Combination of polymeric micelle formulation of TGFβ receptor inhibitors and paclitaxel produces consistent response across different mouse models of Triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is notoriously difficult to treat due to the lack of targetable receptors and sometimes poor response to chemotherapy. The transforming growth factor beta (TGFβ) family of proteins and their receptors (TGFRs) are highly expressed in TNBC and implicated in chemotherapy-induced cancer stemness. Here, we evaluated combination treatments using experimental TGFR inhibitors (TGFβi), SB525334 (SB), and LY2109761 (LY) with paclitaxel (PTX) chemotherapy.

Siglec15/TGF-β bispecific antibody mediates synergistic anti-tumor response against 4T1 triple negative breast cancer in mice.

An ideal tumor-specific immunomodulatory therapy should both preferentially target the tumor, while simultaneously reduce the immunosuppressive environment within the tumor. This guiding principle led us to explore engineering Siglec-15 (S15) targeted bispecific antibody (bsAb) to enhance therapy against triple negative breast cancer (TNBC). S15 appears to be exclusively expressed on macrophages and diverse tumor cells, including human and mouse 4T1 TNBC.

In situ-crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs.

Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity.

The gut microbiome plays critical roles in human homeostasis, disease progression, and pharmacological efficacy through diverse metabolic pathways. Gut bacterial β-glucuronidase (GUS) enzymes reverse host phase 2 metabolism, in turn releasing active hormones and drugs that can be reabsorbed into systemic circulation to affect homeostasis and promote toxic side effects. The FMN-binding and loop 1 gut microbial GUS proteins have been shown to drive drug and toxin reactivation.

Association between dietary intake of creatine and female reproductive health: Evidence from NHANES 2017-2020.

The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES).

Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19.

Soluble angiotensin-converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a "muco-trapping" ACE2-Fc conjugate, termed ACE2-(GS)-Fc, comprised of the extracellular segment of ACE2 (lacking the C-terminal collectrin domain) that is linked to mucin-binding IgG1-Fc via an extended glycine-serine flexible linker. ACE2-(GS)-Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2-Fc decoys or similar truncated ACE2-Fc decoys without flexible linkers, possessing picomolar binding affinity and strong neutralization potency against pseudovirus and live virus.

A rare case of pericardial sarcoidosis presenting as chest pain.

Key Clinical Message: Pericardial sarcoidosis is an uncommon cause of chest pain to consider, and it requires a heightened level of suspicion and thorough history gathering. If there is suspicion of inflammatory disease, pursuing advanced imaging and biopsies is crucial, as early immunosuppressive treatment can enhance outcomes.

Abstract: Pericardial involvement in sarcoidosis is a rare condition with limited research.

Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design.

Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline.

Introduction: Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results.

Techniques for navigating postsurgical adhesions: Insights into mechanisms and future directions.

Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers.

Interarytenoid injection outcomes in pediatric feeding disorders.

Objectives: Type 1 laryngeal clefts (LC1) and deep interarytenoid grooves contribute to pediatric feeding disorders. Management of these defects remains heterogeneous among surgeons and interarytenoid injection augmentation (IIA) is not always offered as a treatment option. This study evaluated IIA outcomes among a pediatric patient cohort comprised mostly of those with deep interarytenoid grooves.

Comparative transcriptomics reveals that a novel form of phenotypic plasticity evolved via lineage-specific changes in gene expression.

Novel forms of phenotypic plasticity may evolve by lineage-specific changes or by co-opting mechanisms from more general forms of plasticity. Here, we evaluated whether a novel resource polyphenism in New World spadefoot toads (genus ) evolved by co-opting mechanisms from an ancestral form of plasticity common in anurans-accelerating larval development rate in response to pond drying. We compared overlap in differentially expressed genes between alternative trophic morphs constituting the polyphenism in versus those found between tadpoles of Old World spadefoot toads (genus ) when experiencing different pond-drying regimes.

A call to address structural barriers to Hispanic/Latino representation in clinical trials on Alzheimer's disease and related dementias: A micro-meso-macro perspective.

Introduction: This perspective paper addresses the US Hispanic/Latino (herein, Latino) experience with regards to a significant public health concern-the underrepresentation of Latino persons in Alzheimer's disease and related dementias (AD/ADRD) clinical trials. Latino individuals are at increased risk for AD/ADRD, experience higher disease burden, and low receipt of care and services. We present a novel theoretical framework-the Micro-Meso-Macro Framework for Diversifying AD/ADRD Trial Recruitment-which considers multi-level barriers and their impact on Latino trial recruitment.

Micro and nanotechnologies: The little formulations that could.

The first publication of micro- and nanotechnology in medicine was in 1798 with the use of the Cowpox virus by Edward Jenner as an attenuated vaccine against Smallpox. Since then, there has been an explosion of micro- and nanotechnologies for medical applications. The breadth of these micro- and nanotechnologies is discussed in this piece, presenting the date of their first report and their latest progression (e.

Territoriality drives patterns of fixed space use in Caribbean parrotfishes.

Animals often occupy home ranges where they conduct daily activities. In many parrotfishes, large terminal phase (TP) males defend their diurnal (i.e.

The next step: Replacing step 1 as a metric for residency application.

Objective: As of January 2022, USMLE Step 1 scores are reported as pass/fail. Historically, Step 1 scores have been a critical component of residency applications, representing one of the few metrics standardized across all applicants independent of the school they attended. In competitive specialties, such as otolaryngology, programs routinely get 100+ applicants for each residency spot and use Step 1 as a screening tool.

Developing a novel integrated geriatric palliative care consultation program for the emergency department.

With the aging of our population, older adults are living longer with multiple chronic conditions, frailty, and life-limiting illnesses, which creates specific challenges for emergency departments (EDs). Older adults and those with serious illnesses have high rates of ED use and hospitalization, and the emergency care they receive may be discordant with their goals and values. In response, new models of care delivery have begun to emerge to address both geriatric and palliative care needs in the ED.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract.

Reconstruction of oral cavity defects using myogenous-only scapular tip free-flaps.

Background: Oral cavity reconstruction is very challenging anatomical subsite to reconstruct. Large defects often require free tissue reconstruction to provide the best chance of form and function. Additionally, free tissue reconstruction aids to prevent fistula formation.

Prediction of patient outcomes through social determinants of health: The Pulmonary Hypertension Association Registry (PHAR) evaluation.

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics.