Prevalence and factors associated with childhood malaria and anaemia in Osun state, Nigeria: a baseline household malariometric study.

Background: Under-5 children have been known to bear a significant burden of malaria in endemic countries. Though significant progress has been made towards malaria prevention and control in Nigeria, it is expected that the addition of new malaria prevention strategy, such as perennial malaria chemoprevention (PMC) can contribute to a more rapid decline in malaria cases. This study aimed to determine the prevalence and factors associated with malaria and anaemia among children aged 2-18 months in Osun State.

Public Interest in Online Information on Recurrent Urinary Tract Infections Is Greatest for Information with the Poorest Publication Quality.

: Urinary tract infections (UTIs) are among the most prevalent bacterial infections. With many patients turning to the Internet as a health resource, this study seeks to understand public engagement with online resources concerning recurrent UTIs (rUTIs), assess their reliability, and identify common questions/concerns about rUTIs. : Social media analysis tool BuzzSumo was used to calculate online engagement (likes, shares, comments, views) with information on rUTIs.

Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2-4 Years with Rett Syndrome.

Introduction: Weight-banded trofinetide dosing improved physician- and caregiver-rated efficacy measures and had acceptable tolerability in patients aged 2‒4 years (DAFFODIL study) and 5‒20 years (LAVENDER study) with Rett syndrome (RTT). Selection of weight-banded dosing regimens for these studies was based on population pharmacokinetic (popPK) modeling and exposure simulations. This study applied an updated popPK model to confirm steady-state trofinetide exposures achieved in DAFFODIL patients were within target range.

Population Pharmacokinetic Modeling to Support Trofinetide Dosing for the Treatment of Rett Syndrome.

Introduction: Oral trofinetide administered using a body weight-banded dosing regimen was approved in the US for the treatment of Rett syndrome (RTT) in patients aged ≥ 2 years. This approval was principally based on efficacy and safety findings of the phase 3 LAVENDER study in girls and women aged 5-20 years with RTT and extended to younger children aged 2-4 years with supporting data from the DAFFODIL study. Weight-banded dosing regimens were selected based on early clinical population pharmacokinetic (popPK) modeling and different scenario simulations.

interference leading to erroneous identification of a pathogenic variant in Black patients.

This study investigates the frequency of a clinically reported variant in , NM_000535.7:c.2523G>A p.

Clinicopathologic Features of Breast Tumors in Germline TP53 Variant-Associated Li-Fraumeni Syndrome.

We present one of the largest cohorts of TP53-pathogenic germline variants (PGVs) associated with patients with Li-Fraumeni syndrome (n = 82) with breast tumors (19 to 76 y; median age: 35). Most had missense variants (77%), followed by large gene rearrangements (LGRs; 12%), truncating (6%), and splice-site (5%) variants. Twenty-one unique germline missense variants were found, with hotspots at codons 175, 181, 245, 248, 273, 334, and 337.

Patient-Reported Pregnancy Outcomes and Survival in Women with Aortic Valve and/or Aortic Root Replacement.

Our objective was to investigate patient-reported maternal and perinatal outcomes and survival among women undergoing aortic valve and/or aortic root replacement (AVR/ARR). This was a single-center observational study of U.S.

Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk.

Purpose: Pathogenic germline variants (PGVs) in a subset of cancer predisposition genes (CPGs) are associated with adult-onset autosomal dominant (AD) cancer susceptibility and life-limiting autosomal recessive (AR) disease. Counseling in adult cancer genetics clinics regarding reproductive risk for PGV heterozygotes is limited.

Methods: Estimated heterozygote frequencies across ancestries were calculated for AD CPGs with AR risk (ATM, BRCA1, BRCA2, BRIP1, FH, NBN, MLH1, MSH2, MSH6, PMS2, RAD51C, SDHA, SDHB, and SDHD) from gnomADv.

Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.

PTEN hamartoma tumor syndrome (PHTS), DICER1-related tumor predisposition (DICER1) and tuberous sclerosis complex (TSC) are rare conditions which each increase risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection and multidisciplinary care. In this manuscript, we present updated surveillance recommendations and considerations for children and adolescents with PHTS, DICER1 and TSC and provide suggestions for further research in each of these conditions.

Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing.

Purpose: National guidelines recommend next generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. We sought to describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race/ethnicity, and overall survival in US Veterans.

Patients And Methods: This retrospective cohort study included Non-Hispanic Black (NHB) and Non-Hispanic white (NHW) Veterans with mPCa who obtained NGS through the Veterans Affairs National Precision Oncology Program.

Delivering insecticide-treated nets (ITNs) through a digitized single-phase door-to-door strategy: lessons from Ondo state, Nigeria.

Background: The use of insecticide-treated nets (ITNs) is a strategy recommended by the World Health Organization (WHO) for malaria prevention. In Nigeria, ITNs have been periodically distributed since 2007 through campaigns. Campaign activities and assets are typically tracked using either a paper-based or digital system.

Program Report: Expanding the Deceased Donor Pool in Manitoba With an Age-Targeted Kidney Transplant Program.

Purpose Of Program: The ongoing shortage of organs for transplant combined with the highest prevalence of end-stage kidney disease (ESKD) in Canada has resulted in long wait times for a deceased donor transplant in Manitoba. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes an age-targeted program intended to increase the use of transplants with a kidney donor profile index (KDPI) >85 by allocating them to suitable pre-consented recipients age ≥65 with low wait times.

Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing.

Background: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities.

CAR-T cell therapy in relapsed or refractory multiple myeloma and access in Turkey.

The past decade has seen the development of immunotherapy for the treatment of multiple myeloma (MM), beginning with monoclonal antibodies (mAbs) in the relapsed and refractory setting and culminating in the market approval of chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAbs). The medical community is evaluating the efficacy and safety of these targeted immunotherapies, most of which currently target B-cell maturation antigen (BCMA) on the surface of plasma cells. Two anti-BCMA CAR-T products are available for treating relapsed or refractory MM: idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel).

Tumor suppressor heterozygosity and homologous recombination deficiency mediate resistance to front-line therapy in breast cancer.

The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, but their combined biologic and clinical significance has not been evaluated. To assess the role of germline-somatic interactions on outcomes in routine practice, we developed an integrated clinicogenomic pipeline to analyze the genomes of over 4,500 patients with breast cancer. We find that germline (g) -associated tumors are enriched for loss-of-function mutations and manifest poor outcomes on standard-of-care, front-line CDK4/6 inhibitor (CDK4/6i) combinations.

Assessing olaparib efficacy in U.S. Veterans with metastatic prostate cancer utilizing a time-indifferent g-rate method ideal for real-world analyses.

Background: We aimed to assess real-world efficacy of the PARP inhibitor, olaparib, in US Veterans with metastatic prostate cancer (mPC) by leveraging the national data repository and evaluate a novel approach to assess treatment efficacy in tumors considered rare or harboring rare mutations.

Methods: Included Veterans had 1) mPC with somatic or germline alterations/mutations in genes involved in homologous recombination repair (HRR), 2) received olaparib monotherapy as well as a novel hormonal therapy/androgen receptor pathway inhibitors (NHT/ARPI), and/or chemotherapy, and 3) estimable rates of tumor growth (g-rate) using PSA values obtained while receiving treatment. Previous work has shown an excellent inverse correlation of g-rate with survival.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

Background: In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking.

Objectives: Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations.

An anti-CRISPR that pulls apart a CRISPR-Cas complex.

In biological systems, the activities of macromolecular complexes must sometimes be turned off. Thus, a wide variety of protein inhibitors has evolved for this purpose. These inhibitors function through diverse mechanisms, including steric blocking of crucial interactions, enzymatic modification of key residues or substrates, and perturbation of post-translational modifications.

Identification of unique cell type responses in pancreatic islets to stress.

Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress.

Diverse Antiphage Defenses Are Widespread Among Prophages and Mobile Genetic Elements.

Bacterial viruses known as phages rely on their hosts for replication and thus have developed an intimate partnership over evolutionary time. The survival of temperate phages, which can establish a chronic infection in which their genomes are maintained in a quiescent state known as a prophage, is tightly coupled with the survival of their bacterial hosts. As a result, prophages encode a diverse antiphage defense arsenal to protect themselves and the bacterial host in which they reside from further phage infection.