bluuebunny/crossref_metadata_2025_split huggingface dataset:
GripAble: An accurate, sensitive and robust digital device for measuring grip strength
Authors: Mace Michael , Mutalib Sharah Abdul , Ogrinc Matjaz , Goldsmith Nicola , Burdet Etienne 
Published: March 2022

Introduction Grip strength is a reliable biomarker of overall health and physiological well-being. It is widely used in clinical practice as an outcome measure. This paper demonstrates the measurement characteristics of GripAble, a wireless mobile handgrip device that measures grip force both isometrically and elastically-resisted for assessment and training of hand function. Methods A series of bench tests were performed to evaluate GripAble's grip force measurement accuracy and sensitivity. Measurement robustness was evaluated through repeated drop tests interwoven with error verification test phases. Results GripAble's absolute measurement error at the central position was under 0.81 and 1.67 kg (95th percentiles; N = 47) when measuring elastically and isometrically, respectively, providing similar or better accuracy than the industry-standard Jamar device. Sensitivity was measured as 0.062 ± 0.015 kg (mean ± std; 95th percentiles: [0.036, 0.089] kg; N = 47), independent of the applied force. There was no significant performance degradation following impact from 30 drops from a height >1.5 m. Conclusion GripAble is an accurate and reliable grip strength dynamometer. It is highly sensitive and robust, which in combination with other novel features (e.g. portability, telerehabilitation and digital data tracking) enable broad applicability in a range of clinical caseloads and environments.
Cracking the Hip: Does Protocol Matter? A Retrospective Cohort Study Investigating the Effect of Protocol Implementation
Authors: Levi Amelia R , Coste Marine , Warshowsky Ethan , Shah Neil V , Suneja Nishant , Schwartz Jeffrey M. , Roudnitsky Valery 
Published: February 2022

Introduction Approximately 300 000 hip fractures occur annually in the USA in patients >65 years old. Early intervention is key in reducing morbidity and mortality. Our institution implemented a collaborative hip fracture protocol, streamlining existing processes to reduce time to OR (TTO) and hospital length of stay (LOS). Our aim was to determine if this protocol improved these outcomes. Study Design We conducted a retrospective cohort study using our level-1 trauma center’s trauma registry, comparing outcomes for patients >60 years old with isolated hip fractures pre-and post-hip protocol implementation in May 2018. Our primary outcomes were TTO and in-hospital mortality. Secondary outcomes included LOS and postoperative complications. Univariate analysis was done using chi-square and T-test. Results We identified 176 patients with isolated hip fractures: 69 post- and 107 pre-protocol. Comparing post- to pre-protocol, TTO decreased by 18hrs (39 vs 57h; P = .013) and patients had fewer postoperative complications (9 vs 23%; P = .016) despite post-protocol patients being more likely to have diabetes (42 vs 27%, P < .05), elevated BMI (22 vs 25; P < .001), and to be current smokers (9 vs 2%; P < .05). LOS and in-hospital mortality also decreased (11 vs 20d; P = .312, 4.3 vs 7.5%; P = .402). Post-protocol patients were more likely to go to the OR within 24hrs of presentation (39 vs 16%; P < .001) and to go straight from ED to OR (32 vs 4%; P < .001). Conclusion TTO, LOS, and postoperative complications for isolated hip fracture patients were lower post-protocol. Though not all statistically significant, this trend indicates that the protocol was helpful in improving hip fracture outcomes but may require further improvement and institution-wide education.
The Utility of ‘Minimal Access and Separation Surgery’ in the Management of Metastatic Spine Disease
Authors: Kumar Naresh , Tan Jiong H. , Thomas Andrew C. , Tan Joel Y. H. , Madhu Sirisha , Shen Liang , Lopez Keith G. , Hey Dennis H. W. , Liu Gabriel , Wong HeeKit 
Published: March 2022

Study Design Retrospective cohort study. Objectives To compare outcomes of percutaneous pedicle screw fixation (PPSF) to open posterior stabilization (OPS) in spinal instability patients and minimal access separation surgery (MASS) to open posterior stabilization and decompression (OPSD) in metastatic spinal cord compression (MSCC) patients. Methods We analysed patients who underwent surgery for thoracolumbar metastatic spine disease (MSD) from Jan 2011 to Oct 2017. Patients were divided into minimally invasive spine surgery (MISS) and open spine surgery (OSS) groups. Spinal instability patients were treated with PPSF/OPS with pedicle screws. MSCC patients were treated with MASS/OPSD. Outcomes measured included intraoperative blood loss, operative time, duration of hospital stay and ASIA-score improvement. Time to initiate radiotherapy and perioperative surgical/non-surgical complications was recorded. Propensity scoring adjustment analysis was utilised to address heterogenicity of histological tumour subtypes. Results Of 200 eligible patients, 61 underwent MISS and 139 underwent OSS for MSD. There was no significant difference in baseline characteristics between MISS and OSS groups. In the MISS group, 28 (45.9%) patients were treated for spinal instability and 33 (54.1%) patients were treated for MSCC. In the OSS group, 15 (10.8%) patients were treated for spinal instability alone and 124 (89.2%) were treated for MSCC. Patients who underwent PPSF had significantly lower blood loss (95 mL vs 564 mL; P < .001) and surgical complication rates( P < .05) with shorter length of stay approaching significance (6 vs 19 days; P = .100) when compared to the OPS group. Patients who underwent MASS had significantly lower blood loss (602 mL vs 1008 mL) and shorter length of stay (10 vs 18 days; P = .098) vs the OPSD group. Conclusion This study demonstrates the benefits of PPSF and MASS over OPS and OPSD for the treatment of MSD with spinal instability and MSCC, respectively.
Incidence and Type of Right Ventricular Diastolic Dysfunction in Postoperative Tetralogy of Fallot Pediatric Patients
Authors: Kidwai Mohammad Moaaz , Azad Sushil , Radhakrishnan Sitaraman , Garg Ankit 
Published: March 2022

Objective: Assessment of right ventricular (RV) diastolic function in postoperative Tetralogy of Fallot (TOF) patients is not routinely done during intermediate follow-up. We have done this study to assess the incidence and type of RV diastolic dysfunction in these patients. Method: Ninety patients who were less than 18 years and underwent total correction for TOF were analyzed in this study. The incidence and type of RV diastolic dysfunction was measured and the effect of degree of pulmonary regurgitation on RV diastolic function was also seen. Results: The total number of patients with RV diastolic dysfunction was 46 (51.1%). Restrictive RV physiology was seen in 8 patients (8.8%) and the most common type of RV diastolic dysfunction seen was pseudonormal filling, seen in 23 (25.6%) patients. Conclusion: Subclinical RV diastolic dysfunction is present in almost half of the postoperative TOF patients of pediatric age group. The most prevalent form of diastolic dysfunction was pseudonormal filling during intermediate follow-up.
Triceps Tendon Repair
Authors: Yalcin Sercan , Maier Jacob , Schickendantz Mark 
Published: March 2022

Background: Triceps tendon tear has a low incidence. Therefore, surgical repair of the triceps tendon is performed only by a small number of orthopedic surgeons. Indications: To provide information regarding the current treatment algorithm and surgical technique. Technique Description: The triceps tendon is exposed through a posterior approach. The tendon is then longitudinally split to expose the deep degenerated tissue. The degenerated tissue and any existing osteophytes are removed. The superficial layer of the tendon is sewn back down to the deeper layer of the tendon. The tendon is advanced distally, and the split incision is closed. This is followed by double–row repair with suture anchors. Results: Excellent clinical outcomes have been reported with re–rupture rates of around 7% at a 4–year follow–up. Discussion/Conclusion: Partial and complete ruptures of the triceps tendon require surgical treatment. Current surgical treatment options yield excellent clinical outcomes.
Evidence supporting a role for the immune checkpoint protein B7-H3 in NK cell-mediated cytotoxicity against AML
Authors: Tyagi Anudishi , Ly Stanley , El-Dana Fouad , Yuan Bin , Jaggupilli Appalaraju , Grimm Sabrina , Konopleva Marina , Bühring Hans-Jörg , Battula V. Lokesh 
Published: March 2022

AbstractWe observed that the immune checkpoint protein B7-H3 is overexpressed in acute myeloid leukemia (AML) patients with poor treatment outcomes. Inhibition of B7-H3 expression or blocking of its activity using a novel monoclonal antibody (T-1A5) in AML cells significantly enhanced natural killer (NK) cell-mediated cytotoxicity in AML cells in vitro and in vivo. Moreover, a human-mouse chimera of this antibody (ChT-1A5) induced antibody-dependent cell-mediated cytotoxicity (ADCC) in B7-H3+ primary AML cells, but not in normal hematopoietic cells, suggesting the specify of this antibody for AML cells. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft (PDX) models. Our results suggest that the ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.
A novel salt-tolerant strain Trichoderma atroviride HN082102.1 isolated from marine habitat alleviates salt stress and diminishes cucumber root rot caused by Fusarium oxysporum
Authors: Zhang Chongyuan , Wang Weiwei , Hu Yihui , Peng Zhongpin , Ren Sen , Xue Ming , Liu Zhen , Hou Jumei , Xing Mengyu , Liu Tong 
Published: March 2022

Abstract
Background
Salt stress threaten the growth of plants, and even aggravate plant disease. In this article, salt-tolerant Trichoderma strain was isolated, and its potential to alleviate salt stress and diminish cucumber root rot caused by Fusarium oxysporum was evaluated.

Results
Twenty-seven Trichoderma isolates were isolated from samples of sea muds and algae collected from the South Sea of China. Among these, the isolate HN082102.1 showed the most excellent salt tolerance and antagonistic activity against F. oxysporum causing root rot in cucumber and was identified as T. atroviride. Its antagonism ability may be due to mycoparasitism and inhibition effect of volatile substances. The application of Trichoderma mitigated the adverse effects of salt stress and promoted the growth of cucumber under 100 mM and 200 mM NaCl, especially for the root. When T. atroviride HN082102.1 was applied, root fresh weights increased by 92.55 and 84.86%, respectively, and root dry weights increased by 75.71 and 53.31%, respectively. Meanwhile, the application of HN082102.1 reduced the disease index of cucumber root rot by 63.64 and 71.01% under 100- and 0-mM saline conditions, respectively, indicating that this isolate could inhibit cucumber root rot under salt stress.

Conclusions
This is the first report of salt-tolerant T. atroviride isolated from marine habitat showing antagonistic activity to F. oxysporum, and the results provide evidence for the novel strain T. atroviride HN082102.1 in alleviating salt stress and diminishing cucumber root rot, indicating that T. atroviride strain HN082102.1 can be used as biological control agent in saline alkali land.
Bayesian identification of structural coefficients in causal models and the causal false-positive risk of confounders and colliders in linear Markovian models
Authors: Kelter Riko 
Published: February 2022

Abstract
Background
Causal inference has seen an increasing popularity in medical research. Estimation of causal effects from observational data allows to draw conclusions from data when randomized controlled trials cannot be conducted. Although the identification of structural causal models (SCM) and the calculation of structural coefficients has received much attention, a key requirement for valid causal inference is that conclusions are drawn based on the true data-generating model.

Methods
It remains widely unknown how large the probability is to reject the true structural causal model when observational data from it is sampled. The latter probability – the causal false-positive risk – is crucial, as rejection of the true causal model can induce bias in the estimation of causal effects. In this paper, the widely used causal models of confounders and colliders are studied regarding their causal false-positive risk in linear Markovian models. A simulation study is carried out which investigates the causal false-positive risk in Gaussian linear Markovian models. Therefore, the testable implications of the DAG corresponding to confounders and colliders are analyzed from a Bayesian perspective. Furthermore, the induced bias in estimating the structural coefficients and causal effects is studied.

Results
Results show that the false-positive risk of rejecting a true SCM of even simple building blocks like confounders and colliders is substantial. Importantly, estimation of average, direct and indirect causal effects can become strongly biased if a true model is rejected. The causal false-positive risk may thus serve as an indicator or proxy for the induced bias.

Conclusion
While the identification of structural coefficients and testable implications of causal models have been studied rigorously in the literature, this paper shows that causal inference also must develop new concepts for controlling the causal false-positive risk. Although a high risk cannot be equated with a substantial bias, it is indicative of the induced bias. The latter fact calls for the development of more advanced risk measures for committing a causal type I error in causal inference.
Enrichment Bayesian design for randomized clinical trials using categorical biomarkers and a binary outcome
Authors: Vinnat Valentin , Chevret Sylvie 
Published: February 2022

Abstract
Background
Adaptive clinical trials have been increasingly commonly employed to select a potential target population for one trial without conducting trials separately. Such enrichment designs typically consist of two or three stages, where the first stage serves as a screening process for selecting a specific subpopulation.

Methods
We propose a Bayesian design for randomized clinical trials with a binary outcome that focuses on restricting the inclusion to a subset of patients who are likely to benefit the most from the treatment during trial accrual. Several Bayesian measures of efficacy and treatment-by-subset interactions were used to dictate the enrichment, either based on Gail and Simon’s or Millen’s criteria. A simulation study was used to assess the performance of our design. The method is exemplified in a real randomized clinical trial conducted in patients with respiratory failure that failed to show any benefit of high flow oxygen supply compared with standard oxygen.

Results
The use of the enrichment rules allowed the detection of the existence of a treatment-by-subset interaction more rapidly compared with Gail and Simon’s criteria, with decreasing proportions of enrollment in the whole sample, and the proportions of enrichment lower, in the presence of interaction based on Millen’s criteria. In the real dataset, this may have allowed the detection of the potential interest of high flow oxygen in patients with a SOFA neurological score ≥ 1.

Conclusion
Enrichment designs that handle the uncertainty in treatment efficacy by focusing on the target population offer a promising balance for trial efficiency and ease of interpretation.
Distributional regression in clinical trials: treatment effects on parameters other than the mean
Authors: Heller Gillian Z. , Robledo Kristy P. , Marschner Ian C. 
Published: February 2022

Abstract
Background
The classical linear model is widely used in the analysis of clinical trials with continuous outcomes. However, required model assumptions are frequently not met, resulting in estimates of treatment effect that can be inefficient and biased. In addition, traditional models assess treatment effect only on the mean response, and not on other aspects of the response, such as the variance. Distributional regression modelling overcomes these limitations. The purpose of this paper is to demonstrate its usefulness for the analysis of clinical trials, and superior performance to that of traditional models.

Methods
Distributional regression models are demonstrated, and contrasted with normal linear models, on data from the LIPID randomized controlled trial, which compared the effects of pravastatin with placebo in patients with coronary heart disease. Systolic blood pressure (SBP) and the biomarker midregional pro-adrenomedullin (MR-proADM) were analysed. Treatment effect was estimated in models that used response distributions more appropriate than the normal (Box-Cox-t and Johnson’s Su for MR-proADM and SBP, respectively), applied censoring below the detection limit of MR-proADM, estimated treatment effect on distributional parameters other than the mean, and included random effects for longitudinal observations. A simulation study was conducted to compare the performance of distributional regression models with normal linear regression, under conditions mimicking the LIPID study. The R package gamlss (Generalized Additive Models for Location, Scale and Shape), which implements maximum likelihood estimation for distributional regression modelling, was used throughout.

Results
In all cases the distributional regression models fit the data well, in contrast to poor fits obtained for traditional models; for MR-proADM a small but significant treatment effect on the mean was detected by the distributional regression model and not the normal model; and for SBP a beneficial treatment effect on the variance was demonstrated. In the simulation study distributional models strongly outperformed normal models when the response variable was non-normal and heterogeneous; and there was no disadvantage introduced by the use of distributional regression modelling when the response satisfied the normal linear model assumptions.

Conclusions
Distributional regression models are a rich framework, largely untapped in the clinical trials world. We have demonstrated a sample of the capabilities of these models for the analysis of trials. If interest lies in accurate estimation of treatment effect on the mean, or other distributional features such as variance, the use of distributional regression modelling will yield superior estimates to traditional normal models, and is strongly recommended.

Trial registration
The LIPID trial was retrospectively registered on ANZCTR on 27/04/2016, registration number ACTRN12616000535471.
Locating and testing the healthy context paradox: examples from the INCLUSIVE trial
Authors: Melendez-Torres G. J. , Warren Emily , Ukoumunne Obioha C , Viner Russell , Bonell Chris 
Published: February 2022

AbstractBackgroundThe healthy context paradox, originally described with respect to school-level bullying interventions, refers to the generation of differences in mental wellbeing amongst those who continue to experience bullying even after interventions successfully reduce victimisation. Using data from the INCLUSIVE trial of restorative practice in schools, we relate this paradox to the need to theorise potential harms when developing interventions; formulate the healthy context paradox in a more general form defined by mediational relationships and cluster-level interventions; and propose two statistical models for testing the healthy context paradox informed by multilevel mediation methods, with relevance to structural and individual explanations for this paradox.MethodsWe estimated two multilevel mediation models with bullying victimisation as the mediator and mental wellbeing as the outcome: one with a school-level interaction between intervention assignment and the mediator; and one with a random slope component for the student-level mediator-outcome relationship predicted by school-level assignment. We relate each of these models to contextual or individual-level explanations for the healthy context paradox.ResultsNeither model suggested that the INCLUSIVE trial represented an example of the healthy context paradox. However, each model has different interpretations which relate to a multilevel understanding of the healthy context paradox.ConclusionsGreater exploration of intervention harms, especially when those accrue to population subgroups, is an essential step in better understanding how interventions work and for whom. Our proposed tests for the presence of a healthy context paradox provide the analytic tools to better understand how to support development and implementation of interventions that work for all groups in a population.Trial registrationCurrent Controlled Trials,ISRCTN10751359.
Feasibility of an online training and support program for dementia carers: results from a mixed-methods pilot randomized controlled trial
Authors: Teles Soraia , Ferreira Ana , Paúl Constança 
Published: March 2022

AbstractBackgroundiSupport is an online program developed by the World Health Organization to provide education, skills training, and social support to informal carers of persons with dementia. This pilot study examines the feasibility of the protocol for a main effectiveness trial of iSupport-Portugal and explores how the intervention and control arms compare over time on well-being outcomes.MethodsA mixed-methods experimental parallel between-group design with two arms is followed. Participants were recruited nationwide, by referral or advertising, through the National Alzheimer’s Association. Inclusion criteria are being Portuguese adults, providing e-consent, providing unpaid care to someone with dementia for at least 6 months, experiencing relevant scores on burden (≥ 21 on ZBI) or depression or anxiety (≥ 8 on HADS), and using webpages autonomously. Participants were consecutively randomized to receive iSupport-Portugal or an education-only e-book and were not blinded to group assignment. Data were collected online with self-administered instruments, at baseline, 3 and 6 months after. Outcomes comprise caregiver burden, depression, anxiety, QoL, positive aspects of caregiving, and self-efficacy. Generalized estimating equations were used to estimate group, time, and group-by-time effects. Intervention engagement data were extracted from iSupport’s platform. Semi-structured interviews were conducted.ResultsForty-two participants were allocated to the intervention (N = 21) and control (N = 21) arms. Participation (78.1%) and retention rates (73.8%) were fair. More carers in the control arm completed the study (N = 20, 95.2%) than in the intervention arm (N = 11; 52.4%) (χ2 = 9.98,p = .002). Non-completers were younger, spent less time caring, and scored higher on anxiety. Among carers in the intervention arm, the average attendance rate was of 53.7%. At post-test 38.9% of participants still used iSupport; the remainder participants interrupted use within 2 weeks (Mdn). For per-protocol analyses, significant group-by-time interaction effects favouring the intervention were found for anxiety (Wald χ2 = 6.17,p = .046) and for environmental QoL (Waldχ2 = 7.06,p = .029). Those effects were not observed in intention-to-treat analyses adjusted for age. Interviewees from the intervention arm (N = 12) reported positive results of iSupport on knowledge and on experiencing positive feelings. No adverse effects were reported.ConclusionsThis study provides information for a forthcoming full-scale effectiveness trial, as on the acceptability and potential results of iSupport-Portugal. iSupport is suggested as a relevant resource for Portuguese carers.Trial registrationClinicalTrials.gov,NCT04104568. 26/09/2019.