bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic Stem Cell Transplantation versus Immunosuppressive Therapy in Patients with Acquired Severe Aplastic Anemia: A Cost-Effectiveness Analysis
Authors: Zhang Meng-Xue , Wang Qian , Wang Xiao-Qin
Published: December 2020

BackgroundControversy remains regarding which therapy to initially select for severe aplastic anemia (SAA) patients aged 35-50-years-old. This analysis of cost-effectiveness using a Markov model compared immunosuppressive therapy (IST) with hematopoietic stem cell transplantation (HSCT) in age-stratified patients with SAA.MethodsIn younger patients (aged 18-35-years-old), HSCT yielded 22.67 quality-adjusted life years (QALYs), compared with 12.21 QALYs for IST therapy, offering an expected benefit with HSCT of 10.46 QALY.ResultsThe HSCT strategy dominated in younger patients, though it was $146,970 more expensive than IST and the ICER of HSCT to IST was $14,054.19/QALY, which was less than the willingness to pay (WTP) value of $25,397.57/QALY. The IST strategy dominated in older patients because it was $72,009 less expensive than HSCT and yielded 3.24 QALYs more than HSCT. The model was vigorous in the sensitivity analyses of the key variables tested through the plausible ranges that were acquired from costing sources and previously-published literature.ConclusionsThe preferred induction strategy for younger patients with SAA appears to be HSCT and the preferred strategy for older patients is IST, which minimizes cost while maximizing QALYs.
WITHDRAWN: Model of human tongue squamous cell line stably transfected with human papillomavirus（HPV) 16 E6 and E7 genes and biological characteristic analysis
Authors: Lan Zilian , Jia Ziyao , Guo Hengyuan , Yang Zhaoshou , Yang Zifan , Pan Xuan
Published: December 2020

Human tongue squamous carcinoma cell lines transfected with HPV16E6E7 gene were established to provide a model for further study of HPV16 E6E7-related human tongue squamous carcinoma cell lines .Plasmid pEGFR/HPV16 of E6E7 and plasmid pEGFR/HPV16 of No E6E7 were constructed.Human tongue squamous carcinoma cell lines including SCC9 and SCC15 were infected by liposome transfection and would be highly selected by antibiotic .Fluorescence imaging, RT-PCR and Westernblot were used to detect the expression of HPV16 E6E7 in cells.The biological characteristics of human tongue squamous carcinoma cell lines infected with HPV16 E6E7 were detected by CCK-8 and wound healing assay. The human tongue squamous carcinoma cell lines transfected with HPV16 E6E7 gene were successfully established and identified, and the proliferation and migration ability of the human tongue squamous carcinoma cell lines infected with HPV16 E6E7 gene was significantly stronger than that of the blank group.Human tongue squamous carcinoma cell lines infected with HPV16 E6E7 were more malignant, and their proliferation and migration ability were higher than those not infected with HPV16 E6E7.
An Intelligent Web-Based Decision Support System for Monitoring the Chronic Kidney Disease in Brazilian Communities
Authors: Sobrinho Álvaro , Queiroz Andressa C. M. da S. , Cavalcanti Gyovanne Bezerra , Silva Josaias de Moura , Silva Leandro Dias da , Costa Evandro de Barros , Perkusich Angelo , Pinheiro Maria Eliete
Published: December 2020

Background: Chronic Kidney Disease (CKD) is a worldwide health problem, usually diagnosed in late stages of the disease, increasing public health costs and mortality rates. The late diagnosis is even more critical in developing countries due to the high levels of poverty, a large number of hard-to-reach locations, and sometimes lack/precarious primary care.Methods: We designed and evaluated an intelligent web-based Decision Support System (DSS) using the J48 decision tree machine learning algorithm, knowledge-based system concepts, the clinical document architecture, Cohen's kappa statistic, and interviews with an experienced nephrologist.Results: We provided a DSS methodology, that guided the development of the system to assist patients, primary care physicians, and the government in identifying and monitoring the CKD in Brazilian communities. The system provides remote monitoring features. A CKD dataset enabled the evaluation of the J48 decision tree algorithm, while Cohen's kappa statistic guided the evaluation of the knowledge-based system by interviews with an experienced nephrologist. Conclusion: The DSS facilitates the identification and monitoring of the CKD considering low-income populations in Brazil. In addition, the methodology and DSS can be re-used in other developing countries with similar scenarios. Trial registration: 47350313.9.0000.5013.
The use of mobile phones for the prevention and control of arboviral diseases: a scoping review
Authors: Carrillo Maria Angelica , Kroeger Axel , Sanchez Rocio Cardenas , Monsalve Sonia Diaz , Ranzinger Silvia Runge
Published: December 2020

Background: The rapid expansion of dengue, Zika and chikungunya with large scale outbreaks are an increasing public health concern in many countries. Additionally, the recent coronavirus pandemic urged the need to get connected for fast information transfer and exchange. As response, health programmes have -among other interventions- incorporated digital tools such as mobile phones for supporting the control and prevention of infectious diseases. However, little is known about the benefits of mobile phone technology in terms of input, process and outcome dimensions. The purpose of this scoping review is to analyse the evidence of the use of mobile phones as an intervention tool regarding the performance, acceptance, usability, feasibility, cost and effectiveness in dengue, Zika and chikungunya control programmes.Methods: We conducted a scoping review of studies and reports by systematically searching: i) electronic databases (PubMed, PLOS ONE, PLOS Neglected Tropical Disease, LILACS, WHOLIS, ScienceDirect and Google scholar), ii) grey literature, using Google web and iii) documents in the list of references of the selected papers. Selected studies were categorized using a pre-determined data extraction form. Finally, a narrative summary of the evidence related to general characteristics of available mobile health tools and outcomes was produced. Results: The systematic literature search identified 1289 records, 32 of which met the inclusion criteria and 4 records from the reference lists. A total of 36 studies were included coming from twenty different countries. Five mobile phone services were identified in this review: mobile applications (n = 18), short message services (n=7), camera phone (n = 6), mobile phone tracking data (n = 4), and simple mobile communication (n = 1). Mobile phones were used for surveillance, prevention, diagnosis, and communication demonstrating good performance, acceptance and usability by users, as well as feasibility of mobile phone under real life conditions and effectiveness in terms of contributing to a reduction of vectors/ disease and improving users-oriented behaviour changes. It can be concluded that there are benefits for using mobile phones in the fight against arboviral diseases as well as other epidemic diseases. Further studies particularly on acceptance, cost and effectiveness at scale are recommended.
Career aspirations among specialty residents in France: a cross-sectional gender-based comparison
Authors: Cathelain Alice , Jourdain Mercedes , Cordonnier Charlotte , Jonard Sophie Catteau , Sebbane Deborah , Copin Marie-Christine , Berlingo Laura , Rubod Chrystele , Garabedian Charles
Published: December 2020

Background – Most studies evaluating career aspirations among gender are issued from Anglo-Saxons countries. Two recent French studies looked at the career choice of residents in obstetrics & gynecology. It seemed useful to us to broaden this questioning to other specialties, by proposing a study to all residents in the same Faculty. The objective of our study was to describe residents career aspirations and possible barriers according to gender.Methods – Declarative cross-sectional survey, using questionnaires sent by email to the specialty residents of the Faculty of Medicine of Lille (France). An analysis by specialty group (i.e. medicine, surgery, obstetrics & gynecology and anesthesia & resuscitation) and a comparison of the results according to gender were performed.Results – Of the 1,384 specialty residents currently in training, 462 answered the questionnaires (33.38%), among whom 289 women and 173 men (average age = 27.08 years +/- 0.091). 17 women (5.9%) were currently considering a university hospital career versus 37 men (21.4%) (p = 0.001).Gender analysis made it possible to identify obstacles to engaging in a university career: lacking female model, more frequent doubting in the ability to lead this type of career among women (61.6%) than men (35.3%) (p <0.001), and gender discrimination felt in the workplace for 51.6% of women (versus 7.5% of men, p <0.001). Subgroup analysis showed specificities related to each specialty.Conclusions – Few residents plan to embark upon a university hospital career, let alone female residents. There are specificities specific to each specialty and marked gender differences regarding career aspirations. Many obstacles have been identified as obstacles to access to university hospital positions for women. It is important to develop strategies to remove these barriers and enable women to pursue such university careers.Trial registration – Not applicable (no intervention)
Collaborative Online Learning in Undergraduate Medical Education: A Scoping Review
Authors: Luk Pauline , Tsang Joyce , Tsoi Hang-Sang , Chan Karina , Chen Julie
Published: December 2020

Background: Collaborative online learning is an active learning method that stimulates interaction between learners and teachers and fosters interest and motivation in learning in a virtual learning environment. Aim:The primary aim of this scoping review is to examine the extent and nature of academic publications on collaborative online learning in undergraduate medical education.Methods:We used a standardized framework for conducting scoping reviews to identify suitable publications and to analyze the content. ResultsThirty-six published articles from January 1990-March 2019 met the inclusion criteria. There were 16 interventional studies, 8 reviews, 7 commentaries and 5 survey studies. Most work originated in the UK or the US. These studies found that collaborative online learning demonstrated educational value by personalizing learning to fit individual needs, promoting social interaction and active learning, and helping to build professional networks Connectivity, ease of use, and accessibility were enablers of collaborative online learning while technical challenges were the main barrier. ConclusionThere is a relatively small but promising body of work currently published on collaborative online learning in undergraduate medical education. Further work and innovation in this area may be forthcoming in response to the need for alternatives to traditional learning in times of crisis.
Pelvic Organ Prolapse Surgery and Health-Related Quality of Life: A Follow-up Study.
Authors: Belayneh Tadesse , Gebeyehu Abebaw , Adefris Mulat , Rortveit Guri , Gjerde Janne Lillelid , Awoke Tadesse
Published: December 2020

Background: Bothersome descent of pelvic organs impairs health-related quality of life (HRQoL). Patient HRQoL is considered an important outcome of pelvic organ prolapse (POP) surgery. However, it is rarely reported and measures are inadequately used. Thus, studies reporting patient-reported surgical outcomes in low-income contexts are needed. This study aimed to evaluate the effect of prolapse surgery on patient HRQoL and to determine the predictive factors for change in HRQoL. Methods: Two-hundred-fifteen women who had POP stage III or IV were enrolled. Patient underwent vaginal native tissue repair and their HRQoL was evaluated at baseline, 3 and 6 months post-operatively. Subjective outcomes were measured using validated Prolapse Quality of Life (P-QoL-20), Prolapse Symptom Score (POP-SS), Body Image in Prolapse (BIPOP), Patient Health Questionnaire (PHQ-9), and Patient Global Index of Improvement (PGI-I) tools. Linear mixed-effect model was used to compare pre and postoperative P-QoL scores and investigate potential predictors of the changes in P-QoL scores. Results: In total, 193 (89.7%) patients were eligible for analysis at 3 months, and 185 (86.0%) at 6 months. Participant’s mean age was 49.3±9.4 years. The majority of patients had prolapse stage III (81.9%) and underwent vaginal hysterectomy (55.3%). All domains of P-QoL improved significantly after surgery. Altogether more than 72% of patients reported clinical meaningful improvement in quality of life measured with P-QoL-20. An improvement in POP-SS, BIPOP, and the PHQ-9 scores were also observed during both follow-up assessments. At 6 months after surgery, only 2.7% of patients reported the presence of bulge symptom. A total of 97.8% of patients had reported improvement in comparison to the preoperative state, according to PGI-I. The change in P-QoL score after surgery was associated with the change in POP-SS, PHQ, and BIPOP scores and marital status (p < 0.001). However, age, type of surgery, and prolapse stage were not associated with P-QoL score change. Conclusions: Surgical repair for prolapse effectively improves patient’s HRQoL and patient satisfaction is high. The result could be useful for patient counseling on the expected HRQoL outcomes of surgical treatment. Surgical service should be accessible for patients suffering from POP to improve HRQoL.
Air sampling for detection of infectious laryngotracheitis (ILT) in commercial poultry flocks.
Authors: Brown Lauren , Premaratna Dilhani , Segal Yonatan , Beddoe Travis
Published: December 2020

ObjectiveInfectious laryngotracheitis (ILT) is an acute and highly contagious viral respiratory disease of poultry, caused by gallid herpesvirus 1 (ILTV), which causes significant economic losses. Due to recent outbreaks of ILT in Australia, it has been proposed that ILT could be transmitted between poultry sheds by airborne transmission; however, there has never been direct detection of ILTV from air samples. We aimed to optimize a sampling system for the detection of airborne ILTV in poultry sheds.ResultsPoultry farms with a known outbreaks of ILT were used for detection of airborne ILTV. Infected chickens were verified by detection of ILTV nucleic acid in feather shafts with all farms being positive. Using a liquid cyclonic impinging device, it was found that recovery and detection of airborne ILTV was possible in alkaline PEG buffer. Additional sampling was performed at different heights to determine the presence of ILTV in the air. In farm 3, all three air samples at both heights were positive for ILTV while at farm 2 only one sample at 45cm was positive. We envisaged in the future air sampling will be able to detect and track potential transmission of ILTV both inside and outside of the poultry shed.
The association between obesity and weight loss after bariatric surgery on the vaginal microbiota
Authors: Raglan Olivia , MacIntyre David A. , Mitra Anita , Lee Yun S. , Smith Ann , Assi Nada , Nautiyal Jaya , Purkayastha Sanjay , Gunter Marc J , Gabra Hani , Marchesi Julian R. , Bennett Phillip R. , Kyrgiou Maria
Published: December 2020

Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021) and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α, and TNFα levels were all higher among obese women, however only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery, however 75% of these women remained obese at six months. Prior to surgery there was no relationship between body mass index (BMI) and VMB structure, however post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.Conclusions: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB, however, those with the greatest weight loss six-months post-surgery are most likely to have a Lactobacillus-dominant VMB.
Immunological analysis and differential genes screening of venous thromboembolism
Authors: Gao Lina , Li Qiang , Xie Jianqin , Yang Wanxia , You Chongge
Published: December 2020

Purpose: To explore the pathogenesis of venous thromboembolism (VTE) and provide bioinformatics basis for the prevention and treatment of VTE. Methods: The R software was used to obtain the gene expression profile data of GSE19151, combining with the CIBERSORT database, obtain immune cells and differentially expressed genes (DEGs) of blood samples of VTE patients and normal control, and analyze DEGs for GO analysis and KEGG pathway enrichment analysis. Then, the protein-protein interaction (PPI) network was constructed by using the STRING database, the key genes (hub genes) and immune differential genes were screened by Cytoscape software, and the transcription factors (TFs) regulating hub genes and immune differential genes were analyzed by the NetworkAnalyst database. Results: Compared with the normal group, monocytes and resting mast cells were significantly expressed in the VTE group, while regulatory T cells were significantly lower. Ribosomes were closely related to the occurrence of VTE. 10 hub genes and immune differential genes were highly expressed in VTE. MYC, SOX2, XRN2, E2F1, SPI1, CREM and CREB1 can regulate the expressions of hub genes and immune differential genes. Conclusions: Ribosomal protein family genes are most relevant to the occurrence and development of VTE, and the immune differential genes may be the key molecules of VTE, which provides new ideas for further explore the pathogenesis of VTE.
Validation of a three-item Fatigue Severity Scale for patients with substance use disorder: a cohort study from Norway for the period 2016-2020
Authors: Vold Jørn Henrik , Gjestad Rolf , Aas Christer , Meland Eivind , Johansson Kjell Arne , Fadnes Lars Thore
Published: December 2020

Background
Little attention has been paid to customising fatigue questionnaires for patients with Substance Use Disorders (SUDs). The present study aims to validate and shorten the nine-item Fatigue Severity Scale (FSS-9) and Visual Analogue Fatigue Scale (VAFS) for use with this population.
Methods
We used data from a nested cohort with annual health assessments with responses on the FSS-9 and VAFS. During the period 2016–2020, 917 health assessments were collected from 655 patients with SUD in Bergen and Stavanger, Norway. A total of 225 patients answered the health assessment at least twice. We defined baseline as the first annual health assessment when the health assessments were sorted chronologically per patient. We checked for internal consistency, and we used longitudinal confirmatory factor analysis (CFA) and linear mixed model (LMM) analysis to validate and shorten the FSS-9 and VAFS.
Results
The internal consistency of the FSS-9 was excellent with a Cronbach’s α of 0.94 at baseline and 0.93 at the second annual health assessment. When shortening the FSS-9 to a three-item FSS (FSS-3, items 5–7), the Cronbach’s α was 0.87 at baseline and 0.84 at the second health assessment. The internal consistency was not affected when the VAFS was added to the FSS-9 and the FSS-3. The longitudinal CFA model showed a well-fitting model for the FSS-3 (χ2 = 13.33, degree of freedom = 8, P = 0.101). The LMM analysis showed equal linear changes at the individual level for the FSS-3 (slope: 0.00, P > 0.05) and FSS-9 (slope: 0.01, P > 0.05) between the health assessments.
Conclusion
The ten items (FSS-9 plus VAFS) could be shortened to a three-item FSS with high validity and reliability for patients with SUDs. Shortened and validated fatigue scales may be a way to ensure reliable results in this population.
Generalised Cost-Effectiveness Analysis of 159 Health Interventions for the Ethiopian Essential Health Service Package
Authors: Eregata Getachew Teshome , Hailu Alemayehu , Stenberg Karin , Johansson Kjell Arne , Norheim Ole Frithjof , Bertram Melanie Y
Published: December 2020

Background: Cost effectiveness was a criterion used to revise Ethiopia’s essential health service package (EHSP) in 2019. However, there are few cost-effectiveness studies from Ethiopia or directly transferable evidence from other low-income countries to inform a comprehensive revision of the Ethiopian EHSP. Therefore, this paper reports average cost-effectiveness ratios (ACERs) of 159 health interventions used in the revision of Ethiopia’s EHSP. Methods: In this study, we estimate ACERs for 77 interventions on reproductive maternal neonatal and child health (RMNCH), infectious diseases and water sanitation and hygiene as well as for 82 interventions on non-communicable diseases. We used the standardised World Health Organization (WHO) CHOosing Interventions that are Cost Effective methodology (CHOICE) for generalised cost-effectiveness analysis. The health benefits of interventions were determined using a population state-transition model, which simulates the Ethiopian population, accounting for births, deaths and disease epidemiology. Healthy life years (HLYs) gained was employed as a measure of health benefits. We estimated the economic costs of interventions from the health system perspective, including programme overhead and training costs. We used the Spectrum generalised cost-effectiveness analysis tool for data analysis. We did not explicitly apply cost-effectiveness thresholds, but we used US$100 and $1,000 as references to summarise and present the ACER results. Results: We found ACERs ranging from less than US$1 per HLY gained (for family planning) to about US$48,000 per HLY gained (for treatment of stage 4 colorectal cancer). In general, 75% of the interventions evaluated had ACERs of less than US$1,000 per HLY gained. The vast majority (95%) of RMNCH and infectious disease interventions had an ACER of less than US$1,000 per HLY while almost half (44%) of non-communicable disease interventions had an ACER greater than US$1,000 per HLY. Conclusion: The present study shows that several potential cost-effective interventions are available that could substantially reduce Ethiopia’s disease burden if scaled up. The use of the World Health Organization’s generalised cost-effectiveness analysis tool allowed us to rapidly calculate country-specific cost-effectiveness analysis values for 159 health interventions under consideration for Ethiopia’s EHSP.
Temporal trends in pre-ART patient characteristics and outcomes before the Test and Treat era in Central Kenya
Authors: Wekesa Paul , McLigeyo Angela , Owuor Kevin , Mwangi Jonathan , Isavwa Linda , Katana Abraham
Published: December 2020

Background Retention of patients who did not to initiate antiretroviral therapy (ART) has been persistently low compared to those initiated ART. Understanding the temporal trends in clinical outcomes prior to ART initiation is important to inform interventions targeting patients who do not initiate ART immediately after diagnosis. Methods A retrospective cohort analysis of known HIV-infected patients who did not initiate ART from healthcare facilities in Central Kenya was done to investigate temporal trends in characteristics, retention, and mortality outcomes. The data were sourced from the Comprehensive Care Clinic Patient Application Database (CPAD) and IQ care electronic patient-level databases for those enrolled between 2004 and 2014. Results A total of 13,779 HIV-infected patients were assessed, of whom 30.7% were men.There were statisitically significant differences in temporal trends relating to marital status, WHO clinical stage, and tuberculosis (TB) status from 2004 to 2014. The proportion of widowed patients decreased from 9.1% to 6.0%. By WHO clinical stage at enrollment in program, those in WHO stage I increased over time from 8.7% to 43.1%, while those in WHO stage III and IV reduced from 28.5% to 10.8% and 4.0% to 1.1% respectively. Those on TB treatment during their last known visit reduced from 8.3% to 3.9% while those with no TB signs increased from 58.5% to 86.8%. Trends in 6 and 12 month retention in the program, loss to follow-up (LTFU) and mortality were statistically significant. At 6 months, program retention ranged between 36.0% in 2004 to a high of 54.1% in 2013. LTFU at six months remained around 50.0% for most of the cohorts, while mortality at 6 months was 7.5% in 2004 but reduced to 3.8% in 2014. At 12 months, LTFU was above 50.0% across all the cohorts while mortality rate reached 3.9% in 2014. Conclusion Trends in pre ART enrollment suggested higher enrollment among patients who were women and at earlier WHO clinical stages. Retention and mortality outcomes at 6 and 12 months generally improved over the 11 year follow-up period, though dipped as enrollment in asymptomatic disease stage increased.
Retrospective analysis of pediatric patients with multiple rare-earth magnets ingestion: a single-center experience from China.
Authors: Zheng Yucan , Zhang Zhihua , Yan Kunlong , Guo Hongmei , Li Mei , Lian Min , Liu Zhifeng
Published: December 2020

Background The aim of this study was to characterize patients who ingested multiple rare-earth magnets, reveal the harm of rare-earth magnet foreign bodies in the digestive tract, and develop a clinical management algorithm. Methods This was a retrospective review of patients with rare-earth magnet foreign bodies in the digestive tract admitted to a university-affiliated pediatric medical center in China, between January 2016 and December 2019; the subset of medical data evaluated included clinical symptoms, signs, treatments and outcomes. Results A total of 51 cases were included in this study, including 36（70.6%） males and 15（29.4%） females. The magnets were passed naturally in 24（47.1%） patients and removed by intervention in 27（52.9%） patients, including 5（9.8%） cases by endoscopy and 22（43.1%） cases by surgery. Twenty-two（43.1%）cases had gastrointestinal obstruction, perforation, and fistula. Compared with the non-surgical group, the time of the surgical group from ingestion to arriving at the hospital was longer（［80（5-336） vs 26（2-216）］hours, p<0.001）while there was no significant difference in the mean age or the number of magnets swallowed. Conclusions Magnets are attractive to children, but lead to catastrophic consequences including gastrointestinal obstruction, perforation, and surgical interventions when ingested multiple magnets. Endoscopic resection should be urgently performed in the presence of multiple magnets as early as possible within 24 hours, even in asymptomatic patients.
An Inexpensive Retrospective Standard Setting Method Based on Item Facilities
Authors: McLachlan John C , Robertson K. Alex , Weller Bridget , Sawdon Marina
Published: December 2020

BackgroundStandard setting is one of the most challenging aspects of assessment in high-stakes healthcare settings. The Angoff methodology is widely used, but poses a number of challenges, including conceptualisation of the just-passing candidate, and the time-cost of implementing the method. Cohen methodologies are inexpensive and rapid but rely on the performance of an individual candidate. A new method of standard setting, based on the entire cohort and every item, would be valuable.MethodsWe identified Borderline candidates by reviewing their performance across all assessments in an academic year. We plotted the item scores of the Borderline candidates in comparison with Facility for the whole cohort and fitted curves to the resulting distribution.ResultsIt is observed that for any given Item, an equation of the form y ≈ C.eFxwhere y is the Facility of Borderline candidates on that Item, x is the observed Item Facility of the whole cohort, and C and F are constants, predicts the probable Facility for Borderline candidates over the test, in other words, the cut score for Borderline candidates. We describe ways of estimating C and F in any given circumstance, and suggest typical values arising from this particular study: that C = 12.3 and F = 0.021.ConclusionsC and F are relatively stable, and that the equation y = 12.3.e0.021xcan rapidly be applied to the item Facility for every item. The average value represents the cut score for the assessment as a whole. This represents a novel retrospective method based on test takers.Compared to the Cohen method which draws on one score and one candidate, this method draws on all items and candidates in a test. We propose that it can be used to standard set a whole test, or a particular item where the predicted Angoff score is very different from the observed Facility.
Genetic and clinical phenotypic analysis of familial stapes sclerosis caused by a NOG mutation
Authors: Yu Rong , Jiang Hong-Qun , Liao Hui-Huang , Luo Wu-Gen
Published: December 2020

Background: The noggin protein encoded by the NOG gene can interfere with the binding of bone morphogenetic protein to its receptor, thus affecting bone and joint development. The symptoms include abnormal skeletal development and conductive deafness.Methods: In a retrospective study, clinical data of the proband and her family members, including 8 people and 50 healthy normal controls, were collected. Second-generation sequencing was performed on peripheral blood samples from them.Results: The sequencing analysis indicated that in the proband, the NOG gene had a c.532T>C, p.C178R (cytosine deletion, NM_005450.6:c.532T>C), leading to an amino acid change. The proband's father, grandmother, second sister, and third sister also had this mutation, whereas family members with normal phenotypes did not have the mutation.Conclusion: Analysis of this family showed that the novel presentation of the c.532T>C, p.C178R mutation in the NOG gene resulted in syndrome-type autosomal dominant inheritance reflected in a mild clinical phenotype, which is of great importance for further studies of the clinical phenotype and pathogenesis of stapes sclerosis.
Integrating expert opinions with clinical trial data to analyse low-powered subgroup analyses: a Bayesian analysis of the VeRDiCT trial
Authors: Thirard Russell , Ascione Raimondo , Blazeby Jane , Rogers Chris A
Published: December 2020

BackgroundTypically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication. MethodsClinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R. ResultsExpert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect. Conclusions In the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned.Trial registration ISRCTN, ISRCTN02159606. Registered 29th October 2008.
Whole-Exome Sequencing in 168 Korean Patients with Inherited Retinal Degeneration
Authors: Ma Dae Joong , Lee Hyun-Seob , Kim Kwangsoo , Choi Seongmin , Jang Insoon , Cho Seo-Ho , Yoon Chang Ki , Lee Eun Kyoung , Yu Hyeong Gon
Published: December 2020

Background To date, no genetic analysis of inherited retinal disease (IRD) using whole-exome sequencing (WES) has been conducted in a large-scale Korean cohort. The aim of this study was to characterise the genetic profile of IRD patients in Korea using WES. Methods We performed comprehensive molecular testing in 168 unrelated Korean IRD patients using WES. The potential pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines, in silico prediction tools, published literature, and compatibility with known phenotypes or inheritance patterns.Results Causative variants were detected in 86/168 (51.2%) IRD patients, including 58/107 (54.2%) with retinitis pigmentosa, 7/15 (46.7%) with cone and cone-rod dystrophy, 2/3 (66.6%) with Usher syndrome, 1/2 (50.0%) with congenital stationary night blindness, 2/2 (100.0%) with Leber congenital amaurosis, 1/1 (100.0%) with Bietti crystalline dystrophy, 1/1 (100.0%) with Joubert syndrome, 9/10 (90.0%) with Stargardt macular dystrophy, 1/10 (10.0%) with vitelliform macular dystrophy, 1/11 (9.1%) with other forms of macular dystrophy, and 3/4 (75.0%) with choroideraemia. USH2A, ABCA4, and EYS were the most common causative genes associated with IRD. For retinitis pigmentosa, variants of USH2A and EYS were the most common causative gene mutations.Conclusions This study demonstrated the distribution of causative genetic mutations in Korean IRD patients. The data will serve as a reference for future genetic screening and development of treatment modalities for Korean IRD patients.
The path linking disease severity and cognitive function with quality of life in Parkinson's disease:the mediating effect of activities of daily living and depression.
Authors: He Yao , Tian Yuling , Han Hongjuan , Cui Jing , Ge Xiaoyan , Qin Yao , Luo Yanhong , Bai Wenlin , Yu Hongmei
Published: December 2020

Background: Research on quality of life (QOL) with Parkinson’s disease (PD) has examined direct influencing factors, not mediators. The study aim was to explore whether PD severity and poor cognitive function may decrease physical and mental QOL by reducing activities of daily living (ADL) and increasing depression in sequence. Methods: We conducted a cross-sectional questionnaire study of 150 PD hospital patients in China. PD severity, cognitive function, ADL, depression, and QOL were evaluated. We used structural equation modeling to analyze the mediating effects of ADL and depression on the association between PD severity/cognition and physical (PCS) and mental (MCS) QOL. Results:There was a significant mediating effect of PD severity on PCS via ADL and depression (95%CI: −0.669, −0.026), and a significant direct effect (p<0.001). The mediating effect of PD severity on MCS via ADL and depression was significant (95%CI: −2.135, −0.726), but there was no direct effect (p = 0.548). There was a significant mediating effect of cognitive function on PCS via ADL and depression (95%CI: 0.025, 0.219) and a significant direct effect (p<0.001). The mediating effect of cognitive function on MCS via ADL and depression was significant (95%CI: 0.256, 0.645), but there was no direct effect (p = 0.313). The PCS models showed a partial mediation, and the MCS models showed a complete mediation, of ADL and depression.Conclusions:PD severity and cognitive function increase depression by reducing ADL, leading to lower QOL, and directly or indirectly affect PCS and MCS through different pathways.
Investigation of the role of AcTPR2 in kiwifruit and its response to Botrytis cinerea infection
Authors: Li Zhexin , Lan Jian-Bin , Liu Yi-Qing , Qi Li-Wang , Tang Jianmin
Published: December 2020

Background: Elucidation of the regulatory mechanism of kiwifruit response to gray mold disease caused by Botrytis cinerea can provide the basis for its molecular breeding to impart resistance against this disease. In this study, 'Hongyang' kiwifruit served as the experimental material; the TOPLESS/TOPLESS-RELATED (TPL/TPR) co-repressor gene AcTPR2 was cloned into a pTRV2 vector (AcTPR2-TRV) and the virus-induced gene silencing technique was used to establish the functions of the AcTPR2 gene in kiwifruit resistance to Botrytis cinerea.Results: Virus-induced silencing of AcTPR2 enhanced the susceptibility of kiwifruit to Botrytis cinerea. Defensive enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and phenylalanine ammonia-lyase (PAL) and endogenous phytohormones such as indole acetic acid (IAA), gibberellin (GA3), abscisic acid (ABA), and salicylic acid (SA) were detected. Kiwifruit activated these enzymes and endogenous phytohormones in response to pathogen-induced stress and injury. The expression levels of the IAA signaling genes—AcNIT, AcARF1, and AcARF2—were higher in the AcTPR2-TRV treatment group than in the control. The IAA levels were higher and the rot phenotype was more severe in AcTPR2-TRV kiwifruits than that in the control. These results suggested that AcTPR2 downregulation promotes expression of IAA and IAA signaling genes and accelerates postharvest kiwifruit senescence. Further, Botrytis cinerea dramatically upregulated AcTPR2, indicating that AcTPR2 augments kiwifruit defense against pathogens by downregulating the IAA and IAA signaling genes.Conclusions: The results of the present study could help clarify the regulatory mechanisms of disease resistance in kiwifruit and furnish genetic resources for molecular breeding of kiwifruit disease resistance.
First report of Thelazia callipaeda infection in Phortica okadai and wildlife in national nature reserves, China
Authors: Jin Yipeng , Liu Zichen , Wei Jiaqi , Wen Yifan , He Nianjun , Tang Liubin , Lin Degui , Lin Jiahao
Published: December 2020

Background: Thelazia callipaeda is a zoonotic parasitic nematode of the family Thelaziidae, with Phortica okadai as the intermediate host and the only confirmed vector in China. China has the largest number of cases of thelaziosis in humans of the world. It is generally believed that the infected domestic animals (dogs and cats) are the most important reservoir hosts of Thelazia callipaeda and directly threaten humans. At present, there is not much research and attention on the role of wildlife in the transmission cycle of thelaziosis in wildlife nature reserves.Methods: During 2016-2019, we selected four wildlife national nature reserve across the country as monitoring points for Phortica okadai and wildlife, and we chose to use fly-trap method for monitoring Phortica okadai density. Morphological analysis of the parasites collected from the conjunctival sac of the wildlife was taken as the first step, and a specific PCR was used for exact confirmation.Results: In 2019, the density of Phortica okadai in Foping National Nature Reserve of China, increased sharply and infected Phortica okadai were newly found in wildlife nature reserves. Wild giant panda, wild boar, leopard cat, and black bear were newly found to be infected by Thelazia callipaeda (one animal of each species). A total of four worms were collected and one worm was collected from each animals. The morphologic characteristics of the four worms led to their identification as Thelazia callipaeda, which was molecularly confirmed by a specific PCR amplification.Conclusions: This is the first report of Phortica okadai as well as a variety of wildlife including wild giant panda infected by Thelazia callipaeda in wildlife nature reserves in China. This indicates that there has been a transmission cycle of thelaziosis among wildlife in wildlife nature reserves. The increasing number of case reports in wildlife suggests the likely risk of infection of Thelazia callipaeda in villagers around wildlife nature reserves.
Mapping the Organizational Readiness to Change Assessment to the Consolidated Framework for Implementation Research
Authors: Kononowech Jennifer , Hagedorn Hildi , Hall Carmen , Helfrich Christian D. , Lambert-Kerzner Anne C. , Miller Susan C. , Sales Anne E. , Damschroder Laura
Published: December 2020

Background: Implementation researchers recognize the influential role of organizational factors and thus, seek to assess these factors using quantitative measurement instruments. However, researchers are hindered by instruments that measure similar constructs but rely on different nomenclature and/or definitions. The Consolidated Framework for Implementation Research (CFIR) provides a taxonomy of constructs derived from prior frameworks and empirical studies of implementation-related constructs. The CFIR includes constructs based on the original Promoting Action Research into Health Services (PARiHS) framework which highlights the key roles of strength of evidence for a specific evidence-based intervention (EBI); favorability of organizational context for change; and capacities to facilitate implementation of the EBI. Although the CFIR is among the most frequently used implementation frameworks, it does not include quantitative measures. The Organizational Resource and Context Assessment (ORCA) is a quantitative measurement instrument that was developed based on PARiHS, assessing its three domains. Factors within these three domains are conceptually similar to constructs in the CFIR but do not match directly. The aim of this work was to map ORCA survey items to CFIR constructs to enable direct comparisons and syntheses of findings across studies using the CFIR and/or ORCA. Methods: Two distinct, independent research teams, each used rigorous constant comparative techniques with deliberation and consensus to map individual items from the ORCA to the five domains and 39 constructs of CFIR. Results: ORCA items were mapped primarily to three of five CFIR domains: Inner Setting, Process and Intervention Characteristics. The two research teams agreed on 88% of mappings at the higher domain level; at the lower construct level, their mappings aligned for 62.2% of the ORCA items. Conclusions: Mapping results reveal that the ORCA focuses measurement prominently on Inner Setting, Process, and Intervention Characteristics. This mapping guide can help improve consistency in measurement and reporting, enabling more efficient comparison and synthesis of findings that use either the ORCA instrument or the CFIR framework. The guide helps advance implementation science utilizing mixed methods by providing CFIR users with quantitative measures for selected constructs and enables ORCA users to map their findings to CFIR constructs.
Myocardial lschemia Reperfusion Injury is Alleviated by Curcumin-Peptide Hydrogel via Upregulating Autophagy and Protecting Mitochondrial Function
Authors: Liao Chilin , Liu Yang , Huang Mengzhao , Liu Huayong , Ye Ziliang , Su Qiang
Published: December 2020

Background: Ischemia-reperfusion injury (IRI) is an important factor limiting the success of cardiac reperfusion therapy. Curcumin has a significant cardioprotective effect against IRI, inhibits ventricular remodeling induced by pressure load or MI, and improve cardiac function. However, the poor water solubility and low bioavailability of curcumin restrict its clinical application. Methods: In this study, we prepared and evaluated a curcumin-hydrogel ( cur-hydrogel ) to reduce cardiomyocyte apoptosis and reactive oxygen species formation induced by hypoxia-reoxygenation injury, promote autophagy, and reduce mitochondrial damage by maintaining the phosphorylation of Cx43. Results: Cur-hydrogel can restore cardiac function, inhibit myocardial collagen deposition and apoptosis, and activate JAK2/STAT3 pathway to alleviate myocardial ischemia-reperfusion injury in rats. Conclusions: This study elucidate the protective effects of cur-hydrogel on myocardial ischemia-reperfusion injury by regulating apoptosis, autophagy and mitochondrial injury in vitro and in vivo , which lays a new theoretical and experimental foundation for the prevention and reduction of IRI.
Relationship between the Severity of Endometriosis Symptoms (Dyspareunia, Dysmenorrhea and Chronic pelvic pain) with the Spread of the Disease on Ultrasound
Authors: Kor Elham , Mostafavi Seyed Reza Saadat , Mazhin Zahra Ahmadian , Dadkhah Adeleh , Kor Anis , Arvanagh Shirin Habibi , Noroozi Shima Ghafourian , Sadri Ghazal
Published: December 2020

Objectives: About 10-15% of women of childbearing age have endometriosis. The present study aimed to investigate the relationship between the severity of symptoms of endometriosis and the spread as well as the stage of the disease on ultrasonography. The present cross-sectional study evaluates the relationship between the severity of endometriosis symptoms and the spread of disease on ultrasonography in patients with endometriosis.Results: Considering different analyses, the cumulative size of posterior Deep Infiltrative Endometriosis (DIE) (less than 1 cm) is significantly correlated with minimal severity of dyspareunia and chronic pelvic pain. The incidence of dyspareunia was more prevalent in patients with complete stenosis of Douglas pouch than those with incomplete stenosis. Furthermore, the incidence of severe and very severe pain in patients with Douglas pouch stenosis is relatively higher than that in patients without stenosis. Only dyspareunia is related to the stage of endometriosis, and patients with dyspareunia are five times more at risk of a higher stage of the disease. The severity of dyspareunia is related to the stage of endometriosis and the severity of Douglas pouch stenosis. The results showed a correlation between chronic pelvic pain and r-ASRM score (revised American Society for Reproductive Medicine score).