A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

A conserved role for ALG10/ALG10B and the -glycosylation pathway in the sleep-epilepsy axis.

Congenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described for , encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP associations with short sleep duration, reduced napping frequency, later sleep timing and evening diurnal preference as well as cardiac traits at a genomic locus containing a pair of paralogous enzymes and .

Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HT Antagonist Antiemetic Drugs.

Cisplatin is a platinum-based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin-containing chemotherapy (n = 33) were prospectively randomized to receive a 5-hydroxytryptamine (5-HT) antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days.

Strategies for the design of biomimetic cell-penetrating peptides using AI-driven in silico tools for drug delivery.

Cell-penetrating peptides (CPP) have gained rapid attention over the last 25 years; this is attributed to their versatility, customisation, and 'Trojan horse' delivery that evades the immune system. However, the current CPP rational design process is limited, as it requires several rounds of peptide synthesis, prediction and wet-lab validation, which is expensive, time-consuming and requires extensive knowledge in peptide chemistry. Artificial intelligence (AI) has emerged as a promising alternative which can augment the design process, for example by determining physiochemical characteristics, secondary structure, solvent accessibility, disorder and flexibility, as well as predicting in vivo behaviour such as toxicity and peptidase degradation.

The Sequence and Reconstructive Modality of Breast Cancer Treatments Affects Wait Times to Adjunctive Therapies in Patients Undergoing Mastectomy with Immediate Breast Reconstruction.

Breast cancer care requires both oncologists and plastic surgeons. Coordinating these specialists and combining extirpative and reconstructive procedures before adjunctive therapies can cause delays in care. For patients with less advanced disease, surgery is performed before adjunctive therapies, requiring early specialist coordination and the possibility of surgical complications.