A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Validation of mortality risk scores after esophagectomy.

Purpose: Oncological esophagectomy is the mainstay in esophageal cancer treatment, but perioperative mortality remains a significant concern. Various scoring systems exist to identify patients at high risk for postoperative complications and death. In the following, we aim to evaluate and compare these different scoring systems.

Bile-Derived cfDNA of Syncytin-1 and SLC7A11 as a Potential Molecular Marker for Early Diagnosis of Cholangiocarcinoma.

Purpose: Liquid biopsy technology has received widespread attention in the early diagnosis of cholangiocarcinoma (CCA).

Methods: We collected bile samples from 48 patients with CCA and 48 patients with gallstones at Shandong Provincial third Hospital. We quantified bile circulating free DNA (cfDNA) of syncytin-1 and SLC7A11, calculated the correlation between syncytin-1 and SLC7A11 expression and clinical parameters by Spearman rank correlation, plotted Receiver Operating Characteristic (ROC) curves, and compared the Area Under Curve (AUC) values to explored early diagnostic utility in patients.

Value of multi-parameter I-MIBG scintigraphy in the differential diagnosis of Parkinson's disease.

Background: I-MIBG scintigraphy plays a significant role in diagnosing Parkinson's disease (PD), with most studies primarily targeting cardiac uptake and relying on traditional ratio-based parameters for assessment. However, due to variations in scanning conditions and image processing methodologies, the clinical utility of different parameters remains a subject of debate. This study aims to evaluate the diagnostic accuracy of multi-parameter I-3-Iodobenzylguanidine (MIBG) scintigraphy and to identify the most reliable metrics for distinguishing PD from Parkinson-plus syndromes.

Clinical performance of minimally invasive full-mouth rehabilitation using different materials and techniques for patients with moderate to severe tooth wear: a systematic review and meta-analysis.

Objective: To evaluate short, mid and long-term clinical outcomes and patients' satisfaction of minimally invasive full-mouth rehabilitation using different materials and techniques for patients with moderate to severe tooth wear. Furthermore, materials were analyzed to identify their influences on clinical results.

Materials And Methods: Search was conducted in PubMed, Cochrane Central Register of Controlled Trial, Embase, Web of science and Scopus until December 19, 2024.

Intraperitoneal chemotherapy is now back for ovarian cancer.

The Intraperitoneal Carboplatin for Ovarian Cancer (iPocc) trial demonstrated that intraperitoneal (IP) administration of carboplatin is more effective than intravenous (IV) administration for advanced ovarian cancer, especially in cases with large residual tumors, challenging previous assumptions that IP chemotherapy is only beneficial for small residual tumors. Additionally, the iPocc trial showed that IP chemotherapy has a comparable safety profile to IV chemotherapy, with the exception of port-related toxicities. This review summarizes the principles, development, and significance of IP chemotherapy and discusses its future potential in light of recent studies.

Pediatric eosinophilic fasciitis: similarities and differences with adult forms.

The purpose of this study was to identify pediatric eosinophilic fasciitis, which is an extremely rare condition, in order to describe their clinical, paraclinical, and therapeutic characteristics. We made a call for observations via societies for pediatric rheumatology in France and surrounding countries and collected clinical and paraclinical data of the cases fulfilling the diagnostic criteria. Eight patients under 18 years of age with confirmed eosinophilic fasciitis followed between April 2004 and July 2022 in France, Germany, Italy, and Spain were included.

Hearing loss and risk of major osteoporotic fracture: a population-based cohort study in the United Kingdom.

Unlabelled: Using the UK Clinical Practice Research Datalink, our cohort study matched 237,297 individuals with hearing loss (HL) to 829,431 without HL. The study found an 8-10% higher risk of major osteoporotic fracture in individuals with HL compared to those without. Additionally, within the HL cohort, we identified risk factors for potential inclusion in fracture risk models.

Management factors affecting milk yield, composition, and quality on smallholder dairy farms.

A cross-sectional study on 156 smallholder dairy farms in Rwanda was carried out to assess the association between farm management practices and milk yield and quality. A pre-tested questionnaire was used to collect data on cow characteristics and farm management practices. Milk yield was recorded at household level, milk composition was monitored using a Lactoscan device (Milk Analyzer).

Childhood BMI trajectories and sociodemographic factors in an Italian pediatric population.

Childhood obesity is a growing global concern due to its long-term health consequences. Yet, more research relying on multiple time-point BMI measurements is warranted to gain further insight into obesity's temporal trends. We aimed to identify BMI trajectories in children aged 2-10 years and evaluate their association with sociodemographic factors.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Rhodamine-functionalized carbon dots with pH-regulated FRET efficiency for ratiometric fluorescence sensing and imaging of extremely alkaline pH.

A ratiometric fluorescent nanoprobe (CDs-Rho), synthesized through the simple covalent amide linkage between carbon dots (CDs) and pH-sensitive rhodamine dye (Rho), was designed for the precise sensing and imaging of extremely alkaline environments. The sensing mechanism involves the opposite pH-dependent fluorescence changes in CDs and Rho, respectively, coupled with pH-regulated FRET efficiency from CDs to Rho. The nanoprobe features a wide pH response window from pH 7.

Epidemiology, mechanisms, and clinical impact of bacterial heteroresistance.

Bacterial heteroresistance, a phenomenon where subpopulations within a bacterial strain exhibit significantly reduced antibiotic susceptibility compared to the main population, poses a major challenge in managing infectious diseases. It is considered an intermediate stage in the evolution of bacteria towards full resistance. Heteroresistant strains often have a minimal inhibitory concentration (MIC) that appears sensitive, making detection and differentiation in clinical settings difficult.

Effectiveness of Pelvic Floor Muscle and Education-based Therapies on Bladder, Bowel, Vaginal, Sexual, Psychological Function, Quality of Life, and Pelvic Floor Muscle Function in Females Treated for Breast Cancer: A Systematic Review.

Purpose Of Review: Breast malignancy is the most common cancer in females. Symptoms of pelvic floor disorders and sexual dysfunction secondary to systemic cancer treatment may occur. Non-surgical, non-pharmaceutical conservative therapies, namely pelvic floor muscle (PFM) and education-based therapies, could be beneficial to reduce these symptoms in this population.

Effects of β-glucans on fatigue: a systematic review and meta-analysis.

Several clinical trials suggest that β-glucans may reduce feelings of fatigue, however the results of clinical trials are inconsistent. Additionally, no systematic reviews or meta-analyses have assessed the effects of β-glucans on fatigue. Therefore, this study investigates the effects of β-glucans on fatigue in healthy subjects through a systematic review and meta-analysis.

Differentiating Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Using Blood Composite Scores: Insights into Clinical Outcomes and Predictive Indices.

The study sought to assess the clinical utility of complete blood count-derived composite scores, suggesting their potential as markers of inflammation and disease severity in Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with Kawasaki-like features. This retrospective study analyzed data from 71 KD and 73 MIS-C patients and 70 healthy controls. The KD group showed a higher rate of coronary involvement (26.

Tumour hypoxia in driving genomic instability and tumour evolution.

Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.

Epidemiology of invasive Haemophilus influenzae infections in Belgium: 2018-2022.

Introduction: Haemophilus influenzae plays a major role in invasive bacterial infections. Resistant strains are emerging, prompting the WHO to include H. influenzae on its list of priority pathogens for research and development of new antibiotics.

Diagnostic utility of chest wall vessel involvement sign on ultra-high-resolution CT for primary lung cancer infiltrating the chest wall.

Objectives: Chest wall infiltration in primary lung cancer affects the surgical and therapeutic strategies. This study evaluates the efficacy of the chest wall vessel involvement in subpleural lung cancer (CWVI)　on ultra-high-resolution CT (UHR-CT) for detecting chest wall invasion.

Materials And Methods: A retrospective analysis of lung cancer cases with confirmed pleural and chest wall invasion was conducted from November 2019 to April 2022.

Can response to ADHD medication be predicted?

Predictors for the pharmacological effect of ADHD medication in children and adolescents are lacking. This study examined clinically relevant factors in a large (N = 638) prospective cohort reflecting real-world evidence. Children and adolescents aged 6-17 diagnosed with ADHD were evaluated at baseline and three months following ADHD medication initiation.

Biomarkers associated with anastomotic leakage after esophagectomy: a systematic review.

Purpose: Anastomotic leakage (AL) is one of the most important complications that occurs after upper gastrointestinal surgery, registering rates of 20-30% after esophagectomy. The role of systemic inflammatory biomarkers to predict anastomotic leaks is controversial and needs systematization.

Methods: A systematic review based on the PRISMA guidelines criteria was performed.