bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of immunoglobulin E levels with glioma risk and survival
Authors: Guerra Geno , Nakase Taishi , Kachuri Linda , McCoy Lucie , Hansen Helen M. , Rice Terri , Wiemels Joseph. L. , Wiencke John K. , Molinaro Annette M. , Wrensch Margaret , Francis Stephen S. 
Published: May 2024

ABSTRACTBackgroundPrevious epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.MethodsWe conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n=1319) and cancer-free controls (n=1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided.ResultsElevated total IgE was associated with reduced risk of IDH-wildtype (RR=0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR=0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR=0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR=0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001).ConclusionElevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.
Optimal Donor Selection Across Multiple Outcomes For Hematopoietic Stem Cell Transplantation By Bayesian Nonparametric Machine Learning
Authors: Sparapani Rodney A , Maiers Martin , Spellman Stephen R. , Shaw Bronwen E , Laud Purushottam W , Devine Steven M. , Logan Brent R 
Published: May 2024

AbstractAllogeneic hematopoietic cell transplantation (HCT) is one of the only curative treatment options for patients suffering from life-threatening hematologic malignancies; yet, the possible adverse complications can be serious even fatal. Matching between donor and recipient for 4 of the HLA genes is widely accepted and supported by the literature. However, among 8/8 allele matched unrelated donors, there is less agreement among centers and transplant physicians about how to prioritize donor characteristics like additional HLA loci (DPB1 and DQB1), donor sex/parity, CMV status, and age to optimize transplant outcomes. This leads to varying donor selection practice from patient to patient or via center protocols. Furthermore, different donor characteristics may impact different post transplant outcomes beyond mortality, including disease relapse, graft failure/rejection, and chronic graft-versus-host disease (components of event-free survival, EFS). We develop a general methodology to identify optimal treatment decisions by considering the trade-offs on multiple outcomes modeled using Bayesian nonparametric machine learning. We apply the proposed approach to the problem of donor selection to optimize overall survival and event-free survival, using a large outcomes registry of HCT recipients and their actual and potential donors from the Center for International Blood and Marrow Transplant Research (CIBMTR). Our approach leads to a donor selection strategy that favors the youngest male donor, except when there is a female donor that is substantially younger.
Development and Iterative Design of Peer-based Discussions about Heart Health for Women
Authors: Spatz Erica S , Park Tina , Breslin Maggie 
Published: May 2024

AbstractObjectiveTo support women in their health journeys around cardiovascular risk reduction, providing: access to information; space to discuss complex and personal issues that may factor into decision making; and skills to support conversations with healthcare providers.MethodsWe used a participatory design approach to develop peer sessions led by a non-clinical facilitator and a cardiologist, for women to learn, think, and discuss information and decision-making around cardiovascular risk. These sessions took place in-person and over video. A host invited her friends, family or network to the events. Sessions were designed to bring information to women at all stages of cardiovascular risk, including women with no prior experiences with heart health and women with established cardiovascular disease. The sessions provided information about cardiovascular risk and facilitated discussion around risk factors and treatment. Sessions were recorded, transcribed and analyzed using a grounded theory approach to identify emerging themes.ResultsWe conducted 12 groups, with an average of 6 women per group. Women were of all ages and spectrums of cardiovascular risk. The three major themes that emerged were: Starting Place (attitudes, beliefs, and behaviors toward cardiovascular care are informed by a blend of one’s family history, personal interactions with their health and the health system, and approach to managing uncertainty); Lack of Sense-Making (seemingly simple recommendations to support heart health were much more complicated when related to their own risk and experience), and Self-Judgement and Judgement by Others (without support or validation, women may feel judged by others for not doing enough).ConclusionPeer sessions can illuminate the complicated issues women face when approaching decisions regarding cardiovascular health. These sessions may offer an alternative to the healthcare setting, for women to wrestle with complex issues that relate to their risk, and better prepare for visits with their healthcare providers.HighlightsPeer-based sessions designed to support cardiovascular risk reduction conversations can support women in their healthcare journeys.Women approach cardiovascular risk from different starting places and are challenged with sense-making of conflicting data.Women are often judged by themselves, and others, about doing ‘enough’ to prevent cardiovascular disease.Peer-based sessions offer a space for women to think, feel, and discuss issues most relevant to them, which may help support conversations with their healthcare providers.
Genetic correlation and causality between smoking and 42 neuropsychiatric and gastrointestinal diseases
Authors: Xiong Jiayi , Wang Zheng , Huang Yuanfeng , Zhang Shiyu , Yang Guang , Yang Jiaqi , Gao Shuo , Wang Tianyang , Li Jinchen , Zhao Guihu , Li Bin 
Published: May 2024

AbstractBackgroundPrevious investigations have elucidated epidemiological associations linking smoking to neuropsychiatric and gastrointestinal diseases, yet the underlying causal relationships remain enigmatic. To shed light on this matter, we undertook a Mendelian randomisation(MR) study with the aim of gauging the potential causal association between smoking and the susceptibility to neuropsychiatric and gastrointestinal tract diseases.MethodsWe meticulously collected and preprocessed genome-wide association study (GWAS) data encompassing smoking (280,508 cases and 180,558 controls) as well as neuropsychiatric and gastrointestinal phenotypes (n = 6,681 to 87,3341). To investigate the genetic correlation between smoking and diseases, we employed linkage disequilibrium score regression. We further applied multi-trait analysis of GWAS to identify the shared risk single-nucleotide polymorphisms (SNPs) implicated in both smoking and diseases. Pleiotropic genes were annotated by enrichment analysis. Subsequently, bidirectional MR analysis was performed to infer causality.ResultsOur findings, supported by robust evidence derived from an expansive sample size, demonstrate that smoking exerts a causal influence on merely six of these diseases, while no disease was found to causally impact smoking. Intriguingly, we discovered 513 pleiotropic genes enriched in pathways such as the regulation of growth and synapses, suggesting a potential shared genetic basis between smoking and these diseases, leading to aberrant neural development. Remarkably, among the 42 diseases scrutinized, a significant genetic correlation was exclusively observed with gastroesophageal reflux disease (GRED). Furthermore, we identified risk SNPs shared by smoking and GRED.ConclusionsThis study revealed the shared genetic basis and causal effects connecting smoking to neuropsychiatric and gastrointestinal diseases, thereby providing novel etiological insights into the role of smoking in these diseases.
A cross-sectional study to evaluate access to antenatal care services in Twifo Hemang Lower Denkyira district of Ghana
Authors: Hammond John , Adjei-Gyamfi Silas , Daniels Doreen Brew , Sarpong Godfred Kwabena , Aiga Hirotsugu , Aoki Tsunenori 
Published: May 2024

AbstractBackgroundAntenatal care (ANC) which is an essential component of the reproductive, maternal, newborn, and child health continuum of care is found to positively correlate with supervised delivery and the reduction of maternal deaths. In Ghana, few studies have explored how ANC is influenced by the community-based health planning and services (CHPS) policy, and in the Central Region, evidence is non-existent. This study aimed to determine factors that influence access to ANC services provided through the CHPS policy in the Twifo Hemang Lower Denkyira district in the Central Region of Ghana.MethodsA cross-sectional study examined 310 women aged 15-49 years, having children less than 12 months, and interviewed using a structured questionnaire. Univariate and multivariate logistic regression analyses were conducted using STATA 17 and results were reported as odds ratios at a confidence level of 95%.ResultsANC coverage and proportion of early ANC initiation were 93.9% and 69.1% respectively.Being unmarried (AOR=0.125, 95%CI=0.012,0.926), and home delivery (AOR=0.013; 95%CI: 0.001,0.176) were associated with decreased odds of at least one ANC visit during pregnancy. Larger (≥11) household size (AOR=3.848; 95%CI=1.914,16.21), lesser (<4) ANC contacts (AOR=6.332; 95%CI=2.049,19.57), and home visitation by CHPS staff (AOR=1.813; 95%CI=1.014,3.243) were associated with higher odds of late ANC initiation while average monthly income (AOR=0.123; 95%CI=0.024,0.630) was associated with reduced odds of late ANC initiation. Interestingly, knowledge about ANC and pregnancy, and geographical variables like receiving ANC services from CHPS zones, and distance to CHPS zones were not statistically significant with either ANC attendance or time of ANC initiation after controlling for the effect of other variables.ConclusionThough ANC and early ANC initiation coverages were relatively high, the complexities in the given correlates of ANC accessibility require a multi-sectoral approach to strengthen community-based services to increase the survival of pregnant women and unborn babies.
USP14 regulates pS129 α-synuclein levels and oxidative stress in human SH-SY5Y dopaminergic cells
Authors: Srinivasan Vignesh , Soliymani Rabah , Ivanova Larisa , Eriksson Ove , Peitsaro Nina , Lalowski Maciej , Karelson Mati , Lindholm Dan 
Published: May 2024

AbstractUbiquitin specific protease-14 (USP14) is critical for controlling protein homeostasis disturbed in human disorders like Parkinsońs disease (PD). Here we investigated the role of USP14 in regulating proteasome and autophagy pathways, and their influence on α-synuclein (α-syn) degradation. Data showed that α-syn and phosphorylated serine129 α-syn (pS129 α-syn) were elevated inUSP14gene-deleted SH-SY5Y dopaminergic cells with concomitant reduction in proteasome activity. Inhibition of proteasomes using MG132 particularly elevated pS129 α-syn in these cells, but the levels were not influenced by inhibiting autophagy using chloroquine. In contrast, autophagy and the CLEAR (Coordinated Lysosomal Expression and Regulation) pathways were elevated in USP14 lacking cells with an upregulation of the transcription factor TFEB. USP14-ablated cells also exhibited increases in reactive oxidative species (ROS) and elongation of mitochondria. The addition of N-Acetylcysteine amide (NACA) to counteract oxidative stress, reduced pS129 α-syn and α-syn levels in USP14 deficient cells. Phospho-proteomic analyses revealed that USP14 is phosphorylated at S143 affecting its function and structure as shown by molecular modeling, and protein interaction studies. Re-expression of wild-type and the phospho-mimetic S143D-USP14 mutant decreased ROS, pS129 α-syn, and α-syn in USP14 lacking cells. These results demonstrate that pS129 α-syn levels are sensitive to oxidative stress in SH-SY5Y dopaminergic cells. USP14 by stimulating the proteasome activity and reducing oxidative stress is a promising factor for targeting α-syn and its pathogenic variants in PD.
Spatial domains identification in spatial transcriptomics by domain knowledge-aware and subspace-enhanced graph contrastive learning
Authors: Gui Yang , Li Chao , Xu Yan 
Published: May 2024

ABSTRACTSpatial transcriptomics (ST) technologies have emerged as an effective tool to identify the spatial architecture of the tissue, facilitating a comprehensive understanding of organ function and tissue microenvironment. Spatial domain identification is the first and most critical step in ST data analysis, which requires thoughtful utilization of tissue microenvironment and morphological priors. To this end, we propose a graph contrastive learning framework, GRAS4T, which combines contrastive learning and subspace module to accurately distinguish different spatial domains by capturing tissue microenvironment through self-expressiveness of spots within the same domain. To uncover the pertinent features for spatial domain identification, GRAS4T employs a graph augmentation based on histological images prior, preserving information crucial for the clustering task. Experimental results on 8 ST datasets from 5 different platforms show that GRAS4T outperforms five state-of-the-art competing methods in spatial domain identification. Significantly, GRAS4T excels at separating distinct tissue structures and unveiling more detailed spatial domains. GRAS4T combines the advantages of subspace analysis and graph representation learning with extensibility, making it an ideal framework for ST domain identification.
Endogenous retrovirus ERV-DC8 highly integrated in domestic cat populations is a replication-competent provirus
Authors: Pramono Didik , Muto Yutaro , Shimazu Yo , Deshapriya R.M.C. , Makundi Isaac , Arnal MaríaCruz , de Luco Daniel Fernández , Ngo Minh Ha , Miyake Ariko , Nishigaki Kazuo 
Published: May 2024

AbstractEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections in vertebrate genomes and are inherited by offspring. ERVs can produce pathogenic viruses through gene mutations or recombination. ERVs in domestic cats (ERV-DCs) generate feline leukemia virus subgroup D (FeLV-D) through viral recombination. Herein, we characterized the locus ERV-DC8, on chromosome B1, as an infectious replication-competent provirus. ERV-DC8 infected several cell lines, including human cells. Transmission electron microscopy of ERV-DC8 identified the viral release as aGammaretrovirus. ERV-DC8 was identified as the FeLV-D viral interference group, with feline copper transporter 1 as its viral receptor. Insertional polymorphism analysis showed high ERV-DC8 integration in domestic cats. This study highlights the role, pathogenicity, and evolutionary relationships between ERVs and their hosts.
3-nitrotyrosine shortens axons of a non-dopaminergic neuron by inhibiting mitochondrial motility
Authors: Hirai Masahiro , Suzuki Kohei , Kassai Yusuke , Konishi Yoshiyuki 
Published: May 2024

Abstract3-nitrotyrosine (3-NT), a byproduct of oxidative/nitrosative stress, is implicated in age-related neurodegenerative disorders. Existing literature indicates that free 3-NT becomes integrated into the carboxy-terminal domain of α-tubulin through the tyrosination/detyrosination cycle. Independently of this integration, 3-NT has been linked to the cell death of dopaminergic neurons. Given the critical role of tyrosination/detyrosination in governing axonal morphology and function, the substitution of tyrosine with 3-NT in this process may potentially disrupt axonal homeostasis, although this aspect remains underexplored. In this study, we examined the impact of 3-NT on the axons of cerebellar granule neurons, representing non-dopaminergic neurons. Our observations revealed axonal shortening, which correlated with the incorporation of 3-NT into α-tubulin. Importantly, this axonal effect was observed prior to the onset of cellular death. Furthermore, 3-NT was found to diminish mitochondrial motility within the axon, resulting in a subsequent reduction in mitochondrial membrane potential. The suppression of syntaphilin, a protein responsible for anchoring mitochondria to microtubules, reversed the 3-NT-induced decrease in mitochondrial motility, consequently restoring axonal elongation. These findings underscore the inhibitory role of 3-NT in axonal elongation by impeding mitochondrial movement, implying its potential involvement in axonal dysfunction within non-dopaminergic neurons.
Natural phasic inhibition of dopamine neurons signals cognitive rigidity
Authors: Burwell Sasha C.V. , Yan Haidun , Lim Shaun S.X. , Shields Brenda C. , Tadross Michael R. 
Published: May 2024

AbstractWhen animals unexpectedly fail, their dopamine neurons undergo phasic inhibition that canonically drives extinction learning—a cognitive-flexibility mechanism for discarding outdated strategies. However, the existing evidence equates natural and artificial phasic inhibition, despite their spatiotemporal differences. Addressing this gap, we targeted a GABAA-receptor antagonist precisely to dopamine neurons, yielding three unexpected findings. First, this intervention blocked natural phasic inhibition selectively, leaving tonic activity unaffected. Second, blocking natural phasic inhibition accelerated extinction learning—opposite to canonical mechanisms. Third, our approach selectively benefitted perseverative mice, restoring rapid extinction without affecting new reward learning. Our findings reveal that extinction learning is rapid by default and slowed by natural phasic inhibition—challenging foundational learning theories, while delineating a synaptic mechanism and therapeutic target for cognitive rigidity.
A comparison among EL-FAME, PLFA, and quantitative PCR methods to detect changes in the abundance of soil bacteria and fungi
Authors: Siles José A. , Gómez-Pérez Roberto , Vera Alfonso , García Carlos , Bastida Felipe 
Published: May 2024

AbstractEL-FAME (ester-linked fatty acid methyl ester), PLFA (phospholipid fatty acid) and qPCR (quantitative PCR) of ribosomal genes are three of the most common methods used to quantify soil microbial communities. The reliability of these three methods has not been simultaneously compared in situations of rapid changes in soil microbial abundances. For this purpose, we (i) incubated badland, cropland, and forest soils with nutrients or antibiotics for 2, 7, 14, and 28 days, (ii) quantified total, bacterial, and fungal abundances through EL-FAME, PLFA, and qPCR methods, and (iii) measured soil basal respiration. The general dynamic patterns of the three soil microbial fractions in response to soil addition of nutrients and antibiotics were captured by the three methods, which led to strong and positive associations between the abundances of total microorganisms, bacteria, and fungi measured by the three techniques. However, these relationships were found to be stronger between the EL-FAME and PLFA results, indicating that reliability of the fatty-acid based methods is higher than that of the qPCR. Further, soil basal respiration was associated to a higher extent with total, bacterial, and fungal abundances captured by EL-FAME and PLFA analyses than with those measured by qPCR, which suggests that the first two methods are most closely related to the soil living microbial community. In general, dynamics in the abundance of total and bacterial communities were better captured than those of fungi. The PLFA analysis seems to perform better than the EL-FAME method in forest soil and in detecting the small antibiotic-induced decreases in microbial abundances. Since the EL-FAME method is cheaper and allows a much faster processing of samples than the PLFA method, and the reliability of both methods is similar in detecting rapid changes of soil microbial abundances, choosing EL-FAME over PLFA may be advantageous in most cases.
Structural and functional analyses of SARS-CoV-2 Nsp3 and its specific interactions with the 5’ UTR of the viral genome
Authors: Lemak Sofia , Skarina Tatiana , Flick Robert , Patel Deepak T. , Stogios Peter J. , Savchenko Alexei 
Published: May 2024

AbstractNon-structural protein 3 (Nsp3) is the largest open reading frame encoded in the SARS-CoV-2 genome, essential for formation of double-membrane vesicles (DMV) wherein viral RNA replication occurs. We conducted an extensive structure-function analysis of Nsp3 and determined the crystal structures of the Ubiquitin-like 1 (Ubl1), Nucleic Acid Binding (NAB), β-coronavirus-Specific Marker (βSM) domains and a sub-region of the Y domain of this protein. We show that the Ubl1, ADP-ribose phosphatase (ADRP), human SARS Unique (HSUD), NAB, and Y domains of Nsp3 bind the 5’ UTR of the viral genome and that the Ubl1 and Y domains possess affinity for recognition of this region, suggesting high specificity. The Ubl1-Nucleocapsid (N) protein complex binds the 5’ UTR with greater affinity than the individual proteins alone. Our results suggest that multiple domains of Nsp3, particularly Ubl1 and Y, shepherd the 5’ UTR of viral genome during translocation through the DMV membrane, priming the Ubl1 domain to load the genome onto N protein.
Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases
Authors: Sokratian Arpine , Zhou Ye , Tatli Meltem , Burbidge Kevin J. , Xu Enquan , Viverette Elizabeth , Duda Addison M. , Yuan Yuan , Strader Samuel , Patel Nirali , Shiell Lauren , Malankhanova Tuyana , Chen Olivia , Mazzulli Joseph R. , Perera Lalith , Stahlberg Henning , Borgnia Mario , Bartesaghi Alberto , Lashuel Hilal A. , West Andrew B. 
Published: May 2024

Short AbstractThe intricate process of α-synuclein aggregation and fibrillization hold pivotal roles in Parkinson’s disease (PD) and multiple system atrophy (MSA). While mouse α-synuclein can fibrillizein vitro, whether these fibrils commonly used in research to induce this process or form can reproduce structures in the human brain remains unknown. Here we report the first atomic structure of mouse α-synuclein fibrils, which was solved in parallel by two independent teams. The structure shows striking similarity to MSA-amplified and PD-associated E46K fibrils. However, mouse α-synuclein fibrils display altered packing arrangements, reduced hydrophobicity, heightened fragmentation sensitivity, and evoke only weak immunological responses. Furthermore, mouse α-synuclein fibrils exhibit exacerbated pathological spread in neurons and humanized α-synuclein mice. These findings provide new insights into the structural underpinnings of α-synuclein pathogenicity and emphasize a need to reassess the role of mouse α-synuclein fibrils in the development of related diagnostic probes and therapeutic interventions.