Miracle-dz/UniFAR-FTUs huggingface dataset:
CTNNB1 S37C mutation causing cells proliferation and migration coupled with molecular mechanisms in lung adenocarcinoma

Background This study aimed to investigate the potential cytological effects and molecular mechanisms of β-catenin (CTNNB1) S37C mutation in lung adenocarcinoma (LUAD). Methods CTNNB1 with S37C mutation were transfected into LUAD cell lines. The expression of β-catenin were determined using Western blot. Cell proliferation and migration were detected using cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. Transcriptome sequencing was performed on LUAD cells with CTNNB1 S37C mutation (CTNNB1 mutation group) and LUAD cells without treatment (Control group), followed by the screening of differentially expressed genes (DEGs). Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed for the DEGs. Finally, the expression of key DEGs were validated by quantitative real-time PCR (qRT-PCR). Results CTNNB1 with S37C mutation was successful expressed in 2 cell lines. Cells proliferation and migration were significantly promoted in mutation group in comparison with that of Control group (P<0.05). A total of 180 DEGs were revealed between Control and CTNNB1 mutation groups. These DEGs were mainly enriched in extracellular matrix function and nicotine addiction pathway. PPI network contained 51 DEGs and 45 interactions. PTPRD, GNG7 and CNTN1 were hub genes in PPI network with higher degree. CGB5 interacted with PTPRU, while IGFBP3 showed interaction with MMP1. Results of qRT-PCR confirmed the expression of several key DEGs in transcriptome analysis. Conclusions CTNNB1 S37C mutation contributed the LUAD cells proliferation and migration. PTPRD, IGFBP-3, MMP1 and PTPRU might play roles in the effect of CTNNB1 S37C mutation in LUAD.
Unprecedented increase of West Nile virus neuroinvasive disease, Spain, summer 2020

Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.
The role of BAG3 in health and disease: A “Magic BAG of Tricks”

The multi‐domain structure of Bcl‐2‐associated athanogene 3 (BAG3) facilitates its interaction with many different proteins that participate in regulating a variety of biological pathways. After revisiting the BAG3 literature published over the past ten years with Citespace software, we classified the BAG3 research into several clusters, including cancer, cardiomyopathy, neurodegeneration, and viral propagation. We then highlighted recent key findings in each cluster. To gain greater insight into the roles of BAG3, we analyzed five different published mass spectrometry data sets of proteins that co‐immunoprecipitate with BAG3. These data gave us insight into universal, as well as cell‐type‐specific BAG3 interactors in cancer cells, cardiomyocytes, and neurons. Finally, we mapped variable BAG3 SNPs and also mutation data from previous publications to further explore the link between the domains and function of BAG3. We believe this review will provide a better understanding of BAG3 and direct future studies towards understanding BAG3 function in physiological and pathological conditions.
Machine learning model on heart rate variability metrics identifies asymptomatic toddlers exposed to zika virus during pregnancy

Objective. Although the Zika virus (ZIKV) seems to be prominently neurotropic, there are some reports of involvement of other organs, particularly the heart. Of special concern are those children exposed prenatally to ZIKV and born without microcephaly or other congenital anomalies. Electrocardiogram (ECG)—derived heart rate variability (HRV) metrics represent an attractive, low-cost, widely deployable tool for early identification of developmental functional alterations in exposed children born without such overt clinical symptoms. We hypothesized that HRV in such children would yield a biomarker of fetal ZIKV exposure. Our objective was to test this hypothesis in young children exposed to ZIKV during pregnancy. Approach. We investigated the HRV properties of 21 children aged 4–25 months from Brazil. The infants were divided into two groups, the ZIKV-exposed (n = 13) and controls (n = 8). Single-channel ECG was recorded in each child at ∼15 months of age and HRV was analyzed in 5 min segments to provide a comprehensive characterization of the degree of variability and complexity of the heart rate. Main results. Using a cubic support vector machine classifier we identified babies as Zika cases or controls with a negative predictive value of 92% and a positive predictive value of 86%. Our results show that a machine learning model derived from HRV metrics can help differentiate between ZIKV-affected, yet asymptomatic, and non-ZIKV-exposed babies. We identified the box count as the best HRV metric in this study allowing such differentiation, regardless of the presence of microcephaly. Significance. We show that it is feasible to measure HRV in infants and toddlers using a small non-invasive portable ECG device and that such an approach may uncover the memory of in utero exposure to ZIKV. We discuss putative mechanisms. This approach may be useful for future studies and low-cost screening tools involving this challenging to examine population.
Epidemiology of Heart Failure

Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.
Surgical treatment for cryptoglandular and Crohn’s perianal fistulas: Protocol of an umbrella review

Introduction A high prevalence of cryptoglandular and Crohn’s perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn’s perianal fistulas through an umbrella review. Methods and analysis A systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn’s perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn’s perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality. Ethics and dissemination Ethics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference. PROSPERO registration number CRD42020200754.
Therapeutic effects and mechanism of ferulic acid and icariin in mammary gland hyperplasia model rats via regulation of the ERK pathway

Background Ferulic acid (FA) and icariin (ICA), as the active compounds derived from Angelica sinensis and Epimedium brevicornum Maxim, respectively, have been shown to promote blood circulation, regulate menstruation, exhibit anti-inflammatory effects, and modulate estrogen levels. The aim of this study was to elucidate the possible mechanism of FA, ICA, and FA-ICA on estrogen-induced mammary gland hyperplasia (MGH) in rats. Methods Hematoxylin and eosin (HE) staining was performed to record the pathological changes in breast tissue, and enzyme-linked immunosorbent assay (ELISA) was utilized to determine the serum levels of luteinizing hormone (LH), PRL (prolactin), testosterone (T), estradiol (E2), follicular stimulating hormone (FSH), and progesterone (P). The message RNA (mRNA) expression levels of extracellular signal-regulated kinase 1 (ERK1), extracellular signal-regulated kinase 2 (ERK2), estrogen receptor (ER), and progesterone receptor (PR) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. Furthermore, ER, phosphorylated-ER, PR, p-PR, ERK1/2, and p-ERK1/2 protein factors in the ERK signaling pathway were evaluated by Western blotting. Simultaneously, changes in breast height, diameter, body weight, and organ index were all recorded. Results We found that FA and ICA could modulate the degree of breast swelling, and reduce the body weight, thymus index, and uterus index. Furthermore, it could also block the pathological changes of MGH, including the number of mammary lobules, and the proliferation or expansion of acini and ducts. Moreover, treatment with FA and ICA remarkably down-regulated the serum expression levels of LH, PRL, T, and E2, as well as the mRNA expression levels of ERα, PR, ERK1, and ERK2. Additionally, protein levels of ERα, p-ERα, PR, p-PR, ERK1/2, and p-ERK1/2 in breast tissue were down-regulated, however the serum content of FSH and P was up-regulated. Conclusions Our outcomes revealed that FA and ICA might potentially inhibit ERα, PR, ERK1/2, and their phosphorylated proteins via the ERK signaling pathway, thus indicating a positive feedback control for the degree of breast hyperplasia.
Do Patients Maintain Proper Long-Term Cardiopulmonary Fitness Levels After Cardiac Rehabilitation? A Retrospective Study Using Medical Records

Objective To examine whether patients who participated in a cardiac rehabilitation (CR) program after hospitalization for acute coronary syndrome maintained cardiorespiratory fitness (CRF) in the community. Methods We conducted a retrospective study including 78 patients who underwent percutaneous coronary intervention or coronary artery bypass graft surgery at our hospital’s cardiovascular center and participated in a CR program and a 5-year follow-up evaluation. Patients were divided into a center-based CR (CBCR) group, participating in an electrocardiography-monitored exercise training in a hospital setting, and a home-based CR (HBCR) group, receiving aerobic exercise training and performed self-exercise at home. Results No significant differences were found between groups (p>0.05), except the proportion of non-smokers (CBCR 59.5% vs. HBCR 31.7%; p=0.01). In both groups, the maximal oxygen consumption (VO2max) increased significantly during the first 12 weeks of follow-up and remained at a steady state for the first year, but it decreased after the 1-year follow-up. Particularly, VO2max at 5 years decreased below the baseline value in the HBCR group. In the low CRF group, the CRF level significantly improved at 12 weeks, peaked at 1 year, and was still significantly different from the baseline value after 5 years. The high CRF group did not show any significant increase over time relative to the baseline value, but most patients in the high CRF group maintained relatively appropriate CRF levels after 5 years. Conclusion Continuous support should be provided to patients to maintain optimal CRF levels after completing a CR program.
Identification of and Surveillance for the SARS-CoV-2 Variants B.1.427 and B.1.429 — Colorado, January–March 2021

The B.1. 427 and B.1. 429 variants of SARS-CoV-2, the virus that causes COVID-19, were first described in Southern California on January 20, 2021 (1); on March 16 they were designated variants of concern* (2). Data on these variants are limited, but initial reports suggest that, compared with other lineages, they might be more infectious (1,2), cause more severe illness (2), and be less susceptible to neutralizing monoclonal antibody products such as bamlanivimab, an investigational treatment for mild-to-moderate COVID-19 (1-3). On January 24, the Colorado Department of Public Health and Environment (CDPHE) identified the first Colorado case of COVID-19 attributed to these variants. B.1. 427 and B.1. 429 were considered a single variant described as CAL.20C or B.1. 427/B.1. 429 in the 20C clade (1,3); in this report "B.1. 427/B.1. 429" refers to B.1. 427 or B.1. 429 lineage, including those reported as B.1. 427/B.1. 429 without further differentiation.
Total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis.

OBJECTIVE & BACKGROUND Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns. METHODS Head-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and the R0 resection rate. RESULTS Eight phase II/III RCTs involving 2,196 LARC patients were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (OR = 1.77, 95% CI: 1.28 to 2.45, P = 0.0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard CRT (HR=0.83, 95% CI: 0.72 to 0.96, P = 0.03; HR=0.88, 95% CI:0.74 to 1.05, P = 0.15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR=0.81, 95% CI: 0.68 to 0.95, P = 0.012). CONCLUSION The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS, and reduce the risk of distant metastasis. IMPLICATIONS FOR PRACTICE Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis due to its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pCR rate, DFS, OS, and DMFS compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
Transcription, mRNA Export, and Immune Evasion Shape the Codon Usage of Viruses

Abstract The nucleotide composition, dinucleotide composition, and codon usage of many viruses differ from their hosts. These differences arise because viruses are subject to unique mutation and selection pressures that do not apply to host genomes; however, the molecular mechanisms that underlie these evolutionary forces are unclear. Here, we analyzed the patterns of codon usage in 1,520 vertebrate-infecting viruses, focusing on parameters known to be under selection and associated with gene regulation. We find that GC content, dinucleotide content, and splicing and m6A modification-related sequence motifs are associated with the type of genetic material (DNA or RNA), strandedness, and replication compartment of viruses. In an experimental follow-up, we find that the effects of GC content on gene expression depend on whether the genetic material is delivered to the cell as DNA or mRNA, whether it is transcribed by endogenous or exogenous RNA polymerase, and whether transcription takes place in the nucleus or cytoplasm. Our results suggest that viral codon usage cannot be explained by a simple adaptation to the codon usage of the host—instead, it reflects the combination of multiple selective and mutational pressures, including the need for efficient transcription, export, and immune evasion.
Interoceptive Awareness, Decision-Making and Impulsiveness in Male Patients with Alcohol or Opioid Use Disorder

Abstract Background The present study was prepared on the assumption that interoceptive awareness (IA) and decision-making processes are implicated in addiction, and that somatic feedback plays an important role in decision-making. Methods The study participants included 80 abstinent male inpatients with alcohol use disorder (n = 40) or opioid use disorder (n = 40) according to DSM-5 criteria (current severity: moderate or severe), along with 40 healthy male volunteers. All participants performed the heart rate tracking task as an objective physiological performance measure of IA and a computerized version of the Iowa gambling task (IGT) as a validated measure of decision-making. Impulsiveness was assessed using the Barratt Impulsiveness Scale 11 (BIS-11). Craving was evaluated with the Penn Alcohol Craving Scale (PACS) or Substance Craving Scale (SCS). Results (1) Heartbeat perception (HBP) and IGT scores were similar between the patients with alcohol or opioid addiction, being significantly lower than those in the control group, and the difference remained significant even when controlling for the factors that were significant in bivariate analyses; (2) HBP scores of patients correlated significantly with IGT scores, even when controlling the effect of the related variables; (3) BIS-11 scores of patients negatively correlated significantly with HBP scores and did not correlate significantly with IGT scores; and (4) PACS/SCS scores did not correlate significantly with HBP and IGT scores. Conclusions Our findings support the hypothesis that IA and decision-making processes are implicated in addiction and that decreased IA is associated with impaired decision-making.
Improvement of renal function after transcatheter aortic valve replacement in patients with chronic kidney disease

Background Chronic kidney disease is commonly found in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and has marked impact in their prognosis. It has been shown however that TAVR may improve renal function by alleviating the hemodynamic barrier imposed by AS. Nevertheless, the predictors of and clinical consequences of renal function improvement are not well established. Our aim was to assess the predictors of improvement of renal function after TAVR. Methods The present work is an analysis of the Brazilian Registry of TAVR, a national non-randomized prospective study with 22 Brazilian centers. Patients with baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) were stratified according to renal function after TAVR: increase >10% in eGFR were classified as TAVR induced renal function improvement (TIRFI); decrease > 10% in eGFR were classified as acute kidney injury (AKI) and stable renal function (neither criteria). Results A total of 819 consecutive patients with symptomatic severe AS were included. Of these, baseline renal dysfunction (estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) was present in 577 (70%) patients. Considering variance in renal function between baseline and at discharge after TAVR procedure, TIRFI was seen in 197 (34.1%) patients, AKI in 203 (35.2%), and stable renal function in 177 (30.7%). The independent predictors of TIRFI were: absence of coronary artery disease (OR: 0.69; 95% CI 0.48–0.98; P = 0.039) and lower baseline eGFR (OR: 0.98; 95% CI 0.97–1.00; P = 0.039). There was no significant difference in 30-day and 1-year all-cause mortality between patients with stable renal function or TIRFI. Nonetheless, individuals that had AKI after TAVR presented higher mortality compared with TIRFI and stable renal function groups (29.3% vs. 15.4% vs. 9.5%, respectively; p < 0.001). Conclusions TIRFI was frequently found among baseline impaired renal function individuals but was not associated with improved 1-year outcomes.