Exploring the role of circulating proteins in multiple myeloma risk: a Mendelian randomization study.

Multiple myeloma (MM) is an incurable blood cancer with unclear aetiology. Proteomics is a valuable tool in exploring mechanisms of disease. We investigated the causal relationship between circulating proteins and MM risk, using two of the largest cohorts with proteomics data to-date.

Systemic inequities and sources of resilience: challenges faced by Indigenous women living with HIV during COVID-19 in the Canadian prairies.

This study explored the challenges faced by, and resilience of First Nations, Métis, and Inuit women living with HIV in Manitoba and Saskatchewan during the COVID-19 pandemic. Through a decolonizing, community-based research approach, guided by a Community Guiding Circle (CGC), interviews were conducted with 45 Indigenous women living with HIV. Participants were recruited via community outreach, peer networks, and social media.

Real-world characteristics and outcomes of patients with multiple myeloma receiving second-line treatment in England.

Introduction: Despite recent advances in first-line therapies for multiple myeloma (MM), most patients relapse or become refractory, underscoring the need for effective second-line (2L) regimens for relapsed/refractory MM (RRMM).

Methods: This study describes the real-world baseline characteristics, treatment patterns and clinical outcomes of adult patients diagnosed with MM between 2013 and 2020 using data collated by the National Cancer Registration and Analysis Service (NCRAS) of the National Health Service in England. The study cohorts were broadly aligned to the eligibility criteria of the ongoing DREAMM-7 (D7) and DREAMM-8 (D8) clinical trials.

CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.