bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1
Authors: Maekawa Hirotsugu , Kawai Shunsuke , Nishio Megumi , Nagata Sanae , Jin Yonghui , Yoshitomi Hiroyuki , Matsuda Shuichi , Toguchida Junya 
Published: May 2020

Abstract
Background
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disease characterized by heterotopic ossification (HO) in soft tissues and caused by a mutation of the ACVR1A/ALK2 gene. Activin-A is a key molecule for initiating the process of HO via the activation of mTOR, while rapamycin, an mTOR inhibitor, effectively inhibits the Activin-A-induced HO. However, few reports have verified the effect of rapamycin on FOP in clinical perspectives.

Methods
We investigated the effect of rapamycin for different clinical situations by using mice conditionally expressing human mutant ACVR1A/ALK2 gene. We also compared the effect of rapamycin between early and episode-initiated treatments for each situation.

Results
Continuous, episode-independent administration of rapamycin reduced the incidence and severity of HO in the natural course of FOP mice. Pinch-injury induced HO not only at the injured sites, but also in the contralateral limbs and provoked a prolonged production of Activin-A in inflammatory cells. Although both early and injury-initiated treatment of rapamycin suppressed HO in the injured sites, the former was more effective at preventing HO in the contralateral limbs. Rapamycin was also effective at reducing the volume of recurrent HO after the surgical resection of injury-induced HO, for which the early treatment was more effective.

Conclusion
Our study suggested that prophylactic treatment will be a choice of method for the clinical application of rapamycin for FOP.
Causes and risk factors for common mental illnesses: the beliefs of paediatric hospital staff in the United Arab Emirates
Authors: Slewa-Younan Shameran , Nguyen Thomas P. , Al-Yateem Nabeel , Rossiter Rachel Cathrine , Robb Walter 
Published: May 2020

Abstract
Background
Children and adolescents with chronic physical health conditions are vulnerable to poor mental health outcomes. The measurement of mental health literacy of health professionals working with such populations is important because of their role in promoting early and appropriate help-seeking. This study sought to determine the beliefs regarding the causes of and risks factors for three types of mental illnesses amongst health professionals in United Arab Emirates.

Method
A culturally validated mental health literacy survey presenting three vignettes of fictional characters meeting diagnostic criteria for posttraumatic stress disorder, depression with suicidal thoughts and psychosis was distributed. The survey measured health care professionals’ beliefs regarding the causes of and risk factors for these disorders.

Results
A total of 317 health care professional (> 90% nurses) were surveyed from across the UAE. Although 43.8% correctly endorsed exposure to a ‘traumatic event’ as the most likely cause for developing posttraumatic stress disorder, there was a more limited understanding of the contribution of biopsychosocial factors to the development of the mental illness, particularly for psychosis. Participant socio-demographic variables were associated with attributions of religious or spiritual beliefs and personal weakness as causal and/or vulnerability factors in the development of depression with suicidal thoughts and psychosis.

Conclusions
Efforts to improve mental health systems and health care providers in UAE and other similar Middle Eastern countries requires targeted mental health literacy programs that seek to integrate biopsychosocial models of mental illness and their treatment with the positive aspects of religious and cultural beliefs that are dominant in this region.
Emerging therapeutic agents for advanced non-small cell lung cancer
Authors: Chen Ruqin , Manochakian Rami , James Lauren , Azzouqa Abdel-Ghani , Shi Huashan , Zhang Yan , Zhao Yujie , Zhou Kexun , Lou Yanyan 
Published: May 2020

AbstractAdvanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
RNA-binding protein MSI2 isoforms expression and regulation in progression of triple-negative breast cancer
Authors: Li Ming , Li An-qi , Zhou Shu-ling , Lv Hong , Wei Ping , Yang Wen-tao 
Published: May 2020

Abstract
Background
The RNA-binding protein Musashi-2 (MSI2) has been implicated in the tumorigenesis and tumor progression of some human cancers. MSI2 has also been reported to suppress tumor epithelial-to-mesenchymal transition (EMT) progression in breast cancer, and low MSI2 expression is associated with poor outcomes for breast cancer patients; however, the underlying mechanisms have not been fully investigated. This study investigated the expression and phenotypic functions of two major alternatively spliced MSI2 isoforms (MSI2a and MSI2b) and the potential molecular mechanisms involved in triple-negative breast cancer (TNBC) progression.

Methods
The Illumina sequencing platform was used to analyze the mRNA transcriptomes of TNBC and normal tissues, while quantitative reverse transcription-polymerase chain reaction and immunohistochemistry validated MSI2 isoform expression in breast cancer tissues. The effects of MSI2a and MSI2b on TNBC cells were assayed in vitro and in vivo. RNA immunoprecipitation (RIP) and RNA sequencing were performed to identify the potential mRNA targets of MSI2a, and RIP and luciferase analyses were used to confirm the mRNA targets of MSI2.

Results
MSI2 expression in TNBC tissues was significantly downregulated compared to that in normal tissues. In TNBC, MSI2a expression was associated with poor overall survival of patients. MSI2a overexpression in vitro and in vivo inhibited TNBC cell invasion as well as extracellular signal-regulated kinase 1/2 (ERK1/2) activity. However, MSI2b overexpression had no significant effects on TNBC cell migration. Mechanistically, MSI2a expression promoted TP53INP1 mRNA stability by its interaction with the 3′-untranslated region of TP53INP1 mRNA. Furthermore, TP53INP1 knockdown reversed MSI2a-induced suppression of TNBC cell invasion, whereas ectopic expression of TP53INP1 and inhibition of ERK1/2 activity blocked MSI2 knockdown-induced TNBC cell invasion.

Conclusions
The current study demonstrated that MSI2a is the predominant functional isoform of MSI2 proteins in TNBC, that its downregulation is associated with TNBC progression and poor prognosis and that MSI2a expression inhibited TNBC invasion by stabilizing TP53INP1 mRNA and inhibiting ERK1/2 activity. Overall, our study provides new insights into the isoform-specific roles of MSI2a and MSI2b in the tumor progression of TNBC, allowing for novel therapeutic strategies to be developed for TNBC.
A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality
Authors: van der Zee Philip , Rietdijk Wim , Somhorst Peter , Endeman Henrik , Gommers Diederik 
Published: May 2020

Abstract
Background
Heterogeneity of acute respiratory distress syndrome (ARDS) could be reduced by identification of biomarker-based phenotypes. The set of ARDS biomarkers to prospectively define these phenotypes remains to be established.

Objective
To provide an overview of the biomarkers that were multivariately associated with ARDS development or mortality.

Data sources
We performed a systematic search in Embase, MEDLINE, Web of Science, Cochrane CENTRAL, and Google Scholar from inception until 6 March 2020.

Study selection
Studies assessing biomarkers for ARDS development in critically ill patients at risk for ARDS and mortality due to ARDS adjusted in multivariate analyses were included.

Data extraction and synthesis
We included 35 studies for ARDS development (10,667 patients at risk for ARDS) and 53 for ARDS mortality (15,344 patients with ARDS). These studies were too heterogeneous to be used in a meta-analysis, as time until outcome and the variables used in the multivariate analyses varied widely between studies. After qualitative inspection, high plasma levels of angiopoeitin-2 and receptor for advanced glycation end products (RAGE) were associated with an increased risk of ARDS development. None of the biomarkers (plasma angiopoeitin-2, C-reactive protein, interleukin-8, RAGE, surfactant protein D, and Von Willebrand factor) was clearly associated with mortality.

Conclusions
Biomarker data reporting and variables used in multivariate analyses differed greatly between studies. Angiopoeitin-2 and RAGE in plasma were positively associated with increased risk of ARDS development. None of the biomarkers independently predicted mortality. Therefore, we suggested to structurally investigate a combination of biomarkers and clinical parameters in order to find more homogeneous ARDS phenotypes.

PROSPERO identifier
PROSPERO, CRD42017078957
Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore
Authors: Knaak Cornelia , Nyvlt Peter , Schuster Friederike S. , Spies Claudia , Heeren Patrick , Schenk Thomas , Balzer Felix , La Rosée Paul , Janka Gritta , Brunkhorst Frank M. , Keh Didier , Lachmann Gunnar 
Published: May 2020

Abstract
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients.

Methods
In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité – Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 μg/L were included. Patients’ charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy.

Results
In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 μg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372–1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009–1.013); p <  0.001] were significantly associated with in-hospital mortality.

Conclusions
An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients.

Clinical trial registration
The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
The Disruptive bEhavior manageMEnt ANd prevention in hospitalized patients using a behaviORal intervention team (DEMEANOR) study protocol: a pragmatic, cluster, crossover trial
Authors:   for the Vanderbilt Learning Healthcare System Investigators, Vanderbilt University, Morrison Jay , Hasselblad Michele , Kleinpell Ruth , Buie Reagan , Ariosto Deborah , Hardiman Erin , Osborn Stephen W. , Lindsell Christopher J. 
Published: May 2020

Abstract
Background
Disruptive behavior in hospitalized patients has become a priority area of safety concern for clinical staff, and also has consequences for patient management and hospital course. Proactive screening and intervention of patients with behavioral comorbidities has been reported to reduce disruptive behavior in some settings, but it has not been studied in a rigorous way.

Methods
The Disruptive bEhavior manageMEnt ANd prevention in hospitalized patients using a behaviORal intervention team (DEMEANOR) study is a pragmatic, cluster, crossover trial that is being conducted. Each month, the behavioral intervention team, comprising a psychiatric-mental health advanced practice nurse and a clinical social worker, with psychiatrist consultation as needed, rotates between an adult medicine unit and a mixed cardiac unit at Vanderbilt University Medical Center in Nashville, TN, USA. The team proactively screens patients upon admission, utilizing a protocol which includes a comprehensive chart review and, if indicated, a brief interview, seeking to identify those patients who possess risk factors indicative of either a potential psychological barrier to their own clinical progress or a potential risk for exhibiting disruptive, aggressive, or self-injurious behavior during their hospitalization. Once identified, the team provides interventions aimed at mitigating these risks, educates and supports the patient care teams (nurses, physicians, and others), and assists non-psychiatric staff in the management of patients who require behavioral healthcare. Patients who are both admitted to and discharged from either unit are included in the study. Anticipated enrollment is approximately 1790 patients. The two primary outcomes are (1) a composite of objective measures related to the patients’ disruptive, threatening, or acting out behaviors, and (2) staff self-reported comfort with and confidence in their ability to manage patients exhibiting disruptive, threatening, or acting out behavior. Secondary outcomes include patient length of stay, patient attendant (sitter) use, and the unit nursing staff retention.

Discussion
This ongoing trial will provide evidence on the real-world effectiveness of a proactive behavioral intervention to prevent disruptive, threatening, or acting out events in adult hospitalized patients.

Trial registration
ClinicalTrials.gov: NCT03777241. Registered on 14 December 2018.
The effectiveness of an electronic pain management programme for the working population with chronic pain: study protocol for a randomized controlled trial
Authors: Tang Shuk Kwan , Tse Mimi Mun Yee , Leung Sau Fong , Fotis Theofanis 
Published: May 2020

Abstract
Background
Chronic pain is highly prevalent in the working population. People tend to attempt self-initiated treatments to manage their pain. The self-efficacy of behavioural change is a suitable model for guiding the development of an electronic pain management programme (ePain). The aim in this study is to develop ePain and to evaluate its effectiveness at improving pain self-efficacy, reducing pain intensity and negative emotions, and increasing quality of life.

Methods
This study will be a randomized controlled trial. ePain will take the form of a 6-week online pain management programme. Participants will be aged 15 years or above, have chronic pain, and be employed. They must complete the baseline questionnaire and will be randomized into intervention and control groups. They will receive notifications to encourage their participation in ePain and complete the evaluation questionnaires. They will complete the process evaluation at week 3, the post assessment at week 6, and the follow-up assessment at week 12. The study will focus on pain self-efficacy; pain situations; negative emotions including levels of depression, anxiety, and stress; and quality of life. The participants’ opinions of ePain will be collected as feedback. Data will be analysed on an intention-to-treat basis and generalized estimating equations will be used to investigate the time-averaged difference and differences at each follow-up time.

Discussion
The study will provide information about the pain situations of online users in the working population. The participants will benefit from improvements in pain self-efficacy, pain situations, emotional status, and quality of life. The study will illustrate whether online learning is an effective intervention for improving the pain self-efficacy of the working population.

Trial registration
ClinicalTrials.gov, NCT03718702. Registered on 23 October 2018.
Comparison of blogshots with plain language summaries of Cochrane systematic reviews: a qualitative study and randomized trial
Authors: Buljan Ivan , Tokalić Ružica , Roguljić Marija , Zakarija-Grković Irena , Vrdoljak Davorka , Milić Petra , Puljak Livia , Marušić Ana 
Published: May 2020

Abstract
Background
Cochrane, an organization dedicated to the production and dissemination of high-quality evidence on health, endeavors to reach consumers by developing appropriate summary formats of its systematic reviews. However, the optimal type of presentation of evidence to consumers is still unknown.

Objective
The aim of this study was to investigate consumer preferences for different summary formats of Cochrane systematic reviews (CSRs), using both qualitative and quantitative approaches.

Methods
Initially, we conducted three focus groups with medical students (n = 7), doctors (n = 4), and patients (n = 9) in 2017 to explore their health information search habits and preferences for CSR summary formats. Based on those findings, we conducted a randomized trial with medical students at the University of Split School of Medicine, Croatia, and with patients from three Dalmatian family practices to determine whether they prefer CSR blogshots (n = 115) or CSR plain language summaries (PLSs; n = 123).

Results
Participants in the focus groups favored brief and explicit CSR summary formats with fewer numbers. Although we found no difference in participants’ preferences for a specific summary format in the overall sample, subgroup analysis showed that patients preferred blogshots over PLSs in comparison to medical students (P = 0.003, eta squared effect size η2 = 0.04).

Conclusion
CSR summaries should be produced in a format that meets the expectations and needs of consumers. Use of blogshots as a summary format could enhance the dissemination of CSRs among patients.

Trial registration
The trial was registered in ClinicalTrials.gov, NCT03542201. Registered on May 31st 2018.
Interactions between Schistosoma haematobium group species and their Bulinus spp. intermediate hosts along the Niger River Valley
Authors: Pennance Tom , Allan Fiona , Emery Aidan , Rabone Muriel , Cable Jo , Garba Amadou Djirmay , Hamidou Amina Amadou , Webster Joanne P. , Rollinson David , Webster Bonnie L. 
Published: May 2020

Abstract
Background
Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology.

Methods
Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20–52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region).

Results
A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2–10 MLG’s) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed.

Conclusions
This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development.