bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of linguistic complexity in Hearthstone: a resource and an example in linguistic game studies
Authors: Jacquin Jérôme , Xanthos Aris 
Published: November 2020

Abstract
The present paper uses corpus linguistics methods to study a born-digital cultural artifact, namely the collectible card game Hearthstone, released in 2014 and still under active development in 2020. As indicated by the developers’ public statements, such a game, which is framed as an ongoing service rather than a final product, needs to strike a balance between two conflicting constraints: while the game must remain easily accessible at any stage of its development to increase the player base, the player’s experience must be constantly renewed to keep the existing player base from getting bored and leaving the game. In practice, this translates into the regular addition of new card sets by the developer. Our hypothesis is that linguistic traces of these opposite forces can be found in the evolution of lexical diversity in the text of the game’s rules, as opposed to its ‘flavour’ text, which plays no role in the game’s mechanics. To test this hypothesis, a corpus documenting the first two years of the game has been built and it is distributed in open access. The analysis of lexical diversity in these data shows that the rule text vocabulary is both highly controlled and subject to steady diversification. We view these features as reflecting stakes that characterise the ongoing management and development of a game-as-a-service like Hearthstone.
COVID-19 Investigational Treatments in Use Among Hospitalized Patients Identified Through the US Coronavirus Disease 2019–Associated Hospitalization Surveillance Network, March 1–June 30, 2020
Authors: Acosta Anna M , Mathis Adria L , Budnitz Daniel S , Geller Andrew I , Chai Shua J , Alden Nisha B , Meek James , Anderson Evan J , Ryan Patricia , Kim Sue , Como-Sabetti Kathryn , Torres Salina , Dufort Elizabeth , Bennett Nancy M , Billing Laurie M , Sutton Melissa , Keipp Talbot H , George Andrea , Pham Huong , Hall Aron J , Fry Alicia , Garg Shikha , Kim Lindsay 
Published: November 2020

Abstract
Using a coronavirus disease 2019 (COVID-19)–associated hospitalization surveillance network, we found that 42.5% of hospitalized COVID-19 cases with available data from March 1–June 30, 2020, received ≥1 COVID-19 investigational treatment. Hydroxychloroquine, azithromycin, and remdesivir were used frequently; however, hydroxychloroquine and azithromycin use declined over time, while use of remdesivir increased.
Light curve analysis of six totally eclipsing W UMa binaries
Authors: Latković Olivera , Čeki Atila 
Published: November 2020

Abstract
We analyze multicolor light curves of six totally eclipsing, short-period W UMa binaries and derive, for the first time, their orbital and stellar parameters. The mass ratios are established robustly through an automated q-search procedure that performs an heuristic survey of the parameter space. Five stars belong to the W and one to the A subtype. The mass ratios range from 0.23 to 0.51 and the fillouts from $10\%$ to $15\%$. We estimate the ages and discuss the evolutionary status of these objects in comparison with a sample of other short-period W UMa binaries from the literature.
Eastern US deciduous tree species respond dissimilarly to declining soil moisture but similarly to rising evaporative demand
Authors: Denham Sander O , Oishi A Christopher , Miniat Chelcy F , Wood Jeffrey D , Yi Koong , Benson Michael C , Novick Kimberly A 
Published: November 2020

Abstract
Hydraulic stress in plants occurs under conditions of low water availability (soil moisture; θ) and/or high atmospheric demand for water (vapor pressure deficit; D). Different species are adapted to respond to hydraulic stress by functioning along a continuum where, on one hand, they close stomata to maintain a constant leaf water potential (ΨL) (isohydric species), and on the other hand, they allow ΨL to decline (anisohydric species). Differences in water-use along this continuum are most notable during hydrologic stress, often characterized by low θ and high D; however, θ and D are often, but not necessarily, coupled at time scales of weeks or longer, and uncertainty remains about the sensitivity of different water-use strategies to these variables. We quantified the effects of both θ and D on canopy conductance (Gc) among widely distributed canopy-dominant species along the isohydric–anisohydric spectrum growing along a hydroclimatological gradient. Tree-level Gc was estimated using hourly sap flow observations from three sites in the eastern United States: a mesic forest in western North Carolina and two xeric forests in southern Indiana and Missouri. Each site experienced at least 1 year of substantial drought conditions. Our results suggest that sensitivity of Gc to θ varies across sites and species, with Gc sensitivity being greater in dry than in wet sites, and greater for isohydric compared with anisohydric species. However, once θ limitations are accounted for, sensitivity of Gc to D remains relatively constant across sites and species. While D limitations to Gc were similar across sites and species, ranging from 16 to 34% reductions, θ limitations to Gc ranged from 0 to 40%. The similarity in species sensitivity to D is encouraging from a modeling perspective, though it implies that substantial reduction to Gc will be experienced by all species in a future characterized by higher D.
Sequence Resource of Bacterial Communities Associated with Hemp in Ohio
Authors: Willman Matthew , Keener Harold M. , Benitez Maria-Soledad 
Published: November 2020

In spite of changes in regulation and increased hemp cultivation and commercialization, information on hemp best production practices in the United States is scarce. Due to hemp’s human consumption, particularly as concentrated oil, hemp is often grown with low synthetic chemical inputs. Therefore, microbiome management and the use of microbial inoculants are important tools to increase hemp productivity. As a first step to characterize the hemp core microbiome, we completed a survey of bacterial communities associated with different tissue types of plants grown in a field in Ohio. This local dataset could be integrated with further hemp microbiome surveys to identify potential beneficial interactions relevant to plant health and productivity but also to evaluate microbiome impacts on product efficacy and safety. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Severity of Chronic Pain in German Adolescent School Students
Authors: Könning Anna , Rosenthal Nicola , Brown Donnamay , Stahlschmidt Lorin , Wager Julia 
Published: November 2020

Objectives:
Prevalence estimates of severe chronic pain in pediatric community samples are rare and inconclusive. This study aimed to (1) examine the prevalence of chronic pain severity grades in school children and (2) investigate differences between pain severity grades for pain-related characteristics, including pain locations, sociodemographic characteristics, emotional functioning, insomnia, school factors, and health care utilization.

Materials and Methods:
This cross-sectional observational study was conducted with 2220 school students in Germany (52% female individuals, age: M=13.0; SD=1.8; range, 10 to 18 y). Pain severity was assessed using the validated Chronic Pain Grades for adolescents. Comparisons between Chronic Pain Grade subgroups of adolescent characteristics were conducted using χ2 tests, Kruskal-Wallis tests, and 1-way analysis of variance.

Results:
In school students, 31.0% had chronic pain with 8.2% categorized as severe. Individuals with higher pain severity tended to be girls and have multisite pain, more symptoms of depression and generalized anxiety, and a higher emotional burden of pain. Individuals with higher pain severity also reported less school satisfaction, lower perceived school performance, and more insomnia. Pain medication intake and physician visits because of pain were more common in those with more severe pain.

Discussion:
Severe chronic pain affects nearly 1 in 10 adolescent school students and is associated with several negative health outcomes and increased health care utilization. It is important to ensure that specialized pain treatment programs are available to these students and that they are aware of the different negative health outcomes associated with the pain condition.
Advances of adeno-associated virus applied in gene therapy to hemophilia from bench work to the clinical use
Authors: Pei Xiaolei , Han Mingzhe , Zhang Lei 
Published: November 2020

AbstractHemophilia A and B are diseases caused by a single gene deficiency and are thus suitable for gene therapy. In recent clinical research, adeno-associated virus (AAV) was employed by several teams in the treatment of hemophilia A and B, and the outcomes were encouraging. In this review, we summarized the most recent research on the mechanism and application of AAV in the treatment of hemophilia, trying to analyze the advantages of AAV gene therapy and the main challenges in its clinical use. We also summarized the clinical trials involving hemophilia, especially those employing AAV gene therapy to treat hemophilia A and B, some of which have already been completed and some that are still ongoing. From the reports of the completed clinical trials, we tried to determine the correlations among AAV dose, AAV serotype, immune response, and gene expression time. Finally, taking into account the most recent studies investigating AAV capsid modification, transgene optimization, and AAV chaperones, we summarized the direction of basic research and clinical applications of AAV in the future.
Aptamer technology: a new approach to treat lymphoma?
Authors: Zu Youli 
Published: November 2020

Abstract
Oligonucleotide aptamers are a class of small-molecule ligands. Functionally similar to protein antibodies, aptamers can specifically bind to their targets with high affinity. Biomedical studies have revealed the potential clinical value of aptamer technology for disease diagnosis and targeted therapy. Lymphoma is a group of cancers originating from the lymphatic system. Currently, chemotherapy is the primary treatment for lymphoma, although it may cause serious side effects in patients due to lack of target specificity. Here, we selectively discuss the recent development of potential applications of aptamer technology for precision lymphoma therapy, which are able to not only achieve high therapeutic efficacy but also do not cause off-target side effects.
T cell response in patients with COVID-19
Authors: Liu Lian , Xu Ling , Lin Chen 
Published: November 2020

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the third zoonotic coronavirus to have an outbreak in the first two decades of the 21st century. Human-to-human transmission of this virus has threatened thousands of lives around the world. SARS-CoV-2 shares 79% and 50% sequence homology with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Like SARS-CoV and MERS-CoV infection, evidence has shown that SARS-CoV-2 infection also causes acute tissue damage due to a pathological immune response, particularly in severe cases. T cells play an important role in virus clearance and prevention, and in this paper, we summarize dynamic changes in the T cell count, subsets, phenotype, and function in Coronavirus Disease 2019 (COVID-19) patients based on current clinical reports. This review may help to better understand the pathological immune response of T cells and facilitate making better therapeutic strategies for patients with SARS-CoV-2 infection.
Cardiac Myosin Activation for the Treatment of Systolic Heart Failure
Authors: Bernier Thomas D. , Buckley Leo F. 
Published: November 2020

Abstract:
Left ventricular systolic dysfunction is the hallmark pathology in heart failure with reduced ejection fraction. Increasing left ventricular contractility with beta-adrenergic receptor agonists, phosphodiesterase-3 inhibitors, or levosimendan has failed to improve clinical outcomes and, in some situations, increased the risk of sudden cardiac death. Beta-adrenergic receptor agonists and phosphodiesterase-3 inhibitors retain an important role in advanced heart failure. Thus, there remains an unmet need for safe and effective therapies to improve left ventricular systolic function. Two novel cardiac myotropes, omecamtiv mecarbil and danicamtiv, target cardiac myosin to increase left ventricular systolic performance. Neither omecamtiv mecarbil nor danicamtiv affects cardiomyocyte calcium handling, the proposed mechanism underlying the life-threatening arrhythmias associated with cardiac calcitropes and calcium sensitizers. Phase 2 clinical trials have demonstrated that these cardiac myosin activators prolong left ventricular systolic ejection time and promote left ventricular and atrial reverse remodeling. At higher plasma concentrations, these agents may be associated with myocardial ischemia and impaired diastolic function. An ongoing phase 3 clinical trial will estimate the clinical efficacy and safety of omecamtiv mecarbil. An additional study of these agents, which have minimal hemodynamic and renal effects, is warranted in patients with advanced heart failure refractory to guideline-directed neurohormonal blockers.
Fetal Hypothyroidism Impairs Aortic Vasorelaxation Responses in Adulthood: Involvement of Hydrogen Sulfide and Nitric Oxide Cross talk
Authors: Nourabadi Davood , Baluchnejadmojarad Tourandokht , Zarch Seyed M. M. , Ramazi Samira , Serenjeh Morteza N. , Roghani Mehrdad 
Published: November 2020

Abstract:
Thyroid hormones have a wide range of effects on growth, differentiation, evolution, metabolism, and physiological function of all tissues, including the vascular bed. In this study, the effect of fetal hypothyroidism on impairment of aortic vasorelaxation responses in adulthood was investigated with emphasis on possible involvement of hydrogen sulfide (H2S)/nitric oxide interaction. Two groups of female rats were selected. After mating and observation of vaginal plaque, one group received propylthiouracil (200 ppm in drinking water) until the end of pregnancy and another group had no propylthiouracil treatment during the fetal period. In adult rats, aortic relaxation responses to l-arginine and GYY4137 were assessed in the presence or absence of Nω-nitro-L-arginine methyl ester hydrochloride and dl-propargylglycine in addition to the biochemical measurement of thyroid hormones and some related factors. Obtained findings showed a lower vasorelaxation response for GYY4137 and l-arginine in the fetal hypothyroidism group, and preincubation with Nω-nitro-L-arginine methyl ester hydrochloride or dl-propargylglycine did not significantly aggravate this weakened relaxation response. In addition, aortic levels of sirtuin 3, endothelial nitric oxide synthase, cystathionine gamma-lyase, and H2S were significantly lower in the fetal hypothyroidism group. Meanwhile, no significant changes were obtained regarding serum levels of thyroid hormones including free triiodothyronine;, total triiodothyronine, free thyroxine, total thyroxine, and thyroid-stimulating hormone in adult rats. It can be concluded that hypothyroidism in the fetal period has inappropriate effects on the differentiation and development of vascular bed with subsequent functional abnormality that persists into adulthood, and part of this vascular abnormality is mediated through weakened interaction and/or cross talk between H2S and nitric oxide.
Tacrolimus Bayesian Dose Adjustment in Pediatric Renal Transplant Recipients
Authors: Marquet Pierre , Cros Florine , Micallef Ludovic , Jacqz-Aigrain Evelyne , Woillard Jean-Baptiste , Monchaud Caroline , Saint-Marcoux Franck , Debord Jean 
Published: November 2020

Background:
Immunosuppressant Bayesian Dose Adjustment (ISBA) is an online expert system that estimates the area under the curve (AUC) of immunosuppressive drugs through pharmacokinetic modelling and Bayesian estimation to propose dose adjustments to reach predefined exposure targets. The ISBA database was retrospectively analyzed to describe tacrolimus pharmacokinetics and exposure, evaluate the efficiency of ISBA dose recommendations, and propose tacrolimus AUC0–12h target ranges for pediatric renal allograft recipients treated with immediate release tacrolimus.

Methods:
The database included 1935 tacrolimus dose adjustment requests from 419 patients <19 years old who were treated with immediate-release tacrolimus and followed in 21 French hospitals. The tacrolimus exposure evolution with patient age and posttransplantation time, the correlation between trough tacrolimus concentration (C0) and AUC0–12h at different periods posttransplantation, and the efficiency of dose recommendations to avoid underexposure and overexposure and to decrease between-patient AUC variability were investigated.

Results:
Tacrolimus AUC showed large between-patient variability (CV% = 40%) but moderate within-patient variability (median = 24.3% over a 3-month period). Dose-standardized exposure but not the AUC/C0 ratio significantly decreased with time posttransplantation and patient age. We derived AUC0–12h ranges from the consensual C0 ranges using linear regression equations. When the ISBA recommended dose was applied, the AUC distribution was narrower and a significantly higher proportion was within the targets (P < 0.0001).

Conclusions:
ISBA efficiently reduced tacrolimus underexposure and overexposure. The AUC0–12h target ranges for pediatric patients derived from the database were similar to those previously reported for adults. Estimating the AUC/C0 ratio could help determine personalized C0 targets.
UTILITY OF ORAL FLUORESCEIN ANGIOGRAPHY WITH ULTRA-WIDEFIELD IMAGING SYSTEM FOR EVALUATION OF VARIOUS RETINAL DISORDERS
Authors: Yamao Sayaka , Tsujioka Taishi , Takada Ryota , Matsumoto Fumiko , Kusaka Shunji 
Published: November 2020

Purpose:
To evaluate the utility of oral fluorescein angiography with ultra-widefield imaging system (oral UWF-FA) predominantly in children.

Methods:
We recruited 17 patients aged 2 years to 22 years with retinal disorders. Each patient ingested a dose of fluorescein sodium set by body weight mixed with 100 mL of juice. Images were scored using four parameters as follows: branch retinal vessel identification, retinal vessels visualization, foveal avascular zone visualization, and clinically important findings such as leakage, microaneurysms, neovascularization, or significant nonperfusion area visualization. Based on the aggregate score, we classified the image quality into three grades.

Results:
Sixteen of 17 patients completely ingested the fluorescein sodium, and ultra-widefield fluorescein angiography was performed. Images were classified as high quality in nine cases, moderate quality in four, and poor quality in three. In 13 cases (81.3%), images had adequate quality to evaluate retinal conditions. Of three patients with poor-quality images, 2 took 10 minutes to ingest fluorescein sodium and the other ingested only half the dose. The adverse event of a mild skin rash was noted in one patient.

Conclusion:
Oral ultra-widefield fluorescein angiography is effective in evaluating retinal pathology and is a useful alternative especially for pediatric patients who cannot tolerate intravenous line placement.
Refractive Outcomes After Descemet Membrane Endothelial Keratoplasty + Cataract/Intraocular Lens Triple Procedure: A Fellow Eye Comparison
Authors: Augustin Victor A. , Weller Julia M. , Kruse Friedrich E. , Tourtas Theofilos 
Published: November 2020

Purpose:
Descemet membrane endothelial keratoplasty is often combined with phacoemulsification and intraocular lens implantation (DMEK + cataract/IOL triple procedure) in phakic patients. This procedure results in a refractive shift that is difficult to predict. The aim of this study was to evaluate the hypothesis that the refractive shift in the second eye follows the shift in the first eye.

Methods:
In this retrospective, single-center, consecutive case series, the refractive outcomes of 254 eyes of 127 patients who underwent DMEK + cataract/IOL triple procedure in both eyes for Fuchs endothelial corneal dystrophy have been analyzed. Main outcome measures were spherical equivalent outcome (shift calculations), best spectacle-corrected visual acuity, central corneal thickness, and posterior simulated keratometry.

Results:
The mean best spectacle-corrected visual acuity before surgery was 0.51 ± 0.24 and increased to 0.19 ± 0.15 (logMAR) after surgery (P < 0.001). After surgery, a mean hyperopic shift of 0.98 ± 0.89 D was observed. The refractive shift was 1.03 ± 0.93 D and 0.92 ± 1.02 D, in the first and second eyes, respectively (P = 0.435). In a paired analysis, the mean difference of the refractive shift between the first and second eyes was 0.49 ± 0.43 D.

Conclusions:
In our fellow eye comparison, the refractive shift after DMEK + cataract/IOL triple procedure in the second eye was comparable with the shift in the first eye. As a consequence, the refractive outcome of the first eye might serve as a reference for optimizing the refractive target in the second eye. Further studies investigating the influence of corneal parameters on refractive shift are needed for a more predictable lens power selection.
Burden of Tuberculosis in South African Children During Treatment for Underlying Malignancies
Authors: Naidu Gita , Izu Alane , Madimabe Metsekae Richard , Poyiadjis Stelios , MacKinnon Diane , Rowe Biance , Madhi Shabir Ahmed 
Published: November 2020

Background:
Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer.

Methods:
Children with cancer were enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings.

Results:
We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death.

Conclusions:
Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.