bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates
Authors: Arend Peter
Published: May 2020

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.
Expression and Characterization of a Novel Recombinant Cytotoxin II from Naja naja oxiana Venom: A Potential Treatment for Breast Cancer
Authors: Derakhshani Afshin , Silvestris Nicola , Haji‐Asgarzadeh Khalil , Mahmoudzadeh Sara , Fereidouni Mohammad , Paradiso Angelo Virgilio , Brunetti Oronzo , Atarod Deyhim , Safarpour Hossein , Baradaran Behzad
Published: May 2020

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 µg mL-1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs.
Optimization of In-Stage Diversion To Promote Uniform Planar Multifracture Propagation: A Numerical Study
Authors: Chen Ming , Zhang Shicheng , Zhou Tong , Ma Xinfang , Zou Yushi
Published: May 2020

Creating uniform multiple fractures is a challenging task due to reservoir heterogeneity and stress shadow. Limited-entry perforation and in-stage diversion are commonly used to improve multifracture treatments. Many studies have investigated the mechanism of limited-entry perforation for multifracture treatments, but relatively few have focused on the in-stage diversion process. The design of in-stage diversion is usually through trial and error because of the lack of a simulator. In this study, we present a fully coupled planar 2D multifracture model for simulating the in-stage diversion process. The objective is to evaluate flux redistribution after diversion and optimize the dosage of diverters and diversion timing under different in-stage in-situ stress difference.

Our model considers ball sealer allocation and solves flux redistribution after diversion through a fully coupled multifracture model. A supertimestepping explicit algorithm is adopted to solve the solid/fluid coupling equations efficiently. Multifracture fronts are captured by using tip asymptotes and an adaptive time-marching approach. The modeling results are validated against analytical solutions for a plane-strain Khristianovic-Geertsma de Klerk (KGD) model. A series of numerical simulations are conducted to investigate the multifracture growth under different in-stage diversion operations. Parametric studies reveal that the in-stage in-situ stress difference is a critical parameter for diversion designs. When the in-situ stress difference is larger than 2 MPa, the fracture in the high-stress zone can hardly be initiated before diversion for a general fracturing design. More ball sealers are required for the formations with higher in-stage in-situ stress difference. The diverting time should be earlier for formations with high in-stage stress differences as well. Adding more perforation holes in the zone with higher in-situ stress is recommended to achieve even flux distribution. The results of this study can help understand the multifracture growth mechanism during in-stage diversion and optimize the diversion design timely.
Knowledge, attitudes and practices of faculty on mentorship: An exploratory interpretivist study at a Sub-Saharan African medical school
Authors: Mubuuke Aloysius , Mbalinda Scovia N. , Munabi Ian G. , Kateete David , Opoka Robert B. , Kiguli Sarah
Published: May 2020

Background

Mentorship has become a routine part of undergraduate training in health professions education. Although many health professions training institutions have successfully incorporated faculty-student mentorship in their formal training, many others especially in Sub-Saharan Africa have not fully embraced this. Institutionalized mentorship programmes are an effective methods of enhancing student learning experiences. Faculty, who are the mentors have an active role to play in driving the mentorship agenda and ensure that students benefit from this important activity. The aim of this study was to explore the knowledge, attitudes and practices of faculty about student mentorship at Makerere University College of Health Sciences.

Methods

It was an exploratory qualitative study using interviewer-administered semi-structured questionnaires. The study participants included faculty at Makerere University College of Health Sciences. Thematic analysis was used to analyse the data using pre-determined themes.

Results

Four themes were identified: 1) Knowledge of mentorship, 2) Attitude towards mentorship, 3) Practice of mentorship and 4) Improving the mentorship process. Majority of the faculty reported being less knowledgeable on mentorship regardless of seniority. The level of knowledge seemed to influence the practice of mentorship. Despite the observed knowledge gap, all faculty demonstrated a positive attitude to participate in mentoring.

Conclusion

Faculty demonstrated a positive attitude towards mentorship despite the knowledge gap of mentorship identified. Continuous faculty development in mentorship as well as using peer mentorship were identified as key in sustaining the mentorship programme.
Formation of ultralong DH regions through genomic rearrangement
Authors: Smider Brevin A. , Smider Vaughn V.
Published: May 2020

Background: Cow antibodies are very unusual in having exceptionally long CDR H3 regions. The genetic basis for this length largely derives from long heavy chain diversity (DH) regions, with a single “ultralong” DH, IGHD8-2, encoding over fifty amino acids. Many bovine IGHD regions have sequence similarity but have several nucleotide repeating units that diversify their lengths. Genomically, most DH regions exist in three clusters that appear to have formed from DNA duplication events. However, the relationship between the genomic arrangement and long CDR lengths is unclear. Results: The DH cluster containing IGHD8-2 underwent a rearrangement and deletion event in relation to the other clusters in the region corresponding to IGHD8-2, with possible fusion of two DH regions and expansion of short repeats to form the ultralong IGHD8-2 gene. Conclusions: Length heterogeneity within DH regions is a unique evolutionary genomic mechanism to create immune diversity, including formation of ultralong CDR H3 regions.
How and why do French medical students choose the specialty of Infectious and Tropical Diseases? A national cross-sectional study
Authors: Peiffer-Smadja Nathan , Ardellier François-Daniel , Thill Pauline , Beaumont Anne-Lise , Catho Gaud , Osei Lindsay , Dubée Vincent , Bleibtreu Alexandre , Lemaignen Adrien , Thy Michaël
Published: May 2020

Background Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students.Methods We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n=100) to assess the factors influencing their choice of specialty and their career plan. Results We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n=100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary. Conclusions The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.
Molecular surveillance of the Pfmdr1 N86Y allele among Congolese pregnant women with asymptomatic malaria
Authors: Dossou-Yovo Louis Regis , Ntoumi Francine , Koukouikila-Koussounda Felix , Vouvoungui Jeannhey Christevy , Adedoja Ayodele , Nderu David , Velavan Thirumalaisamy P , Lenga Arsene
Published: May 2020

Background Malaria in pregnancy is associated with considerable morbidity and mortality. Regular surveillance of artemisinin−based combination therapy tolerance, or molecular makers of resistance, is vital for effective malaria treatment, control and eradication programmes. Plasmodium falciparum multiple drug resistance-1 gene (Pfmdr1) N86Y mutation is associated with reduced susceptibility to lumefantrine. This study assessed the prevalence of Pfmdr1 N86Y in Brazzaville, Republic of Congo. Methods A total 1001 of P. falciparum-infected blood samples obtained from asymptomatic malaria pregnant women having a normal child delivery at the Madibou Integrated Health Centre were analysed. Pfmdr1 N86Y genotyping was conducted using PCR-restriction fragment length polymorphism. Results The wild type Pfmdr1 N86 allele was predominant (>68 %) in this study, whereas a few isolates carrying the either the mutant allele (Pfmdr1 86Y) alone or both alleles (mixed genotype). The dominance of the wildtype allele (pfmdr1 N86) indicates the plausible decline P. falciparum susceptibility to lumefantrine. Conclusion This study gives an update on the prevalence of Pfmdr1 N86Y alleles in Brazzaville, Republic of Congo. It also raises concern on the imminent emergence of resistance against artemether−lumefantrine in this setting. This study underscores the importance to regular artemether−lumefantrine efficacy monitoring to inform the malaria control programme of the Republic of Congo.
Genetic variation in toll like Receptors 2, 7, 9 and interleukin-6 is associated with Cytomegalovirus infection in late pregnancy
Authors: Mhandire Doreen , Mhandire Kudakwashe , Magadze Mulalo , Wonkam Ambroise , Kengne Andre P , Dandara Collet
Published: May 2020

Background: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. Methods: In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R. Results: The TLR7 rs179008A>T (p<0.001) polymorphism was associated while the TLR9 rs352139T>C (p=0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin ( IL)-6 rs10499563T>C (p<0.001) and TLR2 rs1816702C>T (p=0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7 , IL - 6 , IL-10 , IL-28B , IL-1A and interferon AR1 ( IFNAR1 ) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population re generally comparable to other African populations but different when compared to European and Asian populations. Conclusions: Toll like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.
Youth vaping and smoking and parental vaping: a panel survey
Authors: Green Michael , Gray Linsay , Sweeting Helen
Published: May 2020

Background: Concerns remain about potential negative impacts of e-cigarettes including possibilities that: youth e-cigarette use (vaping) increases risk of youth smoking; and vaping by parents may have impacts on their children’s vaping and smoking behaviour.Methods: With panel data from 3291 youth aged 10-15 years from the 7th wave of the UK Understanding Society Survey (2015-2017), we estimated effects of youth vaping on youth smoking (ever, current and past year initiation), and of parental vaping on youth smoking and vaping, and examined whether the latter differed by parental smoking status. Propensity weighting was used to adjust for measured confounders and estimate average effects of vaping for all youth, and among youth who vaped. E-values were calculated to assess the strength of unmeasured confounding influences needed to negate our estimates.Results: Associations between youth vaping and youth smoking were attenuated considerably by adjustment for measured confounders. Estimated average effects of youth vaping on youth smoking were stronger for all youth (e.g. OR for smoking initiation: 32.5; 95% CI: 9.8-107.1) than among youth who vaped (OR: 4.4; 0.6-30.9). Relatively strong unmeasured confounding would be needed to explain these effects. Associations between parental vaping and youth vaping were explained by measured confounders. Estimates indicated effects of parental vaping on youth smoking, especially for youth with ex-smoking parents (e.g. OR for smoking initiation: 11.3; 2.7-46.4) rather than youth with currently smoking parents (OR: 1.0; 0.2-6.4), but these could be explained by relatively weak unmeasured confounding.Conclusions: While measured confounding accounted for much of the associations between youth vaping and youth smoking, indicating support for underlying propensities, our estimates suggested residual effects that could only be explained away by considerable unmeasured confounding or by smoking leading to vaping. Estimated effects of youth vaping on youth smoking were stronger among the general youth population than among the small group of youth who actually vaped. Associations of parental vaping with youth smoking and vaping were either explained by measured confounding or could be relatively easily explained by unmeasured confounding.
Recurrent Sequence Evolution After Independent Gene Duplication
Authors: Dunk Samuel Hermann Alexander Von Der , Snel Berend
Published: May 2020

Background Convergent and parallel evolution provide unique insights into the mechanisms of natural selection. Some of the most striking convergent and parallel (collectively recurrent ) amino acid substitutions in proteins are adaptive, but there are also many that are selectively neutral. Accordingly, genome-wide assessment has shown that recurrent sequence evolution in orthologs is chiefly explained by nearly neutral evolution. For paralogs, more frequent functional change is expected because additional copies are generally not retained if they do not acquire their own niche. Yet, it is unknown to what extent recurrent sequence differentiation is discernible after independent gene duplications in different eukaryotic taxa. Results We develop a framework that detects patterns of recurrent sequence evolution in duplicated genes. This is used to analyze the genomes of 90 diverse eukaryotes. We find a remarkable number of families with a potentially predictable functional differentiation following gene duplication. In some protein families, more than ten independent duplications show a similar sequence-level differentiation between paralogs. Based on further analysis, the sequence divergence is found to be generally asymmetric. Moreover, about 6\% of the recurrent sequence evolution between paralog pairs can be attributed to recurrent differentiation of subcellular localization. Finally, we reveal the specific recurrent patterns for the gene families Hint1/Hint2, Sco1/Sco2 and vma11/vma3. Conclusions The presented methodology provides a means to study the biochemical underpinning of functional differentiation between paralogs. For instance, two abundantly repeated substitutions are identified between independently derived Sco1 and Sco2 paralogs. Such identified substitutions allow direct experimental testing of the biological role of these residues for the repeated functional differentiation. We also uncover a diverse set of families with recurrent sequence evolution and reveal trends in the functional and evolutionary trajectories of this hitherto understudied phenomenon.
Knockdown of hsa_circ_0074298 suppressed the progression of pancreatic cancer by targeting the miR-519/SMOC2 axis
Authors: Chen Hong , Xu Dafang , Wang Lishan , Zhou Jiahua
Published: May 2020

BACKGROUND: Pancreatic cancer (PC) is among the most malignant tumors in the digestive system because of its fast progression, metastasis, as well as its resistance to chemotherapy. Former studies found that circRNAs that were differentially expressed were correlated with progression and gemcitabine (GEM)-resistance in PC, and hsa_circ_0074298 aberrant expression played a role in PC progression, but the regulatory mechanism was unclear. METHODS: RT-qPCR was used to detect hsa_circ_0074298 expression in PC cell lines. CCK8, colony formation, and Transwell assays were used to evaluate the effect of hsa_circ_0074298 on PC cell migration and proliferation. Bioinformatics and luciferase reporter experiments were used to characterize the regulatory mechanism. Nude mouse xenografts were generated to examine the effect of hsa_circ_0074298 on tumor growth. RESULTS: The present study showed that hsa_circ_0074298 expression increased significantly in both PC cell lines and PC tissues. Downregulation of hsa_circ_0074298 caused a significant decrease in PC cell proliferation and in nude mouse xenograft growth. Hsa_circ_0074298 silencing also increased chemotherapy sensitivity to GEM. Bioinformatics analysis indicated that hsa_circ_0074298 was a miR-519 sponge and that the SMOC2 gene was a miR-519 target. MiR-519 downregulation or SMOC2 overexpression restored cell proliferation, migration, and chemoresistance after hsa_circ_0074298 silencing. The dual luciferase reporter assay showed that hsa_circ_0074298 interacted with miR-519, and miR-519 binding to the SMOC2 3′-UTR then suppressed posttranscriptional SMOC2 expression. CONCLUSIONS: Taken together, hsa_circ_0074298 functioned as a tumor promoter through a novel miR-519/SMOC2 axis, highlighting its possibility as a potential therapy for PC.
FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients
Authors: Chen Liang , Han Xiudi , Li YanLi , Zhang Chunxiao , Xing Xiqian
Published: May 2020

Background The pneumonia severity index (PSI) and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) score have been shown to predict mortality in community-acquired pneumonia. Their ability to predict influenza-related pneumonia, however, is less well-established. Methods A total of 693 laboratory-confirmed FluA-p patients diagnosed between Jan 2013 and Dec 2018 and recruited from five teaching hospitals in China were included in the study. The sample included 494 patients in the derivation cohort and 199 patients in the validation cohort. The prediction rule was established based on independent risk factors for 30-day mortality in FluA-p patients from the derivation cohort. Results The 30-day mortality of FluA-p patients was 19.6% (136/693). The FluA-p score was based on a multivariate logistic regression model designed to predict mortality. Results indicated the following significant predictors (regression statistics and point contributions toward total score in parentheses): blood urea nitrogen > 7 mmol/L ( OR 1.604, 95% CI 1.150-4.492, p = 0.040; 1 points), pO 2 /F i O 2 ≤ 250 mmHg ( OR 2.649, 95% CI 1.103-5.142, p = 0.022; 2 points), cardiovascular disease ( OR 3.967, 95% CI 1.269-7.322, p <0.001; 3 points), arterial PH < 7.35 ( OR 3.959, 95% CI 1.393-7.332, p < 0.001; 3 points), smoking history ( OR 5.176, 95% CI 2.604-11.838, p = 0.001; 4 points), lymphocytes < 0.8×10 9 /L ( OR 8.391, 95% CI 3.271-16.212, p <0.001; 5 points), and early neurominidase inhibitor therapy ( OR 0.567, 95% CI 0.202-0.833, p = 0.005; -2 points). Seven points was used as the cut-off value for mortality risk stratification. The model showed a sensitivity of 0.941, a specificity of 0.762, and overall better predictive performance than the PSI risk class (AUROC = 0.908 vs 0.560, p < 0.001) and the CURB-65 score (AUROC = 0.908 vs 0.777, p < 0.001). Conclusions Our results showed that a FluA-p score was easy to derive and that it served as a reliable prediction rule for 30-day mortality in FluA-p patients. The score could also effectively stratify FluA-p patients into relevant risk categories and thereby help treatment providers to make more rational clinical decisions.
Association of serum fibroblast growth factor 19 levels with arteriosclerosis parameters assessed by arterial stiffness and atherogenic index of plasma in patients with type 2 diabetes
Authors: Liu Wangshu , Tang Mengjie , Xu Tianli , Su Jianbin , Wang Xue-Qin , Xu Feng , Zhang Dongmei , Zhu Qing , Cao Jie , Wang Hong
Published: May 2020

Background The role of serum fibroblast growth factor 19 (FGF19) in the arteriosclerosis is not well known. In the present study, we aimed to explore whether serum FGF19 levels were related to the arteriosclerosis parameters, including arterial stiffness and atherogenic index of plasma (AIP), in patients with type 2 diabetes (T2D). Methods 200 patients with type 2 diabetes and 50 healthy controls were recruited for this study from Apr 2017 to Oct 2018. Serum FGF19 levels, arterial stiffness assessed by brachial ankle pulse wave velocity (baPWV), and AIP assessed by ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) were measured in those subjects. In addition, other relevant clinical data were also collected. Results Serum FGF19 levels in T2D patients were significantly lower than that in healthy controls ( p < 0.01). The arteriosclerosis parameters, including baPWV and AIP, significantly decreased across ascending tertiles of serum FGF19 levels (all p for trend < 0.001). Moreover, the baPWV and AIP were all inversely correlated with serum FGF19 levels ( r = –0.351 and –0.303, respectively, p < 0.001). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the serum FGF19 levels were independently associated with baPWV ( β = –0.20, t = –2.23, p = 0.029) and AIP ( β = –0.28, t = –2.66, p = 0.010) in patients with T2D. Conclusions The serum FGF19 levels were independently and inversely associated with baPWV and AIP in patients with T2D, which indicate serum FGF19 may plays a protect role against pathogenesis of the atherosclerosis in those patients.
Explaining the variation in the attained power of a stepped-wedge trial with unequal cluster sizes
Authors: Ouyang Yongdong , Karim Mohammad Ehsanul , Gustafson Paul , Field Thalia S. , Wong Hubert
Published: May 2020

Background In a cross-sectional stepped-wedge trial with unequal cluster sizes, attained power in the trial depends on the realized allocation of the clusters. This attained power may differ from the expected power calculated using standard formulae by averaging the attained powers over all allocations the randomization algorithm can generate. We investigated the effect of design factors and allocation characteristics on attained power and developed models to predict attained power based on allocation characteristics. Method Based on data simulated and analyzed using linear mixed-effects models, we evaluated the distribution of attained powers under different scenarios with varying intraclass correlation coefficient (ICC) of the responses, coefficient of variation (CV) of the cluster sizes, number of cluster-size groups, distributions of group sizes, and number of clusters. We explored the relationship between attained power and two allocation characteristics: the individual-level correlation between treatment status and time period, and the absolute treatment group imbalance. When computational time was excessive due to a scenario having a large number of possible allocations, we developed regression models to predict attained power using the treatment-vs-time period correlation and absolute treatment group imbalance as predictors. Results The risk of attained power falling more than 5% below the expected or nominal power decreased as the ICC or number of clusters increased and as the CV decreased. Attained power was strongly affected by the treatment-vs-time period correlation. The absolute treatment group imbalance had much less impact on attained power. The attained power for any allocation was predicted accurately using a logistic regression model with the treatment-vs-time period correlation and the absolute treatment group imbalance as predictors. Conclusion In a stepped-wedge trial with unequal cluster sizes, the risk that randomization yields an allocation with inadequate attained power depends on the ICC, the CV of the cluster sizes, and number of clusters. To reduce the computational burden of simulating attained power for allocations, the attained power can be predicted via regression modeling. Trial designers can reduce the risk of low attained power by restricting the randomization algorithm to avoid allocations with large treatment-vs-time period correlations.
Measuring and assessing the competencies of preceptors in health professions: a systematic scoping review.
Authors: Bartlett Andrew , Um Irene S , Luca Edward J , Krass Ines , Schneider Carl R
Published: May 2020

Background: In healthcare, preceptors act as a role model and supervisor, thereby facilitating the socialisation and development of the preceptee into a professional fit to practice. To ensure a consistent approach to every preceptorship experience, preceptor competencies should be measured or assessed to ensure that the desired outcomes are achieved. Defining these would ensure quality management and could inform development of an preceptor competency framework.This review aimed to evaluate the evidence for preceptor competencies and assessment in health professions.Methods: This study followed the PRISMA ScR scoping review guidelines. A database search was conducted in Embase, Medline, CINAHL and IPA in 2019. Articles were included if they defined criteria for competency, measured or assessed competency, or described performance indicators of preceptors. A modified GRADE CERQual approach and CASP quality assessment were used to appraise identified competencies, performance indicators and confidence in evidence. Results: Forty one studies identified 17 evidence-based competencies, of which 11 had an associated performance indicator. The competency of preceptors was most commonly measured using a preceptee completed survey (moderate to high confidence as per CERQual), followed by preceptor self-assessment, and peer-assessment. Preceptee outcomes as a measure of preceptor performance had good but limited evidence. Conclusions: Competencies with defined performance indicators allow for effective measurement and may be modifiable with training. To measure preceptor competency, the preceptor perspective, as well as peer and preceptee assessment is recommended. These findings can provide the basis for a common preceptor competency framework in health professions.
Statistical modeling of number of human deaths per road traffic accident in Oromia region, Ethiopia
Authors: Aga Merga Abdissa , Woldeamanuel Berhanu Teshome , Tadesse Mekonnen
Published: May 2020

Background: Globally, road traffic accidents are leading causes of death among young people in general, and the main cause of death among young people aged 15–29 years. Recently, in Ethiopia, the average number of road traffic accidents has been increasing, particularly the Oromia regional state is experiencing a higher road traffic fatalities. This study was conducted to identify the major factors associated with the number of human deaths by road traffic accident in the Oromia Regional State, Ethiopia. Methods: We used data obtained from the Oromia Police Commission Bureau that have been recorded on daily basis road traffic accidents from July, 2016 - July, 2017. Count regression models were was used to assess the factors associated with the number of human deaths from road traffic accidents.Results: Of the total of 3900 road traffic accidents included in the 1188 (30.5%) were giving rise to fatal. The Hurdle models were of better fit than zero inflated Poisson and zero inflated negative binomial model. Thus, the Hurdle Poisson is recommended in this study. Age of the driver 31-50 years (AOR = 0.289, 95%CI: 0.175, 0.479) and higher than 50 years of age (AOR = 0.311, 95%CI: 0.129, 0.751), driver’s years of experience 5-10 years (AOR = 0.014, 95%CI:0.007, 0.027), and more than 10 years (AOR = 0.101, 95%CI:0.057, 0.176), vehicle type automobile (AOR = 8.642, 95%CI:2.7644, 27.023), vehicle years of service 5-10 years (AOR = 2.484, 95%CI:1.194, 5.169), and more than 10 years (AOR = 2.639,95%CI:1.268, 5.497), type of accident, vehicle upside down (AOR = 5.560,95%CI: 2.506, 12.336), causes of accident, turning illegal position (AOR = 0.454, 95%CI:0.226, 0.913), area of accident, residential place (AOR = 108.506, 95%CI: 13.725, 857.798), working areas (AOR = 129.606, 95%CI: 16.448, 1021.263), near hospitals (AOR =23.789, 95%CI: 3.038, 186.298), geographical locations, Western zones (AOR = 0.275, 95%CI: 0.167, 0.455), and South east zones (AOR = 0.624, 95%CI: 0.410, 0.950) were significant associated number of human deaths per road traffic accident factors in the study area.Conclusion: In this study,30.5% of accidents were giving rise to at least one human death per road traffic accident and different associated numbers of human deaths per road traffic accident factors have been identified. Thus, interventions by the bodies concerned with introduction educational programs that will create awareness about road traffic accidents and the associated human deaths, especially targeting road users, young drivers, passengers and pedestrians.
The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm
Authors: Miyamoto Kazuya , Matsumoto Kazuyuki , Kato Hironari , Yoshida Ryuichi , Umeda Yuzo , Matsumi Akihiro , Saragai Yosuke , Fujii Yuki , Yamazaki Tatsuhiro , Uchida Daisuke , Tomoda Takeshi , Horiguchi Shigeru , Yagi Takahito , Okada Hiroyuki
Published: May 2020

Background
Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN.
Methods
We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017.
Results
Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043).
Conclusions
LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.
Complications to 6 months following total hip or knee arthroplasty: Observations from an Australian clinical outcomes registry
Authors: Heo Sung Mu , Harris Ian , Naylor Justine , Lewin Adriane
Published: May 2020

Background
Total hip and total knee arthroplasty (THA/TKA) are increasing in incidence annually. While these procedures are effective in improving pain and function, there is a risk of complications.
Methods
Using data from an arthroplasty registry, we described complication rates including reasons for reoperation and readmission from the acute period to six months following THA and TKA in an Australian context. We also used logistic regression to identify risk factors for complications.
Results
In the 8,444 procedures included for analysis, 39.7% of THA and 53.6% of TKA patients reported a major or minor complication. In THA patients, factors associated with increased risk for complications included increased BMI, previous THA and bilateral surgery, whereas in TKA patient factors were heart disease, neurological disease, and pre-operative back pain and arthritis in a separate joint. Female gender and previous TKA were identified as protective factors for minor complications in TKA patients.
Conclusion
We found moderate rates of major and high rates of minor postoperative complications following THA and TKA in Australia and have identified several patient factors associated with these complications. Efforts should be focused on identifying patients with higher risk and optimising pre- and post-operative care to reduce the rates of these complications.
Endoscopic Endoclip Papilloplasty Preserves Sphincter of Oddi Function After Endoscopic Sphincterotomy in Porcine Models
Authors: Wang YingChun , Chang Hong , Zhang YaoPeng , Wang Kun , Zhang HeJun , Yan XiuE , Meng LingYu , Yao Wei , Li Ke , Huang YongHui
Published: May 2020

Background

Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) function and plays a role in recurrent choledocholithiasis and cholangitis development. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST.
Methods

Seven 26-week-old domestic pigs were divided into control and EEPP groups. Necropsy, hematoxylin-eosin staining, anti-α-smooth muscle actin (α-SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points.
Results

EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation with less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19 /min) reduced after EST. Further reductions to almost 0 were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data recovered to pre-EST levels, such as CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed by Student t-test.
Conclusions

In this porcine study, EEPP had accelerated and improved papillary healing after EST, and preserved SO function.
Dysbiosis of Gut Microbiota with Increased Trimethylamine N-oxide Level in Patients with Large Artery Atherosclerotic and Cardioembolic Strokes
Authors: Xu Dong-Juan , Wang Kaicheng , Yuan Lin-Bo , Lin Qiong-Qiong , Li Hong-Fei , Xu Yun-Yun , Wei Lian-Yan , Chen Li , Jin Ke-Ke
Published: May 2020

Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes.Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes.Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.
Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma
Authors: Tian Zhichao , Zhang Fan , Li Po , Wang Jiaqiang , Yang Jinpo , Zhang Peng , Yao Weitao , Wang Xin
Published: May 2020

Background: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the clinical data and evidence of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare.Methods: The data of 17 patients with metastatic STS who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively reviewed. All patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the median progression-free survival (m-PFS), disease control rate (DCR), objective response rate (ORR) and adverse events (AEs) in these patients.Results: The m-PFS was 6 months (95% CI, 2–9 months), ORR was 41.2% and DCR was 70.6%. The average change in target lesion diameter from baseline was -19.06±45.74%. While the majority of the treatment patients experienced grade 1 or 2 AEs, grade 3 or 4 AEs were not common, but included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. Conclusion: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.
Transcriptomic analysis of a-linolenic acid content and biosynthesis in Paeonia ostii fruits and seeds
Authors: Hu Yonghong , Yu Shui-Yan , Zhang Xiao , Huang Liang-Bo , Lyu Yu-Ping , Zhang Ying , Yao Zu-Jie , Zhang Xiao-Xiao , Yuan Jun-Hui
Published: May 2020

Background
Paeonia ostii is a potentially important oilseed crop because its seed yield is high and the seeds are rich in α-linolenic acid (ALA). However, the molecular mechanisms underlying ALA biosynthesis during seed kernel, seed testa, and fruit pericarp development in this plant are unclear. We used transcriptome data to address this knowledge gap.
Results
Gas chromatograph-mass spectrometry indicated that ALA content was highest in the kernel, moderate in the testa, and lowest in the pericarp. Therefore, we used RNA-sequencing to compare ALA synthesis among these three tissues. We identified 227,837 unigenes, with an average length of 755 bp. Of these, 1371 unigenes were associated with lipid metabolism. The fatty acid (FA) biosynthesis and metabolism pathways were significantly enriched during the early stages of oil accumulation in the kernel. ALA biosynthesis was significantly enriched in parallel with increasing ALA content in the testa, but these metabolic pathways were not significantly enriched during pericarp development. By comparing unigene transcription profiles with patterns of ALA accumulation, specific unigenes encoding crucial enzymes and transcription factors (TFs) involved in de novo FA biosynthesis and oil accumulation were identified. Specifically, the bell-shaped expression patterns of genes encoding SAD, FAD2, FAD3, PDCT, PDAT, OLE, CLE, and SLE in the kernel were similar to the patterns of ALA accumulation in this tissue. Genes encoding BCCP, BC, KAS I– III, and FATA were also upregulated during the early stages of oil accumulation in the kernel. In the testa, the upregulation of the genes encoding SAD, FAD2, and FAD3 was followed by a sharp increase in the concentrations of ALA. In contrast, these genes were minimally expressed (and ALA content was low) throughout pericarp development.
Conclusions
In this study, we used three tissues with high, moderate, and low ALA concentrations as an exemplar system in which to compare tissue-specific ALA accumulation mechanism in P. ostii. The genes and TFs identified herein might be useful targets for future studies of ALA accumulation in the tree peony. This study also provides a framework for future studies of FA biosynthesis in other oilseed plants.
Transcriptome analysis of two contrasting genotypes of pearl millet to gain insight into heat stress responses
Authors: Maibam Albert , Nigombam Sunil , Vishwakarma Harinder , Lone Showkat Ahmad , Gaikwad Kishor , Mithra S. V. Amitha , Singh Madan Pal , Singh Sumer Pal , Dalal Monika , Padaria Jasdeep Chatrath
Published: May 2020

The authors have withdrawn this preprint due to erroneous posting.
Difference Analysis of the Contribution of E-commerce and Modern Logistics to Regional Economy Based on Wireless Network
Authors: Tang Xiaodong , Wang Gangyi
Published: May 2020

The rapid development of e-commerce has greatly promoted the development of the modern logistics industry. The application level of e-commerce and the application status of modern logistics largely determine the development of regional economic structure in a region. Under this circumstance, it is particularly important to comprehensively strengthen the research and analysis of the impact of e-commerce and modern logistics on the regional economic structure and scope, and promote the coordinated development between each other. As one of the most developed regions in China, the Yangtze River Delta region has achieved certain achievements in the development of regional logistics industry and e-commerce, and plays an important role in the process of regional integration in the Yangtze River Delta. Therefore, this paper takes the Yangtze River Delta as the research object, and empirically analyses the development status of the logistics industry and e-commerce in the Yangtze River Delta region and its contribution to regional economic growth. On this basis, it puts forward countermeasures to further increase the contribution of the logistics industry and e-commerce in the Yangtze River Delta region to economic growth. This will provide a reference for the construction of a coordinated regional logistics-e-commerce system and the realization of regional economic integration in the Yangtze River Delta region.
Metal Catalyzed Synthesis of Pentose-Sugar-Based Chiral 2-Substituted-1H-Benzimidazoles
Authors: Halder Samiran
Published: May 2020

The authors have withdrawn this preprint due to author disagreement.