Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Psychotropic Polypharmacy in Dementia: A Retrospective Analysis for People with Neuropsychiatric Symptoms Referred to an Australian Dementia Support Service.

Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution.

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions.

Cigarette Smoking and Symptom Burden: Baseline Results From Nine ECOG-ACRIN Cancer Clinical Trials.

Context: Approximately 11% of cancer survivors smoke postdiagnosis.

Objectives: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017 to 2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.

scTrends: A living review of commercial single-cell and spatial 'omic technologies.

Understanding the rapidly evolving landscape of single-cell and spatial omic technologies is crucial for advancing biomedical research and drug development. We provide a living review of both mature and emerging commercial platforms, highlighting key methodologies and trends shaping the field. This review spans from foundational single-cell technologies such as microfluidics and plate-based methods to newer approaches like combinatorial indexing; on the spatial side, we consider next-generation sequencing and imaging-based spatial transcriptomics.

Biosimilar SB17 versus reference ustekinumab in moderate to severe plaque psoriasis after switching: phase 3 study results up to week 52.

Introduction: SB17 is a biosimilar to reference ustekinumab (UST). We compared the efficacy, safety, and immunogenicity of SB17 to UST up to Week 52, including switching from UST to SB17.

Methods: Subjects were randomized to receive 45 mg of SB17 or UST subcutaneously up to Week 40.

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Background: Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease.

TMEM106B is a lysosomal/late endosome protein that is a potent genetic modifier of multiple neurodegenerative diseases as well as general aging. Recently, TMEM106B was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention to TMEM106B pathology and the potential role of TMEM106B aggregation in disease. In the context of neurodegenerative diseases, TMEM106B has been studied using animal models of neurodegeneration, but these studies rely on overexpression or knockdown approaches.

Early-life upper airway microbiota are associated with decreased lower respiratory tract infections.

Background: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.

Objectives: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.

Medial Opening Wedge (MOW) Versus Lateral Closing Wedge (LCW) High Tibial Osteotomies for Knee Medial Compartment Osteoarthritis Show Similar Outcomes and Survivorship, While MOW Has Higher Rates of Tibial Fracture and LCW Has Higher Rates of Nerve Injury and Conversion to Total Knee.

Purpose: To compare the clinical and radiographic outcomes and complications between medial opening wedge (MOW) and lateral closing wedge (LCW) high tibial osteotomies (HTOs) in the setting of medial compartment osteoarthritis with genu varus alignment.

Methods: This study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Studies that reported on MOW or LCW HTOs in the setting of medial compartment osteoarthritis were included.

Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease.

The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples.

Expression of Myeloperoxidase in Patient-Derived Endothelial Colony-Forming Cells-Associations with Coronary Artery Disease and Mitochondrial Function.

Background And Aims: Myeloperoxidase (MPO) plays a critical role in the innate immune response and has been suggested to be a surrogate marker of oxidative stress and inflammation, with elevated levels implicated in cardiovascular diseases, such as atherosclerosis and heart failure, as well as in conditions like rheumatoid arthritis and cancer. While MPO is well-known in leukocytes, its expression and function in human endothelial cells remain unclear. This study investigates MPO expression in patient-derived endothelial colony-forming cells (ECFCs) and its potential association with CAD and mitochondrial function.

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds.

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV).

Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle Regeneration in Muscle Atrophy.

Muscle atrophy detrimentally impacts health and exacerbates physical disability, leading to increased mortality. In particular, sarcopenia, aging-related degenerative muscle loss, necessitates urgent remedies. Current approaches for treating muscle atrophy include exercise and nutrition, while drug exploration remains in its early stages.

Predictions of Lattice Parameters in NiTi High-Entropy Shape-Memory Alloys Using Different Machine Learning Models.

This work applied three machine learning (ML) models-linear regression (LR), random forest (RF), and support vector regression (SVR)-to predict the lattice parameters of the monoclinic B19' phase in two distinct training datasets: previously published ZrO-based shape-memory ceramics (SMCs) and NiTi-based high-entropy shape-memory alloys (HESMAs). Our findings showed that LR provided the most accurate predictions for a, a, b, and c in NiTi-based HESMAs, while RF excelled in computing β for both datasets. SVR disclosed the largest deviation between the predicted and actual values of lattice parameters for both training datasets.

Characteristics of a Large Database of Healthy Eyes From Optometry Practices: Implications for a Real-World Reference Database.

Purpose: To compare an optical coherence tomography (OCT) real-world reference database (RW-RDB) of "healthy" eyes obtained from optometry practices to a commercial reference database (RDB).

Methods: OCT scans from 6804 individuals 18 years and older were sampled from a larger database tested at 10 optometry practices involved in refractive and screening services. Employing a reading center method, OCT scans from both eyes of 4932 (4.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

Introduction: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations.

Methods: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).