bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of modelling approaches for network meta-analysis of time-to-event outcomes in the presence of non-proportional hazards to aid decision making: Application to a melanoma network
Authors: Freeman Suzanne C , Cooper Nicola J , Sutton Alex J , Crowther Michael J , Carpenter James R , Hawkins Neil 
Published: January 2022

Background Synthesis of clinical effectiveness from multiple trials is a well-established component of decision-making. Time-to-event outcomes are often synthesised using the Cox proportional hazards model assuming a constant hazard ratio over time. However, with an increasing proportion of trials reporting treatment effects where hazard ratios vary over time and with differing lengths of follow-up across trials, alternative synthesis methods are needed. Objectives To compare and contrast five modelling approaches for synthesis of time-to-event outcomes and provide guidance on key considerations for choosing between the modelling approaches. Methods The Cox proportional hazards model and five other methods of estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption, were applied to a network of melanoma trials reporting overall survival: restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models. Results All models fitted the melanoma network acceptably well. However, there were important differences in extrapolations of the survival curve and interpretability of the modelling constraints demonstrating the potential for different conclusions from different modelling approaches. Conclusion The restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can accommodate non-proportional hazards and differing lengths of trial follow-up within a network meta-analysis of time-to-event outcomes. We recommend that model choice is informed using available and relevant prior knowledge, model transparency, graphically comparing survival curves alongside observed data to aid consideration of the reliability of the survival estimates, and consideration of how the treatment effect estimates can be incorporated within a decision model.
Blocking the Increase of Intracellular Deuterium Concentration Prevents the Expression of Cancer-Related Genes, Tumor Development, and Tumor Recurrence in Cancer Patients
Authors: Kovács Beáta Zs. , Puskás László G. , Nagy Lajos I. , Papp András , Gyöngyi Zoltán , Fórizs István , Czuppon György , Somlyai Ildikó , Somlyai Gábor 
Published: January 2022

The possible role of the naturally occurring deuterium in the regulation of cell division was first described in the 1990s. To investigate the mechanism of influence of deuterium (D) on cell growth, expression of 236 cancer-related and 536 kinase genes were tested in deuterium-depleted (40 and 80 ppm) and deuterium-enriched (300 ppm) media compared to natural D level (150 ppm). Among genes with expression changes exceeding 30% and copy numbers over 30 (124 and 135 genes, respectively) 97.3% of them was upregulated at 300 ppm D-concentration. In mice exposed to chemical carcinogen, one-year survival data showed that deuterium-depleted water (DDW) with 30 ppm D as drinking water prevented tumor development. One quarter of the treated male mice survived 344 days, the females 334 days, while one quarter of the control mice survived only 188 and 156 days, respectively. In our human retrospective study 204 previously treated cancer patients with disease in remission, who consumed DDW, were followed. Cumulative follow-up time was 1024 years, and average follow-up time per patient, 5 years (median: 3.6 years). One hundred and fifty-six patients out of 204 (77.9%) did not relapse during their 803 years cumulative follow-up time. Median survival time (MST) was not calculable due to the extremely low death rate (11 cancer-related deaths, 5.4% of the study population). Importantly, 8 out of 11 deaths occurred several years after stopping DDW consumption, confirming that regular consumption of DDW can prevent recurrence of cancer. These findings point to the likely mechanism in which consumption of DDW keeps D-concentration below natural levels, preventing the D/H ratio from increasing to the threshold required for cell division. This in turn can serve as a key to reduce the relapse rate of cancer patients and/or to reduce cancer incidence in healthy populations.
Engaging Adolescents in the Fight Against Drug Abuse and Addiction: A Concept Mapping Approach
Authors: Montgomery LaTrice , Vaughn Lisa M. , Jacquez Farrah 
Published: January 2022

Background To identify contextually-relevant strategies for reducing and eventually eliminating addiction, it is imperative to engage stakeholders that are most affected by drug abuse but typically left out of the conversation, such as adolescents. Aim The aim of this study was to collaborate with 45 adolescent stakeholders participating in a school-based research program to identify areas to address addiction. Methods Guided by a modified version of the mixed-methods concept mapping approach, adolescents were asked to brainstorm and sort a list of statements about how to address addiction in their community. The data were then analyzed via multidimensional scaling and hierarchical cluster analysis. Results The concept map identified eight clusters from 75 edited statements: policing/security (e.g., increase punishment for selling drugs), helping community (e.g., create more jobs), treatment (e.g., make treatments more affordable), increased awareness (e.g., identify and help at-risk youth), communication (e.g., more communication with people who are abusing drugs), increased understanding/education (e.g., online communities for people who are abusing drugs), clean up community (e.g., clean up abandoned houses) and prevent addiction (e.g., effectively deal with peer pressure). Discussion These stakeholder-driven ideas are consistent with the socioecological framework of addressing substance use and add to the credibility and transferability of individual and systemic level approaches to reducing substance use in marginalized communities. Conclusion This study emphasizes the feasibility of engaging adolescents in the development of contextually-relevant addiction education, prevention, and treatment interventions in underserved communities.
Alternative receptive language assessment modalities and stimuli for autistic children who are minimally verbal
Authors: Muller Kristen , Brady Nancy C , Fleming Kandace K 
Published: January 2022

The primary aim of this study was to evaluate and compare alternative modalities and stimuli used to measure receptive vocabulary skills in autistic children who are minimally verbal. This study systematically compared participants’ outcomes on three different receptive vocabulary assessment conditions: a low-tech assessment that used a stimulus book, a touchscreen assessment, and an assessment that used real-object stimuli. A secondary aim of this study was to examine how individual characteristics such as nonverbal cognition, maladaptive behavior, and autism symptomology impact performance on assessment conditions. Participants were 27 autistic students between the ages of 3 and 12 who had minimal verbal skills. Participants responded to 12 items in 3 assessment conditions (972 total items). Results from a crossed random effects model showed that participants’ scores in the real-object assessment condition were significantly higher than in the low-tech book condition and marginally higher than scores in the touchscreen assessment condition. Nonverbal cognition accounted for 44% of the variance in participants’ scores. Lay abstract It is difficult to measure language comprehension abilities in autistic children who have limited expressive language skills. Results from available assessments may underestimate autistic children’s receptive language skills. The primary purpose of this study was to compare alternative modalities and stimuli used to measure receptive vocabulary skills in autistic children who are minimally verbal. This study compared participants’ outcomes on three different receptive vocabulary assessment conditions: an assessment that used a low-tech stimulus book, a touchscreen assessment, and an assessment that used real-object stimuli. Twenty-seven students between the ages of 3 and 12 who had minimal verbal skills and a diagnosis of autism spectrum disorder participated in this study. Results showed that participants’ scores in the real-object assessment condition were significantly higher than in the low-tech condition and marginally higher than scores in the touchscreen condition. These results suggest real-object stimuli may provide a more robust measure of autistic children’s receptive vocabulary skills than traditional low-tech picture stimuli. Although many direct standardized assessments use picture stimuli to measure word understanding, when assessing autistic individuals who have limited expressive language, real objects can be used in replacement of, or in addition to, picture stimuli.
Effects of Medium Cut-Off Versus High-Flux Hemodialysis Membranes on Biomarkers: A Systematic Review and Meta-Analysis
Authors: Kandi Maryam , Brignardello-Petersen Romina , Couban Rachel , Wu Celina , Nesrallah Gihad 
Published: January 2022

Background: Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da. Objectives: We undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers. Methods: We searched MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science from January 2015 to July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults (>18 years) receiving maintenance hemodialysis. We performed study selection, data extraction, and quality appraisals in duplicate and used the Grading of Recommendations Assessment, Development, and Evaluation framework. Outcomes included solute removal (plasma clearance or dialysate quantitation), reduction ratios, and predialysis serum concentrations for a range of prespecified large middle molecules. Results: We identified 26 eligible studies (10 RS and 16 NRS; N = 1883 patients; patient-years = 1366.3). The mean difference (MD) for albumin removal was 2.31 g per session (95% confidence interval [CI], 2.79 to 1.83; high certainty), with a reduction in predialysis albumin of −0.12 g/dl (95% CI, −0.16 to −0.07; I2 = 0%; high certainty) in the first 24 weeks, returning to normal (MD = −0.02 g/dl, 95% CI, −0.07 to −0.03; I2 = 56%; high certainty) after 24 weeks. We also found with high certainty that MCO dialysis resulted in a large increase (standardized mean difference [SMD]> 2.0 for all) in β2-microglobulin, κ- and λ-free light chains, and myoglobin removal, resulting in moderate (SMD > 0.5) to large (SMD > 0.8) reductions in predialysis concentrations for all of these solutes. Medium cut-off dialysis increased the reduction ratio for tumor necrosis factor-alpha (TNF-α) by 7.7% (95% CI, 4.7 to 10.6; moderate certainty), and reduced predialysis TNF-α by SMD −0.48 (95% CI, −0.91 to −0.04; moderate certainty). We found with moderate certainty that MCO dialysis had little to no effect on predialysis interleukin-6 (IL-6) plasma concentrations. Medium cut-off dialysis reduced mRNA expression of TNF-α and IL-6 in peripheral leukocytes by MD −15% (95% CI, −19.6 to −10.4; moderate certainty) and −8.8% (95% CI, −10.2 to −7.4; moderate certainty), respectively. Conclusion: Medium cut-off dialysis increases the clearance of a wide range of large middle molecules and likely reduces inflammatory mediators with a concomitant transient reduction in serum albumin concentration. The net effect of MCO dialysis on large middle molecules could translate into important clinical effects.
Degenerative Cervical Myelopathy: A Practical Approach to Diagnosis
Authors: Tetreault Lindsay , Kalsi-Ryan Sukhvinder , Benjamin Davies  , Nanna-Lohkamp Laura , Garwood Philip , Martin Allan R. , Wilson Jefferson R. , Harrop James S. , Guest James D. , Kwon Brian K. , Milligan James , Arizala Alberto Martinez , Kotter Mark R. , Fehlings Michael G. 
Published: January 2022

Study Design Narrative Review. Objectives The objective of this review is to provide a stepwise approach to the assessment of patients with potential symptoms of degenerative cervical myelopathy (DCM). Methods N/A Results DCM is an overarching term used to describe progressive compression of the cervical spinal cord by age-related changes to the spinal axis. These alterations to normal anatomy narrow the spinal canal, reduce the space available for the spinal cord, and may ultimately compress the ascending and descending neural tracts. Patients with DCM present with a wide range of symptoms that can significantly impact quality of life, including bilateral hand numbness and paresthesia, gait impairment, motor weakness of the upper and lower extremities, and bladder and bowel dysfunction. Unfortunately, DCM is often misdiagnosed, resulting in delayed assessment and management by the appropriate specialist. The proper evaluation of a patient with suspected DCM includes obtaining a detailed patient history, conducting a comprehensive neurological examination, and ordering appropriate tests to rule in or out other diagnoses. Conclusion This review summarizes a stepwise approach to the diagnosis of patients with DCM.
Ideal Combination of Anatomic Tibial and Femoral Tunnel Positions for Single-Bundle ACL Reconstruction
Authors: Yoon Kyoung Ho , Kim Yoon-Seok , Park Jae-Young , Kim Sang-Gyun , Lee Jong-Hwan , Choi Sun Hwan , Kim Sang Jin 
Published: January 2022

Background: Anatomic anterior cruciate ligament reconstruction (ACLR) is preferred over nonanatomic ACLR. However, there is no consensus on which point the tunnels should be positioned among the broad anatomic footprints. Purpose/Hypothesis: To identify the ideal combination of tibial and femoral tunnel positions according to the femoral and tibial footprints of the anteromedial (AM) and posterolateral (PL) anterior cruciate ligament bundles. It was hypothesized that patients with anteromedially positioned tunnels would have better clinical scores, knee joint stability, and graft signal intensity on follow-up magnetic resonance imaging (MRI) than those with posterolaterally positioned tunnels. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 119 patients who underwent isolated single-bundle ACLR with a hamstring autograft from July 2013 to September 2018 were retrospectively investigated. Included were patients with clinical scores and knee joint stability test results at 2-year follow-up and postoperative 3-dimensional computed tomography and 1-year postoperative MRI findings. The cohort was divided into 4 groups, named according to the bundle positions in the tibial and femoral tunnels: AM-AM (n = 33), AM-PL (n = 26), PL-AM (n = 29), and PL-PL (n = 31). Results: There were no statistically significant differences among the 4 groups in preoperative demographic data or postoperative clinical scores (Lysholm, Tegner, and International Knee Documentation Committee subjective scores); knee joint stability (anterior drawer, Lachman, and pivot-shift tests and Telos stress radiographic measurement of the side-to-side difference in anterior tibial translation); graft signal intensity on follow-up MRI; or graft failure. Conclusion: No significant differences in clinical scores, knee joint stability, or graft signal intensity on follow-up MRI were identified between the patients with anteromedially and posterolaterally positioned tunnels.
Prevalence and determinants of activity of daily living and instrumental activity of daily living among elderly in India
Authors: Chauhan Shekhar , Kumar Shubham , Bharti Rupam , Patel Ratna 
Published: January 2022

Abstract
Background
The increase in life expectancy has proliferated the number of elderly and subsequently increased the prevalence of disability among the elderly. This study assesses the prevalence of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL) and analyzes determinants of ADL and IADL among elderly aged 60 and over living in India.

Methods
The study utilized the Longitudinal Ageing Study in India (LASI, 2017–18) data, and information was sought from 31,464 elderly aged 60 years and above. An index of ADL and IADL was created on a scale of three levels, exhibiting no, moderate, or severe levels of ADL/IADL disability. Multinomial logistic regression was used to determine the effect of socio-demographic parameters on ADL and IADL disability among the elderly.

Results
Around 3% of the elderly reported severe ADL disability, and 6% elderly reported severe IADL disability. Elderly who were not involved in any physical activity than their counterparts were more likely to report severe ADL (RRR = 2.68, C.I. = 1.66–4.32) and severe IADL (RRR = 2.70, C.I. = 1.98–3.67) than no ADL and no IADL, respectively.

Conclusion
Amidst the study finding, the study emphasizes the importance of setting-up of geriatric care centers in rural and urban areas. It would be feasible to provide geriatric care under the umbrella of already functioning government health facilities in different parts of the country. Community interventions earmarking the elderly with a focus on physical activity, specifically based in group physical exercise and implemented through existing networks, are rewarding for the elderly.
Association between body mass index, multi-morbidity and activities of daily living among New Zealand nursing home older adults: a retrospective analysis of nationwide InterRAI data
Authors: Amankwaa Isaac , Nelson Katherine , Rook Helen , Hales Caz 
Published: January 2022

Abstract
Background
Obesity is a well-established risk factor for multi-morbidity and disability among older adults in the community and acute care settings. However, nursing home residents with body mass index (BMI) below 18.5 kg/m2 and above 25.0 kg/m2 have been understudied. We examined the prevalence of multi-morbidity and disability in activities of daily living (ADL) by BMI category and further investigated the association between BMI, multi-morbidity, and disability of ADL in a large cohort of older adults in nursing homes in New Zealand.

Methods
A retrospective review of nursing home residents’ data obtained from the New Zealand International Resident Assessment Instrument national dataset from 2015 to 2018. One hundred ninety-eight thousand seven hundred ninety older adults (≥60 years) living in nursing homes were included. BMI was calculated as weight in kilograms (kg) divided by height in meters squared (m2). Multimorbidity was defined as the presence of ≥2 health conditions. The risk of disability was measured by a 4-item ADL self-performance scale. The prevalence ratio (PR) of the association between BMI and multi-morbidity and between BMI and disability in ADL was assessed using Poisson regression with robust variance.

Results
Of the 198,790 residents, 10.6, 26.6, 11.3 and 5.4% were underweight, overweight, obese, and extremely obese, respectively. 26.4, 31.3 and 21.3% had one, two and three disease conditions, respectively, while 14.3% had four or more conditions. 24.1% could perform only one ADL, and 16.1% could perform none. The prevalence of multi-morbidity increased with increasing BMI, whereas mean disability in ADL decreased with increasing BMI. The risk of multi-morbidity was higher for the overweight (PR, 95%CI: 1.03, 1.02–1.03) and obese (PR, 95% CI: 1.07, 1.06–1.08) compared to normal weight after controlling for age, sex, ethnicity, and region. BMI was inversely associated with mean ADL; β, 95% CI for overweight (− 0.30, − 0.32, − 0.28) and obese − 0.43, − 0.45, − 0.40 compared to normal weight.

Conclusion
Being underweight was associated with a decline in the performance of ADL in nursing home residents. In contrast, being overweight and obese positively affected functional performance, demonstrating that the obesity paradox plays an important role in this population. The observed associations highlight areas where detection and management of underweight and healthy aging initiatives may be merited.
Global school-based student health survey: country profiles and survey results in the eastern Mediterranean region countries
Authors: Abdalmaleki Elham , Abdi Zhaleh , Isfahani Sahand Riazi , Safarpoor Sara , Haghdoost Bahar , Sazgarnejad Saharnaz , Ahmadnezhad Elham 
Published: January 2022

AbstractBackgroundThe increasing prevalence of non-communicable diseases (NCDs) has some major implications on many countries to achieve universal health coverage. This study aimed to investigate the implementation of Global School-based Student Health Survey (GSHS), which is used to assess the risk factors of NCDs among children and adolescents in the eastern Mediterranean region (EMR).MethodsThis study was a meta-analysis and systematic literature review of 2001–2018 published studies, which were found by searching PubMed, Google Scholar, WHO, and CDC databases. In this study, the target group was students aged between 13 and 17 years old. GSHS implementation as well as risk factors of NCDs were compared across different countries. The random-effect model for meta-analysis was considered at 95% confidence interval.ResultIn the EMR, 19 countries have implemented GSHS at least once following the survey manual (37 surveys). Overall, 201,795 students were included in our analysis. The overall estimation prevalence rateof the overweight was 24.5% (20.6–28.8), obesity was 7.3% (5.4–9.5), insufficient physical activity was 82.4% (80.7–84.1), tobacco usage was 14.3% (10.53–18.67), and smoking was 9.6% (8.1–11.3), respectively. Among those aged 13 to 17 years old, these rates were estimated as 19.8 (13.2–27.3), 9.7 (6.2–14.0), 86.1 (84.1–87.9), 17.8 (11.8–24.7), and 11.5 (9.4–13.8), respectively.ConclusionGSHS has been widely implemented across EMR countries. Using nationally representative data, the results show that more efforts are needed to target the NCDs risk factors among adolescents in the region.