bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycine maxpolygalacturonase inhibiting protein 11 (GmPGIP11) functions in the root to suppressHeterodera glycinesparasitism
Authors: Acharya Sudha , Troell Hallie A. , Billingsley Rebecca L. , Lawrence Kathy S. , McKirgan Daniel S. , Alkharouf Nadim W. , Klink Vincent P. 
Published: May 2024

ABSTRACTPathogen-secreted polygalacturonases (PGs) alter plant cell wall structure by cleaving the α- (1→4) linkages between D-galacturonic acid residues in homogalacturonan (HG), macerating the cell wall, facilitating infection. Plant PG inhibiting proteins (PGIPs) disengage pathogen PGs, impairing infection. The soybean cyst nematode,Heterodera glycines,obligate root parasite produces secretions, generating a multinucleate nurse cell called a syncytium, a byproduct of the merged cytoplasm of 200-250 root cells, occurring through cell wall maceration. The common cytoplasmic pool, surrounded by an intact plasma membrane, provides a source from whichH. glycinesderives nourishment but without killing the parasitized cell during a susceptible reaction. The syncytium is also the site of a naturally-occurring defense response that happens in specificG. maxgenotypes. Transcriptomic analyses of RNA isolated from the syncytium undergoing the process of defense have identified that one of the 11G. max PGIPs,GmPGIP11, is expressed during defense. Functional transgenic analyses show roots undergoingGmPGIP11overexpression (OE) experience an increase in its relative transcript abundance (RTA) as compared to theribosomal protein 21(GmRPS21) control, leading to a decrease inH. glycinesparasitism as compared to the overexpression control. TheGmPGIP11undergoing RNAi experiences a decrease in its RTA as compared to theGmRPS21control with transgenic roots experiencing an increase inH. glycinesparasitism as compared to the RNAi control. Pathogen associated molecular pattern (PAMP) triggered immunity (PTI) and effector triggered immunity (ETI) components are shown to influenceGmPGIP11expression while numerous agricultural crops are shown to have homologs.
Virtual Growing Child (VGC): A general normative comparative system via quantitative dynamic MRI for quantifying pediatric regional respiratory anomalies with application in thoracic insufficiency syndrome (TIS)
Authors: Tong Yubing , Udupa Jayaram K. , McDonough Joseph M. , Xie Lipeng , Hao You , Akhtar Yusuf , Wu Caiyun , Rajapakse Chamith S. , Gogel Samantha , Mayer Oscar H. , Anari Jason B. , Torigian Drew A. , Cahill Patrick J. 
Published: May 2024

AbstractBackgroundA normative database of regional respiratory structure and function in healthy children does not exist.MethodsVGC provides a database with four categories of regional respiratory measurement parameters including morphological, architectural, dynamic, and developmental. The database has 3,820 3D segmentations (around 100,000 2D slices with segmentations). Age and gender group analysis and comparisons for healthy children were performed using those parameters via two-sided t-testing to compare mean measurements, for left and right sides at end-inspiration (EI) and end-expiration (EE), for different age and gender specific groups. We also apply VGC measurements for comparison with TIS patients via an extrapolation approach to estimate the association between measurement and age via a linear model and to predict measurements for TIS patients. Furthermore, we check the Mahalanobis distance between TIS patients and healthy children of corresponding age.FindingsThe difference between male and female groups (10-12 years) behave differently from that in other age groups which is consistent with physiology/natural growth behavior related to adolescence with higher right lung and right diaphragm tidal volumes for females(p<0.05). The comparison of TIS patients before and after surgery show that the right and left components are not symmetrical, and the left side diaphragm height and tidal volume has been significantly improved after surgery (p <0.05). The left lung volume at EE, and left diaphragm height at EI of TIS patients after surgery are closer to the normal children with a significant smaller Mahalanobis distance (MD) after surgery (p<0.05).InterpretationThe VGC system can serve as a reference standard to quantify regional respiratory abnormalities on dMRI in young patients with various respiratory conditions and facilitate treatment planning and response assessment.FundingThe grant R01HL150147 from the National Institutes of Health (PI Udupa).
Importance of variables from different time frames for predicting self-harm using health system data
Authors: Wolock Charles J. , Williamson Brian D. , Shortreed Susan M. , Simon Gregory E. , Coleman Karen J. , Yeargans Rodney , Ahmedani Brian K. , Daida Yihe , Lynch Frances L. , Rossom Rebecca C. , Ziebell Rebecca A. , Cruz Maricela , Wellman Robert D. , Coley R. Yates 
Published: May 2024

ABSTRACTObjectiveSelf-harm risk prediction models developed using health system data (electronic health records and insurance claims information) often use patient information from up to several years prior to the index visit when the prediction is made. Measurements from some time periods may not be available for all patients. Using the framework of algorithm-agnostic variable importance, we study the predictive potential of variables corresponding to different time horizons prior to the index visit and demonstrate the application of variable importance techniques in the biomedical informatics setting.Materials and MethodsWe use variable importance to quantify the potential of recent (up to three months before the index visit) and distant (more than one year before the index visit) patient mental health information for predicting self-harm risk using data from seven health systems. We quantify importance as the decrease in predictiveness when the variable set of interest is excluded from the prediction task. We define predictiveness using discriminative metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and positive predictive value.ResultsMental health predictors corresponding to the three months prior to the index visit show strong signal of importance; in one setting, excluding these variables decreased AUC from 0.85 to 0.77. Predictors corresponding to more distant information were less important.DiscussionPredictors from the months immediately preceding the index visit are highly important. Implementation of self-harm prediction models may be challenging in settings where recent data are not completely available (e.g., due to lags in insurance claims processing) at the time a prediction is made.ConclusionClinically derived variables from different time frames exhibit varying levels of importance for predicting self-harm. Variable importance analyses can inform whether and how to implement risk prediction models into clinical practice given real-world data limitations. These analyses be applied more broadly in biomedical informatics research to provide insight into general clinical risk prediction tasks.
Poor Sleep Quality is associated with Decreased Brain Glucose Metabolism in Healthy Middle-aged Adults
Authors: Shin Seunghyeon , Seok Ju Won , Kim Keunyoung , Kim Jihyun , Nam Hyun-Yeol , Pak Kyoungjune 
Published: May 2024

ABSTRACTSleep disturbance is associated with the development of neurodegenerative disease. We aimed to address the effects of sleep quality on brain glucose metabolism measured by18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in healthy middle-aged adults. A total of 378 healthy men (mean age: 42.8±3.6 years) were included in this study. Participants underwent brain18F-FDG PET and completed the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). Additionally, anthropometric measurements were obtained. PETs were spatially normalized to MNI space using PET templates from SPM5 with PMOD. The Automated Anatomical Labeling 2 atlas was used to define regions of interest (ROIs). The mean uptake of each ROI was scaled to the mean of the global cortical uptake of each individual and defined as the standardized uptake value ratio (SUVR). After the logarithmic transformation of the regional SUVR, the effects of the PSQI-K on the regional SUVR were investigated using Bayesian hierarchical modeling. Brain glucose metabolism of the posterior cingulate, precuneus, and thalamus showed a negative association with total PSQI-K scores in the Bayesian model ROI-based analysis. Voxel-based analysis using statistical parametric mapping revealed a negative association between the total PSQI-K scores and brain glucose metabolism of the precuneus, postcentral gyrus, posterior cingulate, and thalamus. Poor sleep quality is negatively associated with brain glucose metabolism in the precuneus, posterior cingulate, and thalamus. This finding may provide a link between sleep quality and the risk of neurodegenerative disease. Therefore, the importance of sleep should not be overlooked, even in healthy middle-aged adults.
Hypothalamic integrity is associated with age, sex and cognitive function across lifespan: A comparative analysis of two large population-based cohort studies
Authors: Xu Peng , Estrada Santiago , Etteldorf Rika , Liu Dan , Shahid Mohammad , Zeng Weiyi , Früh Deborah , Reuter Martin , Breteler Monique M.B. , Aziz N. Ahmad 
Published: May 2024

AbstractBackgroundThe hypothalamus is the body’s principal homeostatic center. Emerging findings from animal studies suggest that the hypothalamus could also play a crucial role in the modulation of cognition. However, detailed assessments of age and sex effects on hypothalamic structural integrity and its cognitive correlates across the lifespan are still lacking. Therefore, we aimed to investigate hypothalamic structural integrity in relation to age, sex and cognitive performance across lifespan in the general population.MethodsWe used cross-sectional data from the Rhineland Study (RS) (N=5812, 55.2 ± 13.6 years, 58% women) and the UK Biobank Imaging Study (UKB) (N=45076, 64.2 ± 7.7 years, 53% women), two large-scale population-based cohort studies. Volumes of hypothalamic structures were obtained from 3T structural magnetic resonance images through application of a recently developed automatic parcellation procedure (FastSurfer-HypVINN). The standardized cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regressions to assess age and sex effects on volumes of hypothalamic structures, and to evaluate the associations of these volumes with domain-specific cognitive function.FindingsMean (standard deviation) volumes of the total hypothalamus were 1124.2 mm3(104.8) in RS and 1102.1 mm3(119.9) in UKB. With increasing age, the volumes of the total, anterior and posterior hypothalamus, and mammillary bodies decreased (between -1.20 to -0.14 mm3/year in RS and between -3.82 to -0.49 mm3/year in UKB), and of the medial hypothalamus and tuberal region increased (between 0.33 to 0.65 mm3/year in RS and between 0.21 to 0.68 mm3/year in UKB). Volumes of all hypothalamic structures were larger in men compared to women. Larger total hypothalamus volumes were associated with better global cognition (β ± standard error (SE): 0.025 ± 0.017 [RS] and 0.026 ± 0.007 [UKB], both p<0.005), and total memory (0.030 ± 0.022 [RS] and 0.021 ± 0.009 [UKB], both p<0.007), while larger posterior hypothalamus volumes were associated with better global cognition (0.036 ± 0.014 [RS] and 0.028 ± 0.006 [UKB], both p<0.001), and total memory (0.038 ± 0.018 [RS] and 0.020 ± 0.008 [UKB], both p<0·001).ConclusionWe found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain-specific cognitive functions. Overall, these findings thus implicate specific hypothalamic subregions as potential therapeutic targets against age-associated cognitive decline.
Benchmarking Large Language Models for Extraction of International Classification of Diseases Codes from Clinical Documentation
Authors: Simmons Ashley , Takkavatakarn Kullaya , McDougal Megan , Dilcher Brian , Pincavitch Jami , Meadows Lukas , Kauffman Justin , Klang Eyal , Wig Rebecca , Smith Gordon , Soroush Ali , Freeman Robert , Apakama Donald J , Charney Alexander W , Kohli-Seth Roopa , Nadkarni Girish N , Sakhuja Ankit 
Published: May 2024

AbstractBackgroundHealthcare reimbursement and coding is dependent on accurate extraction of International Classification of Diseases-tenth revision – clinical modification (ICD-10-CM) codes from clinical documentation. Attempts to automate this task have had limited success. This study aimed to evaluate the performance of large language models (LLMs) in extracting ICD-10-CM codes from unstructured inpatient notes and benchmark them against human coder.MethodsThis study compared performance of GPT-3.5, GPT4, Claude 2.1, Claude 3, Gemini Advanced, and Llama 2-70b in extracting ICD-10-CM codes from unstructured inpatient notes against a human coder. We presented deidentified inpatient notes from American Health Information Management Association Vlab authentic patient cases to LLMs and human coder for extraction of ICD-10-CM codes. We used a standard prompt for extracting ICD-10-CM codes. The human coder analyzed the same notes using 3M Encoder, adhering to the 2022-ICD-10-CM Coding Guidelines.ResultsIn this study, we analyzed 50 inpatient notes, comprising of 23 history and physicals and 27 progress notes. The human coder identified 165 unique codes with a median of 4 codes per note. The LLMs extracted varying numbers of median codes per note: GPT 3.5: 7, GPT4: 6, Claude 2.1: 6, Claude 3: 8, Gemini Advanced: 5, and Llama 2-70b:11. GPT 4 had the best performance though the agreement with human coder was poor at 15.2% for overall extraction of ICD-10-CM codes and 26.4% for extraction of category ICD-10-CM codes.ConclusionCurrent LLMs have poor performance in extraction of ICD-10-CM codes from inpatient notes when compared against a human coder.
Global associations of maternal hypertensive disorders and offspring allergic disease burden
Authors: Ni Duan , Nanan Ralph 
Published: May 2024

AbstractObjectivesMaternal hypertensive disorders (MHD) are widespread globally, modifying maternal and fetal immunity, and have been linked to increased allergic diseases in offsprings. Nevertheless, so far, most studies in this field are small-scale and results remain inconclusive.MethodsHarnessing unprecedented global allergic disease and pregnancy data covering more than 150 countries from 1990 to 2019 as proxies, we leveraged the state-of-the-art generalized additive model (GAM) to interrogate the potential link between MHD and common offspring allergic diseases, exemplified by atopic dermatitis (AD) and asthma.ResultsA model considering the main effects from MHD, socioeconomic factor like GDP and time, as well as their interactions was favoured, suggesting their interactive effects on offspring allergic diseases. Generally, MHD in pregnancies were associated with increased AD and asthma in offsprings early in life, and a more pronounced effect was found for AD relative to asthma.ConclusionsGlobally, MHD in pregnancies are linked to increased offspring allergic disease burden, which, with further in-depth investigations, would inform allergic disease preventions in clinic. Our analyses also support the Developmental Origins of Health and Disease (DOHAD) concept and showcase a novel methodology for DOHAD-related research.
Associations Between Stroke Type, Ischemic Stroke Subtypes, and Post-Stroke Cognitive Trajectories
Authors: Levine Deborah A. , Whitney Rachael T. , Ye Wen , Briceño Emily M. , Gross Alden L. , Giordani Bruno J. , Sussman Jeremy B. , Lazar Ronald M. , Howard Virginia J. , Aparicio Hugo J. , Beiser Alexa S. , Elkind Mitchell S. V. , Gottesman Rebecca F. , Koton Silvia , Pendlebury Sarah T. , Kollipara Adam S. , Springer Mellanie V. , Seshadri Sudha , Romero Jose R. , Fitzpatrick Annette L. , Longstreth William T. , Hayward Rodney A. 
Published: May 2024

ABSTRACTBackgroundIt is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline.MethodsThis pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke.ResultsOn average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30];P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations.ConclusionStroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.
Library-based single-cell analysis of CAR signaling reveals drivers ofin vivopersistence
Authors: Perez Caleb R. , Garmilla Andrea , Nilsson Avlant , Baghdassarian Hratch M. , Gordon Khloe S. , Lima Louise G. , Smith Blake E. , Maus Marcela V. , Lauffenburger Douglas A. , Birnbaum Michael E. 
Published: May 2024

SummaryThe anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function—particularly at the molecular level—are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures. Informed by these observations, we functionally characterize transcriptionally distinct ICD variants across various contexts to build comprehensive maps from ICD composition to phenotypic output. We identify a unique tonic signaling signature associated with a subset of ICD architectures that drives durablein vivopersistence and efficacy in liquid, but not solid, tumors. Our findings work toward decoding CAR signaling design principles, with implications for the rational design of next-generation ICD architectures optimized forin vivofunction.
Molecular and neural mechanisms of behavioural integration in the extended-amygdala
Authors: Chang Simon , Fermani Federica , Huang Lianyun , Schneider Steffen , Mathis Mackenzie W. , Deussing Jan M. , Cai Na 
Published: May 2024

AbstractIntegration of diverse stimuli is crucial for organisms to adapt and communicate effectively, enabling overall homeostasis and survival. Studies have been performed on identifying specific neuronal encoding of individual behaviours, but how neurons integrate diverse behaviours across contexts remains elusive. Here we use Ca2+imaging in freely moving mice to identify neural ensembles in the extended amygdala encoding behaviours across six distinct contexts. We found extensive flexibility in these ensemble encodings that may act as reserves for behavioural integration, with those encoding aversive stimuli showing greater specificity. Finally, we identified differential gene expression profiles between ensembles that are enriched in associations with human psychiatric and neurodegenerative disorders. Overall, our results demonstrate the molecular mechanisms behind behavioural integration, and their potential implications in health and disease.
RNA sequencing variants are enriched for eQTL in cattle tissues
Authors: Leonard Alexander S. , Mapel Xena M. , Pausch Hubert 
Published: May 2024

AbstractAssociation testing between molecular phenotypes and genomic variants can help to understand how genotype affects phenotype. RNA sequencing provides access to molecular phenotypes such as gene expression and alternative splicing while DNA sequencing or microarray genotyping are the prevailing options to obtain genomic variants. Here we genotype variants for 74 male Braunvieh cattle from both DNA and deep total RNA sequencing from three tissues. We show that RNA sequencing calls approximately 40% of variants (7-10 million) called from DNA sequencing, with over 80% precision, rising to over 92% of variants called with nearly 98% precision in highly expressed coding regions. Allele-specific expression and putative post-transcriptional modifications negatively impact variant genotyping accuracy from RNA sequencing and contribute to RNA-DNA differences. Variants called from RNA sequencing detect roughly 75% of eGenes identified using variants called from DNA sequencing, demonstrating a nearly 2-fold enrichment of eQTL variants. We observe a moderate-to-strong correlation in nominal association p-values (Spearman ρ2∼0.6), although only 9% of eGenes have the same top associated variant. We also find several highly significant RNA variant-only eQTL, demonstrating that caution must be exercised beyond filtering for variant quality or imputation accuracy when analysing or imputing variants called from RNA sequencing.
Spatiotemporal Orchestration of Mitosis by Cyclin-Dependent Kinase
Authors: Kapadia Nitin , Nurse Paul 
Published: May 2024

AbstractMitotic onset is a critical transition for eukaryotic cell proliferation. The prevailing view for its control is that cyclin-dependent kinase (CDK) is activated first in the cytoplasm, at the centrosome, which then initiates mitosis1–3. Bistability in CDK activation ensures the transition is irreversible but how this unfolds in a spatially compartmentalized cell is unknown4–8. Here using fission yeast, we show that CDK is actually activated in the nucleus first, not the cytoplasm, and that the bistable responses dramatically differ within the nucleus and cytoplasm. There is a stronger response in the nucleus permitting mitotic signal propagation from there to the cytoplasm. Abolishing cyclin-CDK localization to the yeast centrosome led to activation occurring only in the nucleus, spatially uncoupling the nucleus and cytoplasm mitotically, suggesting centrosomal cyclin-CDK acts as a “signal relayer”. We propose that the key mitotic regulatory system operates in the nucleus in proximity to DNA, allowing incomplete DNA replication and DNA damage to be effectively monitored to preserve genome integrity and for integration of ploidy within the CDK control network. This spatiotemporal regulatory framework establishes core principles for control of the onset of mitosisin vivo, which will help inform how CDK controls mitotic onset in other eukaryotes.