bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabic version of the Hayling sentence completion test: scale validation, normative data and factors associated with executive functions in a sample of the Lebanese adults
Authors: Boutros Sarah , El Hachem Emilio , Mattar Joseph , Hallit Souheil , Mattar Hanna 
Published: December 2020

Abstract
Background
This study was conducted for several reasons, primarily because of the lack of an Arabic version of the HSCT that could be beneficial in our clinical practice. Another reason is the need to find potential relationships between various factors with executive functions, especially problematic mobile phone use as suggested by many previous studies, since smartphones have become, nowadays, a daily companion of people from all generations. Thus, it is important to conduct this study in Lebanon to be adapted to the ideas, customs and social behavior of the Lebanese citizens. Hence, the objectives of the current study are to use the Arabic version of the HSCT in healthy community-dwelling Arabic-speaking adults in Lebanon, to check its validity compared to other versions of the test, as well as to identify risk factors that might affect the executive functions in these adults.

Methods
Between August–December 2019, 350 participants were randomly selected. The Arabic version of the HSCT, divided into automatic and inhibition conditions, was used; in each condition, participants’ response-time and number of errors committed were recorded.

Results
None of the scale items was removed. For the automatic condition, response-time items converged over one factor (αCronbach = 0.905) and number of errors converged over seven factors (αCronbach = 0.334). For the inhibition condition, response-time converged over one factor (αCronbach = 0.943) and number of errors converged over four factors (αCronbach = 0.728). Using electricity as a heating method inside the house was significantly associated with a lower response-time, whereas higher problematic mobile phone use was associated with higher response-time. Using wood as a heating system inside the house and higher problematic mobile phone use were associated with higher number of errors, while using Arabian incense (bakhour) inside the house was associated with lower number of errors.

Conclusion
We were able to set normative data for the HSCT Arabic version for use in the Lebanese population. Problematic mobile phone use was associated with lower inhibitory control in terms of response-time and errors number.
Coincidence analysis: a new method for causal inference in implementation science
Authors: Whitaker Rebecca Garr , Sperber Nina , Baumgartner Michael , Thiem Alrik , Cragun Deborah , Damschroder Laura , Miech Edward J. , Slade Alecia , Birken Sarah 
Published: December 2020

AbstractBackgroundImplementation of multifaceted interventions typically involves many diverse elements working together in interrelated ways, including intervention components, implementation strategies, and features of local context. Given this real-world complexity, implementation researchers may be interested in a new mathematical, cross-case method called Coincidence Analysis (CNA) that has been designed explicitly to support causal inference, answer research questions about combinations of conditions that are minimally necessary or sufficient for an outcome, and identify the possible presence of multiple causal paths to an outcome. CNA can be applied as a standalone method or in conjunction with other approaches and can reveal new empirical findings related to implementation that might otherwise have gone undetected.MethodsWe applied CNA to a publicly available dataset from Sweden with county-level data on human papillomavirus (HPV) vaccination campaigns and vaccination uptake in 2012 and 2014 and then compared CNA results to the published regression findings.ResultsThe original regression analysis found vaccination uptake was positively associated only with the availability of vaccines in schools. CNA produced different findings and uncovered an additional solution path: high vaccination rates were achieved by either (1) offering the vaccine in all schools or (2) a combination of offering the vaccine in some schools and media coverage.ConclusionsCNA offers a new comparative approach for researchers seeking to understand how implementation conditions work together and link to outcomes.
Surveillance ultrasonography for conservative treatment of femoral shaft fractures in young children
Authors: Gao Hui , Wang Zhaoxia , Su Yuxi 
Published: December 2020

Abstract
Background
The treatment for femoral shaft fracture (FSF) depends on the age of the patient. While the Pavlik harness is the first choice for patients under 6 months of age, spica casting is preferred for patients over 6 months and under preschool age. Minimally-invasive surgery using elastic stable intramedullary nails is also used in some cases. Skin traction is another treatment choice for some patients who are not candidates for the above methods. This study aimed to evaluate the feasibility of surveillance ultrasonography (US) for the conservative treatment of FSFs in young children.

Materials and methods
This retrospective study included 92 children who were diagnosed with FSF in our hospital from April 2017 to May 2019. After applying the inclusion and exclusion criteria, they were divided into US surveillance (A) and control (B) groups. All patients received conservative treatment by skin traction. For group A, US was used to assess the femur fractures and adjust its reduction on days 1, 3, 5, 7, 10, and 14 until the fracture stabilized. For group B, the fractures were checked by radiographs on days 1, 3, 5, 7, 10, and 14 until the callus appeared. The FSF angle was measured using anteroposterior and lateral radiographs.

Results
All patients were followed up for 18 months. The radiographic evaluation of both groups at the final follow-up showed a significant difference in the FSF angle. The radiograph times and accumulated radiation also showed significant differences between the two groups. However, there was no significant difference in the incidence of complications.

Conclusions
For FSF closed reduction, surveillance US is a better option compared to radiographs in children treated by skin traction. This approach can significantly decrease exposure to X-ray radiation and improve the reduction.

Level of evidence
III
Novel gene variants in Polish patients with Leber congenital amaurosis (LCA)
Authors: Skorczyk-Werner Anna , Niedziela Zuzanna , Stopa Marcin , Krawczyński Maciej Robert 
Published: December 2020

Abstract
Background
Leber congenital amaurosis (LCA) is a rare retinal disease that is the most frequent cause of congenital blindness in children and the most severe form of inherited retinal dystrophies. To date, 25 genes have been implicated in the pathogenesis of LCA. As gene therapy is becoming available, the identification of potential treatment candidates is crucial. The aim of the study was to report the molecular basis of Leber congenital amaurosis in 22 Polish families.

Methods
Single Nucleotide Polymorphism-microarray for LCA genes or Next Generation Sequencing diagnostic panel for LCA genes (or both tests) were performed to identify potentially pathogenic variants. Bidirectional Sanger sequencing was carried out for validation and segregation analysis of the variants identified within the families.

Results
The molecular background was established in 22 families. From a total of 24 identified variants, 23 were predicted to affect protein-coding or splicing, including 10 novel variants. The variants were identified in 7 genes: CEP290, GUCY2D, RPE65, NMNAT1, CRB1, RPGRIP1, and CRX. More than one-third of the patients, with clinical LCA diagnosis confirmed by the results of molecular analysis, appeared to be affected with a severe form of the disease: LCA10 caused by the CEP290 gene variants. Intronic mutation c.2991+1655A>G in the CEP290 gene was the most frequent variant identified in the studied group.

Conclusions
This study provides the first molecular genetic characteristics of patients with Leber congenital amaurosis from the previously unexplored Polish population. Our study expands the mutational spectrum as we report 10 novel variants identified in LCA genes. The fact that the most frequent causes of the disease in the studied group of Polish patients are mutations in one out of three genes that are currently the targets for gene therapy (CEP290, GUCY2D, and RPE65) strongly emphasizes the importance of the molecular background analyses of LCA in Polish patients.
MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents
Authors: Bolomsky Arnold , Vogler Meike , Köse Murat Cem , Heckman Caroline A. , Ehx Grégory , Ludwig Heinz , Caers Jo 
Published: December 2020

AbstractCell death escape is one of the most prominent features of tumor cells and closely linked to the dysregulation of members of the Bcl-2 family of proteins. Among those, the anti-apoptotic family member myeloid cell leukemia-1 (MCL-1) acts as a master regulator of apoptosis in various human malignancies. Irrespective of its unfavorable structure profile, independent research efforts recently led to the generation of highly potent MCL-1 inhibitors that are currently evaluated in clinical trials. This offers new perspectives to target a so far undruggable cancer cell dependency. However, a detailed understanding about the tumor and tissue type specific implications of MCL-1 are a prerequisite for the optimal (i.e., precision medicine guided) use of this novel drug class. In this review, we summarize the major functions of MCL-1 with a special focus on cancer, provide insights into its different roles in solid vs. hematological tumors and give an update about the (pre)clinical development program of state-of-the-art MCL-1 targeting compounds. We aim to raise the awareness about the heterogeneous role of MCL-1 as drug target between, but also within tumor entities and to highlight the importance of rationale treatment decisions on a case by case basis.
RETRACTED ARTICLE: Circular RNA hsa_circ_0001829 promotes gastric cancer progression through miR-155-5p/SMAD2 axis
Authors: Niu Qiuling , Dong Zhijie , Liang Min , Luo Yuanwei , Lin Hai , Lin Mingzhen , Zhong Xiu , Yao Wenxia , Weng Jinsheng , Zhou Xinke 
Published: December 2020

Abstract
Background
Accumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.

Methods
In this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.

Results
We found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p–SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.

Conclusion
Taken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p–SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
CircCDKN2B-AS1 interacts with IMP3 to stabilize hexokinase 2 mRNA and facilitate cervical squamous cell carcinoma aerobic glycolysis progression
Authors: Zhang Yanan , Zhao Lu , Yang Shizhou , Cen Yixuan , Zhu Tingjia , Wang Lingfang , Xia Lili , Liu Yuwan , Zou Jian , Xu Junfen , Li Yang , Cheng Xiaodong , Lu Weiguo , Wang Xinyu , Xie Xing 
Published: December 2020

AbstractBackgroundCircular RNAs (circRNAs) have been reported to play key roles in the development of various cancers. However, the biological functions and clinical significance of most circRNAs are still elusive. The purpose of this study was to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development and its potential value in the clinic.MethodsqRT-PCR was used to verify the expression level of circCDKN2B-AS1. CCK-8, Transwell, and flow cytometry (FCM) assays were performed to detect cellular proliferation, migration, and apoptosis, respectively. A Seahorse XFe96 Analyzer was used to measure glycolysis metabolism level. RNA pull-down, RNA immunoprecipitation (RIP), actinomycin-D addition assays and Western blotting were used to screen and elucidate the potential mechanisms involved. BALB/c nude mice and zebrafish embryos (AB, WT) were used as animal models to investigate tumorigenesis capability.18FDG-microPET/CT imaging and lactic acid (LA) and pyruvic acid (PA) content detection assays were used to detect the level of glucose metabolism in subcutaneous tumors from nude mice.ResultsCircCDKN2B-AS1, a circular isoform of the long noncoding RNA (lncRNA) CDKN2B-AS1, was upregulated in cervical cancer and precancerous tissues. We found that circCDKN2B-AS1 associated with the IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2 (HK2) mRNA, the rate-limiting enzyme of the aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to the 3′ untranslated region (UTR) of HK2 mRNA, consequently affecting the malignant cell phenotype and aerobic glycolysis in cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1, lacking the IMP3 binding site, did not have such effects. Utilization of an inhibitory peptide to block the interaction between circCDKN2B-AS1 and the IMP3 protein impeded the binding of IMP3 to the 3’UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells.ConclusionsOur findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging the IMP3 protein to stabilize HK2 mRNA, consequently promoting the malignant phenotype in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.
Death Cafés for prevention of burnout in intensive care unit employees: study protocol for a randomized controlled trial (STOPTHEBURN)
Authors: Bateman Marjorie E. , Hammer Rachel , Byrne Abigail , Ravindran Nithya , Chiurco Jennifer , Lasky Sasha , Denson Rebecca , Brown Margo , Myers Leann , Zu Yuanhao , Denson Joshua L. 
Published: December 2020

Abstract
Background
Burnout is an occupational syndrome that leads to mental health problems, job turnover, and patient safety events. Those caring for critically ill patients are especially susceptible due to high patient mortality, long hours, and regular encounters with trauma and ethical issues. Interventions to prevent burnout in this population are needed. Preliminary studies suggest debriefing sessions may reduce burnout. This study aims to assess whether participation in regular debriefing can prevent burnout in intensive care unit (ICU) clinicians.

Methods
A randomized controlled trial will be conducted in two large academic medical centers. Two hundred ICU clinicians will be recruited with target enrollment of 100 physicians and 100 non-physicians (nurses, pharmacists, therapists). Participants must have worked in the ICU for the equivalent of at least 1 full time work week in the preceding 4 weeks. Enrolled subjects will be randomized to virtually attend biweekly debriefing sessions facilitated by a psychotherapist for 3 months or to a control arm without sessions. Our debriefs are modeled after Death Cafés, which are informal discussions focusing on death, dying, loss, grief, and illness. These sessions allow for reflection on distressing events and offer community and collaboration among hospital employees outside of work.
The primary outcome is clinician burnout as measured by the Maslach Burnout Inventory (MBI) Score. Secondary outcomes include depression and anxiety, as measured by the Patient Health Questionnaire 8 (PHQ-8) and Generalized Anxiety Disorder 7-item scale (GAD-7), respectively. Questionnaires will be administered prior to the intervention, at 1 month, at 3 months, and at 6 months after enrollment. These values will be compared between groups temporally. Qualitative feedback will also be collected and analyzed.

Discussion
With ICU clinician burnout rates exceeding 50%, Death Café debriefing sessions may prove to be an effective tool to avert this debilitating syndrome. With COVID-19 limiting social interactions and overloading ICUs worldwide, the virtual administration of the Death Café for ICU clinicians provides an innovative strategy to potentially mitigate burnout in this vulnerable population.

Trial registration
ClinicalTrials.gov NCT04347811. Registered on 15 April 2020
Quantitative response of healthy muscle following the induction of capsaicin: an exploratory randomized controlled trial
Authors: Evans Valerie , Behr Michael , Masani Kei , Kumbhare Dinesh 
Published: December 2020

Abstract
Background
Myofascial pain syndrome (MPS) is a prevalent chronic pain disorder primarily characterized by myofascial trigger points (MTrPs). There is limited knowledge on the pathophysiology and mechanisms underlying MTrP and its development. Research has previously demonstrated the identification of MTrPs using ultrasound and vibration sonoelastography, although there is some contradictory evidence regarding if MTrPs present as hyper or hypoechoic regions. Electromyography (EMG) investigations of MTrP have demonstrated that MTrPs are usually located proximal to innervation zones where the peak surface EMG signals are obtained from. Central sensitization has been proposed as the primary mechanism underlying MTrP development. Central sensitization is associated with hyperexcitability of neuronal responses to normal or noxious stimuli. There is a need for a study that measures ultrasound image textural changes and motor unit activity responses in the muscle following sensitization. The purpose of this study is to determine whether sensitizing healthy muscle using capsaicin induces a regional change in image texture variables within the specific and surrounding muscles, as well as the motor unit frequency and amplitude changes that accompany them. This is an exploratory trial that aims to provide preliminary evidence on whether central sensitization is a direct cause of taut band and MTrP development.

Methods
Ethical approval was obtained from the University Health Network (UHN) Research Ethics Board. This proposed study is a single centered, factorial, randomized placebo-controlled trial with two independent variables, depth of capsaicin application and dose of capsaicin, for a total of six treatment arms and three control treatment groups.

Discussion
This will be the first study that assesses the B-mode ultrasound image texture of induced sensitized muscles and will provide more evidence on muscle motor unit activity and regional changes of central sensitization. Findings from this study may support one of few hypotheses proposed delineating the involvement of central sensitization in the development of trigger points.

Trial registration
National Institutes of Health ClinicalTrials.gov NCT03944889. Registered on May 07, 2019
Strategy for addressing research-site overlap in pragmatic clinical trials: lessons learned from the NIH-DOD-VA Pain Management Collaboratory (PMC)
Authors:   on behalf of the NIH-DoD-VA Pain Management Collaboratory, Geda Mary , George Steven Z. , Burgess Diana J. , Scarton Dylan V. , Roddy William T. , Gordon Kirsha S. , Pasquina Paul F. , Brandt Cynthia A. , Kerns Robert D. , Peduzzi Peter 
Published: December 2020

Abstract
Background
The Pain Management Collaboratory (PMC) is a multi-site network of pragmatic clinical trials (PCTs) focused on nonpharmacological approaches to pain management, conducted in health care systems of the US Department of Defense (DoD) and Department of Veterans Affairs (VA) and co-funded by the National Institutes of Health (NIH). Concerns about potential research-site overlap prompted the PMC investigator community to consider strategies to avert this problem that could negatively affect recruitment and contaminate interventions and thus pose a threat to trial integrity.

Methods
We developed a two-step strategy to identify and remediate research-site overlap by obtaining detailed recruitment plans across all PMC PCTs that addressed eligibility criteria, recruitment methods, trial settings, and timeframes. The first, information-gathering phase consisted of a 2-month period for data collection from PIs, stakeholders, and ClinicalTrials.gov. The second, remediation phase consisted of a series of moderated conference calls over a 1-month time period to develop plans to address overlap. Remediation efforts focused on exclusion criteria and recruitment strategies, and they involved collaboration with sponsors and stakeholder groups such as the Military Treatment Facility Engagement Committee (MTFEC). The MTFEC is comprised of collaborating DoD and university-affiliated PIs, clinicians, and educators devoted to facilitating successful pragmatic trials in DoD settings.

Results
Of 61 recruitment sites for the 11 PMC PCTs, 17 (28%) overlapped. Four PCTs had five overlapping Military Treatment Facilities (MTFs), and eight PCTs had 12 overlapping VA Medical Centers (VAMCs). We developed three general strategies to avoid research-site overlap: (i) modify exclusion criteria, (ii) coordinate recruitment efforts, and/or (iii) replace or avoid any overlapping sites. Potential overlap from competing studies outside of the PMC was apparent at 26 sites, but we were not able to confirm them as true conflicts.

Conclusion
Proactive strategies can be used to resolve the issue of overlapping research sites in the PMC. These strategies, combined with open and impartial mediation approaches that include researchers, sponsors, and stakeholders, provide lessons learned from this large and complex pragmatic research effort.