bluuebunny/crossref_metadata_2025 huggingface dataset:
TOP2A and CENPF are synergistic master regulators activated in cervical cancer
Authors: Yu Beiwei , Chen Long , Zhang Weina , Li Yue , Zhang Yibiao , Gao Yuan , Teng Xianlin , Zou Libo , Wang Qian , Jia Hongtao , Liu Xiangtao , Zheng Hui , Hou Ping , Yu Hongyan , Sun Ying , Zhang Zhiqin , Zhang Ping , Zhang Liqin
Published: October 2020

Background

Identification of master regulators (MRs) using transcriptome data in cervical cancer (CC) could help us to develop biomarkers and find novel drug targets to fight this disease.

Methods

We performed differential expression (DE) analyses of public microarray and RNA-seq transcriptome data of CC and normal cervical tissues (N). Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER) was used to convert the DE outcomes to differential activity (DA) signature for MRs. Synergy analysis was conducted to study synergistic effect of MR-pairs. TCGA and microarray data were used to test the association of expression of a MR and a clinical feature or a molecular feature (e.g. somatic mutations). Various bioinformatic tools/websites (DAVID, GEPIA2, Oncomine, cBioPortal) were used to analyze the expression of the top MRs and their regulons.

Results

Ten DE and 10 DA signatures were generated for CC. Two MRs, DNA topoisomerase II alpha (TOP2A) and centromere protein F (CENPF) were found to be up-regulated, activated and synergistic in CC compared to N across the 10 datasets. The two MRs activate a common set of genes (regulons) with functions in cell cycle, chromosome, DNA damage etc. Higher expression of CENPF was associated with metastasis. High expression of both MRs is associated with somatic mutation of a set of genes including tumor suppressors (TP53, MSH2, RB1) and genes involved in cancer pathways, cell cycle, DNA damage and repair. The magnitude of up-regulation and the absolute expression level of both MRs in CC are significantly higher compared to many other cancer types.

Conclusion

TOP2A and CENPF are a synergistic pair of MRs that are overexpressed and activated in CC. Their high expression is correlated with some prognosis features (e.g. metastasis) and molecular features (e.g. somatic mutations) and distinctly high in CC vs. many other cancer types. They may be good biomarkers and anticancer drug targets for CC.
Exploring the association of long noncoding RNA expression profiles with intracranial aneurysms, based on sequencing and related bioinformatics analysis
Authors: Sun Yi , Wen Yeying , Ruan Qishuang , Yang Le , Huang Shuna , Xu Xingyan , Cai Yingying , Li Huangyuan , Wu Siying
Published: October 2020

Background

The present study aims to investigate the complete long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in Intracranial aneurysm (IA) patients and controls by RNA sequencing, which reveals the lncRNA with predictive value for IA risk.

Methods

The comprehensive lncRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs), followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and CNC network construction. Subsequently, qRT-PCR was used to profile the expression levels of selected lncRNA (lncRNA ENST000000576153, lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1, lncRNA ENST00000508090 and lncRNA ENST00000579688) in 30 (small) or 130 (large) peripheral blood leukocytes, respectively. Multivariate logistic regression was utilized to analyze the effects of lncRNA on IA. Receiver operating characteristic (ROC) curve was further drawn to explore the value of lncRNA in predicting IA.

Results

Totally 900 up-regulated and 293 down-regulated lncRNAs, as well as 1297 up-regulated and 831 down-regulated mRNAs were discovered in sequencing. Enrichment analyses revealed that they were actively involved in immune/inflammatory response and cell adhesion/extracellular matrix. Co-expression analysis and further enrichment analyses showed that five candidate lncRNAs might participate in IA’s inflammatory response. Besides, after controlling other conventional risk factors, multivariate logistic regression analysis disclosed that low expression of lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1 in peripheral blood leukocytes were independent risk factors for IA. LncRNA ENST00000607042 has superior diagnostic value for IA.

Conclusions

This study reveals the complete lncRNAs expression profiles in IA. The inflammatory response was closely related to IA. Besides, lncRNA ENST00000607042 might be a novel biomarker for IA risk.
Validity and reliability of a simplified food frequency questionnaire: a cross sectional study among physical health examination adults in southwest region of China
Authors: Cheng Zhengyan , Shuai Ping , Qiao Qichuan , Li Tingxin
Published: October 2020

Background

In China, many people are regarded suitable for participating in regular physical examination for diagnosis and prevention of diseases. Some simplified food frequency questionnaires have been designed and used; however, the accuracy of the questionnaire is absent. This study aimed to examine the reliability and validity of simplified food frequency questionnaire (SFFQ) used among adults undergoing physical examination in southwest region of China.

Methods

This was a cross-sectional study conducted among physical health examination adults in the Southwest region of China. A total of 239 participants aged 20–65 were included from February 2019 to June 2019. The performance of SFFQ was evaluated by means of a three-day 24-h dietary record (3R24). The relative validity and agreement was assessed by Pearson’s correlation and intra-class correlation coefficients (ICC), respectively.

Results

The median energy-adjusted ICC of food groups between SFFQ2 and SFFQ1 was 0.59 (range: 0.49–0.73) and the ICC of nutrients was 0.47(range: 0.39–0.76). The Pearson correlation showed a valid comparisons between SFFQ1 and 3R24, ranging from -0.086 to 0.93 for food and 0.21 to 0.71 for nutrition, respectively. The energy-adjustment slightly increased the correlation coefficients.

Conclusions

The reliability and validity of SFFQ was acceptable, and it could be an appropriate dietary assessment tool for the future epidemiological studies conducted among physical health examination adults of southwest China.

Trial registration

CHiCTR, ChiCTR1900020934, Registered 22 January 2019, https://www.chictr.org.cn/edit.aspx?pid=35414&htm=4.
Sex differences in the management of persons with dementia following a subnational primary care policy intervention
Authors: Sourial Nadia , Arsenault-Lapierre Geneviève , Margo-Dermer Eva , Henein Mary , Vedel Isabelle
Published: October 2020

Background

The influence of sex and gender on the risk of dementia, its clinical presentation and progression is increasingly being recognized. However, current dementia strategies have not explicitly considered sex and gender differences in the management of dementia to ensure equitable care. The objective of this study was to examine the moderating effect of sex on the quality of care following the implementation of the Quebec Alzheimer Plan (QAP).

Methods

We conducted a secondary analysis of the evaluation of the QAP consisting of a retrospective chart review of 945 independent, randomly-selected patient charts of males and females 75+ years old with dementia and a visit to one of 13 participating Family Medicine Groups before (October 2011–July 2013) and after (October 2014 – July 2015). The quality of dementia care score, based on Canadian and international recommendations and consensus guidelines, consisted of documented assessments in 10 domains. We used a mixed linear regression model to measure the interaction between sex and the implementation of the QAP on the quality of dementia care score, adjusting for age and number of medications.

Results

We found that improvements in the quality of dementia care following the QAP were larger for men than women (mean difference = 4.97; 95%CI: 0.08, 9.85). We found that men had a larger improvement in four indicators (driving assessments, dementia medication management, Alzheimer Society referrals, and functional status evaluation), while women had a smaller improvement in three (home care needs, behavioural and psychological symptoms of dementia, and weight). Men were prescribed fewer anticholinergics post-QAP, while women were prescribed more. Cognitive testing improved in men but decreased for women following the QAP; the opposite was observed for caregiver needs.

Conclusion

While the overall quality of care improved after the implementation of the QAP, this study reveals differences in dementia management between men and women. While we identified areas of inequalities in the care received, it is unclear whether this represents inequities in access to care and health outcomes. Future research should focus on better understanding sex and gender-specific needs in dementia to bridge this gap and better inform dementia strategies.
Cross-cultural adaptation and construct validity of the German version of the Adult Social Care Outcomes Toolkit for service users (German ASCOT)
Authors: Trukeschitz Birgit , Litschauer Judith , Hajji Assma , Kieninger Judith , Schoch Adiam , Malley Juliette , Rand Stacey , Linnosmaa Ismo , Forder Julien
Published: October 2020

Background

There has been considerable interest in using the Adult Social Care Outcomes Toolkit (ASCOT), developed in England, to measure quality-of-life outcomes of long-term care (LTC-QoL) service provision in national and cross-national studies.

Objectives

The aim of this study was to translate and culturally adapt the original ASCOT service user measure into German and to evaluate its content and construct validity in Austrian home care service users.

Methods

The translation and cultural adaptation process followed the ISPOR TCA guidelines. We used qualitative data from six cognitive debriefing interviews with Austrian recipients of home care services to assess linguistic and content validity. In addition, cross-sectional survey data (n = 633) were used to evaluate construct validity by testing hypothesized associations established in a previous study for the original English ASCOT service user instrument.

Results

Cognitive debriefing interviews confirmed that the German adaptation of the ASCOT service user instrument was understood as intended, although two domains (‘Control over daily life’ and ‘Dignity’) and selected phrases of the response options were challenging to translate into German. All ASCOT domains were statistically significantly associated with related constructs and sensitive to service user sub-group differences.

Conclusions

We found good evidence for a valid cross-cultural adaptation of the German version of ASCOT for service users. The analysis also supports the construct validity of the translated instrument and its use in evaluations of QoL-effects of LTC service provision in German-speaking countries. Further research on the reliability and feasibility in different care settings is encouraged.
Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US
Authors: Thokala Praveen , Stevenson Matt , Kumar Varun M. , Ren Shijie , Ellis Alexandra G. , Chapman Richard H.
Published: October 2020

Background

Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life expectancy in the absence of treatment. Nusinersen is a disease-modifying therapy for patients with SMA.

Objective

The aim of this study was to estimate the cost-effectiveness of nusinersen compared to best supportive care (BSC) in patients diagnosed with infantile-onset SMA in the US.

Methods

A de novo economic model was developed with the following health states: “permanent ventilation”, “not sitting”, “sitting”, “walking”, and “death”. Short-term data were sourced from the pivotal clinical trials and studies of nusinersen (ENDEAR and SHINE). Motor function milestones achieved at the end of follow-up in the clinical trials were assumed to be sustained until death. Mortality risks were based on survival modelling of relevant published Kaplan–Meier data. Costs, life years (LYs), and quality-adjusted life years (QALYs) were discounted at 3% per annum, and the analyses were performed from a US health care sector perspective. Scenario analyses and sensitivity analyses were conducted to assess the robustness of the results to key parameters.

Results

In our base-case analysis, nusinersen treatment achieves greater QALYs and more LYs (3.24 and 7.64, respectively) compared with BSC (0.46 QALYs and 2.40 LYs, respectively), resulting in an incremental cost per QALY gained of approximately $1,112,000 and an incremental cost per LY gained of $590,000 for nusinersen compared to BSC. The incremental cost effectiveness ratios did not fall below $990,000 per QALY gained in scenario and sensitivity analyses. Results were most sensitive to the length of survival, background health care costs, and utility in the “not sitting” and “sitting” health states.

Conclusions

The estimated incremental cost-effectiveness of nusinersen from a US health care sector perspective exceeded traditional cost-effectiveness thresholds. Cost-effectiveness was dependent on assumptions made regarding survival, costs, utilities, and whether the motor function milestones were sustained over lifetime. Given the relatively short-term effectiveness data available for the treatment, a registry to collect long-term data of infantile-onset SMA patients is recommended.
H. pylori modulates DC functions via T4SS/TNFα/p38-dependent SOCS3 expression
Authors: Sarajlic Muamera , Neuper Theresa , Vetter Julia , Schaller Susanne , Klicznik Maria M. , Gratz Iris K. , Wessler Silja , Posselt Gernot , Horejs-Hoeck Jutta
Published: October 2020

Background

Helicobacter pylori(H. pylori) is a gram-negative bacterium that chronically infects approximately 50% of the world’s human population. While in most cases the infection remains asymptomatic, 10% of infected individuals develop gastric pathologies and 1–3% progress to gastric cancer. AlthoughH. pyloriinduces severe inflammatory responses, the host’s immune system fails to clear the pathogen andH. pylorican persist in the human stomach for decades. As suppressor of cytokine signaling (SOCS) proteins are important feedback regulators limiting inflammatory responses, we hypothesized thatH. pyloricould modulate the host’s immune responses by inducing SOCS expression.

Methods

The phenotype of human monocyte-derived DCs (moDCs) infected withH. pyloriwas analyzed by flow cytometry and multiplex technology. SOCS expression levels were monitored by qPCR and signaling studies were conducted by means of Western blot. For functional studies, RNA interference-based silencing ofSOCS1–3and co-cultures with CD4+T cells were performed.

Results

We show thatH. pyloripositive gastritis patients express significantly higherSOCS3, but notSOCS1andSOCS2, levels compared toH. pylorinegative patients. Moreover, infection of human moDCs withH. pylorirapidly inducesSOCS3expression, which requires the type IV secretion system (T4SS), release of TNFα, and signaling via the MAP kinase p38, but appears to be independent of TLR2, TLR4, MEK1/2 and STAT proteins. Silencing ofSOCS3expression in moDCs prior toH. pyloriinfection resulted in increased release of both pro- and anti-inflammatory cytokines, upregulation of PD-L1, and decreased T-cell proliferation.

Conclusions

This study shows thatH. pyloriinduces SOCS3 via an autocrine loop involving the T4SS and TNFα and p38 signaling. Moreover, we demonstrate that high levels of SOCS3 in DCs dampen PD-L1 expression on DCs, which in turn drives T-cell proliferation.
Zero problems with compositional data of physical behaviors: a comparison of three zero replacement methods
Authors: Rasmussen Charlotte Lund , Palarea-Albaladejo Javier , Johansson Melker Staffan , Crowley Patrick , Stevens Matthew Leigh , Gupta Nidhi , Karstad Kristina , Holtermann Andreas
Published: October 2020

Background

Researchers applying compositional data analysis to time-use data (e.g., time spent in physical behaviors) often face the problem of zeros, that is, recordings of zero time spent in any of the studied behaviors. Zeros hinder the application of compositional data analysis because the analysis is based on log-ratios. One way to overcome this challenge is to replace the zeros with sensible small values. The aim of this study was to compare the performance of three existing replacement methods used within physical behavior time-use epidemiology: simple replacement, multiplicative replacement, and log-ratio expectation-maximization (lrEM) algorithm. Moreover, we assessed the consequence of choosing replacement values higher than the lowest observed value for a given behavior.

Method

Using a complete dataset based on accelerometer data from 1310 Danish adults as reference, multiple datasets were simulated across six scenarios of zeros (5–30% zeros in 5% increments). Moreover, four examples were produced based on real data, in which, 10 and 20% zeros were imposed and replaced using a replacement value of 0.5 min, 65% of the observation threshold, or an estimated value below the observation threshold. For the simulation study and the examples, the zeros were replaced using the three replacement methods and the degree of distortion introduced was assessed by comparison with the complete dataset.

Results

The lrEM method outperformed the other replacement methods as it had the smallest influence on the structure of relative variation of the datasets. Both the simple and multiplicative replacements introduced higher distortion, particularly in scenarios with more than 10% zeros; although the latter, like the lrEM, does preserve the ratios between behaviors with no zeros. The examples revealed that replacing zeros with a value higher than the observation threshold severely affected the structure of relative variation.

Conclusions

Given our findings, we encourage the use of replacement methods that preserve the relative structure of physical behavior data, as achieved by the multiplicative and lrEM replacements, andto avoidsimple replacement. Moreover, we do not recommend replacing zeros with values higher than the lowest observed value for a behavior.
The optimal regimen of oral tranexamic acid administration for primary total knee/hip replacement: a meta-analysis and narrative review of a randomized controlled trial
Authors: Ye Wei , Liu Yafang , Liu Wei Feng , Li Xiao Long , Shao Jianshu
Published: October 2020

Background

Oral tranexamic acid (TXA) has been demonstrated to reduce the blood loss in primary total knee and hip arthroplasty, but the optimal regimen of oral TXA administration is still unknown. This study aimed to find the best number of administrations of oral TXA for primary total knee and hip arthroplasty.

Methods

The PubMed, Embase, and Cochrane Library databases were searched for relevant studies published before March 20, 2020. Studies clearly reporting a comparison of multiple administrations of oral TXA for total hip/knee replacement were included, and the total blood loss (TBL), intraoperative blood loss (IBL), decline in hemoglobin (DHB), deep vein thrombosis (DVT), intramuscular venous thrombosis (IVT), length of hospital stay (LOS), and transfusion rate were evaluated. The weighted mean differences and relative risks were calculated using a fixed effects or random effects model.

Results

Nine studies involving 1678 patients were included in this meta-analysis (TXA 1363 (one administration, 201; two administrations, 496; three administrations, 215; four administrations, 336; five administrations, 115); placebo 315); the results show that compared with placebo groups, oral TXA could significantly reduce the TBL, IBL, DHB, LOS, and transfusion rate. In addition, the incidences of IVT and DVT were similar between the TXA and placebo groups. Moreover, two administrations of oral TXA significantly reduced the TBL and DHB compared with one administration, three administrations of oral TXA were better than two administrations, and four administrations of oral TXA were better than three administrations.

Conclusion

Our results suggested that oral TXA could significantly reduce the blood loss and the length of hospital stay but could not increase the incidence of DVT and IVT for total joint replacement patients; additionally, the effectiveness of oral TXA administration increased as the number of administrations increased.
Long noncoding RNA RP11-757G1.5 sponges miR-139-5p and upregulates YAP1 thereby promoting the proliferation and liver, spleen metastasis of colorectal cancer
Authors: Zhu Xiaojian , Bu Fanqin , Tan Ting , Luo Qilin , Zhu Jinfeng , Lin Kang , Huang Jun , Luo Chen , Zhu Zhengming
Published: October 2020

Background

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) acting as crucial regulators in tumorigenesis. However, its biological functions of lncRNAs in colorectal cancer (CRC) have not been systematically clarified.

Methods

An unbiased screening was performed to identify disregulated lncRNAs revealed to be implicated in CRC carcinogenesis according to an online-available data dataset. In situ hybridization (ISH), RT-qPCR and RNA fluorescence in situ hybridization (RNA-FISH) were applied to detect RP11-757G1.5 expression in CRC tissues and cell lines. The associations of RP11-757G1.5 with clinicopathological characteristics were analyzed. Their effects on prognosis were analyzed by the Kaplan-Meier analysis, Log-rank test, Univariate and Multivariate Cox regression analysis. The potential biological function of RP11-757G1.5 in CRC was investigated by Colony formation, Edu cell proliferation, Flow cytometry, Wound healing and Transwell assays. Bioinformatics binding site analysis, Luciferase reporter assay, Ago2 immunoprecipitation assays, RNA pull-down assay, RT-qPCR and Western blotting were utilized to demonstrate the mechanism of RP11-757G1.5 acts as a molecular sponge of miR-139-5p to regulate the expression of YAP1. Finally, we further explore the potential role of RP11-757G1.5 in CRC orthotopic xenografts in vivo.

Results

We discovered a novel oncogenic lncRNA RP11-757G1.5, that was overexpressed in CRC tissues, especially in aggressive cases. Moreover, up-regulation of RP11-757G1.5 strongly correlated with poor clinical outcomes of patients with CRC. Functional analyses revealed that RP11-757G1.5 promoted cell proliferation in vitro and in vivo. Furthermore, RP11-757G1.5 stimulated cell migration and invasion in vitro and in vivo. Mechanistic studies illustrated that RP11-757G1.5 regulated the expression of YAP1 through sponging miR-139-5p and inhibiting its activity thereby promoting CRC progression and development.

Conclusions

Altogether, these results reveal a novel RP11-757G1.5/miR-139-5p/YAP1 regulatory axis that participates in CRC carcinogenesis and progression.
FPIES in exclusively breastfed infants: two case reports and review of the literature
Authors: Baldo Francesco , Bevacqua Martina , Corrado Cristiana , Nisticò Daniela , Cesca Laura , Declich Valentina , Dall’Amico Roberto , Barbi Egidio
Published: October 2020

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non IgE-mediated food allergy that generally affects children in the first year of life. Usually symptoms break out when formula milk or solid foods are introduced for the first time but they might also appear in exclusively breastfed infants, since the trigger elements, especially cow’s milk proteins, can be conveyed by maternal milk as well. FPIES in exclusively breastfed babies is a very rare clinical condition and only few cases have been reported in the medical literature.

Case presentation

We describe two cases of FPIES in exclusively breastfed babies. The first one is a two-month-old infant with a brief history of vomit and diarrhea that presented to the Emergency Department in septic-like conditions. The main laboratory finding was a significant increase in methemoglobin (13%). Clinically, we noted that, when breastfeeding was suspended, diarrhea drastically improved, and vice versa when maternal milk was reintroduced. An amino acid-based formula allowed a complete normalization of the symptoms. The second one is a three-month-old infant admitted for a 3 days history of persistent vomit and diarrhea. Blood tests showed a raised level of methemoglobin (7%). An esophagogastroduodenoscopy was performed and biopsies showed an eosinophilic infiltration of the duodenal mucosa. A maternal exclusion diet and an amino acid-based formula allowed a rapid regularization of the bowel function.

Conclusions

We searched all the cases of FPIES in exclusively breastfed babies reported in the medical literature, identifying eight patients, with an average age of 3 months (range 15 days – 6 months). The majority of the cases were initially diagnosed as gastroenteritis or sepsis, five cases were characterized by an acute on chronic scenario and cow’s milk was the most frequently involved food. Methemoglobin was never tested. An oral food challenge test was performed in two patients.

FPIES in exclusively breastfed infants is a rare condition that, in the presence of compatible history and symptoms, should be considered also in exclusively breastfed babies. The evaluation of methemoglobin can simplify the diagnostic process.
Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review
Authors: Ehaideb Salleh N. , Abdullah Mashan L. , Abuyassin Bisher , Bouchama Abderrezak
Published: October 2020

Background

Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19.

Methods

We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19.

Result

Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy.

Conclusions

Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.
AlphaBeta: computational inference of epimutation rates and spectra from high-throughput DNA methylation data in plants
Authors: Shahryary Yadollah , Symeonidi Aikaterini , Hazarika Rashmi R. , Denkena Johanna , Mubeen Talha , Hofmeister Brigitte , van Gurp Thomas , Colomé-Tatché Maria , Verhoeven Koen J.F. , Tuskan Gerald , Schmitz Robert J. , Johannes Frank
Published: October 2020

Stochastic changes in DNA methylation (i.e., spontaneous epimutations) contribute to methylome diversity in plants. Here, we describe AlphaBeta, a computational method for estimating the precise rate of such stochastic events using pedigree-based DNA methylation data as input. We demonstrate how AlphaBeta can be employed to study transgenerationally heritable epimutations in clonal or sexually derived mutation accumulation lines, as well as somatic epimutations in long-lived perennials. Application of our method to published and new data reveals that spontaneous epimutations accumulate neutrally at the genome-wide scale, originate mainly during somatic development and that they can be used as a molecular clock for age-dating trees.
Vectors, molecular epidemiology and phylogeny of TBEV in Kazakhstan and central Asia
Authors: Abdiyeva Karlygash , Turebekov Nurkeldi , Yegemberdiyeva Ravilya , Dmitrovskiy Andrey , Yeraliyeva Lyazzat , Shapiyeva Zhanna , Nurmakhanov Talgat , Sansyzbayev Yerlan , Froeschl Guenter , Hoelscher Michael , Zinner Josua , Essbauer Sandra , Frey Stefan
Published: October 2020

Background

In the South of Kazakhstan, Almaty Oblastʼ (region) is endemic for tick-borne encephalitis, with 0.16–0.32 cases/100,000 population between 2016–2018. The purpose of this study was to determine the prevalence and circulating subtypes of tick-borne encephalitis virus (TBEV) in Almaty Oblastʼ and Kyzylorda Oblastʼ.

Methods

In 2015 we investigated 2341 ticks from 7 sampling sites for the presence of TBEV. Ticks were pooled in 501 pools and isolated RNA was tested for the presence of TBEV by RT-qPCR. For the positive samples, the E gene was amplified, sequenced and a phylogenetic analysis was carried out.

Results

A total of 48 pools were TBEV-positive by the RT-qPCR. TBEV-positive ticks were only detected in three districts of Almaty Oblastʼ and not in Kyzylorda Oblastʼ. The positive TBEV pools were found withinIxodes persulcatus,Haemaphysalis punctataandDermacentor marginatus. These tick species prevailed only in Almaty Oblastʼ whereas in Kyzylorda OblastʼHyalomma asiaticumandD. marginatusare endemic. The minimum infection rates (MIR) in the sampling sites were 4.4% in Talgar, 2.8% in Tekeli and 1.1% in Yenbekshikazakh, respectively. The phylogenetic analysis of the generated sequences indicates that TBEV strains found in Almaty Oblastʼ clusters in the Siberian subtype within two different clades.

Conclusions

We provided new data about the TBEV MIR in ticks in Almaty Oblastʼ and showed that TBEV clusters in the Siberian Subtype in two different clusters at the nucleotide level. These results indicate that there are different influences on the circulating TBEV strains in south-eastern Kazakhstan. These influences might be caused by different routes of the virus spread in ticks which might bring different genetic TBEV lineages to Kazakhstan. The new data about the virus distribution and vectors provided here will contribute to an improvement of monitoring of tick-borne infections and timely anti-epidemic measures in Kazakhstan.
Cellular and molecular changes and immune response in the intestinal mucosa during Trichinella spiralis early infection in rats
Authors: Saracino María Priscila , Vila Cecilia Celeste , Cohen Melina , Gentilini María Virginia , Falduto Guido Hernán , Calcagno Marcela Adriana , Roux Estela , Venturiello Stella Maris , Malchiodi Emilio Luis
Published: October 2020

Background:

The main targets of the host’s immune system inTrichinella spiralisinfection are the adult worms (AW), at the gut level, and the migrant or newborn larvae (NBL), at systemic and pulmonary levels. Most of the studies carried out in the gut mucosa have been performed on the Payer’s patches and/or the mesenteric lymph nodes but not on the lamina propria, therefore, knowledge on the gut immune response againstT. spiralisremains incomplete.

Methods

This study aimed at characterizing the early mucosal immune response againstT. spiralis, particularly, the events taking place between 1 and 13 dpi. For this purpose, Wistar rats were orally infected with muscle larvae ofT. spiralisand the humoral and cellular parameters of the gut immunity were analysed, including the evaluation of the ADCC mechanism exerted by lamina propria cells.

Results

A marked inflammation and structural alteration of the mucosa was found. The changes involved an increase in goblet cells, eosinophils and mast cells, and B and T lymphocytes, initially displaying a Th1 profile, characterised by the secretion of IFN-γ and IL-12, followed by a polarization towards a Th2 profile, with a marked increase in IgE, IgG1, IL-4, IL-5 and IL-13 levels, which occurred once the infection was established. In addition, the helminthotoxic activity of lamina propria cells demonstrated the role of the intestine as a place of migrant larvae destruction, indicating that not all the NBLs released in the gut will be able to reach the muscles.

Conclusions

The characterization of the immune response triggered in the gut mucosa duringT. spiralisinfection showed that not only an effector mechanism is directed toward the AW but also towards the NBL as a cytotoxic activity was observed against NBL exerted by lamina propria cells.
Efficacy of semi-annual therapy of an extended-release injectable moxidectin suspension and oral doxycycline in Dirofilaria immitis naturally infected dogs
Authors: Alberigi Bruno , Fernandes Julio I. , Paiva Jonimar P. , Mendes-de-Almeida Flavya , Knackfuss Fabiana , Merlo Alexandre , Labarthe Norma
Published: October 2020

Background

Dirofilaria immitisis a life-threatening nematode spreading globally. Arsenical treatment is currently recommended for removal of adult worms. However, arsenical treatment is not available in some countries, and there are dogs that cannot tolerate the rapid kill of adult worms; therefore, alternative adulticide slow-kill treatments are needed. Criticisms against the use of these alternative protocols include the potential for allowing disease to progress and for the development of ML-resistant worms.

Methods

The efficacy of a protocol that includes semi-annual doses (i.e. every 6 months) of commercially available extended-release injectable moxidectin suspension (ProHeart®SR-12) with 30-day oral administration of doxycycline was studied in 20 dogs with naturally occurringD. immitisinfections. Each dog received treatment with ProHeart®SR-12 (0.5 mg moxidectin/kg) by subcutaneous injection and oral doxycycline (10 mg/kg/bid × 30 days) every 6 months until two consecutive negative antigen test results were obtained. Pulmonary and cardiac evaluations were performed by radiographic and echocardiographic parameters. Physical examinations, complete blood counts, clinical chemistry profiles, microfilariae and antigen tests were performed periodically.

Results

At enrollment, all dogs were positive forD. immitisantigen and 18 were microfilaremic. On day 30, microfilaremia counts decreased, and all dogs became amicrofilaremic by day 150. On day 180, 11 dogs were antigen-negative, and 7 more became negative by day 360. The two remaining antigen-positive dogs converted to negative by day 540 or 810. All antigen tests performed 180 days after the first negative test were negative. There was no decline in cardiac performance of the dogs throughout the study. Overall, pulmonary clinical conditions, presence of worms by echocardiography, and enlargement of caudal and main pulmonary arteries improved after treatment. Physical examinations, complete blood count results, and clinical chemistry profiles were within normal reference values. Respiratory conditions were improved, no damage to the heart was observed, and the treatment protocol was well tolerated by the animals.

Conclusions

This alternative adulticide treatment was efficacious and well tolerated in naturally infected dogs. The injectable formulation provides the advantage of having veterinarians able to administer, monitor, and assess the efficacy and condition of the dog throughout the treatment and post-treatment periods.
Evaluating the effects of behavior change training on the knowledge, confidence and skills of sport and exercise science students
Authors: Matthews James , Hall Amanda M. , Keogh Alison
Published: October 2020

Background

Behavior change interventions have the potential to have a transformative effect on the health of populations. Allied health professionals have a key role to play in delivering these interventions. However, traditionally undergraduate allied health professional programs have not had a behavior change focus. The aim of this study was to assess the effectiveness of a training program on sport and exercise science students’ knowledge, confidence and skills in the provision of behavior change support.

Method

A mixed method convergent design was used to address the research question. Fifteen sport and exercise science students took part in a training program consisting of seven 90-min weekly face to face group sessions. Student satisfaction with training methods was assessed. Pre-to-post training changes in students’ confidence and knowledge in the provision of behavior change support was evaluated. Delivery of behavior change support was assessed by an audio recorded role-play rated by an expert using the Health Care Climate Questionnaire, and an adapted version of the Communication Evaluation in Rehabilitation Tool. Students also completed a reflective assignment.

Results

Students were satisfied with the training. There were increases in students’ confidence and knowledge of certain behavior change components post-training but not behavior change techniques. Students delivered behavior change support in a broadly needs supportive manner. The reflective assignment showed that students found particular behavior change strategies difficult to implement.

Conclusion

It is feasible to train undergraduate students in particular components of behavior change support. Academic institutions should embed behavior change training into the allied health professional curriculum to ensure graduates are job ready with the knowledge, confidence and skills to support health related behavior change within the wider health system.
Dissimilarity of microbial diversity of pond water, shrimp intestine and sediment in Aquamimicry system
Authors: Zeng Shenzheng , Khoruamkid Sukontorn , Kongpakdee Warinphorn , Wei Dongdong , Yu Lingfei , Wang Hao , Deng Zhixuan , Weng Shaoping , Huang Zhijian , He Jianguo , Satapornvanit Kriengkrai
Published: October 2020

The Pacific white shrimp, with the largest production in shrimp industry, has suffered from multiple severe viral and bacterial diseases, which calls for a more reliable and environmentally friendly system to promote shrimp culture. The “Aquamimicry system”, mimicking the nature of aquatic ecosystems for the well-being of aquatic animals, has effectively increased shrimp production and been adapted in many countries. However, the microbial communities in the shrimp intestine and surrounding environment that act as an essential component in Aquamimicry remain largely unknown. In this study, the microbial composition and diversity alteration in shrimp intestine, surrounding water and sediment at different culture stages were investigated by high throughput sequencing of 16S rRNA gene, obtaining 13,562 operational taxonomic units (OTUs). Results showed that the microbial communities in shrimp intestine and surrounding environment were significantly distinct from each other, and 23 distinguished taxa for each habitat were further characterized. The microbial communities differed significantly at different culture stages, confirmed by a great number of OTUs dramatically altered during the culture period. A small part of these altered OTUs were shared between shrimp intestine and surrounding environment, suggesting that the microbial alteration of intestine was not consistent with that of water and sediment. Regarding the high production of Aquamimicry farm used as a case in this study, the dissimilarity between intestinal and surrounding microbiota might be considered as a potential indicator for healthy status of shrimp farming, which provided hints on the appropriate culture practices to improve shrimp production.
Therapeutic interventions in Australian primary care, youth mental health settings for young people with borderline personality disorder or borderline traits
Authors: O’Dwyer Nikki , Rickwood Debra , Buckmaster Dean , Watsford Clare
Published: October 2020

Background

This study aimed to investigate what therapeutic interventions were being applied by clinicians working with young people with a diagnosis of Borderline Personality Disorder or borderline traits in Australian primary mental health care settings. Given the current lack of evidence-based guidelines for treatment with this client population, investigating what is being implemented is needed. The study also aimed to determine whether the interventions clinicians are using are effective in reducing distress and increasing functioning for these clients.

Methods

Participant data came from the national minimum data set for headspace youth mental health centers across Australia. Young people’s data were included in the study if the young person was diagnosed with Borderline Personality Disorder or borderline traits during their first episode of care (N = 701). Clinician data that indicated the type of intervention used at each client session and outcome measures routinely captured were analyzed to determine interventions used and outcomes achieved.

Results

Results demonstrated that CBT was the most frequently used modality of intervention followed by supportive counselling and IPT, but that most clients received a variety of intervention types. There were no or only weak relationships between changes in outcomes and the amount of any type of intervention that was provided. No significant relationship was found with the amount of CBT a client received and changes in symptoms or functioning, despite being the most commonly employed modality.

Conclusions

The study highlights the need for evidence-based treatment guidelines for early intervention in young people with borderline personality disorder traits.
Real-time monitoring of traffic parameters
Authors: Khazukov Kirill , Shepelev Vladimir , Karpeta Tatiana , Shabiev Salavat , Slobodin Ivan , Charbadze Irakli , Alferova Irina
Published: October 2020

This study deals with the problem of rea-time obtaining quality data on the road traffic parameters based on the static street video surveillance camera data. The existing road traffic monitoring solutions are based on the use of traffic cameras located directly above the carriageways, which allows one to obtain fragmentary data on the speed and movement pattern of vehicles. The purpose of the study is to develop a system of high-quality and complete collection of real-time data, such as traffic flow intensity, driving directions, and average vehicle speed. At the same time, the data is collected within the entire functional area of intersections and adjacent road sections, which fall within the street video surveillance camera angle. Our solution is based on the use of the YOLOv3 neural network architecture and SORT open-source tracker. To train the neural network, we marked 6000 images and performed augmentation, which allowed us to form a dataset of 4.3 million vehicles. The basic performance of YOLO was improved using an additional mask branch and optimizing the shape of anchors. To determine the vehicle speed, we used a method of perspective transformation of coordinates from the original image to geographical coordinates. Testing of the system at night and in the daytime at six intersections showed the absolute percentage accuracy of vehicle counting, of no less than 92%. The error in determining the vehicle speed by the projection method, taking into account the camera calibration, did not exceed 1.5 km/h.
Biomechanical comparison of vertical suture techniques for repairing radial meniscus tear
Authors: Hang Guanqi , Yew Andy Khye Soon , Chou Siaw Meng , Wong Yoke Rung , Tay Shian Chao , Lie Denny Tijauw Tjoen
Published: October 2020

Purpose

The aim of this study was to (1) develop suture techniques in repairing radial meniscal tear; (2) to compare the biomechanical properties of the proposed repair techniques with the conventional double horizontal technique.

Methods

Thirty-six fresh-frozen porcine medial menisci were randomly assigned into four groups and a complete tear was made at the midline of each meniscus. The menisci were subsequently repaired using four different repair techniques: double vertical (DV), double vertical cross (DVX), hybrid composing one vertical and one horizontal stitch, and conventional double horizontal (DH) suture technique with suturing parallel to the tibia plateau. The conventional double horizontal group was the control. The repaired menisci were subjected to cyclic loading followed by the load to failure testing. Gap formation and strength were measured, stiffness was calculated, and mode of failure was recorded.

Results

Group differences in gap formation were not statistically significant at 100 cycles (p = .42), 300 cycles (p = .68), and 500 cycles (p = .70). A trend was found toward higher load to failure in DVX (276.8 N, p < .001), DV (241.5 N, p < .001), and Hybrid (237.6 N, p < .001) compared with DH (148.5 N). Stiffness was also higher in DVX (60.7 N/mm, p < .001), DV (55.3 N/mm, p < .01), and Hybrid (52.1 N/mm, p < .01), than DH group (30.5 N/mm). Tissue failure was the only failure mode observed in all specimens.

Conclusion

Our two proposed vertical suture techniques, as well as the double vertical technique, had superior biomechanical properties than the conventional technique as demonstrated by higher stiffness and higher strength.
Decolorization and detoxification of triphenylmethane dyes by isolated endophytic fungus, Bjerkandera adusta SWUSI4 under non-nutritive conditions
Authors: Gao Tiancong , Qin Dan , Zuo Shihao , Peng Yajun , Xu Jieru , Yu Baohong , Song Hongchuan , Dong Jinyan
Published: October 2020

Biodecolorization by microorganisms is a potential treatment technique because they seem to be environmentally safe. In the present study, the decolorization and detoxification of cotton blue, crystal violet, malachite green and methyl violet by endophytic fungi were investigated. Preliminary screening result indicated that SWUSI4, identified as Bjerkandera adusta, demonstrated the best decolorization for the four TPM dyes within 14 days. Furthermore, optimization result demonstrated the decolorization rate could reach above 90% at 24 h by live cells of isolate SWUSI4 when 4 g biomass was added into 100-mL dyes solution with the concentration 50 mg/L and shaking (150 rpm) conditions. Moreover, decolorization mechanism analysis shows that the decolorization was caused by the isolate SWUSI4 that mainly includes both absorption of biomass and/or degradation of enzymes. Biosorption of dyes was attributed to binding to hydroxyl, amino, phosphoryl alkane, and ester–lipids groups based on Fourier transform infrared (FTIR) analyses. The biodegradation potential of SWUSI4 was further suggested by the change of peaks in the ultraviolet–visible (UV–vis) spectra and detection of manganese peroxidase and lignin peroxidase activities. Finally, the phytotoxicity test confirmed that the toxicity of TPM dyes after treatment with SWUSI4 was significantly lower than that before treatment. These results indicate that an endophytic SWUSI4 could be used as a potential TPM dyes adsorption and degradation agent, thus facilitating the study of the plant–endophyte symbiosis in the bioremediation processes.