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In patients with newly diagnosed, transplant-ineligible multiple myeloma, addition of weekly bortzomib to isatuximab, lenalidomide and dexamethasone leads to increased minimal residual disease negativity compared with isatuximab, lenalidomide and dexamethasone.

Gastroesophageal reflux disease is associated with laryngopharyngeal reflux, but the cause and effect relationship between these two clinical entities is far from established. This Review considers studies of the pathogenesis of laryngopharyngeal reflux, the value of diagnostic testing either on or off therapy, and treatment options and duration, that have increased our our understanding of this field.

Arrhythmogenic cardiomyopathy is a genetically inherited disease caused by deletion of an arginine in Phospholamban (PLN), a small protein that regulates intracellular calcium levels. Here the authors show that zebrafish with the PLN p.Arg14del mutation develop severe cardiomyopathy which is preceded by contractile dysfunction and altered calcium dynamics and istaroxime is identified as a small molecule that can rescues some of these phenotypes.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain

Humping defects in high-speed laser welding of stainless steel are investigated here using in situ synchrotron X-ray imaging and fluid dynamics simulations. High welding speeds cause a short keyhole rear wall, high backward melt velocity, and long molten pool tail, leading to humping.

Here, the authors show that sequential treatment with long-acting slow-effective release ART and AAV9- based delivery of CRISPR-Cas9 results in undetectable levels of virus and integrated DNA in a subset of humanized HIV-1 infected mice. This proof-of-concept study suggests that HIV-1 elimination is possible.

Pink-beam synchrotron X-ray tomography combined with mechanical loading at nanometric precision enables the in situ imaging of intact untreated joints, resolving strains at sub-100 nm resolution.

Twisted gastrulation (TWSG1) controls signaling by Bone Morphogenetic Proteins (BMPs) during embryogenesis and cancer. Here, author report crystal structures of TWSG1 in complex with a BMP ligand and show how TWSG1 inhibits signaling in cells and in vivo.

Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

Lipid membrane fusion is an essential function in many biological processes but little is known about membrane fusion in prokaryotes. The authors here study how haloarchaeal pleomorphic viruses (HRPVs) infect archaeal hosts. The structure-function analysis of the spike proteins shed light on prokaryotic membrane fusion.

Here, Kasaragod et al. solve structures of the GABA_A receptor α5 subunit in complex with different classes of positive and negative allosteric modulators to explain the binding modes and the molecular basis of selectivity.

Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

Metal ions play essential roles in myriads of biological processes, from catalytic co-factors to supporting protein and nucleic acid structures. Here the authors use long-wavelength X-ray diffraction to locate hundreds of potassium ions taking part in the formation of rRNA tertiary structure, mediating rRNA–protein interactions and supporting ribosomal protein structures and function.

Activation of neutrophil leukocytes is tightly regulated, and it is important to understand the molecular mechanisms of their response to physiological and pathological stimuli. Here authors show that the adhesion molecule G protein-coupled receptor 97 and its interaction partners play pivotal roles in neutrophil leukocyte activation both in anti-microbial response and in inflammatory diseases.

Glass transition shows dramatic dynamic slowdown, but its origin remains unclear. Here, Xia et al. observe in granular systems the rapid growth of a geometrically frustrated polytetrahedral order with packing fraction, which is spatially correlated with the slow dynamics.

Utrophin is a dystrophin-related protein stabilizing the sarcolemma in absence of dystrophin. Here the authors report that inactivation of the protein deacetylase SIRT6, involved in the deacetylation of the epigenetic mark H3K56ac in muscle cells, increases expression of utrophin and ameliorates dystrophic muscle pathology in mice.

The S-layer is a two-dimensional protein array that covers the cell surface of many bacteria and archaea. Here, the authors use high-resolution X-ray crystallography and electron microscopy to provide detailed insights into S-layer organisation and assembly for the bacterial pathogen Clostridioides difficile.

As corals struggle to survive under climate change, it is crucial to know whether they can withstand increasing seawater temperatures. Using a controlled thermal stress experiment across three divergent coral holobionts, this study examines metatranscriptomic responses to heat stress corresponding to the coral host, photosymbionts and associated microbiota.

ABCC9 encodes the SUR2 subunit of K_ATP channels and dominant genetic variants in ABCC9 have been associated with cardiac phenotypes. Here, the authors report recessive ABCC9 mutations in individuals with mild intellectual disability, myopathy and cardiac systolic dysfunction which is associated with loss of K_ATP channel function.

Understanding the keyhole porosity formation is important in laser powder bed fusion. Here the authors reveal the dynamics of keyhole fluctuation, and collapse that induces bubble formation with three main stages of evolution; growth, shrinkage, and being captured by the solidification front.

Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.