CRISPR-based gene therapy for the induction of fetal hemoglobin in sickle cell disease.

Introduction: Sickle cell disease is ameliorated and perhaps can be 'cured' if enough fetal hemoglobin is present in most erythrocytes. Hydroxyurea, which increases fetal hemoglobin levels, is widely available and effective, especially in children. Nevertheless, only cell-based gene therapy can achieve a 'curative' fetal hemoglobin threshold.

Sex Differences in Protein Biomarkers and Measures of Fat Distribution.

Background: Sex differences in obesity and fat distribution may in part explain differences in cardiovascular risk in men versus women. We sought to examine sex differences in the associations of obesity and adiposity measures with cardiovascular disease-related protein biomarkers.

Methods And Results: In a cross-sectional observational cohort study, we examined whether the association of obesity (body mass index [BMI] and waist circumference) and adiposity measures (visceral adipose tissue) with biomarkers demonstrates effect modification by sex using multiplicative interaction terms in multivariable linear regression models.

Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast.

Purpose: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

Experimental Design: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

Long COVID impacts: the voices and views of diverse Black and Latinx residents in Massachusetts.

Objective: To understand how Long COVID is impacting the health and social conditions of the Black and Latinx communities.

Background: Emerging research on Long COVID has identified three distinct characteristics, including multi-organ damage, persistent symptoms, and post-hospitalization complications. Given Black and Latinx communities experienced significantly higher COVID rates in the first phase of the pandemic they may be disproportionately impacted by Long COVID.

The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.

Background: In South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics.

Objectives: To investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.

Prediction of Alzheimer's disease progression within 6 years using speech: A novel approach leveraging language models.

Introduction: Identification of individuals with mild cognitive impairment (MCI) who are at risk of developing Alzheimer's disease (AD) is crucial for early intervention and selection of clinical trials.

Methods: We applied natural language processing techniques along with machine learning methods to develop a method for automated prediction of progression to AD within 6 years using speech. The study design was evaluated on the neuropsychological test interviews of n = 166 participants from the Framingham Heart Study, comprising 90 progressive MCI and 76 stable MCI cases.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.

Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).

Meningitis in an Immunocompetent Host: A Case Report and Review of the Literature.

Objectives: This study presents a case of meningitis in an immunocompetent injection drug user and provides a literature review of CNS infections related to .

Methods: A 32-year-old man with a history of opioid use disorder presented with seizures and underwent extensive diagnostic evaluations, including imaging, lumbar puncture, and tissue biopsies. Treatment consisted of antifungal therapy and placement of ventriculoperitoneal shunt (VPS).

Geriatric Oncology: A 5-Year Strategic Plan.

The increasing rate of the older adult population across the world over the next 20 years along with significant developments in the treatment of oncology will require a more granular understanding of the older adult population with cancer. The ASCO Geriatric Oncology Community of Practice (COP) herein provides an outline for the field along three fundamental pillars: education, research, and implementation, inspired by ASCO's 5-Year Strategic Plan. Fundamental to improving the understanding of geriatric oncology is research that intentionally includes older adults with clinically meaningful data supported by grants across all career stages.

Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort.

Background: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.

Objective: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort.

Methods: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811).

An Update on Prenatal Diethylstilbestrol Exposure and High-Grade Squamous Intraepithelial Lesions of the Lower Genital Tract.

Women with prenatal diethylstilbestrol exposure are excluded from less frequent cervical cancer screening because of their increased neoplasia risk. We report the results of a prospective follow-up study of prenatal diethylstilbestrol exposure and lower genital tract high-grade (grade 2 or higher) squamous intraepithelial lesions (HSIL). The age-adjusted risk of HSIL among diethylstilbestrol-exposed women (n=4,062) was higher than among the diethylstilbestrol unexposed (n=1,837) through age 44 years (hazard ratio 2.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants.

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function.

Role of minimal residual disease assessment in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a heterogeneous disease, featured by various molecular subtypes with different outcomes. With the advent of very efficient therapies including monoclonal antibodies, bispecific T-cell engagers and chimeric antigen receptor T cells (CAR T cells), most MM patients now have a prolonged survival.

Severe Hyponatremia Correction, Mortality, and Central Pontine Myelinolysis.

BACKGROUND: In clinical practice, sodium correction rates are frequently limited in patients with severe hyponatremia to prevent neurologic complications. The implications of correction rates on overall mortality and length of hospital stay are unclear. METHODS: In this multicenter observational study, we evaluated the association of sodium correction rates with mortality, length of stay, and central pontine myelinolysis (CPM) in patients hospitalized with severe hyponatremia (admission serum sodium level less than 120 mEq/l).

A Qualitative Study of Maternal Perceptions of Stress and Parenting During Early Childhood.

Objective: Exposure to maternal stress in early childhood can increase risk for learning and behavior challenges. We sought to gain in-depth understanding of how mothers perceive stressors to impact child wellbeing and identify mothers' strategies for navigating stressors with their young children.

Methods: We recruited English- and Spanish-speaking mothers from a primary care clinic serving predominantly publicly insured children.

Prospective Study of a System-Wide Adrenal Incidentaloma Quality Improvement Initiative.

Background: Appropriate follow-up of incidental adrenal masses (IAMs) is infrequent. We implemented a quality improvement (QI) program to improve management of IAMs.

Study Design: This system-wide initiative targeted primary care providers (PCPs) after IAM detection.

Giotto Suite: a multi-scale and technology-agnostic spatial multi-omics analysis ecosystem.

Emerging spatial omics technologies continue to advance the molecular mapping of tissue architecture and the investigation of gene regulation and cellular crosstalk, which in turn provide new mechanistic insights into a wide range of biological processes and diseases. Such technologies provide an increasingly large amount of information content at multiple spatial scales. However, representing and harmonizing diverse spatial datasets efficiently, including combining multiple modalities or spatial scales in a scalable and flexible manner, remains a substantial challenge.