Influence of antibody-drug conjugate cleavability, drug-to-antibody ratio, and free payload concentration on systemic toxicities: A systematic review and meta-analysis.

While in theory antibody drug conjugates (ADCs) deliver high-dose chemotherapy directly to target cells, numerous side effects are observed in clinical practice. We sought to determine the effect of linker design (cleavable versus non-cleavable), drug-to-antibody ratio (DAR), and free payload concentration on systemic toxicity. Two systematic reviews were performed via PubMed search of clinical trials published between January 1998-July 2022.

The Impact of Anesthesia on Dermatological Outcomes: A Narrative Review.

Anesthesia is an essential component of dermatologic procedures, influencing pain management and patient outcomes, including wound healing, infection control, and cosmetic appearance. This review examines the impact of various anesthetic techniques, topical, local, regional, and general, on dermatological outcomes. The findings reveal that while local anesthesia is preferred due to its efficacy and safety, specialized considerations are necessary for pediatric, geriatric, and high-risk patients.

Obesity Medications and Their Impact on Cardiovascular Health: A Narrative Review.

Obesity is a major global issue linked to cardiovascular diseases (CVDs). While lifestyle changes are the primary treatment, medications are often required for long-term weight management and reducing risk in patients with obesity. The cardiovascular effects of many obesity medications are still being studied.

Most deprived Louisiana census tracts have higher hepatocellular carcinoma incidence and worse survival.

Background: Liver cancer incidence increased in the US from 1975 through 2015 with heterogeneous rates across subpopulations. Upstream or distal area-level factors impact liver cancer risks.

Objective: The aim of this study was to examine the association between area-level deprivation and hepatocellular carcinoma (HCC) incidence and survival.

The dose-response effect of aerobic exercise on inflammation in colon cancer survivors.

Background: Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer.

Methods: In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose).

Nonconvulsive Status Epilepticus With Generalized Spike-and-Wave Discharges: Pathophysiological and Nosological Considerations.

Absence status epilepticus (ASE) is the most common type of status epilepticus in patients with idiopathic generalized epilepsy (IGE). Like absence seizure, ASE is characterized by generalized spike-and-wave discharges (GSWDs) on the electroencephalogram (EEG). Once considered specific for IGE, GSWDs have increasingly been observed in other forms of epilepsy, as well as in patients with no prior epilepsy.

Thyroid hormone enhances estrogen-mediated proliferation and cell cycle regulatory pathways in steroid receptor-positive breast Cancer.

Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progression.

HER3 functions as an effective therapeutic target in triple negative breast cancer to potentiate the antitumor activity of gefitinib and paclitaxel.

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease.

HER3 targeting augments the efficacy of panobinostat in claudin-low triple-negative breast cancer cells.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes.

Trastuzumab-resistant breast cancer cells-derived tumor xenograft models exhibit distinct sensitivity to lapatinib treatment in vivo.

Background: Resistance to HER2-targeted therapies, including the monoclonal antibody trastuzumab and tyrosine kinase inhibitor lapatinib, frequently occurs and currently represents a significant clinical challenge in the management of HER2-positive breast cancer. We previously showed that the trastuzumab-resistant SKBR3-pool2 and BT474-HR20 sublines were refractory to lapatinib in vitro as compared to the parental SKBR3 and BT474 cells, respectively. The in vivo efficacy of lapatinib against trastuzumab-resistant breast cancer remained unclear.

Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response.

Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in different animals, including mice, making B. bronchiseptica the gold-standard model to investigate host-pathogen interaction at the molecular level. B.

Older Patient Receptivity to the Integration of Patient Portals and Telehealth in Urogynecology: Promoters and Deterrents.

Importance: Limited studies focus on the integration of online portals, including telehealth services, in urogynecology while identifying promoters and deterrents of utilization, especially for the older population.

Objective: This study aimed to identify facilitators, concerns, technical or personal issues encountered, and the desired features of the online patient portals among older urogynecology patients.

Study Design: This is a secondary analysis of a cross-sectional study of older patients (≥65 years).

spp. utilize the type 3 secretion system to manipulate the VIP/VPAC2 signaling and promote colonization and persistence of the three classical in the lower respiratory tract.

Introduction: are respiratory pathogens comprised of three classical species: , and . With recent surges in spp. cases and antibiotics becoming less effective to combat infectious diseases, there is an imperative need for novel antimicrobial therapies.

HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors.

Human epidermal growth factor receptor 3 (HER3) is a unique member of the human epidermal growth factor receptor (HER/EGFR) family, since it has negligible kinase activity. Therefore, HER3 must interact with a kinase-proficient receptor to form a heterodimer, leading to the activation of signaling cascades. Overexpression of HER3 is observed in various human cancers, including non-small cell lung cancer (NSCLC), and correlates with poor clinical outcomes in patients.

Autoimmune Myelitis and Myocarditis in a Patient With Anti-Aquaporin-4, Antinuclear, and Antiphospholipid Autoantibodies: The Neuromyelitis Optica-Systemic Lupus Erythematosus (NMO-SLE) Overlap Syndrome.

The coexistence of two or more autoimmune diseases is well-known, e.g., a person can have neuromyelitis optica (NMO) and systemic lupus erythematosus (SLE) at the same time.

ALKBH5-Mediated m6A Demethylation of GLUT4 mRNA Promotes Glycolysis and Resistance to HER2-Targeted Therapy in Breast Cancer.

Unlabelled: Resistance to HER2-targeted therapy represents a significant challenge for the successful treatment of patients with breast cancer with HER2-positive tumors. Through a global mass spectrometry-based proteomics approach, we discovered that the expression of the N6-methyladenosine (m6A) demethylase ALKBH5 was significantly upregulated in HER2-targeted therapy-resistant breast cancer cells. Elevated expression of ALKBH5 was sufficient to confer resistance to HER2-targeted therapy, and specific knockdown of ALKBH5 rescued the efficacy of trastuzumab and lapatinib in resistant breast cancer cells.

Surgical repair of nasal septal perforations: A systematic review and meta-analysis.

Background: A wide variety of techniques for the surgical repair of nasal septal perforations (NSPs) have been described. Surgical management of NSPs can be broadly divided into open versus endonasal approaches, with additional variables involving unilateral or bilateral flaps, use of grafts, and placement of splints. The objective of this study was to compare surgical approaches and their outcomes.

Upregulation of endogenous TRAIL-elicited apoptosis is essential for metformin-mediated antitumor activity against TNBC and NSCLC.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promising antitumor activity in preclinical studies. However, the efficacy of recombinant TRAIL in clinical trials is compromised by its short serum half-life and low stability. Induction of endogenous TRAIL may overcome the limitations and become a new strategy for cancer treatment.

Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer.

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs.

Exogenous Thyroid Hormone Is Associated with Shortened Survival and Upregulation of High-Risk Gene Expression Profiles in Steroid Receptor-Positive Breast Cancers.

Purpose: Thyroid disease is a frequent comorbidity in women with breast cancer, and many require thyroid hormone replacement therapy (THRT). We postulated that THRT has a deleterious clinical effect mechanistically through hormonal interactions, nuclear receptor cross-talk, and upregulation of high-risk breast cancer genes.

Experimental Design: Observational studies of patients with lymph node-negative (LN) breast cancer ( = 820 and = 160) were performed to test interactions between THRT and clinical, histologic, outcome, and treatment variables.

Global knockout of ROMK potassium channel worsens cardiac ischemia-reperfusion injury but cardiomyocyte-specific knockout does not: Implications for the identity of mitoKATP.

The renal-outer-medullary‑potassium (ROMK) channel, mutated in Bartter's syndrome, regulates ion exchange in kidney, but its extra-renal functions remain unknown. Additionally, ROMK was postulated to be the pore-forming subunit of the mitochondrial ATP-sensitive K channel (mitoK), a mediator of cardioprotection. Using global and cardiomyocyte-specific knockout mice (ROMK-GKO and ROMK-CKO respectively), we characterize the effects of ROMK knockout on mitochondrial ion handling, the response to pharmacological K channel modulators, and ischemia/reperfusion (I/R) injury.

Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of Neprilysin Activity in the Kidney.

Background: Sustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF).

Objectives: This study investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism.

Methods: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and reperfusion for 12 weeks.

Endovascular reconstruction of internal carotid artery dissection in patients with acute ischemic stroke using the Wingspan stent.

Objective: The purpose of this study is to demonstrate our experience in endovascular reconstruction of carotid dissections using the Wingspan Stent System™ (Boston Scientific, Natick, MA, USA), a device we use because of its high radial force and its navigation in extreme curves.

Methods: We treated 11 consecutive patients with acute ischemic stroke due to carotid dissection with the Wingspan stent, in the cervical carotid artery.

Results: Functional evaluation revealed that 10 of the 11 patients were independent at 3 months post surgery and that the 11 stents used were found to be patent at the 6-month follow-up digital subtraction angiography (DSA).

Recruitment of the adaptor protein Nck to PECAM-1 couples oxidative stress to canonical NF-κB signaling and inflammation.

Oxidative stress stimulates nuclear factor κB (NF-κB) activation and NF-κB-dependent proinflammatory gene expression in endothelial cells during several pathological conditions, including ischemia/reperfusion injury. We found that the Nck family of adaptor proteins linked tyrosine kinase signaling to oxidative stress-induced activation of NF-κB through the classic IκB kinase-dependent pathway. Depletion of Nck prevented oxidative stress induced by exogenous hydrogen peroxide or hypoxia/reoxygenation injury from activating NF-κB in endothelial cells, increasing the abundance of the proinflammatory molecules ICAM-1 (intracellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and recruiting leukocytes.