This study analyzed the efficacy and safety of neoadjuvant chemotherapy with liposomal paclitaxel plus platinum in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC).

The data of patients with locally advanced resectable ESCC (staging cT2N + M0, cT3-4aNanyM0, IA-IVA) who received preoperative chemotherapy with liposomal paclitaxel plus platinum (cisplatin, nedaplatin or carboplatin) in HuanXing Cancer Hospital from July 2018 to October 2019 were collected. The primary endpoint of this study was R0 resection rate, and secondary endpoints were pathological complete response (pCR) rate, 1- and 2-year overall survival (OS) rate, 1-year and 18-month disease-free survival (DFS) rate, and safety.

A total of 32 eligible patients were included in this study. All patients received neoadjuvant chemotherapy and surgery. The R0 resection rate was 93.8%, the pCR rate was 12.5%, and down-staging was achieved in 14 patients (47.8%). Median follow-up was 31.0months (95% confidence interval [CI] 30.1-31.9months). The 1- and 2-year OS rates were 96.9% and 78.1%, and the 1-year and 18-month DFS rates were 86.7% and 76.7%, respectively. The median DFS and OS were not reached. The incidence rate of neoadjuvant chemotherapy related grade 3-4 adverse events was 21.9%, including neutropenia (21.9%) and leukopenia (9.4%).

The results of this study suggest that liposomal paclitaxel combined with platinum as neoadjuvant chemotherapy can provide satisfactory R0 resection rate and survival rate, and significant tumor down-staging effect for patients with locally advanced resectable ESCC, with safety profile.

The results of this study suggest that liposomal paclitaxel combined with platinum as neoadjuvant chemotherapy can provide satisfactory R0 resection rate and survival rate, and significant tumor down-staging effect for patients with locally advanced resectable ESCC, with safety profile.

Heart failure (HF) represents a clinical syndrome resulting from different aetiologies and degrees of heart diseases. Among these, a key role is played by primary heart muscle disease (cardiomyopathies), which are the combination of multifactorial environmental insults in the presence or absence of a known genetic predisposition. PI3K inhibitor The aim of the Maastricht Cardiomyopathy registry (mCMP-registry; NCT04976348) is to improve (early) diagnosis, risk stratification, and management of cardiomyopathy phenotypes beyond the limits of left ventricular ejection fraction (LVEF).

The mCMP-registry is an investigator-initiated prospective registry including patient characteristics, diagnostic measurements performed as part of routine clinical care, treatment information, sequential biobanking, quality of life and economic impact assessment, and regular follow-up. All subjects aged ≥16years referred to the cardiology department of the Maastricht University Medical Center (MUMC+) for HF-like symptoms or cardiac screening nd the LVEF limits.

The broad inclusion criteria, systematic routine clinical care data-collection, extensive study-related data-collection, sequential biobanking, and multi-disciplinary approach gives the mCMP-registry a unique opportunity to improve diagnosis, risk stratification, and management of HF and (early) cardiomyopathy phenotypes beyond the LVEF limits.Sodium-glucose cotransporter-2 inhibitor (SGLT2i) in patients with type 2 diabetes reduces the risk of serious heart failure events, specifically the risk of hospitalization for heart failure, and cardiovascular death. The benefit is most apparent in patients with a heart failure with reduced ejection fraction (HFrEF). Dapagliflozin and empagliflozin reduced the risk of cardiovascular death and hospitalizations for heart failure in patients with established HFrEF, including those without diabetes. Considering the magnitude of the problem and the expected benefit on the target population, an Egyptian consensus document was conducted to demonstrate the importance of and the critical knowledge needed for effective and safe implementation of SGLT2i in the daily practice for the management of patients with HFrEF.Drug-drug interaction (DDI) is an important consideration for clinical decision making in prostate cancer treatment. The objective of this study was to evaluate the effect of enzalutamide, an oral androgen receptor inhibitor, on the pharmacokinetics (PK) of digoxin (P-glycoprotein [P-gp] probe substrate) and rosuvastatin (breast cancer resistance protein [BCRP] probe substrate) in men with metastatic castration-resistant prostate cancer (mCRPC). This was a phase I, open-label, fixed-sequence, crossover study (NCT04094519). Eligible men with mCRPC received a single dose of transporter probe cocktail containing 0.25 mg digoxin and 10 mg rosuvastatin plus enzalutamide placebo-to-match on day 1. On day 8, patients started 160 mg enzalutamide once daily through day 71. On day 64, patients also received a single dose of the cocktail. The primary end points were digoxin and rosuvastatin plasma maximum concentration (Cmax ), area under the concentration-time curve from the time of dosing to the last measurable concenrequire dose adjustment in this patient population.Stem cell-based experimental platforms for neuroscience can effectively model key mechanistic aspects of human development and disease. However, conventional culture systems often overlook the engineering constraints that cells face in vivo. This is particularly relevant for neurons covering long range connections such as spinal motor neurons (MNs). Their axons extend up to 1m in length and require a complex interplay of mechanisms to maintain cellular homeostasis. However, shorter axons in conventional cultures may not faithfully capture important aspects of their longer counterparts. Here this issue is directly addressed by establishing a bioengineered platform to assemble arrays of human axons ranging from micrometers to centimeters, which allows systematic investigation of the effects of length on human axonas for the first time. This approach reveales a link between length and metabolism in human MNs in vitro, where axons above a „threshold“ size induce specific molecular adaptations in cytoskeleton composition, functional properties, local translation, and mitochondrial homeostasis. The findings specifically demonstrate the existence of a length-dependent mechanism that switches homeostatic processes within human MNs. The findings have critical implications for in vitro modeling of several neurodegenerative disorders and reinforce the importance of modeling cell shape and biophysical constraints with fidelity and precision in vitro.

Using data from the global burden of disease (GBD) between 1990 and 2019 to report the leading etiological factors and hazards for liver cancer by HBV (LCHB), HCV (LCHC), alcoholic use (LCAL), NASH (LCNA), and other causes (LCOT).

The estimated annual percentage change (EAPC) and age-standardized incidence rate (ASR) in different districts, sex, and age are used to quantify the change of etiologies of liver cancer. Age-period-cohort models were performed to predict the primary liver cancer incidence and case numbers.

Based on the GBD database of the whole world for the five etiologies of liver cancer in 2019, the percentage of incidence of LCAL, LCHB, LCHC, LCNA, and LCOT are 18.4%, 41%, 28.5%, 6.8%, and 5.3%, respectively. Fiver etiologies of liver cancer show gender differences, with LCHB and LCAL being more prevalent in men, and LCHC, LCNA being more prevalent in women. Besides, live cancer of males is because of alcohol using and smoking, while the reason of liver cancer of females is drug use, high BMI and high fasting plasma glucose. Interestingly, the incidence of LCHC in women over 85years old, LCNA in women over 75years old, and LCOT in women over 75years old were all higher than that in men. According to the future prediction, the incidence rate of liver cancer itself, as well as the five causes of liver cancer, tends to decrease gradually after 2019, while the incidence rate of LCNA in males will continue to increase until 2025.

The incidence of liver cancer has been increasing and its major causes vary considerably at global, regional, or national levels, also vary by gender and age group.

The incidence of liver cancer has been increasing and its major causes vary considerably at global, regional, or national levels, also vary by gender and age group.HLA is a critical component of the viral antigen presentation pathway. We investigated the relationship between the severity of SARS-CoV-2 disease and HLA type in 3235 individuals with confirmed SARS-CoV-2 infection. We found only the DPB1 locus to be associated with the binary outcome of whether an individual developed any COVID-19 symptoms. The number of peptides predicted to bind to an HLA allele had no significant relationship with disease severity both when stratifying individuals by ancestry or age and in a pooled analysis. Overall, at the population level, we found HLA type is significantly less predictive of COVID-19 disease severity than certain demographic factors and clinical comorbidities.Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so-called urolithin metabotypes (UM-A, UM-B, and UM-0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.HLA class II molecules, HLA-DR, DP and DQ, together with HLA II-like protein DM, play a dominant role in the processing and presentation of antigens, which may influence vaccine effectiveness. We previously demonstrated that variations in the HLA-DRB1, DPB1 and DQB1 genes may affect the neutralising antibody (NAb) response induced by the inactivated Japanese encephalitis vaccine (IJEV). In the present study, we genotyped HLA-DPA1, DQA1, DMA and DMB genes and used previous HLA-DRB1, DPB1 and DQB1 data to evaluate the association of these genes with IJEV-induced NAbs, at both the seroconversion and geometric mean titres (GMTs). We confirmed the seropositive association of DQB1*0201 and NAbs (0.156 vs. 0.075, p_adj = 0.018; OR = 2.270; 95% CI = 1.285-3.999) and seronegative association of DQB1*0202 (0.014 vs. 0.09, p_adj = 0.0002; OR = 0.130; 95% CI = 0.047-0.400). Furthermore, the DMB*0103-DMA*0101-DPA1*0103-DPB1*0401 haplotype was associated with a negative response (0.020 vs. 0.074; p_adj = 0.03; OR = 0.250; 95% CI = 0.