bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sentence‐Final Particles in Mandarin*
Authors: Fang Hongmei , Hengeveld Kees 
Published: May 2022

AbstractMandarin Chinese is rich in sentence‐final particles, which have to follow a rigid linear order when they cluster. In much of the literature, researchers focus on clarifying the functions of individual particles, with less attention being paid to the explanations of their highly restricted order. Based on corpus data and using the framework of Functional Discourse Grammar (FDG, Hengeveld & Mackenzie 2008), this paper explores the questions which particles can cluster and why they cluster in a specific order. We show that maximally three Mandarin sentence‐final particles can cluster, and we argue that their sequence is restricted by their positioning in a strict four‐layered hierarchical structure, in which each particle pertains to a specific semantic or pragmatic layer. In addition, Mandarin particles provide evidence that there are operators at a higher discourse level than so far assumed to exist in FDG.
Expression of the hedgehog signalling pathway and the effect of inhibition at the level of smoothened in canine osteosarcoma cell lines
Authors: Nam Aryung , Song Woo‐Jin , An Ju‐Hyun , Rebhun Robert B. , Youn Hwa‐Young , Seo Kyoung‐Won 
Published: May 2022

AbstractOsteosarcoma (OSA) is the most common malignant bone cancer in dogs. Canine and human OSA share several features, including tumour environments, response to traditional treatment, and several molecular pathways. Hedgehog (Hh) signalling is known to contribute to tumorigenesis and progression of various cancers, including human OSA. This study aimed to identify the role of the Hh signalling pathway in canine OSA cell lines, including Abrams, D17, and Moresco, focusing on the signal transducer Smoothened (SMO). mRNA and protein levels of Hh pathway components, including SHH, IHH, SMO, and PTCH1, were aberrant in all examined OSA cell lines compared with canine osteoblast cells. The SMO inhibitor cyclopamine significantly decreased cell viability and colony‐forming ability in the canine OSA cell lines in a dose‐dependent manner. Moresco cells, which expressed the highest level of SMO protein, were the most sensitive to the anticancer effect of cyclopamine among the three canine OSA cell lines tested. Hh downstream target gene and protein expression in canine OSA cell lines were downregulated after cyclopamine treatment. In addition, cyclopamine significantly increased apoptotic cell death in Abrams and Moresco cells. The findings that Hh/SMO is activated in canine OSA cell lines and cyclopamine suppresses OSA cell survival via inhibition of SMO suggest that the Hh/SMO signalling pathway might be a novel therapeutic target for canine OSA.
The effects of sex and neuter status on trauma survival in dogs: A Veterinary Committee on Trauma registry study
Authors: Fontes Gabrielle S. , McCarthy Robert J. , Kutzler Michelle A. , Zitek‐Morrison Emily 
Published: May 2022

AbstractObjectiveTo determine the effect of sex and neuter status on trauma survival in dogs.DesignMulti‐institutional prospective case series, September 2013 to March 2019, retrospectively analyzed.SettingLevel I and II Veterinary Trauma Centers.AnimalsConsecutive sample of 2649 dogs in the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma patient registry meeting inclusion criteria. For inclusion, dogs had to have complete data entries, be postpubertal (≥7 months age in females and ≥10 months age in males), and have sustained moderate to severe trauma (animal trauma triage [ATT] score ≥5/18). Dogs that were dead upon arrival, euthanized for financial or unknown reasons alone, or that were presented by a Good Samaritan but subsequently humanely euthanized were excluded.Measurements and Main ResultsData collected included age, sex, neuter status (intact, neutered), trauma type (blunt, penetrating, both), outcome (survived to hospital discharge, died, euthanized), and reason for euthanasia (grave prognosis, financial reasons, or both). Of 2649 eligible dogs, 56% survived to hospital discharge (n = 1469). Neutered females had a significantly higher survival rate (58.3% vs 51.3%; P = 0.03) compared to intact females, and neutered males had a significantly higher survival rate (56.6% vs 50.7%; P = 0.04) compared to intact males. There was no significant difference in survival between intact females and intact males (P = 0.87) or between neutered females and neutered males (P = 0.46). Mean cumulative ATT score was higher in intact groups and was found to be a significant predictor of survival (P < 0.01). Based on logistic models, overall odds of survival were 20.7% greater in neutered dogs.ConclusionsGonadectomy is associated with lower ATT scores and improved survival after moderate to severe trauma in both female and male dogs.
Supplemental Material: Detrital zircon ages from upper Paleozoic–Triassic clastic strata on St. Lawrence Island, Alaska: An enigmatic component of the Arctic Alaska–Chukotka microplate
Authors: Amato J.M. , al. et 
Published: May 2022

<p>Contains locations of petrographic samples, additional plots for geochronology data, and an Excel file containing all of the U-Pb data tables. </p>
Prevalence of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease
Authors: Naimimohasses Sara , O'Gorman Philip , McCormick Emma , Ferguson Damien , Monaghan Ann , McGrath Marie , Robinson Mark W , Gormley John , Norris Suzanne 
Published: May 2022

ObjectiveEnd-stage chronic liver disease is associated with accelerated ageing and increased frailty. Frailty measures have provided clinical utility in identifying patients at increased risk of poor health outcomes, including those awaiting liver transplantation. However, there is limited data on the prevalence and severity of frailty in patients with non-cirrhotic non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of frailty and prefrailty in patients with non-cirrhotic NAFLD and correlate with severity of liver disease.DesignA cross-sectional analysis of functional and laboratory frailty assessments, including the Fried frailty index (FFI), a self-reported frailty index (SRFI) and a lab-based frailty index (FI-LAB), was performed in a cohort of 109 patients with NAFLD, and results compared with fibrosis staging based on transient elastography.ResultsPatients with NAFLD had a high prevalence of prefrailty and frailty, with a median SRFI score of 0.18 (IQR: 0.18), FFI of 1 (IQR: 1) and FI-LAB of 0.18 (IQR: 0.12). Using the SRFI, 45% of F0/F1 patients were classified as prefrail and 20% were classified as frail, while in F2/F3 patients this increased to 36% and 41%, respectively. SRFI, 30 s sit-to-stand and FI-LAB scores increased with increasing liver fibrosis stages (p=0.001, 0.006 and <0.001, respectively). On multivariate linear regression, female gender was identified as a significant predictor of elevated frailty scores.ConclusionThis study identifies a high prevalence of frailty in individuals with non-cirrhotic NAFLD. Addressing frailty through early rehabilitation interventions may reduce overall morbidity and mortality in this population.
Study designs for clinical trials applied to personalised medicine: a scoping review
Authors: Superchi Cecilia , Brion Bouvier Florie , Gerardi Chiara , Carmona Montserrat , San Miguel Lorena , Sánchez-Gómez Luis María , Imaz-Iglesia Iñaki , Garcia Paula , Demotes Jacques , Banzi Rita , Porcher Raphaël 
Published: May 2022

ObjectivePersonalised medicine (PM) allows treating patients based on their individual demographic, genomic or biological characteristics for tailoring the ‘right treatment for the right person at the right time’. Robust methodology is required for PM clinical trials, to correctly identify groups of participants and treatments. As an initial step for the development of new recommendations on trial designs for PM, we aimed to present an overview of the study designs that have been used in this field.DesignScoping review.MethodsWe searched (April 2020) PubMed, Embase and the Cochrane Library for all reports in English, French, German, Italian and Spanish, describing study designs for clinical trials applied to PM. Study selection and data extraction were performed in duplicate resolving disagreements by consensus or by involving a third expert reviewer. We extracted information on the characteristics of trial designs and examples of current applications of these approaches. The extracted information was used to generate a new classification of trial designs for PM.ResultsWe identified 21 trial designs, 10 subtypes and 30 variations of trial designs applied to PM, which we classified into four core categories (namely, Master protocol, Randomise-all, Biomarker strategy and Enrichment). We found 131 clinical trials using these designs, of which the great majority were master protocols (86/131, 65.6%). Most of the trials were phase II studies (75/131, 57.2%) in the field of oncology (113/131, 86.3%). We identified 34 main features of trial designs regarding different aspects (eg, framework, control group, randomisation). The four core categories and 34 features were merged into a double-entry table to create a new classification of trial designs for PM.ConclusionsA variety of trial designs exists and is applied to PM. A new classification of trial designs is proposed to help readers to navigate the complex field of PM clinical trials.
Protocol for updated systematic review and meta-analysis on the burden of non-communicable diseases among people living with HIV in sub-Saharan Africa
Authors: Moyo Maureen , Musekiwa Alfred 
Published: May 2022

IntroductionSub-Saharan Africa (SSA) is faced with the dual epidemics of HIV/AIDS and non-communicable diseases (NCDs). Cardiovascular diseases, cancers, chronic respiratory diseases, diabetes and mental illnesses are the five major NCDs, causing death globally with low-income and middle-income countries, contributing 78% of all NCD deaths and 85% of premature deaths. There has been increased interest in the integration of HIV and NCDs care, especially in SSA that accounts for 55% of people living with HIV (PLHIV) globally. This systematic review and meta-analysis will estimate the overall prevalence or incidence of NCDs (or its risk factors) among adults living with HIV in SSA.Methods and analysisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used. Two authors will independently screen the title and abstracts of the articles identified from the search. Study participants will be any adult (≥18 years old) living with HIV in SSA. Exposure of interest will be HIV (with or without ART). Outcomes of interest are prevalence or incidence of any NCD/NCD risk factors. A random-effects meta-analysis will be used to estimate pooled prevalence or incidence of the five major NCDs among PLHIV, using Stata software. χ2 test and I2 statistic will be used to measure statistical heterogeneity between studies. If there is significant heterogeneity, subgroup analysis will be used to investigate potential sources. Publication bias will be assessed using funnel plots and the Stata ‘metabias’ command.Ethics and disseminationEthical review will not be required because it is a systematic review. Data will be kept in the institutional data repository. Study findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42021258769.
Epicardial injection of allogeneic human-induced-pluripotent stem cell-derived cardiomyocytes in patients with advanced heart failure: protocol for a phase I/IIa dose-escalation clinical trial
Authors: Zhang He , Xue Yunxing , Pan Tuo , Zhu Xiyu , Chong Hoshun , Xu Can , Fan Fudong , Cao Hailong , Zhang Bomin , Pan Jun , Zhou Qing , Yang Gang , Wang Jiaxian , Wang Dong-Jin 
Published: May 2022

IntroductionHeart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery.MethodsThis study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone.Ethics and disseminationThe study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings.Trial registration numberNCT03763136.
Evaluating the efficacy and safety of transdermal electrical stimulation on the visual functions of patients with retinitis pigmentosa: a clinical trial protocol for a prospective, multicentre, randomised, double-masked and sham-controlled design (ePICO trial)
Authors: Miura Gen , Ozawa Yoshihito , Shiko Yuki , Kawasaki Yohei , Iwase Takayuki , Fujiwara Tadami , Baba Takayuki , Hanaoka Hideki , Yamamoto Shuichi 
Published: May 2022

IntroductionPreviously, we conducted a clinical trial to evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes to improve the visual functions in patients with retinitis pigmentosa (RP). No adverse events were related to the treatment during follow-up examinations, and TdES significantly improved the mean visual acuity and visual field sensitivity.Methods and analysisWe developed a study protocol for a prospective, multicentre, randomised, double-masked and sham-controlled clinical trial, planned to commence on June 2021. We intend to compare the maintenance or improvement in best-corrected visual acuity, and safety of TdES using skin electrodes between patients with RP and the sham group. The primary endpoint comprises the superiority of the logarithm of the minimum angle of resolution (logMAR) visual acuity change at week 24 from baseline in the treatment and sham groups. Secondary endpoints involve the comparison of the treatment and sham groups at week 24 for the logMAR visual acuity, early treatment diabetic retinopathy study visual acuity, the mean deviation value of Humphrey field analyser 10-2, monocular Humphrey Esterman visual field test score, ellipsoid zone length, central foveal thickness and 25-item National Eye Institute Visual Function Questionnaire score. We intend to enrol 50 patients from three Japanese institutions within 1 year and follow them up for 1 years.Ethics and disseminationThe protocol was approved by the institutional review board at the Chiba University Hospital and two other institutions, and was registered with the Japan Registry of Clinical Trials on 17 May 2021. The trial will be conducted in accordance with the principles of the Declaration of Helsinki, and is in accordance with Good Clinical Practice standards. The findings will be published in a peer-reviewed journal.Trial registration numberJRCT2032210094.
Psychiatric manifestations and associated risk factors among hospitalised patients with COVID-19 in Edo State, Nigeria: a cross-sectional study
Authors: Okogbenin Esther Osemudiamen , Seb-Akahomen Omonefe Joy , Edeawe Osahogie , Ehimigbai Mary , Eboreime Helen , Odike Angela , Obagaye Michael Olukunle , Aweh Benjamin Efi , Erohubie Paul , Eriyo Williams , Inogbo Chinwe , Akhideno Peter , Eifediyi Gloria , Eifediyi Reuben , Asogun Danny A , Okogbenin Sylvanus 
Published: May 2022

ObjectiveTo estimate the prevalence of depression and anxiety and identify associated risk factors in hospitalised persons with confirmed COVID-19 in Edo, Nigeria.DesignA multicentre cross-sectional survey.SettingPatients with COVID-19 hospitalised at the three government-designated treatment and isolation centres in Edo State, Nigeria.ParticipantsThe study was conducted from 15 April to 11 November 2020 among 489 patients with confirmed COVID-19 and in treatment and isolation centres in Edo State, Nigeria. The mean age of participants was 43.39 (SD=16.94) years. Male participants were 252 (51.5%) and female were 237 (48.5%).Main outcome measuresThe nine-item Patient Health Questionnaire for depression, (total score: 0–27, depression ≥10), Generalized Anxiety Disorder-7 for anxiety (total score: 0–21, anxiety ≥10), and social demographic and clinical characteristics for associated risk factors.ResultsOf the 489 participants, 49.1% and 38.0% had depressive and anxiety symptoms, respectively. The prevalence rates of depression, anxiety and combination of both were 16.2%, 12.9% and 9.0%, respectively. Moderate-severe symptoms of COVID-19, ≥14 days in isolation, worrying about the outcome of infection and stigma increased the risk of having depression and anxiety. Additionally, being separated/divorced increased the risk of having depression and having comorbidity increased the risk of having anxiety.ConclusionA substantial proportion of our participants experienced depression, anxiety and a combination of both especially in those who had the risk factors we identified. The findings underscore the need to address modifiable risk factors for psychiatric manifestations early in the course of the disease and integrate mental health interventions and psychosocial support into COVID-19 management guidelines.
Regular feedback to individual endoscopists is associated with improved adenoma detection rate and other key performance indicators for colonoscopy
Authors: Lim Samuel , Tritto Giovanni , Zeki Sebastian , DeMartino Sabina 
Published: May 2022

ObjectiveMonitoring of key performance indicators (KPIs) is a vital element of endoscopy quality improvement. Adenoma detection rate (ADR) is considered the best marker for colonoscopic quality as it inversely correlates with subsequent colonic cancer incidence and mortality, while polyp detection rate (PDR) is an easier-to-calculate surrogate for ADR. This study assessed whether regular feedback to individual endoscopists about their KPIs improved departmental performance.MethodsIndividual KPIs were calculated for a period of 8 years (January 2012–December 2019) and fed back to all endoscopists at 6 monthly intervals, alongside anonymised indicators for other endoscopists, aggregate departmental performance data and benchmarks. An automated natural language processing software (EndoMineR) was used to identify adenomas in pathology reports and calculate ADR. Linear regressions were calculated for departmental ADR, PDR and other KPIs at 6 monthly intervals.Results39 359 colonoscopies (average 2460 in every 6-month period, range 1799–3059) were performed by an average of 42 (range 34–50) endoscopists. A continuous improvement in collective performance including ADR (12.7%–21.0%, R20.92, p<0.001) and PDR (19.0%–29.6%, R20.77, p<0.001) was observed throughout the study. Other KPIs showed similar improvement. The detection of non-neoplastic polyps did not increase. When analysed separately, ADR and PDR appeared to improve for gastroenterologists and nurse endoscopists but not for surgeons.ConclusionRegular feedback with individual and departmental KPIs was associated with improved ADR and overall performance throughout the 8-year study period. Concomitant monitoring of ADR and PDR may prevent ‘gaming’ behaviour and ensure that genuine improvement is achieved.
Side effects and acceptability measures for thermal ablation as a treatment for cervical precancer in low-income and middle-income countries: a systematic review and meta-synthesis
Authors: Piret Evelyne Marie , Payne Beth A , Smith Laurie W , Trawin Jessica , Orem Jackson , Ogilvie Gina , Nakisige Carolyn 
Published: May 2022

ObjectiveUnderstanding the side effects and acceptability of thermal ablation (TA) is necessary before large-scale application in screen-and-treat programmes can be justified in low-income and middle-income countries (LMICs).DesignArticles were selected for inclusion by two independent reviewers. Risk of bias was assessed using the Downs and Black’s criteria. Summary data were extracted, and authors contacted for data when necessary. Proportions of interest and 95% CIs were estimated using a random effects model. Subgroup analysis was performed based on place of treatment and timing of post-treatment follow-up. Heterogeneity was estimated using the I2.Eligibility criteriaStudies that reported one or more side effects or patient acceptability measures after treatment of the cervix using TA in women living in LMICs who completed a cervical cancer screening test. Included articles were clinical trials or observational studies available in English and published before 18 December 2020.Information sourcesOvid MEDLINE, EMBASE, CINAHL, CAB Global Health and WHO Global Index Medicus were searched for this systematic review and meta-synthesis.ResultsA total of 1590 abstracts were screened, 84 full text papers reviewed and 15 papers selected for inclusion in the qualitative review, 10 for meta-synthesis (N=2039). Significant heterogeneity was found in screening tests used to identify women eligible for TA and in methods to ascertain side effects. The most commonly reported side effect during treatment was pain (70%, 95% CI 52% to 85%; I2=98.01%) (8 studies; n=1454). No women discontinued treatment due to pain. At treatment follow-up, common side effects included vaginal discharge (72%, 95% CI 18% to 100%; I2=99.55%) (5 studies; n=771) and bleeding (38%, 95% CI 15% to 64%; I2=98.14%) (4 studies; n=856). Satisfaction with treatment was high in 99% (95% CI 98% to 100%; I2=0.00%) of women (3 studies; n=679).ConclusionsTA results in a number of common side effects, though acceptability remains high among women treated in LMICs. Standardised side effect and acceptability reporting are needed as TA becomes more readily available.PROSPERO registration numberCRD42020197605.