Development of hyperdiploidy starts at an early age and takes a decade to complete.

Nearly half of multiple myeloma (MM) patients have hyperdiploidy (HMM) at diagnosis. Although HMM occurs early, the mutational processes before and after hyperdiploidy are still unclear. Here, we used 72 WGS samples from patients with HMM and identified pre and post HMM mutation to define the chronology of development of hyperdipoidy.

Functional effects of subsidies and stressors on benthic microbial communities along freshwater to marine gradients.

Leaf litter in coastal wetlands lays the foundation for carbon storage, and the creation of coastal wetland soils. As climate change alters the biogeochemical conditions and macrophyte composition of coastal wetlands, a better understanding of the interactions between microbial communities, changing chemistry, and leaf litter is required to understand the dynamics of coastal litter breakdown in changing wetlands. Coastal wetlands are dynamic systems with shifting biogeochemical conditions, with both tidal and seasonal redox fluctuations, and marine subsidies to inland habitats.

Colloidal 2D Layered SiC Quantum Dots from a Liquid Precursor: Surface Passivation, Bright Photoluminescence, and Planar Self-Assembly.

We report the bottom-up synthesis of colloidal two-dimensional (2D) layered silicon carbide (SiC) quantum dots with a cubic structure, lateral size of 5-10 nm, ⟨110⟩ exfoliation to few atomic layers, and surface passivation with 1-dodecene. Samples shielded from oxygen and plasma-annealed for purity exhibit narrow blue photoluminescence (PL) with quantum yields (QYs) over 60% in exceptional cases, while unshielded nanocrystals (NCs) exhibit broad blue/green/white PL with 10-15% QY. The latter scenario is attributed to excess surface carbon and oxygen accrued during synthesis and processing, with size separation through ultracentrifugation revealing size-dependent impurity emission.

Effects of full-fat high-oleic soybean meal in layer diets on performance, egg quality and chemical composition.

The utilization of full-fat high-oleic soybean meal in layer diets could lead to value-added poultry products. To test this idea, 336 hens were randomly assigned to 4 isonitrogenous (18.5% CP) and isocaloric (2,927 kcal/kg) formulated diets and fed the following diets for eight weeks: conventional control solvent-extracted defatted soybean meal (CON); extruded-expelled defatted soybean meal (EENO); full fat normal-oleic soybean meal (FFNO); or full fat high-oleic soybean meal (FFHO).

Improving Collection and Analysis of Overall Survival Data.

Advances in anticancer therapies have provided crucial benefits for millions of patients who are living long and fulfilling lives. Although these successes should be celebrated, there is certainly room to continue improving cancer care. Increased long-term survival presents additional challenges for determining whether new therapies further extend patients' lives through clinical trials, commonly known as the gold standard endpoint of overall survival (OS).

Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRAS Inhibitor.

Oncogenic mutations in the gene account for 30% of all human tumors; more than 60% of which present as KRAS mutations at the hotspot codon 12. After decades of intense pursuit, a covalent inhibition strategy has enabled selective targeting of this previously "undruggable" target. Herein, we disclose our journey toward the discovery of MK-1084, an orally bioavailable and low-dose KRAS covalent inhibitor currently in phase I clinical trials (NCT05067283).

Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy.

Indolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the gene.

Venetoclax resistance leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies.

To our knowledge, venetoclax is the first example of personalized medicine for multiple myeloma (MM), with meaningful clinical activity as a monotherapy and in combination in patients with myeloma harboring the t(11:14) translocation. However, despite the high response rates and prolonged progression-free survival, a significant proportion of patients eventually relapse. Here, we aim to study adaptive molecular responses after the acquisition of venetoclax resistance in sensitive t(11:14) MM cell models.

Three-dimensional telomere profiling predicts risk of progression in smoldering multiple myeloma.

Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression.

Long-Term Follow-Up Defines the Population That Benefits from Early Interception in a High-Risk Smoldering Multiple Myeloma Clinical Trial Using the Combination of Ixazomib, Lenalidomide, and Dexamethasone.

Background: Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and quadruplet studies have been examined in this same population. However, to date, none of these studies examined the impact of depth of response on long-term outcomes of participants treated with lenalidomide-based therapy, and whether the use of the 20/2/20 model or the addition of genomic alterations can further define the population that would benefit the most from early therapeutic intervention.