrost-affected regions.
Development of supramolecular anticoagulants with on-demand reversibility
Authors: Dockerill Millicent , Ford Daniel J. , Angerani Simona , Alwis Imala , Dowman Luke J. , Ripoll-Rozada Jorge , Smythe Rhyll E. , Liu Joanna S. T. , Pereira Pedro José Barbosa , Jackson Shaun P. , Payne Richard J. , Winssinger Nicolas 
Published: April 2024

Abstract
Drugs are administered at a dosing schedule set by their therapeutic index, and termination of action is achieved by clearance and metabolism of the drug. In some cases, such as anticoagulant drugs or immunotherapeutics, it is important to be able to quickly reverse the drug’s action. Here, we report a general strategy to achieve on-demand reversibility by designing a supramolecular drug (a noncovalent assembly of two cooperatively interacting drug fragments held together by transient hybridization of peptide nucleic acid (PNA)) that can be reversed with a PNA antidote that outcompetes the hybridization between the fragments. We demonstrate the approach with thrombin-inhibiting anticoagulants, creating very potent and reversible bivalent direct thrombin inhibitors (K
i = 74 pM). The supramolecular inhibitor effectively inhibited thrombus formation in mice in a needle injury thrombosis model, and this activity could be reversed by administration of the PNA antidote. This design is applicable to therapeutic targets where two binding sites can be identified.
Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries
Authors: Zheng Zhili , Liu Shouye , Sidorenko Julia , Wang Ying , Lin Tian , Yengo Loic , Turley Patrick , Ani Alireza , Wang Rujia , Nolte Ilja M. , Snieder Harold ,   LifeLines Cohort Study, Aguirre-Gamboa Raul , Deelen Patrick , Franke Lude , Kuivenhoven Jan A. , Lopera Maya Esteban A. , Sanna Serena , Swertz Morris A. , Vonk Judith M. , Wijmenga Cisca , Yang Jian , Wray Naomi R. , Goddard Michael E. , Visscher Peter M. , Zeng Jian 
Published: April 2024

AbstractWe develop a method, SBayesRC, that integrates genome-wide association study (GWAS) summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by allowing them to affect both causal variant probability and causal effect distribution. We analyze 50 complex traits and diseases using ∼7 million common single-nucleotide polymorphisms (SNPs) and 96 annotations. SBayesRC improves prediction accuracy by 14% in European ancestry and up to 34% in cross-ancestry prediction compared to the baseline method SBayesR, which does not use annotations, and outperforms other methods, including LDpred2, LDpred-funct, MegaPRS, PolyPred-S and PRS-CSx. Investigation of factors affecting prediction accuracy identifies a significant interaction between SNP density and annotation information, suggesting whole-genome sequence variants with annotations may further improve prediction. Functional partitioning analysis highlights a major contribution of evolutionary constrained regions to prediction accuracy and the largest per-SNP contribution from nonsynonymous SNPs.
Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children
Authors: Zhong Youjia , Kang Alicia Y. H. , Tay Carina J. X. , Li Hui’ En , Elyana Nurul , Tan Chee Wah , Yap Wee Chee , Lim Joey M. E. , Le Bert Nina , Chan Kuan Rong , Ong Eugenia Z. , Low Jenny G. , Shek Lynette P. , Tham Elizabeth Huiwen , Ooi Eng Eong 
Published: April 2024

AbstractThe paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5–12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children.
Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial
Authors: Schuler Martin , Cuppens Kristof , Plönes Till , Wiesweg Marcel , Du Pont Bert , Hegedus Balazs , Köster Johannes , Mairinger Fabian , Darwiche Kaid , Paschen Annette , Maes Brigitte , Vanbockrijck Michel , Lähnemann David , Zhao Fang , Hautzel Hubertus , Theegarten Dirk , Hartemink Koen , Reis Henning , Baas Paul , Schramm Alexander , Aigner Clemens 
Published: April 2024

AbstractAntibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552.
Study on the adsorption of Zn(II) and Cu(II) in acid mine drainage by fly ash loaded nano-FeS
Authors: Guo Xuying , Fu Honglei , Gao Xinle , Zhao Zilong , Hu Zhiyong 
Published: April 2024

AbstractAiming at the acid mine drainage (AMD) in zinc, copper and other heavy metals treatment difficulties, severe pollution of soil and water environment and other problems. Through the ultrasonic precipitation method, this study prepared fly ash-loaded nano-FeS composites (nFeS-F). The effects of nFeS-F dosage, pH, stirring rate, reaction time and initial concentration of the solution on the adsorption of Zn(II) and Cu(II) were investigated. The data were fitted by Lagergren first and second-order kinetic equations, Internal diffusion equation, Langmuir and Freundlich isotherm models, and combined with SEM, TEM, FTIR, TGA, and XPS assays to reveal the mechanism of nFeS-F adsorption of Zn(II) and Cu(II). The results demonstrated that: The removal of Zn(II) and Cu(II) by nFeS-F could reach 83.36% and 70.40%, respectively (The dosage was 8 g/L, pH was 4, time was 150 min, and concentration was 100 mg/L). The adsorption process, mainly chemical adsorption, conforms to the Lagergren second-order kinetic equation (R2 = 0.9952 and 0.9932). The adsorption isotherms have a higher fitting degree with the Langmuir model (R2 = 0.9964 and 0.9966), and the adsorption is a monolayer adsorption process. This study can provide a reference for treating heavy metals in acid mine drainage and resource utilization of fly ash.
The psychological costs of behavioral immunity following COVID-19 diagnosis
Authors: Spangler Derek P. , Li Evaline Y. , Revi Gabriela S. , Kubota Jennifer T. , Cloutier Jasmin , Lauharatanahirun Nina 
Published: April 2024

AbstractPrior COVID-19 infection may elevate activity of the behavioral immune system—the psychological mechanisms that foster avoidance of infection cues—to protect the individual from contracting the infection in the future. Such “adaptive behavioral immunity” may come with psychological costs, such as exacerbating the global pandemic’s disruption of social and emotional processes (i.e., pandemic disruption). To investigate that idea, we tested a mediational pathway linking prior COVID infection and pandemic disruption through behavioral immunity markers, assessed with subjective emotional ratings. This was tested in a sample of 734 Mechanical Turk workers who completed study procedures online during the global pandemic (September 2021–January 2022). Behavioral immunity markers were estimated with an affective image rating paradigm. Here, participants reported experienced disgust/fear and appraisals of sickness/harm risk to images varying in emotional content. Participants self-reported on their previous COVID-19 diagnosis history and level of pandemic disruption. The findings support the proposed mediational pathway and suggest that a prior COVID-19 infection is associated with broadly elevated threat emotionality, even to neutral stimuli that do not typically elicit threat emotions. This elevated threat emotionality was in turn related to disrupted socioemotional functioning within the pandemic context. These findings inform the psychological mechanisms that might predispose COVID survivors to mental health difficulties.
Identification of gene isoforms and their switching events between male and female embryos of the parthenogenetic crustacean Daphnia magna
Authors: Kato Yasuhiko , Nitta Joel H. , Perez Christelle Alexa Garcia , Adhitama Nikko , Religia Pijar , Toyoda Atsushi , Iwasaki Wataru , Watanabe Hajime 
Published: April 2024

AbstractThe cladoceran crustacean Daphnia exhibits phenotypic plasticity, a phenomenon that leads to diverse phenotypes from one genome. Alternative usage of gene isoforms has been considered a key gene regulation mechanism for controlling different phenotypes. However, to understand the phenotypic plasticity of Daphnia, gene isoforms have not been comprehensively analyzed. Here we identified 25,654 transcripts derived from the 9710 genes expressed during environmental sex determination of Daphnia magna using the long-read RNA-Seq with PacBio Iso-Seq. We found that 14,924 transcripts were previously unidentified and 5713 genes produced two or more isoforms. By a combination of Illumina short-read RNA-Seq, we detected 824 genes that implemented switching of the highest expressed isoform between females and males. Among the 824 genes, we found isoform switching of an ortholog of CREB-regulated transcription coactivator, a major regulator of carbohydrate metabolism in animals, and a correlation of this switching event with the sexually dimorphic expression of carbohydrate metabolic genes. These results suggest that a comprehensive catalog of isoforms may lead to understanding the molecular basis for environmental sex determination of Daphnia. We also infer the applicability of the full-length isoform analyses to the elucidation of phenotypic plasticity in Daphnia.
Saturated fatty acids inhibit unsaturated fatty acid induced glucose uptake involving GLUT10 and aerobic glycolysis in bovine granulosa cells
Authors: Tao Xuelian , Rahimi Maryam , Michaelis Marten , Görs Solvig , Brenmoehl Julia , Vanselow Jens , Baddela Vijay Simha 
Published: April 2024

AbstractFatty acids have been shown to modulate glucose metabolism in vitro and in vivo. However, there is still a need for substantial evidence and mechanistic understanding in many cell types whether both saturated and unsaturated fatty acids (SFAs and UFAs) pose a similar effect and, if not, what determines the net effect of fatty acid mixes on glucose metabolism. In the present study, we asked these questions by treating granulosa cells (GCs) with the most abundant non-esterified fatty acid species in bovine follicular fluid. Results revealed that oleic and alpha-linolenic acids (UFAs) significantly increased glucose consumption compared to palmitic and stearic acids (SFAs). A significant increase in lactate production, extracellular acidification rate, and decreased mitochondrial activity indicate glucose channeling through aerobic glycolysis in UFA treated GCs. We show that insulin independent glucose transporter GLUT10 is essential for UFA driven glucose consumption, and the induction of AKT and ERK signaling pathways necessary for GLUT10 expression. To mimic the physiological conditions, we co-treated GCs with mixes of SFAs and UFAs. Interestingly, co-treatments abolished the UFA induced glucose uptake and metabolism by inhibiting AKT and ERK phosphorylation and GLUT10 expression. These data suggest that the net effect of fatty acid induced glucose uptake in GCs is determined by SFAs under physiological conditions.
Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer
Authors: Nakamoto Shogo , Shien Tadahiko , Iwamoto Takayuki , Kubo Shinichiro , Yamamoto Mari , Yamashita Tetsumasa , Kuwahara Chihiro , Ikeda Masahiko 
Published: April 2024

AbstractCyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 − ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 − ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/μL for ALC and 3 for NLR, and divided into “low” and “high” groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12–0.70; NLR: HR 2.94; 95% CI 1.21–7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 − ABC.
Research on a machine learning-based adaptive and efficient screening model for psychological symptoms of community correctional prisoners
Authors: Xu Zhifei , Pan Zhigeng , Wang Yan , Zhang Yichao , Leng Pengfei 
Published: April 2024

AbstractCommunity correction institutions in China frequently employ the Symptom Checklist-90 (SCL-90) and the health survey brief (SF-12) as primary tools for psychological assessment of community correctional prisoners. However, in practical application, the SCL-90 Checklist faces issues such as complex item numbers, overall low cultural level of the subjects, and insufficient professional level of the administrators. The SF-12 health survey brief, as a preliminary screening tool, although only has 12 questions, to some extent simplifies the evaluation process and improves work efficiency, it is prone to missed screening. The research team collected 17-dimensional basic characteristic data and corresponding SCL-90 and SF-12 data from 25,480 samples of community correctional prisoners in Zhejiang Province, China. This study explored the application of multi-label multi-classification algorithms and oversampling techniques in building machine learning models to delve into the correlation between the psychological health risks of community correctional prisoners and their characteristic data. Inspired by computerized adaptive testing (CAT), we constructed an adaptive and efficient screening model for community correctional prisoners through experimental comparisons, based on the binary relevance algorithm with sample oversampling. This screening model personalize the assessment process by dynamically matching participants with the most relevant subset (s) of the nine dimensions of the SCL-90 based on their individual characteristics. Thus, adaptive dynamic simplification and personalized recommendation of the SCL-90 scale between question groups were achieved for the specific group of community correctional prisoners. As a screening tool for psychological symptoms of community correctional prisoners, this model significantly simplifies the number of questions compared to SCL-90, with a simplification rate of up to 65%. However, it achieves this simplification while maintaining excellent performance. The accuracy reached 0.66, with a sensitivity of 0.754, and an F1 score of 0.649. This innovation simplified the assessment process, reduced the assessment time, improved work efficiency, and enhanced the ability to judge the specificity of community correctional prisoners population. Compared to the SF-12, although the simplification rate and accuracy of the model are slightly lower than those of the SF-12, the sensitivity increased by 42.26%, and the F1 score improved by 15.28%. This means the model greatly reduces the possibility of missed screening, effectively preventing prisoners with abnormal psychological or mental states from losing control due to missed screening, and even committing suicide, self injury, or injuring others.
The differential effect of psychopathy on active and bystander trolling behaviors: the role of dark tetrad traits and lower agreeableness
Authors: Ubaradka Anantha , Khanganba Sanjram Premjit 
Published: April 2024

AbstractThis study aimed to develop the Global Assessment of Active Trolling and Passive Bystanderism (GAATPB) scale and investigate the influence of personality traits on trolling behaviors. Focusing on the Dark Tetrad (DT) traits and agreeableness, the present study examined their associations and predictive utility on active trolling and passive bystanderism. Participants were recruited from social networking sites (SNSs), and eligibility criteria included active SNS usage and engagement in online interactions. A total of 797 healthy adult students participated in the study, with data from 300 used for the initial exploratory factor analysis (EFA) and the remaining 497 (Mage = 22.25 years, SD = 3.37) for the subsequent analyses. Results indicated a significant correlation between DT traits and agreeableness across both active trolling and passive bystanderism, revealing a shared personality profile. Hierarchical multiple regression analyses showed that narcissism, Machiavellianism, and trait sadism were predictors of active trolling, with psychopathy being the strongest predictor. However, psychopathy did not emerge as a predictor for passive bystanderism. The study also highlighted that DT traits mediated the relationship between lower agreeableness and overall trolling behavior, suggesting that trolling manifests from lower agreeableness through the instigation of callous-unemotional, manipulative, and self-centered traits inherent in DT.