Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk factors, clinical features, and outcomes of premature acute myocardial infarction

Aims To investigate the risk factors, clinical features, and prognostic factors of patients with premature acute myocardial infarction (AMI). Materials and methods A retrospective cohort study of patients with AMI included in data from the West China Hospital of Sichuan University from 2011 to 2019 was divided into premature AMI (aged < 55 years in men and < 65 years in women) and non-premature AMI. Patients’ demographics, laboratory tests, Electrocardiography (ECG), cardiac ultrasound, and coronary angiography reports were collected. All-cause death after incident premature MI was enumerated as the primary endpoint. Results Among all 8,942 AMI cases, 2,513 were premature AMI (79.8% men). Compared to the non-premature AMI group, risk factors such as smoking, dyslipidemia, overweight, obesity, and a family history of coronary heart disease (CHD) were more prevalent in the premature AMI group. The cumulative survival rate of patients in the premature AMI group was significantly better than the non-premature AMI group during a mean follow-up of 4.6 years (HR = 0.27, 95% CI 0.22–0.32, p < 0.001). Low left ventricular ejection fraction (LVEF) (Adjusted HR 3.00, 95% CI 1.85–4.88, P < 0.001), peak N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (Adjusted HR 1.34, 95% CI 1.18–1.52, P < 0.001) and the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCEs) (Adjusted HR 2.36, 95% CI 1.45–3.85, P = 0.001) were predictors of poor prognosis in premature AMI patients. Conclusion AMI in young patients is associated with unhealthy lifestyles such as smoking, dyslipidemia, and obesity. Low LVEF, elevated NT-proBNP peak level, and the occurrence of in-hospital MACCEs were predictors of poor prognosis in premature AMI patients.
An imaging-based RNA interference screen for modulators of the Rab6-mediated Golgi-to-ER pathway in mammalian cells

In mammalian cells, membrane traffic pathways play a critical role in connecting the various compartments of the endomembrane system. Each of these pathways is highly regulated, requiring specific machinery to ensure their fidelity. In the early secretory pathway, transport between the endoplasmic reticulum (ER) and Golgi apparatus is largely regulated via cytoplasmic coat protein complexes that play a role in identifying cargo and forming the transport carriers. The secretory pathway is counterbalanced by the retrograde pathway, which is essential for the recycling of molecules from the Golgi back to the ER. It is believed that there are at least two mechanisms to achieve this - one using the cytoplasmic COPI coat complex, and another, poorly characterised pathway, regulated by the small GTPase Rab6. In this work, we describe a systematic RNA interference screen targeting proteins associated with membrane fusion, in order to identify the machinery responsible for the fusion of Golgi-derived Rab6 carriers at the ER. We not only assess the delivery of Rab6 to the ER, but also one of its cargo molecules, the Shiga-like toxin B-chain. These screens reveal that three proteins, VAMP4, STX5, and SCFD1/SLY1, are all important for the fusion of Rab6 carriers at the ER. Live cell imaging experiments also show that the depletion of SCFD1/SLY1 prevents the membrane fusion event, suggesting that this molecule is an essential regulator of this pathway.
Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma

Background Recent evidence increasingly suggests key roles for the tricarboxylic acid cycle and fatty acid metabolism in tumor progression and metastasis. Aconitase 2 (ACO2) is a component of the tricarboxylic acid cycle and represents a key cellular metabolic hub that promotes de novo fatty acid biosynthesis. However, there have been few reports on the role of ACO2 in tumorigenesis and cancer progression. Methods Through the comprehensive use of datasets from The Cancer Genome Atlas, Genotype-Tissue Expression Project, cBioPortal, Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, DNA Methylation Interactive Visualization Database, and TIMER2, we adopted bioinformatics methods to uncover the potential carcinogenic roles of ACO2, including by analysing ACO2 expression and correlations between prognosis, genetic mutations, immune cell infiltration, DNA methylation, tumor mutational burden, and microsatellite instability in different tumors. Additionally, the expression level and tumor-promoting effect of ACO2 were verified in hepatocellular carcinoma (HCC) cells. To explore the underlying mechanisms of ACO2 in human cancer, ACO2-related gene enrichment analysis and lipid metabolomics were performed using LM3 cells with or without ACO2 knockdown. Results The results indicated that ACO2 was highly expressed in most cancers, showing early diagnostic value in six tumor types, and was positively or negatively associated with prognosis in different tumors. Moreover, ACO2 expression was associated with immune cell infiltration, such as CD8+ T cells and tumor-associated neutrophils, in some cancers. For most cancer types, there was a significant association between immune checkpoint-associated genes and ACO2 expression. Compared with normal hepatocytes, ACO2 was upregulated in HCC cells, which promoted their proliferation and migration. Furthermore, to explore the underlying molecular mechanism, we performed KEGG pathway enrichment analysis of ACO2-associated genes and lipidomics using LM3 cells with or without ACO2 knockdown, which screened 19 significantly altered metabolites, including 17 with reduced levels and 2 with increased levels. Conclusion Through pan-cancer analysis, we discovered for the first time and verified that ACO2 could be a useful diagnostic biomarker for cancer detection. Additionally, ACO2 could be used as an auxiliary prognostic marker or as a marker for immunotherapy in some tumor types.
Outcomes of early catheter ablation for ventricular tachycardia in adult patients with structural heart disease and implantable cardioverter-defibrillator: An updated systematic review and meta-analysis of randomized trials

Aims Catheter ablation (CA) for ventricular tachycardia (VT) can improve outcomes in patients with ischemic cardiomyopathy. Data on patients with non-ischemic cardiomyopathy are scarce. The purpose of this systematic review and meta-analysis is to compare early CA for VT to deferred or no ablation in patients with ischemic or non-ischemic cardiomyopathy. Methods and results Studies were selected according to the following PICOS criteria: patients with structural heart disease and an implantable cardioverter-defibrillator (ICD) for VT, regardless of the antiarrhythmic drug treatment; intervention–early CA; comparison–no or deferred CA; outcomes–any appropriate ICD therapy, appropriate ICD shocks, all-cause mortality, VT storm, cardiovascular mortality, cardiovascular hospitalizations, complications, quality of life; published randomized trials with follow-up ≥12 months. Random-effect meta-analysis was performed. Outcomes were assessed using aggregate study-level data and reported as odds ratio (OR) or mean difference with 95% confidence intervals (CIs). Stratification by left ventricular ejection fraction (LVEF) was also done. Eight trials (n = 1,076) met the criteria. Early ablation was associated with reduced incidence of ICD therapy (OR 0.53, 95% CI 0.33–0.83, p = 0.005), shocks (OR 0.52, 95% CI 0.35–0.77, p = 0.001), VT storm (OR 0.58, 95% CI 0.39–0.85, p = 0.006), and cardiovascular hospitalizations (OR 0.67, 95% CI 0.49–0.92, p = 0.01). All-cause and cardiovascular mortality, complications, and quality of life were not different. Stratification by LVEF showed a reduction of ICD therapy only with higher EF (high EF OR 0.40, 95% CI 0.20–0.80, p = 0.01 vs. low EF OR 0.62, 95% CI 0.34–1.12, p = 0.11), while ICD shocks (high EF OR 0.54, 95% CI 0.25–1.15, p = 0.11 vs. low EF OR 0.50, 95% CI 0.30–0.83, p = 0.008) and hospitalizations (high EF OR 0.95, 95% CI 0.58–1.58, p = 0.85 vs. low EF OR 0.58, 95% CI 0.40–0.82, p = 0.002) were reduced only in patients with lower EF. Conclusion Early CA for VT in patients with structural heart disease is associated with reduced incidence of ICD therapy and shocks, VT storm, and hospitalizations. There is no impact on mortality, complications, and quality of life. (The review protocol was registered with INPLASY on June 19, 2022, #202260080). Systematic review registration [https://inplasy.com/], identifier [202260080].
Cystatin B deficiency results in sustained histone H3 tail cleavage in postnatal mouse brain mediated by increased chromatin-associated cathepsin L activity

Cystatin B (CSTB) is a cysteine cathepsin inhibitor whose biallelic loss-of-function mutations in human result in defects in brain development and in neurodegeneration. The physiological function of CSTB is largely unknown, and the mechanisms underlying the human brain diseases remain poorly understood. We previously showed that CSTB modulates the proteolysis of the N-terminal tail of histone H3 (H3cs1) during in vitro neurogenesis. Here we investigated the significance of this mechanism in postnatal mouse brain. Spatiotemporal analysis of H3cs1 intensity showed that while H3cs1 in wild-type (wt) mice was found at varying levels during the first postnatal month, it was virtually absent in adult brain. We further showed that the high level of H3cs1 coincides with chromatin association of de novo synthesized cathepsin L suggesting a role for nuclear cathepsin L in brain development and maturation. On the contrary, the brains of Cstb–/– mice showed sustained H3cs1 proteolysis to adulthood with increased chromatin-associated cathepsin L activity, implying that CSTB regulates chromatin-associated cathepsin L activity in the postnatal mouse brain. As H3 tail proteolysis has been linked to cellular senescence in vitro, we explored the presence of several cellular senescence markers in the maturing Cstb–/– cerebellum, where we see increased levels of H3cs1. While several markers showed alterations in Cstb–/– mice, the results remained inconclusive regarding the association of deficient CSTB function with H3cs1-induced senescence. Together, we identify a molecular role for CSTB in brain with implications for brain development and disease.
Pyroptosis: A new insight of non-small-cell lung cancer treatment

Non-small cell lung cancer (NSCLC) has become one of the most common malignant tumors. Emerging evidence has shown that tumor resistance to apoptosis by damaging or bypassing apoptotic cell death is a major contributor to poor responses to therapy in patients with NSCLC. Pyroptosis is a new type of cytolytic and inflammatory programmed death distinct from apoptosis. Currently, pyroptosis has been reported to cause a strong inflammatory response and significant tumor suppression. It is considered a promising therapeutic strategy and prognosis for NSCLC. In this review, we summarized the characteristics of pyroptosis from its underlying basis and role in NSCLC, thereby providing the potential of pyroptosis as a therapeutic strategy and highlighting the challenges of activating pyroptosis in NSCLC treatment.
Construction and validation of a predictive model for hypocalcemia after parathyroidectomy in patients with secondary hyperparathyroidism

Objective We aimed to construct and validate a predictive model for the risk of hypocalcemia following parathyroidectomy (PTX) for the treatment of secondary(renal) hyperparathyroidism (SHPT). Methods Information regarding patients with SHPT who underwent PTX between January 2019 and April 2022 was collected retrospectively. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for hypocalcemia following PTX and to construct predictive models. The areas under the receiver operating characteristic curve (AUC), the calibration curve, and the clinical decision curve (decision curve analysis, DCA) were used to assess the discrimination, calibration, and level of clinical benefit obtained using the predictive models. Results We studied 238 patients who were randomly allocated in a 7:3 ratio to a training group (n=166) and a test group (n=72). Univariate and multivariate logistic regression analyses were performed, in which three variables (the circulating parathyroid hormone (PTH) and Ca concentrations, and alkaline phosphatase (ALP) activity) were interrogated for possible roles as independent risk factors for hypocalcemia in patients with SHPT who undergo PTX, and used to construct predictive models. The AUCs for the constructed models were high for both the training (0.903) and test (0.948) groups. The calibration curve showed good agreement between the incidence of postoperative hypocalcemia estimated using the predictive model and the actual incidence. The DCA curve indicated that the predictive model performed well. Conclusion A predictive model constructed using a combination of preoperative PTH, Ca, and ALP may represent a useful means of identifying patients with SHPT at high risk of developing hypocalcemia following PTX in clinical practice.
Scrophulariae Radix-Atractylodes sinensis pair and metformin inhibit inflammation by modulating gut microbiota of high-fat diet/streptozotocin-induced diabetes in rats

Introduction Type 2 mellitus (T2DM), a chronic metabolic disorder, causes severe impairment of patients’ quality of life and has attracted global attention. Many studies have suggested the importance of the gut microbiota in the occurrence of T2DM. The Scrophulariae Radix and Atractylodes sinensis (XC) pair, recommended in traditional Chinese medicine (TCM), have been used for treating diabetes for many years. However, research on the role of the XC pair in modulating gut microbial communities is lacking, but it is important to elucidate the underlying mechanism. Methods In this study, we detected bacterial communities by high-throughput 16S rRNA gene sequencing. Results The results showed that XC + MET reduced postprandial hyperglycemia and inflammatory response in diabetic rats more effectively than metformin (MET) alone. The XC + MET treatment reshaped the intestinal microbial composition of diabetic rats. XC can help MET regulate carbohydrate, amino acid, and lipid metabolism, particularly the insulin signaling pathway. Discussion This research would help elucidate potential mechanisms and the treatment methods. Graphical Abstract The graphic abstract of the study. The figure was created with BioRender.com.
Changes in the C-terminal, N-terminal, and histidine regions of amelogenin reveal the role of oligomer quaternary structure on adsorption and hydroxyapatite mineralization

Adsorption interactions between amelogenin and calcium phosphate minerals are believed to be important to amelogenin’s function in enamel formation, however, the role of specific amino acid residues and domains within the protein in controlling adsorption is not well known. We synthesized “mechanistic probes” by systematically removing charged regions of amelogenin in order to elucidate their roles. The probes included amelogenin without the charged residues in the N-terminus (SEKR), without two, three, or eight histidines (H) in the central protein region (H2, H3, H8), or without the C-terminal residues (Delta). In-situ atomic force microscopy (AFM) adsorption studies onto hydroxyapatite (HAP) single crystals confirmed that the C-terminus was the dominant domain in promoting adsorption. We propose that subtle changes in protein-protein interactions for proteins with histidines and N-terminal residues removed resulted in changes in the oligomer quaternary size and structure that also affected protein adsorption. HAP mineralization studies revealed that the oligomer-HAP binding energy and protein layer thickness were factors in controlling the amorphous calcium phosphate (ACP) to HAP induction time. Our studies with mechanistic probes reveal the importance of the oligomer quaternary structure in controlling amelogenin adsorption and HAP mineralization.
Facing the unknown COVID-19 pandemic: A qualitative study with nurses and nursing assistants in three European countries

Background The coronavirus disease (COVID-19) is now a worldwide public health emergency. As essential and central parts of the COVID-19 patient care team, nurses and nurse assistants are facing all kinds of challenges caused by the disease and the pandemic. Understanding these challenges and the way nurses and nurse assistants handle and cope with them provides important knowledge on how to improve management of future pandemics and endemic situations. Thus, the present study explored the challenges faced by nurses and nurse asssitants who cared for COVID-19 patients in hospitals and long term care facilities in Italy, Austria and Germany. Methods The study employed a qualitative design. Purposive sampling was used to select the participants consisting on nurses (n = 30), nurse coordinators (n = 6) and nurse assistants (n = 5) from hospitals (n = 32) and long-term care facilities (n = 9) in Austria, Germany, and Italy. Data were collected between August and December 2020 through semi-structured interviews. The collected data were analyzed using qualitative content analysis. Results The analysis of the data revealed three main themes with twelve sub-categories: (i) Knowledge, skills, and training (lack of knowledge; skills; organizational issues; training); (ii) resources and risk (lack of protective equipment; difficulties with protective equipment; risk and infection; feelings and isolation); (iii) coping strategies (humor; adaption; team effort; self-care; family and friends). Conclusion Nurses and nurse assistants who participated in this study faced many personal and professional challenges, and used different coping strategies to manage the situation. Some of these strategies can be applied to reduce these challenges and create better working conditions for nurses and nurse assistants in similar events. Further research, training of staff, and adaptation of institutional policies may help develop new strategies to face future pandemics successfully.
Association of serum levels of Visfatin, Intelectin-1, RARRES2 and their genetic variants with bone mineral density in postmenopausal females

Background Adipokines are engaged in bone physiology and regulate bone mineral density (BMD) by playing protective or cynical role in bone metabolism. The study is designed to measure and compare BMD, adipokines (retinoic acid receptor responder protein-2 RARRES2, visfatin and Intelectin-1) and their genetic variants in postmenopausal osteoporotic, osteopenic and non-osteoporotic females. Methods This comparative study included postmenopausal non-osteoporotic (n=72), osteopenic (n=72) and osteoporotic (n=100) females with two years of amenorrhea and age between 50 to 70 years. Gold standard DXA was used to measure BMD. Hardy-Weinberg equilibrium was established. Kruskal-Wallis test for comparisons, logistic and multivariate regression analysis were used to rule out the predictors of BMD. Results On comparing the three groups, significant differences were observed in serum RARRES2 (p <0.001) and serum visfatin (p=0.050). The significant positive predictor of BMD at lumbar spine and total hip was serum visfatin. BMD at right and left femoral neck was predicted negatively by serum chemerin while BMD at left femoral neck was also predicted positively by serum calcium levels. There was significant difference in BMD at right femoral neck (p = 0.033) between rs7806429 genotypes. The odds of having low BMD increases with increasing serum levels of chemerin and decreasing serum levels of visfatin and calcium Conclusion The adipokines RARRES2 and visfatin are associated with BMD. RARRES2 is an independent negative and visfatin is positive predictor of BMD in postmenopausal females. BMD at right femoral neck was significantly low in RARRES2 rs7806429 TC heterozygotes.
Correlation between long-term use of metformin and incidence of NAFLD among patients with type 2 diabetes mellitus: A real-world cohort study

Background and aims Studies have demonstrated that the short-term use of metformin benefits liver function among patients with type 2 diabetes mellitus (T2DM). However, few studies have reported on the effects of long-term metformin treatment on liver function or liver histology. This study investigated the correlation between metformin use and the incidence of nonalcoholic fatty liver disease (NAFLD) among patients with T2DM. Methods This population-based study investigated the risk of NAFLD among patients with T2DM who received metformin treatment between 2001-2018. Metformin users and metformin nonusers were enrolled and matched to compare the risk of NAFLD. Results After 3 years, the patients who received <300 cDDD of metformin and those with metformin use intensity of <10 and 10–25 DDD/month had odds ratios (ORs) of 1.11 (95% confidence interval [CI] = 1.06–1.16), 1.08 (95% CI = 1.02–1.13), and 1.18 (95% CI = 1.11–1.26) for NAFLD, respectively. Moreover, metformin users who scored high on the Diabetes Complications and Severity Index (DCSI) were at high risk of NAFLD. Patients with comorbid hyperlipidemia, hyperuricemia, obesity, and hepatitis C were also at high risk of NAFLD. Conclusion Patients with T2DM who received metformin of <300 cDDD or used metformin at an intensity of <10 and 10–25 DDD/month were at a high risk of developing NAFLD. The results of this study also indicated that patients with T2DM receiving metformin and with high scores on the DCSI were at a high risk of developing NAFLD.
A Maugis analysis of adhesive line contact

The Maugis analysis of adhesive circular contacts between spheres is repeated for the band contacts between cylinders. It is found that the same Maugis/Tabor parameter governs the transition between rigid cylinder behaviour and JKR-like behaviour, with the same critical values; however, the pull-off force is not a simple multiple of RΔγ as with circular contacts, but varies from to T = (3/4)(4πE*RΔγ2)1/3.