bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Burden of Familial-associated Early-onset Cancer Risk among Minority Americans Compared to non-Latino Whites
Authors: Feng Qianxi , Nickels Eric , Muskens Ivo S. , de Smith Adam J. , Gauderman W. James , Yee Amy C. , Ricker Charite , Mack Thomas , Leavitt Andrew D. , Godley Lucy A. , Wiemels Joseph L. 
Published: December 2020

AbstractBackgroundThe role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups.MethodsWe used linked California health registries to evaluate the relative cancer risks for first degree relatives of patients diagnosed between ages 0-26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989-2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity.ResultsGiven probands with cancer, there were increased relative risks of any cancer for siblings and mothers [SIR=3.32;95% confidence interval (CI):2.85-3.85)] and of SPMs (SIR=7.27;95%CI:6.56-8.03). Higher relative risk of any cancer in siblings and mothers given a proband with solid cancer (P<0.05) was observed for both Latinos (SIR=4.98;95%CI:3.82-6.39) and for non-Latino Blacks (SIR=7.35;95%CI:3.36-13.95) compared to non-Latino White subjects (SIR=3.02;95%CI:2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR=7.56;95%CI:3.26-14.90) compared to non-Latino whites (SIR:2.69;95%CI:1.62-4.20).ConclusionsThe data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the US.FundingThis work was supported by the V Foundation for funding this work (Grant FP067172).Key MessagesWe identified 29 631 cancer patients and their 62 863 healthy family members in California from 1989 to 2015.The risk of early-onset cancer in siblings and mothers was elevated by having a proband with cancer in the same family.The relative risk of early-onset cancers given a proband with solid cancer was higher for Latinos and Blacks when compared to non-Latino Whites.
Efficacy and safety of tenofovir disoproxil fumarate (TDF) in hepatitis B virus (HBV) monoinfection: longitudinal analysis of a UK cohort
Authors: Wang Tingyan , Smith David A , Campbell Cori , Mokaya Jolynne , Freeman Oliver , Salih Hizni , McNaughton Anna L , Cripps Sarah , Várnai Kinga A , Noble Theresa , Woods Kerrie , Collier Jane , Jeffery Katie , Davies Jim , Barnes Eleanor , Matthews Philippa C 
Published: December 2020

ABSTRACTAimCurrent clinical recommendations suggest treating chronic hepatitis B virus (HBV) infection in a minority of cases, but more data are needed to determine the benefits and risks of Tenofovir disoproxil fumarate (TDF) therapy. We aimed to assess the impact of TDF on liver disease, and the risk of nephrotoxicity.MethodWe studied a longitudinal UK chronic HBV (CHB) cohort attending out-patient clinics between 2005 and 2018, analysing data for 206 ethnically diverse adults (60 on TDF, 146 untreated), with median follow-up 3.3±2.8 years.ResultsPatients prescribed TDF were older (39 vs. 35 years, p=0.004) with a male excess (63% vs. 47%, p=0.04) compared to untreated patients. Reflecting treatment eligibility criteria, at baseline, treated patients were more likely to have elevated ALT (p<0.001), higher HBV DNA viral load (VL) (p<0.001), and higher elastography scores (p=0.002), but with no difference in renal function (p=0.6). In the TDF group, VL declined significantly between baseline and subsequent time points (all p<0.0001) with VL suppressed in 94% at three years, while in the untreated group viraemia was unchanged from baseline. In the TDF group, ALT and elastography scores normalised during treatment and by three years were equivalent to those in the untreated group. Progression of liver fibrosis did not occur in the TDF group but arose in 7.4% of untreated patients, although this difference was non-significant. There was no significant difference in renal impairment during follow-up between two groups.ConclusionTDF may have long-term benefits for a wider pool of the CHB population.
The de novo FAIRification process of a registry for vascular anomalies
Authors: Groenen Karlijn H.J. , Jacobsen Annika , Kersloot Martijn G. , Vieira Bruna , van Enckevort Esther , Kaliyaperumal Rajaram , Arts Derk L. , ‘t Hoen Peter A.C. , Cornet Ronald , Roos Marco , Kool Leo Schultze 
Published: December 2020

AbstractBackgroundPatient data registries that are FAIR - Findable, Accessible, Interoperable, and Reusable for humans and computers - facilitate research across multiple resources. This is particularly relevant to rare diseases, where data often are scarce and scattered. Specific research questions can be asked across FAIR rare disease registries and other FAIR resources without physically combining the data.ResultsWe successfully developed and implemented a process of making a rare disease registry for vascular anomalies FAIR from its conception -de novo. Here, we describe the five phases of this process in detail: i) pre-FAIRification, ii) facilitating FAIRification, iii) data collection, iv) generating FAIR data in real-time, and v) using FAIR data. This includes the creation of an electronic case report form and a semantic data model of the “Set of Common Data Elements for Rare Disease Registration” released by the European Commission, and the technical implementation in the Electronic Data Capture (EDC) system for real-time, automatic data FAIRification. Further, we describe how we contribute to the four facets of FAIR, and how our FAIRification process can be reused by other registries.ConclusionsIn conclusion, a detailed de novo FAIRification process of a registry for vascular anomalies is described. To a large extent, the process may be reused by other rare disease registries, and we envision this work to be a substantial contribution to an ecosystem of FAIR rare disease resources.
Relationships of Alzheimer’s disease and apolipoprotein E genotypes with small RNA and protein cargo of brain tissue extracellular vesicles
Authors: Huang Yiyao , Driedonks Tom A. P. , Cheng Lesley , Turchinovich Andrey , Rajapaksha Harinda , Arab Tanina , Powell Bonita H. , Pletniková Olga , Redding Javier , Troncoso Juan C. , Vella Laura , Zheng Lei , Hill Andrew F. , Mahairaki Vasiliki , Witwer Kenneth W. 
Published: December 2020

ABSTRACTAlzheimer’s disease (AD) is a public health crisis that grows as populations age. Hallmarks of this neurodegenerative disease include aggregation of beta-amyloid peptides and hyperphosphorylated tau proteins in the brain. Variants of the APOE gene are the greatest known risk factors for sporadic AD. As emerging players in AD pathophysiology, extracellular vesicles (EVs) contain proteins, lipids, and RNAs and are involved in disposal of cellular toxins and intercellular communication. AD-related changes in the molecular composition of EVs may contribute to pathophysiology and lend insights into disease mechanisms. We recently adapted a method for separation of brain-derived EVs (bdEVs) from post-mortem tissues. Using this method, we isolated bdEVs from AD patients with different APOE genotypes and controls. bdEVs were counted, sized, and subjected to parallel small RNA sequencing, proteomic analysis. Although overall bdEV concentration was not affected by AD, we observed a shift towards smaller particles in AD. Also, numerous bdEV-associated RNAs (including miRNAs and tRNAs) and proteins were found to be correlated with AD pathology and APOE genotype. Some of the identified entities have been implicated previously in important AD-related pathways, including amyloid processing, neurodegeneration, and metabolic functions, etc. Prominently, AD hallmark Tau and Tau phosphorylated at threonine 231 (phosTau) were significantly increased in AD bdEVs, indicating the involvement of bdEVs in spread of Tau pathology. These findings provide further evidence that bdEVs and their molecular cargo modulate development and progression of AD.
Application of concise machine learning to construct accurate and interpretable EHR computable phenotypes
Authors: Cava William La , Lee Paul C , Ajmal Imran , Ding Xiruo , Solanki Priyanka , Cohen Jordana B , Moore Jason H , Herman Daniel S 
Published: December 2020

ABSTRACTObjectiveElectronic health records (EHRs) can improve patient care by enabling systematic identification of patients for targeted decision support. But, this requires scalable learning of computable phenotypes. To this end, we developed the feature engineering automation tool (FEAT) and assessed it in targeting screening for the underdiagnosed, under-treated disease primary aldosteronism.Materials and MethodsWe selected 1,199 subjects receiving longitudinal care in a large health system and classified them for hypertension (N=608), hypertension with unexplained hypokalemia (N=172), and apparent treatment-resistant hypertension (N=176) by chart review. We derived 331 features from EHR encounters, diagnoses, laboratories, medications, vitals, and notes. We modified FEAT to encourage model parsimony and compared its models’ performance and interpretability to those of expert-curated heuristics and conventional machine learning.ResultsFEAT models trained to replicate expert-curated heuristics had higher area under the precision-recall curve (AUPRC) than all other models (p < 0.001) except random forests and were smaller than all other models (p < 1e-6) except decision trees. FEAT models trained to predict chart review phenotypes exhibited similar AUPRC to penalized logistic regression while being simpler than all other models (p < 1e-6). For treatment-resistant hypertension, FEAT learned a six-feature, clinically intuitive model that demonstrated a positive predictive value of 0.70 and sensitivity of 0.62 in held-out testing data.DiscussionFEAT learns computable phenotypes that approach the performance of expert-curated heuristics and conventional machine learning without sacrificing interpretability.ConclusionBy constructing accurate and interpretable computable phenotypes at scale, FEAT has the potential to facilitate systematic clinical decision support.
How the COVID-19 pandemic has adversely affected the economics of U.S. emergency care
Authors: Pines Jesse M. , Zocchi Mark S. , Black Bernard S. , Kornas Rebecca , Celedon Pablo , Moghtaderi Ali , Venkat Arvind ,   For the US Acute Care Solutions Research Group
Published: December 2020

ABSTRACTObjectiveWe describe how the coronavirus (COVID-19) pandemic impacted emergency department (ED) economics, acuity, and staffing.MethodsWe conducted an observational study of visits during January to September 2020 compared to 2019 in 136 EDs staffed by a national emergency medicine group. We created ratios of three-week moving averages for 2020 visits, acuity, costs divided by 2019 moving averages, by age and ED size. We tabulated reductions in clinician hours and FTEs compared to early 2020 staffing.Results2020-2019 ED visit ratios declined in March nadiring mid-April for both adults (to 0.60) and children (to 0.30) and rose thereafter but remained below 2019 levels through September 2020. The ratio of adult RVUs/visit rose to 1.1 for adults and 1.2 for children in the early pandemic, falling to 1.04 and 1.1 through September. The ratio of direct salary expenses in freestanding (FSED) and small EDs declined less dramatically than in medium and large EDs. Clinical revenues in medium and large EDs declined more sharply and recovered slowly but plateaued well below 2019 levels. By September 2020, expenses were still higher than revenues for small EDs, similar for FSEDs, and somewhat higher for medium and large EDs. During the pandemic, physician hours fell 15% and APP hours 27% during COVID-19 translating to 174 lost physician and 193 lost APP FTEs.ConclusionThe COVID-19 pandemic reduced ED visits and increased acuity in the first 7 months of the pandemic, leading to a contraction of the ED workforce, and threatening ED economics, more so in small and FSEDs.
Public Preferences for Social Distancing Behaviors to Mitigate the Spread of COVID-19: A Discrete Choice Experiment
Authors: Wilson Ingrid Eshun , Mody Aaloke , McKay Ginger , Hlatshwayo Mati , Bradley Cory , Thompson Vetta , Glidden Dave V , Geng Elvin H 
Published: December 2020

AbstractPolicies to promote social distancing can minimize COVID-19 transmission, but come with substantial social and economic costs. Quantifying relative preferences of the public for such practices can inform policy prioritization and optimize uptake. We used a discrete choice experiment (DCE) to quantify relative “utilities” (preferences) for five COVID-19 pandemic social distances strategies (e.g., closure of restaurants, restriction of large gatherings) against the hypothetical risk of acquiring COVID-19 and anticipated income loss. The survey was distributed in Missouri in May-June, 2020. We applied inverse probability sampling weights to mixed logit and latent class models to generate mean preferences and identify preference classes. Overall (n=2,428), the strongest preference was for the prohibition of large gatherings, followed by preferences to keep outdoor venues, schools, and social and lifestyle venues open, 75% of the population showing probable support for a strategy that prohibited large gatherings and closed lifestyle and social venues. Latent class analysis, however revealed four preference sub-groups in the population - “risk eliminators”, “risk balancers”, “altruistic” and “risk takers”, with men twice as likely as women to belong to the risk-taking group. In this setting, public health policies which as a first phase prohibit large gatherings, as well as close social and lifestyle venues may be acceptable and adhered to by the public. In addition, policy messages that address preference heterogeneity, for example by targeting public health messages at men, could improve adherence to social distancing measures and prevent further COVID-19 transmission prior to vaccine distribution and in the event of future pandemics.Significance StatementPreferences drive behavior – DCE’s are a novel tool in public health that allow examination of preferences for a product, service or policy, identifying how the public prioritizes personal risks and cost in relation to health behaviors. Using this method to establish preferences for COVID-19 mitigation strategies, our results suggest that, firstly, a tiered approach to non-essential business closures where large gatherings are prohibited and social and lifestyle venues are closed as a first phase, would be well aligned with population preferences and may be supported by the public, while school and outdoor venue closures may require more consideration prior to a second phase of restrictions. And secondly, that important distinct preference phenotypes - that are not captured by sociodemographic (e.g., age, sex, race) characteristics - exist, and therefore that messaging should be target at such subgroups to enhance adherence to prevention efforts.
Identification of acute exacerbations of chronic obstructive pulmonary disease using simple patient-reported symptoms and cough feature analysis: A diagnostic agreement study
Authors: Claxton Scott , Porter Paul , Brisbane Joanna , Bear Natasha , Wood Javan , Peltonen Vesa , Della Phillip , Smith Claire , Abeyratne Udantha 
Published: December 2020

ABSTRACTAcute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) are commonly encountered in the primary care setting, though accurate and timely diagnosis is problematic. Using technology like that employed in speech recognition technology, we developed a smartphone-based algorithm for rapid and accurate diagnosis of AECOPD. The algorithm incorporates patient-reported features (age, fever, new cough), audio data from five coughs and can be deployed by novice users. We compared the accuracy of the algorithm to expert clinical assessment. In patients with known COPD, the algorithm correctly identified the presence of AECOPD in 82.6% (95% CI: 72.9-89.9%) of subjects (n=86). The absence of AECOPD was correctly identified in 91.0% (95% CI: 82.4-96.3%) of individuals (n=78). Diagnostic agreement was maintained in milder cases of AECOPD (PPA: 79.2%, 95% CI: 68.0-87.8%), who typically comprise the cohort presenting to primary care. The algorithm may aid early identification of AECOPD and be incorporated in patient self-management plans.
Aerobic fitness is associated with cerebral mu-opioid receptor availability and activation in healthy humans
Authors: Saanijoki Tiina , Kantonen Tatu , Pekkarinen Laura , Kalliokoski Kari , Hirvonen Jussi , Tuominen Lauri , Tuulari Jetro J. , Arponen Eveliina , Nuutila Pirjo , Nummenmaa Lauri 
Published: December 2020

ABSTRACTCentral μ-opioid receptors (MORs) modulate affective responses to physical exercise. Individuals with higher aerobic fitness report greater exercise-induced mood improvements than those with lower fitness, but the link between cardiorespiratory fitness and the MOR system remains unresolved. Here we tested whether maximal oxygen uptake (VO2peak) and physical activity level are associated with cerebral MOR availability, and whether these phenotypes predict endogenous opioid release following aerobic exercise. We studied 64 healthy lean men who performed a maximal incremental cycling test for VO2peak determination, completed a questionnaire assessing moderate-to-vigorous physical activity (MVPA, min/week), and underwent positron emission tomography with [11C]carfentanil, a specific radioligand for MOR. A subset of 24 subjects underwent additional PET scan also after a one-hour session of moderate-intensity exercise. Higher VO2peak and self-reported MVPA level was associated with larger decrease in cerebral MOR binding after aerobic exercise in ventral striatum, orbitofrontal cortex and insula. That is, higher fit and more trained individuals showed greater opioid release acutely following exercise in brain regions especially relevant for reward and cognitive processing. Higher VO2peak also associated with lower baseline BPND in the reward and pain circuits, i.e., in frontal and cingulate cortices as well as in temporal lobes and subcortically in thalamus and putamen. We conclude that higher aerobic fitness and regular exercise training may induce neuroadaptation within the MOR system which might contribute to improved emotional and behavioural responses associated with long-term exercise.
The infection-tolerant mammalian reservoir of Lyme disease and other zoonoses broadly counters the inflammatory effects of endotoxin
Authors: Balderrama-Gutierrez Gabriela , Milovic Ana , Cook Vanessa J. , Islam M. Nurul , Zhang Youwen , Kiaris Hippokratis , Belisle John T. , Mortazavi Ali , Barbour Alan G. 
Published: December 2020

ABSTRACTAnimals that are competent natural reservoirs of zoonotic diseases commonly suffer little morbidity from the pathogens they persistently harbor. The mechanisms of this infection tolerance and the trade-off costs are poorly understood. We used exposure to a single dose of lipopolysaccharide (LPS) endotoxin as an experimental model of inflammation to compare the responses of the cricentine rodentPeromyscus leucopus, the white-footed deermouse, to that ofMus musculus, the standard laboratory model for pathogenesis studies. Four hours after injection with either LPS or saline, blood and spleen and liver tissues were collected postmortem and subjected to RNA-seq, untargeted metabolomics, and specific RT-qPCR. This was followed by analysis of differential expression at the gene, pathway, and empirical network levels. The deermice showed the same signs of sickness as the mice with LPS exposure, and in addition demonstrated comparable increases in levels of corticosterone and expression of interleukin (IL)-6, tumor necrosis factor, IL-1β, and acute phase reactants, including C-reactive protein. But whereas theM. musculusresponse to LPS was best-characterized by network analysis as cytokine-associated, theP. leucopusresponse was dominated by pathway terms associated with neutrophil activity. Dichotomies between the species in expression profiles of arginase 1 and nitric oxide synthase 2, as well as the ratios of IL-10 to IL-12, were consistent with a type M1 polarized macrophage response in the mice and a type M2 or alternatively-activated response in the deermice. Analysis of metabolites in the plasma and RNA in the tissues revealed differences between the two species in tryptophan metabolism during response to LPS. Two up-regulated genes in particular signified the difference between the species: Slpi (secretory leukocyte proteinase inhibitor) and Ibsp (integrin-binding protein sialoprotein). The latter was previously unrecognized in the context of inflammation or infection. Key RNA-seq findings inP. leucopuswere replicated in a second LPS experiment with older animals, in a systemic bacterial infection model, and with cultivated fibroblasts. Taken together, the results indicate that the deermouse possesses several adaptive traits to moderate effects of inflammation and oxidative stress ensuing from infection. This seems to be at the cost of infection persistence and that is to the benefit of the pathogen.
Profiling of oral microbiota and cytokines in COVID-19 patients
Authors: Iebba Valerio , Zanotta Nunzia , Campisciano Giuseppina , Zerbato Verena , Di Bella Stefano , Cason Carolina , Morassut Sara , Luzzati Roberto , Confalonieri Marco , Palamara Anna Teresa , Comar Manola 
Published: December 2020

ABSTRACTSARS-CoV-2 presence has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that oral cavity mucosa harbors high levels of ACE2 and TMPRSS2, highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. In the present study, for the first time, we demonstrate the oral microbiota structure and inflammatory profile of COVID-19 patients. Hospitalized COVID-19 patients and matched healthy controls underwent naso/oral-pharyngeal and oral swabs. Microbiota structure was analyzed by 16S rRNA V2 automated targeted sequencing, while oral and sera concentrations of 27 cytokines were assessed using magnetic bead-based multiplex immunoassays. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such asPrevotella salivaeandVeillonella infantiumwere distinctive for COVID-19 patients, whileNeisseria perflavaandGranulicatella eleganswere predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Group (SIGs). Pro-inflammatory cytokines were distinctive for COVID-19 in both oral and serum samples, and we found a specific bacterial consortium able to counteract them, following a novel index called C4 firstly proposed here. We even introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an AUC equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would pave the way for a theranostic approach in fighting COVID-19, trying to enlighten the intimate relationship among microbiota and SARS-CoV-2 infection.