bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classifying information-sharing methods
Authors: Nikolaidis Georgios F. , Woods Beth , Palmer Stephen , Soares Marta O. 
Published: May 2021

AbstractBackgroundSparse relative effectiveness evidence is a frequent problem in Health Technology Assessment (HTA). Where evidence directly pertaining to the decision problem is sparse, it may be feasible to expand the evidence-base to include studies that relate to the decision problem only indirectly: for instance, when there is no evidence on a comparator, evidence on other treatments of the same molecular class could be used; similarly, a decision on children may borrow-strength from evidence on adults. Usually, in HTA, such indirect evidence is either included by ignoring any differences (‘lumping’) or not included at all (‘splitting’). However, a range of more sophisticated methods exists, primarily in the biostatistics literature. The objective of this study is to identify and classify the breadth of the available information-sharing methods.MethodsForwards and backwards citation-mining techniques were used on a set of seminal papers on the topic of information-sharing. Papers were included if they specified (network) meta-analytic methods for combining information from distinct populations, interventions, outcomes or study-designs.ResultsOverall, 89 papers were included. A plethora of evidence synthesis methods have been used for information-sharing. Most papers (n=79) described methods that shared information on relative treatment effects. Amongst these, there was a strong emphasis on methods for information-sharing across multiple outcomes (n=42) and treatments (n=25), with fewer papers focusing on study-designs (n=23) or populations (n=8). We categorise and discuss the methods under four ’core’ relationships of information-sharing: functional, exchangeability-based, prior-based and multivariate relationships, and explain the assumptions made within each of these core approaches.ConclusionsThis study highlights the range of information-sharing methods available. These methods often impose more moderate assumptions than lumping or splitting. Hence, the degree of information-sharing that they impose could potentially be considered more appropriate. Our identification of four ‘core’ methods of information-sharing allows for an improved understanding of the assumptions underpinning the different methods. Further research is required to understand how the methods differ in terms of the strength of sharing they impose and the implications of this for health care decisions.
Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores
Authors: Hu Taobo , Chen Yan , Liu Yiqiang , Zhang Danhua , Pan Jiankang , Long Mengping 
Published: May 2021

AbstractPurposePR loss in ER+/HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER+/HER2- breast cancer remain unrevealed.MethodsIn this study, ER+/PR+/HER2- and ER+/PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression.ResultsER+/PR+/HER2- and ER+/PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER+/PR+/HER2- and ER+/PR-/HER2- groups.ConclusionsIn conclusion, this study indicated in ER+/HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation.
Self-help guided by trained lay providers for generalized anxiety disorder in older adults: study protocol for a randomized controlled trial
Authors: Landreville Philippe , Gosselin Patrick , Grenier Sébastien , Carmichael Pierre-Hugues 
Published: May 2021

Abstract
Background
Only a small proportion of older patients with generalized anxiety disorder (GAD) seek professional help. Difficulties in accessing treatment may contribute to this problem. Guided self-help based on the principles of cognitive-behavioral therapy (GSH-CBT) is one way of promoting access to psychological treatment. Moreover, because the therapist’s role in GSH-CBT is limited to supporting the patient, this role could be assumed by trained and supervised lay providers (LPs) instead of licensed providers. The main goal of this study is to evaluate the efficacy of GSH-CBT guided by LPs for primary threshold or subthreshold GAD in older adults.

Methods
We will conduct a multisite randomized controlled trial comparing an experimental group receiving GSH-CBT guided by LPs (n = 45) to a wait-list control group (n = 45). Treatment will last 15 weeks and will be based on a participant’s manual. Weekly telephone sessions with LPs (30 min maximum) will be limited to providing support. Data will be obtained through clinician evaluations and self-assessment questionnaires. Primary outcomes will be the tendency to worry and severity of GAD symptoms. Secondary outcomes will be anxiety symptoms, sleep difficulties, functional deficit, diagnosis of GAD, and cognitive difficulties. For the experimental group, measurements will take place at pre- and post-treatment and at 6 and 12 months post-treatment. For the control group, three evaluations are planned: two pre-treatment evaluations (before and after the waiting period) and after receiving treatment (post-treatment). The efficacy of GSH-CBT will be established by comparing the change in the two groups on the primary outcomes.

Discussion
This project will provide evidence on the efficacy of a novel approach to treat GAD in older adults. If effective, it could be implemented on a larger scale and provide many older adults with much needed mental health treatment through an expanded workforce.

Trial registration
The trial was registered at ClinicalTrials.gov, number NCT03768544, on December 7, 2018.
Development of an 360-degree virtual reality video-based immersive cycle training system for physical enhancement in older adults: a feasibility study
Authors: Lee Namsu , Choi Wonjae , Lee Seungwon 
Published: May 2021

Abstract
Background
Recently, there is an increased number of studies that use 360° virtual reality (VR) video for medical and rehabilitative purposes. However, the 360° VR video experience for older adults has not yet been investigated. This study aimed to examine the validity of an 360° VR video-based immersive cycling training system (360° VRCTS) for older adults and to provide preliminary evidence of efficacy.

Methods
We developed a new virtual reality training system using an immersive environment 360° VRCTS. Five healthy older adults (2 males and 3 females) participated in this study. The system was tested in a single training session (biking for 20 min while viewing a 360° VR video scene through a large curved screen) to identify its strengths and weakness. The usability and acceptability of our system were measured using the system usability scale (SUS) and the simulator sickness questionnaire (SSQ).

Results
All participants successfully completed the session without any discomfort. The average score for the SUS was 94.60 (range, 90–100), indicating high usability of the technology. The average score for the SSQ was 2.24 (standard deviation = 2.05), indicating that the system is well tolerated and has few side effects.

Conclusions
The 360° VRCTS may be a useful indoor training system for older adults due to its easy manipulation, high usability, and limited cybersickness.

Trial registration number
Clinical Research Information Services (CRiS), KCT0003555, Registered February 25, 2019, https://cris.nih.go.kr/cris/index/index.do.
Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis
Authors: Ledesma Jorge R. , Ma Jianing , Zheng Peng , Ross Jennifer M. , Vos Theo , Kyu Hmwe H. 
Published: May 2021

Abstract
Background
Identifying and treating individuals with high risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease is critical for eliminating the disease. We aimed to conduct a systematic review and meta-regression analysis to quantify the dose-response relationship between interferon-gamma release assay (IGRA) levels and the risk of progression to active TB.

Methods
We searched PubMed and Embase from 1 January 2001 to 10 May 2020 for longitudinal studies that reported the risk of progression from latent to active TB as a function of baseline IGRA values. We used a novel Bayesian meta-regression method to pool effect sizes from included studies and generate a continuous dose-response risk curve. Our modeling framework enabled us to incorporate random effects across studies, and include data with different IGRA ranges across studies. The quality of included studies were assessed using the Newcastle-Ottawa scale (NOS).

Results
We included 34 studies representing 581,956 person-years of follow-up with a total of 788 incident cases of TB in the meta-regression analysis. Higher levels of interferon-gamma were associated with increased risk of progression to active tuberculosis. In the dose-response curve, the risk increased sharply between interferon-gamma levels 0 and 5 IU/ml, after which the risk continued to increase moderately but at a slower pace until reaching about 15 IU/ml where the risk levels off. Compared to 0 IU/ml, the relative risk of progression to active TB among those with interferon-gamma levels of 0.35, 1, 5, 10, 15, and 20 IU/ml were: 1.64 (1.28–2.08), 2.90 (2.02–3.88), 11.38 (6.64–16.38), 19.00 (13.08–26.90), 21.82 (14.65–32.57), and 22.31 (15.43–33.00), respectively. The dose-response relationship remains consistent when limiting the analysis to studies that scored highest in the NOS.

Conclusion
The current practice of dichotomizing IGRA test results simplifies the TB infection disease continuum. Evaluating IGRA test results over a continuous scale could enable the identification of individuals at greatest risk of progression to active TB.
Management of insecticides for use in disease vector control: a global survey
Authors: van den Berg Henk , da Silva Bezerra Haroldo Sergio , Chanda Emmanuel , Al-Eryani Samira , Nagpal Bhupender N. , Gasimov Elkhan , Velayudhan Raman , Yadav Rajpal S. 
Published: May 2021

Abstract
Background
Vector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the management practices of vector control insecticides at country level to identify gaps to inform future strategies on pesticide management, seeking to improve efficacy of interventions and reduce the side-effects of chemicals used on health and the environment.

Methods
A survey by questionnaire on the management practices of vector control insecticides was disseminated among all WHO Member States. Data were analysed using descriptive statistics in MS Excel.

Results
Responses were received from 94 countries, or a 48% response rate. Capacity for insecticide resistance monitoring was established in 68–80% of the countries in most regions, often with external support; however, this capacity was largely lacking from the European & Others Region (i.e. Western & Eastern Europe, North America, Australia and New Zealand). Procurement of vector control insecticides was in 50–75% of countries taking place by agencies other than the central-level procuring agency, over which the central authorities lacked control, for example, to select the product or assure its quality, highlighting the importance of post-market monitoring. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Large fractions (29–78%) of countries across regions showed shortcomings in worker safety, pesticide storage practices and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Region, which has long been relatively free from mosquito-borne diseases but has recently faced challenges of re-emerging vector-borne diseases.

Conclusions
Critical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country levels to address these challenges.
AIDS fighter health defense: protocol for a randomized controlled trial to test a game-based intervention to improve adolescents’ AIDS prevention ability
Authors: Tang Jian , Chen Yanhua , Yu Xingli , Ren Jianlan , Li Mei , Luo Yue , Xie Hong , Wen Jing 
Published: May 2021

Abstract
Background
Although great progress has been made in the prevention and treatment of AIDS, there are still a considerable number of new infections annually, especially in adolescents. With the advance of technology, game-based education has gradually become an important tool for changing healthy behaviors among youth.

Methods
A protocol for conducting a randomized controlled trial to evaluate the “AIDS Fighter · Health Defense”, a game-based AIDS education project aimed at improving the ability of adolescents to prevent AIDS. During the four-week intervention, participants will receive: 1) A virus combat game; 2) Goal setting to eliminate HIV; 3) Questions to be answered to be resurrected in the game; 4) Points ranking; 5) Recognition and Rewards. The primary outcomes include changes in participants’ knowledge, stigma attitude, and risk behaviors attitude related to AIDS after four weeks of intervention. The secondary outcomes are the participants’ AIDS-related risk behaviors three and six months after the intervention.

Discussion
AIDS Fighter· Health Defense may be an innovative approach to help adolescents improve AIDS prevention capabilities, fill the gap in game-based AIDS prevention education in China, and gain experience of AIDS management.

Trial registration
Chinese Clinical Trial Registry: ChiCTR2000040195. Registered 25 November 2020.
Whole brain 3D MR fingerprinting in multiple sclerosis: a pilot study
Authors: Mostardeiro Thomaz R. , Panda Ananya , Campeau Norbert G. , Witte Robert J. , Larson Nicholas B. , Sui Yi , Lu Aiming , McGee Kiaran P. 
Published: May 2021

Abstract
Background
MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis.

Methods
Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1 × 1 × 1 mm3) and a total acquisition time of 4 min 38 s. Data were collected on 18 subjects paired with 18 controls. Regions of interest were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms. Partial least squares discriminant analysis was performed to discriminate NAWM and Splenium in MS compared with controls.

Results
Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65 % (p = 0.21) and approached 90 % (p < 0.01) for the splenium. There was significant positive correlation between time since diagnosis and MS lesions mean T2 (p = 0.015), minimum T1 (p = 0.03) and negative correlation with splenium uniformity (p = 0.04). Perfect discrimination (AUC = 1) was achieved between selected features from MS lesions and F-NAWM.

Conclusions
3D-MRF has the ability to differentiate between MS and controls based on relaxometry properties from the F-NAWM and splenium. Whole brain coverage allows the assessment of quantitative properties within lesions that provide chronological assessment of the time from MS diagnosis.
Quantitative sonographic assessment of quadriceps muscle thickness for fall injury prediction in patients undergoing maintenance hemodialysis: an observational cohort study
Authors: Sai Asuka , Tanaka Kentaro , Ohashi Yasushi , Kushiyama Akifumi , Tanaka Yoshihide , Motonishi Shuta , Sakai Ken , Hara Shigeko , Ozawa Takashi 
Published: May 2021

Abstract
Background
Accidental fall risk is high in patients undergoing maintenance hemodialysis. Falls are associated with fatal injury, comorbidities, and mortality. Risk assessment should be a primary component of fall prevention. This study investigated whether quadriceps muscle thickness measured using ultrasonography can predict fall injury among dialysis patients.

Methods
Using an observational cohort study design, 180 ambulatory hemodialysis patients were recruited from 2015 to 2016 from four dialysis clinics. The sum of the maximum quadriceps muscle thickness on both sides and the average of the maximum thigh circumference and handgrip strength after hemodialysis were calculated. Patients were stratified according to tertiles of quadriceps muscle thickness. Fall injury was surveyed according to the patient’s self-report during the one-year period.

Results
Among the 180 hemodialysis patients, 44 (24.4%) had fall injuries during the 12-month follow-up period. When the quadriceps muscle thickness levels were stratified into sex-specific tertiles, patients in the lowest tertile were more likely to have a higher incidence of fall injury than those in the higher two tertiles (0.52 vs. 0.19 and 0.17 fall injuries/person-year). After adjusting for covariates, lower quadriceps muscle thickness was found to be an independent predictor of fall injury (hazard ratio [95% confidence interval], 2.33 [1.22–4.52], P < 0.05). Receiver operating characteristic curves were constructed to determine the optimal cutoffs of quadriceps muscle thickness, thigh circumference, and handgrip strength that best predicted fall injury (quadriceps muscle thickness, 3.37 cm and 3.54 cm in men and women; thigh circumference, 44.6 cm and 37.2 cm in men and women; and handgrip strength, 23.3 kg and 16.5 kg in men and women). Using these cutoff values, the areas under the curve were 0.662 (95% CI, 0.576–0.738), 0.625 (95% CI, 0.545–0.699), and 0.701 (95% CI, 0.617–0.774), for quadriceps muscle thickness, thigh circumference, and handgrip strength, respectively. Quadriceps muscle thickness was a more precise predictor of fall injury than thigh circumference and had similar diagnostic performance as handgrip strength tests in dialysis patients.

Conclusions
Quadriceps muscle thickness can be measured easily at the bedside using ultrasonography and is a precise predictor of fall injury in patients undergoing maintenance hemodialysis.
First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients
Authors: Mrevlje Maja , Oblak Manca , Mlinšek Gregor , Lindič Jelka , Jadranka-Buturović-Ponikvar  , Arnol Miha 
Published: May 2021

Abstract
Background
Quantification of proteinuria in kidney transplant recipients is important for diagnostic and prognostic purposes. Apart from correlation tests, there have been few evaluations of spot urine protein measurements in kidney transplantation.

Methods
In this cross-sectional study involving 151 transplanted patients, we investigated measures of agreement (bias and accuracy) between the estimated protein excretion rate (ePER), determined from the protein-to-creatinine ratio in the first and second morning urine, and 24-h proteinuria and studied their performance at different levels of proteinuria. Measures of agreement were reanalyzed in relation to allograft histology in 76 patients with kidney biopsies performed for cause before enrolment in the study.

Results
For ePER in the first morning urine, percent bias ranged from 1 to 28% and accuracy (within 30% of 24-h collection) ranged from 56 to 73%. For the second morning urine, percent bias ranged from 2 to 11%, and accuracy ranged from 71 to 78%. The accuracy of ePER (within 30%) in first and second morning urine progressively increased from 56 and 71% for low-grade proteinuria (150–299 mg/day) to 60 and 74% for moderate proteinuria (300–999 mg/day), and to 73 and 78% for high-grade proteinuria (≥1000 mg/day). Measures of agreement were similar across histologic phenotypes of allograft injury.

Conclusions
The ability of ePER to accurately predict 24-h proteinuria in kidney transplant recipients is modest. However, accuracy improves with an increase in proteinuria. Given the similar accuracy of ePER measurements in first and second morning urine, second morning urine can be used to monitor protein excretion.
Midterm prognosis and surgical implication for clival chordomas after extended transsphenoidal tumor removal and gamma knife radiosurgery
Authors: Ogawa Yoshikazu , Jokura Hidefumi , Tominaga Teiji 
Published: May 2021

Abstract
Background
Treating chordoma through surgery alone is often ineffective. Thus, surgery often performed with irradiation, with a reported 5-year survival rate of 60–75%. The clinical course varies, and disease rarity prevents larger number of clinical investigations.

Methods
In total, 19 patients with clival chordomas were retrospectively extracted from our institutional database. They were initially treated with maximal tumor removal using the extended transsphenoidal approach between March 2006 and January 2021. When total tumor removal was achieved, prophylactic irradiation was not performed. If tumor remnants or recurrence were confirmed, Gamma Knife (GK) radiosurgery was performed. The mean follow-up period was 106.7 months (ranged 27–224 months). The clinical course and prognostic factors were investigated.

Results
Total removal was achieved in 10 patients, whereas 4 patients suffered recurrence and required GK. GK was applied to 11 patients with a 50% isodose of 13–18 Gy (mean: 15.4 Gy), and eight patients remained progression free, whereas three patients suffered repeated local recurrence and died of tumor-related complications. The mean overall progression-free interval was 57.2 months (range: 6–169 months). One male patient died of tumor un-related lung cancer 36 months after the initial treatment, and other patients survived throughout the observational periods. The mean overall survival was 106.7 months (range: 27–224 months). Thus, the 5-year survival rate was 94.7%. Statistical analysis indicated that sex (men), > 15 Gy of 50% isodose by GK, and screening brain examinations as prophylactic medicine were significant favorable prognostic factors.

Conclusions
The favorable outcomes in this investigation suggest the importance of early detection and treatment. Surgery may enable better conditions for sufficient GK doses.