Enhanced fetal hemoglobin production via dual-beneficial mutation editing of the HBG promoter in hematopoietic stem and progenitor cells for β-hemoglobinopathies.

Background: Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased.

Epigenetic and Metabolic Landscape of Dementia with Lewy Bodies.

Background: Lewy body diseases, including dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation, leading to dementia. Previous studies suggest distinct epigenetic and metabolomic profiles in DLB.

Objective: This study aims to identify diagnostic biomarkers by analyzing the methylome and metabolome in the Brodmann area 7 of postmortem brain tissues from DLB patients and control subjects using multiomics approaches.

Development of a Body of Knowledge for the Clinical Bioinformatician: Perspectives from the Association for Molecular Pathology's Clinical Genomics Bioinformatician Body of Knowledge Steering Committee.

The use of next-generation sequencing (NGS) and other high-throughput technologies in the clinical molecular diagnostics laboratory requires the application of bioinformatics pipelines and other computational tools to analyze, visualize, and store these clinical data. Clinical Bioinformaticians, individuals with the skills to develop, validate, and deploy these tools in a clinical setting, are needed to ensure that these molecular diagnostic technologies can be appropriately used for clinical care. Building on existing expertise in informatics, NGS, and clinical molecular diagnostics, the Association for Molecular Pathology (AMP) has generated a series to establish an initial Clinical Bioinformatician Body of Knowledge.

Application of deep learning models on single-cell RNA sequencing analysis uncovers novel markers of double negative T cells.

Double negative T (DNT) cells are a unique subset of CD3 + TCRαβ + T lymphocytes that lack CD4, CD8, or NK1.1 expression and constitute 3-5% of the total T cell population in C57BL/6 mice. They have increasingly gained recognition for their novel roles in the immune system, especially under autoimmune conditions.

Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis.

Background: In May 2020, Oakland became the most populous city in California to implement a minimum floor price law (MFPL), requiring tobacco retailers to sell cigarettes and cigars at $8 or more per pack/package. Policy enforcement began in August 2020.

Methods: We estimated changes in cigarette and cigar prices and unit sales for Oakland versus a matched comparator during the first 20 months following MFPL implementation using a synthetic difference-in-differences approach.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder.

Introduction: Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed.

Methods: A multi-center, retrospective study of individuals with DSRD was performed.

Estimated Vaccine Effectiveness for Pediatric Patients With Severe Influenza, 2015-2020.

Importance: Increasing the understanding of vaccine effectiveness (VE) against levels of severe influenza in children could help increase uptake of influenza vaccination and strengthen vaccine policies globally.

Objective: To investigate VE in children by severity of influenza illness.

Design, Setting, And Participants: This case-control study with a test-negative design used data from 8 participating medical centers located in geographically different US states in the New Vaccine Surveillance Network from November 6, 2015, through April 8, 2020.

Physician vs. AI-generated messages in urology: evaluation of accuracy, completeness, and preference by patients and physicians.

Purpose: To evaluate the accuracy, comprehensiveness, empathetic tone, and patient preference for AI and urologist responses to patient messages concerning common BPH questions across phases of care.

Methods: Cross-sectional study evaluating responses to 20 BPH-related questions generated by 2 AI chatbots and 4 urologists in a simulated clinical messaging environment without direct patient interaction. Accuracy, completeness, and empathetic tone of responses assessed by experts using Likert scales, and preferences and perceptions of authorship (chatbot vs.

High-quality draft genomes of ecologically and geographically diverse species.

is a genus of mushroom-forming fungi with ecological, ethnomycological, and clinical importance due to psilocybin production by most species. We present five genomes that enable deeper discovery and analysis of the psilocybin gene cluster and increase taxonomic resolution within : , nom. prov.

How I do it: using physics and progressive defect tensioning to close large hernia defects during MIS ventral hernia repair.

Introduction: Closure of large hernia defects with minimally invasive surgery has long-been a challenge. Barbed sutures have helped us bridge this technical gap, but their off-label use is not well studied.

Materials And Methods: We describe a suturing technique for minimally invasive ventral hernia repair (MIS-VHR) termed "progressive defect tensioning" and explore its theoretical advantages.

No "One-Size-Fits All": chronic "Carryover" diagnoses dilute antibiotic prescribing rates for sinusitis among adults in primary and urgent care settings.

International Classification of Diseases, Tenth Revision (ICD-10) billing data used in outpatient stewardship metrics is under-described for acute and chronic sinusitis. We found that different sinusitis ICD-10 definitions impacted antibiotic prescribing rates (APRs). Chronic sinusitis ICD-10s dilute overall sinusitis APR, particularly in primary care settings and should be examined separately.

Critical Appraisal of Evidence: Synthesis and Recommendations.

This is the fifth article in a new series designed to provide readers with insight into educating nurses about evidence-based decision-making (EBDM). It builds on AJN's award-winning previous series-Evidence-Based Practice, Step by Step and EBP 2.0: Implementing and Sustaining Change (to access both series, go to https://links.

The clinical significance of open vs. minimally invasive surgical approaches in the management of thymic epithelial tumors and myasthenia gravis.

Though advancements have been made in the pharmacologic treatment of myasthenia gravis (MG), surgical resection is not only an option as a last line of defense for those patients who do not respond to medical therapy but also remains vital for those with thymic epithelial tumors (TET). While prior studies have shown the potential superiority of minimally invasive approaches via robotic- and video-assisted thoracoscopic surgery (RATS/VATS) for thymectomy compared to open surgery, in the setting of malignancies, this outcome delineation is controversial. As RATS/VATS may be associated with less post-operative complications in the treatment of TET, some surgeons argue that the open approach is necessary for complete resection (R0 resection) and to prevent potential seeding of the malignancy.

Patterns of physical activity, sedentary behavior, and sleep across pregnancy before and during two COVID pandemic years.

Background: Physical activity is recommended during pregnancy, and high sedentary behavior and poor sleep may increase the risk of pregnancy complications. Activity patterns and sleep were negatively impacted by the COVID pandemic in many segments of the population, but the impact of the pandemic on pregnant people is understudied. We aimed to compare patterns of physical activity, sedentary time, and sleep during pregnancy between a pre-COVID and a COVID-era cohort.

Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV.

Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods: We followed individuals from ART initiation (protease inhibitor [PI]-, non-nucleoside reverse transcriptase inhibitor [NNRTI]-, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, 12/31/2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses).

Labeling and isolating cell specific neuronal mitochondria and their functional analysis in mice post stroke.

Dendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN) and CaMKIIa positive (CaMKIIa) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke.

Early detection of high blood pressure from natural speech sounds with graph diffusion network.

This study presents an innovative approach to cuffless blood pressure prediction by integrating speech and demographic features. With a focus on non-invasive monitoring, especially in remote regions, our model harnesses speech signals and demographic data to accurately estimate blood pressure. We found a strong correlation between our predictive model and early-stage high blood pressure, highlighting its potential for early detection.

Baseline kidney function and the effects of dapagliflozin on health status in heart failure in DEFINE-HF and PRESERVED-HF.

Aims: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).

Osteomyelitis and Septic Arthritis of the Upper Extremity in Pediatric Patients.

Purpose Of Review: For pediatric osteomyelitis and septic arthritis, 10-24% of cases occur in the upper extremity (UE). Due to delays in presentation and diagnosis, UE infections are often more complex and severe than infections of the lower extremity (LE). This review evaluates the literature from the past 6 years related to pediatric osteomyelitis and septic arthritis of the UE and provides a guide for professionals managing these conditions in children.

Advancing the Teaching of Equilibrium Potential: Five Small Yet Transformative Additions.

The equilibrium potential of an ion species is a crucial concept for medical students, as it is a prerequisite to fully understanding the pathophysiology of K imbalances (hyperkalemia and hypokalemia) in clinical practice. However, it remains a challenging concept because current medical physiology textbooks are too simplistic and overlook several essential points. In this article, we present a total of five small but impactful additions to advance the introduction of the equilibrium potential that will eliminate confusion and facilitate mastery-level comprehension.

Prevalence and Outcomes of Sepsis in Patients With Colon Carcinoma: Organism-Specific Analysis.

Background Sepsis is a challenging condition, especially in patients with malignancy, that is associated with worse mortality and increased complications. This study aimed to analyze the prevalence of sepsis, its complications, healthcare outcomes, and associated organism-specific mortality in patients with colorectal carcinoma using the National Inpatient Sample database. Methodology We included patients aged >18 years with a primary diagnosis of colon cancer.