bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical Genome Mapping of the human reference iPSC line KOLF2.1J reveals new smaller structural variants in neurodevelopmental genes
Authors: Yang Madison James , Sedov Kamilla , Chen Max Y. , Zafar Faria , Schüle Birgitt 
Published: October 2024

SummaryThe INDI consortium curated the KOLF2.1J human iPSC line to create a reference cell line for neurological disease modeling. However, despite careful assessments, two separate studies found using SNP arrays identified five structural variants (SVs) with sizes >100kbp. Two heterozygous SVs overlap the genesJARID2, DTNBP1, andASTN2, raising concerns about KOLF2.1J’s suitability as a reference line. To investigate further, we screened KOLF2.1J for SVs smaller than 100kbp using optical genome mapping (OGM) to produce a high-resolution karyotype. OGM, validated by qPCR, indicated that one of the five known SVs contained a previously undetected overlap withRYBP. RYBP plays regulatory roles in neuronal differentiation, PAX6 expression and Notch signaling. Furthermore, OGM identified 11 SVs smaller than 100kbp, whose overlaps include the genesPER2, CSMD1,andPALS1. In summary, these mutations should be considered by researchers when using KOLF2.1J as a reference iPSC line for designing studies and experiments.
Collective dynamics ofEscherichia coligrowth under near-lethal acid stress
Authors: Segura Munoz Rafael R. , Sourjik Victor 
Published: October 2024

AbstractMany neutralophilic bacteria, includingEscherichia coli, can withstand acidic conditions due to the action of several protective mechanisms. While the survival ofE. coliunder growth-inhibitory extreme acid stress is well understood, less is known about the physiology ofE. coligrowth under severe but permissive acidity. Here, we observed that growth ofE. coliMG1655 in a rich medium with pH of 4.1 to 4.4 exhibits a characteristic multi-phasic growth pattern, consisting of an initial exponential elongation in the absence of cell division, followed by growth arrest and subsequent resumption of exponential growth. The duration of the growth arrest phase was strongly dependent on the pH of the medium, but also on the initial cell density of the culture, suggesting the collective nature of this phenomenon. Cell-density dependent multiphasic growth at the near-lethal pH, including the initial increase in cell volume associated with either elongation or widening of the cell body, was also observed for all tested naturalE. coliisolates and forSalmonella entericaserovar Typhimurium. Such transient increase in volume apparently enables bacteria to induce acid resistance systems, including the lysine-dependent Cad system, to subsequently modify pH of the medium in the density-dependent manner. Consistent with the collective recovery, even a minor fraction of acid-tolerant cells could fully cross-protect acid-sensitive cells enabling them to resume growth in coculture. Thus, collective dynamics plays a central role in bacterial growth under near-lethal acid stress.ImportanceSince manyE. coliand other Enterobacteriaceae isolates are gastrointestinal pathogens for humans, it is important to understand their growth under acidic conditions imposed by the host physiology in the stomach, colon, and inside macrophages. Here we show thatE. coligrowth under near-lethal acidic conditions is a collective phenomenon that critically depends on cell density. This collective behavior is favored by changes in cell morphology as a response to high acidity. The observed density dependence might have implications for pathogen proliferation in the acidic environment of the human gastrointestinal tract and possibly also for their interactions with immune cells.
Information Technology in Screening and Identifying Unmet Social Needs: A Scoping Review
Authors: Sezgin Emre , Jackson Daniel I , Boch Samantha , Davenport Mattina , Skeens Micah , Dolce Millie , Franklin Bianca , Militello Lisa K. , Lyman Elizabeth , Kelleher Kelly 
Published: October 2024

AbstractBackgroundSocial determinants of health (SDOH) affect health outcomes, with unmet social needs like food insecurity, housing instability, and lack of services contributing to poor outcomes, health disparities, and higher healthcare costs. Identifying these needs is vital for improving health and achieving equity. Information technology has emerged as a tool for screening and identifying unmet social needs.ObjectivesThis scoping review examines how information technology is used to screen and identify unmet social needs among vulnerable populations and its impact on the assessment process.MethodsFollowing PRISMA-ScR guidelines, we searched databases including MEDLINE, Embase, Scopus, ACM Digital Library, and Web of Science for studies published from 2010 to 2023. Eligible studies used technology to screen for and identify unmet social needs in populations with health and socioeconomic challenges. Data extraction focused on the types of technology, screening processes, and social needs identified.ResultsOur findings highlight a limited yet evolving landscape of technological applications. We identified 13 studies using tools like self-assessment surveys, tablet-based systems, and electronic portals. These tools were applied across diverse groups, such as refugees and patients in emergency departments. Innovative approaches, such as chatbots and multi-dimensional risk appraisal systems for older adults, showed potential. However, challenges included single-site studies, small samples, and integration issues with medical records. Effectiveness varied. The effectiveness of these tools in screening for unmet social needs shows mixed outcomes.ConclusionsInformation technology plays a pivotal role in improving the identification of unmet social needs. The findings underscore the need for broader, more integrated research to fully understand the impact of technology-based assessments and screening processes for social needs. Future efforts should focus on facilitated screening using technology both within and outside of the visit, ensuring the linkage to appropriate resources and care.
Perceptual discrimination of complex objects: APOE e4 gene-dose effects in mid-life
Authors: Lancaster Claire , Berens Sam , Daly Jessica , Rusted Jennifer , Bird Chris M. 
Published: October 2024

AbstractINTRODUCTIONComplex perceptual discrimination is supported by tau-vulnerable regions of the medial temporal lobe; notably the perirhinal cortex. This research tests whether there is a gene-dose effect of Apolipoprotein e4 on perceptual discrimination in mid-life.METHODS313 adults (45-65 years; grouped by APOE e4 gene-dose (142 APOE33, 135 APOE34, 36 APOE44)) completed a Greebles ‘odd-one-out’ task.RESULTSAPOE44 carriers were significantly less accurate in their perceptual judgements than APOE33 and APOE34 individuals. There was a significant Age x APOE e4 gene-dose interaction in response speed, with the slope of age-related slowing increasing stepwise with the number of e4 alleles carried. Estimates suggest high-risk individuals are quicker than the APOE33 control group until age 54, but slower thereafter.DISCUSSIONPerceptual disadvantages specific to APOE44 individuals suggest this high-risk group show compromised MTL-function by mid-life, potentially through accelerated tau-aggregation. Task performance in APOE34 carriers is relatively preserved across the studied age range.Research in ContextSystematic review:A review of the literature (e.g., PubMed; Google Scholar databases) revealed perceptual discrimination is impaired in the mild to moderate stages of Alzheimer’s Disease. No prior study, however, tests for an effect of APOE e4 gene-dose in healthy adulthood.Interpretation:Homozygous carriers of an APOE e4 genetic risk variant show perceptual disadvantages in mid-life. This may possibly reflect compromised MTL-function in this group, consistent with the theory perceptual discrimination will be vulnerable to early transentorhinal tau-accumulation. There is limited evidence of impairment in individuals carrying one copy of APOE e4 in mid-life.Future directions:Whether transentorhinal and hippocampal tau mediates the relationship between APOE e4 gene-dose and perceptual discrimination remains to be established. Future research may also explore the utility of perceptual discrimination tasks in clinical trials targeting the preclinical stages of Alzheimer’s Disease.
Interdisciplinary modelling and forecasting of dengue
Authors: Mills Cathal , Kraemer Moritz U. G. , Donnelly Christl A. 
Published: October 2024

AbstractUnderstanding the past, current, and future dynamics of dengue epidemics is challenging yet increasingly important. To date, many techniques across statistics, mathematics, and machine learning have provided us with quantitative tools for studying dengue epidemics. Here, using data from provinces in northern Peru across 2010 to 2021, we provide a new interdisciplinary pipeline that draws on a new and existing techniques to provide comprehensive understanding and robust prediction of dengue epidemic dynamics.Wavelet analyses can unveil spatiotemporal patterns in epidemic dynamics across annual and multi-annual time periods. Here, these included climatic forcing and greater spatial similarity in large outbreak years. Space-varying epidemic drivers included climatic influences and shorter pairwise distances driving greater epidemic similarity in more northerly coastal provinces. Then, using a Bayesian model, we can probabilistically quantify the timing, structure, and intensity of such climatic influences on Dengue Incidence Rates (DIRs), while simultaneously considering other influences. Recognising that a single model is generally sub-optimal for any forecasting task, we demonstrate how to form trained and untrained probabilistic ensembles for forecasting dengue cases in settings reflective of real-world conditions. We introduce a suite of climate-informed and covariate-free deep learning approaches that leverage big data and foundational time series, temporal convolutional networks, and conformal inference. We complement these modern techniques with statistically principled training and assessment of ensemble frameworks, while explicitly considering strong benchmark models, computational costs, public health priorities, and data availability limitations. In doing so, we show how ensemble frameworks consistently outperform individual models across space and time, and produce sharp and accurate forecasts with robust, reliable descriptions of uncertainty. We report interpretable classification metrics for detection of outbreaks to communicate our outputs with the wider public and public health authorities.Looking forward, whether the objective is to understand and/or to predict epidemic dynamics, our modelling pipeline can be used in any dengue setting to robustly inform the decision-making and planning of public health authorities.
Salivary IgG antibody response against SARS-CoV-2 differs between vaccinated children and adults
Authors: Badano María Noel , Keitelman Irene , Pereson Matías Javier , Aloisi Natalia , Sabbione Florencia , Baré Patricia 
Published: October 2024

AbstractStudies comparing antibody responses against SARS-CoV-2 between children and adults show conflicting results in blood and are limited in the mucosa. Furthermore, as the results of studies comparing systemic and salivary immune responses are inconsistent, it is unclear whether determination of salivary antibodies against SARS-CoV-2 could be a non-invasive approach to evaluate the humoral immune response.In this work, by studying and comparing systemic and salivary IgG antibody responses in vaccinated adults, we observed that the salivary immune response against SARS-CoV-2 in vaccinated adults largely reflects that observed at systemic levels. Higher salivary and systemic antibody concentrations were observed in adults who had schedules that included mRNA-based vaccines, a greater number of exposures, a shorter interval time between last exposure and saliva collection and had been exposed to SARS-CoV-2. Detection of salivary antibodies was associated with schedules that included mRNA-based vaccines, time between last exposure and sample collection, and systemic antibody concentrations. This suggests that salivary antibody detection might be compromised in subjects with lower systemic antibody levels.Comparison of salivary antibody levels between vaccinated children and adults showed a stronger salivary antibody response against SARS-CoV-2 in vaccinated children. This also remained when antibody levels were compared between children and adults who had similar vaccination schedules or the same number of exposures or interval time between last exposure and saliva collection. A multivariable linear regression analysis confirmed these results showing that age, symptomatic exposure, number of vaccine doses and schedules that included mRNA-based vaccines associated with salivary anti-SARS-CoV-2 IgG antibody levels.Determination of salivary antibodies against SARS-CoV-2 could be a non-invasive approach to evaluate the short-term immune response in children and adults with multiple exposures, especially in settings where blood sampling cannot be fulfilled. The higher levels of salivary anti-SARS-CoV- 2 IgG antibodies observed in children align with studies reporting stronger systemic antibody responses in children, suggesting their adaptive immune responses might be more efficient both locally and systemically. Further studies are required to characterize the salivary microenvironment for a better understanding of the difference observed in the local humoral immune response between children and adults.
Plasma acellular transcriptome contains Parkinson’s disease signatures that can inform clinical diagnosis
Authors: Beric Aleksandra , Cisterna-García Alejandro , Martin Charissa , Kumar Ravindra , Alfradique-Dunham Isabel , Boyer Kevin , Saliu Ibrahim Olabayode , Yamada Shinnosuke , Sanford Jessie , Western Daniel , Liu Menghan , Alvarez Ignacio , Perlmutter Joel S. , Norris Scott A. , Pastor Pau , Zhao Guoyan , Botia Juan , Ibanez Laura 
Published: October 2024

ABSTRACTWe aimed to identify plasma cell-free transcripts (cfRNA) associated with Parkinson’s disease (PD) that also have a high predictive value to differentiate PD from healthy controls. Leveraging two independent populations from two different movement disorder centers we identified 2,188 differentially expressed cfRNAs after meta-analysis. The identified transcripts were enriched in PD relevant pathways, such as PD (p=9.26×10-4), ubiquitin-mediated proteolysis (p=7.41×10-5) and endocytosis (p=4.21×10-6). Utilizing in-house and publicly available brain, whole blood, and acellular plasma transcriptomic and proteomic PD datasets, we found significant overlap across dysregulated biological species in the different tissues and the different biological layers. We developed three predictive models containing increasing number of transcripts that can distinguish PD from healthy control with an area under the ROC Curve (AUC) ≥0.85. Finally, we showed that several of the predictive transcripts significantly correlate with symptom severity measured by UPDRS-III. Overall, we have demonstrated that cfRNA contains pathological signatures and has the potential to be utilized as biomarker to aid in PD diagnostics and monitoring.
Loss of Peripheral Retinal Vessels in Retinitis Pigmentosa
Authors: Ameri Hossein , Hong Alexander T. , Chwa Jason 
Published: October 2024

AbstractObjectiveRetinitis pigmentosa (RP) is the most common inherited retinal disease and a major cause of irreversible vision loss. The purpose of this study was to assess peripheral retinal vessels in RP.DesignCross-sectional studySubjectsPatients with RP and age-matched controls.MethodsUsing ultra-wide field fundus images, the retina was divided into three zones: posterior, mid periphery, and far periphery. To evaluate vascularity of the retina, the vessels were counted at the border of posterior and mid peripheral zones (Z1/2) and the border of mid peripheral and far peripheral zones (Z2/3).Main outcome measuresVessel counts at Z1/2 and Z2/3Results181 eyes of 107 RP patients and 130 eyes of 84 controls were included. In the RP group, the median vessel counts at Z1/2 and Z2/3 were 8 and 3, respectively. These were strikingly lower than the control group with the median vessels of 42 and 43.5 at Z1/2 (p<0.001) and Z2/3 (p<0.001), respectively. 22% of RP eyes were entirely avascular in the far periphery and 7% were avascular in the mid periphery and far periphery. Only 5% of RP eyes had more than 25 vessels at Z2/3. There were significantly fewer vessels in the temporal retina at both Z1/2 (p=0.01) and Z2/3 (p<0.001) in RP eyes. Furthermore, eyes with visual acuity of 20/200 or worse had significantly fewer vessels at Z1/2 (p<0.001) and Z2/3 (p<0.001). There were no significant differences in the number of vessels at Z1/2 and 2/3 between the right and left eyes of RP patients with both eyes included in the study.ConclusionsThis study provides compelling evidence of substantial symmetrical peripheral retinal vascular loss in RP. This finding may aid in clinical diagnosis of the disease and have significant therapeutic implications.
Exploring social determinants of childhood vaccination based on the National Immunization Surveys Data
Authors: Pabon-Rodriguez Felix M. 
Published: October 2024

AbstractEnsuring children receive vaccinations is essential for their health and community well-being, preventing serious diseases and fostering overall immunity. Nevertheless, the impact of social determinants of health on vaccination access underscores the urgent need for targeted interventions to address disparities and ensure equitable healthcare delivery for all children. This study investigates the impact of several social determinants on childhood vaccination in the United States using data from the National Immunization Surveys from 2010-2022. As a simple approach, ordinal logistic mixed-effect models is used to analyze vaccination patterns among children aged 19– 35 months as reported by parents or guardians. The study findings highlight associations between vaccination and key social factors, including the child’s age group, parents’ or guardians’ education level, and vaccination awareness due to the child being the firstborn. The results from this basic study provide insights into the nuanced relationships that influence vaccination practices.
Effect of Data Heterogeneity in Clinical MALDI-TOF Mass Spectra Profiles on Direct Antimicrobial Resistance Prediction through Machine Learning
Authors: Park Youngjun , Weig Michael , Noll Christine , Bader Oliver , Hauschild Anne-Christin 
Published: October 2024

AbstractThe matrix-assisted laser desorption-ionization time-of-flight mass spectrometry has become a powerful tool for accurate species identification in routine diagnostic microbiology. Recently, the application of machine learning models with MALDI-TOF mass spectra data indicated that rapid prediction of antimicrobial resistance patterns might facilitate even timelier and improved antimicrobial treatment. Although MALDI-TOF mass spectra data have proven valuable for clinical decision support, the issue of class imbalance in routine clinical data is often overlooked. This imbalance arises from factors such as local epidemiology, selective pressure from antibiotics, culture conditions, the methodology of phenotypic antimicrobial susceptibility testing, and sample preparation processes. Here, we provide a large mass spectra dataset, MS-UMG, for antimicrobial resistance prediction model training. With previously available public datasets, our dataset is evaluated and validated for usage in AMR prediction. We further explore the mass spectra data and identify informative regions on the spectra profile for AMR prediction. Moreover, we investigate the composition of this clinical dataset and present the implications of data heterogeneity on machine learning model performance. In conclusion, our findings highlight that accurate comprehension of clinical routine data and consideration of diverse hospital protocols are critical for effective clinical decision support systems with machine learning models.Key PointsIntroduced a large-scale clinical mass spectrometry dataset to the scientific community for research on antimicrobial resistance.Conducted a comparison and evaluation of this dataset with other existing large-scale MS datasets, highlighting its value for developing and validating predictive models in clinical settings.Demonstrated the robustness of machine learning models for antimicrobial resistance prediction using large-scale clinical mass spectra profiles.Analyzed the impact of data heterogeneity on the training and performance of machine learning models, emphasizing the need to account for variability in clinical routine data to enhance model reliability and generalizability.
Endothelial cells stably infected with recombinant Kaposi’s sarcoma-associated herpesvirus display distinct viscoelastic and morphological properties
Authors: Shabangu Majahonkhe M , Blumenthal Melissa J , Sass Danielle T , Lang Dirk M , Schafer Georgia , Franz Thomas 
Published: October 2024

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus that has a tropism for endothelial cells and leads to the development of Kaposi’s sarcoma, especially in people living with HIV. The present study aimed to quantify morphological and mechanical changes in endothelial cells after infection with KSHV to assess their potential as diagnostic and therapeutic markers. Vascular (HuARLT2) and lymphatic endothelial cells (LEC) were infected with recombinant KSHV (rKSHV) by spinoculation, establishing stable infections (HuARLT2-rKSHV and LEC-rKSHV). Cellular changes were assessed using mitochondria-tracking microrheology and morphometric analysis. rKSHV infection increased cellular deformability, indicated by higher mitochondrial mean squared displacement (MSD) for short lag times. Specifically, MSD at τ = 0.19 s was 49.4% and 42.2% higher in HuARLT2-rKSHV and LEC-rKSHV, respectively, compared to uninfected controls. There were 23.9% and 36.7% decreases in the MSD power law exponents for HuARLT2-rKSHV and LEC-rKSHV, respectively, indicating increased cytosolic viscosity associated with rKSHV infection. Infected cells displayed a marked spindloid phenotype with an increase in aspect ratio (29.7%) and decreases in roundness (26.1%) and circularity (25.7%) in HuARLT2-rKSHV, with similar changes observed in LEC-rKSHV. The quantification of distinct KSHV-induced morpho-mechanical changes in endothelial cells demonstrates the potential of these changes as diagnostic markers and therapeutic targets.
Nonlinear EEG Analysis for Distinguishing Mind Wandering and Focused Attention: A Machine Learning Approach
Authors: Kheiri Farshad , Sundaram Shyam , Bragin Anatol 
Published: October 2024

AbstractThis study uses nonlinear analysis techniques to distinguish between mind wandering (MW) and focused attention (FA) states using EEG data. EEG recordings from 21 sessions were segmented into intervals of 2, 3, 5, 6, 10, and 15 seconds, and seven nonlinear features were extracted to capture the brain’s dynamic complexity. Machine learning models, including gradient boosting trees, were applied to classify MW and FA states, with the highest accuracy of 75% achieved using 5-second segments.Frequency-related features, particularly mean frequency and global frequency, were the most important in distinguishing between MW and FA. These findings emphasize the role of nonlinear EEG analysis in understanding the chaotic brain patterns underlying cognitive states. Future work should focus on temporal dynamics and personalized models to improve classification accuracy, with potential applications in cognitive enhancement and mental health.