Advancing outcome measure development and analytical approaches: Pain in Animals Workshop 2023.

Annually, millions of humans and animals suffer from chronic and acute pain, creating welfare and quality of life concerns for both humans and animals who suffer this pain. In developing new therapeutic approaches, the challenge is to accurately measure this pain to ascertain the efficacy of novel therapeutics. Additionally, there is a need to develop new and effective analgesic options that may offer alternatives to using opioids that contribute to the opioid epidemic.

Lamivudine and tenofovir pharmacokinetic variability in people with HIV in Papua New Guinea.

Aims: Demographics and kidney function contribute to variability in lamivudine and tenofovir drug concentrations. The aim was to assess, for the first time, the pharmacokinetic variability of lamivudine and tenofovir in Papua New Guinean (PNG) HIV/AIDS patients.

Methods: For 121 PNG HIV/AIDS patients receiving combination antiretroviral therapy (300 mg lamivudine, 300 mg tenofovir disoproxil fumarate, 600 mg efavirenz, single tablet once daily), age, body weight, sex and serum creatinine concentrations data were recorded.

A semi-supervised prototypical network for prostate lesion segmentation from multimodality MRI.

Prostate lesion segmentation from multiparametric magnetic resonance images is particularly challenging due to the limited availability of labeled data. This scarcity of annotated images makes it difficult for supervised models to learn the complex features necessary for accurate lesion detection and segmentation.We proposed a novel semi-supervised algorithm that embeds prototype learning into mean-teacher (MT) training to improve the feature representation for unlabeled data.

Discovery of 6-Fluoro-5-{4-[(5-fluoro-2-methyl-3-oxo-3,4-dihydroquinoxalin-6-yl)methyl]piperazin-1-yl}--methylpyridine-2-carboxamide (AZD9574): A CNS-Penetrant, PARP1-Selective Inhibitor.

PARP inhibitors have attracted considerable interest in drug discovery due to the clinical success of first-generation agents such as olaparib, niraparib, rucaparib, and talazoparib. Their success lies in their ability to trap PARP to DNA; however, first-generation PARP inhibitors were not strictly optimized for trapping nor for selectivity among the PARP enzyme family. Previously we described the discovery of the second-generation PARP inhibitor AZD5305, a selective PARP1-DNA trapper.

Global Proteomics Indicates Subcellular-Specific Anti-Ferroptotic Responses to Ionizing Radiation.

Cells have many protective mechanisms against background levels of ionizing radiation orchestrated by molecular changes in expression, post-translational modifications, and subcellular localization. Radiotherapeutic treatment in oncology attempts to overwhelm such mechanisms, but radioresistance is an ongoing challenge. Here, global subcellular proteomics combined with Bayesian modeling identified 544 differentially localized proteins in A549 cells upon 6 Gy X-ray exposure, revealing subcellular-specific changes of proteins involved in ferroptosis, an iron-dependent cell death, suggestive of potential radioresistance mechanisms.