bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signatures of the Shock Interaction as an Additional Power Source in the Nebular Spectra of SN 2023ixf
Authors: Kumar Amit , Dastidar Raya , Maund Justyn R , Singleton Adam J , Sun Ning-Chen 
Published: February 2025

Abstract
Red supergiants may lose significant mass during the final 100–1000 years before core collapse, shaping their circumstellar environment. The supernova (SN) shockwave propagating through this environment forms a shock-swept dense shell that interacts with the surrounding circumstellar material (CSM), generating secondary shocks that energise the ejecta and may power the SN during the nebular phase. In the present work, we investigate the nebular spectrum of SN 2023ixf, observed one-year post-explosion (at +363 d) with the recently commissioned WEAVE instrument on the 4.2m William Herschel Telescope. This marks the first supernova spectrum captured with WEAVE. In this spectrum, H α exhibits a peculiar evolution, flanked by blueward and redward broad components centred at ∼±5650 km s−1, features that have been observed in only a few SNe as early as one-year post-explosion. These features may indicate energy deposition from shock generated by the interaction of shock-swept dense shell with CSM expelled a few hundred years prior to the explosion. Comparisons of the +363 d spectrum with model spectra from the literature suggest a shock power of at least ∼5 × 1040 erg s−1 at this epoch. Additionally, analysis of the [O i] doublet and other emission lines helped to constrain the oxygen mass (≲ 0.07 − 0.30M⊙), He-core mass (≲ 3M⊙), and zero-age main sequence mass (≲ 12M⊙) for SN 2023ixf. The comparison with other Type II SNe highlights SN 2023ixf’s unique shock interaction signatures and evidence of dust formation, setting it apart in terms of evolution and dynamics.
Genetics of Recurrent Miscarriage and Pregnancy Loss in Women’s Reproductive Health
Authors: Mirakbarova Zebinisa , Pascat Vincent , Akramkhanova Surayyo , Chu Chia-Yi , Yusupov Ulugbek , Scapoli Chiara , Rakhmatullaev Abdushukur , Kapralova Yuliya , Nishanova Sevara , Nazirova Mehribon , Atamurotova Gulsanam , Rudometkin Konstantin , Sodiqova Maftuna , Karimova Lutfiya , Esonova Gulnoza , Meylikov Hurshid , Rejapova Marguba , Nishanova Feruza , Abdurakhimov Abrorjon , Prokopenko Inga , Dalimova Dilbar , Turdikulova Shahlo , Sharhorodska Yevheniya , Abdullaev Alisher 
Published: February 2025

AbstractAdverse pregnancy outcomes, such as sporadic and recurrent miscarriages and stillbirths, are significant medical concerns, impacting up to 15% of clinically recognised pregnancies. These outcomes are highly complex and multifactorial, with up to 50% of cases classified as idiopathic, highlighting a substantial gap in our understanding of their biological basis. Along with external risk factors, polygenic variability contributes to idiopathic pregnancy loss, suggesting that large-scale genetic studies could offer insights into its mechanisms, reveal novel drug targets, and lead to new treatments. This study assesses current knowledge from genome-wide association studies (GWAS) using genotyping arrays, whole-genome imputation, and sequencing for variant discovery, emphasising genetic predisposition to adverse pregnancy outcomes. We summarise existing efforts identifying 30 genetic loci associated with pregnancy loss and related endophenotypes, integrating them into a polygenic score (PGS) and conducting a phenome-wide PGS association analysis of 280 ICD-10 outcomes in nearly 500,000 UK Biobank participants. We report associations between pregnancy loss PGS and an increased risk for diaphragmatic hernia (OR[95%CI]=1.02[1.01–1.03], P=9.15×10⁻⁷), eosinophilic esophagitis (OR[95%CI]=1.05[1.03–1.06], P=1.44×10⁻⁶), and asthma with exacerbation (OR[95%CI]=1.02[1.01–1.03], P=1.71×10⁻⁵), significant after correction for multiple testing and suggesting new mechanistic pathophysiology in pregnancy loss susceptibility. Additionally, Mendelian Randomisation (MR) studies identified higher BMI and smoking as risk factors for pregnancy loss, while the roles of caffeine and alcohol intake, maternal age, and family history of miscarriage warrant further investigation through adequately powered MR analyses. Well-designed and comprehensive GWAS studies, particularly across diverse ancestry groups, are urgently needed for idiopathic recurrent pregnancy loss. Such studies should overcome issues with identification of women suffering for this condition and related pregnancy losses to support better care and timely interventions, aiming for healthy live birth outcomes.
Synthesis and Biological Evaluation of Nipecotic Acid Derivatives with Terminally Double-Substituted Allenic Spacers as mGAT4 Inhibitors
Authors: Jung Maren , Höfner Georg , Sałat Kinga , Furgała-Wojas Anna , Wanner Klaus T. 
Published: February 2025

AbstractA series of nipecotic acid derivatives, featuring a four- and five-carbon atom allenic spacer connecting the nitrogen of the polar nipecotic acid head with up to two aromatic residues, has been synthesized. For the synthesis of the respective nipecotic acid derivatives displayingN-substituents consisting of carbon chains with a terminal allenic function with two, mostly aryl residues a CuI-catalyzed cross-coupling of diaryldiazomethanes orN-tosylhydrazones with nipecotic acid derived terminal alkynes served as a key step. Upon characterization of these compounds regarding their inhibitory potency at mGAT1-4 and binding affinity for mGAT1, a highly potent mGAT4 inhibitor has been identified, which is defined as nipecotic acid derivative with a four-carbon atom allenic spacer terminally carrying two 4-chlorophenyl residues. The (S)-enantiomer of this compound, (S)-1-[4,4-bis(4-chlorophenyl)buta-2,3-dien-1-yl]piperidine-3-carboxylic acid [(S)-8d, DDPM-3960], displays potencies in the higher nanomolar range at mGAT4 and its human equivalent hGAT-3 with pIC50values of 6.59 ± 0.01 and 6.49 ± 0.10, respectively, which are significantly higher than that of the well-known mGAT4 inhibitor (S)-SNAP-5114.In vivoevaluation of this compound revealed its significant anticonvulsant activity in several mouse models of chemically- and electrically-induced seizures. In addition to this, anxiolytic-like properties of DDPM-3960 were shown. These beneficial biological effects observed in mice were not accompanied by any serious motor deficits, making DDPM-3960 an interesting lead structure for further development.
Loss of plasma membrane conductance in outside-xylem zone explains non-stomatal control of transpiration
Authors: Jain Piyush , Sen Sabyasachi , Rockwell Fulton E. , Twohey Robert J. , Huber Annika E. , Desai Sahil A. , Wu I-Feng , De Swaef Tom , Ilman Mehmet M. , Studer Anthony J. , Holbrook N. Michele , Stroock Abraham D. 
Published: February 2025

AbstractThe conventional assumption is that stomatal conductance (gs) dominates the regulation of water and carbon dioxide fluxes between leaves and the atmosphere. Here, a nanoreporter of water status at the mesophyll cell surface and local xylem within intact maize leaves documents significant undersaturation of water vapor in the outside-xylem zone (OXZ) and a large loss of conductance of this zone (goxz) at moderate xylem water stress (no turgor loss). The ratio of the resistances (1/goxz)/(1/gs) serves as a predictive phenotype of undersaturation, non-stomatal regulation of transpiration, errors in standard gas exchange analysis, and an increase of intrinsic water use efficiency (iWUE). Cell-scale access to water status reveals symplasmic-apoplasmic disequilibrium and informs a biophysical model that can explain experimental observations quantitatively based on localization of variable conductance to the plasma membrane. This work opens new paths of inquiry into the molecular basis and functional consequences of non-stomatal regulation of transpiration.
Lipid peroxidation and colorectal cancer risk: a time-varying relationship
Authors: Yang Gong , Milne Ginger L. , Nogueira Marina S. , Yi Haoyang , Lan Qing , Gao Yu-Tang , Shu Xiao-Ou , Zheng Wei , Chen Qingxia 
Published: February 2025

ABSTRACTImportanceWe recently observed an inverse and time-dependent association between systemic oxidative stress (OxS), measured by urinary biomarkers of nucleic acid oxidation, and colorectal cancer (CRC) risk. Further investigations into other types of OxS markers are warranted.ObjectiveTo extend the investigation into systemic lipid peroxidation and CRC risk.Design, Setting, and ParticipantsUtilizing a nested case-control design, this study’s primary analysis was performed in two large prospective cohorts in Shanghai, China, and replicated in an independent cohort in the US.ExposuresSystemic lipid peroxidation was assessed by urinary F2-isoprostanes (F2-IsoPs) using UPLC-MS/MS assays.Main Outcomes and MeasuresDuring 15.1-year follow-up in the Shanghai cohorts, 1938 incident CRC cases were identified and matched to one control each through incidence-density sampling. In the US cohort, 285 incident CRC cases were included, each matched to two controls. Odds ratios (ORs) for CRC were calculated using multivariable conditional logistic regression models.ResultsElevated levels of urinary 5-F2t-IsoP (5-iPF2α-VI), a major isomer of F2-IsoPs induced solely by free radicals, were associated with reduced risk of CRC in the Shanghai cohorts. This finding was replicated in the US cohort. Moreover, this inverse association was time-dependent, manifesting only in the later years of cancer development. Multivariable-adjusted ORs (95% CI) for CRC diagnosed within 5 years of enrollment at the 10th and 90th percentiles of 5-F2t-IsoP levels, relative to the median, were 1.57 (1.26-1.96) and 0.61 (0.42-0.89), respectively, indicating a 2.2-fold difference in risk between the two groups. A stronger association was observed when using the composite index of DNA, RNA and lipid OxS markers, showing a 3.9-fold difference in risk between the two groups. No significant association was found for CRC diagnosed beyond 5 years of enrollment.ConclusionsThis study provides new evidence that systemic OxS is inversely and time-dependently associated with CRC risk in humans.Key PointsQuestionIs the time-dependent relationship between oxidative stress and tumorigenesis observed at the cellular level in experimental models also present at the systemic level in a population-based setting?FindingsElevated systemic lipid peroxidation, measured by urinary F2-isoprostanes, was associated with a reduced risk of colorectal cancer (CRC) in two large prospective cohort studies in Shanghai, China, which was replicated in an independent cohort in the United States. This association varied over time, showing a stronger effect as cancer advanced.MeaningThis study provides new evidence that systemic oxidative stress is inversely and time-dependently associated with CRC risk in humans.
Emergent Tissue Shapes from the Regulatory Feedback between Morphogens and Cell Growth
Authors: Kaity Bivash , Lobo Daniel 
Published: February 2025

AbstractPatterning and morphogenesis in multicellular organisms require precise dynamic coordination between cellular behaviors and mechano-chemical signals. However, the mechanisms underlying the pathways that coordinate and integrate these signals into emergent cellular behaviors and tissue shapes remain poorly understood. Here, we present a cell-centered agent-based mathematical approach to shed light on the feedback mechanisms underlying tissue growth and pattern formation. The model includes cell size dynamics governed by both intercellular diffusible morphogen concentrations and mechanical stress between cells to control their spatial organization, and does not require the use of any superimposed lattice, increasing its applicability and performance. The results show how the precise integration of the feedback loop between cellular behaviors and mechano-chemical signaling is essential for the regulation of shape and spatial patterns across the tissue scale. Furthermore, the regulation of cellular dynamics by patterning processes, such as Turing activator-inhibitor systems, can drive the formation of emergent stable tissue shapes, which, in turn, specify the domain for morphogen patterning— closing the self-regulated loop between tissue shape and morphogenetic signals. Overall, this study highlights the importance of the feedback loop between morphogen patterning and cellular behaviors in regulating tissue growth dynamics and stable shape formation. Moreover, this study establishes a framework for further experiments to understand the regulatory dynamics of whole-body development and regeneration using high spatiotemporal resolution models.SignificanceTight coordination and interpretation of the multitude of signals at different biological scales are essential during the development of multicellular organisms to control their shape, size, and pattern. In this work, we investigated the leading role of the feedback between mechano-chemical signaling networks and tissue shape through cellular behaviors such as growth, proliferation, and apoptosis. The model explains the interdependence between tissue growth and pattern formation mechanisms in regulating the fundamental properties of morphogenesis. Overall, this study provides mechanistic insights into the regulatory feedback interactions between tissue morphogenesis and patterning dynamics.
Themis and Grb2 form a constitutive structural hub in T cell receptor signalling
Authors: Clancy Danielle M. , Sanz-Sanjuan Alba , Gilis Elisabeth , Tougaard Peter , Velghe Imke , Van Droogenbroeck Yana , Felix Jan , Bloch Yehudi , Cuadrado Álvaro Furones , Merceron Romain , Schenck Stephan , Vandenabeele Peter , Brunner Janine D. , Taghon Tom , Elewaut Dirk , Savvides Savvas N. 
Published: February 2025

AbstractPositive selection of thymocytes is essential for laying the foundations of the mammalian immune system that include the T cell repertoire, self-tolerance, and prevention of autoimmunity. Themis, the archetypal member of a metazoan protein family featuring distinctive CABIT domains, crucially regulates thymocyte positive selection by linking signalling by the T cell receptor (TCR) to the linker of activation of TCR (LAT). Intriguingly, Themis has been proposed to function via a constitutive complex with the multifunctional adaptor Grb2. Although poised to represent a paradigm shift in our understanding of TCR signalling, the structural and mechanistic basis of such an assembly has remained enigmatic. Here, we present the cryo-EM structure of Themis in complex with Grb2, which reveals how the tandem CABIT domains of Themis engulf the C-terminal SH3 domain of Grb2 (Grb2SH3C) to enable its latching onto the proline rich sequence of Themis. The remaining two domains of Grb2 adopt at least three conformational poses set to interact with other binding partners such as Sos1. Structural insights from unbound Themis unmask the pronounced flexibility of the CABIT domains of Themis, which becomes ordered upon binding to Grb2 to create a binding hotspot for their constitutive complex. Indeed, Themis variants that abrogate interactions with Grb2 also fail to activate the tyrosine phosphatase SHP-1 after TCR stimulation, analogous to the functional phenotype of Themis-deficient cells. Collectively, our study draws the blueprint of the Themis-Grb2 complex as a dynamic structural hub in T cell development.
Does diet contribute to socioeconomic differences in the prevalence of obesity among Indian adolescents?
Authors: Kalita Neelam 
Published: February 2025

ABSTRACTBackgroundIn India, the risk of obesity in adolescents between 10 and 19 years of age increases with socioeconomic advantage. Diet is a contributing factor to obesity, and obesity is a key risk factor for cardiovascular diseases (CVDs). However, the contribution of diet to socio-economic inequalities in overweight or obesity remains unclear.AimTo assess the mediating role of diet in the association between socioeconomic status (SES) and obesity among Indian adolescents.Data & MethodsData were obtained from the Comprehensive National Nutrition Dataset survey, a cross-sectional sample of the Indian adolescent population (N=35,830). Maternal educational attainment and household wealth index are used as proxies for SES. Diet quality was estimated using the Dietary Diversity Score (DDS) based on reported weekly intake of different categories of food. BMI for age Z-scores was used as a marker for obesity. Cross-section mediation was applied to estimate the proportions of obesity mediated by diet quality. Robustness checks were conducted by using alternative measures of diet quality.ResultsThe log-odds of obesity were estimated to rise by 0.603 (95% CI: 0.334,0.926) and 0.714 (95% CI: 0.573, 0.865) in rural and urban adolescents, respectively, with higher levels of maternal education (post-secondary or above), compared to those from lower maternal education (secondary or below). In wealthier adolescents (from middle-, rich-, richest quintiles), the log-odds of obesity were estimated to rise by 0.710 (95% CI: 0.529, 0.891) and 1.325 (95% CI: 0.924, 0.1.726) in rural and urban adolescents, respectively, compared to poorer adolescents (from poorest and poor quintiles). The proportion of the association mediated by diet varied between <1% and over 4%.ConclusionsThe findings suggested that diet quality mediates socio-economic inequalities in obesity among Indian adolescents, but only a small proportion. Therefore, differences in diet quality might not be the primary route by which SES translates into differences in risk for obesity among Indian adolescents. Focussing on improving diet quality and other risk factors (behavioural, environmental, demographic, socio-cultural) could prevent obesity among Indian adolescents and, therefore, the future burden of CVD in India.
Structural basis of ATP release and ion selectivity in Pannexin1 channels
Authors: Zhang Qingyang , Wang Junjie , Gaullier Guillaume , Kotol David , Blikstad Cecilia , Dahl Gerhard , Barro-Soria Rene , Mim Carsten 
Published: February 2025

SummaryThis study investigated the structural basis of adenosine triphosphate (ATP) release and ion selectivity by Pannexin1 (Panx1). The microinjection of active SRC tyrosine kinase increased Panx1-mediated currents in Panx1-expressing oocytes. Furthermore, a mutation mimicking phosphorylation at Y308 turned Panx1 into a constitutively open ATP-releasing channel with broad ion permeability. Cryogenic electron microscopy showed that for most maps, the channel alternated between wide and narrow conformations. However, in the map of the phosphomimetic Y308E mutation, Panx1 remains in a wide ATP-releasing conformation. The pore-lining residues, W74 and R75, are flexible and create, in concert with the sequestered N-terminal helix, a path for ATP. The data point to phosphorylation as a reversible switch that activates ATP permeability by stabilizing Panx1 in the ATP-releasing conformation, which is crucial for developing modulators for diseases such as cancer and chronic pain.
Cell type transcriptomics reveal shared genetic mechanisms in Alzheimer’s and Parkinson’s disease
Authors: Bhattacharya Anwesha , Fon Edward A. , Dagher Alain , Iturria-Medina Yasser , Stratton Jo Anne , Savignac Chloe , Stanley Jack , Hodgson Liam , Hammou Badr Ait , Bennett David A , Bzdok Danilo 
Published: February 2025

ABSTRACTHistorically, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have been investigated as two distinct disorders of the brain. However, a few similarities in neuropathology and clinical symptoms have been documented over the years. Traditional single gene-centric genetic studies, including GWAS and differential gene expression analyses, have struggled to unravel the molecular links between AD and PD. To address this, we tailor a pattern-learning framework to analyze synchronous gene co-expression at sub-cell-type resolution. Utilizing recently published single-nucleus AD (70,634 nuclei) and PD (340,902 nuclei) datasets from postmortem human brains, we systematically extract and juxtapose disease-critical gene modules. Our findings reveal extensive molecular similarities between AD and PD gene cliques. In neurons, disrupted cytoskeletal dynamics and mitochondrial stress highlight convergence in key processes; glial modules share roles in T-cell activation, myelin synthesis, and synapse pruning. This multi-module sub-cell-type approach offers insights into the molecular basis of shared neuropathology in AD and PD.
Epidemiological Analysis of Common Infections in Rural Pakistan: Implications for Public Health Interventions
Authors: Mahmood Shahzad , Chaudary Nauman Ali , Kataria Jafar Riaz , Tahir Muhammad Naveed , Noor Maham 
Published: February 2025

AbstractInfectious diseases remain a major public health challenge in rural Pakistan due to limited healthcare access and infrastructure. This cross-sectional study examines the prevalence of gastrointestinal, respiratory, and dermatological infections across different age and gender groups in a rural population. Data were collected over 45 days from a basic health unit serving seven villages with a population of 50,000. Patients were categorized based on infection type, gender, and age group. The findings revealed distinct epidemiological patterns: respiratory and dermatological infections peaked in the 15-49 age group before declining in older adults, while gastrointestinal infections were most prevalent in children aged 1-4 years. Males exhibited a slightly higher prevalence of dermatological infections, whereas gastrointestinal and respiratory infections showed minor gender-based variations. The study highlights key risk factors contributing to disease prevalence and underscores the need for targeted public health interventions, improved healthcare access, and preventive measures tailored to specific demographic groups. Future research should incorporate longitudinal data to establish causal relationships and enhance disease mitigation strategies.Short DescriptionThis study focuses on the distribution of infectious diseases including: respiratory tract infections, gastrointestinal tract infections and dermatological infections. It not only explores the disease’s frequency among different genders and among different age groups, but also provides a thematic analysis of policy recommendations to control the diseases in rural Pakistan
Classifying the severity of diabetic macular oedema from optical coherence tomography scans using deep learning: a feasibility study
Authors: Breathnach Cathal , Harney Fiona , Townley Deirdre , Hickey Rachel , Simpkin Andrew , O’Keeffe Derek 
Published: February 2025

ABSTRACTBackgroundDiabetic macular oedema (DME) is a vision-threatening complication of diabetes mellitus. It is reliably detected using optical coherence tomography (OCT). This work evaluates a deep learning system (DLS) for the automated detection and classification of DME severity from OCT images.MethodsAnonymised OCT images were retrospectively obtained from 950 patients at University Hospital Galway, Ireland. Images were graded by a consultant ophthalmologist to classify the level of DME on a novel scale (Normal, DME not affecting the foveal contour and DME affecting the foveal contour), excluding other pathologies. A DLS was trained using cross-validation, then evaluated on a test dataset and an external dataset. The test set was graded by a second ophthalmologist.ResultsIn detecting the presence of DME, the DLS achieved a mean area under the receiver operating characteristic curve (AUC) of 0.98 on cross-validation. AUCs of 0.94 (95% CI 0.90-0.98) and 0.91 (0.86-0.95) were achieved on evaluation of DME detection for the test dataset when graded by the first and second ophthalmologist respectively. An AUC of 0.94 (0.92-0.96) was achieved on evaluation with the external dataset. When detecting the DME severity, AUCs of 0.97, 0.87 and 0.98 were achieved per class on cross validation. For the test dataset, AUCs of 0.93, 0.83 and 0.97 were achieved when graded by the first ophthalmologist and AUCs of 0.89, 0.75 and 0.96 were achieved when graded by the second ophthalmologist.ConclusionThis study suggests promising results for the use of deep learning in the classification of severity of DME.