bluuebunny/crossref_metadata_2025_split huggingface dataset:
An epigenetic and transcriptomic signature of immune tolerance in human monocytes through multi-omics integration
Authors: Brands Xanthe , Haak Bastiaan W. , Klarenbeek Augustijn M. , Butler Joe , Uhel Fabrice , Qin Wanhai , Otto Natasja A. , Jakobs Marja E. , Faber Daniël R. , Lutter René , Wiersinga W. Joost , van der Poll Tom , Scicluna Brendon P. 
Published: August 2021

AbstractBackgroundThe plasticity of monocytes enables them to exert multiple roles during an immune response, including promoting immune tolerance. How monocytes alter their functions to convey immune tolerance in the context of lower respiratory tract infections in humans is not well understood. Here, we sought to identify epigenetic and transcriptomic features of cytokine production capacity in circulating monocytes during community-acquired pneumonia (CAP).MethodsCirculating CD14+ monocytes were obtained from the blood of CAP patients included in a longitudinal, observational cohort study, on hospitalization (acute stage,n=75), and from the same patients after a 1-month follow-up (recovery stage,n=56). Age and sex-matched non-infectious participants were included as controls (n=41). Ex vivo cytokine production after lipopolysaccharide (LPS) exposure was assessed by multiplex assay. Transcriptomes of circulating monocytes were generated by RNA-sequencing, and DNA methylation levels in the same monocytes were measured by reduced representation bisulfite sequencing. Data were integrated by fitting projection-to-latent-structure models, and signatures derived by partial least squares discrimination.ResultsMonocytes captured during the acute stage exhibited impaired TNF, IL-1β, IL-6, and IL-10 production after ex vivo stimulation with LPS, relative to controls. IL-6 production was not resolved in recovery monocytes. Multivariate analysis of RNA-sequencing data identified 2938 significantly altered RNA transcripts in acute-stage monocytes (fold expression ≤−1.5 or ≥1.5; adjustedp≤ 0.01), relative to controls. Comparing DNA methylation levels in circulating monocytes of CAP patients to controls revealed minimal differences, specifically in DNAse hypersensitive sites (HS) of acute-stage monocytes. Data integration identified a cholesterol biosynthesis gene signature and DNAse HS axis of IL-1β and IL-10 production (R2=0.51).ConclusionsCirculating monocytes obtained from CAP patients during the acute stage exhibited impaired cytokine production capacities, indicative of reprogramming to a state of immune tolerance, which was not fully resolved after 1 month. Our split-sample study showed that 51% of the immune tolerance phenotype can be explained, at least in part, by coordinated shifts in cholesterol biosynthesis gene expression and DNAse HS methylation levels. A multi-scale model identified an epigenetic and transcriptomic signature of immune tolerance in monocytes, with implications for future interventions in immunosuppression.Trial registrationNCT numberNCT02928367
Elucidating mechano-pathology of osteoarthritis: transcriptome-wide differences in mechanically stressed aged human cartilage explants
Authors: Houtman Evelyn , Tuerlings Margo , Riechelman Janne , Suchiman Eka H. E. D. , van der Wal Robert J. P. , Nelissen Rob G. H. H. , Mei Hailiang , Ramos Yolande F. M. , Coutinho de Almeida Rodrigo , Meulenbelt Ingrid 
Published: August 2021

AbstractBackgroundFailing of intrinsic chondrocyte repair after mechanical stress is known as one of the most important initiators of osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage is still lacking. Such insights are needed to advance clinical development. To highlight important molecular processes of osteoarthritis mechano-pathology, the transcriptome-wide changes following injurious mechanical stress on human aged osteochondral explants were characterized.MethodsFollowing mechanical stress at a strain of 65% (65%MS) on human osteochondral explants (n65%MS= 14 versusncontrol= 14), RNA sequencing was performed. Differential expression analysis between control and 65%MS was performed to determine mechanical stress-specific changes. Enrichment for pathways and protein-protein interactions was analyzed with Enrichr and STRING.ResultsWe identified 156 genes significantly differentially expressed between control and 65%MS human osteochondral explants. Of note,IGFBP5(FC = 6.01; FDR = 7.81 × 10−3) andMMP13(FC = 5.19; FDR = 4.84 × 10−2) were the highest upregulated genes, whileIGFBP6(FC = 0.19; FDR = 3.07 × 10−4) was the most downregulated gene. Protein-protein interactions were significantly higher than expected by chance (P= 1.44 × 10−15with connections between 116 out of 156 genes). Pathway analysis showed, among others, enrichment for cellular senescence, insulin-like growth factor (IGF) I and II binding, and focal adhesion.ConclusionsOur results faithfully represent transcriptomic wide consequences of mechanical stress in human aged articular cartilage withMMP13, IGF binding proteins, and cellular senescence as the most notable results. Acquired knowledge on the as such identified initial, osteoarthritis-related, detrimental responses of chondrocytes may eventually contribute to the development of effective disease-modifying osteoarthritis treatments.
Dietary inflammatory index (DII) may be associated with hypertriglyceridemia waist circumference phenotype in overweight and obese Iranian women: a cross sectional study
Authors: Tavakoli Atefeh , Mirzababaei Atieh , Moosavi Hanieh , Mehranfar Sanaz , Keshavarz Seyed-Ali , Mirzaei Khadijeh 
Published: August 2021

Abstract
Objective
Recent studies have shown that increased dietary inflammatory index (DII) score or consumption of pro-inflammatory foods can lead to increased waist circumference (WC) as well as triglyceride (TG) concentrations in obese people. The purpose of this study is to examine the association between DII and hypertriglyceridemic waist circumference phenotype (HTGWCP) in women with overweight and obesity.

Results
There was a positive significant correlation between DII and HTGWCPs. In other words, with an increase in DII score or higher consumption of pro-inflammatory foods, the odds of having abnormal phenotypes including; enlarged waist normal TG (EWNT) (OR = 2.85, 95% CI 1.02 to 7.98, P for trend = 0.04), normal waist enlarged TG (NWET) (OR = 5.85, 95% CI 1.1 to 31.11, P for trend = 0.03) and enlarged waist enlarged TG (EWET) (OR = 3.13, 95% CI 0.95 to 10.27, P for trend = 0.05) increase compared to normal waist normal TG (NWNT) phenotype. In conclusion; increasing DII scores can increase abnormal phenotypes and therefore may increase WC and TG levels in overweight and obese women.
Optimization of a suite of flathead catfish (Pylodictis olivaris) microsatellite markers for understanding the population genetics of introduced populations in the northeast United States
Authors: White Shannon L. , Eackles Michael S. , Wagner Tyler , Schall Megan , Smith Geoff , Avery Julian , Kazyak David C. 
Published: August 2021

AbstractObjectiveFlathead catfish are rapidly expanding into nonnative waterways throughout the United States. Once established, flathead catfish may cause disruptions to the local ecosystem through consumption and competition with native fishes, including species of conservation concern. Flathead catfish often become a popular sport fish in their introduced range, and so management strategies must frequently balance the need to protect native and naturalized fauna while meeting the desire to maintain or enhance fisheries. However, there are currently few tools available to inform management of invasive flathead catfish (Pylodictis olivaris). We describe a suite of microsatellite loci that can be used to characterize population structure, predict invasion history, and assess potential mitigation strategies for flathead catfish.ResultsOur panel of 13 microsatellite loci were polymorphic and appear to be informative for population genetic studies of flathead catfish. We found moderate levels of diversity in four nonnative collections of flathead catfish in the Pennsylvania and Maryland sections of the Susquehanna River and the Schuylkill River, Pennsylvania. Analyses suggested patterns of genetic differentiation within- and among-rivers, highlighting the utility of this marker panel for understanding the structure and assessing the degree of connectivity among flathead catfish populations.
A physiologically based pharmacokinetic (PBPK) model to describe organ distribution of 68Ga-DOTATATE in patients without neuroendocrine tumors
Authors: Siebinga H. , de Wit-van der Veen B. J. , Beijnen J. H. , Stokkel M. P. M. , Dorlo T. P. C. , Huitema A. D. R. , Hendrikx J. J. M. A. 
Published: August 2021

Abstract
Background
Physiologically based pharmacokinetic (PBPK) models combine drug-specific information with prior knowledge on the physiology and biology at the organism level. Whole-body PBPK models contain an explicit representation of the organs and tissue and are a tool to predict pharmacokinetic behavior of drugs. The aim of this study was to develop a PBPK model to describe organ distribution of 68Ga-DOTATATE in a population of patients without detectable neuroendocrine tumors (NETs).

Methods
Clinical 68Ga-DOTATATE PET/CT data from 41 patients without any detectable somatostatin receptor (SSTR) overexpressing tumors were included. Scans were performed at 45 min (range 30–60 min) after intravenous bolus injection of 68Ga-DOTATATE. Organ (spleen, liver, thyroid) and blood activity levels were derived from PET scans, and corresponding DOTATATE concentrations were calculated. A whole-body PBPK model was developed, including an internalization reaction, receptor recycling, enzymatic reaction for intracellular degradation and renal clearance. SSTR2 expression was added for several organs. Input parameters were fixed or estimated using a built-in Monte Carlo algorithm for parameter identification.

Results
68Ga-DOTATATE was administered with a median peptide amount of 12.3 µg (range 8.05–16.9 µg) labeled with 92.7 MBq (range 43.4–129.9 MBq). SSTR2 amounts for spleen, liver and thyroid were estimated at 4.40, 7.80 and 0.0108 nmol, respectively. Variability in observed organ concentrations was best described by variability in SSTR2 expression and differences in administered peptide amounts.

Conclusions
To conclude, biodistribution of 68Ga-DOTATATE was described with a whole-body PBPK model, where tissue distribution was mainly determined by variability in SSTR2 organ expression and differences in administered peptide amounts.
The finite volume element method for the two-dimensional space-fractional convection–diffusion equation
Authors: Bi Yanan , Jiang Ziwen 
Published: August 2021

AbstractWe develop a fully discrete finite volume element scheme of the two-dimensional space-fractional convection–diffusion equation using the finite volume element method to discretize the space-fractional derivative and Crank–Nicholson scheme for time discretization. We also analyze and prove the stability and convergence of the given scheme. Finally, we validate our theoretical analysis by data from three examples.
Citizens, doctors, politicians - who´s an expert in times of COVID-19? A survey in Austria and Germany
Authors: Schaffler-Schaden Dagmar , Herfert Juergen , O´Brien James , Johansson Tim , Seymer Alexander , Ludwig Stephan , Stöggl Thomas , Osterbrink Juergen , Flamm Maria , van der Zee-Neuen Antje 
Published: August 2021

AbstractBackgroundThis study aimed to explore which measures and risk factors for a COVID − 19 infection are considered most important in the general population, health experts and policymakers and to assess the level of agreement across the groups from Austria and Germany.MethodsA two-phased survey was conducted, participants were matched according to age and gender. Three different groups were asked which measures they considered most relevant in reducing a COVID-19 transmission, to determine which factors contribute most to the risk of disease, and to evaluate the level of agreement in the assessment of risk factor relevance for (a) the transmission of the disease and (b) the risk of a severe course of COVID-19.ResultsRisk factors for an infection that were selected from all three groups were immunosuppression/deficiency, cancer, chronic lung disease, smoking, age and working as a health care professional. Interrater agreement per population was only poor to slight and results were highly heterogeneous.ConclusionsOur survey shows a broad spectrum of opinions and the associated general uncertainty about the risk factors for infection and a severe course of disease across the groups. Profound knowledge of politicians and experts is of high relevance to provide the public with valid information to ensure cooperation fighting the pandemic.Trial registrationhttps://apps.who.int/trialsearch/(ID: DRKS00022166). Registered 15 June 2020.
Design matters in patient-level prediction: evaluation of a cohort vs. case-control design when developing predictive models in observational healthcare datasets
Authors: Reps Jenna M. , Ryan Patrick B. , Rijnbeek Peter R. , Schuemie Martijn J. 
Published: August 2021

AbstractBackgroundThe design used to create labelled data for training prediction models from observational healthcare databases (e.g., case-control and cohort) may impact the clinical usefulness. We aim to investigate hypothetical design issues and determine how the design impacts prediction model performance.AimTo empirically investigate differences between models developed using a case-control design and a cohort design.MethodsUsing a US claims database, we replicated two published prediction models (dementia and type 2 diabetes) which were developed using a case-control design, and trained models for the same prediction questions using cohort designs. We validated each model on data mimicking the point in time the models would be applied in clinical practice. We calculated the models’ discrimination and calibration-in-the-large performances.ResultsThe dementia models obtained area under the receiver operating characteristics of 0.560 and 0.897 for the case-control and cohort designs respectively. The type 2 diabetes models obtained area under the receiver operating characteristics of 0.733 and 0.727 for the case-control and cohort designs respectively. The dementia and diabetes case-control models were both poorly calibrated, whereas the dementia cohort model achieved good calibration. We show that careful construction of a case-control design can lead to comparable discriminative performance as a cohort design, but case-control designs over-represent the outcome class leading to miscalibration.ConclusionsAny case-control design can be converted to a cohort design. We recommend that researchers with observational data use the less subjective and generally better calibrated cohort design when extracting labelled data. However, if a carefully constructed case-control design is used, then the model must be prospectively validated using a cohort design for fair evaluation and be recalibrated.
Common animal models lack a distinct glenoid labrum: a comparative anatomy study
Authors: Como Christopher J. , Rothrauff Benjamin B. , Alexander Peter G. , Lin Albert , Musahl Volker 
Published: August 2021

Abstract
Purpose
Development and validation of an animal model of labral healing would facilitate translation of novel surgical and biological strategies to improve glenolabral healing. The purpose of this study was to characterize the anatomic and histological properties of the shoulder labrum in rat, rabbit, dog, pig, goat, and humans. Given the demonstrated similarities in size and structural morphology in other joints, it was hypothesized that the goat glenoid with surrounding capsulolabral complex would most closely resemble that of humans in terms of dimensions and structure, as observed grossly and histologically.

Methods
Cadaveric glenohumeral joints from rats (n = 8), New Zealand white rabbits (n = 13), Mongrel dogs (n = 9), Spanish goats (n = 10), Yorkshire pigs (n = 10), and humans (n = 9) were freshly harvested. Photographs were taken of the glenoid with its surrounding capsulolabral complex. Linear dimensions of the glenoid articular surface were measured. It was determined where the capsulolabral complex was continuous with, or recessed from, the articular glenoid surface. The glenoid was divided into 6 equal segments radiating out toward 12, 2, 4, 6, 8, and 10 o’clock positions. Samples were sectioned and stained with Safranin O/Fast green and Mallory Trichrome. Insertion of the capsulolabral tissue onto the glenoid was qualitatively assessed and compared with gross morphology.

Results
Dimensions of the goat glenoid most closely paralleled dimensions of the human glenoid. A capsulolabral complex was continuous with the glenoid surface from ~ 9 to 12 o’clock in the rats, 7 to 12 o’clock in rabbits, 5 to 12 o’clock in the dogs, and 9 to 12 o’clock in goats, 6 to 12 o’clock in pigs, and 2 to 8 o’clock in humans. In contrast to humans, no other species demonstrated an organized fibrocartilaginous labrum either macroscopically or histologically.

Conclusion
The animals in the present study did not possess a discrete fibrocartilaginous labrum by gross or histological evaluation, as directly compared to humans. While models using these animals may be acceptable for examining other shoulder pathologies, they are not adequate to evaluate labral pathology.

Level of evidence
Basic Science Study; Anatomy and Histology; Cadaveric Animal Model.
Protocol for a randomised controlled feasibility study of psychologically informed vestibular rehabilitation for people with persistent dizziness: INVEST trial
Authors: Herdman David , Norton Sam , Pavlou Marousa , Murdin Louisa , Moss-Morris Rona 
Published: August 2021

Abstract
Background
Dizziness is a common complaint that often persists and leads to disability and distress. Several cognitive and behavioural responses may contribute to the neurobiological adaptations that maintain persistent vestibular symptoms. This paper will present the protocol of a two-arm parallel group feasibility randomised controlled trial designed to determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of an integrated cognitive behavioural therapy and vestibular rehabilitation (CBT-VR) treatment for people with persistent dizziness.

Methods
Forty adult patients will be recruited from a tertiary vestibular clinic with persistent movement–triggered dizziness for 3 months or longer who have moderate–high levels of dizziness handicap. Participants will be 1:1 randomised, using a minimisation procedure, to six sessions of either CBT-VR (intervention arm) or VR only (control arm). Measures will be collected at baseline and 4 months post randomisation. The primary feasibility outcomes include descriptive data on numbers meeting eligibility criteria, rates of recruitment, numbers retained post randomisation, treatment adherence and an acceptability questionnaire. Treatment effects on self-report outcomes will be estimated to determine that 95% confidence intervals for the effects are consistent with anticipated effects and minimum clinically important differences, and to provide information needed for the power calculation of an efficacy trial. A nested qualitative study will be conducted post-intervention (intervention group only) to explore the acceptability of the intervention and identify any areas in need of improvement.

Discussion
If a trial of CBT-VR is feasible, acceptability data will be used to enhance the intervention if needed and refine the multicentre RCT protocol. Future studies will need to consider the training required for other physiotherapists to deliver the intervention.

Trial registration
ClinicalTrials.gov, ISRCTN 10420559
Has COVID-19 changed the stock return-oil price predictability pattern?
Authors: Zhang Fan , Narayan Paresh Kumar , Devpura Neluka 
Published: August 2021

AbstractIn this paper, we examine if COVID-19 has impacted the relationship between oil prices and stock returns predictions using daily Japanese stock market data from 01/04/2020 to 03/17/2021. We make a novel contribution to the literature by testing whether the COVID-19 pandemic has changed this predictability relationship. Employing an empirical model that controls for seasonal effects, return-related control variables, heteroskedasticity, persistency, and endogeneity, we demonstrate that the influence of oil prices on stock returns declined by around 89.5% due to COVID-19. This implies that when COVID-19 reduced economic activity and destabilized financial markets, the influence of oil prices on stock returns declined. This finding could have implications for trading strategies that rely on oil prices.
Take Bitcoin into your portfolio: a novel ensemble portfolio optimization framework for broad commodity assets
Authors: Li Yuze , Jiang Shangrong , Wei Yunjie , Wang Shouyang 
Published: August 2021

AbstractThe emergence and growing popularity of Bitcoins have attracted the attention of the financial world. However, few empirical studies have considered the inclusion of the newly emerged commodity asset in the global commodity market. It is of great importance for investors and policymakers to take advantage of this asset and its potential benefits by incorporating it as a part of the broad commodity trading portfolio. In this study, we propose a novel ensemble portfolio optimization (NEPO) framework utilized for broad commodity assets, which integrates a hybrid variational mode decomposition-bidirectional long short-term memory deep learning model for future returns forecast and a reinforcement learning-based model for optimizing the asset weight allocation. Our empirical results indicate that the NEPO framework could effectively improve the prediction accuracy and trend prediction ability across various commodity assets from different sectors. In addition, it could effectively incorporate Bitcoins into the asset pool and achieve better financial performance compared to traditional asset allocation strategies, commodity funds, and indices.
Scabies as a part of the World Health Organization roadmap for neglected tropical diseases 2021–2030: what we know and what we need to do for global control
Authors: El-Moamly Amal A. 
Published: August 2021

AbstractBackgroundScabies is an under-recognized global health problem with an unacceptably high prevalence in many settings worldwide. Fortunately, the World Health Organization (WHO) has formally designated scabies as a neglected tropical disease in 2017, in the hope of increasing awareness and encouraging efforts to eradicate it. Also, scabies has recently been included as part of the WHO roadmap for neglected tropical diseases 2021–2030, aimed at ending the neglect to attain the Sustainable Development Goals.Main abstract bodyThis review article places scabies in focus. The literature was reviewed to explore discussions on controversial issues in scabies control, with the aim of clarifying whether global control of scabies is a feasible and worthwhile objective. The existing status of scabies and its burden are discussed along with future prospects for its global control. The article investigates the feasibility of scabies control and provides updates on the various impediments to this goal, such as challenges related to transmission, diagnosis, treatment, and vaccine development. Also examined are relevant research needs, success factors, and reasons for failure. This article aims to increase the global awareness of scabies and promote discussion, enhance coordinated international efforts, and ultimately, enact change at the national and worldwide levels toward the control of this preventable disease of the poor.ConclusionDespite the current challenges, scabies control is now within reach. With sustained interventions, continuous resources, and sincere commitment and support, scabies global control appears to be a worthwhile, realistic goal that is potentially achievable in the not so distant future.