Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Impact of Myocardial Extracellular Volume Fraction Assessment Using Dual‐Energy Computed Tomography in Patients Treated With Aortic Valve Replacement for Severe Aortic Stenosis

Background Myocardial extracellular volume fraction (ECV), measured by cardiac magnetic resonance imaging, is a useful prognostic marker for patients who have undergone aortic valve replacement (AVR) for aortic stenosis. However, the prognostic significance of ECV measurements based on computed tomography (CT) is unclear. This study evaluated the association between ECV measured with dual‐energy CT and clinical outcomes in patients with aortic stenosis who underwent transcatheter or surgical AVR. Methods and Results We retrospectively enrolled 95 consecutive patients (age, 84.0±5.0 years; 75% women) with severe aortic stenosis who underwent preprocedural CT for transcatheter AVR planning. ECV was measured using iodine density images obtained by delayed enhancement dual‐energy CT. The primary end point was a composite outcome of all‐cause death and hospitalization for heart failure after AVR. The mean ECV measured with CT was 28.1±3.8%. During a median follow‐up of 2.6 years, 22 composite outcomes were observed, including 15 all‐cause deaths and 11 hospitalizations for heart failure. In Kaplan‐Meier analysis, the high ECV group (≥27.8% [median value]) had significantly higher rates of composite outcomes than the low ECV group (<27.8%) (log‐rank test, P=0.012). ECV was the only independent predictor of adverse outcomes on multivariable Cox regression analysis (hazards ratio, 1.25; 95% CI, 1.10‒1.41; P<0.001). Conclusions Myocardial ECV measured with dual‐energy CT in patients who underwent aortic valve intervention was an independent predictor of adverse outcomes after AVR.
Epidemiology and genetic characteristics of murine kobuvirus from faecal samples of Rattus losea, Rattus tanezumi and Rattus norvegicus in southern China

Recently, murine kobuvirus (MuKV), a novel member of the family Picornaviridae, was identified in faecal samples of Rattus norvegicus in China. The limited information on the circulation of MuKV in other murine rodent species prompted us to investigate its prevalence and conduct a genetic characterization of MuKV in Rattus losea, Rattus tanezumi and Rattus norvegicus in China. Between 2015 and 2017, 243 faecal samples of these three murine rodent species from three regions in southern China were screened for the presence of MuKV. The overall prevalence was 23.0% (56/243). Three complete MuKV polyprotein sequences were acquired, and the genome organization was determined. Phylogenetic analyses suggested that our sequences were closely related to Chinese strains and belong to the species Aichivirus A in the genus Kobuvirus. Additional studies are required to understand the true prevalence of MuKV in murine rodent populations in China.
Should a third booster dose be scheduled after two doses of CoronaVac? A single‐center experience

In the 10th month of the pandemic, coronavirus disease 2019 (COVID‐19) vaccination was given first to healthcare workers in Turkey after receiving emergency use approval from the Ministry of Health. This study, which was performed at the COVID‐19 reference center in Ankara (the capital of Turkey) aimed to evaluate the seroconversion rate of the CoronaVac vaccine. The anti‐spike immunoglobulin G response to the two‐dose vaccination was retrospectively examined in healthcare workers who had no previous history of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. The postvaccine seroconversion rate was investigated by measuring the antibody levels of healthcare workers who had received CoronaVac. Vaccination was administered as 600 SU in 28‐day intervals. The healthcare workers' anti‐SARS‐CoV‐2 immunoglobulin G levels were used to determine the seroconversion rate 2 months after the second dose of the vaccine. Of the healthcare workers, 22.9% (n = 155) were seronegative. The younger the age of the participant, the higher the level of anti‐SARS‐CoV‐2 immunoglobulin G. Furthermore, anti‐SARS‐CoV‐2 immunoglobulin G levels were much higher in women than men.
CTCF binding modulates UV damage formation to promote mutation hot spots in melanoma

Somatic mutations in DNA‐binding sites for CCCTC‐binding factor (CTCF) are significantly elevated in many cancers. Prior analysis has suggested that elevated mutation rates at CTCF‐binding sites in skin cancers are a consequence of the CTCF‐cohesin complex inhibiting repair of UV damage. Here, we show that CTCF binding modulates the formation of UV damage to induce mutation hot spots. Analysis of genome‐wide CPD‐seq data in UV‐irradiated human cells indicates that formation of UV‐induced cyclobutane pyrimidine dimers (CPDs) is primarily suppressed by CTCF binding but elevated at specific locations within the CTCF motif. Locations of CPD hot spots in the CTCF‐binding motif coincide with mutation hot spots in melanoma. A similar pattern of damage formation is observed at CTCF‐binding sites in vitro, indicating that UV damage modulation is a direct consequence of CTCF binding. We show that CTCF interacts with binding sites containing UV damage and inhibits repair by a model repair enzyme in vitro. Structural analysis and molecular dynamic simulations reveal the molecular mechanism for how CTCF binding modulates CPD formation.
GWAS for genetics of complex quantitative traits: Genome to pangenome and SNPs to SVs and k‐mers

The development of improved methods for genome‐wide association studies (GWAS) for genetics of quantitative traits has been an active area of research during the last 25 years. This activity initially started with the use of mixed linear model (MLM), which was variously modified. During the last decade, however, with the availability of high throughput next generation sequencing (NGS) technology, development and use of pangenomes and novel markers including structural variations (SVs) and k‐mers for GWAS has taken over as a new thrust area of research. Pangenomes and SVs are now available in humans, livestock, and a number of plant species, so that these resources along with k‐mers are being used in GWAS for exploring additional genetic variation that was hitherto not available for analysis. These developments have resulted in significant improvement in GWAS methodology for detection of marker‐trait associations (MTAs) that are relevant to human healthcare and crop improvement.
Mild COVID-19 and Impaired Blood Cell–Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?

Abstract Background Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient. Methods We analyzed erythrocytes, circulating endothelial cells, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 (n = 31) and matched healthy controls (n = 32) on admission and at hospital discharge. Results All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endothelial cells was significantly (40–100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. COVID-19 also provoked formation of stacked aggregated erythrocytes capable of clogging microvascular bed and of diminishing oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining intracellular penetration of SARS-CoV-2 where it may be replicated and returned to circulation. Conclusion These observational and descriptive data suggest that persistent viral cell injury may cause blood vessel damage; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. There is a residual blood cell damage following the acute phase in some COVID-19 survivors. Controlled outcome-driven trials are urgently needed for exploring optimal use of long-term antithrombotics and vascular protection strategies even after mild COVID-19.
Effectiveness of an HIV care model integrated into addiction care based on medication-assisted treatment for HIV-positive people who use drugs

ABSTRACT Our objective was to evaluate the effectiveness of initiated or reinitiated antiretroviral therapy (ART) in HIV-positive active drug users receiving integrated HIV and addiction care in a harm reduction setting. We performed a study of HIV-positive persons who use drugs (PWUD) in a harm reduction unit in Madrid, Spain. Participants received HIV care integrated into addiction care and received at least one dose of observed ART based on medication-assisted treatment between January 2013 and December 2019. Individuals newly diagnosed with HIV (n = 13) had a greater median CD4 cell count at baseline were less likely to be late presenters, had a greater CD4 cell count increase, and were less likely to have AIDS in comparison to those who were aware of their HIV status (n = 87) at initiation or reinitiation of ART. The overall VS was 73% in the intention-to-treat (ITT) analysis and 92.4% in the modified intention-to-treat (mITT) analysis. People who were engaged in OST, people with >90% adherence to ART, and older people were positively associated with VS in the multivariate analysis. An HIV care model integrated into a harm reduction facility demonstrated a high uptake of HIV treatment, retention in care, improvement in adherence, and achievement of VS.
Genotyping, drug resistance and virulence factors of Candida species isolated from patients using long‐term inhaled steroids

In this study, it was aimed to determine the isolation frequency and species distribution of Candida species isolated from asthmatic patients using long‐term inhaled steroids. It was also aimed to determine the drug resistance patterns and the frequency of erg11, HWP1, ALS1, INT1, SAP1 PLB1 genes in isolates.
A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

ABSTRACT Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers and hence changes the cytoskeleton to affect the invasiveness and metastasis of tumors. This study aimed to investigate the function and clinical significance of ACTB in pan-cancer. The role of ACTB for prognosis and immune regulation across 33 tumors was explored based on the datasets of gene expression omnibus and the cancer genome atlas. Differential expression of ACTB was found between cancer and adjacent normal tissues, and significant associations was found between ACTB expression and prognosis of tumor patients. In most cancers, ACTB expression was associated with immune cells infiltration, immune checkpoints and other immune modulators. Relevance between ACTB and metastasis and invasion was identified in various types of cancers by CancerSEA. Moreover, focal adhesion and actin regulation-associated pathways were included in the functional mechanisms of ACTB. The expression of ACTB was verified by quantitative real-time polymerase chain reaction. Knockdown of ACTB inhibited head and neck squamous carcinoma cell migration and invasion by NF-κB and Wnt/β-catenin pathways. Our first pan-cancer study of ACTB offers insight into the prognostic and immunological roles of ACTB across different tumors, indicating ACTB may be a potential biomarker for poor prognosis and immune infiltration in cancers, and the role of ACTB as a reference gene in cancers was challenged.
The Health of Gulf War and Gulf Era Veterans Over Time

Objective: The aim of this study was to describe the self-reported physical and mental health over the course over 19 years of follow up of a population-based cohort of Gulf War and Gulf Era veterans. Methods: A multi-modal health survey of 6338 Gulf War and Gulf Era veterans who participated in all three waves of the longitudinal study. Results: Gulf War and Gulf War Era veterans experienced an increase in prevalence of chronic disease over time. The adjusted odds ratios suggest that Gulf War veterans not only had significantly higher odds of reporting medical conditions, but also began to report them earlier. Conclusions: The findings from this analysis suggest that Gulf War veterans are not only more likely than their non-deployed counterparts to report chronic disease, they were more likely to report it earlier.
CD303 (BDCA-2) – a potential novel target for therapy in hematologic malignancies

Abstract Plasmacytoid dendritic cells (pDCs) serve as immunoregulatory antigen-presenting cells that play a role in various inflammatory, viral, and malignant conditions. Malignant proliferation of pDCs is implicated in the pathogenesis of certain hematologic cancers, specifically blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myelogenous leukemia with clonal expansion of pDC (pDC-AML). In recent years, BPDCN and pDC-AML have been successfully treated with targeted therapy of pDC-specific surface marker, CD123. However, relapsed and refractory BPDCN remains an elusive cancer, with limited therapeutic options. CD303 is another specific surface marker of human pDCs, centrally involved in antigen presentation and immune tolerance. Monoclonal antibodies directed against CD303 have been studied in preclinical models and have achieved disease control in patients with cutaneous lupus erythematosus. We performed a comprehensive review of benign and malignant disorders in which CD303 have been studied, as there may be a potential future CD303-directed therapy for many of these conditions.
Extreme temperatures and cardiovascular mortality: assessing effect modification by subgroups in Ganzhou, China

ABSTRACT Background Many people die from cardiovascular diseases each year, and extreme temperatures are regarded as a risk factor for cardiovascular deaths. However, the relationship between temperature and cardiovascular deaths varies in different regions because of population density, demographic inequality, and economic situation, and the evidence in Ganzhou, China is limited and inconclusive. Objective This study aimed to assess extreme temperature-related cardiovascular mortality and identify the potential vulnerable people. Methods After controlling other meteorological measures, air pollution, seasonality, relative humidity, day of the week, and public holidays, we examined temperature-related cardiovascular mortality along 21 lag days by Poisson in Ganzhou, China. Results A J-shaped relationship was observed between mean temperature and cardiovascular mortality. Extremely low temperatures substantially increased the relative risks (RR) of cardiovascular mortality. The effect of cold temperature was delayed by 2–6 days and persisted for 4–10 days. However, the risk of cardiovascular mortality related to extremely high temperatures was not significant (p > 0.05). Subgroup analysis indicated that extremely low temperatures had a stronger association with cardiovascular mortality in people with cerebrovascular diseases (RR: 1.282, 95% confidence interval [CI]: 1.020–1.611), males (RR: 1.492, 95% CI: 1.175–1.896), married people (RR: 1.590, 95% CI: 1.224–2.064), and people above the age of 65 years (RR: 1.641, 95% CI: 1.106–2.434) than in people with ischemic heart disease, females, unmarried people, and the elderly (≥65 years old), respectively. Conclusions The type of cardiovascular disease, sex, age, and marital status modified the effects of extremely low temperatures on the risk of cardiovascular mortality. These findings may help local governments to establish warning systems and precautionary measures to reduce temperature-related cardiovascular mortality.
Anthocyanin Copigmentation - Evaluation, Mechanisms and Implications for the Colour of Red Wines

Copigmentation is the main colour-stabilizing mechanism in plants and in food products of vegetable origin. It is a spontaneous and exothermic process that consists of the stacking of an organic molecule, called copigment, on the planar polarizable moieties of the anthocyanin coloured forms. Although this phenomenon has long been described, there are some aspects that are still not well understood or controversial like the nature of the interaction pigment to copigment, the way to quantify the extent of the process, its effect on other anthocyanin properties like astringency or reactivity. In this article a review of the most significant advances achieved in the last years in the field of intramolecular and intermolecular copigmentation is presented. Also, the most recent findings regarding wine copigments and their effects on the colour of red wines are revised.
Single cell DNA sequencing reveals punctuated and gradual clonal evolution in hepatocellular carcinoma.

BACKGROUND & AIMS Copy number alterations (CNAs), elicited by genome instability, is a major source of intratumor heterogeneity. How CNAs evolve in hepatocellular carcinoma (HCC) remains unknown. METHODS We performed single cell DNA sequencing (scDNA-seq) on 1275 cells isolated from 10 HCC patients, ploidy-resolved scDNA-seq of 356 cells from 1 additional patient, and single cell RNA sequencing (scRNA-seq) on 27344 cells from 3 additional patients. Three statistical fitting models were compared to investigate the CNA accumulation pattern. RESULTS Cells in the tumor were categorized into three subpopulations: euploid, pseudoeuploid, and aneuploid. Our scDNA-seq analysis revealed that CNA accumulation followed a dual-phase copy number evolution (DPCNE) model, i.e. a punctuated phase followed by a gradual phase. Patients exhibited prolonged gradual phase showed higher intratumor heterogeneity and worse disease-free survival. Integrating bulk RNA-seq of 17 HCC patients, published datasets of 1196 liver tumors, and immunohistochemical staining of 202 HCC tumors, we showed that high expression of CAD, a gene involved in pyrimidine synthesis, was correlated with rapid tumorigenesis and reduced survival. The DPCNE model was validated by our scRNA-seq data and published scDNA-seq datasets of other cancer types. Furthermore, ploidy-resolved scDNA-seq revealed the common clonal origin of diploid- and polyploid-aneuploid cells, suggesting that polyploid tumor cells were generated by whole genome doubling of diploid tumor cells. CONCLUSIONS Our work revealed a novel DPCNE model, showed HCC with longer gradual phase were more severe, identified CAD as a promising biomarker for early recurrence of HCC, and supported the diploid origin of polyploid HCC.
Scoping review of tests to assess tactical knowledge and tactical performance of young soccer players

ABSTRACT This scoping review aimed to systematically map studies/tests for assessing the tactical domain of young soccer players. The study followed the PRISMA-ScR and Joanna Briggs Institute guidelines. The databases searched were Scopus, SPORTDiscus, SciELO, LILACS, and BDTD. The eligibility criteria were defined based on the elements of population, context, and concept, without restrictions on the period, language, and type of publication. Twenty-four papers were included, from 1997 to 2020, totalling 29 tests/instruments for the assessment of the tactical domain, with the majority of studies having an European sample. Twelve terms were used to nominate the tactical component, regardless of the assessment method and approach. Six tests met eight or nine criteria in the critical appraisal: TCTOF, TACSIS Spanish version, Semi-Structured Interview, TCTP-OE, GPET, and FUTSAT. Thus, it is concluded that studies and tests for the assessment of the tactical domain of young soccer players are recent and mainly European; there is no consensus about the adopted terminology; and few tests met the majority of the quality criteria. Therefore, we suggest: a) the construction/adaptation of tests with samples from other continents; b) the use of the proposed criteria; and c) that the terms tactical knowledge and tactical performance are adopted.
Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey

Sickle cell disease (SCD) and thalassemias are the most common monogenic diseases in the world. The number of migrants and refugees in Europe and Turkey, in the past decade, has increased dramatically due to war, violence or prosecutions in their homeland. Prevention and management of haemoglobin disorders is well established and managed in countries where these conditions were traditionally endemic or in countries that have a longstanding tradition of receiving migrants. Therefore, preventive and diagnostic programmes regarding hemoglobinopathies in immigrant populations have been implemented. The purpose of this paper it to report a summary of the experience gained in Italy, Spain and Turkey in migrants, asylum seekers and refugees. (www.actabiomedica.it)
Interrelationship between body mass index and asthma in children suffering from asthma-analytical cross-sectional study.

OBJECTIVE Bronchial asthma and obesity are correlated diseases that are highly prevalent among children. The effect of increased body mass index (BMI), aggravating asthma, is currently controversial in this group. The aim of this study is to determine the association between Body Mass Index and severity of asthma among obese children with asthma and normal-weight children with asthma in Riyadh, Saudi Arabia. PATIENTS AND METHODS Data from a cross-sectional analysis of 64 participants from Riyadh, Saudi Arabia, were analyzed. Symptoms were assessed through children's and caregivers' responses to a pretested questionnaire. Grouping of children into obese (18) and non-obese (46) was based on their body mass index (BMI) percentile. Association between obesity and final asthma score was estimated by chi-square test using SPSS software and p-value set at 0.005. RESULTS The mean age was 10.13 ± 2.54 years (ranged 5 to 14), and the majority, 46 (71.88%), were boys. Most of the participants, 46 (71.88%), were normal to underweight and 18 (28.13%) were overweight or obese. Most of the children, 35 (54.69%), complained of cough because of asthma sometimes. Out of 64 participants, 21 (32.81%) had uncontrolled asthma, and 43 (67.19%) had controlled asthma calculated using a questionnaire. Out of 46 non-obese children with asthma, 7 (15.22%) had uncontrolled asthma, and out of 18 obese children with asthma, 14 (77.78%) had uncontrolled asthma, and the difference in the proportion of Asthma severity was significant statistically across the groups (p-value <0.001). CONCLUSIONS Poor control of asthma symptoms was significantly higher in both obese and normal-weight children with asthma.