Assessing pathogenicity of mismatch repair variants of uncertain significance by molecular tumor analysis.

Functional analyses are the main method to classify mismatch repair (MMR) gene variants of uncertain significance (VUSs). However, the pathogenicity remains unclear for many variants because of conflicting results between clinical, molecular, and functional data. In this study, we evaluated whether whole exome sequencing (WES) could add another layer of evidence to elucidate the pathogenicity of MMR variants with conflicting interpretations.

Comparison of the performance of two targeted metagenomic virus capture probe-based methods using reference control materials and clinical samples.

Unlabelled: Viral enrichment by probe hybridization has been reported to significantly increase the sensitivity of viral metagenomics. This study compares the analytical performance of two targeted metagenomic virus capture probe-based methods: (i) SeqCap EZ HyperCap by Roche (ViroCap) and (ii) Twist Comprehensive Viral Research Panel workflow, for diagnostic use. Sensitivity, specificity, and limit of detection were analyzed using 25 synthetic viral sequences spiked in increasing proportions of human background DNA, eight clinical samples, and American Type Culture Collection (ATCC) Virome Virus Mix.

Impact of a pharmacy-driven culture callback protocol on antimicrobial therapy optimization in the emergency department.

Background: Timely assessment of cultures for discharged patients from the emergency department (ED) is crucial for quality patient care and safety outcomes. The purpose of this study was to evaluate the efficacy of implementing a standardized pharmacy-driven culture callback protocol on antimicrobial therapy optimization for patients discharged from the ED with positive urine, blood, or sexually transmitted infection (STI) cultures.

Objective: To assess the impact of a pharmacy-driven culture callback process on antimicrobial therapy optimization in the ED.

A patient-centred and multi-stakeholder co-designed observational prospective study protocol: Example of the adolescent experience of treatment for X-linked hypophosphataemia (XLH).

The importance of patient centricity and keeping the patient at the heart of research design is now well recognised within the healthcare community. The involvement of patient, caregiver and clinician representatives in the study design process may help researchers to achieve this goal and to ensure robust and meaningful data generation. Real-world data collection allows for a more flexible and patient-centred research approach for gaining important insights into the experience of disease and treatments, which is acutely relevant for rare diseases where knowledge about the disease is more likely to be limited.

Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients.

Background: Colibactin, a genotoxin produced by polyketide synthase harboring (pks) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pksEscherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas.

Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed.

Fibroblast growth factor 23 and calcium-phosphate metabolism in relation to cardiovascular risk factors in patients with type 1 diabetes.

Background: Cardiovascular disease (CVD) is the major cause of mortality in type 1 diabetes (T1D). The objective of this study is to evaluate fibroblast growth factor 23 (FGF23) and calcium-phosphate metabolism in relation to cardiovascular risk factors in adults with and without T1D.

Methods: A case-control study was conducted using data from patients with T1D and age- and sex matched controls without T1D from the Lifelines Cohort Study.

Integrative multiomics enhancer activity profiling identifies therapeutic vulnerabilities in cholangiocarcinoma of different etiologies.

Objectives: Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA.

Predicting the contribution of climate change on North Atlantic underwater sound propagation.

Since the industrial revolution, oceans have become substantially noisier. The noise increase is mainly caused by increased shipping, resource exploration, and infrastructure development affecting marine life at multiple levels, including behavior and physiology. Together with increasing anthropogenic noise, climate change is altering the thermal structure of the oceans, which in turn might affect noise propagation.

Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients.

Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients.

A novel mutation in in a family with a variable phenotype with brachydactyly, short stature, oligodontia and developmental delay.

Mutations in (PTH-like hormone), cause brachydactyly type E (BDE) characterized by shortening of metacarpals, metatarsals and/or phalanges with short stature. In this report we describe three siblings and their mother with a novel heterozygous mutation c.25 T > C, p.

What's Trending on Twitter Regarding the Most Recently Approved Oral Agent for HIV Pre-Exposure Prophylaxis (PrEP)?

Pre-exposure prophylaxis (PrEP) is a key therapeutic strategy for HIV prevention. Descovy is the most recently approved oral agent for PrEP. Despite availability, there continues to be suboptimal PrEP use among at-risk individuals.

mSigHdp: hierarchical Dirichlet process mixture modeling for mutational signature discovery.

Mutational signatures are characteristic patterns of mutations caused by endogenous or exogenous mutational processes. These signatures can be discovered by analyzing mutations in large sets of samples-usually somatic mutations in tumor samples. Most programs for discovering mutational signatures are based on non-negative matrix factorization (NMF).

Osteoporosis in children and adolescents: how to treat and monitor?

Unlabelled: Osteoporosis is a condition of increased bone fragility associated with fractures. Apart from primary genetic osteoporotic conditions, secondary osteoporosis in children is being increasingly recognized. As a result, there is growing interest in its prevention and treatment.

Changes in body size and body composition in survivors of childhood cancer: seven years follow-up of a prospective cohort study.

Background & Aims: Cancer treatment is known to have impact on nutritional status, and both underweight and overweight have been reported in several studies in survivors. A limitation of most studies is that they relied on retrospective data or were limited to a subgroup of patients. The current study aims to describe changes in body size and body composition prospectively seven years after diagnosis in a heterogeneous sample of childhood cancer survivors and to evaluate associated factors.

A longitudinal analysis of conspiracy beliefs and Covid-19 health responses.

Background: Little is known about how conspiracy beliefs and health responses are interrelated over time during the course of the coronavirus disease 2019 (Covid-19) pandemic. This longitudinal study tested two contrasting, but not mutually exclusive, hypotheses through cross-lagged modeling. First, based on the consequential nature of conspiracy beliefs, we hypothesize that conspiracy beliefs predict an increase in detrimental health responses over time.