bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smartphone-based cough monitoring as a near real-time digital pneumonia biomarker
Authors: Boesch Maximilian , Rassouli Frank , Baty Florent , Schwärzler Anja , Widmer Sandra , Tinschert Peter , Shih Iris , Cleres David , Barata Filipe , Fleisch Elgar , Brutsche Martin H. 
Published: March 2023

Background
Cough represents a cardinal symptom of acute respiratory tract infections. Generally associated with disease activity, cough holds biomarker potential and might be harnessed for prognosis and personalised treatment decisions. Here, we tested the suitability of cough as a digital biomarker for disease activity in coronavirus disease 2019 (COVID-19) and other lower respiratory tract infections.

Methods
We conducted a single-centre, exploratory, observational cohort study on automated cough detection in patients hospitalised for COVID-19 (n=32) and non-COVID-19 pneumonia (n=14) between April and November 2020 at the Cantonal Hospital St Gallen, Switzerland. Cough detection was achieved using smartphone-based audio recordings coupled to an ensemble of convolutional neural networks. Cough levels were correlated to established markers of inflammation and oxygenation.

Measurements and main results
Cough frequency was highest upon hospital admission and declined steadily with recovery. There was a characteristic pattern of daily cough fluctuations, with little activity during the night and two coughing peaks during the day. Hourly cough counts were strongly correlated with clinical markers of disease activity and laboratory markers of inflammation, suggesting cough as a surrogate of disease in acute respiratory tract infections. No apparent differences in cough evolution were observed between COVID-19 and non-COVID-19 pneumonia.

Conclusions
Automated, quantitative, smartphone-based detection of cough is feasible in hospitalised patients and correlates with disease activity in lower respiratory tract infections. Our approach allows for near real-time telemonitoring of individuals in aerosol isolation. Larger trials are warranted to decipher the use of cough as a digital biomarker for prognosis and tailored treatment in lower respiratory tract infections.
Short-acting β2-agonists and exacerbations in children with asthma in England: SABINA Junior
Authors: Morgan Ann , Maslova Ekaterina , Kallis Constantinos , Sinha Ian , Roberts Graham , Tran Trung N. , van der Valk Ralf J.P. , Quint Jennifer K. 
Published: March 2023

BackgroundPrescription of three or more short-acting β2-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited.MethodsThis study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or moreversusfewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders.ResultsOverall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or moreversusfewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICSConclusionIn children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations.
Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial
Authors: Balasubramanian Aparna , Holbrook Janet T. , Canning Brendan J. , Que Loretta G. , Castro Mario , Make Barry J. , Rogers Linda , Busk Michael F. , Rea Alexis , McCook-Veal Ashley A. , He Jiaxian , McCormack Meredith C. , Wise Robert A. 
Published: March 2023

Background:Cough is the most reported symptom in the United States, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway. We sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.Study design and methods:This was a randomised, placebo-controlled, parallel-design pilot trial of individuals with chronic refractory cough. The effects of 6 weeks of zinc acetateversusplacebo on quality of life and symptoms as measured by the Cough Quality-of-Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), cough visual analogue score (C-VAS) and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome.Results:34 participants, 17 in each group, were enrolled and randomised. Participants were primarily white females with moderate–severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks, while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS and GACC scores, but the treatment effects of zinc acetateversusplacebo were small with confidence intervals that did not include the MCIDs.Interpretation:We observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.
Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
Authors: Kroes Johannes A. , Alfonso-Cristancho Rafael , Bansal Aruna T. , Berret Emmanuelle , Bieksiene Kristina , Bourdin Arnaud , Brussino Luisa , Canhoto Diogo , Cardini Cristina , Celik Gulfem , Csoma Zsuzsanna , Dahlén Barbro , Damadoglu Ebru , Eger Katrien , Gauquelin Lisa , Gemicioglu Bilun , Goksel Ozlem , Graff Sophie , Heffler Enrico , Hofstee Hendrik B. , Howarth Peter , Jakes Rupert W. , Jaun Fabienne , Kalinauskaite-Zukauske Virginija , Kopač Peter , Kwon Namhee , Loureiro Claudia C. , Lozoya García Victor , Masoli Matthew , Rezelj Mariana Paula , Pérez De Llano Luis , Popović-Grle Sanja , Ramos-Barbón David , Sà Sousa Ana , Samitas Konstantinos , Schleich Florence , Sirena Concetta , Skrgat Sabina , Zervas Eleftherios , Zichnalis George , Bel Elisabeth H. , Sont Jacob K. , Hashimoto Simone , Ten Brinke Anneke 
Published: March 2023

Background
An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.

Methods
In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately.

Results

In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day
−1
, 95% CI −5.24–2.62 mg·day
−1
) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.

Conclusions
By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
Device-measured movement behaviors and cardiac biomarkers in older adults without major cardiovascular disease: the Seniors-ENRICA-2 study
Authors: Fabre-Estremera Blanca , Buño-Soto Antonio , García-Esquinas Esther , Cabanas-Sánchez Verónica , Martínez-Gómez David , Rodríguez-Artalejo Fernando , Ortolá Rosario 
Published: March 2023

AbstractBackgroundHigh-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are biomarkers of myocardial infarction and heart failure, respectively, and indicate cardiovascular risk. Since low physical activity (PA) and sedentary behavior (SB) are also associated with higher cardiovascular risk, and this association could be a consequence of higher levels of cardiac biomarkers, we examined the association of device-measured movement behaviors with hs-cTnT and NT-proBNP in older men and women without major cardiovascular disease (CVD).MethodsWe used data from 1939 older adults from the Seniors-ENRICA-2 study. Accelerometers were used to assess time spent in sleep, SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). Linear regression models were fitted separately in eight strata defined by sex, by median total PA time, and by the presence of subclinical cardiac damage according to cardiac biomarkers levels.ResultsIn the less active men with subclinical cardiac damage, spending 30 min/day more of MVPA was associated with a mean percentage difference (MPD) (95% confidence interval) in hs-cTnT of − 13.1 (− 18.3, − 7.5); MPDs in NT-proBNP per 30 min/day increment were 5.8 (2.7, 8.9) for SB, − 19.3 (− 25.4, − 12.7) for LPA and − 23.1 (− 30.7, − 14.6) for MVPA. In women with subclinical cardiac damage who were less physically active, 30 min/day more of SB, LPA and MVPA were associated with MPDs in hs-cTnT of 2.1 (0.7, 3.6), − 5.1 (− 8.3, − 1.7) and − 17.5 (− 22.9, − 11.7), respectively, whereas in those more active, LPA and MVPA were associated with MPDs of 4.1 (1.2, 7.2) and − 5.4 (− 8.7, − 2.0), respectively. No associations were found with NT-proBNP in women.ConclusionsThe relationship between movement behaviors and cardiac biomarkers in older adults without major CVD depends on sex, subclinical cardiac damage and PA level. More PA and less SB were generally related to lower cardiac biomarkers levels among less active individuals with subclinical cardiac damage, with greater benefits for hs-cTnT in women than men and no benefits for NT-proBNP in women.
Trajectory of physical activity frequency and cancer risk: Findings from a population-based cohort study
Authors: Tran Thi Phuong Thao , Luu Ngoc Minh , Bui Thi Tra , Han Minji , Lim Min Kyung , Oh Jin-Kyoung 
Published: March 2023

AbstractBackgroundPhysical activity (PA) changes throughout an individual’s life, but the association between such changes and cancer risk seems to be overlooked in the literature. Thus, this study aimed to examine the association between the trajectories of PA frequency and cancer incidence among middle-aged Korean adults.MethodsA total of 1,476,335 eligible participants (992,151 men and 484,184 women) aged ≥40 years from the National Health Insurance Service cohort (2002–2018) were included. Assessment of PA frequency was a self-reported measure, based on the question: “How many times per week do you perform exercise that makes you sweat?”. PA frequency trajectories (i.e., trajectory classes of change in PA frequency) from 2002 to 2008 were identified using group-based trajectory modeling. Cox proportional hazards regression was used to assess the associations between the PA trajectories and cancer incidence.ResultsFive PA frequency trajectories over 7 years were identified: persistently low (men:73.5%; women:74.7%), persistently moderate (men:16.2%; women:14.6%), high-to-low (men:3.9%; women:3.7%), low-to-high (men:3.5%; women:3.8%), and persistently high (men:2.9%; women:3.3%). Compared with persistently low frequency, maintaining a high PA frequency was associated with a lower risk of all cancers (Hazard ratio (HR) = 0.92, 95%CI = 0.87–0.98) and breast cancer (HR = 0.82, 95%CI = 0.70–0.96) among women. There was a lower risk for thyroid cancer among men in the high-to-low (HR = 0.83, 95%CI = 0.71–0.98), low-to-high (HR = 0.80, 95%CI = 0.67–0.96), and high PA trajectories (HR = 0.82, 95%CI = 0.68–0.99). There was a significant association between moderate trajectory and lung cancer in men (HR = 0.88, 95%CI = 0.80–0.95), in both smoking and non-smoking men.ConclusionLong-term persistent high frequency of PA as part of the daily routine should be widely promoted and encouraged to reduce the risk for all cancer development in women.
Evaluating the quality of the public transport service during the COVID-19 pandemic from the perception of two user groups
Authors: Ismael Karzan , Esztergár-Kiss Domokos , Duleba Szabolcs 
Published: March 2023

AbstractThe current paper focuses on a comparative analysis of both public transport (PT) and private vehicle (PV) users’ perceptions on the quality of the service. To detect the key components of PT attributes a new hybrid methodology is applied, combining the importance-performance analysis and the importance-performance map analysis. The proposed hybrid approach is simpler and more integrated than the existing methods in the literature. The sample comprises an online panel and a total of 1028 questionnaires for PV and PT users surveyed during the pandemic period in Budapest. The results of the applied methods show that among the different groups, the service hour, the proximity, and the frequency attributes are important and performed well in the years of COVID-19. On the other hand, the temperature and the cleanliness factors are not significant predictors of the PV and PT users’ general satisfaction. The obtained results can be used by local governments and authorities, who seek to identify areas to enhance the service quality of PT during movement restrictions in a pandemic wave.
Effect of environmental variance-based resilience selection on the gut metabolome of rabbits
Authors: Casto-Rebollo Cristina , Argente María José , García María Luz , Blasco Agustín , Ibáñez-Escriche Noelia 
Published: March 2023

Abstract
Background
Gut metabolites are key actors in host-microbiota crosstalk with effect on health. The study of the gut metabolome is an emerging topic in livestock, which can help understand its effect on key traits such as animal resilience and welfare. Animal resilience has now become a major trait of interest because of the high demand for more sustainable production. Composition of the gut microbiome can reveal mechanisms that underlie animal resilience because of its influence on host immunity. Environmental variance (VE), specifically the residual variance, is one measure of resilience. The aim of this study was to identify gut metabolites that underlie differences in the resilience potential of animals originating from a divergent selection for VE of litter size (LS). We performed an untargeted gut metabolome analysis in two divergent rabbit populations for low (n = 13) and high (n = 13) VE of LS. Partial least square-discriminant analysis was undertaken, and Bayesian statistics were computed to determine dissimilarities in the gut metabolites between these two rabbit populations.

Results
We identified 15 metabolites that discriminate rabbits from the divergent populations with a prediction performance of 99.2% and 90.4% for the resilient and non-resilient populations, respectively. These metabolites were suggested to be biomarkers of animal resilience as they were the most reliable. Among these, five that derived from the microbiota metabolism (3-(4-hydroxyphenyl)lactate, 5-aminovalerate, and equol, N6-acetyllysine, and serine), were suggested to be indicators of dissimilarities in the microbiome composition between the rabbit populations. The abundances of acylcarnitines and metabolites derived from the phenylalanine, tyrosine, and tryptophan metabolism were low in the resilient population and these pathways can, therefore impact the inflammatory response and health status of animals.

Conclusions
This is the first study to identify gut metabolites that could act as potential resilience biomarkers. The results support differences in resilience between the two studied rabbit populations that were generated by selection for VE of LS. Furthermore, selection for VE of LS modified the gut metabolome, which could be another factor that modulates animal resilience. Further studies are needed to determine the causal role of these metabolites in health and disease.
Improved computations for relationship inference using low-coverage sequencing data
Authors: Mostad Petter , Tillmar Andreas , Kling Daniel 
Published: March 2023

AbstractPedigree inference, for example determining whether two persons are second cousins or unrelated, can be done by comparing their genotypes at a selection of genetic markers. When the data for one or more of the persons is from low-coverage next generation sequencing (lcNGS), currently available computational methods either ignore genetic linkage or do not take advantage of the probabilistic nature of lcNGS data, relying instead on first estimating the genotype. We provide a method and software (see familias.name/lcNGS) bridging the above gap. Simulations indicate how our results are considerably more accurate compared to some previously available alternatives. Our method, utilizing a version of the Lander-Green algorithm, uses a group of symmetries to speed up calculations. This group may be of further interest in other calculations involving linked loci.
Genome-wide identification and expression analysis of the anthocyanin-related genes during seed coat development in six Brassica species
Authors: Chen Daozong , Chen Haidong , Dai Guoqiang , Zhang Haimei , Liu Yi , Shen Wenjie , Zhu Bo , Cui Cheng , Tan Chen 
Published: March 2023

AbstractYellow seed is one favorite trait for the breeding of Brassica oilseed crops, but the performance of seed coat color is very complicated due to the involvement of various pigments. The change of seed coat color of Brassica crops is related to the specific synthesis and accumulation of anthocyanin, and the expression level of structural genes in anthocyanin synthesis pathway is specifically regulated by transcription factors. Despite some previous reports on the regulations of seed coat color from linkage marker development, gene fine-mapping and multi-omics association analysis, the trait of Brassica crops is affected by the evolutionary events such as genome triploidization, the regulatory mechanism is still largely unknown. In this study, we identified genes related to anthocyanin synthesis in six Brassica crops in U-triangle at the genome-wide level and performed collinearity analysis. A total of 1119 anthocyanin-related genes were identified, the collinear relationship of anthocyanin-related genes on subgenomic chromosomes was the best in B. napus (AACC) and the worst in B. carinata (BBCC). The comparisons of gene expressions for anthocyanin metabolic pathways in seed coats during seed development revealed differences in its metabolism among these species. Interestingly, the R2R3-MYB transcription factors MYB5 and TT2 were differentially expressed at all eight stages of seed coat development, indicating that they might be the key genes that caused the variation of the seed coat color. The expression curve and trend analyses of the seed coat development period showed that the main reason for the unexpressed copies of MYB5 and TT2 was likely gene silencing caused by gene structural variation. These results were valuable for the genetic improvement of Brassica seed coat color, and also provided new insights into gene multicopy evolution in Brassica polyploids.
Identification and examination of nitrogen metabolic genes in Lelliottia amnigena PTJIIT1005 for their ability to perform nitrate remediation
Authors: Thakur Preeti , Gauba Pammi 
Published: March 2023

AbstractLelliottia amnigena PTJIIT1005 is a bacterium that utilizes nitrate as the sole nitrogen source and can remediate nitrate from media. The annotation was done related to nitrogen metabolic genes using the PATRIC, RAST tools, and PGAP from the genome sequence of this bacterium. Multiple sequence alignments and phylogenetic analysis of respiratory nitrate reductase, assimilatory nitrate reductase, nitrite reductase, glutamine synthetase, hydroxylamine reductase, nitric oxide reductase genes from PTJIIT1005 were done to find out sequence identities with the most similar species. The identification of operon arrangement in bacteria was also identified. The PATRIC KEGG feature mapped the N-metabolic pathway to identify the chemical process, and the 3D structure of representative enzymes was also elucidated. The putative protein 3D structure was analyzed using I-TASSER software. It gave good quality protein models of all nitrogen metabolism genes and showed good sequence identity with reference templates, approximately 81–99%, except for two genes; assimilatory nitrate reductase and nitrite reductase. This study suggested that PTJIIT1005 can remove N-nitrate from water because of having N-assimilation and denitrification genes.