Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Serum miRNAs with Serum Exosomal miRNAs in Early Diagnosis for Non-Small-Cell Lung Cancer

Purpose Circulating microRNAs (miRNAs) have shown the potential for non-invasive diagnosis of various types of malignancies at an early stage. The aim of the study was to explore the feasibility of a combination of 8 serum miRNAs related to non-small-cell lung cancer (NSCLC) with the corresponding serum exosomal miRNAs in early diagnosis for the patients with NSCLC. Methods We measured 8 serum miRNAs and the corresponding serum exosomal miRNAs including miR-21-5p, miR-126-3p, miR-141-3p, miR-146a-5p, miR-155-5p, miR-222-3p, miR-223-3p, and miR-486-5p in 48 patients with early NSCLC at stages I/II, 32 patients with lung benign lesion (LBL), and 48 healthy control (HC) by quantitative real-time polymerase chain reaction (qRT-PCR). Results The expression levels of 4 serum miRNAs including miR-21-5p, miR-141-3p, miR-222-3p, and miR-486-5p, and 2 serum exosomal miRNAs including miR-146a-5p and miR-486-5p in the early NSCLC group were significantly different from that in the LBL group and the HC group (P < 0.01). The areas under the receiver operating characteristic curves (AUC) of the 4 serum miRNAs and 2 serum exosomal miRNAs in the early NSCLC group were ≥0.697, of which serum exosomal miR-146a-5p and miR-486-5p were 0.813 and 0.886, respectively, and higher than that of the 4 serum miRNAs. Additionally, a combination of 4 serum miRNAs with 2 serum exosomal miRNAs improved the AUC to 0.960 for the patients with NSCLC at early stages, with a sensitivity of 85.42% and a specificity of 92.50%. Conclusion This study suggests that serum exosomal miRNAs other than serum miRNAs might be preferable biomarkers for the patients with NSCLC at early stages, and a combination of serum miRNAs with serum exosomal miRNAs contributes to the further improvement of early diagnosis for NSCLC.
Essential updates 2018/2019: Colorectal (benign)

This review outlines current topics on the surgical treatment of benign colorectal diseases, with a focus on inflammatory bowel disease (IBD) and diverticulitis. Treatment options for IBD and diverticulitis have evolved in the last few years as a result of medical advances in technology and new clinical trials. Therefore, treatment options and strategies need to be updated to provide optimal care for patients. The purpose of this review is to elucidate recent global trends and update the surgical treatment strategy for IBD and diverticulitis based on literature published in the past 2 years. Prevalence of IBD, including ulcerative colitis and Crohn's disease, has increased over the last few decades. During this period, many new medical therapies were introduced for the treatment of IBD, including biological therapy, immunomodulators, and leukocyte apheresis therapy. As a result, new surgical strategies for IBD are required. In order to improve surgical outcomes in IBD patients, the influence of preoperative treatment on postoperative complications needs to be considered. The incidence of diverticulitis is also increasing with lifestyle changes and increasing numbers of older people. For diverticulitis with perforation and generalized peritonitis, surgery is the gold standard. Elective surgery after conservative treatment of diverticulitis is also an option because of high recurrence rates. With an increase in diverticulitis, systematic strategies are essential for an appropriate approach to diverticulitis, taking into account various factors, including the patient's background.
LncRNA FTX Promotes Proliferation and Invasion of Gastric Cancer via miR-144/ZFX Axis

Background Long non-coding RNAs are important regulators in cancer cell tumorigenesis. We have demonstrated in a prior study that lncRNA FTX is dysregulated in gastric cancer (GC). In this study, we aim to report gastric cancer-related lncRNA FTX as a main regulator in GC development and progression. Methods In vitro and in vivo assays of FTX alterations have been performed to reveal a complex integrated phenotype affecting cell growth, migration, and invasion. lncRNA FTX expression levels in gastric cancer cells and normal cells were measured by RT-PCR. Luciferase reporter assays, Western blotting, and many immune, microscopy technologies were utilized to investigate the expressions of FTX- related proteins and RNAs. The functional role of FTX in cell growth, migration, and invasion were observed in vitro and in vivo. Results We explored the underlying mechanisms of FTX in GC development, and the microRNAs’ relationship with FTX. We found that FTX promoted cell proliferation, migration, and invasion, as well as tumor growth, and this effect could latterly be attenuated by miR-144. ZFX attenuated the effects of FTX/miR-144 axis by sponging with miR-144. Conclusion In summary, the above results support a model in which the FTX/miR-144/ZFX act as important effectors in GC tumorigenesis and progression, indicating new therapeutic methods in GC.
Tumor Cell-associated Exosomes Robustly Elicit Anti-tumor Immune Responses through Modulating Dendritic Cell Vaccines in Lung Tumor

DC vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment, however, antitumor effect of DC vaccines based on tumor cell lysates (TCLs) remains unsatisfactory due to poor immunogenicity of tumor antigens. Although tumor-associated exosomes (TAEs) have been reported as a promising antigen for DC vaccines, it remains unclear how TAE-based DC vaccine induced antitumor immunity in lung cancer. Methods: In the present study, we extracted TAEs from the supernatant of tumor cell culture medium, and compared the effect of TAEs with TCLs on DCs. To further evaluate the therapeutic effect of DCTAE, we used immunofluorescence and flow cytometry to evaluate the apoptosis of tumor tissue, tumor-infiltrating CD8+ T cells and Tregs in TDLNs and spleen. Then the levels of cytokines of IL-12, IFN-γ, L-10 and TGF-β were quantified by ELISA assays. Results: Our data showed that TAEs were more potent than TCLs to promote DC maturation and enhance MHC cross presentation, which directly contributed to more robust tumor-specific cytotoxic T lymphocyte (CTL) response. More importantly, TAEs reduced the expression of PD-L1 of DCs, thereby led to down-regulated population of Tregs in vitro. Moreover, DCTAE remarkably suppressed the tumor growth and prolonged survival rate in vivo, due to participance of CD8+ T cells and decreased Tregs in TDLNs and spleen. Conclusion: TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment.
Medical Students’ and Internal Medicine Trainees’ Knowledge of Drug Prescribing Recommendations in Older Patients with Impaired Kidney Function

Background Numerous medications used in older adults require dose modification or should be avoided in individuals with impaired kidney function. Purpose To assess medical students’ and physicians’ knowledge of drug prescribing recommendations in older patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2. Patients and Methods A survey comprising a list of 64 drugs conducted in 183 medical students (Students), and 138 post-graduate trainees in internal medicine (Physicians). The respondents were asked to classify each drug into one of three categories: 1) no renal precautions; 2) dose should be reduced; and 3) medication should be avoided. Results A range of 16.9–68.3% students and 14.5–81.2% physicians correctly classified drugs in the category “No renal precautions. ” Drugs requiring dose reduction were correctly classified by 6–67.2% students, and 24.6–85.5% physicians. For drugs that should be avoided in subjects with eGFR < 30 mL/min/1.73m2, the range was 6–44.8% in the Students, and 8.7–76.1% in the Physicians. The Physicians did better than the Students by classifying five drugs that do not require renal precautions, 12 drugs requiring dose reduction, and six medications that should be avoided. The Students had a higher percentage of correct answers for seven drugs in the category “no renal precautions,” and one drug requiring dose reduction. Conclusion Medical students and post-graduate trainees in internal medicine have poor knowledge of drug prescribing recommendations in older patients with renal impairment.
Prevalence of Type 2 Diabetes Mellitus in Adult Population of Pakistan: A Meta-Analysis of Prospective Cross-Sectional Surveys

Background: The clinical and methodological diversity observed in national and regional diabetes surveys, emphasized on the need of the weighted average prevalence of diabetes. Objective: To measure the pooled prevalence of type 2 diabetes mellitus in the adult population of Pakistan. Methods: The prospective cross-sectional studies reporting adult diabetes in Pakistan and published on any date were retrieved from PubMed, ScienceDirect and PakMediNet databases. In the meta-analysis, PRISMA guidelines were used for reporting; the AXIS tool for assessing quality and risk of bias within studies; I2 statistics for measuring heterogeneity between studies and subgroups; and Tableau Public 10.4 for geographic mapping of included studies. Using Meta-Analyst 3.13 βeta, overall and subgroup pooled estimates were measured by random effects model. Results: The pooled sample of twelve studies included 42,051 adults (≥20 years) comprised of both sexes from urban and rural Pakistan. The pooled prevalence of diabetes was 13.7% (95% CI, 10.7–17.3). None of the twelve studies was of poor quality (<10 scores). Ten studies were published in ISI indexed journals, and nine of them were indexed for Medline. The level of heterogeneity observed across studies and between subgroups was moderate (<50%). The subgroup analysis revealed a higher pooled estimate of diabetes in males than in females (13.1 vs. 12.4%). It was also higher in urban than in rural patients (15.1 vs. 1.6%), and in HbA1c than in OGTT tests (23.9 vs. 14.4%). However, pooled estimates of the WHO and the ADA criteria were similar (13.8 vs. 13.5%). Conclusions: The prevalence of diabetes is on the rise in the adult population of Pakistan. The heterogeneity across studies observed in the meta-analysis suggested that the design of future diabetes surveys should be efficient and purposeful, and that valid tools and methods should be used to generate more precise data. Moreover, harmony between the stakeholders is much needed to seek a true picture of the diabetes burden in the country.
miR-939-5p Contributes to the Migration and Invasion of Pancreatic Cancer by Targeting ARHGAP4

Objective Rho GTPase-activating protein 4 (ARHGAP4) is a GTPase‐activating protein for the small GTPases of the Rho family that is involved in tumorigenesis. We recently reported that ARHGAP4 can mediate Warburg effect and malignant phenotype of pancreatic cancer. However, the regulation of ARHGAP4 remains unclear. Methods ARHGAP4 and miR-939-5p expressions in pancreatic cancer tissues and cell lines were measured by real-time PCR or Western blotting. Pancreatic cancer cells were transfected with miR-939-5p inhibitor, miR-939-5p mimic and/or lentivirus expressing ARHGAP4, and the cell viability, invasion and migration were measured by CCK-8 and Transwell assay, respectively. The suppression of ARHGAP4 expression by miR-939-5p was revealed by luciferase reporter assay, real-time PCR or Western blotting. Results ARHGAP4 expression was decreased, while miR-939-5p was increased in pancreatic cancer tissues compared with adjacent-normal pancreatic tissues. Higher miR-939-5p expression was correlated with advanced pathological stages and poor prognosis of pancreatic cancer patients. miR-939-5p directly targeted ARHGAP4. Either miR-939-5p down-regulation or ARHGAP4 overexpression inhibited viability, invasion and migration of pancreatic cancer cells. However, ARHGAP4 overexpression markedly inhibited the increased viability, migration, and invasion induced by miR-939-5p up-regulation in pancreatic cancer cells. Conclusion These observations suggested that miR-939-5p regulates the malignant phenotype of pancreatic cancer cells by targeting ARHGAP4, establishing miR-939-5p as a novel regulator of ARHGAP4 with a critical role in tumorigenesis in pancreatic cancer.
Prostate-specific antigen (PSA) screening rates and factors associated with screening in Eastern Canadian men: Findings from cross-sectional survey data.

INTRODUCTION The prostate-specific antigen (PSA) test is used in Canada to detect prostate cancer (PCa) despite mixed recommendations. Complications arising from false-positives are common, posing as a cancer-screening concern. This work estimates some Canadian rates of PSA screening and identifies men at increased odds for PSA screening. METHODS The Canadian Community Health Survey (CCHS) from 2009/10 (Atlantic Canada; ATL), 2011/2012 (Ontario; ON), and 2013/2014 (Quebec; QC) were used. Lifetime and recent PSA screening with confidence intervals were constructed to estimate PSA screening in ATL, ON, and QC. Two logistic regression models (for men <50 and ≥50 years of age) were used to determine associations between factors and lifetime PSA screening. RESULTS PSA screening rates have increased in most age groups for ATL, ON, and QC since 2000/2001. Factors positively associated with lifetime PSA screening in men of all ages were: having a digital rectal exam, having a regular doctor, and having a colorectal exam. Fruit and vegetables consumption and non-smoking status were positively associated with lifetime PSA screening in men <50 years of age. High income and the presence of chronic health conditions were positively associated with lifetime PSA screening in men ≥50 years of age. CONCLUSIONS PSA screening rates have generally increased since 2000/2001 in Canada. Physician-related factors play a role in men at all ages, while different factors are associated in men <50 years of age and men ≥50 years of age. Limitations include the generalizability to all of Canada and the potential for recall bias.
Biofilm formation by South-African Shiga toxigenic non-O157 Escherichia coli on stainless steel coupons.

This study examined the biofilm-forming ability of six non-O157 STEC serotypes: O116:H21, wzx-Onovel5:H19, O129:H21, O129:H23, O26:H11 and O154:H10 on stainless steel coupons after 24, 48 and 72 h of incubation at 22 °C and 168 h at 10 °C. Based on crystal violet staining, O129:H23 and O154:H10 were able to form biofilms on both the submerged surface and the air-liquid interface of coupons whereas, O116:H21, wzx-Onovel5:H19, O129:H21 and O26:H11 formed biofilm only at the air-liquid interface. Viable cell counts and scanning electron microscopy showed that biofilm formation increased (p < 0.05) over time. The biofilm-forming ability of non-O157 STEC was strongest (p < 0.05) at 22 °C after 48 h incubation. The strongest biofilm former regardless of temperature was O129:H23. Generally, at 10 °C, weak to no biofilm was observed for isolates O154:H10, O116:H21, wzx-Onovel5:H19, O26:H11 and O129:H21 after 168 h. This study found that temperature affected biofilm-forming ability of non-O157 STEC strains. Overall, our data indicate that the high potential biofilm formation abilities of isolates at 22 °C, suggests that non-O157 STEC strains could colonize stainless steel within food-processing facilities. This could serve as a potential source of adulteration and promote the dissemination of these potential pathogens in food.
Adoption of Precision Farming Tools: The Case of Italian Farmers

The process of adopting innovation, especially with regard to precision farming (PF), is inherently complex and social, and influenced by producers, change agents, social norms and organizational pressure. An empirical analysis was conducted among Italian farmers to measure the drivers and clarify “bottlenecks” in the adoption of agricultural innovation. The purpose of this study was to analyze the socio-structural and complexity factors that affect the probability to adopt innovations and the determinants that drive an individual’s decisions. Preliminary results found high levels of adoption among younger farmers, those that had a high level of education, those with high intensity of information, with large farm sizes, and high labor intensity. A logit model was used to understand the role played by labor intensity and perceived in the adoption process. In light of the Common Agricultural Policy Reform post 2020, the findings suggest relevant policy implications, such as the need to increase awareness of PF tools and foster dissemination of information aimed at reducing the degree of perceived complexity.
Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer.

BACKGROUND Muscle-invasive bladder cancer (MIBC) can be cured by radical radiotherapy (RT). We previously found tumour MRE11 expression to be predictive of survival following RT in MIBC, and this was independently validated in a separate institute. Here, we investigated germline MRE11A variants as possible predictors of RT outcomes in MIBC, using next-generation sequencing (NGS). PATIENTS AND METHODS The MRE11A gene was amplified in germline DNA from 186 prospectively recruited MIBC patients treated with RT and sequenced using bar-coded multiplexed NGS. Germline variants were analysed for associations with cancer-specific survival (CSS). For validation as a prognostic or predictive marker, rs1805363 was then genotyped in a cystectomy-treated MIBC cohort of 256 individuals. MRE11A mRNA isoform expression was measured in bladder cancer cell lines and primary tumour samples. RESULTS Carriage of at least one of six (five novel) rare variants was associated with the worse RT outcome (hazard ratio [HR] 4.04, 95% confidence interval [95% CI] 1.42-11.51, P = 0.009). The single-nucleotide polymorphism (SNP), rs1805363 (minor allele frequency 11%), was also associated with worse CSS (per-allele HR 2.10, 95% CI 1.34-3.28, Ptrend = 0.001) following RT in MIBC, with a gene-dosage effect observed, but no effect seen on CSS in the cystectomy cohort (Ptrend = 0.89). Furthermore, rs1805363 influenced relative MRE11A isoform expression, with increased isoform 2 expression with carriage of the rs1805363 minor A allele. CONCLUSIONS Germline MRE11A SNP rs1805363 was predictive of RT, but not of cystectomy outcome in MIBC. If successfully validated in an independent RT-treated cohort, this SNP could be a useful clinical tool for selecting patients for bladder-conserving treatment.
The African Swine Fever Epidemic in Wild Boar (Sus scrofa) in Lithuania (2014–2018)

In January 2014 the first case of African swine fever (ASF) in wild boar of the Baltic States was reported from Lithuania. It has been the first occurrence of the disease in Eastern EU member states. Since then, the disease spread further affecting not only the Baltic States and Poland but also south-eastern Europe, the Czech Republic and Belgium. The spreading pattern of ASF with its long-distance spread of several hundreds of kilometers on the one hand and the endemic situation in wild boar on the other is far from being understood. By analyzing data of ASF cases in wild boar along with implemented control measures in Lithuania from 2014–2018 this study aims to contribute to a better understanding of the disease. In brief, despite huge efforts to eradicate ASF, the disease is now endemic in the Lithuanian wild boar population. About 86% of Lithuanian’s territory is affected and over 3225 ASF cases in wild boar have been notified since 2014. The ASF epidemic led to a considerable decline in wild boar hunting bags. Intensified hunting might have reduced the wild boar population but this effect cannot be differentiated from the population decline caused by the disease itself. However, for ASF detection sampling of wild boar found dead supported by financial incentives turned out to be one of the most effective tools.
Health scores for farmed animals: Screening pig health with register data from public and private databases

There are growing demands to ensure animal health and, from a broader perspective, animal welfare, especially for farmed animals. In addition to the newly developed welfare assessment protocols, which provide a harmonised method to measure animal health during farm visits, the question has been raised whether data from existing data collections can be used for an assessment without a prior farm visit. Here, we explore the possibilities of developing animal health scores for fattening pig herds using a) official meat inspection results, b) data on antibiotic usage and c) data from the QS (QS Qualität und Sicherheit GmbH) Salmonella monitoring programme in Germany. The objective is to aggregate and combine these register-like data into animal health scores that allow the comparison and benchmark of participating pig farms according to their health status. As the data combined in the scores have different units of measure and are collected in different abattoirs with possibly varying recording practices, we chose a relative scoring approach using z-transformations of different entrance variables. The final results are aggregated scores in which indicators are combined and weighted based on expert opinion according to their biological significance for animal health. Six scores have been developed to describe different focus areas, such as "Respiratory Health", "External Injuries/ Alterations", "Animal Management", "Antibiotic Usage", "Salmonella Status" and "Mortality". These "focus" area scores are finally combined into an "Overall Score". To test the scoring method, existing routine data from 1,747 pig farm units in Germany are used; these farm units are members of the QS Qualität und Sicherheit GmbH (QS) quality system. In addition, the scores are directly validated for 38 farm units. For these farm units, the farmers and their veterinarians provided their perceptions concerning the actual health status and existing health problems. This process allowed a comparison of the scoring results with actual health information using kappa coefficients as a measure of similarity. The score testing of the focus area scores using real information resulted in normalised data. The results of the validation showed satisfactory agreement between the calculated scores for the project farm units and the actual health information provided by the related farmers and veterinarians. In conclusion, the developed scoring method could become a viable benchmark and risk assessment instrument for animal health on a larger scale under the conditions of the German system.
Pulse Wave Velocity in Chronic Obstructive Pulmonary Disease and the Impact of Inhaled Therapy (SUMMIT): A Randomized Double-blind Clinical Trial.

Citation for published version: Crim, C, Anderson, JA, Calverley, PMA, Celli, BR, Cowans, NJ, Martinez, FJ, Newby, DE, Vestbo, J, Yates, JC & Brook, RD 2020, 'Pulse Wave Velocity in Chronic Obstructive Pulmonary Disease and the Impact of Inhaled Therapy (SUMMIT): A Randomized Double-blind Clinical Trial', American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.201908-1639LE