bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival after invasive pneumococcal disease – a matched cohort study using electronic health records in England
Authors: Suffel Anne , Abdullahi Fariyo , Barry Eleanor , Walker Jemma , Andrews Nick , Amin-Chowdhury Zahin , Ladhani Shamez N , Grint Daniel , McDonald Helen I. , Douglas Ian , Mansfield Kathryn E. , Parker Edward P.K. 
Published: February 2025

AbstractBackgroundInvasive pneumococcal disease (IPD) is associated with increased long-term mortality, but it is unclear if this can be explained by pre-existing comorbidities that predispose individuals to pneumococcal infection.MethodsWe conducted a matched cohort study comparing long-term survival (beyond 120 days after infection) in individuals with IPD and comparators without IPD. Cases were individuals in England aged ≥65+ years with laboratory-confirmed IPD (2012–2019) identified through enhanced national surveillance. Comparators matched on age, sex, and calendar date were drawn from primary care electronic health records in Clinical Practice Research Datalink GOLD. We used Cox regression (stratified by matched set) to compare mortality in people with and without IPD, adjusting for relevant comorbidities, deprivation, and ethnicity.ResultsWe included 13,401 IPD cases and 67,005 comparators. After adjusting for comorbidities, deprivation, and ethnicity, we found increased all-cause mortality in IPD cases compared to comparators (hazard ratio 3.74, 95% CI: 3.50–3.99). The predicted median survival from adjusted models was 4.7 years (IQR: 2.9-7.4) for IPD cases and >11.9 (IQR : 8.7->11.9) for comparators. This increased mortality was consistent across subgroups defined by age, vaccination history, and comorbidity status (including diabetes, chronic respiratory disease, and chronic heart disease).ConclusionsIPD was associated with increased mortality at least 5 years after infection. These findings demonstrate the long-term consequences of IPD, emphasising the value of IPD prevention and the need for more research into clinical management of IPD survivors. Long-term mortality should be incorporated in cost–effectiveness analyses for pneumococcal vaccines.Article summaryCompared to people without infection, people who survived invasive pneumococcal disease in England had a 3.7-fold increase in mortality up to 10 years after infection. This increased mortality remained after accounting for age, sex, underlying comorbidities, deprivation, and ethnicity.
Profiling and Predicting Faculty Assessment Behavior in Surgical Education
Authors: Patel Ranish K. , Jenkins Phillip D , Lee Emily , Nitzkorwski James , Seshadri Ramanathan , Rhee Rebecca , Cook Mackenzie , Shelton Julia , Doberne Julie , Jesneck Jonathan , Thanawala Ruchi 
Published: February 2025

AbstractObjectiveTo study and profile the digital assessment behaviors of surgical faculty and residents, and to build a classifier to predict assessment completion, enhancing formative feedback initiatives.BackgroundAs competency-based paradigms are integrated into surgical training, developing digital education tools for measuring competency and providing rapid feedback is crucial. Simply making assessments available is inadequate and results in disappointingly low user participation. To optimize engagement and efficacy of these tools, user assessment behaviors need to be studied.MethodsUser data was aggregated from a HIPAA-compliant electronic health record (EHR)-integrated medical education platform. Faculty and resident behaviors were analyzed with respect to factors, such as time, day, device type, automated reminders, and EHR integration. A graphical convolutional neural network (GCN) model was trained to predict faculty participation in completing assessments.Results10,729 assessments were completed by 254 attendings for 428 residents across 22 institutions, from 2022 to 2024. 86% of assessments were completed by faculty on weekdays, were significantly influenced by automated platform triggers and EHR integration, and distinct faculty behavior profiles contingent upon time to completion and comment length were established. Residents opened assessments at a median of 1.5 hours of faculty assessment completion, with 96% of assessments viewed by 24 hours. The GCN model successfully predicted faculty assessment completion with 93.5% accuracy and an area under the ROC curve of 0.97.ConclusionsFaculty assessment behaviors represent an actionable bottleneck which can be leveraged to optimize and tailor the design of digital education tools, to enhance formative feedback.
Sexual Initiation and the Timing of First Union among women in Uganda
Authors: Lwanga Charles , Nsimbe Dick , kalule-Sabiti Ishmael , Mangombe Kudzaishe , Otim Jude 
Published: February 2025

Summary (Abstract)The aim of this paper was to examine the socioeconomic correlates of the length of the gap between onset of sex initiation and the age at first union, and also estimate the waiting time to first union after sexual debut. Self-reported data from the individual record file were extracted from the 2016 Uganda Demographic and Health Survey (UDHS), comprising of a subsample of 4293 women aged 15-25. Chi-square tests and the logistic regression of multivariable event history analysis were used to investigate the relationship between socioeconomic factors and the length of the gap. Descriptive findings show that the average and mean waiting time in years is about 5.6 and 5.5 respectively. Age at sexual initiation and current age of the woman were the only significant factors. Women who had their sexual debut before age 15 would take longer to transit to first union and this is perhaps attributed to serial monogamy, and having multiple and concurrent partners which leads to a failure in subsequent union formation. Women aged 20-25 had a disproportionally lower risk of transiting to first union, which is attributed to social development aspects, diverging from earlier thinking that a woman is supposed to either be one’s wife or one’s mother. In conclusion, efforts to address what might influence the length of the gap between sexual union and first union need to take into account the age at sexual debut and the current age of the women.
A within-host birth–death and time–dose–response model for Legionnaires’ disease
Authors: Jamieson Nyall , Charalambous Christiana , Schultz David M. , Hall Ian 
Published: February 2025

AbstractUnderstanding the dose–response relationship for infectious diseases is important for quantitative microbial risk assessment studies to mitigate risk. To capture the dose–response dynamics, understanding the pathogenesis of the infectious agent is desirable. Typically, attempting to understand the dose–response dynamics would involve within-host mathematical modelling and fitting dose–response curves to experimental data. No mathematical model exists that describes the within-host dynamics that occur within an individual infected with Legionnaires’ disease. Further, most dose–response models are based either on a single-hit or threshold hypothesis for the cause of illness. Here, we derive a model to explain within-host dynamics post-infection with Legionnaires’ disease that incorporates heterogeneity at the cellular and population levels. We develop a new dose–response model that allows for either of two hypotheses for the cause of illness, adding a new level of flexibility not currently seen in the literature. We extend the dose–response model to incorporate time as we develop a dose-dependent incubation-period model that is based on biological mechanisms. Our within-host models provide an ID50 of between eight and nineLegionellaand median incubation periods close to four days, which is consistent with evidence obtained from animal experiments and human outbreaks in the literature.
GWAS linksAPOEto neuropsychiatric symptoms in mild cognitive impairment and dementia
Authors: Vattathil Selina M. , Blostein Freida , Miller-Fleming Tyne W. , Davis Lea K. ,   Alzheimer’s Disease Genetics Consortium (ADGC),   Alzheimer’s Disease Neuroimaging Initiative, Wingo Thomas S. , Wingo Aliza P. 
Published: February 2025

AbstractINTRODUCTIONNeuropsychiatric symptoms in dementia (NPS) collectively refer to behavioral and psychological symptoms affecting individuals with mild cognitive impairment (MCI) or Alzheimer’s disease or related dementia (ADRD). NPS are among the most troubling aspects of living with dementia and their treatments have limited efficacy. We aim to investigate genetic variants contributing to NPS to identify new therapeutic targets.METHODSWe performed a genome-wide association study (GWAS) for nine NPS domains measured by the NPI-Q in 12,800 participants of European ancestry with MCI or ADRD recruited by Alzheimer’s disease research centers across the U.S.RESULTSWe found genome-wide significant signals for agitation, anxiety, apathy, delusions, and hallucinations in theAPOElocus that were driven by theAPOEε4 allele. We replicated these findings in two independent datasets. Mediation analyses revealed that MCI/ADRD severity only partially mediated the GWAS signals, except for apathy.DISCUSSIONThese findings suggest theAPOEε4 allele influences NPS independently of and beyond its effect on ADRD.
Mammo-Bench: A Large-scale Benchmark Dataset of Mammography Images
Authors: Bhole Gaurav , Suba S , Parekh Nita 
Published: February 2025

AbstractBreast cancer remains a significant global health concern, and machine learning algorithms and computer-aided detection systems have shown great promise in enhancing the accuracy and efficiency of mammography image analysis. However, there is a critical need for large, benchmark datasets for training deep learning models for breast cancer detection. In this work we developed Mammo-Bench, a large-scale benchmark dataset of mammography images, by collating data from seven well-curated resources,viz., DDSM, INbreast, KAU-BCMD, CMMD, CDD-CESM, DMID, and RSNA Screening Dataset. To ensure consistency across images from diverse sources while preserving clinically relevant features, a preprocessing pipeline that includes breast segmentation, pectoral muscle removal, and intelligent cropping is proposed. The dataset consists of 74,436 high-quality mammographic images from 26,500 patients across 7 countries and is one of the largest open-source mammography databases to the best of our knowledge. To show the efficacy of training on the large dataset, performance of ResNet101 architecture was evaluated on Mammo-Bench and the results compared by training independently on a few member datasets and an external dataset, VinDr-Mammo. An accuracy of 78.8% (with data augmentation of the minority classes) and 77.8% (without data augmentation) was achieved on the proposed benchmark dataset, compared to the other datasets for which accuracy varied from 25 – 69%. Noticeably, improved prediction of the minority classes is observed with the Mammo-Bench dataset. These results establish baseline performance and demonstrate Mammo-Bench's utility as a comprehensive resource for developing and evaluating mammography analysis systems.
A Sensitive Soma-localized Red Fluorescent Calcium Indicator for Multi-Modality Imaging of Neuronal Populations In Vivo
Authors: Zhou Shihao , Zhu Qiyu , Eom Minho , Fang Shilin , Subach Oksana M. , Ran Chen , Alvarado Jonnathan Singh , Sunkavalli Praneel S. , Dong Yuanping , Wang Yangdong , Hu Jiewen , Zhang Hanbin , Wang Zhiyuan , Sun Xiaoting , Yang Tao , Mu Yu , Yoon Young-Gyu , Guo Zengcai V. , Subach Fedor V. , Piatkevich Kiryl D. 
Published: February 2025

AbstractRecent advancements in genetically encoded calcium indicators, particularly those based on green fluorescent proteins, have optimized their performance for monitoring neuronal activities in a variety of model organisms. However, progress in developing red-shifted GECIs, despite their advantages over green indicators, has been slower, resulting in fewer options for end-users. In this study, we explored topological inversion and soma-targeting strategies, which are complementary to conventional mutagenesis, to re-engineer a red genetically encoded calcium indicator, FRCaMP, for enhancedin vivoperformance. The resulting sensors, FRCaMPi and soma-targeted FRCaMPi (SomaFRCaMPi), exhibit up to 2-fold higher dynamic range and peak ΔF/F0per single AP compared to widely used jRGECO1a in neurons in culture andin vivo. Compared to jRGECO1a and FRCaMPi, SomaFRCaMPi reduces erroneous correlation of neuronal activity in the brains of mice and zebrafish by two- to four-fold due to diminished neuropil contamination without compromising the signal-to-noise ratio. Under wide-field imaging in primary somatosensory and visual cortex in mice with high labeling density (80-90%), SomaFRCaMPi exhibits up to 40% higher SNR and decreased artifactual correlation across neurons. Altogether, SomaFRCaMPi improves the accuracy and scale of neuronal activity imaging at single-neuron resolution in densely labeled brain tissues due to a 2-3-fold enhanced automated neuronal segmentation, 50% higher fraction of responsive cells, up to 2-fold higher SNR compared to jRGECO1a. Our findings highlight the potential of SomaFRCaMPi, comparable to the most sensitive soma-targeted GCaMP, for precise spatial recording of neuronal populations using popular imaging modalities in model organisms such as zebrafish and mice.
Low relative air humidity leads to smaller, denser stomata and higher stomatal ratios in Arabidopsis
Authors: Tulva Ingmar , Jalakas Pirko , Ivandi Elena , Wierzchula Alexander , Obinwanne Patricia Kika , Hõrak Hanna 
Published: February 2025

AbstractAtmospheric dryness is increasing, bringing about decreases in plant productivity. Stomatal pores mediate plant gas-exchange with the environment, balancing CO2uptake with water loss. Stomatal anatomical and physiological traits respond to changes in environment, potentially affecting plant growth and yield under future environments. Designing stomatal patterns to suit future climate conditions has the potential to improve plant water use efficiency or productivity. By combining mutations in signaling pathways that control stomatal development and apertures, we designed plants that combine high stomatal densities with more open stomata and show that respective mutations independently affect stomatal conductance and density. Analyses of adaxial and abaxial stomatal conductances showed that in Arabidopsis, adaxial stomata are responsible for a significant proportion of leaf gas-exchange. Adaxial and abaxial stomatal physiology were largely similarly affected by mutations in stomatal regulation pathways but adaxial stomata tended to be relatively more closed than abaxial stomata. We show that growth under low relative air humidity leads to higher stomatal densities and smaller stomata. Stomatal development in the adaxial and abaxial leaf surface responded differently to dry air conditions: adaxial stomatal index increased, whereas abaxial stomatal index decreased. Stomatal ratio increased under dry air conditions, leading to a higher degree of amphistomaty. Plant growth was independently suppressed by dry air and high stomatal density and index. Our results suggest that acclimation to decreasing air humidity leads to stomatal anatomical adjustments that help to maximize plant gas-exchange potential under conditions where water supply may be limited and sporadic.
Lack ofAtMC1 catalytic activity triggers autoimmunity dependent on NLR stability
Authors: Salguero-Linares Jose , Armengot Laia , Ayet Joel , Ruiz-Solaní Nerea , Saile Svenja C. , Salas-Gómez Marta , Fernandez Esperanza , Denolf Lode , Navarrete Fernando , Krumbach Jenna , Kaiser Markus , Stael Simon , Breusegem Frank Van , Gevaert Kris , Kaschani Farnusch , Petersen Morten , El Kasmi Farid , Valls Marc , Coll Núria S. 
Published: February 2025

ABSTRACTPlants utilize cell surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors to detect non-self and elicit robust immune responses. Fine-tuning the homeostasis of these receptors is critical to prevent their hyperactivation. Here, we show that Arabidopsis plants lacking metacaspase 1 (AtMC1) display autoimmunity dependent on immune signalling components downstream of NLR and PRR activation. Overexpression of a catalytically inactiveAtMC1 in anatmc1background triggers severe autoimmunity partially dependent on the same immune signalling components. Overexpression of the E3 ligase SNIPER1, a master regulator of NLR homeostasis, fully reverts the AtMC1-dependent autoimmunity phenotype, inferring that a broad defect in NLR turnover may underlie the severe phenotype observed. Catalytically inactiveAtMC1 localizes to punctate structures that are degraded through autophagy. Altogether and considering previous evidence on the proteostatic functions ofAtMC1, we speculate that WtAtMC1 may either directly or indirectly control NLR protein levels, thereby preventing autoimmunity.
DiversePseudomonasspecies engage in beneficial and suppressive interactions with the kiwifruit pathogenPsaacrossActinidiagermplasm
Authors: Patterson Haileigh R. , Hemara Lauren M. , Templeton Matthew D. , Jayaraman Jay 
Published: February 2025

AbstractIn 2010, aPseudomonas syringaepv.actinidiaebiovar 3 (Psa3) incursion into New Zealand kiwifruit orchards devastated susceptibleActinidia chinensiscultivars. In contrast, manyActinidiaspecies maintained in germplasm collections were resistant to Psa3 and showed limited symptoms. Recent genome biosurveillance revealed the emergence of widespread leaf spot symptoms in Psa3-resistantActinidiagermplasm. Surprisingly, few Psa3 isolates were recovered from symptomatic tissues, despite the frequent isolation of phenotypicalPseudomonasisolates on selective agar. Despite the poor recovery of Psa3 isolates, Psa3 was found in all symptomatic leaf tissue through qPCR and metabarcoding analysis. Metabarcoding revealed stark differences in bacterial community composition from samples taken from lesion-carrying or lesion-free material from the same leaf. Host genotype also appeared to influence community composition but to a lesser extent. Whole genome sequencing of diversePseudomonasspp. isolates revealed that many belonged to theP. syringaespecies complex. Curiously, the kiwifruit-associatedP. syringaepv.actinidifoliorum(Pfm), was never recovered, nor were any other phylogroup 1 pathovars. Pathogenicity and competitive assays revealed that while individually diversePseudomonasisolates were not more pathogenic than Pfm or Psa3 on resistantActinidiahosts, they could interact with Psa to sometimes improve their growth, suggesting that these isolates may form pathogenic consortia in these disease-associated phyllosphere communities on typically Psa3-resistant hosts.Graphical Abstract
Unique Behavior Profiles that Specify Mental Distress in Autism
Authors: Strobl Eric V. 
Published: February 2025

AbstractObjectivePatients with autism spectrum disorder (ASD) often have difficulty describing their emotions, leaving clinicians to infer mental distress from aberrant behaviors. Unfortunately, aberrant behaviors are non-specific and can differ from those of typically developing peers. However, aberrant behavior profiles (ABPs), or weighted combinations ofmultipleaberrant behaviors, may be specific and recognizable. We thus sought to identify ABPs that correlate with distinct types of mental distress, and also correlate differently in ASD than in typical development (TD).MethodWe integrated three studies that measured diagnostic symptom severity using the Child and Adolescent Symptom Inventory, and aberrant behaviors using the Aberrant Behavior Checklist. We then performed a component analysis to identify maximally non-overlapping severity scores that correlate with ABPs differently in ASD than in TD.ResultsBehaviors associated with impulsivity and distractibility correlated more positively with the severity of specific phobia and social anxiety in ASD than in TD. Hyperactivity and tantrums correlated more positively with attention-deficit hyperactivity disorder and oppositional defiant disorder in ASD than in TD. Emotional reactivity correlated more positively with obsessions and somatization, but social withdrawal and self-injurious behaviors correlated more negatively; the opposite pattern held in a second phenotype of social anxiety. Finally, preoccupation correlated positively with schizophrenia, but depression and inactivity correlated negatively; the opposite pattern held with the severity of post-traumatic stress disorder and a second phenotype of specific phobia.ConclusionPatients with ASD (1) externalize more in attention-deficit hyperactivity disorder and oppositional defiant disorder, (2) exhibit unique signs of internal distress in post-traumatic stress and psychosis, and (3) display highly distinct ABPs in specific forms of anxiety.
Increasing severity, importance of viral transmission, and environmental exposures for pediatric asthma in a large urban health system, 2018-2023
Authors: McCuskee Sarah , Kowalski Rishi , Mei Cindy , Zebrowski Alexis , Patel Aman , Zajac Lauren , Zikry Hashem , Ayyash Ali , DeFelice Nicholas 
Published: February 2025

AbstractObjectivePediatric asthma is multifactorial: social, environmental, and infectious exposures trigger exacerbations. Policies adopted to mitigate COVID-19 transmission in schools including school closures, mask mandates, and full reopening, provide a natural experiment to investigate the importance of socially-driven exposures, including viral transmission, in pediatric asthma.MethodsThis observational study used retrospective review of all electronic health records from the largest urban health system in New York City over five school years from 2018-2023. We investigated the epidemiology of acute, unscheduled care for pediatric asthma in children ages 5-17 years, including emergency department (ED) visits, hospital admissions, intensive care unit (ICU) stays, and viral testing. Comparison groups were drawn from citywide surveillance data and all-cause visits. We investigated population-level exposures: COVID-19 mitigation policies and wildfire smoke events.ResultsIn the post-pandemic period, ED volume for pediatric asthma dropped (p<0.0001); however, children who presented were significantly more likely to require hospital admission and ICU care (p<0.001). Viral testing was employed more frequently, and more frequently positive, in the post-pandemic period (p<0.0001), with rhinovirus driving a greater proportion of pediatric asthma than all-cause adult or pediatric visits (p=0.02). After mask mandates were dropped in early 2022, pediatric asthma peaked during the immediate return-to-school fall period, slightly preceding the winter 2022 peak in viral illnesses. Wildfire smoke events were not significantly associated with pediatric asthma visits.ConclusionsSocially-driven factors including viral transmission and school policies were important in driving pediatric asthma during and after the COVID-19 pandemic. Increased acuity despite lower volumes may help guide health systems as they strive to increase readiness to care for pediatric populations.