bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suicide in Nigeria: observations from the content analysis of newspapers
Authors: Oyetunji Tosin Philip , Arafat S M Yasir , Famori Stephen Oluwaseyi , Akinboyewa Timilehin Blessing , Afolami Michael , Ajayi Moyo Faith , Kar Sujita Kumar 
Published: January 2021

BackgroundSuicide is a global public health problem and Nigeria is one of the epicentres of suicide in the world. However, there is a dearth of research exploring the epidemiological aspects of suicide in Nigeria.AimTo examine the demographic information and precipitating events for suicides in Nigeria by analysing the contents of newspaper reports of suicide.MethodsWe searched, collected, and analysed published news reports about suicide from 10 English newspapers in Nigeria. A total of 350 suicide reports were assessed between January 2010 and December 2019 after screening and sorting.ResultsThe mean (SD) age of the reported cases was 36.33 (15.48) years. Majority of the reported cases were male (80.6%), married (51.8%), students (33.6%), living in a semi-urban area (40.3%) and among the age group of 25–34 (25.3%). Hanging (48.6%) and poisoning (32.2%) were the most commonly reported methods of suicide. Financial constraints and marital conflicts were most commonly assumed precipitating factors.ConclusionThis study suggests that being male, married, or living in semi-urban areas are associated with suicide in Nigeria. Further community-based studies are warranted to generalise the findings and adopt appropriate preventive strategies.
Synbindin restrains proinflammatory macrophage activation against microbiota and mucosal inflammation during colitis
Authors: Ai Luoyan , Ren Yimeng , Zhu Mingming , Lu Shiyuan , Qian Yun , Chen Zhaofei , Xu Antao 
Published: January 2021

ObjectiveAs a canonical membrane tethering factor, the function of synbindin has been expanding and indicated in immune response. Here, we investigated the role of synbindin in the regulation of toll-like receptor 4 (TLR4) signalling and macrophage response to microbiota during colitis.DesignThree distinct mouse models allowing global, myeloid-specific or intestinal epithelial cell-specific synbindin heterozygous deletion were constructed and applied to reveal the function of synbindin during dextran sodium sulfate (DSS) colitis. Effects of synbindin on TLR4 signalling and macrophage activation in response to bacterial lipopolysaccharide (LPS) or Fusobacterium nucleatum were evaluated. The colocalisation and interaction between synbindin and Rab7b were determined by immunofluorescence and coimmunoprecipitation. Synbindin expression in circulating monocytes and intestinal mucosal macrophages of patients with active IBD was detected.ResultsGlobal synbindin haploinsufficiency greatly exacerbated DSS-induced intestinal inflammation. The increased susceptibility to DSS was abolished by gut microbiota depletion, while phenocopied by specific synbindin heterozygous deletion in myeloid cells rather than intestinal epithelial cells. Profoundly aberrant proinflammatory gene signatures and excessive TLR4 signalling were observed in macrophages with synbindin interference in response to bacterial LPS or Fusobacterium nucleatum. Synbindin was significantly increased in intestinal mucosal macrophages and circulating monocytes from both mice with DSS colitis and patients with active IBD. Interleukin 23 and granulocyte-macrophage colony-stimulating factor were identified to induce synbindin expression. Mechanistic characterisation indicated that synbindin colocalised and directly interacted with Rab7b, which coordinated the endosomal degradation pathway of TLR4 for signalling termination.ConclusionSynbindin was a key regulator of TLR4 signalling and restrained the proinflammatory macrophage activation against microbiota during colitis.
Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett’s carcinoma
Authors: Ehlken Hanno , Schmitz Rüdiger , Riethdorf Sabine , Riethdorf Lutz , Krause Jenny , Karstens Karl-Frederick , Schrader Jörg , Viol Fabrice , Giannou Anastasios , Sterlacci William , Vieth Michael , Clauditz Till , Kähler Christian , Mann Oliver , Izbicki Jakob R , Huber Samuel , Pantel Klaus , Rösch Thomas 
Published: January 2021

Background and aimsEndoscopic resection has been established as curative therapy for superficial cancer arising from Barrett’s oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation.MethodsThis hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625–10 mg/mL); cell growth was determined on a Multiwell plate reader.ResultsCancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls.ConclusionsTumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
Firearm injuries in children: a missed opportunity for firearm safety education
Authors: Stokes Sarah C , McFadden Nikia R , Salcedo Edgardo S , Beres Alana L 
Published: January 2021

BackgroundSurgeons frequently care for children who have sustained gunshot wounds (GSWs). However, firearm safety education is not a focus in general surgery training. We hypothesised that firearm safety discussions do not routinely take place when children present to a trauma centre with a GSW.MethodA retrospective review of patients <18 years presenting with GSWs to a level 1 paediatric trauma centre from 2009 to 2019 was performed. The primary outcome was discussion of firearm safety with the patient or family. The secondary outcome was notification of child protective services (CPS).ResultsA total of 226 patients with GSWs were identified, 22% were unintentional and 63% were assault. Firearm safety discussions took place in 10 cases (4.4%). Firearm safety discussions were more likely to occur after unintentional injuries compared with other mechanisms (16.0% vs 1.3%, p<0.001). CPS was contacted in 29 cases (13%). CPS notification was more likely for unintentional injuries compared with other mechanisms (40% vs 3.9%, p<0.001) and for younger patients (7 years vs 15 years, p<0.001).ConclusionAt a paediatric trauma centre, firearm safety discussions occurred in 4.4% of cases of children presenting with a GSW. There is a significant room for improvement in providing safety education interventions.
Mapping of colorectal carcinoma diseases with activation of Wnt/beta-catenin signalling pathway using hierarchical clustering approach
Authors: Mosnier Jean-François , Airaud Fabrice , Métairie Sylvie , Volteau Christelle , Bezieau Stéphane , Denis Marc 
Published: January 2021

AimsTo map the colorectal carcinoma (CRC) diseases with significant Wnt signalling pathway activation for delineating their clinicopathological and molecular profiles.MethodsMapping is based on hierarchical clustering analyses of a series of 283 CRCs. Data tabulated were histopathological patterns, immunophenotypic differentiation,RAS,RAF,CTNNB1mutations and microsatellite instability status, tumour-infiltrating lymphocytes (TILs) and genetic setting. Beta-catenin expression in more than 10% of cell nuclei in the centre of tumour serves as a surrogate marker of significant activation of Wnt signalling pathway.ResultsNuclei beta-catenin expression was present in 95% of CRCs; 56% of them met the criteria of high level of nuclei beta-catenin expression (≥10%). Proportion of beta-catenin positive nuclei was significantly higher in younger patients, rectal and left-sided colonic carcinomas. CRCs with high level of nuclei beta-catenin expression were regrouped into three clusters: (1) microsatellite stability (MSS) CRCs with no constitutive MAPK pathway activation including 90% of low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs; (2)RAS-mutated MSS CRCs including low-grade adenocarcinoma, NOS, with intestinal differentiation and mucinous adenocarcinoma without TILs; (3) MSI-H CRCs including bothBRAF-mutated CRCs evolving from serrated pathway andCTNNB1-mutated CRCs associated with Lynch syndrome.ConclusionsMSS low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs (‘crypt-like adenocarcinoma’) might be the morphological pending of canonical molecular subtype of CRC defined as displayed molecular epithelial differentiation and upregulation of WNT in consensus molecular classification of CRC.
Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression
Authors: Natoli Marina , Gallon John , Lu Haonan , Amgheib Ala , Pinato David J , Mauri Francesco A , Marafioti Teresa , Akarca Ayse U , Ullmo Ines , Ip Jacey , Aboagye Eric O , Brown Robert , Karadimitris Anastasios , Ghaem-Maghami Sadaf 
Published: January 2021

BackgroundEndogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC.MethodsERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells.ResultsERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells.ConclusionsThese findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity.
Unexpected role ofSIX1variants in craniosynostosis: expanding the phenotype ofSIX1-related disorders
Authors: Calpena Eduardo , Wurmser Maud , McGowan Simon J , Atique Rodrigo , Bertola Débora R , Cunningham Michael L , Gustafson Jonas A , Johnson David , Morton Jenny E V , Passos-Bueno Maria Rita , Timberlake Andrew T , Lifton Richard P , Wall Steven A , Twigg Stephen R F , Maire Pascal , Wilkie Andrew O M 
Published: January 2021

BackgroundPathogenic heterozygousSIX1variants (predominantly missense) occur in branchio-otic syndrome (BOS), but an association with craniosynostosis has not been reported.MethodsWe investigated probands with craniosynostosis of unknown cause using whole exome/genome (n=628) or RNA (n=386) sequencing, and performed targeted resequencing ofSIX1in 615 additional patients. Expression of SIX1 protein in embryonic cranial sutures was examined in theSix1nLacZ/+reporter mouse.ResultsFrom 1629 unrelated cases with craniosynostosis we identified seven differentSIX1variants (three missense, including two de novo mutations, and four nonsense, one of which was also present in an affected twin). Compared with population data, enrichment ofSIX1loss-of-function variants was highly significant (p=0.00003). All individuals with craniosynostosis had sagittal suture fusion; additionally four had bilambdoid synostosis. Associated BOS features were often attenuated; some carrier relatives appeared non-penetrant. SIX1 is expressed in a layer basal to the calvaria, likely corresponding to the dura mater, and in the mid-sagittal mesenchyme.ConclusionCraniosynostosis is associated with heterozygousSIX1variants, with possible enrichment of loss-of-function variants compared with classical BOS. We recommend screening ofSIX1in craniosynostosis, particularly when sagittal±lambdoid synostosis and/or any BOS phenotypes are present. These findings highlight the role ofSIX1in cranial suture homeostasis.
Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study
Authors: Buron Mathias Due , Kalincik Tomas , Sellebjerg Finn , Sørensen Per Soelberg , Magyari Melinda 
Published: January 2021

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.
Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis
Authors: Chan Vicky , Lo Kenneth 
Published: January 2021

AbstractPurposeDifferent dietary supplements aimed at improving sleep quality are available on the market, but there has not been a comprehensive review to evaluate the efficacy of these dietary supplements on subjective sleep quality. We aimed to summarise up-to-date research evidence and to identify the types of dietary supplement that improve subjective sleep quality.MethodsMultiple databases (Ovid Emcare, Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and APA PsycInfo) were used for searching papers published until August 2020. The changes in sleep quality indices, intervention duration and sample size were extracted from every paper. To analyse the effect of dietary supplements on sleep quality, a random effects model with mean difference (MD) and 95% CI was adopted. The heterogeneity across studies was measured by I2 statistics. The quality of included studies was evaluated by Cochrane's risk of bias tool.ResultsThirty-one randomised controlled trials of dietary supplements were included. Subjective sleep quality was significantly improved by supplementation of amino acids (MD −1.27, 95% CI −2.35 to –0.20; I2=0%), melatonin (MD −1.21, 95% CI −2.17 to –0.24; I2=79%) and vitamin D (MD −1.63, 95% CI −3.15 to –0.10; I2=85%). Although not all studies provided adequate data for meta-analysis, we also discussed how magnesium, zinc, resveratrol and nitrate supplementation may improve sleep quality.ConclusionsAmino acids, vitamin D and melatonin supplements were significantly beneficial to improve sleep quality. However, high heterogeneity and wide confidence levels were observed in vitamin D and melatonin. Further research on the effect of magnesium, zinc, resveratrol and nitrate supplementation on improving sleep quality is required.
Engaging in advocacy during medical training: assessing the impact of a virtual COVID-19-focused state advocacy day
Authors: Yu Zizi , Moustafa Danna , Kwak Ruby , O'Connor Daniel M , Cavanaugh-Hussey Margaret W , Huang Jennifer T , LaChance Avery H 
Published: January 2021

AbstractPurposeThe physician voice is crucial to shaping health policy and public health guidelines, particularly during COVID-19. However, there are gaps in health policy and advocacy education within graduate medical education. This study sought to characterise the impact of a virtual COVID-19 focused advocacy day among medical trainees in Massachusetts.Study designThe half-day event featured speakers drawn from government relations experts, physician advocates, and state and federal legislators as well as breakout discussions among attendees. A 25-question Redcap survey and list of resources/opportunities for continued advocacy was administered to all participants at event's conclusion on 19 May 2020.ResultsThere were 60 responses from 141 participants (43% response rate). One-third reported no prior formal health policy instruction, and over half reported getting information from news publications, social media and peers. 58% believed physician involvement in advocacy to be ‘extremely important’ prior to COVID-19; 83% believed the same after onset of COVID-19 (p&lt;0.0001). The most common barriers to advocacy engagement were lack of time and knowledge. Most attendees felt participation increased their knowledge and likelihood to engage in the COVID-19 response, imparted useful skills/knowledge for continued advocacy, increased their interest in future similar events, and that such events should be available to all trainees.ConclusionsTrainees recognise the importance of health policy and advocacy and value opportunities to gain the necessary skills/knowledge to effect tangible change. Virtual advocacy days can be replicated nationwide to help trainees learn about advocacy efforts and find their legislative voices during COVID-19 and beyond.
Prevalence of frailty and reliability of established frailty instruments in adult elective colorectal surgical patients: a prospective cohort study
Authors: Dale MacLaine Thomas , Baker Oliver , Burke Dermot , Howell Simon J 
Published: January 2021

AbstractPurposeLarge population studies now demonstrate that frailty is prevalent in all adult age groups. Limited data exist on the association between frailty and surgical outcome in younger patients. The aim of the study was to explore the agreement between frailty identification tools and collect pilot data on their predictive value for frailty-associated outcomes in an adult surgical population.Study designProspective cohort study.ResultsFrailty scores were recorded in 200 patients (91 men), mean (range) age 57 (18–92) years. The prevalence of prefrailty was 52%–67% and that of frailty 2%–32% depending on the instrument used. Agreement between the instruments was poor, kappa 0.08–0.17 in pairwise comparisons. Outcome data were available on 160 patients. Only the frailty phenotype was significantly associated with adverse outcomes, RR 6.1 (1.5–24.5) for postoperative complications. The three frailty scoring instruments studies had good sensitivity (Clinical Frailty Scale (CFS)—90%, Accumulation Deficit (AD)—96%, Frailty Phenotype (FP)—97%) but poor specificity (CFS—12%, AD—13%, FP—18%) for the prediction of postoperative complications. All three instruments were poorly predictive of adverse outcomes with likelihood ratios of CFS—1.02, AD—1.09 and FP—1.17.ConclusionsThis study showed a significant prevalence of prefrailty and frailty in adult colorectal surgical patients of all ages. There was poor agreement between three established frailty scoring instruments. Our data do not support the use of current frailty scoring instruments in all adult colorectal surgical patients. However, the significant prevalence of prefrailty and frailty across all age groups of adult surgical patient justifies further research to refine frailty scoring in surgical patients.
HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis
Authors: Ye Yuanfan , Burkholder Greer A , Wiener Howard , Aslibekyan Stella , Khan Ashraf E , Shrestha Sadeep 
Published: January 2021

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts.MethodsElectronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD.ResultsOf the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD.ConclusionsThere were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.