bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non–heat inactivated autologous serum increases accuracy of in vitro CFSE lymphocyte proliferation test (LPT) for nickel
Authors: de Graaf Niels P. J. , Bontkes Hetty J. , Roffel Sanne , Kleverlaan Cornelis J. , Rustemeyer Thomas , Gibbs Sue , Feilzer Albert J. 
Published: March 2020

AbstractBackgroundSkin patch testing is still seen as the gold standard for the diagnosis of allergic hypersensitivity. For several metals and for patients with a suspected adverse reaction to their medical device implant material, patch testing can be unreliable. The current alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LPT) using tritiated thymidine. This method is well‐established but requires handling of radioactive material, often uses heat‐inactivated allogenic human pooled serum and cannot determine T cell subsets.ObjectiveTo develop a radioactive free LPT by using carboxyfluorescein succinimidyl ester (CFSE) and to evaluate the influence of serum source (heat‐inactivated human pooled serum [HI HPS] vs autologous serum) on the sensitivity and specificity of the nickel‐specific LPT.MethodsPeripheral blood mononuclear cells derived from nickel‐allergic patients and healthy controls were collected, labelled with CFSE and cultured in medium containing 10% HI HPS or 10% autologous serum with or without additional T cell skewing cytokine cocktails (Th1: IL‐7/IL‐12, Th2: IL‐7/IL‐4 or Th17: IL‐7/IL‐23/IL‐1β) in the absence or presence of NiSO4. The stimulation index (SI) was calculated as the ratio of divided cells, that is the percentage of CFSElow/neg CD3+CD4+ T‐lymphocytes upon nickel stimulation compared to the percentage of CFSElow/neg CD3+CD4+ T‐lymphocytes without antigen. These results were compared with the history of Ni allergy, patch test results and the MELISA test.ResultsAutologous serum positively influenced Ni‐specific proliferation while HI HPS negatively influenced Ni‐specific proliferation. The test protocol analysing CD4+ cells and autologous serum without skewing cytokines scored the best diagnostic values (sensitivity 95%; specificity 93%; and overall accuracy 94%) compared to the parallel test using HI HPS (accuracy 60%). Cytokine supplements did not further improve the test protocol which used autologous serum. The protocol using HI HPS could be further improved by addition of the cytokine skewing cocktails.ConclusionsHere, we describe an optimized and highly accurate flow cytometric LPT which comprises of CFSE‐labelled cells cultured in autologous serum (not heat inactivated) and without the presence of T cell skewing cytokines.Clinical relevanceThe sensitivity and specificity of LPT is enhanced, compared to HI HPS, when autologous serum without skewing cytokines is used.
Assessing the Impact of the NIH CTSA Program on Clinical Trials Registered With ClinicalTrials.gov
Authors: Berg Arthur 
Published: March 2020

Since 2006, the US Congress has appropriated ~ 7 billion dollars in total toward the (CTSA) program of the National Institutes of Health (NIH), representing ~ 1.5% of the NIH total budget. There is no doubt this investment has led to substantial improvements in clinical and translational research, but the impact of these large NIH‐sponsored awards to academic medical centers have largely been documented by anecdotal accomplishments. This paper provides a purely quantitative assessment of the impact of these awards on clinical trials registered on ClinicalTrials.gov. In particular, we find a dramatic increase in the number of registered clinical trials and clinical trial enrollment associated with the CTSA grant award. Additionally, the impact is shown to be magnified with the number of years of receiving CTSA funding.
Associations of CYP2C9 and CYP2C19 Pharmacogenetic Variation with Phenytoin‐Induced Cutaneous Adverse Drug Reactions
Authors: Fohner Alison E. , Rettie Allan E. , Thai Khanh K. , Ranatunga Dilrini K. , Lawson Brian L. , Liu Vincent X. , Schaefer Catherine A. 
Published: March 2020

The role of cytochrome P450 (CYP)2C9 and CYP2C19 genetic variation in risk for phenytoin‐induced cutaneous adverse drug events is not well understood independently of the human leukocyte antigen B (HLA‐B)*15:02 risk allele. In the multi‐ethnic resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, we identified 382 participants who filled a phenytoin prescription between 2005 and 2017. These participants included 21 people (5%) who self‐identified as Asian, 18 (5%) as black, 29 (8%) as white Hispanic, and 308 (81%) as white non‐Hispanic. We identified 264 (69%) CYP2C9*1/*1, 77 (20%) CYP2C9*1/*2, and 29 (8%) CYP2C9*1/*3. We also determined CYP2C19 genotypes, including 112 with the increased activity CYP2C19*17 allele. Using electronic clinical notes, we identified 32 participants (8%) with phenytoin‐induced cutaneous adverse events recorded within 100 days of first phenytoin dispensing. Adjusting for age, sex, daily dose, and race/ethnicity, participants with CYP2C9*1/*3 or CYP2C9*2/*2 genotypes were more likely to develop cutaneous adverse events compared with CYP2C9*1/*1 participants (odds ratio 4.47; 95% confidence interval 1.64–11.69; P < 0.01). Among participants with low‐intermediate and poor CYP2C9 metabolizer genotypes, eight (22%) who also had extensive and rapid CYP2C19 metabolizer genotypes experienced cutaneous adverse events, compared with none of those who also had intermediate CYP2C19 metabolizer genotypes (P = 0.17). Genetic variation reducing CYP2C9 metabolic activity may increase risk for phenytoin‐induced cutaneous adverse events in the absence of the HLA‐B*15:02 risk allele.
Tag‐less patency capsule for suspected small bowel stenosis: Nationwide multicenter prospective study in Japan
Authors: Nakamura Masanao , Watanabe Kenji , Ohmiya Naoki , Hirai Fumihito , Omori Teppei , Tokuhara Daisuke , Nakaji Konosuke , Nouda Sadaharu , Esaki Motohiro , Sameshima Yukinori , Goto Hidemi , Terano Akira , Tajiri Hisao , Matsui Toshiyuki ,   J‐POP study group
Published: March 2020

Study aimsThe PillCam patency capsule (PPC) is an Agile tag‐less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention.MethodsThis prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively.ResultsOf 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn’s disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non‐confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels <4.0 g/dL, and previous small bowel obstruction (adjusted odds ratios: 4.21, 2.60, 2.47, 2.12, and 2.00; 95% confidence intervals: 2.62–6.78, 1.62–4.17, 1.43–4.27, 1.32–3.40, and 1.15–3.47, respectively).ConclusionsThe PillCam™ patency capsule helped preclude SBCE retention in most patients, but its accurate localization was essential for cases without excretion (Study registered the University Hospital Medical Information Network, #UMIN000010513).
Disentangling the effects of plant species invasion and urban development on arthropod community composition
Authors: Jesse Wendy A. M. , Molleman Jasper , Franken Oscar , Lammers Mark , Berg Matty P. , Behm Jocelyn E. , Helmus Matthew R. , Ellers Jacintha 
Published: March 2020

AbstractUrban development and species invasion are two major global threats to biodiversity. These threats often co‐occur, as developed areas are more prone to species invasion. However, few empirical studies have tested if both factors affect biodiversity in similar ways. Here we study the individual and combined effects of urban development and plant invasion on the composition of arthropod communities. We assessed 36 paired invaded and non‐invaded sample plots, invaded by the plant Antigonon leptopus, with half of these pairs located in natural and the other half in developed land‐use types on the Caribbean island of St. Eustatius. We used several taxonomic and functional variables to describe community composition and diversity. Our results show that both urban development and A. leptopus invasion affected community composition, albeit in different ways. Development significantly increased species richness and exponential Shannon diversity, while invasion had no effect on these variables. However, invasion significantly increased arthropod abundance and caused biotic homogenization. Specifically, uninvaded arthropod communities were distinctly different in species composition between developed and natural sites, while they became undistinguishable after A. leptopus invasion. Moreover, functional variables were significantly affected by species invasion, but not by urban development. Invaded communities had higher community‐weighted mean body size and the feeding guild composition of invaded arthropod communities was characterized by the exceptional numbers of nectarivores, herbivores, and detritivores. With the exception of species richness and exponential Shannon diversity, invasion influenced four out of six response variables to a greater degree than urban development did. Hence, we can conclude that species invasion is not just a passenger of urban development but also a driver of change.
Pharmacokinetics of low‐dose methotrexate in horses
Authors: Rostang Antoine , Desjardins Isabelle , Espana Bernadette , Panzuti Pauline , Berny Philippe , Prouillac Caroline , Pin Didier 
Published: March 2020

AbstractThis study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long‐term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10‐week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC‐MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min−1 kg−1 (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7‐hydroxy‐MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg−1 week−1 may be safe and relevant in horses, although this has yet to be clinically confirmed.
Synergistic effects: a common theme in mixed‐species litter decomposition
Authors: Liu Jun , Liu Xiaoyu , Song Qingni , Compson Zacchaeus G. , LeRoy Carri J. , Luan Fenggang , Wang Hui , Hu Yalin , Yang Qingpei 
Published: March 2020

Summary

Litter decomposition plays a key role in nutrient cycling across ecosystems, yet to date, we lack a comprehensive understanding of the nonadditive decomposition effects in leaf litter mixing experiments.

To fill that gap, we compiled 69 individual studies with the aim to perform two meta‐analyses on nonadditive effects.

We show that a significant synergistic effect (faster decomposition in mixtures than expected) occurs at a global scale, with an average increase of 3–5% in litter mixtures. In particular, low‐quality litter in mixtures shows a significant synergistic effect, while additive effects are observed for high‐quality species. Additionally, synergistic effects turn into antagonistic effects when soil fauna are absent or litter is in very late stages of decomposition (near‐humus). In contrast to temperate and tropical areas, studies in boreal regions show significant antagonistic effects.

Our two meta‐analyses provide a systematic evaluation of nonadditive effects in mixed litter decomposition studies and show that litter quality alters the effects of litter mixing. Our results indicate that nutrient transfer, soil fauna and inhibitory secondary compounds can influence mixing effects. We also highlight that synergistic and antagonistic effects occur concurrently, and the final litter mixing effect results from the interplay between them.
Moral Explanations of Moral Beliefs: Inappropriate to Demand Them?
Authors: Tilley John J. 
Published: March 2020

AbstractA familiar claim, meant as a challenge to moral knowledge, is that we can credibly accept putative moral facts just in case they explain natural facts. This article critically addresses Elizabeth Tropman's response to a version of that claim. Her response has interest partly because it falls within, and extends, an influential philosophical tradition – that of trying to expose (some) sceptical challenges as spurious or ill‐conceived. Also, Tropman's target is not just any version of the claim just mentioned. It is Gilbert Harman's classic version, according to which putative moral facts must earn credibility by explaining the formation of moral beliefs. This version has wide influence, and variations of it are possible in many areas. Tropman's response is thus well worth attention.
Feline post‐sterilization hyphema
Authors: Schenk Alex P. , McGrath Ann M. , Beatty Cheryl A. , Ottney Jennifer L. , Gratch Ellen K. , Robertson Sheilah A. , Komáromy András M. 
Published: March 2020

AbstractObjectiveTo determine incidence and risk factors of post‐sterilization hyphema in shelter cats.Animals studiedRetrospective medical record review of 1204 cats and prospective screening of 195 cats.ProceduresThe study consisted of three parts: (a) Survey responses were collected from 20 veterinarians, who perform high‐quality high‐volume spay‐neuter (HQHVSN) in both shelter and public clinic settings; (b) medical records of 1204 cats were analyzed retrospectively over a 14‐month time period; and (c) ophthalmic examinations, including tonometry, were performed prospectively on 195 cats before and after sterilization surgery over 8 weeks.ResultsNine of 20 surveyed veterinarians reported having witnessed hyphema in cats following sterilization surgery. Retrospective review of 1204 medical record and prospective screening of 195 cats showed that three juvenile (<1 year of age) male cats (<2 kg) developed hyphema within 1 hour following surgery (0.2% incidence). In all three affected cats, anesthesia was induced with tiletamine/zolazepam (3 of 523 cats induced with this drug combination; 0.6% incidence), and hyphema resolved within 20 hours. Mean intraocular pressures as measured by Icare® TonoVet were (mean ± standard deviation) 11.5 ± 3.8 mm Hg and 21.7 ± 4.6 mm Hg for juvenile (<1 year of age) and adult (>1 year of age) cats, respectively.ConclusionsSurvey responses and three observed cases confirm the existence of feline post‐sterilization hyphema with an estimated incidence of 0.2%. The underlying mechanism for this occurrence remains unknown.
Advances in Bayesian Probabilistic Modeling for Industrial Applications
Authors: Ghosh Sayan , Pandita Piyush , Atkinson Steven , Subber Waad , Zhang Yiming , Kumar Natarajan Chennimalai , Chakrabarti Suryarghya , Wang Liping 
Published: March 2020

Abstract
Industrial applications frequently pose a notorious challenge for state-of-the-art methods in the contexts of optimization, designing experiments and modeling unknown physical response. This problem is aggravated by limited availability of clean data, uncertainty in available physics-based models and additional logistic and computational expense associated with experiments. In such a scenario, Bayesian methods have played an impactful role in alleviating the aforementioned obstacles by quantifying uncertainty of different types under limited resources. These methods, usually deployed as a framework, allows decision makers to make informed choices under uncertainty while being able to incorporate information on the fly, usually in the form of data, from multiple sources while being consistent with the physical intuition about the problem. This is a major advantage that Bayesian methods bring to fruition especially in the industrial context. This paper is a compendium of the Bayesian modeling methodology that is being consistently developed at GE Research. The methodology, called GE's Bayesian hybrid modeling (GEBHM), is a probabilistic modeling method, based on the Kennedy and O'Hagan framework, that has been continuously scaled-up and industrialized over several years. In this work, we explain the various advancements in GEBHM's methods and demonstrate their impact on several challenging industrial problems.
The evolutionary dynamics and fitness landscape of clonal hematopoiesis
Authors: Watson Caroline J. , Papula A. L. , Poon Gladys Y. P. , Wong Wing H. , Young Andrew L. , Druley Todd E. , Fisher Daniel S. , Blundell Jamie R. 
Published: March 2020

Evolutionary dynamics in hematopoiesisCells accumulate mutations as we age, and these mutations can be a source of diseases such as cancer. How cells containing mutations evolve, are maintained, and proliferate within the body has not been well characterized. Using a quantitative framework, Watsonet al.applied population genetic theory to estimate mutation accumulation in cells in blood from sequencing data derived from nearly 50,000 healthy individuals (see the Perspective by Curtis). By evaluating how mutations differ between blood cell populations, a phenomenon known as clonal hematopoiesis, the researchers could observe how recurrent mutations can drive certain clonal lineages to high frequencies within an individual. The risk of specific mutations, some of which are associated with leukemias, rising to high frequencies may therefore be a function of cellular selection and the age at which the mutation originated.Science, this issue p.1449; see also p.1426
Costs and consequences of using average demand to plan baseline nurse staffing levels: a computer simulation study
Authors: Saville Christina , Monks Thomas , Griffiths Peter , Ball Jane Elisabeth 
Published: March 2020

BackgroundPlanning numbers of nursing staff allocated to each hospital ward (the ‘staffing establishment’) is challenging because both demand for and supply of staff vary. Having low numbers of registered nurses working on a shift is associated with worse quality of care and adverse patient outcomes, including higher risk of patient safety incidents. Most nurse staffing tools recommend setting staffing levels at the average needed but modelling studies suggest that this may not lead to optimal levels.ObjectiveUsing computer simulation to estimate the costs and understaffing/overstaffing rates delivered/caused by different approaches to setting staffing establishments.MethodsWe used patient and roster data from 81 inpatient wards in four English hospital Trusts to develop a simulation of nurse staffing. Outcome measures were understaffed/overstaffed patient shifts and the cost per patient-day. We compared staffing establishments based on average demand with higher and lower baseline levels, using an evidence-based tool to assess daily demand and to guide flexible staff redeployments and temporary staffing hires to make up any shortfalls.ResultsWhen baseline staffing was set to meet the average demand, 32% of patient shifts were understaffed by more than 15% after redeployment and hiring from a limited pool of temporary staff. Higher baseline staffing reduced understaffing rates to 21% of patient shifts. Flexible staffing reduced both overstaffing and understaffing but when used with low staffing establishments, the risk of critical understaffing was high, unless temporary staff were unlimited, which was associated with high costs.ConclusionWhile it is common practice to base staffing establishments on average demand, our results suggest that this may lead to more understaffing than setting establishments at higher levels. Flexible staffing, while an important adjunct to the baseline staffing, was most effective at avoiding understaffing when high numbers of permanent staff were employed. Low staffing establishments with flexible staffing saved money because shifts were unfilled rather than due to efficiencies. Thus, employing low numbers of permanent staff (and relying on temporary staff and redeployments) risks quality of care and patient safety.
Integrated care programmes for sport and work participation, performance of physical activities and quality of life among orthopaedic surgery patients: a systematic review with meta-analysis
Authors: Coenen Pieter , Hulsegge Gerben , Daams Joost G , van Geenen Rutger C , Kerkhoffs Gino M , van Tulder Maurits W , Huirne Judith A , Anema Johannes R , Kuijer P Paul 
Published: March 2020

ObjectivesOrthopaedic surgery is primarily aimed at improving function and pain reduction. Additional integrated care may enhance patient’s participation in sports and work, possibly improving performance of physical activities and quality of life (QoL). We aimed to assess the effectiveness of integrated care among orthopaedic surgery patients.DesignSystematic review with meta-analysis.Data sourceMedline, EMBASE and CINAHL (until 17 June 2019).Eligibility for selecting studiesWe searched for controlled studies on integrated care interventions consisting of active referral to case managers, rehabilitation with participation-based goals and/or e/mHealth, with outcomes of sports and work participation, performance of physical activities and/or QoL. Outcomes were normalised to 0–100 scales and statistically pooled.ResultsSeventeen articles (n=2494) of moderate quality were included reporting on patients receiving back, upper limb, knee or hip surgery. Only one study reported on return to sports and found no significant benefit. For return to work, one study did (90% vs 82%) and one did not (relative risk=1.18 (0.80 to 1.70)) observe significant benefits. Integrated care showed small effects for improving performance of physical activities (2.69 (–0.20 to 5.58); eight studies, n=1267) and QoL (2.62 (1.16 to 5.05); nine studies, n=1158) compared with usual care.Summary/ConclusionWe found insufficient and inconsistent evidence for the effectiveness of integrated care for orthopaedic surgery patients regarding sport and work participation. Small effects were found for performance of physical activities and QoL. High quality research on integrated care focusing on sports and work participation is needed before integrated care can be implemented for orthopaedic surgery patients.