bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of deep electroacupuncture with strong deqi and shallow electroacupuncture with no deqi for lumbar disk herniation: study protocol for a randomised controlled trial
Authors: Huang Ziling , Zhao Jianxin , Pei Xinghong , Wang Bobo 
Published: November 2020

IntroductionLumbar disk herniation (LDH) is a common cause of low back pain and dysfunction. Studies have shown that electroacupuncture (EA) can achieve pain relief in patients with LDH. However, there is a lack of evidence regarding the effectiveness of deep EA with strong deqi and shallow EA with no deqi in patients with LDH. This study aims to evaluate the effectiveness of deep EA with strong deqi and shallow EA with no deqi in the treatment of LDH.Methods and analysisIn this randomised controlled trial, patients with LDH who have low back pain with or without radiculopathy for at least 12 weeks will be enrolled. In total, 44 patients will be recruited from the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China. Patients will be randomised into the deep EA group and the shallow EA group in a ratio of 1:1 and will be administered 12 sessions of EA treatment (three times a week for 4 weeks, 20 min for each session). The follow-up duration will be 4 weeks. Low back pain intensity and leg pain intensity (in patients with radicular pain) measured using the Visual Analogue Scale (VAS) will be assessed as the primary outcomes. Function (measured using the Roland-Morris Disability Questionnaire), quality of life (measured using the EuroQol Five-Dimensional Five-Level Questionnaire) and patient-evaluated therapeutic effect will be assessed as the secondary outcomes. Patients’ expectations of EA, the success of the blinding method and safety will also be evaluated. Statistical analyses will be followed by the intention-to-treat analysis.Ethics and disseminationThis study was approved by the Ethics Committee of the Third Affiliated Hospital of Beijing University of Chinese Medicine (approval number: 2019-XS-ZB06). Study results will be disseminated through publication in an open access journal.Trial registration numberChiCTR-1900026518.
Discontinuing antidepressant medication after mindfulness-based cognitive therapy: a mixed-methods study exploring predictors and outcomes of different discontinuation trajectories, and its facilitators and barriers
Authors: Huijbers Marloes J , Wentink Carolien , Simons Esther , Spijker Jan , Speckens Anne 
Published: November 2020

ObjectivesThis study aimed to explore predictors and outcomes associated with different trajectories of discontinuing antidepressant medication (ADM), in recurrently depressed individuals after participation in mindfulness-based cognitive therapy (MBCT). Facilitators and barriers of discontinuation were explored qualitatively.DesignMixed-methods study combining quantitative and qualitative data, drawn from a randomised controlled trial.SettingTwelve secondary and tertiary psychiatric outpatient clinics in the Netherlands.ParticipantsRecurrently depressed individuals (N=226) who had been using ADM for at least 6 months and in partial or full remission. Regardless of trial condition, we made post-hoc classifications of patients’ actual discontinuation trajectories: full discontinuation (n=82), partial discontinuation (n=34) and no discontinuation (n=110) of ADM within 6 months after baseline. A subset of patients (n=15) and physicians (n=7) were interviewed to examine facilitators and barriers of discontinuation.InterventionsAll participants were offered MBCT, which consisted of eight weekly sessions in a group.Primary and secondary outcome measuresDemographic and clinical predictors of successful discontinuation within 6 months, relapse risk within 15 months associated with different discontinuation trajectories, and barriers and facilitators of discontinuation.ResultsOf the 128 patients assigned to MBCT with discontinuation, only 68 (53%) fully discontinued ADM within 6 months, and 17 (13%) discontinued partially. Predictors of full discontinuation were female sex, being employed and lower levels of depression. Relapse risk was lower after no discontinuation (45%) or partial discontinuation (38%), compared with full discontinuation (66%) (p=0.02). Facilitators and barriers of discontinuation were clustered within five themes: (1) pre-existing beliefs about depression, medication and tapering; (2) current experience with ADM; (3) life circumstances; (4) clinical support and (5) mindfulness.ConclusionsDiscontinuing antidepressants appears to be difficult, stressing the need to support patients and physicians in this process. MBCT may offer one of these forms of support.Trial registration numberClinicalTrials.gov Registry (NCT00928980); post-results.
Assessing the benefits on quality of life of a multicomponent intervention for fibromyalgia syndrome in primary care: patients’ and health professionals’ appraisals: a qualitative study protocol
Authors: Arfuch Victoria Mailen , Caballol Angelats Rosa , Aguilar Martín Carina , Carrasco-Querol Noèlia , Sancho Sol Maria Cinta , González Serra Gemma , Fusté Anguera Immaculada , Gonçalves Alessandra Queiroga , Berenguera Anna 
Published: November 2020

IntroductionFibromyalgia syndrome (FMS) is a complex condition still scarcely understood and with ambiguity when prescribing treatment. Both patients and healthcare providers can supply valuable information for the development of new treatment strategies. The qualitative narrative analysis of participant’s accounts is potentially helpful to reveal new insights about their opinions, needs, and experiences and, consequently, to model healthcare interventions accurately. International treatment guidelines suggest a promising future for multicomponent intervention (MI) approaches for FMS. This study aims to assess the benefits of a MI for patients with FMS in the context of primary care (PC) inTerres de L’Ebre,Catalonia (Spain). Furthermore, it is intended to detect the overall perception of effectiveness and to understand patients’ lived experience and its impact on the quality of life.Method and analysisQualitative research from a socioconstructivism paradigm perspective and a Hermeneutic Phenomenological method. For data collection, four focus group discussions (FGDs) of 8–12 people (2 FGDs of patients and 2 of professionals) and 10–12 key informant interviews with the participants in the MI group will be carried out. All the information will be recorded and verbatim transcribed to perform an interpretive thematic analysis.Ethics and disseminationThis study protocol has been approved by the Clinical Research Ethics Committee from the IDIAPJGol Institute, on 25 April 2018 (code P18/068), according to the Declaration of Helsinki/Tokyo. All participants will receive oral/written information about the study, and they will be required to sign an informed consent sheet. Data anonymity will be guaranteed. Dissemination will be carried out through publications in scientific journals, presentations in academic meetings, workshops and through the local and national media.Trial registration numberClinicalTrials.gov:NCT04049006; Pre-results.
Understanding the underlying drivers of obesity in Africa: a scoping review protocol
Authors: Jaca Anelisa , Iwu Chinwe , Durão Solange , Onyango Adelheid W , Wiysonge Charles Shey 
Published: November 2020

IntroductionThe worldwide prevalence of obesity and overweight has doubled since 1980, such that approximately a third of the world’s population is reported as obese or overweight. Obesity rates have increased in all ages and both sexes irrespective of geographical area, ethnicity or socioeconomic status. Due to the high prevalence, related health consequences and costs of childhood and adult obesity, there is a need to comprehensively identify and assess the major underlying drivers of obesity and overweight in the African context.Methods and analysisThis scoping review will be carried out as per the methodological outline by Arksey and O’Malley. The search strategy will be developed and search performed in the Scopus and PubMed electronic databases. In the first search, we will identify concepts that are used as an equivalent to obesity and overweight. Subsequently, we will search for studies comprising of search terms on the underlying factors that drive the development of obesity and overweight. Lastly, we will check reference lists for additional publications. Abstracts and full-text studies will independently be screened by two authors.Ethics and disseminationThe proposed study will generate evidence from published data and hence does not require ethics approval. Evidence generated from this review will be disseminated through journal publications and conference presentations.
Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial
Authors: Tavernier Elsa , McNicholas Bairbre , Pavlov Ivan , Roca Oriol , Perez Yonatan , Laffey John , Mirza Sara , Cosgrave David , Vines David , Frat Jean-Pierre , Ehrmann Stephan , Li Jie 
Published: November 2020

IntroductionProne positioning (PP) is an effective first-line intervention to treat patients with moderate to severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, as it improves gas exchanges and reduces mortality. The use of PP in awake spontaneous breathing patients with ARDS secondary to COVID-19 was reported to improve oxygenation in few retrospective trials with small sample size. High-level evidence of awake PP for hypoxaemic patients with COVID-19 patients is still lacking.Methods and analysisThe protocol of this meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled open label superiority trials. This design is particularly adapted to a rapid scientific response in the pandemic setting. It will take place in multiple sites, among others in USA, Canada, Ireland, France and Spain. Patients will be followed up for 28 days. Patients will be randomised to receive whether awake PP and nasal high flow therapy or standard medical treatment and nasal high flow therapy. Primary outcome is defined as the occurrence rate of tracheal intubation or death up to day 28. An interim analysis plan has been set up on aggregated data from the participating research groups.Ethics and disseminationEthics approvals were obtained in all participating countries. Results of the meta-trial will be submitted for publication in a peer-reviewed journal. Each randomised controlled trial was registered individually, as follows: NCT04325906, NCT04347941, NCT04358939, NCT04395144 and NCT04391140.
Factors associated with COVID-19 infections and mortality in Africa: a cross-sectional study using publicly available data
Authors: Okeahalam Charles , Williams Victor , Otwombe Kennedy 
Published: November 2020

IntroductionThe current COVID-19 pandemic is a global threat. This elicits questions on the level of preparedness and capacity of health systems to respond to emergencies relative to other parts of the world.MethodsThis cross-sectional study uses publicly available core health data for 53 African countries to determine risk factors for cumulative COVID-19 deaths and cases per million in all countries in the continent. Descriptive statistics were determined for the indicators, and a negative binomial regression was used for modelling the risk factors.ResultsIn sub-Saharan Africa, an increase in the number of nursing and midwifery personnel decreased the risk of COVID-19 deaths (p=0.0178), while a unit increase in universal healthcare (UHC) index of service coverage and prevalence of insufficient physical activity among adults increased the risk of COVID-19 deaths (p=0.0432 and p=0.0127). An increase in the proportion of infants initiating breast feeding reduced the number of cases per million (p<0.0001), while an increase in higher healthy life expectancy at birth increased the number of cases per million (p=0.0340).ConclusionDespite its limited resources, Africa’s preparedness and response to the COVID-19 pandemic can be improved by identifying and addressing specific gaps in the funding of health services delivery. These gaps impact negatively on service delivery in Africa, which requires more nursing personnel and increased UHC coverage to mitigate the effects of COVID-19.
Parental perceptions of the impact of neonatal unit visitation policies during COVID-19 pandemic
Authors: Muniraman Hemananda , Ali Mahmoud , Cawley Paul , Hillyer Jessica , Heathcote Adam , Ponnusamy Vennila , Coleman Zoe , Hammonds Kendall , Raiyani Chandni , Gait-Carr Eleanor , Myers Sarah , Hunt Katie , Govande Vinayak , Jain Anoo , Clark Reese , Doherty Cora , Raju Venkata , Clarke Paul 
Published: November 2020

ObjectivesTo ascertain parental perceptions of the impact of restricted visiting policies to neonatal intensive care units during the current COVID-19 pandemic.DesignCross-sectional survey of parents impacted by visitation policies.SettingSix tertiary level neonatal units, four from the UK and two from the USA, participated in the study.ParticipantsParents and families of infants hospitalised in the participating centres between 1 May 2020 and 21 August 2020.MethodsOnline-based and/or paper-based survey, querying the visitation policies and their impact on parents’ ability to visit, care for and bond with their infants.ResultsA total of 231 responses were received. Visitation limited to a single visitor with no restrictions on duration was the most frequently reported policy; 140/217 (63%). Visitation policies were perceived as being restrictive by 62% (138/219) of the respondents with 37% (80/216) reporting being able to visit less often than desired, 41% (78/191) reporting being unable to bond enough and 27% (51/191) reporting not being able to participate in their baby’s daily care. Mild to severe impact on breast feeding was reported by 36% (75/209) of respondents. Stricter policies had a higher impact on families and were significantly associated with a lack of bonding time, inability to participate in care and an adverse impact on breast feeding.ConclusionsVisitation policies during the COVID-19 pandemic varied between centres and over time with stricter restrictions implemented earlier on in the pandemic. Parents reported significant impacts on their ability to visit, care for and bond with their infants with perceived severity of impact worse with stricter restrictions.
What is the normal composition of pericardial fluid?
Authors: Buoro Sabrina , Tombetti Enrico , Ceriotti Ferruccio , Simon Caterina , Cugola Diego , Seghezzi Michela , Innocente Francesco , Maestroni Silvia , del Carmen Baigorria Vaca Maria , Moioli Valentina , Previtali Giulia , Manenti Barbara , Adler Yehuda , Imazio Massimo , Brucato Antonio 
Published: November 2020

ObjectiveBiochemical and cytological pericardial fluid (PF) analysis is essentially based on the knowledge of pleural fluid composition. The aim of the present study is to identify reference intervals (RIs) for PF according to state-of-art methodological standards.MethodsWe prospectively collected and analysed the PF and venous blood of consecutive subjects undergoing elective open-heart surgery from July 2017 to October 2018. Exclusion criteria for study enrolment were evidence of pericardial diseases at preoperatory workup or at intraoperatory assessment, or any other condition that could affect PF analysis.ResultsThe final study sample included 120 patients (median age 69 years, 83 men, 69.1%). The main findings were (1) High levels of proteins, albumin and lactate dehydrogenase (LDH), but not of glucose and cholesterol (2) High cellularity, mainly represented by mesothelial cells. RIs for pericardial biochemistry were: protein content 1.7–4.6 g/dL PF/serum protein ratio 0.29–0.83, albumin 1.19–3.06 g/dL, pericardium-to-serum albumin gradient 0.18–2.37 g/dL, LDH 141–2613 U/L, PF/serum LDH ratio 0.40–2.99, glucose 80–134 mg/dL, total cholesterol 12–69 mg/dL, PF/serum cholesterol ratio 0.07–0.51. RIs for pericardial cells by optic microscopy were: 278–5608 × 106 nucleated cells/L, 40–3790 × 106 mesothelial cells/L, 35–2210 × 106 leucocytes/L, 19–1634 × 106 lymphocytes/L.ConclusionsPF is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Physicians should stop to interpret PF as exudate or transudate according to tools not validated for this setting.
A Bispecific Antibody Antagonizes Prosurvival CD40 Signaling and Promotes Vγ9Vδ2 T cell–Mediated Antitumor Responses in Human B-cell Malignancies
Authors: de Weerdt Iris , Lameris Roeland , Scheffer George L. , Vree Jana , de Boer Renate , Stam Anita G. , van de Ven Rieneke , Levin Mark-David , Pals Steven T. , Roovers Rob C. , Parren Paul W.H.I. , de Gruijl Tanja D. , Kater Arnon P. , van der Vliet Hans J. 
Published: November 2020

Abstract
Novel T cell–based therapies for the treatment of B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), are thought to have strong potential. Progress, however, has been hampered by low efficacy and high toxicity. Tumor targeting by Vγ9Vδ2 T cells, a conserved T-cell subset with potent intrinsic antitumor properties, mediated by a bispecific antibody represents a novel approach promising high efficacy with limited toxicity. Here, we describe the generation of a bispecific Vγ9Vδ2 T-cell engager directed against CD40, which, due to its overexpression and biological footprint in malignant B cells, represents an attractive target. The CD40-targeting moiety of the bispecific antibody was selected because it can prevent CD40L-induced prosurvival signaling and reduce CD40-mediated resistance of CLL cells to venetoclax. Selective activation of Vγ9Vδ2 T cells in the presence of CD40+ tumor cells induced potent Vγ9Vδ2 T-cell degranulation, cytotoxicity against CLL and MM cells in vitro, and in vivo control of MM in a xenograft model. The CD40-bispecific γδ T-cell engager demonstrated lysis of leukemic cells by autologous Vγ9Vδ2 T cells present in patient-derived samples. Taken together, our CD40 bispecific γδ T-cell engager increased the sensitivity of leukemic cells to apoptosis and induced a potent Vγ9Vδ2 T cell–dependent antileukemic response. It may, therefore, represent a potential candidate for the development of novel treatments for B-cell malignancies.
Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer
Authors: Lin Wen-Der , Fan Tan-Chi , Hung Jung-Tung , Yeo Hui-Ling , Wang Sheng-Hung , Kuo Chu-Wei , Khoo Kay-Hooi , Pai Li-Mei , Yu John , Yu Alice L. 
Published: November 2020

AbstractAltered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells. ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension. In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade. In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1. CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity. CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated. Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA–treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing. The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing. We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity. These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
Improved T-cell Receptor Diversity Estimates Associate with Survival and Response to Anti–PD-1 Therapy
Authors: Bortone Dante S. , Woodcock Mark G. , Parker Joel S. , Vincent Benjamin G. 
Published: November 2020

AbstractT-cell receptor (TCR) repertoire profiling has emerged as a powerful tool for biological discovery and biomarker development in cancer immunology and immunotherapy. A key statistic derived from repertoire profiling data is diversity, which summarizes the frequency distribution of TCRs within a mixed population. Despite the growing use of TCR diversity metrics in clinical trial correlative studies in oncology, their accuracy has not been validated using published ground-truth datasets. Here, we reported the performance characteristics of methods for TCR repertoire profiling from RNA-sequencing data, showed undersampling as a prominent source of bias in diversity estimates, and derived a model via statistical learning that attenuates bias to produce corrected diversity estimates. This modeled diversity improved discrimination in The Cancer Genome Atlas data and associated with survival and treatment response in patients with melanoma treated with anti–PD-1 therapy, where the commonly used diversity normalizations did not. These findings have the potential to increase our understanding of the tumor immune microenvironment and improve the accuracy of predictions of patient responses to immunotherapy.
Unraveling the Genotype‐Phenotype Relationship in Hypertrophic Cardiomyopathy: Obesity‐Related Cardiac Defects as a Major Disease Modifier
Authors: Nollet Edgar E. , Westenbrink B. Daan , de Boer Rudolf A. , Kuster Diederik W. D. , van der Velden Jolanda 
Published: November 2020

Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric septal thickening and diastolic dysfunction. More than 1500 mutations in genes encoding sarcomere proteins are associated with HCM. However, the genotype‐phenotype relationship in HCM is incompletely understood and involves modification by additional disease hits. Recent cohort studies identify obesity as a major adverse modifier of disease penetrance, severity, and clinical course. In this review, we provide an overview of these clinical findings. Moreover, we explore putative mechanisms underlying obesity‐induced sensitization and aggravation of the HCM phenotype. We hypothesize obesity‐related stressors to impact on cardiomyocyte structure, metabolism, and homeostasis. These may impair cardiac function by directly acting on the primary mutation‐induced myofilament defects and by independently adding to the total cardiac disease burden. Last, we address important clinical and pharmacological implications of the involvement of obesity in HCM disease modification.
Four Technopaegnia in Musaeus’ Hero and Leander
Authors: Stępień Piotr 
Published: November 2020

Abstract
This article discusses four newly discovered technopaegnia in Musaeus’s Hero and Leander. The author argues that they are interconnected and constitute a complex literary game that spreads almost over the whole poem. The characteristic elements of the technopaegnia discussed in the article are the apostrophes, their palindromic character, and the numbers 9 and 10. Based on the latter feature, the author tries to show that lines 1-10 hide references to the Pythagoreans’ teachings about the first ten numbers.