bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile App-based documentation of patient-reported outcomes — 3-months results from a proof-of-concept study on modern rheumatology patient management
Authors: Richter Jutta G. , Nannen Christina , Chehab Gamal , Acar Hasan , Becker Arnd , Willers Reinhart , Huscher Dörte , Schneider Matthias 
Published: April 2021

Abstract
Background
Mobile medical applications (Apps) offer innovative solutions for patients’ self-monitoring and new patient management opportunities. Prior to routine clinical application feasibility and acceptance of disease surveillance using an App that includes electronic (e) patient-reported outcome measures (PROMs) warrant evaluation. Therefore, we performed a proof-of-concept study in which rheumatoid arthritis (RA) patients used an App (RheumaLive) to document their disease.

Methods
Accurate PROM reporting via an App in comparison to paper-based versions was investigated to exclude media bias. Sixty participants recruited from 268 consecutive RA outpatients completed paper-based and electronic PROMs (Hannover Functional Questionnaire/derived HAQ; modified RA disease activity index) using the App at baseline and follow-up visits. Between visits, patients used their App on their own smartphone according to their preferences. The equivalence of PROM data and user experiences from patients and physicians were evaluated.

Results
Patients’ (78.3% female) mean (SD) age was 50.1 (13.1) years, disease duration 10.5 (9.1) years, and paper-based HAQ 0.78 (0.59). Mean confidence in Apps scored 3.5 (1.1, Likert scale 1 to 6). ePROMs’ scores obtained by patients’ data entry in the App were equivalent to paper-based ones and preferred by the patients. After 3 months, the App retention rate was 71.7%. Patients' overall satisfaction with the App was 2.2 (0.9, Likert scale 1 to 6). Patients and physicians valued the App, i.e., for patient-physician interaction: 87% reported that it was easier for them to document the course of the disease using the App than “only” answering questions about their current health during routine outpatient visits. Further App use was recommended in 77.3% of the patients, and according to physicians, in seven patients, the App use contributed to an increased adherence to therapy.

Conclusion
Our study provides an essential basis for the broader implementation of medical Apps in routine care. We demonstrated the feasibility and acceptance of disease surveillance using a smartphone App in RA. App use was convincing as a reliable option to perform continuous, remote monitoring of disease activity and treatment efficacy.

Trial registration
ClinicalTrials.gov, NCT02565225. Registered on September 16, 2015 (retrospectively registered).
Genetic variants of the EGFR ligand-binding domain and their association with structural alterations in Arab cancer patients
Authors: Marzouq Maryam , Nairouz Ali , Ben Khalaf Noureddine , Bourguiba-Hachemi Sonia , Quaddorah Raed , Ashoor Dana , Fathallah M. Dahmani 
Published: April 2021

AbstractObjectiveThis study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. It also aimed to investigate the effects of these variants on the EGFR structure and their eventual relevance to tumorigenesis.ResultsWe detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. A SNP rs374670788 was more frequent in bladder cancer but not significantly associated to. However, a missense mutation (V550M) was significantly associated to colon, ovary, lung, bladder and thyroid cancer samples (p < 0.05). Three mutations (H590R, E602K and T605T) were found in the heterozygous form only in colon cancer patients. Genomic analysis of the synonymous mutation (G632G) showed that the T/A genotype could be associated to thyroid cancer in Arab patients (p < 0.05). An additional novel SNP rs571064657 was observed in control individuals. Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (− ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor’s function and promote tumorigenesis.
New guidance to seekers of autism biomarkers: an update from studies of identical twins
Authors: Constantino John N. 
Published: April 2021

Abstract
Background
The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers.

Main body
This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a “tipping point” at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development.

Conclusion
Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case–control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism.
Dietary isoleucine improved flesh quality, muscle antioxidant capacity, and muscle growth associated with AKT/TOR/S6K1 and AKT/FOXO3a signaling in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂)
Authors: Jiang Qin , Yan Mingyao , Zhao Ye , Zhou Xiaoqiu , Yin Long , Feng Lin , Liu Yang , Jiang Weidan , Wu Pei , Wang Yan , Chen Defang , Yang Shiyong , Huang Xiaoli , Jiang Jun 
Published: April 2021

Abstract
Background
Muscle is the complex and heterogeneous tissue, which comprises the primary edible part of the trunk of fish and mammals. Previous studies have shown that dietary isoleucine (Ile) exerts beneficial effects on growth in aquatic animals. However, there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth. Thus, this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

Methods
A total of 630 hybrid fish, with an initial average body weight of 33.11 ± 0.09 g, were randomly allotted into seven experimental groups with three replicates each, and respectively fed seven diets with 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, and 20.0 g Ile/kg diets for 8 weeks.

Results
In the present study, we demonstrated that Ile significantly: (1) increased muscle protein and lipid contents and the frequency distribution of myofibers with ≤ 20 μm and ≥ 50 μm of diameter; (2) improved pH value, shear force, cathepsin B and L activities, hydroxyproline content, resilience, cohesiveness, and decreased cooking loss, lactate content, hardness, springiness, gumminess, and chewiness; (3) decreased reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) contents, GCLC and Keap1 mRNA levels, and up-regulated CuZnSOD, CAT, GPX1a, GST, and Nrf2 mRNA levels; (4) up-regulated the insulin-like growth factor 1, 2 (IGF-1, IGF-2), insulin-like growth factor 1 receptor (IGF-1R), proliferating cell nuclear antigen (PCNA), Myf5, Myod, Myog, Mrf4, and MyHC mRNA levels, and decreased MSTN mRNA level; (5) increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.

Conclusion
These results revealed that dietary Ile improved flesh quality, which might be due to increasing nutritional content, physicochemical, texture parameters, and antioxidant ability; promoting muscle growth by affecting myocytes hyperplasia and hypertrophy, and muscle protein deposition associated with protein synthesis and degradation signaling pathways. Finally, the quadratic regression analysis of chewiness, ROS, and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19, 12.36, and 12.78 g/kg diet, corresponding to 36.59, 31.87, and 32.96 g/kg dietary protein, respectively.
Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non–Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%
Authors: Reck Martin , Rodríguez-Abreu Delvys , Robinson Andrew G. , Hui Rina , Csőszi Tibor , Fülöp Andrea , Gottfried Maya , Peled Nir , Tafreshi Ali , Cuffe Sinead , O'Brien Mary , Rao Suman , Hotta Katsuyuki , Leal Ticiana A. , Riess Jonathan W. , Jensen Erin , Zhao Bin , Pietanza M. Catherine , Brahmer Julie R. 
Published: April 2021

PURPOSE We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non–small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738 ) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS). METHODS Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point. RESULTS Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti–PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure. CONCLUSION Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.
Effects of Overweight and Obesity on Running Mechanics in Children
Authors: BOWSER BRADLEY J , ROLES KRISTEN 
Published: April 2021

ABSTRACT
Although obesity has been linked to several differences in walking mechanics, few studies have examined movement mechanics of overweight and obese (OW/OB) children performing higher impact activities, such as running.

Purpose
The purpose of this study is to determine differences in running mechanics between healthy weight (HW) children and children classified as OW/OB.

Methods
Forty-two children (17 OW/OB, 25 HW) ran overground while kinematic and kinetic data were recorded using a motion capture system and force plate. Kinematic variables of interest included stance time, step length, and frontal and sagittal plane joint angles and excursions at the hip, knee, and ankle. Kinetic variables of interest included ground reaction forces and hip, knee, and ankle moments in the sagittal and frontal planes.

Results
The OW/OB group spent more time in stance, took shorter steps, displayed less hip flexion during the first half of stance, had greater ankle inversion at foot strike, had greater knee abduction throughout stance, and had smaller knee flexion, knee adduction, and hip adduction excursions. In comparing unscaled ground reaction forces, the OW/OB group displayed greater peak vertical force, vertical impact peaks, and vertical loading rates. The OW/OB group also displayed greater unscaled plantar and dorsiflexion moments, knee flexion and extension moments, ankle inversion moments, and knee and hip abduction moments.

Conclusion
These data suggest that increased body weight in children is associated with changes in running mechanics. Higher joint moments and ground reaction forces may indicate increased injury risk or the development of joint degeneration among overweight/obese children.
Do fluorocarbons substantially increase transdermal oxygen delivery? A proof-of-principle study in mice
Authors: Kaestner Lars , Laschke Matthias W. , John Thomas , Wagner Christian , Bogdanova Anna 
Published: April 2021

Background: Coronavirus disease 2019 (COVID-19) patients who need intensive medical care often require oxygen ventilation, but the number of ventilation machines is limited, and in some parts of the world, they are not available at all. In addition to patients for whom there is no access to ventilation machines there is also a considerable population of patients for whom ventilation is not sufficient for them to survive a critical state. Methods: Here, we propose and test an alternative oxygen supply through accelerated transdermal oxygen delivery. Covering the entire body with liquid fluorocarbons, which can dissolve 20 times more oxygen than water, we hypothesized to increase the contribution of transcutaneous respiration by a sustained amount. Results: Experiments applying pure medical grade perfluorodecalin on nude mice did not change their oxygenation in the blood under induced hypoxic conditions compared to control mice. However, increases in blood oxygenation below 2% could not be detected with the applied method. Conclusions: We could not establish a proof-of-principle for a substantial increase in oxygen supply by transdermal oxygen delivery in mammals.
Comparing Objective and Subjective Measures of Sleep Loss with Balance Performance in Farmers
Authors: Sedlacek Devan , Beacom Matthew , Bista Sabin R. , Rautiainen Risto , Siu Ka-Chun 
Published: April 2021

HighlightsThe farming population is at risk of injury due to sleep deprivation.Loss of sleep during previous night affects balance performance in farmers.Objective measures of sleep are more reliable than subjective measures for predicting balance performance.Abstract. This study aimed to investigate the ability of both subjective and objective sleep measures to predict balance difficulty in agricultural workers. Seven male farmers from rural Nebraska were analyzed for static balance performance following a bout of sleep. Actiwatches were used to measure objective sleep hours and subjective questionnaires, including the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, were used to measure subjective hours of sleep and sleep quality. The participants were observed for 12 sessions, with six in planting season and six in harvest season. Static balance testing consisted of measuring the area, total displacement, and maximum range in the anteroposterior and mediolateral directions of the individual’s center of pressure with Tekscan pressure mats. Overall, it was found that objective measures had a higher correlation with the magnitude of balance deviations than subjective measures. Keywords: Actiwatch, Agricultural worker, Injury, Sleep deprivation.
Agricultural Safety and Health Learning Methods for Agricultural Workforces
Authors: Gorucu Serap , Fetzer Linda 
Published: April 2021

HighlightsDemonstrations and one-on-one training were the most preferred learning methods.The most-used learning methods were electronic methods.Printed materials were preferred and perceived as effective by Baby Boomers.Abstract. The purpose of this study was to investigate differences among generational cohorts in the agricultural workforce in learning methods, including frequency of use, perceived effectiveness, and preference. A total of 211 participants representing the agricultural workforce completed either a paper-based or online questionnaire. Generational cohorts were determined using participants’ birth years. The results show that regardless of the generational cohort, demonstrations and one-on-one training were the most preferred learning methods and were also perceived as the most effective methods. Participants indicated that they mostly use electronic methods to learn about agricultural safety and health. Generational differences were found for some learning methods. Printed materials were found to be preferred and perceived as effective by Baby Boomers more so than the other cohorts. Electronic methods were mostly used by Gen X and Millennial participants. For learning about agricultural safety, demonstrations are the most preferred and most effective methods but are not used as frequently as the other learning methods. Agricultural safety education should continue delivering safety demonstrations. Keywords: Learning methods, Multigenerational, Safety and health, Training.
Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis
Authors: Gao Yaqing , Zhang Long , Kc Ashish , Wang Yinping , Zou Siyu , Chen Chunyi , Huang Yue , Mi Xiaoyi , Zhou Hong 
Published: April 2021

BackgroundThe influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child’s health and a parent’s ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA).Methods and findingsFrom 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social–emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children’s mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children’s cognitive and social–emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child’s gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24,p< 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14,p= 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28,p= 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10,p= 0.018). On-track social–emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25,p= 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes.ConclusionsIn this study, we observed that improved housing was associated with on-track cognitive development and with on-track social–emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children’s physical health but also with broader aspects of healthy child development.
The copy number variation and stroke (CaNVAS) risk and outcome study
Authors: Cole John W. , Adigun Taiwo , Akinyemi Rufus , Akpa Onoja Matthew , Bell Steven , Chen Bowang , Jimenez Conde Jordi , Lazcano Dobao Uxue , Fernandez Israel , Fornage Myriam , Gallego-Fabrega Cristina , Jern Christina , Krawczak Michael , Lindgren Arne , Markus Hugh S. , Melander Olle , Owolabi Mayowa , Schlicht Kristina , Söderholm Martin , Srinivasasainagendra Vinodh , Soriano Tárraga Carolina , Stenman Martin , Tiwari Hemant , Corasaniti Margaret , Fecteau Natalie , Guizzardi Beth , Lopez Haley , Nguyen Kevin , Gaynor Brady , O’Connor Timothy , Stine O. Colin , Kittner Steven J. , McArdle Patrick , Mitchell Braxton D. , Xu Huichun , Grond-Ginsbach Caspar 
Published: April 2021

Background and purpose
The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap.

Methods
Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data.

Results
The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism.

Conclusion
The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.