Design, synthesis and biological evaluation of camptothecin analogue FL118 as a payload for antibody-drug conjugates in targeted cancer therapy.

FL118, a camptothecin derivative with dual mechanisms of action through topoisomerase I inhibition and proteasome-mediated degradation of anti-apoptotic proteins exhibits potent anti-tumor activity while remaining resistant to drug efflux transporters. This work describes the targeted delivery of FL118 to tumors via antibody-drug conjugates (ADCs) using the pH-sensitive CL2A linker. ADCs targeting Trop2, HER2, and EGFR exhibited potent in vitro cytotoxicity, with IC values as low as 0.

Clinical and research applications of natural language processing for heart failure.

Natural language processing (NLP) is a burgeoning field of machine learning/artificial intelligence that focuses on the computational processing of human language. Researchers and clinicians are using NLP methods to advance the field of medicine in general and in heart failure (HF), in particular, by processing vast amounts of previously untapped semi-structured and unstructured textual data in electronic health records. NLP has several applications to clinical research, including dramatically improving processes for cohort assembly, disease phenotyping, and outcome ascertainment, among others.

Confirmatory Cytopathology and Potential Impact on the Predictive Value of Gene Expression Profiling in Patients With Uveal Melanoma.

To determine whether the availability of a cytopathology-confirming diagnosis is correlated with the prognostic accuracy of a gene expression profiling assay. A single-center retrospective review was performed of patients diagnosed with uveal melanoma who had a fine-needle aspiration biopsy and gene expression profiling before proton therapy from 2012 to 2020. The development of metastases was compared in patients with gene expression profiling and cytopathology (gene expression profiling+cytopathology group) and patients with gene expression profiling only (gene expression profiling only group).

Biomarker Panels for Predicting Progression of Kidney Disease in Acute Kidney Injury Survivors.

Background: Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). We aimed to identify combinations of clinical variables and biomarkers that predict long-term kidney disease risk after AKI.

Methods: We analyzed data from a prospective cohort of 723 hospitalized patients with AKI in the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) Study.

Possibilities and Limitations in Substituting anti-Drug Antibody Titers with Signal-to-Noise Ratios: A Comprehensive Comparison Using Two Clinical Trial Datasets of Adalimumab.

Immunogenicity assessment is vital in clinical trials and is measured through a multi-tiered approach (screening, confirmatory and titer assays). However, recent studies have suggested that titer results could be reported from ADA signal-to-noise ratios (S/N ratios=sample mean signal/negative control mean signal). More data analysis using two clinical trials of adalimumab: SB5-1003 (single-dose, healthy participants) and SB5-4001 (multiple-dose, interchangeability study, patients with plaque psoriasis), therefore, is indispensable whether substituting ADA S/N ratio as an alternative way of reporting titer results has no impact on interpretation on clinical outcome.