bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using genetics to understand the role of antihypertensive drugs modulating angiotensin‐converting enzyme in immune function and inflammation
Authors: Zhao Jie V. , Schooling C. Mary , Leung Gabriel M. 
Published: October 2020

AimAngiotensin‐converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARSCoV‐2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy.MethodsWe used a Mendelian randomization study to obtain unconfounded associations of antihypertensives, instrumented by published genetic variants in genes regulating target proteins of these drugs, with immune (lymphocyte and neutrophil percentage) and inflammatory (tumour necrosis factor alpha [TNF‐α]) markers in the largest available genome‐wide association studies.ResultsGenetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (−0.64, 95% CI −1.09, −0.20) and possibly lowered TNF‐α (−4.92, 95% CI −8.50, −1.33). CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage −0.23, 95% CI −0.39 to −0.08) but had no effect on TNF‐α, as did potassium‐sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives. ARBs and other classes of hypertensives had no effect on immune function or TNF‐α.ConclusionVarying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV‐2.
Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients
Authors: Francke Marith I. , Hesselink Dennis A. , Li Yi , Koch Birgit C.P. , de Wit Lucia E.A. , van Schaik Ron H.N. , Yang Lin , Baan Carla C. , van Gelder Teun , de Winter Brenda C.M. 
Published: October 2020

AimsTacrolimus is a critical dose drug and to avoid under‐ and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug‐related toxicity occur despite whole‐blood tacrolimus pre‐dose concentrations ([Tac]blood) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac]cells) may better correlate with drug‐efficacy. The aim of this study was to (1) investigate the relationship between [Tac]blood and [Tac]cells, (2) identify factors affecting the tacrolimus distribution in cells and whole‐blood, and (3) study the relationship between [Tac]cells and clinical outcomes after kidney transplantation.MethodsA total of 175 renal transplant recipients were prospectively followed. [Tac]blood and [Tac]cells were determined at Months 3, 6 and 12 post‐transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus‐related nephrotoxicity and post‐transplant diabetes mellitus were collected.ResultsCorrelations between [Tac]blood and [Tac]cells were moderate to poor (Spearman's r = 0.31; r = 0.41; r = 0.61 at Months 3, 6 and 12, respectively). The [Tac]cells/[Tac]blood ratio was stable over time in most patients (median intra‐patient variability 39.0%; range 3.5%–173.2%). Age, albumin and haematocrit correlated with the [Tac]cells/[Tac]blood ratio. CYP3A5 and CYP3A4 genotype combined affected both dose‐corrected [Tac]blood and [Tac]cells. ABCB1 was not significantly related to tacrolimus distribution. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes.ConclusionsThe correlation between [Tac]blood and [Tac]cells is poor. Age, albumin and haematocrit correlate with the [Tac]cells/[Tac]blood ratio, whereas genetic variation in ABCB1, CYP3A4 and CYP3A5 do not. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes.
Continent diversion: five decades of developments and evolution
Authors: Stangl Fabian P. , Thalmann George N. 
Published: October 2020

ObjectiveTo provide a chronological overview of the evolution of continent urinary diversion (CUD) over the last 50 years and to highlight important milestones.MethodsWe performed an extensive literature review and analysed different forms of urinary diversion worldwide. After the evaluation of surgical techniques, we assessed the advantages and disadvantages of assorted CUD approaches based on published long‐term follow‐up data.ResultsA wide variety of surgical options for CUD is available and feasible to date, although consensus among urologists regarding the 'gold standard' is still lacking. Several forms of orthotopic bladder substitutes and continent cutaneous urinary reservoirs have been shown to provide excellent long‐term results.ConclusionThe last 50 years of CUD have seen constant evolution and refinement of techniques, but the best surgical approach remains unclear and there is no ‘one‐size‐fits‐all’ option, but rather tailor‐made approaches are necessary to ensure patient satisfaction.
Multi‐institutional validation of a perfused robot‐assisted partial nephrectomy procedural simulation platform utilizing clinically relevant objective metrics of simulators (CROMS)
Authors: Ghazi Ahmed , Melnyk Rachel , Hung Andrew J. , Collins Justin , Ertefaie Ashkan , Saba Patrick , Gurung Pratik , Frye Thomas , Rashid Hani , Wu Guan , Mottrie Alex , Costello Tony , Dasgupta Prokar , Joseph Jean 
Published: October 2020

ObjectiveTo conduct a multi‐institutional validation of a high‐fidelity, perfused, inanimate, simulation platform for robot‐assisted partial nephrectomy (RAPN) using incorporated clinically relevant objective metrics of simulation (CROMS), applying modern validity standards.Materials and MethodsUsing a combination of three‐dimensional (3D) printing and hydrogel casting, a RAPN model was developed from the computed tomography scan of a patient with a 4.2‐cm, upper‐pole renal tumour (RENAL nephrometry score 7×). 3D‐printed casts designed from the patient’s imaging were used to fabricate and register hydrogel (polyvinyl alcohol) components of the kidney, including the vascular and pelvicalyceal systems. After mechanical and anatomical verification of the kidney phantom, it was surrounded by other relevant hydrogel organs and placed in a laparoscopic trainer. Twenty‐seven novice and 16 expert urologists, categorized according to caseload, from five academic institutions completed the simulation.ResultsClinically relevant objective metrics of simulators, operative complications, and objective performance ratings (Global Evaluative Assessment of Robotic Skills [GEARS]) were compared between groups using Wilcoxon rank‐sum (continuous variables) and parametric chi‐squared (categorical variables) tests. Pearson and point‐biserial correlation coefficients were used to correlate GEARS scores to each CROMS variable. Post‐simulation questionnaires were used to obtain subjective supplementation of realism ratings and training effectiveness.ResultsExpert ratings demonstrated the model’s superiority to other procedural simulations in replicating procedural steps, bleeding, tissue texture and appearance. A significant difference between groups was demonstrated in CROMS [console time (P < 0.001), warm ischaemia time (P < 0.001), estimated blood loss (P < 0.001)] and GEARS (P < 0.001). Six major intra‐operative complications occurred only in novice simulations. GEARS scores highly correlated with the CROMS.ConclusionsThis perfused, procedural model offers an unprecedented realistic simulation platform, which incorporates objective, clinically relevant and procedure‐specific performance metrics.
Inclusive approaches to developing content valid patient‐reported outcome measure response scales for youth with intellectual/developmental disabilities
Authors: Schwartz Ariel E. , Kramer Jessica M. ,   PEDI‐PRO Youth Team
Published: October 2020

Accessible Summary

People with disabilities have the right to use patient‐reported outcome measures (PROMs) to tell their doctors and therapists what they think and feel. Therefore, PROMs need to be accessible for people with disabilities. This means that the questions and the response choices for the questions need to be easy to understand. Response choices can be words like, “yes” and “no,” or “agree” and “disagree,” or “easy” and “hard.”

To make sure that the response choices are easy to understand, it is a good idea to collaborate with people with disabilities when designing PROM response choices, or response scales.

We describe how we worked with 8 young people with disabilities to make an easy‐to‐use response scale for a PROM.

After our data collection and work together, we decided the best response scale was “very easy,” “a little easy,” “a little hard.”

This research is important, because other researchers and people making PROMs can use our process to help make their response scales easy to use.

AbstractBackgroundPatient‐reported outcome measures (PROMs) are increasingly used in health care to evaluate service quality and client progress. Response scales are a critical component of PROM content validity and must be designed to be relevant and comprehensible by users.MethodsIn collaboration with eight youth co‐researchers with intellectual/developmental disabilities ages 14–21, we used an iterative, three‐stage approach to develop and select a response scale for the PEDI‐PRO. Stages: 1) inclusive development of response scale options; 2) Collecting data about response scale options during focus groups with youth with intellectual/ developmental disabilities (n = 62); and 3) Analysing data to refine response options.ResultsThrough two cycles of the three‐stage process, the inclusive research approach led to the development of a content valid response scale that describes functional performance of everyday activities (“very easy,” “a little easy,” “a little hard”).ConclusionAn inclusive research approach can support the development of content valid PROM scales. We identified four broad strategies that supported youth co‐researchers to engage in this response scale development process: universal design for learning, use of lived experiences, breaking down tasks, and peer support. Researchers may adopt and/or adapt the accessible inclusive research approaches described in this manuscript for measurement development and other research projects.
Forest biomass stocks and dynamics across the subtropical Andes
Authors: Blundo Cecilia , Malizia Agustina , Malizia Lucio R. , Lichstein Jeremy W. 
Published: October 2020

AbstractForest biomass plays an important role in the global carbon cycle. Therefore, understanding the factors that control forest biomass stocks and dynamics is a key challenge in the context of global change. We analyzed data from 60 forest plots in the subtropical Andes (22–27.5° S and 300–2300 m asl) to describe patterns and identify drivers of aboveground biomass (AGB) stocks and dynamics. We found that AGB stocks remained roughly constant with elevation due to compensating changes in basal area (which increased with elevation) and plot‐mean wood specific gravity (which decreased with elevation). AGB gain and loss rates both decreased with elevation and were explained mainly by temperature and rainfall (positive effects on both AGB gains and losses). AGB gain was also correlated with forest‐use history and weakly correlated with forest structure. Mean annual temperature and rainfall showed minor effects on AGB stocks and AGB change (gains minus losses) over recent decades. Although AGB change was only weakly correlated with climate variables, increases in AGB gains and losses with increasing rainfall—together with observed increases in rainfall in the subtropical Andes—suggest that these forests may become increasingly dynamic in the future.Abstract in Spanish is available with online material
Impacts of rodent eradication on seed predation and plant community biomass on a tropical atoll
Authors: Miller‐ter Kuile Ana , Orr Devyn , Bui An , Dirzo Rodolfo , Klope Maggie , McCauley Douglas , Motta Carina , Young Hillary 
Published: October 2020

AbstractInvasive rodent eradications are frequently undertaken to curb island biodiversity loss. However, the breadth of rodents’ ecological impact, even after eradication, is not always fully recognized. For example, the most widespread invasive rodent, the black rat (Rattus rattus), while omnivorous, eats predominantly seeds and fruit. Yet, the effects of seed predation release after eradication on plant communities and ecological functions are not well understood, posing a gap for island restoration. We examined the role of seed predation release following black rat eradication in changes to tree composition and aboveground biomass across an islet network (Palmyra Atoll) in the Central Pacific. We conducted repeated surveys of seed, juvenile, and adult tree biomass and survival in permanent vegetation plots before and after the eradication of rats. We observed a 95% reduction in seed predation for an introduced, previously cultivated tree population (Cocos nucifera). Juvenile tree biomass of all species increased 14‐fold, with C. nucifera increasing the most, suggesting that eradication increased this tree's competitive advantage. Indeed, based on stage‐structured demographic models, rat eradication led to a 10% increase in C. nucifera population growth rate. The effect of invasive rodent seed predation varies considerably among the plant species in a community and can shift competitive dynamics, sometimes in favor of invasive plants. These bottom‐up effects should be considered in evaluating the costs and benefits of eradication. Documenting the variation in invasive rodent diet items, along with long‐term surveys, can help prioritize island eradications where restoration is most likely to be successful.
Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients
Authors: Boix F , Legaz I , Minhas A , Alfaro R , Jiménez–Coll V , Mrowiec A , Martínez–Banaclocha H , Galián J A , Botella C , Moya–Quiles M R , Sanchez–Bueno F , Robles R , de la Peña–Moral J , Ramirez P , Pons J A , Minguela A , Muro M 
Published: October 2020

SummaryDecreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient–donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+CD154+ T cells (P = 0·001) and a low percentage of CD8+CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (P = 0·001) and CD8+CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+CD154+ and CD8+CD154+ T cells in parallel with other transplant factors.
Turbulent Details Simulation for SPH Fluids via Vorticity Refinement
Authors: Liu Sinuo , Wang Xiaokun , Ban Xiaojuan , Xu Yanrui , Zhou Jing , Kosinka Jiří , Telea Alexandru C. 
Published: October 2020

AbstractA major issue in smoothed particle hydrodynamics (SPH) approaches is the numerical dissipation during the projection process, especially under coarse discretizations. High‐frequency details, such as turbulence and vortices, are smoothed out, leading to unrealistic results. To address this issue, we introduce a vorticity refinement (VR) solver for SPH fluids with negligible computational overhead. In this method, the numerical dissipation of the vorticity field is recovered by the difference between the theoretical and the actual vorticity, so as to enhance turbulence details. Instead of solving the Biot‐Savart integrals, a stream function, which is easier and more efficient to solve, is used to relate the vorticity field to the velocity field. We obtain turbulence effects of different intensity levels by changing an adjustable parameter. Since the vorticity field is enhanced according to the curl field, our method can not only amplify existing vortices, but also capture additional turbulence. Our VR solver is straightforward to implement and can be easily integrated into existing SPH methods.
Moving from trends to benchmarks by using regression tree analysis to find inbreeding thresholds in a critically endangered bird
Authors: Flanagan Alison M. , Masuda Bryce , Grueber Catherine E. , Sutton Jolene T. 
Published: October 2020

AbstractUnderstanding how inbreeding affects endangered species in conservation breeding programs is essential for their recovery. The Hawaiian Crow (‘Alalā) (Corvus hawaiiensis) is one of the world's most endangered birds. It went extinct in the wild in 2002, and, until recent release efforts starting in 2016, nearly all of the population remained under human care for conservation breeding. Using pedigree inbreeding coefficients (F), we evaluated the effects of inbreeding on Hawaiian Crow offspring survival and reproductive success. We used regression tree analysis to identify the level of inbreeding (i.e., inbreeding threshold) that explains a substantial decrease in ‘Alalā offspring survival to recruitment. Similar to a previous study of inbreeding in ‘Alalā, we found that inbreeding had a negative impact on offspring survival but that parental (vs. artificial) egg incubation improved offspring survival to recruitment. Furthermore, we found that inbreeding did not substantially affect offspring reproductive success, based on the assumption that offspring that survive to adulthood breed with distantly related mates. Our novel application of regression tree analysis showed that offspring with inbreeding levels exceeding F = 0.098 were 69% less likely to survive to recruitment than more outbred offspring, providing a specific threshold value for ongoing population management. Our results emphasize the importance of assessing inbreeding depression across all life history stages, confirm the importance of prioritizing parental over artificial egg incubation in avian conservation breeding programs, and demonstrate the utility of regression tree analysis as a tool for identifying inbreeding thresholds, if present, in any pedigree‐managed population.
Preordering in Luxury Fashion: Will Additional Demand Information Bring Negative Effects to the Retailer?*
Authors: Shen Bin , Zhang Ting , Xu Xiaoyan , Chan Hau‐Ling , Choi Tsan‐Ming 
Published: October 2020

ABSTRACTPreordering is an emerging business model in luxury fashion, which provides consumers the opportunity to preorder new collection products immediately after fashion runway shows and helps retailers collect preordering information for updating demand forecast. Based on our observations of industrial practices, we establish stylized analytical models for a supply chain consisting of a luxury brand (supplier) and a retailer. In addition, we explore the consequences of preordering for the supply chain, its members, and conspicuous consumers. Results show that preordering information incentivizes the retailer to increase product scarcity and leverage consumers’ conspicuous consumption to charge a premium retail price, which consequently allows the supplier to increase the wholesale price. However, preordering information updating may have negative effects on the retailer due to the increased wholesale price, but this case always benefits the supplier. We recognize that preordering has two effects, a service‐extending effect and a precision‐improving effect, which positively and negatively affect consumers, respectively. Thus, retailers offering the preorder services should provide consumers with incentives (e.g., gifts or coupons) to achieve an all‐win scenario with preordering information updating. This finding is consistent with widely observed industrial practices in e‐commerce. In addition, our numerical studies interestingly show that all supply chain members can benefit from an increase in the level of conspicuous consumption in the market.
Global perspective of COVID‐19 epidemiology for a full‐cycle pandemic
Authors: Ioannidis John P. A. 
Published: October 2020

AbstractAs of October 2020, there are >1 million documented deaths with COVID‐19. Excess deaths can be caused by both COVID‐19 and the measures taken. COVID‐19 shows extremely strong risk stratification across age, socioeconomic factors, and clinical factors. Calculation of years‐of‐life‐lost from COVID‐19 is methodologically challenging and can yield misleading over‐estimates. Many early deaths may have been due to suboptimal management, malfunctional health systems, hydroxychloroquine, sending COVID‐19 patients to nursing homes, and nosocomial infections; such deaths are partially avoidable moving forward. About 10% of the global population may be infected by October 2020. Global infection fatality rate is 0.15‐0.20% (0.03‐0.04% in those <70 years), with large variability across locations with different age‐structure, institutionalization rates, socioeconomic inequalities, population‐level clinical risk profile, public health measures, and health care. There is debate on whether at least 60% of the global population must be infected for herd immunity, or, conversely, mixing heterogeneity and pre‐existing cross‐immunity may allow substantially lower thresholds. Simulations are presented with a total of 1.58‐8.76 million COVID‐19 deaths over 5‐years (1/2020‐12/2024) globally (0.5‐2.9% of total global deaths). The most favorable figures in that range would be feasible if high risk groups can be preferentially protected with lower infection rates than the remaining population. Death toll may also be further affected by potential availability of effective vaccines and treatments, optimal management and measures taken, COVID‐19 interplay with influenza and other health problems, reinfection potential, and any chronic COVID‐19 consequences. Targeted, precise management of the pandemic and avoiding past mistakes would help minimize mortality.