bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of microglia/macrophages in the granuloma microenvironment of encephalic schistosomiasis japonicum
Authors: Tan Zhoubin , Lei Zhuowei , Zhang Zhuo , Zhang Huaqiu , Shu Kai , Hu Feng , Lei Ting
Published: December 2019

Background

Egg-induced immune response and granuloma formation are thought to be the basis of central nervous system (CNS)-related clinical symptoms of Schistosoma japonicum. Microglia/macrophages are the major immune cells involved in detection and subsequent elimination of pathogens and injured tissue in the brain. However, little is known about their role in the pathogenesis of neuroschistosomiasis. The main purpose of the study is to clarify the pathological involvement of microglia/macrophages in the pathogenesis of neuroschistosomiasis (NS).

Methods

Staining techniques were applied to the granuloma tissues excised from 4 patients, as well as mice model which was established by microinjecting viable S. japonicum eggs into the brain. Clinical features of the patients and neurological symptoms in mice were also collected and analyzed in terms of their correlation with microglia/macrophages.

Results

Microglia/macrophages constituted the major portions of the granulomas surrounding the eggs in both all human cases and S. japonicum egg-injected mice. Granuloma persisted in all patients accompanied by unremitted neurological symptoms, while in mice granuloma formation initiated on day 3, peaked on day 7 and subsided on day 30 post injection with S. japonicum eggs. No neurological abnormalities were observed in egg-injected mice except for significant weight decrease on day 3 compared with saline-injected control. M1 polarization of microglia/macrophages was confirmed in egg-injected mice 3 days post injection and in all human cases. M2 polarization was absent in human patients despite the duration of complaints but dominated in the whole progression of egg-induced pathology in mice until the elimination of eggs and subsidence of neuroinflammation on day 30 post injection.

Conclusions

Microglia/macrophages participated actively in the granuloma microenvironment of encephalic schistosomiasis japonicum in both human and mice. The polarization pattern of microglia/macrophages coincided with the symptomatic features in human cases and S. japonicum egg-injected mice, indicating M2 instead of M1 activation as a probably more important mediator in the battle against egg-induced pathology and concomitant manifestations. These new findings will shed light on the pathogenesis of NS from a brand-new perspective, and may contribute to the immunotherapy development for such disease, favoring perhaps M2 polarization of microglia/macrophages as a feasible strategy.
Women’s psychosocial outcomes following an emergency caesarean section: A systematic literature review
Authors: Benton Madeleine , Salter Amy , Tape Nicole , Wilkinson Chris , Turnbull Deborah
Published: December 2019

Background

Given the sudden and unexpected nature of an emergency caesarean section (EmCS) coupled with an increased risk of psychological distress, it is particularly important to understand the psychosocial outcomes for women. The aim of this systematic literature review was to identify, collate and examine the evidence surrounding women’s psychosocial outcomes of EmCS worldwide.

Methods

The electronic databases of EMBASE, PubMed, Scopus, and PsycINFO were searched between November 2017 and March 2018. To ensure articles were reflective of original and recently published research, the search criteria included peer-reviewed research articles published within the last 20 years (1998 to 2018). All study designs were included if they incorporated an examination of women’s psychosocial outcomes after EmCS. Due to inherent heterogeneity of study data, extraction and synthesis of both qualitative and quantitative data pertaining to key psychosocial outcomes were organised into coherent themes and analysis was attempted.

Results

In total 17,189 articles were identified. Of these, 208 full text articles were assessed for eligibility. One hundred forty-nine articles were further excluded, resulting in the inclusion of 66 articles in the current systematic literature review. While meta-analyses were not possible due to the nature of the heterogeneity, key psychosocial outcomes identified that were negatively impacted by EmCS included post-traumatic stress, health-related quality of life, experiences, infant-feeding, satisfaction, and self-esteem. Post-traumatic stress was one of the most commonly examined psychosocial outcomes, with a strong consensus that EmCS contributes to both symptoms and diagnosis.

Conclusions

EmCS was found to negatively impact several psychosocial outcomes for women in particular post-traumatic stress. While investment in technologies and clinical practice to minimise the number of EmCSs is crucial, further investigations are needed to develop effective strategies to prepare and support women who experience this type of birth.
Prevalence of positional skull deformities in 530 premature infants with a corrected age of up to 6 months: a multicenter study
Authors: Yang Wang , Chen Jianping , Shen Wenzhi , Wang Chengju , Wu Zhifeng , Chang Qing , Li Wenzao , Lv Kuilin , Pan Qiuming , Li Hongxia , Ha Duyao , Zhang Yuping
Published: December 2019

Background

Positional deformities (PD) are common during early infancy. Severe cases may result in facial abnormalities and be associated with delayed neurological development in infants. The earlier the detection of PD, the better the intervention effect and the lower the cost of treatment. Currently, there are many studies on PD in Europe and the United States. However, in China, there is little data on the basic metrics and incidence of PD. Premature infants have a high risk of PD. However, there are few studies on PD in premature infants globally, and none in Asia. This study aimed to investigate PD and its characteristics inpremature infants to help its early detection and intervention and thus improve the quality of life for premature infants.

Methods

We analyzed 530 preterm infants who visited the outpatient departments at Xinqiao Hospital of Army Medical University and Maternal and Child Health Care Hospitals of Wanzhou and Yongchuan Districts in Chongqing from September 1, 2016, to August 31, 2017. The head shape data measured by a simple manual method were recorded. The diagonal difference (DD) between the transcranial diagonals and the cranial index (CI) was calculated. PD and its incidences indifferent gestational ages and corrected age groups were analyzed.

Results

According to previously defined international diagnostic criteria, the incidence of plagiocephaly, brachycephaly, and dolichocephaly were 51.1, 85.1, and 3.0% respectively, and those of right and left plagiocephalywere69.4 and 30.6%, respectively. The incidence of PD was highest among infants with a gestational age of < 32 weeks and decreased as the gestational age increased. As the corrected age (CA) increased, the incidence of plagiocephaly and dolichocephaly decreased, and the incidence of brachycephaly increased.

Conclusions

PD incidence is high among preterm infants. As gestational age decreased, PD incidence and severity increased. Therefore, healthcare providers should implement early PD detection and intervention to prevent the adverse outcomes. The extremely high incidence of brachycephaly and extremely low incidence of dolichocephaly in this study are likely to be due to the variance of cranial metrics caused by cultural differences. The Chinese standards for infant cranial measurements must be established.
Prevalence and correlates of suicidal ideation in Korean firefighters: a nationwide study
Authors: Park Heyeon , Kim Johanna Inhyang , Min Beomjun , Oh Sohee , Kim Jeong-Hyun
Published: December 2019

Background

It is generally known that firefighters are at increased risk of suicide. However, the prevalence and correlates of suicidal ideation in firefighters have not been thoroughly described to date. The aim of this study was to measure the 1-year prevalence of suicidal ideation in firefighters and to investigate the correlates of past-year suicidal ideation among the demographic, occupational and clinical characteristics.

Method

A web-based survey was conducted using a self-reported questionnaire. A total of 45,698 Korean firefighters were included for analysis. The prevalence of suicidal ideation in the past year was calculated and its correlates were elucidated using a multivariable logistic regression analysis.

Results

The 1-year prevalence of suicidal ideation was 10.66% in Korean firefighters. Recent traumatic experience, high levels of occupational stress from physical work environment and emotional labor, as well as current duty of officer were significant correlates of suicidal ideation in the previous year, even after controlling for the effects of PTSD and depressive symptoms. With respect to demographic factors, female gender and marital status of divorced/separated/widowed were identified to be associated with suicidal ideation in the previous year among firefighters.

Conclusions

The 1-year prevalence of suicidal ideation was high in Korean firefighters and was associated with various occupational factors as well as psychiatric symptoms. Early detection and management of these risk factors could reduce the risk of suicidal ideation in firefighters.
Economic burden of Huntington’s disease in Peru
Authors: Silva-Paredes Gustavo , Urbanos-Garrido Rosa M. , Inca-Martinez Miguel , Rabinowitz Danielle , Cornejo-Olivas Mario R.
Published: December 2019

Background

Huntington’s disease (HD) is a devastating and fatal neurodegenerative disorder that leads to progressive disability, and over time to total dependence. The economic impact of HD on patients living in developing countries like Peru is still unknown. This study aims to estimate the economic burden by estimating direct and indirect costs of Huntington’s disease in Peru, as well as the proportion of direct costs borne by patients and their families.

Methods

Disease-cost cross-sectional study where 97 participants and their primary caregivers were interviewed using a common questionnaire. Prevalence and human capital approaches were used to estimate direct and indirect costs, respectively.

Results

The average annual cost of HD reached USD 8120 per patient in 2015. Direct non-healthcare costs represented 78.3% of total cost, indirect costs 14.4% and direct healthcare costs the remaining 7.3%. The mean cost of HD increased with the degree of patient dependency: from USD 6572 for Barthel 4 & 5 (slight dependency and total independency, respectively) to USD 23,251 for Barthel 1 (total dependency). Direct costs were primarily financed by patients and their families.

Conclusions

The estimated annual cost of HD for Peruvian society reached USD 1.2 million in 2015. The cost impact of HD on patients and their families is very high, becoming catastrophic for most dependent patients, and thus making it essential to prioritize full coverage by the State.
Analysis of affecting factors on patient safety culture in public and private hospitals in Iran
Authors: Khoshakhlagh Amir Hossein , Khatooni Elham , Akbarzadeh Isa , Yazdanirad Saeid , Sheidaei Ali
Published: December 2019

Background

Patient safety culture is one of the main components of the quality of health services and is one of the main priorities of health studies. Accordingly, this study aimed to determine and compare the views of healthcare staff on the patient safety culture and the impact of effective factors on patient safety culture in public and private hospitals in Tehran, Iran.

Methods

This cross-sectional study was carried out on a sample of 1203 health care workers employed in three public and three private hospitals in Tehran, Iran. Stratified random sampling was used in this study. Data were collected using the Maslach burnout inventory and patient safety culture questionnaire (HSOPSC). IBM SPSS v22 and Amos v23 were used to perform path analysis.

Results

Eight hundred sixty-seven (72.57%) females and 747 (27.43%) males with a mean age of 33.88 ± 7.66 were included. The average percentage of positive responses to the safety culture questionnaire in public and private hospitals was 65.5 and 58.3%, respectively. The strengths of patient safety culture in public hospitals were in three dimensions including non-punitive response to errors (80%), organizational learning—continuous improvement (79.77%), and overall perceptions of patient safety (75.16%), and in private hospitals, were three dimensions including non-punitive responses to errors (71.41%), organizational learning & continuous improvement (69.24%), and teamwork within units (62.35%). The type of hospital and work-shift hours influenced the burnout and patient safety questionnaire scores (P-value < 0.05). The path analysis results indicate the fitness of the proposed model (RMSEA = 0.024). The results showed a negative impact of a work shift (β = − 0.791), occupational burnout (β = − 0.554) and hospital type (β = − 0.147) on the observance of patient safety culture.

Conclusion

Providing feedback on errors and requirements for the frequent incident reporting, and patient information exchange seem necessary to promote the patient safety culture. Also, considering the negative impact of the shift work and burnout on patient safety culture, by planning and managing these factors appropriately, correct actions could be designed to improve the safety culture.
Multi-species annotation of transcriptome and chromatin structure in domesticated animals
Authors: Foissac Sylvain , Djebali Sarah , Munyard Kylie , Vialaneix Nathalie , Rau Andrea , Muret Kevin , Esquerré Diane , Zytnicki Matthias , Derrien Thomas , Bardou Philippe , Blanc Fany , Cabau Cédric , Crisci Elisa , Dhorne-Pollet Sophie , Drouet Françoise , Faraut Thomas , Gonzalez Ignacio , Goubil Adeline , Lacroix-Lamandé Sonia , Laurent Fabrice , Marthey Sylvain , Marti-Marimon Maria , Momal-Leisenring Raphaelle , Mompart Florence , Quéré Pascale , Robelin David , Cristobal Magali San , Tosser-Klopp Gwenola , Vincent-Naulleau Silvia , Fabre Stéphane , Pinard-Van der Laan Marie-Hélène , Klopp Christophe , Tixier-Boichard Michèle , Acloque Hervé , Lagarrigue Sandrine , Giuffra Elisabetta
Published: December 2019

Background

Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells).

Results

RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic A/B compartments annotated from Hi-C data were consistent with RNA-seq and ATAC-seq data. Multi-species comparisons showed that conserved TAD boundaries had stronger insulation properties than species-specific ones and that the genomic distribution of orthologous genes in A/B compartments was significantly conserved across species.

Conclusions

We report the first multi-species and multi-assay genome annotation results obtained by a FAANG project. Beyond the generation of reference annotations and the confirmation of previous findings on model animals, the integrative analysis of data from multiple assays and species sheds a new light on the multi-scale selective pressure shaping genome organization from birds to mammals. Overall, these results emphasize the value of FAANG for research on domesticated animals and reinforces the importance of future meta-analyses of the reference datasets being generated by this community on different species.
The NASSS framework for ex post theorisation of technology-supported change in healthcare: worked example of the TORPEDO programme
Authors: Abimbola Seye , Patel Bindu , Peiris David , Patel Anushka , Harris Mark , Usherwood Tim , Greenhalgh Trisha
Published: December 2019

Background

Evaluation of health technology programmes should be theoretically informed, interdisciplinary, and generate in-depth explanations. The NASSS (non-adoption, abandonment, scale-up, spread, sustainability) framework was developed to study unfolding technology programmes in real time—and in particular to identify and manage their emergent uncertainties and interdependencies. In this paper, we offer a worked example of how NASSS can also inform ex post (i.e. retrospective) evaluation.

Methods

We studied the TORPEDO (Treatment of Cardiovascular Risk in Primary Care using Electronic Decision Support) research programme, a multi-faceted computerised quality improvement intervention for cardiovascular disease prevention in Australian general practice. The technology (HealthTracker) had shown promise in a cluster randomised controlled trial (RCT), but its uptake and sustainability in a real-world implementation phase was patchy. To explain this variation, we used NASSS to undertake secondary analysis of the multi-modal TORPEDO dataset (results and process evaluation of the RCT, survey responses, in-depth professional interviews, videotaped consultations) as well as a sample of new, in-depth narrative interviews with TORPEDO researchers.

Results

Ex post analysis revealed multiple areas of complexity whose influence and interdependencies helped explain the wide variation in uptake and sustained use of the HealthTracker technology: the nature of cardiovascular risk in different populations, the material properties and functionality of the technology, how value (financial and non-financial) was distributed across stakeholders in the system, clinicians’ experiences and concerns, organisational preconditions and challenges, extra-organisational influences (e.g. policy incentives), and how interactions between all these influences unfolded over time.

Conclusion

The NASSS framework can be applied retrospectively to generate a rich, contextualised narrative of technology-supported change efforts and the numerous interacting influences that help explain its successes, failures, and unexpected events. A NASSS-informed ex post analysis can supplement earlier, contemporaneous evaluations to uncover factors that were not apparent or predictable at the time but dynamic and emergent.
Molecular evidence of Babesia in pet cats in mainland China
Authors: Zhang Xue-Lian , Li Xiao-Wen , Li Wen-Jun , Huang Hui-Lan , Huang Shu-Jian , Shao Jian-Wei
Published: December 2019

Background

Babesiaspp. are important emerging tick-borne protozoan hemoparasites, and pose a great impact on companion animals. Canine babesiosis has been well described worldwide, while felis babesiosis has primarily been reported from South Africa. To the best of our knowledge,Babesiaspp. infections in dogs have been well elucidated in pet dog population in China, no report aboutBabesiaspp. infection in cat population in mainland China.

Results

In this study, a total of 203 blood samples were collected from pet cats in Shenzhen city, and detected the presence ofBabesiaspp. with nested-PCR. Sequence comparison based on the 18S rRNA gene and ITS region revealed that three cats (1.48%) were infected withBabesia.vogeli. Notably, the sequences of ITS region obtained in this study shared the highest nucleotide identity with the sequence ofB.vogelistrain isolated in cat from Taiwan.

Conclusions

This study is the first report about babesiosis in domestic cats, and also provides molecular evidence ofBabesiaspp. infection in cat in mainland China. The data present in this study suggestB.vogelimay be circulating in cat population in mainland China. Further study to investigate the epidemiology ofBabesiainfection in cat nationwide is warranted.
Methicillin-resistant Staphylococcus aureus and glycopeptide-resistant enterococci in fecal samples of birds from South-Eastern Poland
Authors: Kutkowska Jolanta , Turska-Szewczuk Anna , Kucharczyk Marek , Kucharczyk Halina , Zalewska Joanna , Urbanik-Sypniewska Teresa
Published: December 2019

Background

The incidence of human infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) has increased in the recent years. Environmental sources, including bird droppings, might play an important role as resistance reservoirs.

Results

Fresh fecal samples were collected from rooks and wild-living birds during the autumn-winter period of 2016/2017, and tested for the presence of bacteria associated with human diseases. Besides bacteria representing the genera Enterococcus, Campylobacter, Escherichia, and Staphylococcus, Enterobacter, Citrobacter, Proteus, Hafnia, and Pseudomonas were also identified. The susceptibility of S. aureus and Enterococcus spp. isolates to methicillin, and vancomycin and teicoplanin, respectively, was analyzed to assess the avian wildlife as a reservoir of MRSA and VRE strains. Twenty-two percent of all S. aureus isolates were methicillin-resistant. These strains were screened by polymerase chain reaction (PCR), using the most widely used primer sets specific for the mecA gene. Twenty percent of all Enterococcus strains were phenotypically vancomycin-resistant. The presence of van resistance genes in these strains was investigated by PCR using vanA and vanB gene-specific primers. A good correlation between mecA gene detection and disc diffusion data was observed, while some discrepancy was noted between the PCR data and the vancomycin/teicoplanin phenotypic resistance pattern. The incidence of strains resistant to methicillin and glycopeptide antibiotics in wild-living birds was twice that in rooks.

Conclusions

The study suggests that rooks from urban areas and passerine birds from the natural habitat carry antibiotic-resistant Enterococcus spp. and S. aureus strains, probably reflecting the presence of such isolates in the environmental food sources.
Directional association test reveals high-quality putative cancer driver biomarkers including noncoding RNAs
Authors: Zhong Hua , Song Mingzhou
Published: December 2019

Background

Most statistical methods used to identify cancer driver genes are either biased due to choice of assumed parametric models or insensitive to directional relationships important for causal inference. To overcome modeling biases and directional insensitivity, a recent statistical functional chi-squared test (FunChisq) detects directional association via model-free functional dependency. FunChisq examines patterns pointing from independent to dependent variables arising from linear, non-linear, or many-to-one functional relationships. Meanwhile, the Functional Annotation of Mammalian Genome 5 (FANTOM5) project surveyed gene expression at over 200,000 transcription start sites (TSSs) in nearly all human tissue types, primary cell types, and cancer cell lines. The data cover TSSs originated from both coding and noncoding genes. For the vast uncharacterized human TSSs that may exhibit complex patterns in cancer versus normal tissues, the model-free property of FunChisq provides us an unprecedented opportunity to assess the evidence for a gene’s directional effect on human cancer.

Results

We first evaluated FunChisq and six other methods using 719 curated cancer genes on the FANTOM5 data. FunChisq performed best in detecting known cancer driver genes from non-cancer genes. We also show the capacity of FunChisq to reveal non-monotonic patterns of functional association, to which typical differential analysis methods such as t-test are insensitive. Further applying FunChisq to screen unannotated TSSs in FANTOM5, we predicted 1108 putative cancer driver noncoding RNAs, stronger than 90% of curated cancer driver genes. Next, we compared leukemia samples against other samples in FANTOM5 and FunChisq predicted 332/79 potential biomarkers for lymphoid/myeloid leukemia, stronger than the TSSs of all 87/100 known driver genes in lymphoid/myeloid leukemia.

Conclusions

This study demonstrated the advantage of FunChisq in revealing directional association, especially in detecting non-monotonic patterns. Here, we also provide the most comprehensive catalog of high-quality biomarkers that may play a causative role in human cancers, including putative cancer driver noncoding RNAs and lymphoid/myeloid leukemia specific biomarkers.
MECoRank: cancer driver genes discovery simultaneously evaluating the impact of SNVs and differential expression on transcriptional networks
Authors: Hui Ying , Wei Pi-Jing , Xia Junfeng , Wang Yu-Tian , Zheng Chun-Hou
Published: December 2019

Background

Although there are huge volumes of genomic data, how to decipher them and identify driver events is still a challenge. The current methods based on network typically use the relationship between genomic events and consequent changes in gene expression to nominate putative driver genes. But there may exist some relationships within the transcriptional network.

Methods

We developed MECoRank, a novel method that improves the recognition accuracy of driver genes. MECoRank is based on bipartite graph to propagates the scores via an iterative process. After iteration, we will obtain a ranked gene list for each patient sample. Then, we applied the Condorcet voting method to determine the most impactful drivers in a population.

Results

We applied MECoRank to three cancer datasets to reveal candidate driver genes which have a greater impact on gene expression. Experimental results show that our method not only can identify more driver genes that have been validated than other methods, but also can recognize some impactful novel genes which have been proved to be more important in literature.

Conclusions

We propose a novel approach named MECoRank to prioritize driver genes based on their impact on the expression in the molecular interaction network. This method not only assesses mutation’s effect on the transcriptional network, but also assesses the differential expression’s effect within the transcriptional network. And the results demonstrated that MECoRank has better performance than the other competing approaches in identifying driver genes.
A network clustering based feature selection strategy for classifying autism spectrum disorder
Authors: Tang Lingkai , Mostafa Sakib , Liao Bo , Wu Fang-Xiang
Published: December 2019

Background

Advanced non-invasive neuroimaging techniques offer new approaches to study functions and structures of human brains. Whole-brain functional networks obtained from resting state functional magnetic resonance imaging has been widely used to study brain diseases like autism spectrum disorder (ASD). Auto-classification of ASD has become an important issue. Existing classification methods for ASD are based on features extracted from the whole-brain functional networks, which may be not discriminant enough for good performance.

Methods

In this study, we propose a network clustering based feature selection strategy for classifying ASD. In our proposed method, we first apply symmetric non-negative matrix factorization to divide brain networks into four modules. Then we extract features from one of four modules called default mode network (DMN) and use them to train several classifiers for ASD classification.

Results

The computational experiments show that our proposed method achieves better performances than those trained with features extracted from the whole brain network.

Conclusion

It is a good strategy to train the classifiers for ASD based on features from the default mode subnetwork.
A new method for mining information of co-expression network based on multi-cancers integrated data
Authors: Hou Mi-Xiao , Gao Ying-Lian , Liu Jin-Xing , Shang Junliang , Zhu Rong , Yuan Sha-Sha
Published: December 2019

Background

Gene co-expression network is a favorable method to reveal the nature of disease. With the development of cancer, the way to build gene co-expression networks based on cancer data has been become a hot spot. However, there are still a limited number of current node measurement methods and node mining strategies for multi-cancers network construction.

Methods

In this paper, we introduce a new method for mining information of co-expression network based on multi-cancers integrated data, named PMN. We construct the network by combining the different types of relevant measures (linear and nonlinear rules) for different nodes based on integrated gene expression data of multi-cancers from The Cancer Genome Atlas (TCGA). For mining genes, we combine different properties (local and global characteristics) of the nodes.

Results

We uncover more suspicious abnormally expressed genes and shared pathways of different cancers. And we have also found some proven genes and pathways; of course, there are some suspicious factors and molecules that need clinical validation.

Conclusions

The results demonstrate that our method is very effective in excavating gene co-expression genes of multi-cancers.
Identifying driver genes involving gene dysregulated expression, tissue-specific expression and gene-gene network
Authors: Song Junrong , Peng Wei , Wang Feng , Wang Jianxin
Published: December 2019

Background

Cancer as a kind of genomic alteration disease each year deprives many people’s life. The biggest challenge to overcome cancer is to identify driver genes that promote the cancer development from a huge amount of passenger mutations that have no effect on the selective growth advantage of cancer. In order to solve those problems, some researchers have started to focus on identification of driver genes by integrating networks with other biological information. However, more efforts should be needed to improve the prediction performance.

Methods

Considering the facts that driver genes have impact on expression of their downstream genes, they likely interact with each other to form functional modules and those modules should tend to be expressed similarly in the same tissue. We proposed a novel model named by DyTidriver to identify driver genes through involving the gene dysregulated expression, tissue-specific expression and variation frequency into the human functional interaction network (e.g. human FIN).

Results

This method was applied on 974 breast, 316 prostate and 230 lung cancer patients. The consequence shows our method outperformed other five existing methods in terms of Fscore, Precision and Recall values. The enrichment and cociter analysis illustrate DyTidriver can not only identifies the driver genes enriched in some significant pathways but also has the capability to figure out some unknown driver genes.

Conclusion

The final results imply that driver genes are those that impact more dysregulated genes and express similarly in the same tissue.
Genome analysis and knowledge-driven variant interpretation with TGex
Authors: Dahary Dvir , Golan Yaron , Mazor Yaron , Zelig Ofer , Barshir Ruth , Twik Michal , Iny Stein Tsippi , Rosner Guy , Kariv Revital , Chen Fei , Zhang Qiang , Shen Yiping , Safran Marilyn , Lancet Doron , Fishilevich Simon
Published: December 2019

Background

The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants.

Results

We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters. Examining use-cases from a variety of TGex users world-wide, we demonstrate its high diagnostic yields (42% for single exome and 50% for trios in 1500 rare genetic disease cases) and critical actionable genetic findings. The platform’s support for integration with EHR and LIMS through dedicated APIs facilitates automated retrieval of patient data for TGex’s customizable reporting engine, establishing a rapid and cost-effective workflow for an entire range of clinical genetic testing, including rare disorders, cancer predisposition, tumor biopsies and health screening.

Conclusions

TGex is an innovative tool for the annotation, analysis and prioritization of coding and non-coding genomic variants. It provides access to an extensive knowledgebase of genomic annotations, with intuitive and flexible configuration options, allows quick adaptation, and addresses various workflow requirements. It thus simplifies and accelerates variant interpretation in clinical genetics workflows, with remarkable diagnostic yield, as exemplified in the described use cases.

TGex is available athttp://tgex.genecards.org/
MEG3 promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-361-5p/FOXO1 axis
Authors: Wang Anying , Hu Naixia , Zhang Yefeng , Chen Yuanzhen , Su Changhui , Lv Yao , Shen Yong
Published: December 2019

Background

This study aimed to investigate the role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) and related molecular mechanisms, in osteoarthritis (OA).

Methods

Cartilage tissues of OA patients and healthy volunteers were isolated and cultured. After transfection with the appropriate constructs, chondrocytes were classified into Blank, pcDNA3.1-NC, pcDNA3.1-MEG3, si-NC, si-MEG3, pcDNA3.1-NC + mimics NC, pcDNA3.1-MEG3 + mimics NC, pcDNA3.1-NC + miR-361-5p mimics and pcDNA3.1-MEG3 + miR-361-5p mimics groups. qRT-PCR was used to detect the expression of MEG3, miR-361-5p and FOXO1. Western blot, luciferase reporter assay, RIP, CCK-8, and flow cytometry analysis were performed to reveal the morphology, proliferation, and apoptotic status of cartilage cells. Histological analysis and immunostaining were conducted in the OA rat model.

Results

Expression of MEG3 and FOXO1 was significantly decreased in OA compared with the normal group, while the expression of miR-361-5p was increased. MEG3 might serve as a ceRNA of miR-361-5p in OA chondrocytes. Moreover, using western blot analyses and the CCK-8 assay, MEG3 was shown to target miR-361-5p/FOXO1, elevate cell proliferation, and impair cell apoptosis. Functional analysis in vivo showed that MEG3 suppressed degradation of the cartilage matrix.

Conclusion

MEG3 can contribute to cell proliferation and inhibit cell apoptosis and degradation of extracellular matrix (ECM) via the miR-361-5p/FOXO1 axis in OA chondrocytes.
Retraction Note to: IL‑2 augments the sorafenib‑induced apoptosis in liver cancer by promoting mitochondrial fission and activating the JNK/TAZ pathway
Authors: Ding Xiaoyan , Sun Wei , Chen Jinglong
Published: December 2019

The editor has retracted this article [1] because Figures 2 and 4 contain duplicated and modified figures from [2–4]. The data reported in this article are therefore unreliable.
Retraction Note to: LATS2 overexpression attenuates the therapeutic resistance of liver cancer HepG2 cells to sorafenib‑mediated death via inhibiting the AMPK–Mfn2 signaling pathway
Authors: Song Jie , Zhao Wei , Lu Chang , Shao Xue
Published: December 2019

The editor has retracted this article [1] because Fig. 2f has been duplicated from Fig. 6j in a previously published article [2]. In addition, the article contains sections that substantially overlap with a previously published article [3]. The data reported in this article are therefore unreliable.
Atrial fibrillation hospitalization is associated with exposure to fine particulate air pollutants
Authors: Lee Hsiu Hao , Pan Shih Chun , Chen Bing Yu , Lo Shih Hsiang , Guo Yue Leon
Published: December 2019

Background

Although air pollutants have been associated with cardiopulmonary mortality, their effects on the occurrence of atrial fibrillation (Afib) remain unclear. This study examined the association between ambient air pollutants and Afib occurrence.

Methods

Using a representative sample from the National Health Insurance Database of Taiwan, we applied a case–crossover study design to explore the associations between air pollutants and patients hospitalized with Afib from 2006 to 2011. The event day was when a patient was hospitalized with Afib, and the control days were the same days of the following weeks of the same month. The association between Afib occurrence and levels of ambient air pollutants (including particulate matter [PM] 2.5 PM10, NO2, SO2, and O3) was examined after adjusting for temperature and relative humidity. A two-pollutant model was used to examine the effect of the second pollutant when the first pollutant was determined to be significantly related to Afib.

Results

During 2006–2011, 670 patients hospitalized with the first onset of Afib were identified. The occurrence of Afib was associated with PM2.5, in which a 22% (95% confidence interval = 3–44%) increase was related to an interquartile range increase (26.2 μg/m3) on the same day and a 19% (95% confidence interval = 0–40%) increase on the second day. A two-pollutant model was applied, and the results indicated that the effect of PM2.5 was significantly associated with the occurrence of Afib. Patients aged over 65 years with DM and with hyperlipidemia were more susceptible to the effect of PM2.5.

Conclusions

In conclusion, the occurrence of Afib was associated with short-term exposure to fine particulate air pollutants in the general population.
Associations between vaping and relapse to smoking: preliminary findings from a longitudinal survey in the UK
Authors: Brose Leonie S. , Bowen Julia , McNeill Ann , Partos Timea R.
Published: December 2019

Background

Most smokers attempting to quit relapse. There is little evidence whether the use of e-cigarettes (‘vaping’) increases or decreases relapse. This study aimed to assess 1) whether vaping predicted relapse among ex-smokers, and 2) among ex-smokers who vaped, whether vaping characteristics predicted relapse.

Methods

Longitudinal web-based survey of smokers, recent ex-smokers and vapers in the UK, baseline in May/June 2016 (n = 3334), follow-up in September 2017 (n = 1720). Those abstinent from smoking ≥ 2 months at baseline and followed up were included. Aim 1: Relapse during follow-up was regressed onto baseline vaping status, age, gender, income, nicotine replacement therapy use and time quit smoking (n = 374). Aim 2: Relapse was regressed onto baseline vaping frequency, device type, nicotine strength and time quit smoking (n = 159).

Results

Overall, 39.6% relapsed. Compared with never use (35.9%), past/ever (45.9%; adjOR = 1.13; 95% CI, 0.61–2.07) and daily vaping (34.5%; adjOR = 0.61; 95% CI, 0.61–1.89) had similar odds of relapse, for non-daily vaping evidence of increased relapse was inconclusive (65.0%; adjOR = 2.45; 95% CI, 0.85–7.08). Among vapers, non-daily vaping was associated with higher relapse than daily vaping (adjOR = 3.88; 95% CI, 1.10–13.62). Compared with modular devices (18.9% relapse), tank models (45.6%; adjOR = 3.63; 95% CI, 1.33–9.95) were associated with increased relapse; evidence was unclear for disposable/cartridge refillable devices (41.9%; adjOR = 2.83; 95% CI, 0.90–8.95). Nicotine strength had no clear association with relapse.

Conclusion

Relapse to smoking is likely to be more common among ex-smokers vaping infrequently or using less advanced devices. Research into the effects of vaping on relapse needs to consider vaping characteristics.
Significance of bile culture surveillance for postoperative management of pancreatoduodenectomy
Authors: Sugimachi Keishi , Iguchi Tomohiro , Mano Yohei , Morita Masaru , Mori Masaki , Toh Yasushi
Published: December 2019

Background

The management of infectious complications is important in pancreatoduodenectomy (PD). We sought to determine the significance of preoperative surveillance bile culture in perioperative management of PD.

Methods

This study enrolled 69 patients who underwent PD for malignant tumors at a single institute between 2014 and 2017. Surveillance bile culture was performed before or during surgery. Correlations between the incidence of infectious postoperative complications and clinicopathological parameters, including bile cultures, were evaluated.

Results

Preoperative positive bile culture was confirmed in 28 of 51 patients (55%). Bile culture was positive in 27 of 30 cases (90%) with preoperative biliary drainage, and 1 of 21 cases (5%) without drainage (p < 0.01). Preoperative isolated microorganisms in bile were consistent with those detected in surgical sites in 11 of 27 cases (41%). Cases with positive multi-drug-resistant bacteria in preoperative bile culture showed significantly higher incisional SSI after PD (p = 0.01). The risk factors for the incidence of organ/space SSI were soft pancreatic texture (p = 0.01) and smoking history (p = 0.02) by multivariate analysis. Preoperative positive bile culture was neither associated with organ/space SSI nor overall postoperative complications.

Conclusions

Preoperative surveillance bile culture is useful for the management of wound infection, prediction of causative pathogens for infectious complications, and the selection of perioperative antibiotic prophylaxis.
Optimisation: defining and exploring a concept to enhance the impact of public health initiatives
Authors: Wolfenden Luke , Bolsewicz Katarzyna , Grady Alice , McCrabb Sam , Kingsland Melanie , Wiggers John , Bauman Adrian , Wyse Rebecca , Nathan Nicole , Sutherland Rachel , Hodder Rebecca Kate , Fernandez Maria , Lewis Cara , Taylor Natalie , McKay Heather , Grimshaw Jeremy , Hall Alix , Moullin Joanna , Albers Bianca , Batchelor Samantha , Attia John , Milat Andrew , Bailey Andrew , Rissel Chris , Reeves Penny , Sims-Gould Joanie , Mildon Robyn , Doran Chris , Yoong Sze Lin
Published: December 2019

Background

Repeated, data-driven optimisation processes have been applied in many fields to rapidly transform the performance of products, processes and interventions. While such processes may similarly be employed to enhance the impact of public health initiatives, optimisation has not been defined in the context of public health and there has been little exploration of its key concepts.

Methods

We used a modified, three-round Delphi study with an international group of researchers, public health policy-makers and practitioners to (1) generate a consensus-based definition of optimisation in the context of public health and (2i) describe key considerations for optimisation in that context.

A pre-workshop literature review and elicitation of participant views regarding optimisation in public health (round 1) were followed by a daylong workshop and facilitated face-to-face group discussions to refine the definition and generate key considerations (round 2); finally, post-workshop discussions were undertaken to refine and finalise the findings (round 3). A thematic analysis was performed at each round. Study findings reflect an iterative consultation process with study participants.

Results

Thirty of 33 invited individuals (91%) participated in the study. Participants reached consensus on the following definition of optimisation in public health: “A deliberate, iterative and data-driven process to improve a health intervention and/or its implementation to meet stakeholder-defined public health impacts within resource constraints”.

A range of optimisation considerations were explored. Optimisation was considered most suitable when existing public health initiatives are not sufficiently effective, meaningful improvements from an optimisation process are anticipated, quality data to assess impacts are routinely available, and there are stable and ongoing resources to support it. Participants believed optimisation could be applied to improve the impacts of an intervention, an implementation strategy or both, on outcomes valued by stakeholders or end users. While optimisation processes were thought to be facilitated by an understanding of the mechanisms of an intervention or implementation strategy, no agreement was reached regarding the best approach to inform decisions about modifications to improve impact.

Conclusions

The study findings provide a strong basis for future research to explore the potential impact of optimisation in the field of public health.
Preventing type 2 diabetes mellitus in Qatar by reducing obesity, smoking, and physical inactivity: mathematical modeling analyses
Authors: Awad Susanne F. , O’Flaherty Martin , El-Nahas Katie G. , Al-Hamaq Abdulla O. , Critchley Julia A. , Abu-Raddad Laith J.
Published: December 2019

Background

The aim of this study was to estimate the impact of reducing the prevalence of obesity, smoking, and physical inactivity, and introducing physical activity as an explicit intervention, on the burden of type 2 diabetes mellitus (T2DM), using Qatar as an example.

Methods

A population-level mathematical model was adapted and expanded. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status, and parameterized by nationally representative data. Modeled interventions were introduced in 2016, reached targeted level by 2031, and then maintained up to 2050. Diverse intervention scenarios were assessed and compared with a counter-factual no intervention baseline scenario.

Results

T2DM prevalence increased from 16.7% in 2016 to 24.0% in 2050 in the baseline scenario. By 2050, through halting the rise or reducing obesity prevalence by 10–50%, T2DM prevalence was reduced by 7.8–33.7%, incidence by 8.4–38.9%, and related deaths by 2.1–13.2%. For smoking, through halting the rise or reducing smoking prevalence by 10–50%, T2DM prevalence was reduced by 0.5–2.8%, incidence by 0.5–3.2%, and related deaths by 0.1–0.7%. For physical inactivity, through halting the rise or reducing physical inactivity prevalence by 10–50%, T2DM prevalence was reduced by 0.5–6.9%, incidence by 0.5–7.9%, and related deaths by 0.2–2.8%. Introduction of physical activity with varying intensity at 25% coverage reduced T2DM prevalence by 3.3–9.2%, incidence by 4.2–11.5%, and related deaths by 1.9–5.2%.

Conclusions

Major reductions in T2DM incidence could be accomplished by reducing obesity, while modest reductions could be accomplished by reducing smoking and physical inactivity, or by introducing physical activity as an intervention.