bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma
Authors: Nguyen Phuong , Ma Siming , Phua Cheryl , KAYA Neslihan , Lai Hannah , Lim Chun Jye , Lim Jia Qi , Lai Liyun , Tam Wai Leong , Lim Kiat Hon , Wan Wei Keat , Loh Tracy , Leow Wei Qiang , Pang Yin Huei , Chan Chung Yip , Lee Ser Yee , Cheow Peng Chung , Toh Han Chong , Ginhoux Florent , Iyer Shridhar , Kow Alfred , Dan Yock Young , Chung Alexander , Goh Brian , Albani Salvatore , Chow Pierce Kah‐Hoe , Zhai Wei Wei , Chew Valerie 
Published: July 2020

Abstract
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncovered significant spatial and phenotypic immune–ITH from multiple tumour sectors and deciphered its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune–ITH was associated with RNA-ITH and distinct immune microenvironments. Tumours with low immune–ITH experienced higher immunoselective pressure and underwent escape mechanisms via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH were associated with a more immunosuppressive/exhausted microenvironment. This immune pressure gradient along with immune-ITH represents a hallmark of tumour evolution closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature were predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides novel evidence on tumour-immune co-evolution along HCC progression.
Molecular characteristics and pathogenicity of porcine epidemic diarrhea virus in some areas of China from 2015 to 2018
Authors: Yu Linyang , Dong Jianguo , Wang Shuangyun , Liu Yanling , Zhang Leyi , Liang Pengshuai , Wang Lei , Chen Bin , Huang Li , song Changxu 
Published: July 2020

Abstract
Background

Since 2010, porcine epidemic diarrhea virus (PEDV) has caused severe diarrhea disease in piglets, which has led to large economic losses in China. To understand the genetic characteristics of PEDV strains that have been circulating in some provinces of China from 2015 to 2018, 362 feces and small intestine samples in pigs were collected and tested.
Methods

The S gene of PEDV in collected samples were amplified by RT-PCR. A phylogenetic tree was constructed using MEGA6.0 software with the neighbor-joining method to analyze the evolutionary relationship. Nucleotide and deduced amino acid (AA) sequences of S were aligned using the MegAlign program of DNASTAR7.1 software to determine sequence homology. PEDV GDgh16 strain isolation, IFA identification and titer detection were performed in Vero cells. Six 4-day-old healthy colostrum deprived suckling piglets were used for challenging experiment of PEDV GDgh16 strain. Virus copies from the small intestine were detected by RT-qPCR. The other section was stained with the anti-N protein McAb at 1:1000 dilution for immunohistochemical (IHC) examinations.
Results

The results showed that 160 samples tested positive and the PEDV-positive prevalence was 44.20%. Phylogenetic tree analysis of entire S genes showed that these strains were clustered into four subgroups, G1-b, G1-c, G2-a and G2-b, and that the G2-b strains had become dominant in recent years. Compared with previous strains, these strains had multiple variations in the SP and S1-NTD domains and in the neutralizing epitope of the S protein. Furthermore, we successfully isolated and identified a new virulent G2-b strain, GDgh16, which was well adapted to Vero cells and had a high mortality rate in piglets through challenge experiments.
Conclusions

Our study provides full insights into the genetic characteristics of prevalent PEDV strains in parts of China, suggesting that the development of novel effective vaccines is necessary and urgent.
The prevalent RNA modification on SARS-CoV-2 RNAs may confound the SNP profile and evolutionary patterns revealed by previous studies
Authors: Wang Yan , Gai Yanhong , Li Yuefan , Li Chunxiao , Li Ziliang , Wang Xuekun 
Published: July 2020

Abstract
Background

The recent outbreak of SARS-CoV-2 has caused severe damage to the world. The concomitant papers on the evolutionary patterns of SARS-CoV-2 is continuously emerging. Studies has utilized the publically available RNA-seq data to find out the so-called SNPs in the virus genome and analyzed their selection patterns.
Methods

We downloaded a set of RNA-seq data and performed a well-established but modified variant calling pipeline to allow the identification of multiple clustered mutations.
Results

We found prevalent “putative” but reliably detected A-to-G RNA modifications in the RNA-seq data of SARS-CoV-2 with high signal to noise ratios, presumably caused by the host’s deamination enzymes. Importantly, since SARS-CoV-2 is an RNA virus, it is technically impossible to truly distinguish SNPs and RNA modifications from the RNA-seq data alone.
Conclusions

The technically indistinguishable RNA modifications and SNPs of SARS-CoV-2 have complicated the situation where many researchers intend to unveil the evolutionary patterns behind the mutation spectrum. This is not a problem for DNA organisms but should be seriously considered when we are investigating the RNA viruses.
The influence of South East Asia Forest Fires on ambient Particulate Matter concentrations in Singapore: An Ecological Study using Random Forest and Vector Autoregressive Models
Authors: Rajarethinam Jayanthi , Aik Joel , Tian Jing 
Published: July 2020

Abstract
Background In recent decades, haze, due to biomass burning, has become a recurring problem in Southeast Asia (SEA). Haze degrades air quality, thus, causing detrimental effects on human health. Exposure to atmospheric particulate matter (PM) remains an important public health concern.Methods In this paper, we examined the long-term seasonality of PM2.5 and PM10 in Singapore. To study the association between forest fires in SEA and air quality in Singapore, we built two machine learning models, including the random forest (RF) model and the vector autoregressive (VAR) model, using a benchmark air quality dataset containing daily PM2.5 and PM10 from 2009 to 2018. Furthermore, we incorporated weather parameters as independent variables, to understand their effects on air quality.Results We observed two annual peaks, one in the middle of the year and one at the end of the year for both PM2.5 and PM10. Singapore was more affected by fires from Kalimantan compared to fires from other SEA countries. In our experimental results, VAR models performed better than RF with Mean Absolute Percentage Error (MAPE) values being 0.8% and 6.1% lower for PM2.5 and PM10, respectively.Conclusions Our study findings suggest that air quality in Singapore can be reasonably anticipated with predictive models that incorporate information on forest fires and weather variations. The public communication of anticipated air quality at the national level benefit who are at higher risk of experiencing poorer health due to poorer air quality.
Clinical Variables Responsible for Early and Late Diagnosis of Foreign Body Aspiration in Pediatrics age Group
Authors: Goyal Samarth , Jain Shubhika , Rai Guruprasad , Vishnu Rajkamal , Kamath Ganesh Sevagur , Bishnoi Arvind Kumar , Gaude Yogesh , Kumara Vijaya , Joshi Harshil , Reddy Revanth 
Published: July 2020

Abstract
Background
Incidence of foreign body aspiration ( FBA ) has been noticed maximally in age group ranging from 12 months-3 years. Foreign body in the trachea is a medical emergency as presentation is of respiratory distress. Obstruction of only one main or distal bronchus, leads to severe cough, choking sensation and breathlessness. Without early intervention it can lead to collapse, consolidation and pneumonia of the affected lung.
Methods
We retrospectively analysed 37 pediatric case records who presented from January 2014-December 2018 with FBA. Our primary aim was to assess the parameters responsible for early and late diagnosis of FBA. We concluded with a diagnostic algorithm for management of FBA on the basis of this outcomes.
Results
Around 32.5% came with a history of aspiration, 43% were referred from primary centers with a suspicion for the same and the rest came our tertiary care hospital directly. Those who presented within a week came with complaints of wet cough, wheeze and tachypnea where as those who came in after a week had dry cough and fever as their main complaint. Majority of ingested foreign body was vegetative type (80%) as compared to the non -vegetative material (20%).
Conclusion
Unlike adults, FBA in children is most commonly diagnosed on history, suspicion and clinical findings. Chest x ray has been the primary investigation of choice but in majority of the cases it was normal with subtle changes. Early diagnosis is the key to avoid complication.
Analysis of Evidence-Rating Systems Used in Meta-Analyses of Pharmacotherapy
Authors: Pérez-Surio Alberto Frutos , Hernando José Manuel Vinuesa , Mendoza Mercedes Arene , Bandrés María Ángeles Allende , López María Aránzazu Alcácera , Gómez Tránsito Salvador 
Published: July 2020

Abstract
Background: Evidence-rating systems (ERSs) provide a framework for the systematic evaluation of the quality of individual interventional or observational studies and the overall body of evidence in meta-analyses. Authors and users of meta-analyses require a familiarity with ERSs to determine the level of confidence in the application of results. Many ERSs have been published, but no consensus exists regarding best practice for their use. Objective: The aim is to describe patterns of use of ERSs in meta-analyses of drug therapy published in contemporary high-impact medical journals.Methods: We design a review. Medline / PubMed was searched to identify meta-analyses evaluating drug therapy from the top 5 ranked general medical journals from 2012 to 2016. Methods of full-texts were reviewed to ensure the meta-analyses evaluated drug therapy and to identify the ERS used to rate individual studies and the overall body of evidence. Frequency of ERS use was analyzed using descriptive statistics.Results: The top-ranked journals were Ann Intern Med, BMJ, JAMA, Lancet and PLoS Medicine. Of the 309 results, manual review excluded 111 meta-analyses. In 198 evaluated meta-analyses, 86.4% (171) utilized an ERS; the most commonly used was the Cochrane Risk of Bias Tool in 80.7% (138) of all meta-analyses. An ERS was used to evaluate the body of literature in 19.1% (38) of meta-analyses; the most commonly used of three systems was the GRADE methodology. Overall, 14 unique ERSs, including author-defined systems, were usedConclusions: Most meta-analyses of drug effects in high-impact medical journals evaluated individual studies with an ERS, most commonly the Cochrane Risk of Bias Tool, while the use of ERSs to evaluate the body of literature was less frequent. The familiarity of authors and users of meta-analyses with commonly used ERSs may facilitate the evaluation and application of findings of meta-analyses.
MicroRNA-219c-5p Regulates Bladder Fibrosis by Targeting FN1
Authors: Liu Bowen , Ding Yafei , Li Peng , He Siyuan , Wang Tao , Jia Zhankui , Yang Jinjian 
Published: July 2020

Abstract
BackgroundWe found that the bladders of multiple sclerosis mice were significantly fibrotic. This study aimed to investigate the relationship between fibronectin 1 (FN1) and bladder fibrosis, as well as the microRNAs involved in FN1 regulation. Methods The degree of bladder smooth muscle fibrosis was observed by immunohistochemistry. In addition, we used quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting to determine FN1 expression in bladders with different grades of fibrosis. Bioinformatics analysis revealed that miR-199a-3p, miR-219c-5p and miR-3572-3p could inhibit FN1 synthesis. Therefore, miR-199a-3p, miR-219c-5p and miR-3572-3p were overexpressed or knocked down in bladder smooth muscle cells (BSMCs), and the respective transfection and FN1 knockdown efficiencies were detected by RT-qPCR. Only miR-219c-5p overexpression and knockdown produced the expected results. A dual luciferase reporter assay was used to determine the targeting relationship between miR-219c-5p and FN1. Flow cytometry and Cell Counting Kit 8 (CCK8) experiments confirmed that miR-219c-5p reduced FN1 expression and affected the biological activity of smooth muscle cells. Agomir and anagomir of miR-219c-5p were transfected in vivo to observe the change of bladder fibrosis in mice.ResultsWith increasing bladder fibrosis, FN1 expression increased, while miR-199a-3p, miR-219c-5p, and miR-3572-3p expression levels decreased. The RT-qPCR results after transfection showed that only miR-219c-5p could regulate FN1. Indeed, the dual luciferase reporter assay results indicated that miR-219c-5p targeted FN1 directly. CCK8 and cell cycle assays showed that miR-219c-5p overexpression inhibited BSMC proliferation, while miR-219c-5p knockdown promoted BSMC proliferation. An apoptosis assay showed that miR-219c-5p overexpression promoted apoptosis, while miR-219c-5p knockdown inhibited BSMC apoptosis. The agomir and anagomir transfected with miR-219c-5p in vivo found that the bladder fibrosis of the mice in the agomir group was reduced, and the anagomir group was worse.ConclusionsOur findings indicate that FN1 up-regulation and miR-219c-5p down-regulation play an important role in the development of bladder fibrosis, and miR-219c-5p participates in bladder fibrosis by regulating FN1 expression. Thus, a novel antifibrotic function of miR-219c-5p is proposed, which may represent a potential target for the diagnosis and treatment of bladder fibrosis.
Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America
Authors: Badizadegan Kamran , Vanlandingham David M. , Hampton Wesley , Thompson Kimberly M. 
Published: July 2020

Abstract
Background: Healthcare systems implement change at different rates because of differences in incentives, organizational processes, key influencers, and management styles. A comparable set of forces may play out at the national and international levels as demonstrated in significant differences in the diagnostic management of pediatric Celiac Disease (CD) between European and North American practioners. Methods: We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7,907 upper gastrointestinal endoscopy pathology reports to create a dataset of 793 pathology reports with matching tTG results between July 1 of 2014 and July 1 of 2018. We use this dataset to characterize histopathological findings in the duodenum, stomach and esophagus of patients as a function of serum tTG levels. In addition, we use the dataset to estimate the local and national cost of endoscopies performed in patients with serum tTG levels greater than 10 times the upper limit of normal. Results: Using evidence from a US tertiary care center, we show that in the cohort of pediatric patients with high pre-test probability of CD as determined by serum tTG levels, biopsy provides no additional diagnostic value for CD, and that it counter-intuitively introduces diagnostic uncertainty in a number of patients. We estimate that using the European diagnostic algorithms could avoid between 4,891 and 7,738 pediatric endoscopies per year in the US for evaluation of CD. Conclusions: This study considers the North American and European management guidelines for the diagnosis of pediatric CD and highlights the slow adoption in North America of evidence-based algorithms developed and applied in Europe for triage of endoscopy and biopsy. We suggest that the forces that maintain the status quo in North America go beyond medical evidence and include a variety of social and economic factors. This work contributes to the growing body of evidence that suggests that the dynamics that largely favor maintaining status quo management policies extend to clinical medicine and influence a variety of clinical decisions at the level of individual patients and the population.
First Report of New Delhi Metallo-β-Lactamase-1 (NDM-1) Among Escherichia Coli Strains Isolated from Leukemia Patients in Iran
Authors: Roshani Mahdane , Goodarzi Alireza , Dehbashi Sanaz , Afrasiabi Farhad , Goudarzi Hossein , Hashemi Ali , Arabestani Mohammad Reza 
Published: July 2020

Abstract
Background: Escherichia coli has appeared as an important opportunistic pathogen responsible for nosocomial infections in Patients with immunodeficiency particularly in leukemia patients. New Delhi metallo-β-lactamase (NDM-1) is an enzyme that class of beta-lactam antibiotics and is used in treatment of multi-drug resistant (MDR) infections. Case Presentation: In this study, 80 isolates of Escherichia coli and Klebsiella pneumoniae collected over the course of two years from two medical centers of Tehran, Iran. Production of carbapenemase was detected of the isolates using MHT. New Delhi metallo-beta-lactamase 1 (blaNDM-1) genes were detected by polymerase chain reaction (PCR) ampliﬁcation with speciﬁc primers 2 blaNDM-1 producing E.coli strains were isolated from 2 leukemia of patients, The isolates were resistant to carbapenems (imipenem, meropenem),two isolates were positive for carbapenemase production by Modified Hodge test.Conclusions: The emerging of NDM-1 producing E. coli is a threat for leukemia patients in Oncology and hematology departments. We concluded that the incidence of MDR pathogens increased amang patients with leukemia and is life threatening.
Radiofrequency ablation combined with conductive fluid-based dopants (saline normal and colloidal gold): Computer modeling and ex vivo experiments.
Authors: Castro-Lopez Dora Luz , Berjano Enrique , Romero-mendez Ricardo 
Published: July 2020

Abstract
Background: The coagulation zone volume created during radiofrequency ablation (RFA) is limited by the appearance of roll-off. Doping the tissue with conductive fluids, e.g. gold nanoparticles (AuNPs) could enlarge the coagulation zones by delaying the roll-off. Our goal was to characterize the electrical conductivity of a substrate doped with AuNPs and to study by computer modeling and ex vivo experiments the effect on coagulation zone volumes.Methods: The electrical conductivity of substrates doped with normal saline or AuNPs was assessed experimentally using agar phantoms. The computer models, built and solved on COMSOL Multiphysics, consisted of a cylindrical domain mimicking liver tissue and a spherical domain mimicking a doped zone with diameters of 2, 3 and 4 cm. Ex vivo experiments were conducted on bovine liver fragments and under three different doping conditions: 1) non-doped tissue (ND Group), 2 mL of 0.9% NaCl (NaCl Group), and 2 mL of AuNPs 0.1 wt% (AuNPs Group).Results: The theoretical analysis showed that adding normal saline or colloidal gold in concentrations lower than 10% only modify the electrical conductivity of the doped substrate with practically no change of the thermal characteristics. The computer results showed a relationship between doped zone size and electrode length regarding the created coagulation zone. We observed a good agreement between ex vivo and computational results in terms of transverse diameter of the coagulation zone.Conclusions: Both computer and ex vivo experiments showed that doping with AuNPs can enlarge the coagulation zone, specially the transverse diameter, hence achieving more spherical coagulation zones.
Voluntary Exercise in Mesothelioma: Effects on Tumour Growth and Treatment Response in a Murine Model
Authors: FISHER Scott A , Peddle-McIntyre Carolyn J , Burton Kimberley , Newton Robert U , Marcq Elly , Lake Richard A , Nowak Anna K 
Published: July 2020

Abstract
Objective
There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogeninduced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.
Results
Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, nonasbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some preclinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.
Effects of hearing impairment and hearing aid use on the incidence of cognitive impairment among community-dwelling older adults: evidence from the Taiwan Longitudinal Study on Aging (TLSA)
Authors: Tai Chi-Jung , Tseng Tzyy-Guey , Hsiao Yu-Han , Kuo Tsu-Ann , Huang Ching-Ya , Yang Yi-Hsin , Lee Meng-Chih 
Published: July 2020

Abstract
Background: Previous studies have reported associations between hearing impairment (HI) and cognitive impairment, but the evidence is not conclusive while considering concurrent geriatric syndromes. Especially, evidence from previous studies rarely came from Asian studies. This study aimed to evaluate the independent effects of HI and hearing aid use on the incidence of cognitive impairment while considering most geriatric confounders.Methods: This population-based, propensity-score matched cohort study used cohort from Waves IV­–VII (1999–2011) survey of the Taiwan Longitudinal Study on Aging (TLSA). Cognitive impairment was identified based on Short Portable Mental Status Questionnaire (SPMSQ) scores. The hazard ratio (HR) was calculated using the Cox proportional hazard regression adjusting for age, sex, comorbidities, socioeconomic status, Center for Epidemiologic Studies Depression (CES-D) scores, the instrumental activities of daily living scale, mobility condition and quality of life. In addition, social support and participation were also considered as confounders in the analysis. To assess the robustness of our findings, we conducted a sensitivity analysis designed to access unmeasured confounding factors by calculating E-values.Results: After 1:1 propensity-score matching, we included 709 participants in both the HI and non-HI groups with a mean age of 73.4 years and 39.4% of participants were female. The mean follow-up was 8.9±3.9 years. The HI group had a higher incidence of cognitive impairment than the non-HI group (74.5% vs. 69.1%, respectively), with an adjusted HR of 1.16 (95% confidence interval [CI], 1.03–1.32) based on a 12-year follow up. The E-value was 1.45 for the estimate, which provided evidence for this study’s robustness. Although, a subgroup analysis showed that hearing aid use was associated with lower incidences of cognitive impairment (66.3% vs. 75.6%) when compared to non-users in the HI group, the adjusted HR of 0.82 (95% CI, 0.61–1.09) revealed no significant differences.Conclusions: HI was an independent risk factor of incident cognitive impairment on top of concurrent geriatric syndromes. Early HI detection may thus be effective for preventing cognitive decline. Further studies are needed to evaluate the effect of hearing aid use on the prevention of cognitive decline.