Determining Clinicopathologic Factors That Influence Treatment in Advanced Breast Cancer in Argentina After CDK4/6 Inhibitors.

Purpose: The optimal treatment sequence for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated.

Materials And Methods: This is a retrospective analysis of a real-world cohort including patients with HR+/HER2- ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment.

High mobility group box 1 (HMGB1) is a potential disease biomarker in cell and mouse models of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder affecting 1:3500 male births and is associated with myofiber degeneration, regeneration, and inflammation. Glucocorticoid treatments have been the standard of care due to immunomodulatory/immunosuppressive properties but novel genetic approaches, including exon skipping and gene replacement therapy, are currently being developed. The identification of additional biomarkers to assess DMD-related inflammatory responses and the potential efficacy of these therapeutic approaches are thus of critical importance.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

Background: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients.

Methods: We conducted an international retrospective study of MeVO cases.

Codeveloping theories of change for improved community-based violence intervention evaluation.

Background: Community-based violence intervention (CVI) programs are considered important strategies for preventing community violence and promoting health and safety. Mixed and inconclusive results from some prior CVI evaluations, as well as our general lack of understanding about the reasons for such varied findings, may be explained in part by misalignment of program theories of change and evaluation measures. Furthermore, most prior evaluations have focused solely on deficit-based outcomes; this narrow focus is inconsistent with the premise of CVI and may fail to capture improvements in health and well-being that are on the hypothesized pathway from intervention to violence reduction.

Sex differences in brain atrophy in dementia with Lewy bodies.

Introduction: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI).

Methods: We included 436 patients from the European-DLB consortium and the Mayo Clinic.

A pan-cancer clinical platform to predict immunotherapy outcomes and prioritize immuno-oncology combinations in early-phase trials.

Background: Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing.

Methods: We implemented VIGex using the nCounter platform (Nanostring) on a large clinical cohort encompassing 909 tumor samples across 45 tumor types.

A new Karyopherin-β2 binding PY-NLS epitope of HNRNPH2 linked to neurodevelopmental disorders.

The HNRNPH2 proline-tyrosine nuclear localization signal (PY-NLS) is mutated in HNRNPH2-related X-linked neurodevelopmental disorder, causing the normally nuclear HNRNPH2 to accumulate in the cytoplasm. We solved the cryoelectron microscopy (cryo-EM) structure of Karyopherin-β2/Transportin-1 bound to the HNRNPH2 PY-NLS to understand importin-NLS recognition and disruption in disease. HNRNPH2 RPGPY is a typical R-X-P-Y motif comprising PY-NLS epitopes 2 and 3, followed by an additional Karyopherin-β2-binding epitope, we term epitope 4, at residues DRP; no density is present for PY-NLS epitope 1.

Engineered tRNAs suppress nonsense mutations in cells and in vivo.

Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation.

Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study.

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone.

Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871).

Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa.

Background: Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in , which encodes type VII collagen (C7). Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering .

Methods: We conducted a phase 3, double-blind, intrapatient randomized, placebo-controlled trial involving patients 6 months of age or older with genetically confirmed dystrophic epidermolysis bullosa.

Digital culturally tailored marketing for enrolling Latino participants in a web-based registry: Baseline metrics from the Brain Health Registry.

Introduction: This culturally tailored enrollment effort aims to determine the feasibility of enrolling 5000 older Latino adults from California into the Brain Health Registries (BHR) over 2.25 years.

Methods: This paper describes (1) the development and deployment of culturally tailored BHR websites and digital ads, in collaboration with a Latino community science partnership board and a marketing company; (2) an interim feasibility analysis of the enrollment efforts and numbers, and participant characteristics (primary aim); as well as (3) an exploration of module completion and a preliminary efficacy evaluation of the culturally tailored digital efforts compared to BHR's standard non-culturally tailored efforts (secondary aim).

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

Background: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year.

Method: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners.

Blood-Meal Sources and Infection in Coastal and Insular Triatomine Bugs from the Atacama Desert of Chile.

is one of the lesser known and less abundant sylvatic triatomine species naturally infected by the protozoan , the etiological agent of Chagas disease. lives in sympatry with -infected rodents, but only birds, reptiles, and marine mammals have been reported as blood-meal sources of this vector species by serology. The distribution range of this kissing bug overlaps with fishers' settlements and tourist areas, and therefore the study of the blood-meal sources of this triatomine species is relevant.

Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial.

Background: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined.

Methods: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial.

Anti-latent TGFβ binding protein 4 antibody improves muscle function and reduces muscle fibrosis in muscular dystrophy.

Duchenne muscular dystrophy, like other muscular dystrophies, is a progressive disorder hallmarked by muscle degeneration, inflammation, and fibrosis. Latent transforming growth factor β (TGFβ) binding protein 4 (LTBP4) is an extracellular matrix protein found in muscle. LTBP4 sequesters and inhibits a precursor form of TGFβ.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

Background: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied.

Methods: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.