The Journal of Clinical Investigation’s Post

Opioid use disorder and misuse remain a major public health crisis: https://lnkd.in/eNNMBnv6 Eric O. Johnson et al. highlight GWAS-identified biological pathways linked to opioid misuse that may lead to breakthroughs in managing this devastating disease.

The burn behind chronic lower back pain: https://lnkd.in/eZr8qDjq Xue, Zhang et al. investigate a spinal degeneration mouse model and identify an acid-sensing ion channel as a target in lower back pain. The figure shows lower endplate porosity from lumbar-injury mice with bone-resorbing immune cells that lack proton-activated chloride channels compared with those that express Pacc1.

Polygenic scores (PGS) summarize the gene/trait associations of multiple GWAS. For substance use disorders (SUDs), which are heavily influenced by complex genetic and environmental factors, PGS have the potential to personalize predictions of risk as well as treatment outcomes. However, inadequate diversity in the ancestry composition of existing SUD GWAS as well as concerns about responsible use have limited implementation. Rachel Kember et al. discuss the progress and pitfalls in applying PGS to SUDs in their contribution to JCI's latest review series. https://lnkd.in/e6T5NrMy

Conversations with JCI editors-in-chief: https://lnkd.in/ePJG92hZ In this episode, Ushma Neill speaks with the living Editors-in-chief of the @jclinicalinvest. They were asked to reflect on their time as editors and their favorite memories. Article: https://lnkd.in/eG7n9_X6

Substance use disorders are characterized by heavy, regular use of one or more psychoactive substances, such as alcohol, nicotine, opioids, cannabis, and stimulants, as well as the development of tolerance and loss of control over use, risk-taking behavior, and physiological dependence. Misuse of psychoactive substances constitutes a growing worldwide burden with broad-ranging health consequences. Early studies identified a shared risk of substance use disorders in related individuals and GWAS have confirmed the strong influence of genetic factors across these diseases. Guest editor Dr. Henry R. Kranzler designed JCI's latest review series to provide detailed updates that emphasize the genetics, biology, and evolving treatment of substance use disorders. https://lnkd.in/e2ynbsiS

Inflammation as the strong arm in muscle regeneration? https://lnkd.in/dkwKeAK5 This issue's cover features work by Patsalos et al. reporting on diverse myeloid cell subsets that organize in functional multilayered tissue zones, crucial for effective muscle repair. The image shows a generative AI depiction of macrophage subtypes navigating through a regenerating muscle, highlighting their pivotal role in the healing process. Image credit: Andreas Patsalos/Adobe Firefly.

This comprehensive analysis of variants in cystic kidney disease leveraged 100,000 genomes! https://lnkd.in/eejkZzta Omid Sadeghi-Alavijeh et al. highlight the contributions to disease risk of different types of variants across the allelic spectrum.

Understanding androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer: https://lnkd.in/gbeTBSCi Xiaolin Zhu et al. analyzed paired metastatic biopsies and found a candidate biomarker for predicting response to second-line ARSIs.

IFN-γ and YAP lead epithelial cells astray after severe respiratory infection: https://lnkd.in/es9manYe Bradley E. Hiller and Joseph P. Mizgerd comment on new research by Lin et al. (https://lnkd.in/dSHkgVKd)