Target product profile for cell-based and gene-based therapies to achieve a cure for HIV.

This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding.

The impact of ABO blood group on the prevalence of transfusion-transmitted infections among blood donors in a tertiary-care hospital.

Objectives: Transfusion-transmitted infections are a serious complication of blood transfusion. Devising a means of detecting at-risk blood donors may be beneficial in low- and middle-income countries such as Nigeria. We sought to determine the impact of ABO blood group on the prevalence of transfusion transmitted infections.

Practical approach to quantitative liver and pancreas MRI in children.

Quantitative abdominal magnetic resonance imaging (MRI) offers non-invasive, objective assessment of diseases in the liver, pancreas, and other organs and is increasingly being used in the pediatric population. Certain quantitative MRI techniques, such as liver proton density fat fraction (PDFF), R2* mapping, and MR elastography, are already in wide clinical use. Other techniques, such as liver T1 mapping and pancreas quantitative imaging methods, are emerging and show promise for enhancing diagnostic sensitivity and treatment monitoring.

Trends in stroke-related mortality in atrial fibrillation patients in the United States: Insights from the CDC WONDER database.

Background: Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This study analyzed demographic trends and disparities in mortality rates due to stroke in AF patients aged ≥25 years.

Methods: A retrospective analysis was conducted to acquire death data using the Centers for Disease Control and Prevention database from 1999 to 2020.

The doctor will polygraph you now.

Artificial intelligence (AI) methods have been proposed for the prediction of social behaviors that could be reasonably understood from patient-reported information. This raises novel ethical concerns about respect, privacy, and control over patient data. Ethical concerns surrounding clinical AI systems for social behavior verification can be divided into two main categories: (1) the potential for inaccuracies/biases within such systems, and (2) the impact on trust in patient-provider relationships with the introduction of automated AI systems for "fact-checking", particularly in cases where the data/models may contradict the patient.

Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study.

Background & Aims: Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Methods: Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets.

Three-year-old development: The relationship of child health and parenting stress to neurocognition.

Purpose: This study examined parenting stress and child special healthcare needs to child neurocognitive development (NCD).

Design And Methods: This secondary analysis used data from the primary study, a longitudinal cohort study of mother-child dyads. Multivariable regression models examined the associations between parenting stress and child special healthcare needs with NCD.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Donor Type Does Not Impact Late Graft Failure Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Based Graft-Versus-Host Disease Prophylaxis.

Background: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12-20% in haplo-HCT recipients using PTCy. The objective of this study was to determine if donor type influenced the risk of late graft failure following RIC HCT using PTCy-based GVHD prophylaxis.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

Integrating Pharmacogenomics into the Broader Construct of Genomic Medicine: Efforts by the ClinGen Pharmacogenomics Working Group (PGxWG).

Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene-drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene-disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants.

Integrating electronic health records and GWAS summary statistics to predict the progression of autoimmune diseases from preclinical stages.

Autoimmune diseases often exhibit a preclinical stage before diagnosis. Electronic health record (EHR) based-biobanks contain genetic data and diagnostic information, which can identify preclinical individuals at risk for progression. Biobanks typically have small numbers of cases, which are not sufficient to construct accurate polygenic risk scores (PRS).

Whole exome sequencing identifies ABHD14A and MRNIP as novel candidate genes for developmental language disorder.

Developmental language disorder (DLD) is a neurodevelopmental disorder involving impaired language abilities. Its genetic etiology is heterogeneous, involving rare variations in multiple susceptibility loci. However, family-based studies on gene mutations are scarce.

Nutritional Support in the ICU.

Critical illness is a complex condition that can have a devastating impact on health and quality of life. Nutritional support is a crucial component of critical care that aims to maintain or restore nutritional status and muscle function. A one-size-fits-all approach to the components of nutritional support has not proven beneficial.

Physicians-in-training and advanced practice providers perceptions in managing perioperative obstructive sleep apnea: a multi-institutional survey.

Study Objectives: Physicians-in-training (residents, fellows) and Advanced Practice Providers (APPs) receive limited education on sleep disorders, including obstructive sleep apnea (OSA). They often assess patients first. We aimed to understand their views on OSA and screening for OSA in the perioperative period.

Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication.

Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.

Clinical Outcomes of Acute Pyelonephritis in Type 2 Diabetes Mellitus.

Background Diabetes mellitus (DM) is a prevalent predisposing factor for urinary tract infections (UTIs). Among hospitalized patients with acute pyelonephritis, UTIs are more common, severe, and associated with worse outcomes, particularly in those with type 2 DM. Pyelonephritis in DM patients is more frequently bilateral and linked to greater complications, with 90% of emphysematous pyelonephritis (EMPN) and cystitis cases occurring in diabetic individuals.