bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using high-resolution functional MRI to differentiate impacts of strabismic and anisometropic amblyopia on evoked ocular dominance activity in humans
Authors: Nasr Shahin , Skerswetat Jan , Gaier Eric D. , Malladi Sarala N. , Kennedy Bryan , Tootell Roger B.H. , Bex Peter , Hunter David G. 
Published: February 2024

AbstractWe employed high-resolution functional MRI (fMRI) to distinguish the impacts of anisometropia and strabismus (the two most frequent causes of amblyopia) on the evoked ocular dominance (OD) response. Sixteen amblyopic participants (8 females), comprising 8 individuals with strabismus, 7 with anisometropia, 1 with deprivational amblyopia, along with 8 individuals with normal visual acuity (1 female), participated in this study for whom, we measured the difference between the response to stimulation of the two eyes, across early visual areas (V1-V4).In controls, as expected from the organization of OD columns, the evoked OD response formed a striped pattern that was mostly confined to V1. Compared to controls, the OD response in amblyopic participants formed larger fused patches that extended into downstream visual areas. Moreover, both anisometropic and strabismic participants showed stronger OD responses in V1, as well as in downstream visual areas V2-V4. Although this increase was most pronounced in V1, the correlation between the OD response level and the interocular visual acuity difference (measured behaviorally) was stronger in higher-level visual areas (V2–V4).Beyond these common effects, and despite similar densities of amblyopia between the anisometropic and strabismic participants, we found a greater increase in the size of V1 portion that responded preferentially to fellow eye stimulation in anisometropic compared to strabismic individuals. We also found a greater difference between the amplitudes of the response to binocular stimulation, in those regions that responded preferentially to the fellow vs. amblyopic eye, in anisometropic compared to strabismic subjects. In contrast, strabismic subjects demonstrated increased correlation between the OD responses evoked within V1 superficial and deep cortical depths, whereas anisometropic subjects did not.These results provide some of the first direct functional evidence for distinct impacts of strabismus and anisometropia on the mesoscale functional organization of the human visual system, thus extending what was inferred previously about amblyopia from animal models.
Clinical and economic inpatient burden of respiratory syncytial virus (RSV) infections in children < 2 years of age in Germany, 2014-2019: a retrospective health claims analysis
Authors: Lade Caroline , Bayer Lea , Huebbe Bennet , Riedel Jennifer , Melnik Sima , Brestrich Gordon , von Eiff Christof , Tenenbaum Tobias 
Published: February 2024

ABSTRACTBackgroundRespiratory syntactical virus (RSV) is a common cause for severe lower respiratory tract infections (LRTI) in children <2 years of age in Germany – though little is known about the clinical and economic burden of RSV in children with and without risk factors per month of life.MethodsIn a retrospective health claims analysis, we identified RSV inpatient cases between 2014 and 2019. We assessed incidence rates, mortality rate, health resource utilization, associated direct costs per case and excess costs for 30, 90 and 365 days after hospital admission matched to a control group. The outcomes are reported separately for the first and second year of life (i.e., for infants and toddlers) and were stratified by month of life, preterm and risk status (i.e., presence of underlying disease: chronic respiratory or cardiac disease, immunosuppression, neurological diseases, diabetes, conditions originating in the perinatal period).ResultsRSV-attributable hospital incidence rate was higher in infants (30.25/1,000) than toddlers (14.52/1,000), highest in the first three months of life (44.21/1,000), in infants born preterm (64.76/1,000) or with any underlying disease (54.85/1,000). Mortality rate was also higher for infants (0.08/1,000) than toddlers (0.04/1,000). Mean 30-day excess costs ranged from 2,953 € for infants born full-term at no risk, hospitalized for 5 days, to 6,694 € for infants born extremely premature, hospitalized for 7 days.ConclusionIn Germany, the clinical and economic burden of RSV is substantial, especially in the most vulnerable population, that is, very young infants, those born premature and/or those with an underlying disease.
EQUALITY OF OPPORTUNITY FOR TIMELY DEMENTIA DIAGNOSIS (EQUATED): A QUALITATIVE STUDY OF HOW PEOPLE FROM MINORITIZED ETHNIC GROUPS EXPERIENCE THE EARLY SYMPTOMS OF DEMENTIA AND SEEK HELP
Authors: Carter Christine , Roche Moïse , Whitfield Elenyd , Budgett Jessica , Morgan-Trimmer Sarah , Zabihi Sedigheh , Birks Yvonne , Walter Fiona , Wilberforce Mark , Jiang Jessica , Ahmed Refah Z , Dowridge Wesley , Marshall Charles R , Cooper Claudia 
Published: February 2024

ABSTRACTIntroductionPeople from minoritized ethnic groups are diagnosed with dementia later in the disease. We explored pathways that may determine the timing of diagnoses in an ethnically diverse, urban area.MethodsWe conducted 61 semi-structured interviews: 10 community-dwelling older people from minoritized ethnic backgrounds with diagnosed and undiagnosed dementia (mean age = 72 years; males = 5/10), 30 family members (51, 10/30), 16 health or social care professionals (42; 3/15) three paid carers and two interpreters for people with dementia. We used reflexive thematic analysis, and the Model of Pathways to Treatment to consider diagnostic delay.FindingsWe identified three themes: (1)Cultural identity and practices shape responses: gendered expectations that families relieve elders of household roles reduce awareness or concern when functioning declines; expectations that religious practices are maintained mean problems doing so triggers help-seeking. Second generation family members often held insider and outsider identities, balancing traditional and Western perspectives. (2)Becoming like a tourist:daily experiences became unfamiliar for people developing dementia in an adopted country, sometimes engendering a need to reconnect with a home country. For professionals and interpreters, translating meanings faithfully, and balancing relatives’ and clients’ voices, were challenging. (3)Naming and conceptualising dementia:the term dementia was stigmatised, with cultural nuances in how it was understood; initial presentations often included physical symptoms with cognitive concerns.ConclusionGreater understanding of dilemmas faced by minoritized ethnic communities, closer collaboration with interpreters and workforce diversity could reduce time from symptom appraisal to diagnosis, and support culturally competent diagnostic assessments.
Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis
Authors: Varghese Jithin Sam , Guo Yi , Ali Mohammed K. , Donahoo W. Troy , Chakkalakal Rosette J. 
Published: February 2024

ABSTRACTObjectiveTo study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection.Subjects/MethodsUsing real-world data from the One Florida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020 – January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018 – January 2020). Body mass index (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at baseline and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race-ethnicity, age, and hospitalization status.ResultsThe study sample consisted of 44,436 (Exposed cohort), 164,118 (Unexposed cohort), and 41,189 (Historical cohort). Cumulatively, 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic Other. Patients had an average age of 51.9 years (SD: 18.9). At baseline, relative to the Exposed cohort (mean BMI: 29.3 kg/m2[95%CI: 29.0, 29.7]), the Unexposed (–0.07 kg/m2[95%CI; –0.12, –0.01]) and Historical controls (–0.27 kg/m2[95%CI; – 0.34, –0.20]) had lower BMI. Relative to no change in the Exposed over 100 days (0.00 kg/m2[95%CI; –0.03,0.03]), the BMI of those Unexposed decreased (–0.04 kg/m2[95%CI; –0.06, – 0.01]) while the Historical cohort’s BMI increased (+0.03 kg/m2[95%CI;0.00,0.06]). BMI changes were consistent between Exposed and Unexposed cohorts for most population groups, except at start of follow-up period among Males and those 65 years or older, and in changes over 100 days among Males and Hispanics.ConclusionsIn a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.
To weight or not to weight? Studying the effect of selection bias in three large EHR-linked biobanks
Authors: Salvatore Maxwell , Kundu Ritoban , Shi Xu , Friese Christopher R , Lee Seunggeun , Fritsche Lars G , Mondul Alison M , Hanauer David , Pearce Celeste Leigh , Mukherjee Bhramar 
Published: February 2024

AbstractObjectiveTo explore the role of selection bias adjustment by weighting electronic health record (EHR)-linked biobank data for commonly performed analyses.Materials and methodsWe mapped diagnosis (ICD code) data to standardized phecodes from three EHR-linked biobanks with varying recruitment strategies: All of Us (AOU; n=244,071), Michigan Genomics Initiative (MGI; n=81,243), and UK Biobank (UKB; n=401,167). Using 2019 National Health Interview Survey data, we constructed selection weights for AOU and MGI to be more representative of the US adult population. We used weights previously developed for UKB to represent the UKB-eligible population. We conducted four common descriptive and analytic tasks comparing unweighted and weighted results.ResultsFor AOU and MGI, estimated phecode prevalences decreased after weighting (weighted-unweighted median phecode prevalence ratio [MPR]: 0.82 and 0.61), while UKB’s estimates increased (MPR: 1.06). Weighting minimally impacted latent phenome dimensionality estimation. Comparing weighted versus unweighted PheWAS for colorectal cancer, the strongest associations remained unaltered and there was large overlap in significant hits. Weighting affected the estimated log-odds ratio for sex and colorectal cancer to align more closely with national registry-based estimates.DiscussionWeighting had limited impact on dimensionality estimation and large-scale hypothesis testing but impacted prevalence and association estimation more. Results from untargeted association analyses should be followed by weighted analysis when effect size estimation is of interest for specific signals.ConclusionEHR-linked biobanks should report recruitment and selection mechanisms and provide selection weights with defined target populations. Researchers should consider their intended estimands, specify source and target populations, and weight EHR-linked biobank analyses accordingly.
Analysis of signs and symptoms of SARS-CoV-2 virus infection considering different waves using Machine Learning
Authors: Ulrichsen Felipe C. , Sena Alexandre C. , Porto Luís Cristóvao , Figueiredo Karla 
Published: February 2024

AbstractIn March 2020, the World Health Organization declared a world pandemic of COVID-19, which can manifest in humans as a consequence of virus infection of SARS-CoV-2. On this context, this work uses Data Mining and Machine Learning techniques for the infection diagnosis. A methodology was created to facilitate this task and can be applied in any outbreak or pandemic wave. Besides generating diagnosis models based only on signals and symptoms, the method can evaluate if there are differences in signals and symptoms between waves (or outbreaks) through explainable techniques of the machine learning models. Another aspect is identifying possible quality differences between exams, for example, Rapid Test (RT) and Reverse Transcription–Polymerase Chain Reaction (RT-PCR). The case study in this work is based on data from patients who sought care at Piquet Carneiro Polyclinic of the State University of Rio de Janeiro. In this work, the results obtained with the tests were used to diagnose symptomatic infection of the SARS-CoV-2 virus, based on related signals and symptoms, and the date of the initial of these signals and symptoms. Using the Random Forrest model, it was possible to achieve the result of up to 76% sensitivity, 86% specificity, and 79% accuracy in the results of tests in one contagion wave of the SARS-CoV-2 virus. Moreover, differences were found in signals and symptoms between contagion waves, in addition to the observation that examsRT-PCRandRT Antigen testsare more reliable thanRT antibody test.
Knowledge, Attitude, and Practices towards COVID-19 Infection and Prevention Measures among Medical Students
Authors: Ruyeras Jade Monica Marie J. , Basi Priya Kaur V. , Cañete Louise Anne C. , Capoy Neal Abram M. , Castillo Mary Ysabelle S. , Colonia Cristine Jayne T. , Gantuangco Bea Lou Marie E. , Jumamil Primo Andrio V. , Mantilla Hubert Paul S. , Talili Giovanni Sergius C. , Untal Riana Camille G. 
Published: February 2024

ABSTRACTThe COVID-19 pandemic has rapidly led to an unprecedented health threat worldwide. During this time, disease prevention is considered to be the best way for general health protection. This is achieved through public health education by extending proper knowledge, promoting an optimistic attitude, and keeping the public compliant with preventive measures. As components of the healthcare system, medical students should also play a role in disease prevention more so in the Philippines where the Department of Health has called upon medical graduates to render services in response to the national emergency. In this study, the knowledge, attitude, and practices (KAP) of medical students from Cebu Institute of Medicine (CIM) towards COVID-19 infection and preventive measures were assessed. Demographic factors, their respective effect size on KAP, as well as the relationship between KAP variables were determined. The revised questionnaire, drafted based on qualitative and quantitative validity tests, was then used for the pilot study to generate the final questionnaire. Responses from participants underwent descriptive and correlational analysis. The results showed that the majority of the medical students of CIM have adequate knowledge (78.24%), positive attitude (80.68%), and good practices (94.38%) towards COVID-19 infection and prevention measures. Females have a significant association (p-value = 0.03) with better practices than male counterparts. Knowledge (p-value = 0.004) and attitude (p-value = 0.003) also showed significant correlation with practices, implying that knowledge and attitude play a role in shaping compliance to health practices. Therefore, health interventions should aim to disseminate accurate, evidence-based information and improve attitude towards the implemented precautionary measures in order to increase effectiveness of policies.
KDM6A Regulates Immune Response Genes in Multiple Myeloma
Authors: Dupéré-Richer Daphne , Riva Alberto , Maji Sayantan , Barwick Benjamin G. , Román Heidi Casellas , Sobh Amin , Quickstad Gabrielle , Li Jianping , De Umasankar , Piper Crissandra , Kulis Marta , Ezponda Teresa , Martin-Subero José Ignacio , Tonon Giovanni , Zhang Weizhou , Mitsiades Constantine S , Boise Lawrence H , Bennett Richard L. , Licht Jonathan D. 
Published: February 2024

AbstractThe histone H3K27 demethylase KDM6A is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activatesNLRC5andCIITAencoding regulators of Major Histocompatibility Complex (MHC) genes. Patient data indicate that NLRC5 and CIITA, are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A and decreased gene expression. Reestablishing histone acetylation with an HDAC3 inhibitor leads to upregulation of MHC expression, offering a strategy to restore immunogenicity of KDM6A deficient tumors. Loss ofKdm6ain murine RAS-transformed fibroblasts led to increased growthin vivoassociated with decreased T cell infiltration.Statement of significanceWe show that KDM6A participates in immune recognition of myeloma tumor cells by directly regulating the expression of the master regulators of MHC-I and II, NLRC5 and CIITA. The expression of these regulators can by rescued by the HDAC3 inhibitors in KDM6A-null cell lines.
A new archaeal virus that suppresses the transcription of host immunity genes
Authors: Turgeman-Grott Israela , Golan Noam , Neri Uri , Naki Doron , Altman-Price Neta , Eizenshtein Kim , Choudhary Deepak K. , Levy Rachel , Shalev Yarden , Himani Himani , Reshef Leah , Gophna Uri 
Published: February 2024

AbstractIn some extreme environments, archaeal cells have been shown to have chronic viral infections, and such infections are well-tolerated by the hosts and may potentially protect against more lethal infections by lytic viruses. We have discovered that a naturalHaloferaxstrain (48N), which is closely related to the model organismHaloferax volcanii,is chronically-infected by a lemon-shaped virus, which we could purify from the medium. The chronic infection by this virus, which we named LSV-48N, is never cleared, despite the multiple defense systems of the host that include CRISPR-Cas, and two CBASS systems. Curing 48N of its virus by genetic engineering, led to radical changes in the gene expression profile of 48N and a dramatic improvement in its growth rate. Remarkably, the cured 48N is the fastest-growing haloarchaeon reported to date, with a generation time of approximately 1 hour at 45°C compared to the typical 2.5 hours ofH. volcaniior its infected isogen, and faster than any known haloarchaeon. The virus subverts host defenses by reducing their transcription and interfering with the CRISPR spacer acquisition machinery. Our results suggest that the slow growth of many halophilic archaea could be due to the effects of proviruses within their genomes that consume resources and alter the gene expression of their hosts.
Surface tension-driven sorting of human perilipins on lipid droplets
Authors: Araujo Ana Rita Dias , Bello Abdoul Akim , Bigay Joëlle , Franckhauser Céline , Gautier Romain , Cazareth Julie , Kovacs David , Brau Frédéric , Fuggetta Nicolas , Copic Alenka , Antonny Bruno 
Published: February 2024

AbstractPerilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was dependent on tension, even with polar lipids favoring packing defects, and showed an inverse correlation between protein and phospholipid densities on LDs. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the huge difference in LD avidity observedin vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.Significance statementLipid droplets (LDs) are highly dynamic organelles, whose size and surface properties vary during their life-time and also differ between different tissues. Here, we analyze the mode of binding of human perilipins (PLINs), the most abundant LD proteins, to LDs. We have developed a new reconstitution method, which shows that the purified PLIN family members have very different affinities for LDs, which might explain how they handle LDs of different dynamics in the cell.
Direct, bisulfite-free 5mC and 5hmC sequencing at single-cell resolution
Authors: Chen Xiufei , Cheng Jingfei , Kong Linzhen , Shu Xiao , Xu Haiqi , Inoue Masato , Berrocal Marion Silvana Fernández , Døskeland Dagny Sanden , Sivakumar Shivan , Liu Yibin , Ye Jing , Song Chun-Xiao 
Published: February 2024

AbstractWe report the first direct sequencing methodologies for quantitative detection of 5mC and 5hmC at single-base resolution and single-cell level, termed scTAPS (for 5mC + 5hmC) and scCAPS+ (for 5hmC specifically). With ∼90% mapping efficiency, our methods accurately benchmark 5mC and 5hmC profiles in CD8+ T and mES cells, respectively. Notably, scCAPS+ revealed a global increase in 5hmC within the hippocampus of aging mice, both in neurons and in non-neurons.
Rapid growth and the evolution of complete metamorphosis in insects
Authors: Manthey Christin , E Metcalf C Jessica , Monaghan Michael T , Steiner Ulrich Karl , Rolff Jens 
Published: February 2024

AbstractMore than 60% of all animal species are insects that undergo complete metamorphosis. The key innovation of these holometabolous insects is a pupal stage between the larva and adult when most structures are completely rebuilt. Why this extreme lifestyle evolved is unclear. Here we test the hypothesis that a trade-off between growth and differentiation explains the evolution of this novelty. Using a comparative approach, we find that holometabolous insects grow much faster than hemimetabolous insects. Using a theoretical model, we then show how holometaboly evolves under a growth-differentiation trade-off and identify conditions under which such temporal decoupling of growth and differentiation is favored. Our work supports the notion that the holometabolous life history evolved to remove developmental constraints on fast growth, primarily under high mortality.
Genetic insertion of mouse Myxovirus-resistance gene 1 increases innate resistance against both high and low pathogenic avian influenza virus by significantly decreasing replication in chicken DF1 cell line
Authors: Briggs Kelsey , Chrzastek Klaudia , Segovia Karen , Mo Jongsuk , Kapczynski Darrell R. 
Published: February 2024

AbstractAvian influenza virus (AIV) is a constant threat to animal health with recent global outbreaks resulting in the death of hundreds of millions of birds with spillover into mammals. Myxovirus-resistance (Mx) proteins are key mediators of the antiviral response that block virus replication. Mouse (Mu) Mx (Mx1) is a strong antiviral protein that interacts with the viral nucleoprotein to inhibit polymerase function. The ability of avian Mx1 to inhibit AIV is unclear. In these studies, Mu Mx1 was stably introduced into chicken DF1 cells to enhance the immune response against AIV. Following infection, titers of AIV were significantly decreased in cells expressing Mu Mx1. In addition, considerably less cytopathic effect (CPE) and matrix protein staining was observed in gene-edited cells expressing Mu Mx1, suggesting Mu Mx1 is broadly effective against multiple AIV subtypes. This work provides foundational studies for use of gene-editing to enhance innate disease resistance against AIV.