Treatment outcomes among children and adolescents with extensively drug-resistant (XDR) and pre-XDR tuberculosis: Systematic review and meta-analysis.

Extensively drug-resistant (XDR) and pre-XDR- tuberculosis (TB) account for approximately a third of pediatric MDR-TB cases globally. Clinical management is challenging; recommendations are based on limited evidence. We assessed the clinical outcomes for children and adolescents treated for XDR-and pre-XDR-TB.

An evolved, orthogonal ssDNA generator for targeted hypermutation of multiple genomic loci.

Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.

Educational attainment as a potential effect modifier of alcohol use and 100% alcohol-attributable mortality in the United States-A longitudinal analysis of mortality linked survey data from 1997 to 2018.

Aims: To measure effects between educational attainment and alcohol use as a driver of unequal alcohol-attributable mortality.

Design: Nation-wide cohort study using a longitudinal design, linking data from the 1997-2018 National Health Interview Survey to mortality data of the National Death Index in 2019. The study has an average follow-up time of 10.

Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.

Background: Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.

A splice donor in influences keratinocyte immortalization by beta-HPV49.

Human papillomaviruses (HPV) from the genus beta have been implicated in the development of cutaneous squamous cell cancer in and organ transplant patients. In contrast to alpha-high-risk HPV, which cause ano-genital and oropharyngeal cancers, beta-HPV replication is not well understood. The beta-HPV49 transcriptome was analyzed by RNA sequencing using stable keratinocyte cell lines maintaining high levels of extrachromosomally replicating E8- genomes, which can be established due to a lack of the viral E8^E2 repressor protein.

The long way from raw data to NAM-based information: Overview on data layers and processing steps.

Toxicological test methods generate raw data and provide instructions on how to use these to determine a final outcome such as a classification of test compounds as hits or non-hits. The data processing pipeline provided in the test method description is often highly complex. Usually, multiple layers of data, ranging from a machine-generated output to the final hit definition, are considered.

Increase of nitrous oxide-induced neurological disorders - a German multicenter experience.

Background: Nitrous oxide (N₂O), commonly known as laughing gas, is widely recognized for its anesthetic and analgesic effects, and is frequently used in medical contexts. However, its misuse can lead to significant neurological complications, which are often under-recognized in clinical practice. Recent data on such cases in Germany are rare.

Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments dedicated to each. Active involvement of consortium leadership, buy-in from its members at all levels, and support from NIH program staff at pivotal stages were essential to the success of this effort.

Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000-2021.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.

GREGoR: Accelerating Genomics for Rare Diseases.

Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis.

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.

Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.

Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available.

Selective Decarboxylative Fluorination of β-Keto Acids in Aqueous Media: F-NMR-Assisted Batch Optimization and Transfer to Continuous Flow.

The selective decarboxylative fluorination of 3-oxo-3-phenylpropionic acid is used as a benchmark reaction to optimize it under biocompatible conditions in batch and to transfer it to continuous flow mode. The reaction conditions are varied with respect to temperature, fluorinating reagents, inorganic base additives, and pH, as these parameters have been identified as having a significant impact on the process. The formation of the products and any by-products is analyzed using gas chromatography (GC) and F nuclear magnetic resonance spectroscopy (NMR).

Highly Efficient Transpeptidase-Catalyzed Isopeptide Ligation.

Transpeptidases are specialized enzymes that have evolved for site-selective modification of peptides and proteins at their backbone termini. Approaches for adapting transpeptidases to catalyze side chain modifications are substantially more restricted, and typically rely on large recognition tags or require specific reaction conditions that are not easily compatible with broader applications. Here we show that the engineered asparaginyl ligase AEP1 catalyzes direct isopeptide ligation by accepting an internal 2,3-diaminopropionic acid (Dap) residue adjacent to Leu, a motif that mimics the canonical N-terminal Gly-Leu substrate.

Framework for developing self-actualization skills in young adults with autism.

Purpose: Young adults with autism spectrum disorder (YAASD) often lack the skills needed for successful adult living and subsequently develop lower quality of life and health in adulthood. Therefore, we developed a framework to support resilience and improve quality of life in YAASD, which will be used to develop a life-skills curriculum for YAASD.

Methods: We conducted a qualitative study of YAASD, parents of YAASD and service providers recruited from agencies that serve YAASD using Grounded Theory.

Enhancing multi-sectoral collaborations for the prevention and control of NCDs in Thailand with a new approach.

Background: To achieve the Sustainable Development Goals (SDGs) by 2030, Thailand must engage in effective multi-sectoral collaboration (MSC). However, implementing MSC in Thailand presents significant challenges. Although Thailand had a 2011-2020 MSC strategic plan for the control of non-communicable diseases (NCDs) with the prime minister taking the lead, joined by many non-health ministers, not a single meeting was called over those 10 years.

Medical chart-reported alcohol consumption, substance use, and mental health issues in association with HIV pre-exposure prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

Background: Although some evidence suggests that alcohol, substance use, and mental health issues diminish adherence to HIV Pre-Exposure Prophylaxis (PrEP) among gay, bisexual, and other men-who-have-sex-with-men (gbMSM), findings are somewhat inconsistent and have primarily derived from studies involving non-random samples. Medical chart extraction can provide unique insight by in part surmounting sampling-related limitations, as data for entire PrEP clinic populations can be examined. Our investigation entailed comprehensive chart extraction to assess the extent to which chart-reported alcohol, substance use, and mental health issues were associated with chart-reported PrEP nonadherence.

Antimicrobial activity of iron-depriving pyoverdines against human opportunistic pathogens.

The global rise of antibiotic resistance calls for new drugs against bacterial pathogens. A common approach is to search for natural compounds deployed by microbes to inhibit competitors. Here, we show that the iron-chelating pyoverdines, siderophores produced by environmental spp.

Discovery of ianthelliformisamines D-G from the sponge and the total synthesis of ianthelliformisamine D.

The marine sponge was investigated for new chemistry after the recent discovery that polyamines ianthelliformisamines A-C (-) - originally sourced from this Australian sponge - act as biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D-G (-) and the known steroid, aplysterol (). Compounds - were fully characterised following 1D/2D NMR, MS and UV data analyses.

Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing datasets.

Purpose: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome or panel sequencing datasets aligned to a GRCh37, GRCh38, or T2T reference genome.

Methods: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs.