bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare Performance of Leprosy Management in Peripheral Health Facilities of Dhanusa and Mahottari, Nepal
Authors: Mahato Ram Kumar , Ghimire Uttam , Bajracharya Bijay , Binod KC , Bam Deepak , Ghimire Deepak , Pyakurel Uttam Raj , Hayman David TS , Pandey Basudev , Das Chuman Lal , Paudel Krishna Prasad 
Published: December 2022

AbstractBackgroundThe global elimination of leprosy transmission by 2030 is a World Health Organization (WHO) target. Nepal’s leprosy elimination program depends on early case diagnosis and the performance of health workers and facilities. The knowledge and skills of paramedical staff (Leprosy Focal Person, LFP) and case documentation and management by health facilities is therefore key to the performance of health care services.MethodsThe performance of health workers and facilities was evaluated through a combined cross sectional and retrospective study approach of 31 health facilities and their LFPs in Dhanusa and Mahottari Districts in Madhesh Province, Nepal. An average of 6 patients (paucibacillary, PB, or multibacillary, MB) per health facility registered within the 2018/2019 fiscal year were also enrolled in the study. LFP knowledge (e.g., of the three cardinal signs) and skills (e.g., nerve palpation) and facility processes (e.g., record keeping) were scored (e.g., 0, 1) and then rescaled to a proportion, where 1 is perfect. Internal benchmarking was used to guide performance management.ResultsOverall LFP knowledge and skill scores ranged from 0.16 to 0.63 (median 0.53, 95% confidence interval (CI), 0.46-0.6). Case documentation scores ranged from 0.15 to 0.87 (median 0.37, 95% CI 0.36-0.38), case management scores from 0.38 to 0.79 (median 0.54, 95% CI 0.53-0.55) and the overall healthcare scores ranged from 0.36-0.62 (median 0.48, 95% CI 0.47-0.49). Leprosy-related training was significantly related to the knowledge and skill of the health workers. All identified cases (n =187) adhered to the complete treatment and release after treatment (RFT) scheme, out of which 84.5% were satisfied with the service they were provided. Leprosy disability and Ear Hand and Feet (EHF) scores were not significantly reduced in treated patients during the study period, but counseling by LFPs significantly improved cases’ positive belief and practices regarding self-care.ConclusionOverall leprosy care performance was low (43%) and can be improved by evidenced-based training, onsite coaching, monitoring, and supervision to facilitate leprosy transmission elimination. The results highlight many of the challenges facing leprosy elimination programs.
Trends in self-reported cost barriers to dental care in Ontario
Authors: Abdelrehim Mona , Ravaghi Vahid , Quiñonez Carlos , Singhal Sonica 
Published: December 2022

AbstractBackgroundThe affordability of dental care continues to receive attention in Canada. Since most dental care is privately financed, the use of dental care is largely influenced by insurance coverage and the ability to pay-out-of pocket.Objectives1) To explore trends in self-reported cost barriers to dental care in Ontario; 2) To determine the socio-economic and demographic characteristics of Ontarians reporting cost barriers to dental care; and 3) To identify what predicts reporting cost barriers to dental care in Ontario.MethodsA secondary data analysis of five cycles (2003, 2005, 2009-10, 2013-14 and 2017-18) of the Canadian Community Health Survey (CCHS) was undertaken. The CCHS is a cross-sectional survey that collects information related to health status, health care utilization, and health determinants for the Canadian population. Univariate and bivariate analyses were conducted to determine the characteristics of Ontarians who reported cost barriers to dental care. Poisson regression was used to calculate unadjusted and adjusted prevalence ratios to determine the predictors of reporting a cost barrier to dental care.ResultsIn 2014, 34% of Ontarians avoided visiting a dental professional in past three years due to cost, up from 22% in 2003. Having no insurance was the strongest predictor for reporting cost barriers to dental care, followed by being 20-39 years of age and having a lower income.ConclusionSelf-reported cost barriers to dental care have generally increased in Ontario but more so for those with no insurance, low income, and aged 20-39 years.
A probabilistic view of protein stability, conformational specificity, and design
Authors: Stern Jacob A. , Free Tyler J. , Stern Kimberlee L. , Gardiner Spencer , Dalley Nicholas A. , Bundy Bradley C. , Price Joshua L. , Wingate David , Corte Dennis Della 
Published: December 2022

AbstractSeveral recently introduced approaches use neural networks as probabilistic models for protein sequence design. These models use various objective functions and optimization schemes. The choice of objective function and optimization scheme comes with trade-offs that are not always well explained. We introduce probabilistic definitions of protein stability and conformational specificity and show how these chemical properties relate to thep(structure| seq) objective used in recent protein design algorithms. This links probabilistic objective functions to experimentally testable outcomes. We present a new sequence decoding algorithm, termed “BayesDesign”, that uses Bayes’ Rule to maximize thep(structure| seq) objective. We evaluate BayesDesign in the context of two protein model systems, the NanoLuc enzyme and the WW structural motif.
The BRUTUS-LIKE E3 ligases BTSL1 and BTSL2 fine-tune transcriptional responses to balance Fe and Zn homeostasis
Authors: Stanton Camilla , Rodríguez-Celma Jorge , Kraemer Ute , Sanders Dale , Balk Janneke 
Published: December 2022

AbstractThe mineral micronutrients zinc (Zn) and iron (Fe) are essential for plant growth and human nutrition, but interactions between the homeostatic networks of these two elements are not fully understood. Here we show that loss-of-function ofBTSL1andBTSL2, which encode partially redundant E3 ubiquitin ligases that negatively regulate Fe uptake, confers tolerance to Zn excess inArabidopsis thaliana. Doublebtsl1 btsl2mutant seedlings grown on high Zn medium accumulated similar amounts of Zn in roots and shoots as the wild type, but suppressed the accumulation of excess Fe in roots. RNA-seq analysis showed that roots of mutant seedlings had relatively higher expression of genes involved in Fe uptake (IRT1, FRO2, NAS) and in Zn storage (MTP3, ZIF1). Surprisingly, mutant shoots did not show the transcriptional Fe-deficiency response which is normally induced by Zn excess. Split-root experiments suggested that within roots the BTSL proteins act locally and downstream of systemic Fe deficiency signals. Together, our data show that constitutive low-level induction of the Fe-deficiency response protectsbtsl1 btsl2mutants from Zn toxicity. We propose that BTSL protein function is disadvantageous in situations of external Zn and Fe imbalances, and formulate a general model for Zn-Fe interactions in plants.HighlightMutation of two E3 ligases that suppress iron uptake in roots also confers tolerance to zinc toxicity, identifying a regulatory point of interaction between iron and zinc homeostasis.
Bariatric surgery: preparations and quality of life consequences
Authors: Lozano Liis , Põder Triin , Lozano George A. 
Published: December 2022

AbstractIntroductionObesity is a major threat to global health. When more conventional methods have failed, obesity can be addressed via bariatric surgery. Here we examine the reasons why patients choose bariatric surgery and the behavioral consequences thereafter.MethodsA qualitative study with a phenomenological design was used to analyze detailed interview responses from recipients of bariatric surgery.ResultsBefore surgery, (a) bariatric surgery was chosen for obvious reasons: patients had been overweight, had obesity-related health problems, and had difficulties moving. (b) Information was obtained from medical practitioners and online discussion groups. (c) Fear, anxiety, and apprehension were common. Friends and family were sometimes supportive and sometimes disapproving. After surgery, (1) many chronic health problems disappeared or eased significantly. (2) Subjects had difficulties adjusting to small portions and altered food preferences. (3) Physical activity increased. (4) Self-esteem increased but the worry of regaining the weight remained. (5) As before surgery, there were both supportive and condemning attitudes by relatives, friends, and society. (6) A desire for further nutritional and psychological counseling was indicated. (7) Relationships and quality of sex improved in most cases but not always. Single women, particularly, became more active in potential relationships.DiscussionWith a few exceptions, our results agree with the literature, supporting the idea that bariatric surgery leads to extensive physical, psychological, and social changes. Hence, patients ought to be better prepared for these changes, and medical practitioners ought to be aware of the magnitude of the changes this surgery will bring about in their patients’ lives.
Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease
Authors: Paul Kimberly C , Zhang Keren , Walker Douglas I , Sinsheimer Janet , Yu Yu , Kusters Cynthia , Rosario Irish Del , Folle Aline Duarte , Keener Adrienne M , Bronstein Jeff , Jones Dean P , Ritz Beate 
Published: December 2022

AbstractObjectivesRecent advances in high-resolution metabolomics platforms allow the simultaneous measurement of thousands of small molecules produced from metabolism (metabolites), providing a map of disease-related perturbations across interconnected pathways. We used high performance, untargeted metabolomics to identify metabolic disturbances and molecular events associated with Parkinson’s disease (PD) in two population-based studies.MethodsWe performed a metabolome-wide association study (MWAS) on PD, using serum-based untargeted metabolomics data derived from high resolution liquid chromatography, mass spectrometry (LCMS). We used two independent, case-control populations for discovery and replication (n=642 PD patients, n=277 controls).ResultsFrom the LCMS, 5,145 metabolites were detected across the two study populations in ≥50% of the samples (HILIC: 2913 metabolites; C18: 2063 metabolites). Using logistic regression and an FDR to correct for multiple testing, we determined 236 metabolites were associated with PD in a meta-analysis at an FDR<0.05. Of these, 110 metabolites were independently associated with PD in both discovery and replication studies at p<0.05 (187 at p<0.10), while 24 were associated with levodopa-equivalent dose among the PD patients. Intriguingly, the microbial related metabolite, p-cresol (meta-OR=1.29, 95% CI=1.13, 1.47, FDR=0.01), and it’s two metabolites, p-cresol sulfate and p-cresol glucuronide, were found at higher intensity among the PD patients relative to controls. P-cresol glucuronide was also associated with motor symptoms among patients. Pyroglutamic acid (meta OR=3.79, 95% CI=2.60, 5.54; FDR=5.30E-09), the anti-inflammatory metabolite itaconate (meta OR=0.47, 95% CI=0.36, 0.61; FDR=8.44E-06), and cysteine-S-sulfate (meta OR=1.56, 95% CI=1.32, 1.83; FDR=1.66E-05) were also among the most strongly associated metabolites. Seventeen pathways were also enriched, including several related to amino acid and lipid metabolism.ConclusionsOur results revealed PD-associated metabolites in two independent study populations, implicating individual metabolites including p-cresol and itaconate, as well as suggesting metabolic disturbances in amino acid and lipid metabolism and inflammatory processes.
Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use
Authors: Fang Fang , Quach Bryan , Lawrence Kaitlyn G. , van Dongen Jenny , Marks Jesse A. , Lundgren Sara , Lin Mingkuan , Odintsova Veronika V. , Costeira Ricardo , Xu Zongli , Zhou Linran , Mandal Meisha , Xia Yujing , Vink Jacqueline M. , Bierut Laura J , Ollikainen Miina , Taylor Jack A. , Bell Jordana T. , Kaprio Jaakko , Boomsma Dorret I. , Xu Ke , Sandler Dale P. , Hancock Dana B. , Johnson Eric O. 
Published: December 2022

AbstractCannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9,436 participants (7,795 European and 1,641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05 (p< 5.85 × 10−7): cg22572071 near geneADGRF1, cg15280358 inADAM12, cg00813162 inACTN1, and cg01101459 nearLINC01132. Additionally, our EWAS analysis in participants who never smoked cigarettes identified another epigenome-wide significant CpG site, cg14237301 annotated toAPOBR. We used a leave-one-out approach to evaluate methylation scores constructed as a weighted sum of the significant CpGs. The best model can explain 3.79% of the variance in lifetime cannabis use. These findings unravel the DNA methylation changes associated with lifetime cannabis use that are independent of cigarette smoking and may serve as a starting point for further research on the mechanisms through which cannabis exposure impacts health outcomes.
Linking air pollution exposure to blood-based metabolic features in a community-based aging cohort
Authors: Kalia Vrinda , Kulick Erin R. , Vardarajan Badri , Gu Yian , Manly Jennifer J. , Elkind Mitchell S.V. , Kaufman Joel D. , Jones Dean P. , Baccarelli Andrea A. , Mayeux Richard P. , Kioumourtzoglou Marianthi-Anna , Miller Gary W. 
Published: December 2022

ABSTRACTLong-term exposure to air pollution has been associated with changes in levels of several metabolites measured in the peripheral blood. However, most work has been conducted in ethnically homogenous populations. We studied the relationship between the plasma metabolome and long-term exposure to three air pollutants: particulate matter (PM) less than 2.5 µm in aero diameter (PM2.5), PM less than 10 µm in aero diameter (PM10) and nitrogen dioxide (NO2) among 107 participants of the Washington Heights and Inwood Community Aging Project (WHICAP) in New York City. Plasma metabolomic profiles were generated using untargeted liquid chromatography coupled with high-resolution mass spectrometry. We estimated the association between each metabolic feature and predicted annual mean exposure to the air pollutants using three approaches: 1. A metabolome wide association study (MWAS) framework; 2. Feature selection using elastic net regression; and 3. A multivariate approach using partial least squares discriminant analysis. Additionally, we identified the pathways enriched by metabolic features associated with exposure through pathway analysis. The samples were collected from 1995 – 2015 and included non-Hispanic white, Caribbean Hispanic, and non-Hispanic Black older adults. Through the MWAS, we found 79 features associated with exposure to PM2.5(false discovery rate at 5%) but none associated with PM10or NO2. Pathway analysis revealed that PM2.5exposure was associated with altered amino acid metabolism, energy production, and oxidative stress response. Six features were found to be associated with PM2.5exposure through all three approaches, annotated as: cysteinylglycine disulfide, a diglyceride, and a dicarboxylic acid. Additionally, we found that the relationship between several features and PM2.5exposure was modified by diet and metabolic diseases. These signals, identified in a neighborhood-representative older population, could help understand the mechanisms through which PM2.5exposure can lead to altered metabolic outcomes in an older population.HIGHLIGHTSLong-term exposure to PM2.5is associated with altered plasma metabolic features in an aging populationThese associations are modified by a dementia diagnosis, history of diabetes, APOE-ε4 allele, and dietPathways related to energy production, amino acid metabolism, and redox homeostasis are associated with exposure to PM2.5GRAPHICAL ABSTRACT
Drivers of plant intraspecific variation are trait-specific
Authors: Zhou Jianhong , Cieraad Ellen , van Bodegom Peter M. 
Published: December 2022

SummaryThe importance of intraspecific trait variation (ITV) in community dynamics is increasingly being recognised, but the drivers of ITV have not yet been well-studied. Here, we analysed whether environmental conditions, biotic interactions and species features are related to ITV on a global scale.We compiled a global species’ ITV database including 2064 species which occurred in 1068 communities (plots) across 19 countries with 11 functional traits. The magnitudes of species’ ITV in this database were calculated according to the trait-gradient analysis which is independent of the length of the environmental gradient.We found that different traits had different main drivers, so we consider the drivers of ITV to be trait-specific. However, our findings still brought some order among these idiosyncratic patterns: leaf economics spectrum traits were more related to environmental conditions and leaf morphology traits were more related to biotic interactions. Size-related traits were related to both abiotic and biotic conditions.Our research suggests that the drivers of ITV deviated from the drivers of the mean trait values and that some trait coordination may fall apart upon climate change. Thus, our analysis enhances our understanding of trait variation and has important implications for models predicting vegetation responses to environmental change.
TAD border deletion at theKitlocus causes tissue-specific ectopic activation of a neighboring gene
Authors: Kabirova Evelyn , Ryzhkova Anastasiya , Lukyanchikova Varvara , Khabarova Anna , Korablev Alexey , Shnaider Tatyana , Nuriddinov Miroslav , Belokopytova Polina , Kontsevaya Galina , Serova Irina , Battulin Nariman 
Published: December 2022

AbstractTopologically associated domains (TADs) restrict promoter-enhancer interactions, thereby maintaining the spatiotemporal pattern of gene activity. However, rearrangements of the TADs boundaries do not always lead to significant changes in the activity pattern. Here, we investigated the consequences of the TAD boundaries deletion on the expression of developmentally important genes encoding tyrosine kinase receptors:Kit, Kdr, Pdgfra. We used genome editing in mice to delete the TADs boundaries at theKitlocus and characterized chromatin folding and gene expression in pure cultures of fibroblasts, mast cells, and melanocytes. We found that althoughKitis highly active in both mast cells and melanocytes, deletion of the TAD boundary between theKitandKdrgenes results in ectopic activation only in melanocytes. Thus, the epigenetic landscape, namely the mutual arrangement of enhancers and actively transcribing genes, is important for predicting the consequences of the TAD boundaries removal. We also found that mice without a TAD border between theKitandKdrgenes have a phenotypic manifestation of the mutation — a lighter coloration. Thus, the data obtained shed light on the principles of interaction between the 3D chromatin organization and epigenetic marks in the regulation of gene activity.
How collectively integrated are ecological communities?
Authors: Zelnik Yuval R. , Galiana Nuria , Barbier Matthieu , Loreau Michel , Galbraith Eric , Arnoldi Jean-François 
Published: December 2022

AbstractBeyond abiotic conditions, do population dynamics mostly depend on the species’ direct predators, preys and conspecifics? Or can indirect feedbacks that ripple across the whole community be equally important? Here we show that the spectral radius of a community’s interaction matrix controls the length of indirect interaction pathways that actually contribute to community-level dynamical patterns, such as the depth of a perturbation’s reach, or the contribution of biotic processes to realized species niches. The spectral radius is a measure of collectivity that integrates existing approaches to complexity, interaction structure and indirect interactions, while also being accessible from imperfect knowledge of biotic interactions. Our work provides an original perspective on the question of to what degree communities are more than loose collections of species or simple interaction motifs; and explains when reductionist approaches focusing on particular species and small interaction motifs, ought to suffice or fail when applied to ecological communities.
Genetic adaptation rates differ by trait and plant type --a comprehensive meta-analysis
Authors: Zhou Jianhong , Cieraad Ellen , van Bodegom Peter M. 
Published: December 2022

SummaryPlants can respond to changing climatic conditions through genetic adaptation of their functional traits. Despite the relevance of adaptation to climate change, much remains unknown about plant genetic adaptation rates, including whether these rates differ among plant characteristics and trait types.We performed a meta-analysis to investigate patterns of genetic adaptation rates and assess how these rates differ among plant species groups, growth forms and trait types, using a newly compiled database from 74 studies, comprising 35 functional traits across 72 angiosperm species. This database specifically focuses on genetic adaptation of plant functional traits, as separating from phenotypic plasticity.Both annual and generational adaptation rates of plant traits decrease non-linearly with increasing elapsed time since divergence. Plants adapt fastest when first introduced to a changing environment, but these rates go slow subsequently. Overall, shrubs have higher adaptation rates than trees, which confers shrubs an adaptive advantage over trees. Different adaptation rates among growth forms, life histories and trait types suggest an important additional mechanism through which climate change may affect community composition.Our study has important implications regarding plant adaptation to new environments and will improve the prediction of vegetation responses and ecosystem functioning upon climate change.