bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape
Authors: Hedlin Haley , Garcia Ariadna , Weng Yingjie , He Ziyuan , Sundaram Vandana , Bunning Bryan , Balasubramanian Vidhya , Cunanan Kristen , Kapphahn Kristopher , Gummidipundi Santosh , Purington Natasha , Boulos Mary , Desai Manisha 
Published: February 2021

Background: Clinical trials, conducted efficiently and with the utmost integrity, are a key component in identifying effective vaccines, therapies, and other interventions urgently needed to solve the COVID-19 crisis. Yet launching and implementing trials with the rigor necessary to produce convincing results is a complicated and time-consuming process. Balancing rigor and efficiency involves relying on designs that employ flexible features to respond to a fast-changing landscape, measuring valid endpoints that result in translational actions and disseminating findings in a timely manner. We describe the challenges involved in creating infrastructure with potential utility for shared learning. Methods: We have established a shared infrastructure that borrows strength across multiple trials. The infrastructure includes an endpoint registry to aid in selecting appropriate endpoints, a registry to facilitate establishing a Data & Safety Monitoring Board, common data collection instruments, a COVID-19 dedicated design and analysis team, and a pragmatic platform protocol, among other elements. Results: The authors have relied on the shared infrastructure for six clinical trials for which they serve as the Data Coordinating Center and have a design and analysis team comprising 15 members who are dedicated to COVID-19. The authors established a pragmatic platform to simultaneously investigate multiple treatments for the outpatient with adaptive features to add or drop treatment arms. Conclusion: The shared infrastructure provides appealing opportunities to evaluate disease in a more robust manner with fewer resources and is especially valued during a pandemic where efficiency in time and resources is crucial. The most important element of the shared infrastructure is the pragmatic platform. While it may be the most challenging of the elements to establish, it may provide the greatest benefit to both patients and researchers.
Hospital admissions in inflammatory rheumatic diseases during the peak of COVID-19 pandemic: incidence and role of disease-modifying agents
Authors: Fernandez-Gutierrez Benjamin , Leon Leticia , Madrid Alfredo , Rodriguez-Rodriguez Luis , Freites Dalifer , Font Judit , Mucientes Arkaitz , Culebras Esther , Colome Jose Ignacio , Jover Juan Angel , Abasolo Lydia 
Published: February 2021

Aims: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. Results: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.
Morphological Changes of the Hip Commonly Associated With Femoroacetabular Impingement Are Not Correlated With Rotational Range of Hip Motion in Elite Soccer Athletes
Authors: Bento André Orlandi , Falótico Guilherme , Enseki Keelan , Cunha Ronaldo Alves , Ejnisman Benno , Arliani Gustavo , Cohen Moisés 
Published: February 2021

Background: Morphological changes characteristic of femoroacetabular impingement (FAI) are common in soccer players. However, the clinical relevance of such anatomical variations is still not well-defined. Hypothesis: We hypothesized that high alpha angle values and/or acetabular retroversion index (ARI) are correlated with rotational range of motion (ROM) of the hip and that there are clinical-radiological diferences between the dominant lower limb (DLL) and nondominant lower limb (NDLL) in professional soccer players. Study Design: Cross-sectional. Level of Evidence: Level 3. Methods: A total of 59 male professional soccer players (average age 25.5 years, range 18-38 years) were evaluated in the preseason. As main outcome measures, we evaluated the alpha angle and the ARI and hip IR and ER ROM with radiographic analysis. Results: The measurements taken on DLL and NDLL were compared and a significant difference was found between the sides in the ER ( P = 0.027), where the DLL measures were 1.54° (95% CI, 0.18-2.89) greater than the NDLL. There were no significant differences between the sides in the measures of IR ( P > 0.99), total ROM ( P = 0.07), alpha angle ( P = 0.250), and ARI ( P = 0.079). The correlations between the rotation measurements and the alpha angle in each limb were evaluated and the coefficient values showed no correlation; so also between the ARI and rotation measures. Conclusion: Morphological changes of the femur or acetabulum are not correlated with hip IR and ER ROM in male professional soccer players. ER on the dominant side was greater than on the nondominant side. There was no significant difference in the other measurements between sides. Clinical Relevance: In clinical practice, it is common to attribute loss of hip rotational movement to the presence of FAI. This study shows that anatomical FAI may not have a very strong influence on available hip rotational movement in professional soccer athletes.
Growth Trajectories of HIV Exposed and HIV Unexposed Infants. A Prospective Study in Gweru, Zimbabwe
Authors: Mabaya Lucy , Matarira Hilda Tendisa , Tanyanyiwa Donald Moshen , Musarurwa Cuthbert , Mukwembi Johannes 
Published: February 2021

Background: With the increasing HIV seroprevalence among women of childbearing age in sub-Saharan Africa, limited data on growth outcomes of HIV exposed infants under current policies of universal maternal antiretroviral therapy exist. Methods: The longitudinal growth patterns of 114 HIV exposed and unexposed infants were assessed and compared. The prevalence and factors associated with malnutrition were established. Infants under prevention of mother to child transmission care were recruited at 6 weeks post-delivery as were their HIV unexposed counterparts. Weight and length measurements were recorded at birth, 6 and 16 weeks postpartum. Results: HIV vertical transmission rate was 8.8%. HIV exposed infants had significantly lower mean birth weights compared to HIV unexposed infants (2.9 ± 0.3; 3.2 ± 0.5; P < .001) respectively. Mean weight/length-for-age z-scores for HIV exposed, uninfected (HEU) infants were significantly below those of the HIV unexposed infants during follow up. By 6 weeks of age, 28.5% of HEU infants were malnourished while no malnutrition was evident in HIV unexposed infants. A gestational age <37 weeks (OR: 3.83; 95% CI: 1.03-14.30; P = .045) and HIV exposure (OR: 1.62; 95% CI: 0.17-15.73; P = .017) substantially increased the risk of stunting. Conclusion: Growth deficits were witnessed in HIV exposed infants compared to HIV unexposed infants. There is need for early nutritional monitoring and support among HIV exposed infants.
Investigation of Pancreatic Sonography Findings in Patients With Beta-Thalassemia Major
Authors: Behzadmehr Razieh , Shahramian Iraj , Ostad Rahimi Pouya , Sheikh Mahboobeh , Keikha Soosan , Salarzaei Morteza , Parooie Fateme 
Published: February 2021

Objective: Some structural abnormalities have been reported on sonography of pancreas in patients with beta-thalassemia which can indicate that the patient is developing diabetes. In this study, the aim was to investigate the findings of pancreatic sonography in patients, with beta-thalassemia major. Methods: This cross-sectional study included information extracted from the medical record and entered into an information form. A cohort of 190 people were split into case and control groups, retrospectively. The required data were extracted from patient’s documents. Data were analyzed with SPSS software, version 22; with the chi-square statistical tests. A P value of < .05 was considered statistically significant. Results: This study consisted of 33 males and 61 females in the case group and 32 males and 64 females in the control group. The most common echogenicity observed during pancreatic sonography, in the control group, was an isoechoic feature (72.3%), followed by hyper and hypoechogenicity (18.1% and 9.6%, respectively). The prevalence of an isoechoic texture in the patient case group was 58.3%, while hyper and hypoechogenicity were seen in 26% and 2.1%, respectively ( P = .070). There was a poor negative correlation between diabetes and pancreatic echogenicity ( P = .002 and r = −.226). Also, there was a poor positive correlation between fasting serum glucose levels and pancreatic echogenicity ( P = .034, n = 96 and r = .217). Conclusion: This study demonstrates, in this patient group, that there was a poor relationship between pancreatic head size with serum ferritin levels and pancreatic echogenicity with diabetes. These results may suggest using sonography to diagnose early stages of diabetes in patients with thalassemia.
Low 5-year health care burden after umbilical cord blood transplantation
Authors: Garcia Jesus Garcia , Grillo Sonya , Cao Qing , Brunstein Claudio G. , Arora Mukta , MacMillan Margaret L. , Wagner John E. , Weisdorf Daniel J. , Holtan Shernan G. 
Published: February 2021

Abstract
Recipients of allogeneic hematopoietic cell transplantation (HCT) experience a substantial health care burden, with potentially differing patterns of long-term health care requirements using peripheral blood stem cells, bone marrow, and umbilical cord blood (UCB) grafts. We analyzed data from 1077 consecutive adult allogeneic HCT recipients who underwent transplant at the University of Minnesota between 2000 and 2016. To estimate health care burden over time, we compared the number of visits, laboratory studies, medications, and relative value units billed. Health care elements were analyzed both individually and together (ie, total health care elements used per patient days into a density composite score). UCB had the lowest density health care burden composite score from the time of transplant through year 5 (median score 64.0 vs 70.5 for peripheral blood stem cells and 88.0 for bone marrow; P &lt; .01). In multivariate analysis of health care burden between years 1 and 5, recipients of either bone marrow (odds ratio [OR] 0.49 [95% confidence interval (CI) 0.29-0.84]) or peripheral blood stem cells (OR 0.49 [95% CI 0.36-0.67]) were half as likely to experience low health care burden compared with UCB. Adult recipients of UCB have a lower long-term health care burden compared with other graft sources, possibly reflecting a better quality of life.
Vogt-Koyanagi-Harada disease is always bilateral: reports of unilateral cases failed to use choroidal investigations showing subclinical involvement of the fellow eye
Authors: Papasavvas Ioannis , Herbort Carl P. 
Published: February 2021

Abstract
Background/purpose
Vogt-Koyanagi-Harada (VKH) disease is a primary stromal choroiditis and a bilateral granulomatous panuveitis which, if not treated early and properly, could have a deleterious evolution. The purpose of our case report is to demonstrate that “so called” unilateral VKH disease should be investigated further with an Indocyanine Green Angiography (ICGA), in order to detect subclinical choroidal involvement of the other eye.

Case report
We present a case of 42-year old woman who came to see us for second opinion. She had consulted elsewhere for a left uveitis and had been treated with a periocular corticosteroid injection. At presentation she mentioned persistent headaches. Visual acuity on the Snellen scale was 1.0 OD and 0.5 OS. Slit-lamp examination showed granulomatous (rare mutton-fat KPs) signs in her left eye. Laser flare photometry showed a subclinical flare of 17.8 ph/ms OD and a flare of 66.4 ph/ms OS (normal values 3–6 ph/ms). Fundus examination showed left discoloration due to choroidal infiltration with a normal fundus aspect OD. ICGA showed a diffuse choroiditis also in the apparently normal right eye. Lumbar puncture confirmed the diagnosis of VKH and appropriate treatment was introduced.

Conclusion
VKH disease results from a generalized autoimmune process against melanocyte associated antigens starting in the choroidal stroma. It can be asymmetrical but is always bilateral, as long as investigations such as ICGA, able to detect subclinical choroiditis, are performed.
Quantification and evolution of mitochondrial genome rearrangement in Amphibians
Authors: Zhang Jifeng , Miao Guopen , Hu Shunjie , Sun Qi , Ding Hengwu , Ji Zhicheng , Guo Pen , Yan Shoubao , Wang Chengrun , Kan Xianzhao , Nie Liuwang 
Published: February 2021

AbstractBackgroundRearrangement is an important topic in the research of amphibian mitochondrial genomes ("mitogenomes" hereafter), whose causes and mechanisms remain enigmatic. Globally examining mitogenome rearrangements and uncovering their characteristics can contribute to a better understanding of mitogenome evolution.ResultsHere we systematically investigated mitogenome arrangements of 232 amphibians including four newly sequenced Dicroglossidae mitogenomes. The results showed that our new sequenced mitogenomes all possessed atrnMtandem duplication, which was not exclusive to Dicroglossidae. By merging the same arrangements, the mitogenomes of ~ 80% species belonged to the four major patterns, the major two of which were typical vertebrate arrangement and typical neobatrachian arrangement. Using qMGR for calculating rearrangement frequency (RF) (%), we found that the control region (CR) (RF = 45.04) andtrnL2(RF = 38.79) were the two most frequently rearranged components. Forty-seven point eight percentage of amphibians possessed rearranged mitogenomes including all neobatrachians and their distribution was significantly clustered in the phylogenetic trees (p < 0.001). In addition, we argued that the typical neobatrachian arrangement may have appeared in the Late Jurassic according to possible occurrence time estimation.ConclusionIt was the first global census of amphibian mitogenome arrangements from the perspective of quantity statistics, which helped us to systematically understand the type, distribution, frequency and phylogenetic characteristics of these rearrangements.
Transcriptome analysis and molecular mechanism of linseed (Linum usitatissimum L.) drought tolerance under repeated drought using single-molecule long-read sequencing
Authors: Wang Wei , Wang Lei , Wang Ling , Tan Meilian , Ogutu Collins O. , Yin Ziyan , Zhou Jian , Wang Jiaomei , Wang Lijun , Yan Xingchu 
Published: February 2021

Abstract
Background
Oil flax (linseed, Linum usitatissimum L.) is one of the most important oil crops., However, the increases in drought resulting from climate change have dramatically reduces linseed yield and quality, but very little is known about how linseed coordinates the expression of drought resistance gene in response to different level of drought stress (DS) on the genome-wide level.

Results
To explore the linseed transcriptional response of DS and repeated drought (RD) stress, we determined the drought tolerance of different linseed varieties. Then we performed full-length transcriptome sequencing of drought-resistant variety (Z141) and drought-sensitive variety (NY-17) under DS and RD stress at the seedling stage using single-molecule real-time sequencing and RNA-sequencing. Gene Ontology (GO) and reduce and visualize GO (REVIGO) enrichment analysis showed that upregulated genes of Z141 were enriched in more functional pathways related to plant drought tolerance than those of NY-17 were under DS. In addition, 4436 linseed transcription factors were identified, and 1190 were responsive to stress treatments. Moreover, protein-protein interaction (PPI) network analysis showed that the proline biosynthesis pathway interacts with stress response genes through RAD50 (DNA repair protein 50) interacting protein 1 (RIN-1). Finally, proline biosynthesis and DNA repair structural gene expression patterns were verified by RT- PCR.

Conclusions
The drought tolerance of Z141 may be related to its upregulation of drought tolerance genes under DS. Proline may play an important role in linseed drought tolerance by maintaining cell osmotic and protecting DNA from ROS damage. In summary, this study provides a new perspective to understand the drought adaptability of linseed.
Radiomics based on multiparametric MRI for extrathyroidal extension feature prediction in papillary thyroid cancer
Authors: Wei Ran , Wang Hao , Wang Lanyun , Hu Wenjuan , Sun Xilin , Dai Zedong , Zhu Jie , Li Hong , Ge Yaqiong , Song Bin 
Published: February 2021

Abstract
Background
To determine the predictive capability of MRI-based radiomics for extrathyroidal extension detection in papillary thyroid cancer (PTC) pre-surgically.

Methods
The present retrospective trial assessed individuals with thyroid nodules examined by multiparametric MRI and subsequently administered thyroid surgery. Diagnosis and extrathyroidal extension (ETE) feature of PTC were based on pathological assessment. The thyroid tumors underwent manual segmentation, for radiomic feature extraction. Participants were randomized to the training and testing cohorts, at a ratio of 7:3. The mRMR (maximum correlation minimum redundancy) algorithm and the least absolute shrinkage and selection operator were utilized for radiomics feature selection. Then, a radiomics predictive model was generated via a linear combination of the features. The model’s performance in distinguishing the ETE feature of PTC was assessed by analyzing the receiver operating characteristic curve.

Results
Totally 132 patients were assessed in this study, including 92 and 40 in the training and test cohorts, respectively). Next, the 16 top-performing features, including 4, 7 and 5 from diffusion weighted (DWI), T2-weighted (T2 WI), and contrast-enhanced T1-weighted (CE-T1WI) images, respectively, were finally retained to construct the radiomics signature. There were 8 RLM, 5 CM, 2 shape, and 1 SZM features. The radiomics prediction model achieved AUCs of 0.96 and 0.87 in the training and testing sets, respectively.

Conclusions
Our study indicated that MRI radiomics approach had the potential to stratify patients based on ETE in PTCs preoperatively.
Cardiovascular disease prevalence in type 2 diabetes – an analysis of a large German statutory health insurance database
Authors: Gabler Maximilian , Geier Silke , Mayerhoff Lukas , Rathmann Wolfgang 
Published: February 2021

Abstract
Background
The aim of this study was to determine the prevalence of cardiovascular disease in persons with type 2 diabetes mellitus (T2D) in Germany.

Methods
A claims database with an age- and sex-stratified sample of nearly 4 million individuals insured within the German statutory health system was used. All patients aged ≥18 years with T2D documented between 1 January 2015 and 31 December 2015 and complete retrospective documentation of ≥5 years (continuous enrollment in the German statutory health system) before 2015 were selected based on a validated algorithm. Cardiovascular disease (CVD) events were identified based on ICD-10 and OPS codes according to a previous clinical study (EMPA-REG OUTCOME trial).

Results
The prevalence of T2D in Germany in 2015 was 9.9% (n = 324,708). Using a narrow definition of CVD, the 6-year observation period prevalence of CVD was estimated as 46.7% [95% CI: 46.52%;46.86%]. Applying a wider CVD definition, the proportion of T2D patients who showed a history of CVD was 57.1% [95% CI: 56.9%;57.24%]. The prevalence of CVD in patients with T2D ranged from 36.3 to 57.1%, depending on the observation period and definition of CVD.

Conclusions
The results underline the need for a population-based registration of cardiovascular complications in T2D.
Qualitative exploration of sexual life among breast cancer survivors at reproductive age
Authors: Maleki Maryam , Mardani Abbas , Ghafourifard Mansour , Vaismoradi Mojtaba 
Published: February 2021

Abstract
Background
Our understanding of the experiences of women at reproductive age regarding sexual life and issues they may face after starting the treatment of breast cancer is limited. Therefore, this qualitative study aimed to explore sexual life and its related issues among breast cancer survivors at reproductive age in Iran.

Methods
A qualitative research was conducted. Participants were 21 breast cancer survivors who were under 51 years of age that were chosen using purposeful sampling. In-depth semi-structured interviews were carried out for data collection and the content analysis method was used for data analysis.

Results
The data analysis led to the development of main theme of ‘unfulfilled sexual life’. Also, four subthemes were: ‘undesirable sexual function’, ‘context-based beliefs’, ‘unmet information and supportive needs’, and ‘emotional crisis’.

Conclusions
Our research findings inform healthcare providers about the experiences of breast cancer survivors and related changes in their sexual and marriage life at reproductive age. Nurses and other healthcare providers in the multidisciplinary team should proactively identify health-related problems and design appropriate caring strategies to mitigate sexual and marriage issues among breast cancer survivors. Also, the establishment of sexual health counseling units for breast cancer survivors can help this vulnerable group of women with the improvement of their long-term sexual satisfaction.