bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effectiveness of Dexamethasone in Treatment of Hospitalized COVID-19 Patients during the First Year of the Pandemic: The N3C Data Repository
Authors: Zhou Richard , Johnson Kaitlyn E. , Rousseau Justin F. , Rathouz Paul J. ,   The N3C Consortium
Published: October 2022

ABSTRACTBackgroundDexamethasone, a widely available glucocorticoid, was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial; however, evidence is still needed to support its real-world effectiveness in patients with a wide range of comorbidities and in diverse care settings.ObjectivesTo conduct a comparative effectiveness analysis of dexamethasone use with and without remdesivir in hospitalized COVID-19 patients using electronic health record data.MethodsWe conducted a retrospective real-world effectiveness analysis using the harmonized, highly granular electronic health record data of the National COVID Cohort Collaborative (N3C) Data Enclave. Analysis was restricted to COVID-19 patients in an inpatient setting, prior to vaccine availability. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome as defined by use of ECMO or mechanical ventilation during stay. Missing data were imputed with single imputation. Matching of dexamethasone-treated patients to non-dexamethasone-treated controls was accomplished using propensity score (PS) matching, stratified by remdesivir treatment and based on demographics, baseline laboratory values, and comorbidities. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS.ResultsRegression analysis revealed a statistically significant association between dexamethasone use and reduced risk of in-hospital mortality for those not receiving remdesivir (OR=0.77, 95% CI: 0.62 to 0.95, p=0.017), and a borderline statistically significant risk for those receiving remdesivir (OR=0.74, 95% CI: 0.53 to 1.02, p=0.054). Treatment also showed secondary outcome benefit. In sensitivity analyses, treatment effect size generally remained similar with some heterogeneity of benefit across strata of PS.ConclusionsWe add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.
Association of Acculturation and Cardiometabolic Disease Incidence Among Immigrants of South Asian Ancestry in a National Biobank
Authors: Kathiresan Nikhil , Khera Amit V. , Patel Aniruddh P. 
Published: October 2022

AbstractBackgroundIndividuals of South Asian ancestry experience higher risk of cardiometabolic disease compared with most other groups, and the impact of acculturation on this risk warrants further study.MethodsWe studied individuals of South Asian (n=8,420) and European (n=441,696) ancestry free of baseline cardiometabolic disease in the UK Biobank prospective cohort. South Asians were divided into 3 acculturation groups based on time lived in UK: born in UK (n=801); born abroad, in UK >5yrs (n=7213), and born abroad, in UK ≤5yrs (n=406). We estimated the risk for incident coronary artery disease (CAD), type 2 diabetes mellitus, chronic kidney disease, ischemic stroke, and non-alcoholic fatty liver disease, comparing South Asian acculturation groups vs. European ancestry individuals using Cox proportional hazards regression.ResultsOver a median follow-up of 12 yrs, individuals of South Asian ancestry, regardless of acculturation group, had a higher risk of cardiometabolic disease when compared with European ancestry individuals. After adjusting for age and sex, the HR for CAD was 1.76 (95%CI 1.26-2.45;p=0.001) for UK-born South Asians; 2.00 (95%CI 1.86-2.16;p<0.001) for South Asians born abroad, in UK >5 yrs; and 2.03 (95%CI 1.42-2.91;p<0.001) for South Asians born abroad, lived in UK ≤5 yrs. Similarly elevated risk across groups was observed for DM and CKD.ConclusionIn a large prospective study, we show that individuals of South Asian (vs. European) ancestry are at higher risk for cardiometabolic disease, regardless of time lived in UK.
Identifying patients with rapid progression from hormone-sensitive to castration-resistant prostate cancer: a retrospective study
Authors: Pan Chenxi , He Yi , Wang He , Yu Yang , Li Lu , Huang Lingling , Lyu Mengge , Ge Weigang , Yang Bo , Sun Yaoting , Guo Tiannan , Liu Zhiyu 
Published: October 2022

AbstractBackgroundProstate cancer (PCa) is the second most prevalent malignancy and the fifth cause of cancer-related deaths in men. A crucial challenge is identifying the population at risk of rapid progression from hormone-sensitive PCa (HSPC) to the lethal castration-resistant PCa (CRPC).MethodsWe collected 78 HSPC biopsies and measured their proteomes using pressure cycling technology and a pulsed data-independent acquisition pipeline. The proteomics data and clinical metadata were used to generate models for classifying HSPC patients and predicting the development of each case.ResultsWe quantified 7,961 proteins using the HSPC biopsies. A total of 306 proteins were differentially expressed between patients with a long- or short-term progression to CRPC. Using a random forest model, we identified ten proteins that significantly discriminated long-from short-term cases, which were used to classify PCa patients with an 86% accuracy. Next, two clinical parameters (Gleason sum and total PSA) and five proteins (DPT, ARGEF1, UTP23, CMAS, and ANAPC4) were found to be significantly associated with rapid disease progression. A nomogram model using these seven features was generated for stratifying patients into groups with significant progression disparities (p-value = 5.2 × 10−9).ConclusionWe identified proteins associated with a fast progression to CRPC and an unfavorable prognosis. Based on these proteins, our machine learning and nomogram models stratified HSPC into high- and low-risk groups and predict their prognoses. These tools may aid clinicians in predicting the progression of patients, guiding individualized clinical management and decisions.
Scoping review and meta-analysis of COVID-19 epidemiological parameters for modeling from early Asian studies
Authors: Fonfría Eva S. , Vigo M. Isabel , García-García David , Herrador Zaida , Navarro Miriam , Bordehore Cesar 
Published: October 2022

AbstractRetrospective epidemiological models are powerful tools to understand its transmission dynamics and to assess the efficacy of different control measures. This study summarises key epidemiological parameters of COVID-19 for retrospective mathematical and clinical modeling. A review of scientific papers and preprints published in English between 1 January and 15 April 2020 in PubMed, MedRxiv and BioRxiv was performed to obtain epidemiological parameters of the initial stage of COVID-19 pandemic in Asia. After excluding articles with unacceptable risks of bias and those that remained as preprints as of 15 November 2021, meta-analyses were performed to derive summary effect estimates from the data collected using the statistical software R. Out of 4,893 articles identified, 88 provided data for 22 parameters for the overall population and 7 specifically for children. Meta-analyses were conducted considering time period as a categorical moderator when it was statistically significant. The results obtained are essential for building more reliable models to help clinicians and policymakers improve their knowledge on COVID-19 and apply it in future decisions.
What is the impact of high-profile end-of-life disputes on Paediatric Intensive Care (PIC) trainees? Original research
Authors: Bell Clare , Dittborn Mariana , Brierley Joe 
Published: October 2022

AbstractIntroductionThis study explores UK Paediatric Intensive Care (PIC) trainees’ thoughts and feelings about high-profile end-of-life cases recently featured in the press and social media and the impact on their career intentions.MethodsSemi-structured interviews were conducted with nine PIC-GRID trainees (Apr-Aug 2021). Interview transcripts were analysed using thematic analysis.ResultsSix main themes were identified: (i) All participants wished to do what was best for the child, feeling conflicted if this meant disagreeing with parents. (ii) Interviewees felt unprepared and expressed deep concern about the effect of high-profile cases on their future career. (iii) They highlighted too often being shielded from involvement in challenging discussions. (iv) Working in a supportive environment is crucial, underscoring the importance of clear and unified team communication, but specific training on the ethical and legal nuances of such cases is required. (vi) All had purposefully minimised their social media presence. (vi) All had reconsidered training in PIC due to concerns about future high-profile end-of-life disputes; despite describing this as a cause of concern and anxiety, all were still in training.ConclusionUK PIC trainees feel unprepared and anxious about future high-profile cases. A parallel can be drawn to child protection improvements following significant educational investment after Government reports into preventable child abuse deaths. Models for supporting trainees and establishing formal PIC training are required to improve trainees’ confidence and skills in managing high-profile cases. Further research with other professional groups, the families involved, and other stakeholders would provide a more rounded picture.What is already known on this topic– PIC trainees report high levels of distress associated to children’s death and disagreements with the families.What this study adds– PIC doctors are extremely concerned about future high-profile end-of-life disputes, the effect on themselves and their career. They feel unprepared to manage them and require more training, experience and recognition of this.How this study might affect research, practice or policy– PIC trainee curriculum and training scheme should prepare doctors to deal with high-profile end-of-life cases to ensure children and families receive appropriate care and avoid PIC-induced moral injury and workforce burdens.
The association between mitochondrial DNA copy number, low-density lipoprotein cholesterol, and cardiovascular disease risk
Authors: Liu Xue , Sun Xianbang , Zhang Yuankai , Jiang Wenqing , Meng Lai , Wiggins Kerri L. , Raffield Laura M. , Bielak Lawrence F. , Zhao Wei , Pitsillides Achilleas , Haessler Jeffrey , Zheng Yinan , Blackwell Thomas W. , Yao Jie , Guo Xiuqing , Qian Yong , Thyagarajan Bharat , Pankratz Nathan , Rich Stephen S. , Taylor Kent D. , Peyser Patricia A. , Heckbert Susan R. , Seshadri Sudha , Boerwinkle Eric , Grove Megan L. , Larson Nicholas B. , Smith Jennifer A. , Vasan Ramachandran S. , Fitzpatrick Annette L. , Fornage Myriam , Ding Jun , Carson April P. , Abecasis Goncalo , Dupuis Josée , Reiner Alexander , Kooperberg Charles , Hou Lifang , Psaty Bruce M. , Wilson James G. , Levy Daniel , Rotter Jerome I. , Bis Joshua C. ,   TOPMed mtDNA Working Group in NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Satizabal Claudia L. , Arking Dan E. , Liu Chunyu 
Published: October 2022

AbstractMitochondria are the primary organelle to generate cellular energy. Our group and others have reported that lower mitochondrial DNA copy number (mtDNA CN) is associated with higher risk of cardiovascular disease outcomes (CVD) and higher LDL levels. However, the causal relationship between mtDNA CN and CVD remains to be studied. Here we performed cross-sectional and prospective association analyses of blood-derived mtDNA CN and CVD outcomes in up to 27,316 participants from different racial/ethnic groups with whole genome sequencing. We validated most of the previously reported associations but effect sizes were smaller in this study. For example, one SD unit decrease in mtDNA CN was significantly associated with 1.08-fold (95% CI, 1.04, 1.12;P=1.7E-04) hazard for developing incident coronary heart disease (CHD) adjusting for age, sex and race/ethnicity. We conducted Mendelian randomization (MR) to explore causal relationships between mtDNA CN, LDL, and CHD. Bi-directional univariable MR analyses provided strong evidence indicating higher LDL level is causally associated with lower mtDNA CN, and CHD was weakly associated with lower mtDNA CN. We found no evidence supporting a causal association for lower mtDNA CN with higher CHD risk or higher LDL. In multivariable MR, no associations were observed between mtDNA CN and CHD controlling for LDL level (P =0.92), whereas strong evidence for a direct causal effect was found for higher LDL on lower mtDNA CN, adjusting for CHD status (P =8.3E-10). Findings from this study indicate high LDL underlies the complex relationships between vascular atherosclerosis and lower mtDNA CN.
Cytosolic pH controls fungal MAPK signaling and pathogenicity
Authors: Fernandes Tânia R. , Mariscal Melani , Serrano Antonio , Segorbe David , Fernández-Acero Teresa , Martín Humberto , Turrà David , Di Pietro Antonio 
Published: October 2022

AbstractIn fungi, ambient pH acts as a key regulator of development and virulence. The vascular wilt pathogenFusarium oxysporumuses host alkalinization to promote infection of plant hosts through activation of the invasive growth mitogen-activated protein kinase (MAPK) Fmk1. The molecular events underlying pH-driven MAPK regulation are unknown. Using the ratiometric GFP-based pH sensor pHluorin, we find that bothF. oxysporumandSaccharomyces cerevisiaerespond to extracellular alkalinization or acidification with a transitory shift in cytosolic pH (pHc) and rapid changes in phosphorylation levels of the three fungal MAPKs Fmk1, Mpk1/Slt2 (cell wall integrity) and Hog1 (hyperosmotic stress). Pharmacological inhibition of the essential plasma membrane H+-ATPase Pma1, which leads to pHcacidification, is sufficient to trigger reprogramming of MAPK phosphorylation even in the absence of an extracellular pH shift. Screening of a subset ofS. cerevisiaemutants identified the sphingolipid-regulated AGC kinase Ypk1/2 as a key upstream component of pHc-modulated MAPK responses. We further show that acidification of pHcinF. oxysporumleads to an increase of the long chain base (LCB) sphingolipid dihydrosphingosine (dhSph) and that exogenous addition of dhSph activates Mpk1 phosphorylation. Our results reveal a pivotal role of pHcin the regulation of MAPK signaling and suggest new ways to control fungal growth and pathogenicity.
A Case-Control Study of the Association BetweenKarenia Brevis(Red Tide) and Biliary Atresia
Authors: Wyrebek Rita , Fierstein Jamie L , Wells Rebecca G. , Machry Joana , Karjoo Sara 
Published: October 2022

AbstractObjectiveThe study objective was to evaluate the association between maternalKarenia brevis (K. brevis)exposure during pregnancy and the prevalence of biliary atresia (BA) in offspring. Study Design This was a hospital-based, case-control study in which cases were infants diagnosed with BA at Johns Hopkins All Children’s Hospital from October 2001 to December 2019. Controls were matched 4:1 by age, randomly selected from healthy infants hospitalized during the study period for common pediatric diagnoses. Infants were excluded if they had congenital anomalies and/or were non-Florida residents. GestationalK. brevisexposure levels (cells/liter) were determined from Florida Fish and Wildlife Conservation Commission exposure data at 10- and 50-mile radii from the mother’s zip code of residence. Multivariable conditional logistic regression determined adjusted odds of BA in offspring based on maternal gestationalK. brevisexposure.ResultsOf 38 cases and 152 controls, no significant inter-group differences were observed in race/ethnicity, season of birth or coastal residence. Median gestational exposure at the 10-mile radius was 0 cells/liter in both groups. A greater proportion of cases had noK. brevisexposure (63.2%, n = 24) in comparison to controls (37.5%, n = 57; p = .04) at a 10-mile radius. At the 50-mile radius, cases had a peak median exposure at 6 months of gestation compared to controls’ peak at 9 months. After adjustment for sex, seasonality, race/ethnicity, and coastal residence, there was no significant association between BA and maximumK. brevisexposure per trimester of pregnancy at the 10-or 50-mile radius.ConclusionWe observed no association between gestationalK. brevis(cells/liter) exposure at a 10- and 50-mile radius from maternal zip code of residence and BA in offspring.Key pointsEnvironmental toxins may cause biliary atresia (BA)Red tide is caused by algal blooms (Karenia brevis)Red tide is debilitating to marine wildlifeGestational exposure toK. brevisdoes not cause BA
Impacts of weather and air pollution on Legionnaires’ disease in Switzerland: a national case-crossover study
Authors: Fischer Fabienne B. , Saucy Apolline , Vienneau Danielle , Hattendorf Jan , Fanderl Julia , de Hoogh Kees , Mäusezahl Daniel 
Published: October 2022

AbstractBackgroundThe number of cases of Legionnaires’ disease (LD) has risen markedly in Switzerland (6.5/100,000 inhabitants in 2021) and abroad over the last decade.Legionella, the causative agent of LD, are ubiquitous in the environment. Therefore, environmental changes can affect the incidence of LD, for example by increasing bacterial concentrations in the environment or facilitating transmission.ObjectivesThe aim of this study is to understand the environmental determinants, in particular weather conditions, for the regional and seasonal distribution of LD in Switzerland.MethodsWe conducted a series of analyses based on the Swiss LD notification data from 2017 to 2021. First, we used a descriptive and hotspot analysis to map LD cases and identify regional clusters. Second, we applied an ecological model to identify environmental determinants on case frequency at the district level. Third, we applied a case-crossover design using distributed lag non-linear models to identify short-term associations between seven weather variables and LD occurrence. Lastly, we performed a sensitivity analysis for the case-crossover design including NO2levels available for the year 2019.ResultsCanton Ticino in southern Switzerland was identified as a hotspot in the cluster analysis, with a standardised notification rate of 14.3 cases/100,000 inhabitants (CI: 12.6, 16.0). The strongest association with LD frequency in the ecological model was found for large-scale factors such as weather and air pollution. The case-crossover study confirmed the strong association of elevated daily mean temperature (OR 2.83; CI: 1.70, 4.70) and mean daily vapour pressure (OR: 1.52, CI: 1.15, 2.01) 6-14 days before LD occurrence.DiscussionOur analyses showed an influence of weather with a specific temporal pattern before the onset of LD, which may provide insights into the effect mechanism. The relationship between air pollution and LD and the interplay with weather should be further investigated.
Accelerated MRI using intelligent protocolling and subject-specific denoising applied to Alzheimer’s disease imaging
Authors: Ravi Keerthi Sravan , Nandakumar Gautham , Thomas Nikita , Lim Mason , Qian Enlin , Manso Jimeno Marina , Poojar Pavan , Jin Zhezhen , Quarterman Patrick , Srinivasan Girish , Fung Maggie , Vaughan John Thomas , Geethanath Sairam ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2022

AbstractMagnetic Resonance Imaging (MRI) is expensive and time-consuming. Protocol optimization to accelerate MRI requires local expertise since each MR sequence involves multiple configurable parameters that need optimization for contrast, acquisition time, and signal-to-noise ratio (SNR). The availability and access to technical training are limited in under-served regions, resulting in a scarcity of local expertise required to operate the hardware and perform MR examinations. Along with other cultural and temporal constraints, these factors contribute to the highly inefficient utilization of MRI services diminishing their clinical value. In this work, we extend our previous effort and demonstrate accelerated MRI via intelligent protocolling of the modified brain screen protocol, referred to as the Gold Standard (GS) protocol. We leverage deep learning-based contrast-specific image-denoising to improve the image quality of data acquired using the accelerated protocol. Since the SNR of MR acquisitions depends on the volume of the object being imaged, we demonstrate subject-specific (SS) image-denoising. Utilizing the accelerated protocol resulted in a 1.94x gain in imaging throughput over the GS protocol. The minimum /maximum PSNR gains (measured in dB) were 1.18/11.68 and 1.04/13.15, from the baseline and SS image-denoising models, respectively.Alzheimer’s Disease (AD) accounts for up to 60-80% of dementia cases and a global trend of longer lifespans has resulted in an increase in the prevalence of dementia/AD. Therefore, an accurate differential diagnosis of AD is crucial to determine the right course of treatment. The GS protocol constitutes 44.44% of the comprehensive AD imaging protocol defined by the European Prevention of Alzheimer’s Disease project. Therefore, we also demonstrate the potential for AD-imaging via automated volumetry of relevant brain anatomies whose atrophies have been shown to be reliable indicators of the onset of the disease. The volumetric measurements of the hippocampus and amygdala from the GS and accelerated protocols were in excellent agreement, as measured by the intra-class correlation coefficient.In conclusion, accelerated brain imaging with the potential for AD imaging was demonstrated, and image quality was recovered post-acquisition using DL-based image denoising models.
Airborne environmental DNA captures terrestrial vertebrate diversity in nature
Authors: Lynggaard Christina , Frøslev Tobias Guldberg , Johnson Matthew S. , Olsen Morten Tange , Bohmann Kristine 
Published: October 2022

AbstractThe current biodiversity and climate crises highlight the need for efficient tools to monitor terrestrial ecosystems. Here, we provide evidence for the use of airborne eDNA analyses as a novel method to detect terrestrial vertebrate communities in nature. Metabarcoding of 143 airborne eDNA samples collected during three days in Åmosen Nature Park, Denmark yielded 64 bird, mammal, fish and amphibian taxa, representing about a quarter of the around 210 wild terrestrial vertebrates that have been registered in the greater Åmosen area through years of compiling observational data. We provide evidence for the spatial movement and temporal patterns of airborne eDNA and for the influence of weather conditions on vertebrate detections. This study demonstrates airborne eDNA for high-resolution biomonitoring of vertebrates in terrestrial systems and elucidates its potential to guide global nature management and conservation efforts in the ongoing biodiversity crisis.