bluuebunny/crossref_metadata_2025 huggingface dataset:
Students’ perception of online learning during the COVID-19 pandemic
Authors: Bączek Michał , Zagańczyk-Bączek Michalina , Szpringer Monika , Jaroszyński Andrzej , Wożakowska-Kapłon Beata
Published: February 2021

The COVID-19 pandemic has disrupted teaching in a variety of institutions, especially in medical schools. Electronic learning (e-learning) became the core method of teaching the curriculum during the pandemic. After 8 weeks of only online learning, a survey was conducted to investigate perception of this type of learning among medical students.

A survey was conducted by distributing an online questionnaire to Polish medical students. Data gathered from the survey were analyzed with routine statistical software.

Eight hundred four students answered the questionnaire. According to respondents’ answers, the main advantages of online learning were the ability to stay at home (69%), continuous access to online materials (69%), learning at your own pace (64%), and comfortable surroundings (54%). The majority of respondents chose lack of interactions with patients (70%) and technical problems with IT equipment (54%) as the main disadvantages. There was no statistical difference between face-to-face and online learning in terms of opinions on the ability of the learning method to increase knowledge (P = .46). E-learning was considered less effective than face-to-face learning in terms of increasing skills (P < .001) and social competences (P < .001). Students assessed that they were less active during online classes compared to traditional classes (P < .001). E-learning was rated as enjoyable by 73% of respondents.

E-learning is a powerful tool for teaching medical students. However, successful implementation of online learning into the curriculum requires a well thought-out strategy and a more active approach.
Identification of prognostic miRNA biomarkers for esophageal cancer based on The Cancer Genome Atlas and Gene Expression Omnibus
Authors: Xue Jinru , Jia Erna , Ren Na , Xin Hua
Published: February 2021

MicroRNAs (miRNAs) in tumor and tumor-adjacent tissues can be effective diagnostic and prognostic markers to monitor tumor occurrence and progression. Despite improvements in the diagnosis and treatment of esophageal cancer (EC), the survival rate is <25%; consequently, more effective EC-specific prognostic biomarkers are urgently needed to design effective treatment regimens. In this study, we focused on identifying independent prognostic miRNA signatures in tumor and tumor-adjacent tissues in EC.

We screened candidate miRNAs using a genome-wide miRNA transcriptome dataset from The Cancer Genome Atlas (TCGA) database that included 82 patients with esophageal adenocarcinoma (EADC) and 83 patients with esophageal squamous cell carcinoma (ESCC). We validated potential prognostic miRNA markers using a microarray profiling dataset that included information of 32 patients with EADC and 44 patients with ESCC from the Gene Expression Omnibus database. TCGA dataset was additionally used to identify differentially expressed mRNAs (DEMs) between the tumor and tumor-adjacent tissues. Univariate and multivariate Cox analyses were performed to detect the relationship between miRNAs and the overall survival of patients with EC. Kaplan–Meier method was applied to assess the survival differences between groups with differential miRNA expression. Lastly, functional enrichment analysis was conducted using miRWalk 2.0 online database for annotation.

Although there was a considerable difference between the DEMs of EADC and ESCC, 73 DEMs were differentially expressed in both EADC and ESCC samples in TCGA dataset. Cox regression and Kaplan–Meier survival analyses showed that a higher expression of hsa-miR-186-5p and hsa-let-7d-5p was independently associated with a poor prognosis of EADC and ESCC, respectively. Furthermore, gene functional enrichment analysis revealed that the target genes of hsa-miR-186-5p and hsa-let-7d-5p participated in various cancer-related pathways, including the MAPK signaling pathway, proteoglycans in cancer, and AGE-RAGE signaling pathway.

Our results revealed that hsa-miR-186-5p and hsa-let-7d-5p could be used as independent prognostic biomarkers for EADC and ESCC, respectively.
The effects of teriparatide and bisphosphonates on new fractures in postmenopausal women with osteoporosis
Authors: Ouyang YuLong , Chen ShuiLin , Wan Ting , Zheng GuiHao , Sun GuiCai
Published: February 2021

Background:

To systematically evaluate the efficacy of teriparatide and bisphosphonates in preventing fractures in postmenopausal women with osteoporosis.

Materials and methods:

We performed a systematic search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that compared teriparatide and bisphosphonates for osteoporosis treatment. Searches were performed without language restrictions and included studies from beginning of time to March 2019. Two authors independently screened and extracted the selected article. The quality of the included studies was evaluated using the Cochrane system evaluation method. Data were extracted and analysed using RevMan 5.2 software.

Results:

Nine RCTs were included for a total of 2990 postmenopausal women with osteoporosis. Of these, 1515 patients were treated with teriparatide and 1475 were treated with bisphosphonates. After pooling the data of 9 studies, there were significant differences between teriparatide and bisphosphonates [relative risk (RR): 0.61, 95% confidence interval (CI) (0.51, 0.74)] in the prevention of fractures according to different follow-up durations (P < .05), whatever alendronate [RR: 0.51, 95% CI (0.27, 0.95)] and other bisphosphonates [RR: 0.63, 95% CI (0.51, 0.77)]. In addition, we found significant differences between teriparatide and bisphosphonates in the prevention of vertebral fractures [RR: 0.47, 95% CI (0.35, 0.64)] and non-vertebral fractures [RR: 0.76, 95% CI (0.58,0.99)]. There were no significant differences in adverse effects between teriparatide and bisphosphonates [RR: 0.89, 95% CI (0.76, 1.03)].

Conclusions:

Based on the results of our meta-analysis, teriparatide was better than bisphosphonates in preventing fractures in postmenopausal women with osteoporosis both in the short-term and long-term follow-up periods. Teriparatide was superior to bisphosphonates in preventing vertebral and non-vertebral fractures. These drugs did not differ in terms of their adverse effects. More high-quality studies are needed to compare other factors such as costs and adverse reactions.
Analysis of risk factors, pathogenic bacteria of maternal sepsis in term pregnant women with positive blood culture during hospitalization
Authors: Wen Yanqing , Chen Hong , Ming Xin , Chen Xiaoyan , Zhou Wei
Published: February 2021

The objective of this study was to evaluate the risk factors, pathogenic bacteria and drug sensitivity of maternal sepsis, and provide evidence for clinical prevention and treatment.

A retrospective investigation of pregnant women with full-term maternal sepsis was performed to analyze the risk factors, pathogenic bacteria, and drug sensitivity of maternal sepsis.

Univariate analysis showed that temperature, serum procalcitonin (PCT) and C-reactive protein (CRP) at admission, white blood cell count (WBC), PCT, CRP and neutrophilic granulocyte percentage (N%) during fever, premature rupture of membranes (PROM), antibiotic use within 1 week, mode of production, onset and duration of fever, between groups were statistically significant (P < .05). Logistic regression analysis showed that cesarean section was an independent risk factor for sepsis (OR = 11.839, 95%CI: 3.121–44.906). Apparent increase was found in body temperature (OR = 3.664, 95%CI: 1.722–7.795), duration of fever (OR = 1.953, 95%CI: 1.242–3.071), and PCT (OR = 1.080, 95%CI: 1.002–1.163). Also, increasing neutrophil ratio (OR = 1.180, 95%CI: 1.073–1.297) indicated a high possibility of maternal sepsis. The organism Escherichia coli (E. coli) was the most common pathogenic bacteria in the positive blood culture group (90%), and the sensitivity to carbapenems (meropenem and imipenem/cilastatin) was 100%, that to piperacillin-tazobactam and amoxicillin sulbactam was over 90%, and that to ceftazidime was 95%.

Cesarean section was an independent risk factor for maternal sepsis in term pregnant women with positive blood culture. Besides, the E. coli was the most common pathogenic bacteria in the positive blood culture group. Antibiotics should be used in time and reasonably when the temperature was significantly increased with elevated PCT and N% after a cesarean section.
Prevalence of recessive infection of pathogens of hand, foot, and mouth disease in healthy people in China
Authors: Zhou Yu-Jie , Niu Xiu-De , Ding Ya-Qing , Qian Zheng , Zhao Bao-Lin
Published: February 2021

Background:

To analyze the prevalence of latent infection of pathogens of hand, foot, and mouth disease (HFMD) in Chinese healthy population and its influencing factors, so as to provide reference for the prevention and control of HFMD.

Methods:

A systematic literature searching about the incidence of latent infection of HFMD was conducted in Chinese and English databases. The inclusion and exclusion criteria of the retrieved literature were established. The qualified literatures were screened and the data were extracted. The pooled rate and its 95% confidence interval was used to assess the latent infection rate of HFMD pathogens in healthy Chinese population, and subgroup analysis was conducted based on gender and age. All statistical analyses were performed using the STATA version 12.0 software.

Results:

A total of 31 literatures were included in this meta-analysis. The recessive infection rate of HFMD pathogens reported in the literature of Chinese healthy people ranged from 4.59% to 44.12%. The results of meta-analysis showed that the latent infection rate of human enteroviruses (HEVs) in healthy Chinese population was 17.5% (14.9–20.1%), among which, the latent infection rates of EV-A71, CV-A16, and other HEVs were 3.3% (2.2–4.4%), 1.7% (1.0–2.5%), and 15.1% (11.1–17.1%), respectively. The latent infection rates of HEVs in healthy men and women in China were 16.7% (12.9–20.4%) and 14.4% (10.8–18.0%), respectively. The latent infection rates of HEVs in the healthy population aged 0 to 5 years and over 5 years were 24.4% (20.4–28.5%) and 9.4% (6.5–12.2%), respectively. Meta regression showed that the factors affecting the latent infection rate of HEVs in Chinese healthy population included sampling period, sampling area, and study population.

Conclusion:

The latent infection rate of HEVs is high in healthy people in China, but it is mainly caused by other enteroviruses. The latent infection rate of HEVs in male was higher than that of female and was greater in people aged 0 to 5 than that of aged over 5 years. Limited by the quantity and quality of the included studies, more high-quality studies are needed for further verification in the future.
The effect of health-care Qigong Baduanjin combined with auricular point sticking on athletes’ pre-competition anxiety
Authors: Li Lujia , Li Xiaozheng , Xie Pingping , Li Yan , Ma Li , Ding Baoyu
Published: February 2021

Background:

Competition anxiety is also known as pre-competition anxiety (PCA), because this anxiety state often occurs before the athletes face the competition. If it is not adjusted in time, which will greatly affect the performance of athletes, even the mental health and physical health of athletes. Therefore, the selection of appropriate methods to intervene the athletes, reducing the PCA of athletes, and it has an important effect on the competition performance of athletes. Therefore, based on the basic theory of traditional Chinese medicine and sports psychology principles, this study adopts a way of systematic evaluation to study the effect of health-care Qigong Baduanjin (HCQB) combined with auricular point sticking (APS)in the treatment of athletes’ PCA (APA), the purpose is to help the majority of athletes to eliminate the PCA.

Methods:

Two searchers independently retrieve CNKI, WANFANG databases, VIP, CBM, Web of Science, Embase, PubMed, The Cochran Library and other Chinese and English databases. It is supplemented by manual retrieval to comprehensively collect the relevant literature data of the clinical controlled study of HCQB combined with APS in the treatment of APA. The retrieval time is from January 1, 1990 to October 1, 2020, using the subject word and keywords to retrieve, developing a retrieval style according to the characteristics of the database. The two evaluators independently use the above-mentioned retrieval methods to retrieve the main literature database, summarizing and removing the duplicate literature, then reading the title and abstract of the literature separately, excluding the literature that clearly does not meet the inclusion criteria, and finally reading the literature, and finally including the literature in line with the study, in case of disagreement, with the third researcher to decide. The quality evaluation of the literature is independently evaluated using the bias risk assessment criteria for randomized controlled trials in Cochrane Manual 5.1.0. Using the RevMan 5.3 software for meta-analysis.

Results:

This study will study the effect of HCQB combined with APS on reducing APA, and the results of the study will be published in high-impact academic journals.

Conclusion:

The quality of athletes’ mental state is related to whether athletes can play their true level of sports in the competition, and good mental state is also the prerequisite to ensure that athletes get better results. The conclusions reached by this study will provide quantifiable reference for coaches and athletes, with the aim of providing theoretical basis for helping the athletes eliminate PCA.

Ethics and dissemination:

The type of this study belongs to the category of systematic evaluation, the data in this study are derived from published research papers and public data in the Internet, so ethical review is not suitable for this study.

PROSPERO registration number:

2021 CRD42021228254.
Peutz-Jeghers syndrome
Authors: Tacheci Ilja , Kopacova Marcela , Bures Jan
Published: February 2021

Purpose of review

Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients.

Recent findings

A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence.

Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.
Small bowel radiology
Authors: Olson Michael C. , Navin Patrick J. , Welle Christopher L. , Goenka Ajit H.
Published: February 2021

Purpose of review

Recent advances in computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), and nuclear radiology have improved the diagnosis and characterization of small bowel pathology. Our purpose is to highlight the current status and recent advances in multimodality noninvasive imaging of the small bowel.

Recent findings

CT and MR enterography are established techniques for small bowel evaluation. Dual-energy CT is a novel technique that has shown promise for the mesenteric ischemia and small bowel bleeding. Advanced US techniques and MRI sequences are being investigated to improve assessment of bowel inflammation, treatment response assessment, motility, and mural fibrosis. Novel radiotracers and scanner technologies have made molecular imaging the new reference standard for small bowel neuroendocrine tumors. Computational image analysis and artificial intelligence (AI) have the potential to augment physician expertise, reduce errors and variability in assessment of the small bowel on imaging.

Advances in translational imaging research coupled with progress in imaging technology have led to a wider adoption of cross-sectional imaging for the evaluation and management of small bowel entities. Ongoing developments in image acquisition and postprocessing techniques, molecular imaging and AI have the strongest potential to transform the care and outcomes of patients with small bowel diseases.
Hepatitis C-positive liver transplantation: outcomes and current practice
Authors: Danford Christopher J. , Redman Joseph S. , Alonso Diane
Published: February 2021

Purpose of review

The coincidence of the opioid epidemic and the approval of direct-acting antivirals for the treatment of hepatitis C virus (HCV) has resulted in an imbalance in HCV viraemic donors relative to HCV viraemic patients awaiting liver transplantation. Although ethical concerns exist about knowingly infecting patients with HCV in the absence of prospective, protocolized studies, transplantation of HCV-positive liver allografts into HCV-negative recipients has increased exponentially in recent years. For this reason, we sought to review outcomes, cost-effectiveness and ethical concerns associated with this practice.

Recent findings

Short-term outcomes in terms of patient and graft survival are equivalent to those who received HCV-negative allografts without an increase in acute rejection, biliary or vascular complications. Few cases of treatment failure have been reported and complications related to the virus itself such as fibrosing cholestatic hepatitis and membranous glomerulonephritis are rare and reversible with prompt direct-acting antiretroviral treatment. The practice appears cost-effective and modelling suggests a survival benefit for patients willing to accept HCV-positive organs compared with those who do not.

In light of the preponderance of current data, one could argue it is unethical to withhold HCV-positive grafts from HCV-negative recipients who have undergone thorough informed consent.
Current status of left lobe adult to adult living donor liver transplantation
Authors: Braun Hillary J. , Roberts John P.
Published: February 2021

Purpose of review

This review describes the history and current state of left lobe living donor liver transplantation (LDLT). The transplant community continues to face an organ shortage on a global scale, and the expansion of LDLT is attractive because it allows us to provide life-saving liver transplants to individuals without drawing from, or depending on, the limited deceased donor pool. Donor safety is paramount in LDLT, and for this reason, left lobe LDLT is particularly attractive because the donor is left with a larger remnant.

Recent findings

This article reviews the donor and recipient evaluations for left lobe LDLT, discusses small for size syndrome and the importance of portal inflow modification, and reviews recipient outcomes in right lobe versus left lobe LDLT.

Left lobe LDLT was the first adult-to-adult LDLT ever to be performed in Japan in 1993. Since that time, the use of both right and left lobe LDLT has expanded immensely. Recent work in left lobe LDLT has emphasized the need for inflow modification to reduce portal hyperperfusion and early graft dysfunction following transplant. Accumulating evidence suggests, however, that even though early graft dysfunction following LDLT may prolong hospitalization, it does not predict graft or patient survival.
Identification of a Novel De Novo COMP Gene Variant as a Likely Cause of Pseudoachondroplasia
Authors: Tuncel Gulten , Akcan Nese , Gul Seref , Sag Sebnem O. , Bundak Ruveyde , Mocan Gamze , Temel Sehime G. , Ergoren Mahmut C.
Published: February 2021

Next-generation sequencing technology and advanced sequence analysis techniques are markedly speeding up the identification of gene variants causing rare genetic diseases. Pseudoachondroplasia (PSACH, MIM 177170) is a rare disease inherited in an autosomal dominant manner. It is known that variations in the cartilage oligomeric matrix protein (COMP) gene are associated with the disease. Here, we report a 39-month-old boy with short stature. He gave visible growth and development delayed phenotype after 12 months. Further genetic resequencing analysis was carried out to identified the disease-causing variant. Furthermore, computational approaches were used to characterize the effect of the variant. In this study, we identify and report a novel variation in the COMP gene, c.1420_1422del (p.Asn47del), causing a spontaneous form of PSACH in our patient. Our in silico model indicated that any mutational changes in this region are very susceptible to PASCH phenotype. Overall, this study is the first PSACH case in the Turkish Cypriot population. Moreover, this finding contributes to the concept that the genotype-phenotype correlation in COMP is still unknown and also improves our understanding of this complex disorder.
Association Between Repeated Tracheal Intubation Attempts and Adverse Events in Children in the Emergency Department
Authors: Funakoshi Hiraku , Kunitani Yuri , Goto Tadahiro , Okamoto Hiroshi , Hagiwara Yusuke , Watase Hiroko , Hasegawa Kohei
Published: February 2021

Study Objectives

Studies have shown that multiple intubation attempts are associated with a higher risk of intubation-related adverse events. However, little is known about the relationship in children in the emergency department (ED).

Methods

This is an analysis of the data from 2 prospective, observational, multicenter registries of emergency airway management. The data were collected from consecutive patients who underwent emergency airway management in 19 EDs across Japan from March 2010 to November 2017. We included children 18 years or younger who underwent tracheal intubation in the ED. The primary exposure was the number of intubation attempts (1 vs ≥2). The primary outcome was an adverse event during or immediately after the intubation.

Results

A total of 439 children were eligible for the analysis. Of 279 children with first-pass success, 24 children (9%) had an adverse event. By contrast, of 160 children with ≥2 intubation attempts, 50 children patients (31%) had an adverse event. In the unadjusted model, multiple intubation attempts were significantly associated with a higher rate of adverse events (unadjusted odds ratio, 4.83; 95% confidence interval, 2.57–9.06; P < 0.001). This association remained significant after adjusting for 7 potential confounders and patient clustering within the hospital (adjusted odds ratio, 4.49; 95% confidence interval, 2.36–8.53; P < 0.001). Similar associations were found across different age groups and among children without cardiac arrest (all, P < 0.05).

Conclusions

In this analysis of large prospective multicenter data, multiple intubation attempts were associated with a significantly higher rate of intubation-related adverse events in children in the ED.
Costs of integrating hypertension care into HIV care in rural East African clinics
Authors: Shade Starley B. , Osmand Thomas , Kwarisiima Dalsone , Brown Lillian B. , Luo Alex , Mwebaza Betty , Mwesigye Aine Ronald , Kwizera Enos , Imukeka Haawa , Mwanga Florence , Ayieko James , Owaraganise Asiphas , Bukusi Elizabeth A. , Cohen Craig R. , Charlebois Edwin D. , Black Douglas , Clark Tamara D. , Petersen Maya L. , Kamya Moses R. , Havlir Diane V. , Jain Vivek
Published: February 2021

Objective:

Sub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care. Here, we estimate costs for integrated hypertension/HIV care for HIV-positive individuals, and costs for hypertension care for HIV-negative individuals in the same clinics.

Design:

Microcosting analysis of healthcare expenditures within Ugandan HIV clinics.

Methods:

SEARCH (NCT: 01864603) conducted community health campaigns for diagnosis and linkage to care for both HIV and hypertension. HIV-positive patients received hypertension/HIV care jointly including blood pressure monitoring and medications; HIV-negative patients received hypertension care at the same clinics. Within 10 Ugandan study communities during 2015–2016, we estimated incremental annual per-patient hypertension care costs using micro-costing techniques, time-and-motion personnel studies, and administrative/clinical records review.

Results:

Overall, 70 HIV-positive and 2355 HIV-negative participants received hypertension care. For HIV-positive participants, average incremental cost of hypertension care was $6.29 per person per year, a 2.1% marginal increase over prior estimates for HIV care alone. For HIV-negative participants, hypertension care cost $11.39 per person per year, a 3.8% marginal increase over HIV care costs. Key costs for HIV-positive patients included hypertension medications ($6.19 per patient per year; 98% of total) and laboratory testing ($0.10 per patient per year; 2%). Key costs for HIV-negative patients included medications ($5.09 per patient per year; 45%) and clinic staff salaries ($3.66 per patient per year; 32%).

Conclusion:

For only 2–4% estimated additional costs, hypertension care was added to HIV care, and also expanded to all HIV-negative patients in prototypic Ugandan clinics, demonstrating substantial synergy. Our results should encourage accelerated scale-up of hypertension care into existing clinics.
Risk of adverse coronavirus disease 2019 outcomes for people living with HIV
Authors: Mellor Maya M. , Bast Anne C. , Jones Nicholas R. , Roberts Nia W. , Ordóñez-Mena José M. , Reith Alastair J.M. , Butler Christopher C. , Matthews Philippa C. , Dorward Jienchi
Published: February 2021

Objective:

To assess whether people living with HIV (PLWH) are at increased risk of coronavirus disease 2019 (COVID-19) mortality or adverse outcomes, and whether antiretroviral therapy (ART) influences this risk.

Design:

Rapid review with meta-analysis and narrative synthesis.

Methods:

We searched databases including Embase, Medline, medRxiv and Google Scholar up to 26 August 2020 for studies describing COVID-19 outcomes in PLWH and conducted a meta-analysis of higher quality studies.

Results:

We identified 1908 studies and included 19 in the review. In a meta-analysis of five studies, PLWH had a higher risk of COVID-19 mortality [hazard ratio 1.95, 95% confidence interval (CI): 1.62–2.34] compared with people without HIV. Risk of death remained elevated for PLWH in a subgroup analysis of hospitalized cohorts (hazard ratio 1.60, 95% CI: 1.12–2.27) and studies of PLWH across all settings (hazard ratio 2.08, 95% CI: 1.69–2.56). Eight other studies assessed the association between HIV and COVID-19 outcomes, but provided inconclusive, lower quality evidence due to potential confounding and selection bias. There were insufficient data on the effect of CD4+ T-cell count and HIV viral load on COVID-19 outcomes. Eleven studies reported COVID-19 outcomes by ART-regimen. In the two largest studies, tenofovir disoproxil fumarate-based regimens were associated with a lower risk of adverse COVID-19 outcomes, although these analyses are susceptible to confounding by co-morbidities.

Conclusion:

Emerging evidence suggests a moderately increased risk of COVID-19 mortality among PLWH. Further investigation into the relationship between COVID-19 outcomes and CD4+ T-cell count, HIV viral load, ART and the use of tenofovir disoproxil fumarate is warranted.
HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into T lymphoid cells
Authors: Zou Wei , Xing Juanjuan , Wang Fen , Chen Xinping , Liu Qian , Wang Jinyong , Zou Shijie , Chen Limin , Fu Xin , Zhou Zhengping , Wan Zhikai
Published: February 2021

Objective:

Despite successful antiviral therapy, the recovery of CD4+ T cells may not be complete in certain HIV-1-infected individuals. In our previous work with humanized mice infected with CXCR4-tropic HIV-1LAI (LAI), viral protein Nef was found the major factor determining rapid loss of both CD4+ T cells and CD4+CD8+ thymocytes but its effect on early T-cell development is unknown. The objective of this study is to investigate the influence of LAI Nef on the development of hematopoietic stem/progenitor cells (HSPCs) into T lymphoid cells.

Design:

HSPC-OP9-DL1 cell co-culture and humanized mouse model was used to investigate the objective of our study in vitro and in vivo. RNA-seq was exploited to study the change of gene expression signature after nef expression in HSPCs.

Results:

Nef expression in HSPCs was found to block their development into T lymphoid cells both in vitro and in the mice reconstituted with nef-expressing HSPCs derived from human cord blood. More surprisingly, in humanized mice nef expression preferentially suppressed the production of CD4+ T cells. This developmental defect was not the result of CD34+ cell loss. RNA-seq analysis revealed that Nef affected the expression of 176 genes in HSPCs, including those involved in tumor necrosis factor, Toll-like receptor, and nucleotide-binding oligomerization domain-like receptor signaling pathways that are important for hematopoietic cell development.

Conclusion:

Our results demonstrate that Nef compromises the development of HSPCs into T lymphoid cells, especially CD4+ T cells. This observation suggests that therapeutics targeting Nef may correct HIV-1-associated hematopoietic abnormalities, especially defects in T-cell development.
Outcomes of acute hepatitis B virus (HBV) in HIV infection with and without HBV-active antiretroviral therapy
Authors: Falade-Nwulia Oluwaseun , Seaberg Eric C. , Snider Anna E. , Rinaldo Charles R. , Wolinsky Steven M. , Witt Mallory D. , Thio Chloe L.
Published: February 2021

Men with acute hepatitis B virus (HBV) infection in the Multicenter AIDS Cohort Study from 1985 to 2013 had serological testing to determine proportions with HBV recovery or chronic hepatitis B (CHB). A similar proportion of men without human immunodeficiency virus (HIV) and men with HIV receiving HBV-active antiretroviral therapy (ART) developed CHB [8.2%, 95% confidence interval (CI) 3.8–15.0% vs. 7.7%, 95% CI 2.00–36.0%]. In contrast, 17.5% (95% CI 8.7–29.9%) of men living with HIV, not on HBV-active ART developed CHB. HBV-active ART protects against developing CHB.
Fibril density reduction in keratoconic corneas
Authors: Zhou Dong , Abass Ahmed , Lopes Bernardo , Eliasy Ashkan , Hayes Sally , Boote Craig , Meek Keith M. , Movchan Alexander , Movchan Natalia , Elsheikh Ahmed
Published: February 2021

This study aims to estimate the reduction in collagen fibril density within the central 6 mm radius of keratoconic corneas through the processing of microstructure and videokeratography data. Collagen fibril distribution maps and topography maps were obtained for seven keratoconic and six healthy corneas, and topographic features were assessed to detect and calculate the area of the cone in each keratoconic eye. The reduction in collagen fibril density within the cone area was estimated with reference to the same region in the characteristic collagen fibril maps of healthy corneas. Together with minimum thickness and mean central corneal refractive power, the cone area was correlated with the reduction in the cone collagen fibrils. For the corneas considered, the mean area of keratoconic cones was 3.30 ± 1.90 mm
2
. Compared with healthy corneas, fibril density in the cones of keratoconic corneas was lower by as much as 35%, and the mean reduction was 17 ± 10%. A linear approximation was developed to relate the magnitude of reduction to the refractive power, minimum corneal thickness and cone area (
R
2
= 0.95,
p
< 0.001). Outside the cone area, there was no significant difference between fibril arrangement in healthy and keratoconic corneas. The presented method can predict the mean fibril density in the keratoconic eye's cone area. The technique can be applied in microstructure-based finite-element models of the eye to regulate its stiffness level and the stiffness distribution within the areas affected by keratoconus.
Machine learning-based single cell and integrative analysis reveals that baseline mDC predisposition predicts protective Hepatitis B vaccine response
Authors: Aevermann Brian , Shannon Casey P. , Novotny Mark , Ben-Othman Rym , Cai Bing , Zhang Yun , Ye Jamie C. , Kobor Michael S. , Gladish Nicole , Lee Amy , Blimke Travis M , Hancock Robert E. , Llibre Alba , Duffy Darragh , Koff Wayne C. , Sadarangani Manish , Tebbutt Scott J. , Kollmann Tobias R. , Scheuermann Richard H.
Published: February 2021

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine. Why some, but not all, recipients responded in this way was not clear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) predicted immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. Genes expressed in these mDC subsets were used as an approach for feature selection prior to the construction of a predictive model using supervised canonical correlation machine learning. The resulting model showed an improved ability to predict serum antibody titers in response to vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype”, could dictate response to vaccination. The fact that these mDCs could be modulated via TLR stimulation could guide progress towards design of effective single dose vaccination strategies.
An integrated framework for building trustworthy data-driven epidemiological models: Application to the COVID-19 outbreak in New York City
Authors: Zhang Sheng , Ponce Joan , Zhang Zhen , Lin Guang , Karniadakis George
Published: February 2021

Epidemiological models can provide the dynamic evolution of a pandemic but they are based on many assumptions and parameters that have to be adjusted over the time when the pandemic lasts. However, often the available data are not sufficient to identify the model parameters and hence infer the unobserved dynamics. Here, we develop a general framework for building a trustworthy data-driven epidemiological model, consisting of a workflow that integrates data acquisition and event timeline, model development, identifiability analysis, sensitivity analysis, model calibration, model robustness analysis, and forecasting with uncertainties in different scenarios. In particular, we apply this framework to propose a modified susceptible–exposed–infectious–recovered (SEIR) model, including new compartments and model vaccination in order to forecast the transmission dynamics of COVID-19 in New York City (NYC). We find that we can uniquely estimate the model parameters and accurately predict the daily new infection cases, hospitalizations, and deaths, in agreement with the available data from NYC’s government’s website. In addition, we employ the calibrated data-driven model to study the effects of vaccination and timing of reopening indoor dining in NYC.
Contact patterns and HPV-genotype interactions yield heterogeneous HPV-vaccine impacts depending on sexual behaviours: an individual-based model
Authors: Bonneault Mélanie , Poletto Chiara , Flauder Maxime , Guillemot Didier , Delarocque-Astagneau Elisabeth , Thiébaut Anne CM , Opatowski Lulla
Published: February 2021

Human papillomaviruses are common sexually transmitted infections, caused by a large diversity of genotypes. In the context of vaccination against a subgroup of genotypes, better understanding the role of genotype interactions and human sexual behavior on genotype ecology is essential. Herein, we present an individual-based model that integrates realistic heterosexual partnership behaviors and simulates interactions between vaccine and non-vaccine genotypes. Genotype interactions were considered, assuming a previous vaccine-genotype infection shortened (competition) or extended (synergy) the duration of a secondary non-vaccine-genotype infection. Sexual behavior determined papillomavirus acquisition and transmission: only 19.5% of active individuals with 0–1 partner during the year, but >80% of those with ≥2 partners, were infected before vaccine introduction. Genotype interactions, despite being silent during the pre-vaccination era, markedly impacted genotype ecology after vaccination started, with a significant increase/decrease of non-vaccine prevalence for competitive/synergistic interactions. These changes were more pronounced in individuals with ≤3 partners (up to 30% of prevalence modification assuming 65% vaccine coverage) but barely visible for individuals with >3 partners (at most 0.30%). Results suggest that considering genotype interactions, in conjunction with heterogeneous sexual behaviors, is essential to anticipate the impact of existing and future anti-papillomavirus vaccines targeting a subgroup of genotypes.
The acoustic quality and health in urban environments (SALVE) project: Study design, rationale and methodology
Authors: Haselhoff Timo , Lawrence Bryce , Hornberg Jonas , Ahmed Salman , Sutcliffe Robynne , Gruehn Dietwald , Moebus Susanne
Published: February 2021

Sound pressure levels expressed in variations of decibel (dB) formulations are a common approach to describe the urban acoustic environment (AE). In recent years, different approaches gained traction to describe the urban AE, like the soundscape ecology approach, which focuses on the natural environment. To determine the feasibility of applying this approach to cities, a comprehensive dataset of high-quality sound recordings with high spatial and temporal resolution is essential.

The acoustic quality and health in urban environments (SALVE) project aims to establish a spatially and temporally high-resolution dataset of the urban AE using land use categories. Since 2019, we assess the AE at selected places in the densely populated city of Bochum, Germany. For a high temporal resolution, we used automatic devices at 52 locations that recorded every 26 minutes for three minutes. For a high spatial resolution, we used manual devices to perform a five-minute recording four times a year at 730 selected locations. Altogether, we ended up with 1,500,493 minutes of sound recordings.

Aim here is to outline our sampling design, methods used, and applied quality procedures in order to achieve a well-defined and high quality dataset presented for further scientific analysis. To the best of our knowledge, this represents one of the most extensive datasets currently available, which will provide a comprehensive database for future in-depth analyses of the associations between the urban AE, urban fabric and human health.

Highlights

A conceptual sampling framework for measuring the urban acoustic environment is given

One of the most extensive datasets of the urban acoustic environment is introduced

Experiences and results of the field work of the SALVE-Project are presented
Scientific modelling can be accessible, interoperable and user friendly: An example for pasture and livestock modelling
Authors: Torres Alba Marquez , Balbi Stefano , Villa Ferdinando
Published: February 2021

This article describes the adaptation of a non-spatial model of pastureland dynamics, including vegetation life cycle, livestock management and nitrogen cycle, for use in a spatially explicit and modular modelling platform (k.LAB) dedicated to make data and models more interoperable. The aim is to deliver an existing, locally successful monolithic model, into a more modular, transparent and accessible approach to potential end users, regional managers, farmers and other stakeholders. This allows better usability and adaptability of the model beyond its originally intended geographical scope (the Cantabrian Region in the North of Spain). The original model, named Puerto, is developed in the R language and includes 1,491 lines of code divided into 13 script files and linked to 19 input tables. The spatiotemporal rewrite is structured around a set of 10 namespaces called PaL (Pasture and Livestock), which includes 198 interoperable but independent models. The end user chooses the spatial and temporal context of the analysis through an intuitive web-based user interface called k.Explorer. Each model can be called individually or in conjunction with the others, by querying any PaL-related concepts in a search bar. A scientific workflow is built as a response, which is run to produce result datasets and a report with information on the data sources and modelling processes used, delivering results with full transparency. We argue that this work demonstrates key steps needed to create more Findable, Accessible, Interoperable and Reusable (FAIR) models. This is particularly essential in environments as complex as agricultural systems, where multidisciplinary knowledge needs to be integrated across diverse spatial and temporal scales in order to understand complex and changing problems.
Improved transformation efficiency of group AStreptococcusby inactivation of a type I restriction modification system
Authors: Finn Meredith B. , Ramsey Kathryn M. , Dove Simon L. , Wessels Michael R.
Published: February 2021

Streptococcus pyogenesor group AStreptococcus(GAS) is a leading cause of bacterial pharyngitis, skin and soft tissue infections, life-threatening invasive infections, and the post-infectious autoimmune syndromes of acute rheumatic fever and post-streptococcal glomerulonephritis. Genetic manipulation of this important pathogen is complicated by resistance of the organism to genetic transformation. Very low transformation efficiency is attributed to recognition and degradation of introduced foreign DNA by a type I restriction-modification system encoded by thehsdRSMlocus. DNA sequence analysis of this locus in ten GAS strains that had been previously transformed with an unrelated plasmid revealed that six of the ten harbored a spontaneous mutation inhsdR, S, orM. The mutations were all different, and at least five of the six were predicted to result in loss of function of the respectivehsdgene product. The unexpected occurrence of such mutations in previously transformed isolates suggested that the process of transformation selects for spontaneous inactivating mutations in the Hsd system. We investigated the possibility of exploiting the increased transformability ofhsdmutants by constructing a deletion mutation inhsdMin GAS strain 854, a clinical isolate representative of the globally dominant M1T1 clonal group. Mutant strain 854ΔhsdMexhibited a 5-fold increase in transformation efficiency compared to the wild type parent strain and no obvious change in growth or off-target gene expression. We conclude that genetic transformation of GAS selects for spontaneous mutants thehsdRSMrestriction modification system. We propose that use of a definedhsdMmutant as a parent strain for genetic manipulation of GAS will enhance transformation efficiency and reduce the likelihood of selecting spontaneoushsdmutants with uncharacterized genotypes.
Machine learning to predict the source of campylobacteriosis using whole genome data
Authors: Arning Nicolas , Sheppard Samuel K. , Clifton David A. , Wilson Daniel J.
Published: February 2021

Campylobacteriosis is among the world’s most common foodborne illnesses, caused predominantly by the bacteriumCampylobacter jejuni. Effective interventions require determination of the infection source which is challenging as transmission occurs via multiple sources such as contaminated meat, poultry, and drinking water. Strain variation has allowed source tracking based upon allelic variation in multi-locus sequence typing (MLST) genes allowing isolates from infected individuals to be attributed to specific animal or environmental reservoirs. However, the accuracy of probabilistic attribution models has been limited by the ability to differentiate isolates based upon just 7 MLST genes. Here, we broaden the input data spectrum to include core genome MLST (cgMLST) and whole genome sequences (WGS), and implement multiple machine learning algorithms, allowing more accurate source attribution. We increase attribution accuracy from 64% using the standard iSource population genetic approach to 71% for MLST, 85% for cgMLST and 78% for kmerized WGS data using machine learning. To gain insight beyond the source model prediction, we use Bayesian inference to analyse the relative affinity ofC. jejunistrains to infect humans and identified potential differences, in source-human transmission ability among clonally related isolates in the most common disease causing lineage (ST-21 clonal complex). Providing generalizable computationally efficient methods, based upon machine learning and population genetics, we provide a scalable approach to global disease surveillance that can continuously incorporate novel samples for source attribution and identify fine-scale variation in transmission potential.

Author summary

C. jejuniare the most common cause of food-borne bacterial gastroenteritis but the relative contribution of different sources are incompletely understood. We traced the origin of humanC. jejuniinfections using machine learning algorithms that compare the DNA sequences of bacteria sampled from infected people, contaminated chickens, cattle, sheep, wild birds and the environment. This approach achieved improvement in accuracy of source attribution by 33% over existing methods that use only a subset of genes within the genome and provided evidence for the relative contribution of different infection sources. Sometimes even very similar bacteria showed differences, demonstrating the value of basing analyses on the entire genome when developing this algorithm that can be used for understanding the global epidemiology and other important bacterial infections.