bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Bujing Yishi tablet for glaucoma with controlled IOP: study protocol for a multi-centre randomized controlled trial
Authors: Liu Hongji , Li Xiang , Zhang Zongduan , Zeng Jieping , Dai Yan , Wang Chao , Xie Zhao , Cheng Lin , Cui Linru 
Published: May 2020

Abstract
Background
As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety.

Methods
This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18–75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will be randomly assigned to the BJYSP group or control group at a ratio of 1:1. Following randomization, participants in the BJYSP group and control group will receive BJYSP and mecobalamin tablets, respectively, for the same 6-month period. The primary outcomes will include the best-corrected visual acuity (BCVA), visual field assessment, visual evoked potential (VEP) test, and Heidelberg retina tomography II (HRT II); the secondary outcomes will include intraocular pressure (IOP) and Traditional Chinese medicine (TCM) clinical symptom scales. The primary and secondary outcomes will be measured at baseline and 8, 16, and 24 weeks thereafter. Safety assessments will also be evaluated at baseline and 12 and 24 weeks thereafter.

Discussion
This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of BJYSP as a novel therapeutic strategy for improving visual function in patients with GPCI.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1800016431. Registered on 1 June 2018.
Efficacy of a training programme to support the application of the guideline evidence-based health information: study protocol of a randomised controlled trial
Authors: Lühnen Julia , Berger-Höger Birte , Haastert Burkhard , Hinneburg Jana , Kasper Jürgen , Steckelberg Anke 
Published: May 2020

Abstract
Background
The evidence-based guideline entitled guideline evidence-based health information emerged from the German Network for Evidence-based Medicine (DNEbM) and was published in February 2017. The guideline addresses providers of health information and its goal is to improve the quality of health information. In addition, we explored the competences of providers of health information and developed a training programme.
The aim of this study is to evaluate the efficacy of a training programme addressing providers of health information to support the application of the guideline evidence-based health information. We expected the intervention to improve the quality of health information in comparison to the provision of the guideline on its own.

Methods/design
The trial uses a superiority randomised control group design with 10 months’ follow-up. Twenty-six providers of health information (groups with up to ten members) will be enrolled to compare the intervention (guideline and training programme) with usual care (a publicly available guideline). The 5-day training programme comprises an evidence-based medicine training module and a module to prepare the application of the guideline. The primary outcome parameter is the quality of the health information. Quality is operationalised as the extent of adherence to the guideline’s recommendations. Each provider will prepare a single health information item informing a health-related decision on a topic freely chosen before randomisation. The quality of this information will be rated using the Mapping Health Information Quality (MAPPinfo) Checklist. An accompanying process evaluation will then be conducted.

Discussion
The study results should show whether the efficacy of the intervention justifies implementation of the training programme to enhance health information developers’ competences in evidence-based medicine and to ensure high-quality evidence-based health information (EBHI) in the long term.

Trial registration
ISRCTN registry, ID: ISRCTN96941060. Registered on 7 March 2019.
Update to the AWED (Applying Wolbachia to Eliminate Dengue) trial study protocol: a cluster randomised controlled trial in Yogyakarta, Indonesia
Authors: Anders Katherine L. , Indriani Citra , Ahmad Riris Andono , Tantowijoyo Warsito , Arguni Eggi , Andari Bekti , Jewell Nicholas P. , Dufault Suzanne M. , Ryan Peter A. , Tanamas Stephanie K. , Rancès Edwige , O’Neill Scott L. , Simmons Cameron P. , Utarini Adi 
Published: May 2020

Abstract
Background
The AWED (Applying Wolbachia to Eliminate Dengue) trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Yogyakarta, Indonesia, with the aim of measuring the efficacy of Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting. Enrolment began in January 2018 and is ongoing. The original study protocol was published in April 2018. Here, we describe amendments that have been made to the study protocol since commencement of the trial.

Methods
The key protocol amendments are (1) a revised study duration with planned end of participant enrolment in August 2020, (2) the addition of new secondary objectives (i) to estimate serotype-specific efficacy of the Wolbachia intervention and (ii) to compare Ae. aegypti abundance in intervention versus untreated clusters, (3) an additional exposure classification for the per-protocol analysis where the Wolbachia exposure index is calculated using only the cluster-level Wolbachia prevalence in the participant’s cluster of residence, (4) power re-estimation using a multinomial sampling method that better accounts for randomness in sampling, and (5) the addition of two trial stopping rules to address the potential for persistently low rates of virologically confirmed dengue case enrolment and Wolbachia contamination into untreated clusters. Additional minor changes to the protocol are also described.

Discussion
The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Enrolment in the trial will conclude this year (2020) and results will be reported shortly thereafter.

Trial registration
ClinicalTrials.gov, identifier: NCT03055585. Registered on 14 February 2017. Last updated 22 March 2020.
Force production during the sustained phase of Rugby scrums: a systematic literature review
Authors: Martin Eric , Beckham George 
Published: May 2020

Abstract
Background
Since World Rugby changed the laws regarding scrums in the 2013–2014 season, the sustained push phase of the scrum has increased in tactical importance. Therefore, the purpose of this systematic literature review was to examine the biomechanical demands during the sustained push phase of individual, unit, and full pack scrummaging.

Methods
Pubmed, EBSCO (specifically and simultaneously searching Academic Search Premier, CINAHL, and SPORTDiscus), and Google Scholar were searched for any research that presented force production in a live or simulated rugby scrum. Study quality was appraised using the National Institute of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Recorded scrum forces, positioning of players including joint angles, and testing procedures were extracted and narratively synthesized.

Results
Twenty six studies were included in the review. 50% of included studies were rated good, 31% fair, and 19% poor. Major limitations included not reporting any effect size, statistical power, or reliability. Reported group mean values for average sustained forces against a machine generally ranged from 1000 to 2000 N in individual scrums and 4000–8000 N for full packs of male rugby players older than high school age. Individuals seem to optimize their force generation when their shoulders are set against scrum machine pads at approximately 40% of body height, with feet parallel, and with knee and hip angles around 120°. A 10% difference in pack force seems to be necessary for one pack to drive another back in the scrum, but little data exist to quantify differences in force production between winning and losing packs during live scrums. Data collection within studies was not standardized, making comparisons difficult. There is a lack of data in live scrums, and the current research indicates that machine scrums may not replicate many of the demands of live scrums. There is a lack of data for female rugby players.

Conclusions
This review indicates an optimal individual body position for players to strive to achieve during scrummaging, consisting of a low body height (40% of stature) and large extended hip and knee angles (120° each).
Therapeutic strategies against hDOT1L as a potential drug target in MLL-rearranged leukemias
Authors: Banday Shahid , Farooq Zeenat , Ganai Shabir Ahmad , Altaf Mohammad 
Published: May 2020

AbstractTherapeutic intervention of proteins participating in chromatin-mediated signaling with small-molecules is a novel option to reprogram expression networks for restraining disease states. Protein methyltransferases form the prominent family of such proteins regulating gene expression via epigenetic mechanisms thereby representing novel targets for pharmacological intervention. Disruptor of telomeric silencing, hDot1L is the only non-SET domain containing histone methyltransferase that methylates histone H3 at lysine 79. H3K79 methylation mediated by hDot1L plays a crucial role in mixed lineage leukemia (MLL) pathosis. MLL fusion protein mediated mistargeting of DOT1L to aberrant gene locations results in ectopic H3K79 methylation culminating in aberrant expression of leukemogenic genes like HOXA9 and MEIS1. hDOT1L has thus been proposed as a potential target for therapeutic intervention in MLL. This review presents the general overview of hDOT1L and its functional role in distinct biological processes. Furthermore, we discuss various therapeutic strategies against hDOT1L as a promising drug target to vanquish therapeutically challenging MLL.
Impact of sex and gender on COVID-19 outcomes in Europe
Authors: Gebhard Catherine , Regitz-Zagrosek Vera , Neuhauser Hannelore K. , Morgan Rosemary , Klein Sabra L. 
Published: May 2020

AbstractBackgroundEmerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men.ContentThe present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies.ConclusionThe sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.
Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma
Authors: Liu Furong , Qin Lu , Liao Zhibin , Song Jia , Yuan Chaoyi , Liu Yachong , Wang Yu , Xu Heze , Zhang Qiaofeng , Pei Youliang , Zhang Hongwei , Pan Yonglong , Chen Xiaoping , Zhang Zhanguo , Zhang Wanguang , Zhang Bixiang 
Published: May 2020

AbstractBackgroundImmune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients’ prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated.MethodsWe performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures.ResultsWe defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, we developed an SVM classifier to identify the patient’s immunological status, which was divided into Type A and Type B, in which Type A had poorer prognosis, higher T cell dysfunction despite higher T cell infiltration, and had better immunotherapeutic response. At the same time, MMP9 may be a potential predictor of the immune characteristics and immunotherapeutic response in HCC.ConclusionsOur work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response.
Heart failure supported by veno-arterial extracorporeal membrane oxygenation (ECMO): a systematic review of pre-clinical models
Authors:   on behalf of the European Extracorporeal Life Support Organisation (EuroELSO) Innovations Workgroup & the National Health Medical Research Council Australia Centre of Research Excellence for Advanced Cardio-respiratory Therapies Improving Organ Support (NHMRC CREACTIONS), Heinsar Silver , Rozencwajg Sacha , Suen Jacky , Bassi Gianluigi Li , Malfertheiner Maximilian , Vercaemst Leen , Broman Lars Mikael , Schmidt Matthieu , Combes Alain , Rätsep Indrek , Fraser John F. , Millar Jonathan E. 
Published: May 2020

Abstract
Objectives
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to treat patients with refractory severe heart failure. Large animal models are developed to help understand physiology and build translational research projects. In order to better understand those experimental models, we conducted a systematic literature review of animal models combining heart failure and VA-ECMO.

Studies selection
A systematic review was performed using Medline via PubMed, EMBASE, and Web of Science, from January 1996 to January 2019. Animal models combining experimental acute heart failure and ECMO were included. Clinical studies, abstracts, and studies not employing VA-ECMO were excluded.

Data extraction
Following variables were extracted, relating to four key features: (1) study design, (2) animals and their peri-experimental care, (3) heart failure models and characteristics, and (4) ECMO characteristics and management.

Results
Nineteen models of heart failure and VA-ECMO were included in this review. All were performed in large animals, the majority (n = 13) in pigs. Acute myocardial infarction (n = 11) with left anterior descending coronary ligation (n = 9) was the commonest mean of inducing heart failure. Most models employed peripheral VA-ECMO (n = 14) with limited reporting.

Conclusion
Among models that combined severe heart failure and VA-ECMO, there is a large heterogeneity in both design and reporting, as well as methods employed for heart failure. There is a need for standardization of reporting and minimum dataset to ensure translational research achieve high-quality standards.
iStent inject trabecular microbypass stent implantation with cataract extraction in open-angle glaucoma: early clinical experience
Authors: Ferguson Tanner J. , Dockter Zachary , Bleeker Adam , Karpuk Kayla L. , Schweitzer Justin , Ibach Mitch J. , Berdahl John P. 
Published: May 2020

Abstract
Background
Retrospective, consecutive case series to evaluate the implantation of two second-generation trabecular microbypass stents in combination with cataract surgery in a real-world, clinical setting.

Methods
The series included 56 eyes implanted with the iStent inject device with phacoemulsification. The series consisted of eyes with primary open-angle glaucoma (n = 52) and pseudoexfoliative glaucoma (n = 4). Primary outcome measures included intraocular pressure (IOP) and number of glaucoma medications. Safety outcomes included the need for secondary surgical intervention and the incidence of IOP spikes ≥10 mmHg and ≥ 15 mmHg.

Results
IOP was reduced by 21% to 14.7 ± 2.9 mmHg (p < 0.01) at 6 months postoperative from 18.7 ± 5.8 mmHg at baseline. Preoperatively, the mean number of glaucoma medications was 1.5 ± 0.9 and reduced by 39% to 0.9 ± 1.2 (p < 0.01) at 6 months. At 6 months, 68% of eyes had an IOP ≤15 mmHg, increased from 30% at baseline. 55% of eyes were medication-free at 6 months, up from 18% at baseline. There were no severe postoperative complications. No eyes underwent an additional glaucoma procedure.

Conclusions
Implantation of the iStent inject device with concomitant cataract surgery effectively provides a sustained reduction in IOP with a markedly improved medication burden out to 6 months postoperative. The safety profile is excellent.
Physical modeling and arbitrary Lagrangian–Eulerian finite element analysis of indentation of a sensitive clay by a flat-ended axisymmetrical indenter
Authors: Abou-Samra Ghassan , Ewane Mireille Sandrine , Silvestri Vincenzo 
Published: May 2020

AbstractBecause indentation tests which are used in several engineering fields allow obtaining material strength parameters in a fast, reliable and reproducible manner, the present study was initiated with the aim of finding out whether such tests could also be used in geotechnical engineering. Experimental results are obtained from undrained indentation tests performed with a rigid flat-tipped, cylindrical indenter on Champlain clay specimens in order to deduce values of elastic moduli and yield stresses. These values are compared to those deduced from unconfined compression tests. Results of an Arbitrary Lagrangian–Eulerian (ALE) based finite element analysis that simulates such test are also presented. It is assumed that the clay behaves as a linear-elastic, perfectly plastic material obeying von-Mises yield criterion. A frictionless contact interface is chosen to realistically model interactions on the indenter-clay, clay-platen and clay-ring interfaces. The paper presents distributions of contact pressures beneath the indenter and along lateral and lower boundaries. Typical contours of von Mises deviator stress and equivalent plastic strain corresponding to different indentation depths in the clay specimen are presented. It is also shown that the presence of hairline cracks on the clay along the perimeter of the indenter and the limited thickness of the sample affect the deduced values of Young’s modulus and yield stress.
Quantification of three-dimensional facial asymmetry for diagnosis and postoperative evaluation of orthognathic surgery
Authors: Cao Hua-Lian , Kang Moon-Ho , Lee Jin-Yong , Park Won-Jong , Choung Han-Wool , Choung Pill-Hoon 
Published: May 2020

Abstract
Background
To evaluate the facial asymmetry, three-dimensional computed tomography (3D-CT) has been used widely. This study proposed a method to quantify facial asymmetry based on 3D-CT.

Methods
The normal standard group consisted of twenty-five male subjects who had a balanced face and normal occlusion. Five anatomical landmarks were selected as reference points and ten anatomical landmarks were selected as measurement points to evaluate facial asymmetry. The formula of facial asymmetry index was designed by using the distances between the landmarks. The index value on a specific landmark indicated zero when the landmarks were located on the three-dimensional symmetric position. As the asymmetry of landmarks increased, the value of facial asymmetry index increased. For ten anatomical landmarks, the mean value of facial asymmetry index on each landmark was obtained in the normal standard group. Facial asymmetry index was applied to the patients who had undergone orthognathic surgery. Preoperative facial asymmetry and postoperative improvement were evaluated.

Results
The reference facial asymmetry index on each landmark in the normal standard group was from 1.77 to 3.38. A polygonal chart was drawn to visualize the degree of asymmetry. In three patients who had undergone orthognathic surgery, it was checked that the method of facial asymmetry index showed the preoperative facial asymmetry and the postoperative improvement well.

Conclusions
The current new facial asymmetry index could efficiently quantify the degree of facial asymmetry from 3D-CT. This method could be used as an evaluation standard for facial asymmetry analysis.