bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi-City COVID-19 Categorical Forecasting Model Utilizing Wastewater-Based Epidemiology
Authors: Rankin Naomi , Saiyed Samee , Du Hongru , Gardner Lauren 
Published: September 2024

AbstractThe COVID-19 pandemic highlighted shortcomings in forecasting models, such as unreliable inputs/outputs and poor performance at critical points. As COVID-19 remains a threat, it is imperative to improve current forecasting approaches by incorporating reliable data and alternative forecasting targets to better inform decision-makers.Wastewater-based epidemiology (WBE) has emerged as a viable method to track COVID-19 transmission, offering a more reliable metric than reported cases for forecasting critical outcomes like hospitalizations. Recognizing the natural alignment of wastewater systems with city structures, ideal for leveraging WBE data, this study introduces a multi-city, wastewater-based forecasting model to categorically predict COVID-19 hospitalizations.Using hospitalization and COVID-19 wastewater data for six US cities, accompanied by other epidemiological variables, we develop a Generalized Additive Model (GAM) to generate two categorization types. The Hospitalization Capacity Risk Categorization (HCR) predicts the burden on the healthcare system based on the number of available hospital beds in a city. The Hospitalization Rate Trend (HRT) Categorization predicts the trajectory of this burden based on the growth rate of COVID-19 hospitalizations. Using these categorical thresholds, we create probabilistic forecasts to retrospectively predict the risk and trend category of six cities over a 20-month period for 1, 2, and 3 week forecasting windows.We also propose a new methodology to measure forecasting model performance at change points, or time periods where sudden changes in outbreak dynamics occurred. We also explore the influence of wastewater as a predictor for hospitalizations, showing its inclusion positively impacts the model’s performance. With this categorical forecasting study, we are able to predict hospital capacity risk and disease trends in a novel and useful way, giving city decision-makers a new tool to predict COVID-19 hospitalizations.
Shade Inhibits Cambial Activity inPopulusStems by the SPL16/SPL23-Mediated Cytokinin Pathway
Authors: Wei Hongbin , Xiao Xingyue , Deng Jiao , Li Yi , Luo Mengting , Zhang Chengshan , Xu Jinyi , Luo Keming 
Published: September 2024

AbstractTrees in natural forests or plantations often encounter neighbor proximity signal that negatively impacts wood production. However, the molecular basis underlying shade-regulation of vascular cambial activity during stem radial growth remains unknown in woody species. Here, we revealed that high stand density and simulated shade (low R/FR ratio) suppress the division and differentiation of cambial cells in poplar stems. A genome-wide screen forPopulus SQUAMOSA PROMOTER BINDING PROTEIN-LIKE(SPL) genes identified thatSPL16andSPL23are preferentially expressed in the phloem and cambium, being downregulated by simulated shade. Knocking outSPL16/23impaired cambial activity, whereas phloem-specific overexpression ofSPL16stimulated cambial proliferation and mitigated the shade-inhibition of cambial activity. Additionally, shade decreased bioactive cytokinin (CK) levels by suppressing the expression of CK biosynthesis genesIPT5a,IPT5bandLOG1bin poplar stems. Molecular and genetic studies reveled that SPL16/23 directly activateIPT5s/LOG1bexpression to promote CK biosynthesis and cambial activity. Moreover, elevated miR156 expression in shade-treated stems regulatedSPL16/23at the post-transcriptional level, mediating shade’s effects on cambial activity. Collectively, our findings unravel that the miR156-SPL16/23-IPT5/LOG1-cytokinin pathway operates in the shade-mediated inhibition of cambial activity, providing potential targets for the genetic improvement of shade-tolerant trees.
A Qualitative Study of People with Alzheimer’s Disease in a Memory Clinic Considering Lecanemab Treatment
Authors: Parks Anna L , Thacker Ayush , Dohan Daniel , Ramirez Gomez Liliana A , Ritchie Christine S , Paladino Joanna , Shah Sachin J 
Published: September 2024

AbstractBackgroundPeople with Alzheimer’s disease (AD) now have access to disease-modifying treatment with anti-amyloid monoclonal antibodies (mAbs). Their perception of risks and benefits and approach to treatment decisions remain unknown.ObjectiveWe aimed to understand how people with AD weigh the benefits and costs of anti-amyloid mAbs and incorporate these into decisions about treatment.MethodsWe conducted semi-structured interviews with people with biomarker- or imaging-confirmed AD and mild or moderate cognitive impairment who were seen at memory care clinics and discussed lecanemab with a clinician. Interviews were recorded, transcribed, and deidentified. Thematic analysis identified themes and subthemes.ResultsAmong 22 participants (mean age 70, 8 [36%] women, 22 [100%] White), analysis revealed 3 major themes and associated subthemes: 1) People with AD sought and obtained information from different sources—advocacy organizations, the Internet, and clinicians; 2) Hopes, expected benefits, and the existential threat of dementia drove willingness and readiness to start lecanemab; 3) Individual traits, family factors, and degree of trust in expertise influenced how people balanced risks and benefits. Some would accept treatment at any cost; others carefully weighed risks and burdens, but were motivated by supportive families, insurance coverage, and trust in expertise; for a few, costs decidedly outweighed their personal benefits. People with AD desired more individualized information and to hear more from patients who took the medication.ConclusionResults from this first qualitative study of people with AD considering treatment with anti-amyloid mAbs can inform clinician, health system and policy efforts to individualize decisions.
Identifying individuals at risk for surgical supravalvar aortic stenosis by polygenic risk score with graded phenotyping
Authors: Liu D. , Mervis C.B. , Levin M.D. , Biamino E. , Bedeschi M.F. , Digilio M.C. , Squeo G.M. , Villa R. , Osgood S. , Freeman J.A. , Raja N. , Merla G. , Roberts A.E. , Morris C.A. , Osborne L.R. , Kozel B.A. 
Published: September 2024

AbstractIn a previous pathway-based, extreme phenotype study, we identified 1064 variants associated with supravalvar aortic stenosis (SVAS) severity in people with Williams syndrome (WS) and either no SVAS or surgical SVAS. Here, we use those variants to develop and test polygenic risk scores (PRS). We used the clumping and thresholding (CT) approach on the full 1064 variants and a 427-variant subset that was part of 13 biologically relevant pathways identified in the previous study. We also used a lasso approach on the full set. We were able to achieve an area under the curve (AUC) of >0.99 for the two CT PRS methods, using only 622 and 320 variants respectively when 2/3 of the initial 217 participants data were used for training and 1/3 for testing. The lasso performed less well. We then evaluated the performance of those PRS variant sets on an additional group of 138 patients with WS with intermediate severity SVAS and found a misclassification rate of <10% between the surgical and intermediate groups, suggesting potential for clinical utility of the score.
Exome wide association study for blood lipids in 1,158,017 individuals from diverse populations
Authors: Koyama Satoshi , Yu Zhi , Choi Seung Hoan , Jurgens Sean J. , Selvaraj Margaret Sunitha , Klarin Derek , Huffman Jennifer E. , Clarke Shoa L. , Trinh Michael N. , Ravi Akshaya , Dron Jacqueline S. , Spinks Catherine , Surakka Ida , Bhatnagar Aarushi , Lannery Kim , Hornsby Whitney , Damrauer Scott M. , Chang Kyong-Mi , Lynch Julie A , Assimes Themistocles L. , Tsao Philip S. , Rader Daniel J. , Cho Kelly , Peloso Gina M. , Ellinor Patrick T. , Sun Yan V. , Wilson Peter WF. , Program Million Veteran , Natarajan Pradeep 
Published: September 2024

AbstractRare coding alleles play crucial roles in the molecular diagnosis of genetic diseases. However, the systemic identification of these alleles has been challenging due to their scarcity in the general population. Here, we discovered and characterized rare coding alleles contributing to genetic dyslipidemia, a principal risk for coronary artery disease, among over a million individuals combining three large contemporary genetic datasets (the Million Veteran Program, n = 634,535, UK Biobank, n = 431,178, and the All of Us Research Program, n = 92,304) totaling 1,158,017 multi-ancestral individuals. Unlike previous rare variant studies in lipids, this study included 238,243 individuals (20.6%) from non-European-like populations.Testing 2,997,401 rare coding variants from diverse backgrounds, we identified 800 exome-wide significant associations across 209 genes including 176 predicted loss of function and 624 missense variants. Among these exome-wide associations, 130 associations were driven by non-European-like populations. Associated alleles are highly enriched in functional variant classes, showed significant additive and recessive associations, exhibited similar effects across populations, and resolved pathogenicity for variants enriched in African or South-Asian populations. Furthermore, we identified 5 lipid-related genes associated with coronary artery disease(RORC, CFAP65, GTF2E2, PLCB3, and ZNF117). Among them,RORCis a potentially novel therapeutic target through the down regulation of LDLC by its silencing.This study provides resources and insights for understanding causal mechanisms, quantifying the expressivity of rare coding alleles, and identifying novel drug targets across diverse populations.
Human papillomavirus vaccination at the national level in Tunisia: a cost-effectiveness analysis using a comparative modeling study
Authors: Laraj Oumaima , Benzina Beya , Gzara Ahlem , Kebir Amira , Abbas Kaja , Miled Slimane Ben 
Published: September 2024

AbstractCervical cancer is one of the most prevalent cancer diseases in women caused by persistent infection with one of 13 sexually transmitted high-risk human papillomavirus (HPV) types. Vaccination can significantly reduce the prevalence of this burden in low-middle income countries. However, HPV vaccination is not included in the Tunisian immunization program. Since the economic evaluation of HPV vaccines is crucial to inform public-health decisions, the World Health Organization (WHO) recommends that a cost-effectiveness analysis of HPV vaccination is conducted before nationwide introduction. This study aimed to conduct a cost-effectiveness analysis of incorporating different HPV vaccines into the national immunisation schedule in Tunisia. The potential health and economic impacts of human papillomavirus (HPV) vaccination were evaluated through comparative modelling analysis using two published static models (UNIVAC and Papillomavirus Rapid Interface for Modelling and Economics (PRIME)). Academic literature and anecdotal evidence were included on the demographic variables, cervical cancer incidence and mortality, treatment costs, vaccine delivery costs and other model parameters.The cost of vaccination, treatment costs saved, net costs, cases and deaths averted, life years saved, disability-adjusted life years (DALYs) prevented, and incremental cost-effectiveness ratios were predicted and reported as primary outcomes. The incremental cost-effectiveness ratios (ICERs) were estimated per disability-adjusted life years (DALYs) averted using the cost-effectiveness threshold (CET) defined by the World Health Organisation (WHO). All HPV vaccines were very cost effective (with every disability-adjusted life-year averted costing less than the cost-effectiveness threshold). The analyses were done from a health system and societal perspective. Despite model differences, the PRIME and UNIVAC models yielded similar vaccine-impact estimates.
Exploratory functional and quality of life outcomes with daily consumption of the ketone ester bis-octanoyl (R)-1,3-butanediol in healthy older adults: a randomized, parallel arm, double-blind, placebo-controlled study
Authors: Stubbs Brianna J , Stephens Elizabeth B , Senadheera Chatura , Diaz Stephanie Roa , Peralta Sawyer , Alexander Laura , Silverman-Martin Wendie , Kurtzig Jamie , Fernando B. Ashen , Yurkovich James T , Garcia Thelma Y , Yukawa Michi , Morris Jennifer , Johnson James B , Newman John C 
Published: September 2024

AbstractBackgroundKetone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on the inflammatory and metabolic aging pathways underpinning frailty inin vivomodels. Ketone esters (KEs) are compounds that induce hyperketonemia without dietary changes and that may impact physical and cognitive function in young adults. The functional effects of KEs have not been studied in older adults.ObjectivesOur long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. Here, we report the exploratory functional and quality-of-life outcome measures collected during a 12-week safety and tolerability study of KE (NCT05585762).DesignRandomized, placebo-controlled, double-blinded, parallel-group, pilot trial of 12-weeks of daily KE ingestion.SettingThe Clinical Research Unit at the Buck Institute for Research on Aging, California. Participants: Community-dwelling older adults (≥ 65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30).InterventionSubjects were randomly allocated (1:1) to consume 25 g daily of either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil.MeasurementsLongitudinal change in physical function, cognitive function and quality of life were assessed as exploratory outcomes in n = 23 completers (n = 11 PLA, n = 12 KE). A composite functional outcome to describe the vigor-frailty continuum was calculated. Heart rate and activity was measured throughout the study using digital wearables.ResultsThere were no statistically significant longitudinal differences between groups in exploratory functional, activity-based or quality of life outcomes.ConclusionDaily ingestion of 25 g of KE did not affect exploratory functional or quality-of-life end points in this pilot cohort of healthy older adults. Future work will address these endpoints as primary and secondary outcomes in a larger trial of pre-frail older adults.
Relationship between blood-cerebrospinal fluid barrier integrity, cardiometabolic and inflammatory factors in schizophrenia-spectrum disorders
Authors: Yakimov Vladislav , Jäger Iris , Roell Lukas , Boudriot Emanuel , Meisinger Verena , Campana Mattia , Krčmář Lenka , Halstead Sean , Warren Nicola , Siskind Dan , Maurus Isabel , Hasan Alkomiet , Falkai Peter , Schmitt Andrea , Raabe Florian J. , Keeser Daniel ,   CDP-Working Group, Wagner Elias , Moussiopoulou Joanna 
Published: September 2024

AbstractThe blood-cerebrospinal fluid barrier (BCB) builds an integral interface between the central nervous system and the periphery and appears to be impaired in a substantial proportion of individuals with schizophrenia-spectrum disorders (SSD). Even though a disruption of the BCB is associated with higher symptom severity, factors linked to BCB disruption in SSDs have been minimally investigated.To address this gap, 57 inpatients with SSD underwent cerebrospinal fluid (CSF) and blood analyses as well as comprehensive clinical assessments. In a subgroup of 28 participants structural magnetic resonance imaging (MRI) was performed. We developed a BCB dysfunction score, employing principal component analysis of CSF/serum albumin, CSF/serum IgG ratios and total protein levels in CSF, with higher values indicating stronger abnormalities. We calculated multiple regression models to explore the associations between BCB integrity and cardiometabolic, inflammatory, brain morphometric, and clinical measures respectively.BCB dysfunction score was negatively associated with high-density lipoprotein cholesterol and positively associated with total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Furthermore, we observed a trend towards a positive association between BCB dysfunction score and treatment resistance that did not survive multiple testing correction. We did not find significant associations between the BCB composite score and any other assessed cardiometabolic, inflammatory or cerebroventricular measures.These findings suggest that BCB integrity is associated with dyslipidemia in SSD, highlighting the interplay between cardiometabolic risk factors and brain health in SSD. Addressing cardiometabolic health in individuals with SSD might thus have implications beyond physical health, potentially influencing the integrity of the BCB and, consequently, clinical trajectories.
Statin use is associated with reduction in risk ofde novoprimary sclerosing cholangitis among patients with inflammatory bowel disease: A National Database Study
Authors: Kulkarni Chiraag , Gubatan John , Pike C. William , Hui Gavin , Gombar Saurabh , Kramer Jennifer , Jackson Michael L. , Goel Aparna , Vierling John , Cholankeril George , Sinha Sidhartha R. 
Published: September 2024

AbstractBackground and AimsPrimary sclerosing cholangitis (PSC) is a liver disease without medical therapy that significantly increases the risk of malignancies, acute cholangitis and cirrhosis. Approximately 2-7% of patients with inflammatory bowel disease (IBD) develop PSC. No drug has been shown to preventde novoPSC in patients with IBD. Statin use, however, has been associated with increased liver transplant-free survival. Yet, the impact of statins on development of new PSC among those with IBD is unknown.MethodsWe conducted a retrospective cohort study of patients diagnosed with IBD with and without statin exposure using a large, representative national database. Patients were followed from the date of diagnosis of IBD. Patient demographics, co-morbidities, medications, and type of IBD were extracted. Unmatched and propensity score-matched Cox regression analyses were performed.ResultsOur analysis included 33,813 patients with IBD of whom 8,813 were exposed to statins. PSC developed in 181 patients over a median follow-up of 3.7 years. Only nine patients (0.1%) who were exposed to statins developed PSC compared to 173 (0.69%) in the non-exposed population. In propensity score-matched analysis, statin therapy was associated with an 86% lower risk of developing PSC (HR 0.14; 95% CI 0.06-0.33, p<0.001). The findings were consistent when accounting for unmeasured confounders (E-value) in sensitivity analyses, including stratification by age group, duration of statin use, and type of statin.ConclusionIn a propensity score-matched analysis, statin use was associated with an 86% risk reduction in new PSC diagnosis among patients with known IBD, suggesting a potential benefit as a prophylactic agent. These findings warrant prospective validation.
Plant BCL-Domain Homologues play a conserved role in SWI/SNF complex stability
Authors: Candela-Ferre Joan , Pérez-Alemany Jaime , Diego-Martin Borja , Pandey Vijaya , Wohlschlegel James A. , Lozano-Juste Jorge , Gallego-Bartolomé Javier 
Published: September 2024

AbstractThe SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are evolutionarily conserved, ATP-dependent chromatin remodelers crucial for multiple nuclear functions in eukaryotes. Recently, plant BCL-Domain Homolog (BDH) proteins were identified as shared subunits of all plant SWI/SNF complexes, significantly impacting chromatin accessibility and various developmental processes in Arabidopsis. In this study, we performed a comprehensive characterization ofbdhmutants, revealing a previously overlooked impact on hypocotyl cell elongation. Through detailed analysis of BDH domains, we identified a plant-specific N-terminal domain that facilitates the interaction between BDH and the rest of the complex. Additionally, we uncovered the critical role of the BDH β-hairpin domain, which is phylogenetically related to metazoan BCL7 SWI/SNF subunits. While phylogenetic analyses did not identify BDH/BCL7 orthologs in fungi, structure prediction modeling demonstrated strong similarities between the SWI/SNF catalytic modules of plants, animals, and fungi, and revealed the yeast Rtt102 protein as a structural homolog of BDH and BCL7. This finding is supported by the ability of Rtt102 to interact with the Arabidopsis catalytic module subunit ARP7 and partially rescue thebdhmutant phenotypes. Further experiments revealed that BDH promotes the stability of the ARP4-ARP7 heterodimer, leading to the partial destabilization of ARP4 in the SWI/SNF complexes. In summary, our study unveils the molecular function of BDH proteins in plant SWI/SNF complexes and suggests that β-hairpin-containing proteins are evolutionarily conserved subunits crucial for ARP heterodimer stability and SWI/SNF activity across eukaryotes.
Hypoperfusion Profiles in outcome after Endovascular Therapy for Isolated Internal Carotid Artery Occluded Patients
Authors: Shi Feina , Chen Yigang , Zheng Xu , Jiang Yun , Xu Ziqi , Wang En , Wu Changzhu , Xu Chuan , Gao Qingqing , Hu Xi , Zhang Jinhua 
Published: September 2024

AbstractBackgroundPatients with acute symptomatic isolated internal carotid artery occlusions (iICAO), also known as ICA-I occlusion, frequently presented with minor neurological deficits. However, they remained at risk for subsequent neurological deterioration even after intravenous thrombolysis. The efficacy of endovascular treatment (EVT) in iICAO patients remains uncertain. Recently, some retrospective studies revealed EVT for acute iICAO was safe and might confer potential benefits. Our aim was to identify the hypoperfusion profiles associated with neurological deterioration and functional outcome following EVT in iICAO patients.MethodsWe performed a multi-center, real-world cohort study involving acute symptomatic iICAO patients who underwent EVT from August 2018 to February 2024 across 3 stroke centers. Hypoperfusion profiles were assessed using Tmaxvolumes (>4s, >6s, >8s, and >10s) and Tmaxmismatch ratios (>10s/>8s, >10s/>6s, >10s>4s, >8s/>6s, >8s/>4s, and >6s/>4s). Neurological deterioration was defined as an increase of ⩾4 points in the NIHSS score prior to EVT. Good outcome was defined as modified Rankin Score 0 - 1 at 90 days.ResultsA total of 63 patients were included in the final analysis. Multivariable models showed that a lower Tmaxratio of >6s/>4s was an independent predictor for increased risk of neurological deterioration (OR, 0.003; 95% CI: 0.000-0.133; P = 0.003) and was associated with a better outcome following EVT (OR, 0.066; 95% CI: 0.005-0.874; P = 0.039) after adjustment. The optimal threshold for the Tmax>6s/>4s ratio was identified as 0.5.ConclusionsA perfusion defect severity ratio of Tmax>6s/>4s less than 0.5 might indicate the likelihood of neurological deterioration, yet it would be associated with achieving a good outcome following EVT for iICAO patients. The hypoperfusion profile characterized by a Tmax>6s/>4s might be useful to the neurointerventionists for facilitating appropriate patient triage and guiding prognosis for EVT in iICAO patients.
WITHDRAWN: Filovirus outbreak responses and occupational health effects of chlorine spraying in healthcare workers: a systematic review and meta-analysis of alternative disinfectants and application methods
Authors: Fontana Luca , Stabile Luca , Caracci Elisa , Chaillon Antoine , Ait-Ikhlef Kamal , Buonanno Giorgio 
Published: September 2024

Withdrawal statementThe authors have withdrawn this manuscript because of data issues that affect the validity of the findings. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.