bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiplatelet Therapy After Noncardioembolic Stroke
Authors: Greving Jacoba P. , Diener Hans-Christoph , Reitsma Johannes B. , Bath Philip M. , Csiba László , Hacke Werner , Kappelle L. Jaap , Koudstaal Peter J. , Leys Didier , Mas Jean-Louis , Sacco Ralph L. , Algra Ale ,   for the Cerebrovascular Antiplatelet Trialists’ Collaborative Group
Published: June 2019

Background and Purpose—
We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients’ demographic and clinical characteristics.

Methods—
We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization.

Results—

Aspirin/dipyridamole combination (RR
NMA-adj
, 0.83; 95% CI, 0.74–0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RR
NMA-adj
, 0.88; 95% CI, 0.78–0.98), and aspirin/clopidogrel combination (RR
NMA-adj
, 0.83; 95% CI, 0.71–0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RR
NMA-adj
, 0.99; 95% CI, 0.93–1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RR
NMA-adj
, 3.9 versus 1.7).

Conclusions—
Results favor clopidogrel and aspirin/dipyridamole combination for long-term secondary prevention after noncardioembolic stroke or transient ischemic attack, regardless of patient characteristics. Aspirin/clopidogrel combination was associated with a significantly higher risk of major bleeding compared with other antiplatelet regimens.
Changes in Frequency of Large Precipitation Accumulations over Land in a Warming Climate from the CESM Large Ensemble: The Roles of Moisture, Circulation, and Duration
Authors: Norris Jesse , Chen Gang , Neelin J. David 
Published: June 2019

ABSTRACTProjected changes in the frequency of major precipitation accumulations (hundreds of millimeters), integrated over rainfall events, over land in the late twenty-first century are analyzed in the Community Earth System Model (CESM) Large Ensemble, based on the RCP8.5 scenario. Accumulation sizes are sorted by the local average recurrence interval (ARI), ranging from 0.1 to 100 years, for the current and projected late-twenty-first-century climates separately. For all ARIs, the frequency of exceedance of the given accumulation size increases in the future climate almost everywhere, especially for the largest accumulations, with the 100-yr accumulation becoming about 3 times more frequent, averaged over the global land area. The moisture budget allows the impacts of individual factors—moisture, circulation, and event duration—to be isolated. In the tropics, both moisture and circulation cause large future increases, enhancing the 100-yr accumulation by 23% and 13% (average over tropical land), and are individually responsible for making the current-climate 100-yr accumulation 2.7 times and 1.8 times more frequent, but effects of shorter durations slightly offset these effects. In the midlatitudes, large accumulations become about 5% longer in duration, but are predominantly controlled by enhanced moisture, with the 100-yr accumulation (land average) becoming 2.4 times more frequent, and 2.2 times more frequent due to moisture increases alone. In some monsoon-affected regions, the 100-yr accumulation becomes more than 5 times as frequent, where circulation changes are the most impactful factor. These projections indicate that changing duration of events is a relatively minor effect on changing accumulations, their future enhancement being dominated by enhanced intensity (the combination of moisture and circulation).
A systematic review of factors that influence the efficacy of cognitive remediation therapy in schizophrenia
Authors: Reser Maree P , Slikboer Reneta , Rossell Susan L 
Published: June 2019

Objective: Cognitive remediation therapy is a moderately effective intervention for ameliorating cognitive deficits in individuals with schizophrenia-related disorders. With reports of considerable variability in individual response to cognitive remediation therapy, we need to better understand factors that influence cognitive remediation therapy efficacy to realise its potential. A systematic review was conducted to identify and evaluate predictors of cognitive outcome. Methods: An electronic database search was conducted identifying peer-reviewed articles examining predictors of cognitive response to cognitive remediation therapy. Results: A total of 40 articles accounting for 1681 cognitive remediation therapy participants were included; 81 distinct predictors of cognitive response were identified. Data synthesis and discussion focused on 20 predictors examined a minimum three times in different studies. Few of the examined predictors of cognitive outcome following cognitive remediation therapy were significant when examined through systematic review. A strong trend was found for baseline cognition, with reasoning and problem solving and working memory being strongly predictive of within-domain improvement. Training task progress was the most notable cross-domain predictor of cognitive outcome. Conclusion: It remains unclear why a large proportion of participants fail to realise cognitive benefit from cognitive remediation therapy. However, when considering only those variables where a majority of articles reported a statistically significant association with cognitive response to cognitive remediation therapy, three stand out: premorbid IQ, baseline cognition and training task progress. Each of these relates in some way to an individual’s capacity or potential for change. There is a need to consolidate investigation of potential predictors of response to cognitive remediation therapy, strengthening the evidence base through replication and collaboration.
Artificial neural network optimizes self-examination of osteoporosis risk in women
Authors: Meng Jia , Sun Ning , Chen Yali , Li Zhangming , Cui Xiaomeng , Fan Jingxue , Cao Hailing , Zheng Wangping , Jin Qiying , Jiang Lihong , Zhu Wenliang 
Published: June 2019

Objective This study aimed to investigate the application of an artificial neural network (ANN) in optimizing the Osteoporosis Self-Assessment Tool for Asians (OSTA) score. Methods OSTA score was calculated for each female participant that underwent dual-energy X-ray absorptiometry examination in two hospitals (one in each of two Chinese cities, Harbin and Ningbo). An ANN model was built using age and weight as input and femoral neck T-score as output. Osteoporosis risk screening by joint application of ANN and OSTA score was evaluated by receiver operating characteristic curve analysis. Results Nearly 90% of women with dual-energy X-ray absorptiometry-determined femoral neck osteoporosis were ≥60 years old. The ANN with age and weight as input and OSTA score both identified osteoporosis, with respective accuracy rates of 78.8% and 78.3%. However, both methods failed to identify osteoporosis in women < 60 years old. Compared with OSTA score alone, combined use of the two tools increased the rate of osteoporosis recognition among women > 80 years old. Conclusions OSTA score-mediated osteoporosis risk screening should be restricted to women ≥60 years old. Joint application of ANN and OSTA improved osteoporosis risk screening among Chinese women > 80 years old.
Ipsilateral Hypertrophy of the Mastoid Process in Surgical Cases of Congenital Muscular Torticollis
Authors: Kim Hyun Gi , Yim Shin-Young 
Published: June 2019

Objective: This study was to investigate ipsilateral hypertrophy of the mastoid process in the patients with congenital muscular torticollis (CMT). Design: Retrospective cross-sectional study. Patients: Children with CMT. Methods: A total of 212 surgical cases of patients with CMT (age: 50.9 ± 44.3 months) and 212 age- and gender-matched controls (age: 50.4 ± 44.2 months) were included. The mastoid process volume was calculated and compared for both groups on the computed tomography axial images. A linear regression analysis was performed between the age and the intrasubject volume difference in the mastoid process. Results: The volume of the mastoid process in the CMT side was significantly larger than that of the non-CMT side in the CMT group (32.2 ± 30.3 cm3 vs 21.9 ± 22.8 cm3; P < .001). In the control group, there was no significant difference between the volume of the right and left mastoid process (21.6 ± 24.6 cm3 vs 21.2 ± 23.8 cm3; P = .472). The intrasubject volume difference in the mastoid process in the CMT group showed a linear increase with the age (adjusted R 2 = 0.286; P < .001), and the volumetric asymmetry of the mastoid process became more severe over age compared to the control group. Conclusion: We showed ipsilateral hypertrophy of the mastoid process in patients with CMT and demonstrated that the volumetric asymmetry increased with age.
Reconstruction of Nasal Defects With Dermal Skin Substitutes—A Retrospective Study of 36 Defects
Authors: Moratin Katharina , Koch Philipp-Sebastian , Benecke Johannes , Orouji Azadeh , Bauer Corinne , Faulhaber Jörg , Koenen Wolfgang , Felcht Moritz 
Published: June 2019

Objectives: It is uncertain whether dermal regeneration templates (DRTs) are helpful to reconstruct nasal defects. The aim of this study was to assess whether the aesthetic subunits determine the outcome. Methods: In this unicentric, retrospective study, the surgical procedures and outcomes of patients who received DRTs to reconstruct nasal defects were assessed and compared with the involved aesthetic subunits. Results: DRTs were used for reconstruction of 36 nasal defects in 35 patients with involvement of 76 aesthetic subunits: nasal sidewall (n = 21), nasal ala (n = 13), nasal tip/columella (n = 12, n = 1, respectively), nasal dorsum (n = 12), and extranasal aesthetic areas (n = 17). Fifty-eight nasal and 8 extranasal aesthetic subunits were reconstructed with DRTs, 10 subunits with a flap. Twenty-nine of 36 defects healed without any complications (80.5%). All reconstructed nasal tips/columella and the nasal dorsa healed without any complications. Region-specific complications were retraction of the ala rim (4/12; 33.3% of the patients with involvement of the nasal ala) and the formation of a fistula in the nasal sidewall (1/21; 4.8%). Region-specific complications of extranasal subunits were the development of an ectropium (2/3; 66.7% of the patients with involvement of the lower lid). Conclusions: DRTs can be helpful to reconstruct nasal defects. However, if the defect involves the aesthetic subunits nasal ala or the infraorbital region, different techniques should be preferred.
Analyzing ICU Patient Room Environmental Quality Through Unoccupied, Normal, and Emergency Procedure Modes: An EQI Evaluation
Authors: Wagner Jennifer A. , Greeley Damon G. , Gormley Thomas C. , Markel Troy A. 
Published: June 2019

Background: There is increasing need to perform invasive surgical procedures in intensive care units (ICUs). Traditional ICUs differ from operating rooms (ORs) in several ways including air changes per hour (ACH) and pressurization. Increased ACH and positive pressurization of ORs intend to provide more aseptic environments for surgery. Development of procedure ready ICUs that transition through unoccupied, occupied, and procedure modes is one solution to improve environmental quality when performing surgery in ICUs. This study assessed the efficacy of two airflow control systems, variable air volume (VAV) and Venturi control, in preventing contaminants from entering ICU from adjacent corridors. Study Design: Controlled contaminants, sulfur hexafluoride (SF6) and baker’s yeast (CFU/m3), were released in the corridor adjacent to the ICU. SF6 and CFU/m3 were detected inside the ICU at the patient bed during a dynamic simulation of code blue event. VAV and Venturi were compared as they cycled the room through unoccupied, occupied, and procedure modes. Results: VAV and Venturi showed significantly fewer CFU/m3 at the patient bed than corridor point of release ( p < .05). Although not significant, Venturi cultured 14% fewer CFU/m3 than VAV at the patient bed. There was less SF6 detected at the patient bed with VAV and Venturi ( p < .05). There was less SF6 detected at the patient bed with Venturi compared to VAV ( p < .05). Venturi transitioned between modes faster than VAV ( p < .05). Conclusion: Using efficient mode transitioning systems in ICUs may be effective in creating a more aseptic environment that mimics that of the OR.
STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial
Authors:   The STARRT-AKI Investigators
Published: June 2019

Background: The optimal timing of renal replacement therapy (RRT) initiation in critically ill patients with acute kidney injury (AKI) remains controversial. Objective: In critically ill patients with AKI, to determine whether the accelerated initiation of RRT reduces mortality compared to a strategy of standard RRT initiation whereby RRT is initiated if urgent complications of AKI arise or based on clinician judgment. Design: Pragmatic allocation-concealed open-label randomized controlled trial. Setting: Up to 170 centers in Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Ireland, Italy, Finland, New Zealand, Switzerland, the United Kingdom, and the United States. Patients: We will enroll at least 2,866 critically ill patients with AKI stages 2 or 3 (defined as doubling of serum creatinine from baseline or serum creatinine ≥354 µmol/L with increase of ≥27 µmol/L from baseline or urine output <6 mL/kg in preceding 12 hours). Patients will be excluded if 1 or more of the following is/are present: potassium >5.5 mmol/L; bicarbonate <15 mmol/L; concomitant intoxication necessitating RRT; philosophy of care precluding escalation to RRT; any RRT in preceding 2 months; kidney transplant within the past year; preexisting estimated glomerular filtration rate <20 mL/min/1.73 m2; AKI etiology attributable to obstruction, glomerulonephritis, vasculitis, microangiopathy, or acute interstitial nephritis; clinician opinion that urgent RRT is mandated; or clinician opinion that RRT must be deferred. Methods: Participants will be randomized to one of two strategies: accelerated RRT initiation, which entails the initiation of RRT within 12 hours of the patient fulfilling all eligibility criteria, or standard RRT initiation, whereby clinicians would be discouraged from initiating RRT unless a conventional trigger for RRT initiation arises or if AKI persists for ≥72 hours. Measurements: The primary outcome is all-cause mortality at 90 days following randomization. Key secondary outcomes include RRT dependence, residual kidney function, health services use, and health-related quality of life, all assessed at 90 days after randomization. In jurisdictions where it is feasible, participants will be followed through day 365 using linked administrative data. Results: Through March 18, 2019, we have recruited 2623 (92% of target) participants. Limitations: Reliance on physician declaration of equipoise may create heterogeneity across the trial population; open-label design may introduce bias and uneven postrandomization cointerventions; variations in practice (eg, choice of RRT modality and RRT prescription) likely exist across sites. Conclusions: Once complete, the STARRT-AKI trial will provide the most robust evidence to date to guide clinical practice on the optimal timing of RRT initiation among critically ill patients with AKI. Trial registration: Clinicaltrials.gov NCT02568722.
Confounding of linkage disequilibrium patterns in large scale DNA based gene-gene interaction studies
Authors: Joiret Marc , Mahachie John Jestinah M. , Gusareva Elena S. , Van Steen Kristel 
Published: June 2019

AbstractBackgroundIn Genome-Wide Association Studies (GWAS), the concept of linkage disequilibrium is important as it allows identifying genetic markers that tag the actual causal variants. In Genome-Wide Association Interaction Studies (GWAIS), similar principles hold for pairs of causal variants. However, Linkage Disequilibrium (LD) may also interfere with the detection of genuine epistasis signals in that there may be complete confounding between Gametic Phase Disequilibrium (GPD) and interaction. GPD may involve unlinked genetic markers, even residing on different chromosomes. Often GPD is eliminated in GWAIS, via feature selection schemes or so-called pruning algorithms, to obtain unconfounded epistasis results. However, little is known about the optimal degree of GPD/LD-pruning that gives a balance between false positive control and sufficient power of epistasis detection statistics. Here, we focus on Model-Based Multifactor Dimensionality Reduction as one large-scale epistasis detection tool. Its performance has been thoroughly investigated in terms of false positive control and power, under a variety of scenarios involving different trait types and study designs, as well as error-free and noisy data, but never with respect to multicollinear SNPs.ResultsUsing real-life human LD patterns from a homogeneous subpopulation of British ancestry, we investigated the impact of LD-pruning on the statistical sensitivity of MB-MDR. We considered three different non-fully penetrant epistasis models with varying effect sizes. There is a clear advantage in pre-analysis pruning using sliding windows atr2of 0.75 or lower, but using a threshold of 0.20 has a detrimental effect on the power to detect a functional interactive SNP pair (power < 25%). Signal sensitivity, directly using LD-block information to determine whether an epistasis signal is present or not, benefits from LD-pruning as well (average power across scenarios: 87%), but is largely hampered by functional loci residing at the boundaries of an LD-block.ConclusionsOur results confirm that LD patterns and the position of causal variants in LD blocks do have an impact on epistasis detection, and that pruning strategies and LD-blocks definitions combined need careful attention, if we wish to maximize the power of large-scale epistasis screenings.
Gait-based age estimation using multi-stage convolutional neural network
Authors: Sakata Atsuya , Takemura Noriko , Yagi Yasushi 
Published: June 2019

Abstract
Gait-based age estimation has been extensively studied for various applications because of its high practicality. In this paper, we propose a gait-based age estimation method using convolutional neural networks (CNNs). Because gait features vary depending on a subject’s attributes, i.e., gender and generation, we propose the following three CNN stages: (1) a CNN for gender estimation, (2) a CNN for age-group estimation, and (3) a CNN for age regression. We conducted experiments using a large population gait database and confirm that the proposed method outperforms state-of-the-art benchmarks.
The Use and Abuse of Growth Hormone in Sports
Authors: Holt Richard I G , Ho Ken K Y 
Published: June 2019

AbstractGH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes’ biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.
A trap mutant reveals the physiological client spectrum of TRC40
Authors: Coy-Vergara Javier , Rivera-Monroy Jhon , Urlaub Henning , Lenz Christof , Schwappach Blanche 
Published: June 2019

ABSTRACT
The transmembrane recognition complex (TRC) pathway targets tail-anchored (TA) proteins to the membrane of the endoplasmic reticulum (ER). While many TA proteins are known to be able to use this pathway, it is essential for the targeting of only a few. Here, we uncover a large number of TA proteins that engage with TRC40 when other targeting machineries are fully operational. We use a dominant-negative ATPase-impaired mutant of TRC40 in which aspartate 74 was replaced by a glutamate residue to trap TA proteins in the cytoplasm. Manipulation of the hydrophobic TA-binding groove in TRC40 (also known as ASNA1) reduces interaction with most, but not all, substrates suggesting that co-purification may also reflect interactions unrelated to precursor protein targeting. We confirm known TRC40 substrates and identify many additional TA proteins interacting with TRC40. By using the trap approach in combination with quantitative mass spectrometry, we show that Golgi-resident TA proteins such as the golgins golgin-84, CASP and giantin as well as the vesicle-associated membrane-protein-associated proteins VAPA and VAPB interact with TRC40. Thus, our results provide new avenues to assess the essential role of TRC40 in metazoan organisms.
This article has an associated First Person interview with the first author of the paper.