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Identification of genomic rearrangements by microarrays or short-read sequencing frequently lacks information about the exact architecture and breakpoints of variants due to technical limitations. Independent verification of complex structural variants (SVs) is often performed using custom targeted assays, making confirmation of clinically relevant findings time consuming and laborious. In this study we evaluate Oxford Nanopore long-read adaptive sampling for flexible and rapid confirmation and...

BACKGROUND: The number and type of genetic alterations required to initiate breast and ovarian cancer remain unclear. While germline BRCA1/2 carriers show markedly elevated cancer risk, it is uncertain whether point mutations or copy number alterations constitute the rate-limiting events of tumourigenesis.

CONCLUSIONS: We find strong support for the use of a genetic threshold to identify epidemiologically linked strains. We find genomic evidence for persistent environmental reservoirs as sources of ICU-associated PA infection. This work underscores the importance of environmental monitoring and infection control measures to mitigate the risk posed by contaminated sinks and other environmental sources.

CONCLUSIONS: Establishing an MCID is important for determining clinically relevant change in the LEAPS, both for treatment studies and for individual patients in clinical care. For clinical use, the proposed MCID is 3 points for the LEAPS total score and 2 points for the LEAPS productivity subscale score.

Cell-free DNA analysis via methylation and fragmentation profiling has advanced minimally invasive cancer detection; however, broader application has been limited by small cohorts and inconsistent data processing. Here we collated 1,074 cfMeDIP-seq profiles across 9 studies, comprising cancer samples from 11 cancer types, carriers of Li-Fraumeni syndrome and healthy controls. We developed a uniform computational workflow to mitigate technical and biological confounders across cohorts. This...

Human DNA polymerase θ (Polθ) is essential for microhomology-mediated end-joining (MMEJ) and represents a therapeutic vulnerability in homologous recombination (HR)-deficient cancers. Although reversible inhibitors of Polθ have advanced into clinical development, covalent chemical probes remain unexplored. Analysis of a previously described structure of the reversible inhibitor compound 37 bound to Polθ identified Cys2411 as an accessible residue 7.4 Å adjacent to the inhibitor binding site....

Antimicrobial resistance is driven by inappropriate use of antibiotics for acute respiratory infections (ARIs), which is a major challenge in primary care in low- and middle-income countries. Here we conducted a pragmatic, cluster randomized controlled trial in 34 township hospitals in two rural counties of Guangdong, China, to evaluate whether a digitally enabled stewardship program could reduce antibiotic prescribing. The intervention combined training and guidelines for doctors; concise,...

Biomanufacturing can play a pivotal role in the transition away from fossil fuel dependence for the production of chemicals and fuels. There is growing interest in inexpensive alternative bioproduction feedstocks from renewable sources that avoid competing with food production for land use. Ethylene glycol, a C2 compound that can be recovered from plastic waste or derived from carbon dioxide, is gaining attention as a carbon source for microbial processes. Here, we systematically evaluate...