bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma
Authors: An Shejuan , Camarillo Jeannie M. , Huang Tina Yi-Ting , Li Daphne , Morris Juliette A. , Zoltek Madeline A. , Qi Jin , Behbahani Mandana , Kambhampati Madhuri , Kelleher Neil L. , Nazarian Javad , Thomas Paul M. , Saratsis Amanda M. 
Published: November 2020

Abstract
Background
Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of the H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles.

Methods
We performed targeted mass spectrometry on H3.3K27M mutant and wild-type tissues (n = 12) and cell lines (n = 7).

Results
We found 29.2 and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in modification states were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors, relative to wild-type. Further, H3.3K36me2 was the most abundant co-occurring modification on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro, including increased H3K9me3. JQ1 treatment resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro.

Conclusion
Taken together, our findings provide insight into the effects of the H3K27M mutation on histone modification states and response to treatment, and suggest that H3K36me2 and H4K16ac may represent unique tumor epigenetic signatures for targeted DIPG therapy.
CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomised controlled phase II clinical trial
Authors:   on behalf of the CLASH study group, Koopman Inez , Rinkel Gabriel J. E. , Vergouwen Mervyn D. I. 
Published: November 2020

AbstractBackgroundThe inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve the outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH.MethodsA randomised, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group.DiscussionThe CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH.Trial registrationNetherlands Trial RegisterNTR6752. Registered on 27 October 2017European Clinical Trials Database (EudraCT)2017-004307-51
Effect of “motivational interviewing” and “information, motivation, and behavioral skills” counseling interventions on choosing the mode of delivery in pregnant women: a study protocol for a randomized controlled trial
Authors: Shirzad Mahboubeh , Shakibazadeh Elham , Rahimi Foroushani Abbas , Abedini Mehrandokht , Poursharifi Hamid , Babaei Sohrab 
Published: November 2020

Abstract
Background
Cesarean section is an important surgical procedure, when normal vaginal delivery imposes a risk to mother and/or baby. The World Health Organization states the ideal rate for Cesarean section to be between 10 and 15% of all births. In recent decades, the rate has been increased dramatically worldwide. This paper explains the protocol of a randomized controlled trial that aims to compare the effect of “motivational interviewing” and “information, motivation, and behavioral skills” counseling interventions on choosing mode of delivery in pregnant women.

Methods
A four-armed, parallel-design randomized controlled trial will be conducted on pregnant women. One hundred and twenty women will be randomly assigned to four groups including three intervention groups and one control group. The intervention groups included the following: (1) motivational interviewing; (2) face-to-face information, motivation, and behavioral skills model; and (3) information, motivation, and behavioral skills model provided using a mobile application. The inclusion criteria include being literate, being in gestational age from 24 to 32 weeks, being able to speak Persian, having no complications in the current pregnancy, having no indications for Cesarean section, and having enough time to participate in the intervention. The primary outcome of the study is the mode of delivery. The secondary outcomes are women’s intention to undergo Cesarean section and women’s self-efficacy.

Discussion
The interventions of this protocol have been programmed to reduce unnecessary Cesarean sections. Findings may contribute to a rise in normal vaginal delivery, and the effective intervention may be extended for use in national Cesarean section plans.

Trial registration
Iran Randomized Clinical Trial Center IRCT20151208025431N7. Registered on December 07, 2018.
Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical analysis plan for the trials and for the individual patient data meta-analysis
Authors:   On behalf of the FOCUS, AFFINITY and EFFECTS trialists, Mead Gillian Elizabeth , Graham Catriona , Billot Laurent , Näsman Per , Lundström Erik , Lewis Steff , Hankey Graeme J. , Hackett Maree L. , Forbes John , Dennis Martin 
Published: November 2020

Abstract
Background
Three large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM.

Methods/design
Data from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses.
The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics.
We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures.

Discussion
An IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies.

Trial registration
FOCUS: ISRCTN ISRCTN83290762. Registered on 23 May 2012. EudraCT 2011-005616-29. Registered on 3 February 2012.
AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921. Registered on 22 July 2011.
EFFECTS: ISRCTN ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov NCT02683213. Registered on 2 February 2016. EudraCT 2011-006130-16. Registered on 8 August 2014.
Metabolism, morphology and transcriptome analysis of oscillatory behavior of Clostridium butyricum during long-term continuous fermentation for 1,3-propanediol production
Authors: Zhou Jin-Jie , Shen Jun-Tao , Wang Xiao-Li , Sun Ya-Qin , Xiu Zhi-Long 
Published: November 2020

AbstractBackgroundOscillation is a special cell behavior in microorganisms during continuous fermentation, which poses threats to the output stability for industrial productions of biofuels and biochemicals. In previous study, a spontaneous oscillatory behavior was observed inClostridium butyricum-intensive microbial consortium in continuous fermentation for 1,3-propanediol (1,3-PDO) production from glycerol, which led to the discovery of oscillation in speciesC. butyricum.ResultsSpontaneous oscillations byC. butyricumtended to occur under glycerol-limited conditions at low dilution rates. At a glycerol feed concentration of 88 g/L and a dilution rate of 0.048 h−1, the oscillatory behavior ofC. butyricumwas observed after continuous operation for 146 h and was sustained for over 450 h with an average oscillation period of 51 h. During oscillations, microbial glycerol metabolism exhibited dramatic periodic changes, in which productions of lactate, formate and hydrogen significantly lagged behind that of other products including biomass, 1,3-PDO and butyrate. Analysis of extracellular oxidation–reduction potential and intracellular ratio of NAD+/NADH indicated that microbial cells experienced distinct redox changes during oscillations, from oxidized to reduced state with decreasing of growth rate. Meanwhile,C. butyricumS3 exhibited periodic morphological changes during oscillations, with aggregates, elongated shape, spores or cell debris at the trough of biomass production. Transcriptome analysis indicated that expression levels of multiple genes were up-regulated when microbial cells were undergoing stress, including that for pyruvate metabolism, conversion of acetyl-CoA to acetaldehyde as well as stress response.ConclusionThis study for the first time systematically investigated the oscillatory behavior ofC. butyricumin aspect of occurrence condition, metabolism, morphology and transcriptome. Based on the experimental results, two hypotheses were put forward to explain the oscillatory behavior: disorder of pyruvate metabolism, and excessive accumulation of acetaldehyde.
Partial laryngectomy and reconstruction with rotation of the epiglottis in the treatment of a rare laryngeal schwannoma: a case report
Authors: Costa Claudiney Candido , Ramos Hugo Valter Lisboa , Alves Wilder , Lamounier Pauliana , Velasco Leandro de Castro , El Cheikh Mikhael Romanholo 
Published: November 2020

AbstractBackgroundNeurogenic tumors of the larynx are rare, with few cases having been reported in the literature. Schwannomas are responsible for 0.1% of all benign tumors of the larynx. They arise in the sheaths of the peripheral, autonomic, and cranial nerves. The objective of this report is to describe a case of a bulky laryngeal schwannoma, the surgical procedure for its removal, and the long-term patient follow-up.Case presentationA 19-year-old Brazilian woman presented to our institution with a complaint of progressive dyspnea over the preceding year, as well as dysphonia, dysphagia for solids, and globus pharyngeus. Direct rigid laryngoscopy showed a supraglottic tumor obstructing approximately 90% of the larynx. With the symptoms progressing to severe dyspnea, an emergency tracheostomy was performed. After infusion of intravenous contrast, magnetic resonance imaging revealed a mass lesion with intense, heterogeneous contrast enhancement along the posterior wall of the hypopharynx, blocking all of the lumen and measuring 2.8 cm and 2.2 cm at its largest diameters. The image suggested a neoplastic lesion. The patient underwent open surgery for tumor resection. Her postsurgical recovery was uncomplicated. Histopathology and immunohistochemistry revealed the tumor to be a laryngeal schwannoma.ConclusionThe definitive diagnosis of laryngeal lesions can be difficult, and histopathology plays a pivotal role. Laryngeal schwannomas are rare; however, tumors can become large and may ultimately lead to airway obstruction.
Factors affecting the delivery of complex rehabilitation interventions in research with neurologically impaired adults: a systematic review
Authors: Holmes Jain Anne , Logan Philippa , Morris Richard , Radford Kathryn 
Published: November 2020

AbstractBackgroundRehabilitation research does not always improve patient outcomes because of difficulties implementing complex health interventions. Identifying barriers and facilitators to implementation fidelity is critical. Not reporting implementation issues wastes research resources and risks erroneously attributing effectiveness when interventions are not implemented as planned, particularly progressing from single to multicentre trials. The Consolidated Framework for Implementation Research (CFIR) and Conceptual Framework for Implementation Fidelity (CFIF) facilitate identification of barriers and facilitators. This review sought to identify barriers and facilitators (determinants) affecting implementation in trials of complex rehabilitation interventions for adults with long-term neurological conditions (LTNC) and describe implementation issues.MethodsImplementation, complex health interventions and LTNC search terms were developed. Studies of all designs were eligible. Searches involved 11 databases, trial registries and citations. After screening titles and abstracts, two reviewers independently shortlisted studies. A third resolved discrepancies. One reviewer extracted data in two stages; 1) descriptive study data, 2) units of text describing determinants. Data were synthesised by (1) mapping determinants to CFIF and CFIR and (2) thematic analysis.ResultsForty-three studies, from 7434 records, reported implementation determinants; 41 reported both barriers and facilitators. Most implied determinants but five used implementation theory to inform recording. More barriers than facilitators were mapped onto CFIF and CFIR constructs. “Patient needs and resources”, “readiness for implementation”, “knowledge and beliefs about the intervention”, “facilitation strategies”, “participant responsiveness” were the most frequently mapped constructs. Constructs relating to the quality of intervention delivery, organisational/contextual aspects and trial-related issues were rarely tapped. Thematic analysis revealed the most frequently reported determinants related to adherence, intervention perceptions and attrition.ConclusionsThis review has described the barriers and facilitators identified in studies implementing complex interventions for people with LTNCs. Early adoption of implementation frameworks by trialists can simplify identification and reporting of factors affecting delivery of new complex rehabilitation interventions. It is vital to learn from previous experiences to prevent unnecessary repetitions of implementation failure at both trial and service provision levels. Reported facilitators can provide strategies for overcoming implementation issues. Reporting gaps may be due to the lack of standardised reporting methods, researcher ignorance and historical reporting requirements.Systemic review registrationPROSPERO CRD42015020423
Respiratory syncytial virus prophylaxis for prevention of recurrent childhood wheeze and asthma: a systematic review
Authors: Quinn Lauren Alexandra , Shields Michael D. , Sinha Ian , Groves Helen E. 
Published: November 2020

AbstractBackgroundAcute bronchiolitis caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and asthma. However, it is unclear whether this association is causal. RSV-specific monoclonal antibodies have been shown to reduce RSV-related hospitalisations in high-risk infants, but the longer-term follow-up has given conflicting evidence for prevention of recurrent wheeze or asthma.ObjectiveWe performed a systematic review and meta-analysis to determine whether monoclonal antibody prophylaxis against RSV bronchiolitis reduces the risk of subsequent recurrent wheeze or asthma. If so, this may support the hypothesis of causality.MethodsStudies were identified via an online database search using Embase, MEDLINE, PubMed, Web of Science and the Cochrane Library. Manufacturers of monoclonal antibodies were contacted directly for unpublished data. The intervention of interest was RSV monoclonal antibody prophylaxis, and the primary outcome measure was recurrent wheeze and/or asthma. Studies were screened according to inclusion/exclusion criteria. Included studies were evaluated for quality and assessed for bias independently by 3 reviewers using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) approach. Results were extracted into 2 × 2 outcome tables and a meta-analysis carried out producing forest plots based on relative risk. Heterogeneity was assessed using theI2statistic.ResultsThe search identified 141 articles, which, after screening, resulted in eight studies (2 randomised controlled trials), thus including 11,195 infants in the meta-analysis. The overall result demonstrated a non-statistically significant reduction in relative risk of developing recurrent wheeze or asthma (RR 0.60; 95% CI 0.31 to 1.16). Study quality was generally low with evidence of publication bias and statistical heterogeneity. However, sub-group analysis excluding studies deemed to be ‘very low’ quality showed a relative risk of 0.42 (95% CI 0.22 to 0.80,p= 0.008). A further sub-group analysis for infants aged 32 to < 36 weeks showed a statistically significant relative risk of 0.35 (95% CI 0.14 to 0.86,p= 0.02).DiscussionWe did not identify an overall statistically significant benefit. However, our two sub-group analyses did find statistically significant benefits of monoclonal antibody therapy on the risk of recurrent wheeze and asthma. The main limitation of this study is the lack of high-quality randomised controlled trials, highlighting the need for more research in this field.
A linearized conservative Galerkin–Legendre spectral method for the strongly coupled nonlinear fractional Schrödinger equations
Authors: Fei Mingfa , Zhang Guoyu , Wang Nan , Huang Chengming 
Published: November 2020

AbstractIn this paper, based on Galerkin–Legendre spectral method for space discretization and a linearized Crank–Nicolson difference scheme in time, a fully discrete spectral scheme is developed for solving the strongly coupled nonlinear fractional Schrödinger equations. We first prove that the proposed scheme satisfies the conservation laws of mass and energy in the discrete sense. Then a prior bound of the numerical solutions in$L^{\infty }$L∞-norm is obtained, and the spectral scheme is shown to be unconditionally convergent in$L^{2}$L2-norm, with second-order accuracy in time and spectral accuracy in space. Finally, some numerical results are provided to validate our theoretical analysis.
Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation
Authors: Khodabandehloo Fatemeh , Taleahmad Sara , Aflatoonian Reza , Rajaei Farzad , Zandieh Zahra , Nassiri-Asl Marjan , Eslaminejad Mohamadreza Baghaban 
Published: November 2020

AbstractBackgroundAdult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0.ResultsGene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE.ConclusionsThese findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.
Marital separation and contact with primary healthcare services for mental health problems: a register-based study
Authors: Reneflot Anne , Øien-Ødegaard Carine , Hauge Lars Johan 
Published: November 2020

Abstract
Background
Marital separation is associated with mental health problems, but little is known about how this translates into healthcare use. In this study, we examine the relationship between marital separation and primary healthcare use for mental health problems.

Methods
We used data covering the period from 2005 to 2015 from the Norwegian Population Register, Statistics Norway’s Educational Registration System and the Norwegian Health Economics Database. Data were analyzed using logistic regression analysis. To control for time invariant characteristics, we estimated fixed-effect models.

Results
Marital separation was associated with increased contact with primary healthcare services for mental health problems (MH-consultations). The prevalence of MH-consultations peaked during the year of marital separation. MH-consultations were more common following marital separation than prior to the separation. This pattern remained significant in the fixed-effect models.

Conclusions
Men and women who experienced marital separation were more likely to consult primary healthcare services for mental health problems than those who remained married. Our study suggests that several mechanisms are in play. The prevalence of MH-consultations of those who eventually separated were higher several years prior to the separation. This lends support to selection mechanisms, whereas the sharp rise in the prevalence of MH-consultations around the time of marital separation coupled to higher levels several years after separation, indicate that marital separation induces both transient stress and leads to more lasting strain.