Prevalence of High-Risk CTA-Based Carotid Plaque-RADS Subtypes in Patients With Embolic Stroke of Undetermined Source.

Background: A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability.

Methods: A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for Clinical Staging of Patients Newly Diagnosed with Breast Cancer.

The accurate staging of breast cancer is fundamental for guiding treatment decisions and predicting patient outcomes. However, there can be considerable variation in routine clinical practice based on individual interpretation of guidelines and depending on the healthcare provider initially involved in working up patients newly diagnosed with breast cancer, ranging from primary care providers, triage nurses, surgeons, and/or oncologists. The optimal approach for clinical staging, particularly in asymptomatic patients presenting with intermediate-risk disease, remains a topic of dialogue among clinicians.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for the Systemic Treatment of Patients with HER2+ Breast Cancer in Both the Early and Metastatic Setting.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of breast cancer associated with a poor prognosis when sub-optimally treated. Recent advances include new and effective targeted therapies that have significantly improved outcomes for patients. Despite these advances, there are significant gaps across Canada, underscoring the need for evidence-based consensus guidance to inform treatment decisions.

A Multi-Enzyme Nanocascade to Target Disease-Relevant Metabolites.

Metabolic processes in living organisms depend on the synergistic actions of enzymes working in proximity and in concert, catalyzing reactions effectively while regulating the formation of metabolites. This enzyme synergy offers promising therapeutic application for diseases such as alcohol intoxication, cancer, and hyperinflammation. Despite their potential, the clinical translation of enzyme cascades is restricted by challenges including poor enzyme stability, short half-life, and a lack of delivery strategies that maintain enzyme proximity.

Spatial structural abnormality maps associated with cognitive and physical performance in relapsing-remitting multiple sclerosis.

Objectives: We aimed to characterize the brain abnormalities that are associated with the cognitive and physical performance of patients with relapsing-remitting multiple sclerosis (RRMS) using a deep learning algorithm.

Materials And Methods: Three-dimensional (3D) nnU-Net was employed to calculate a novel spatial abnormality map by T1-weighted images and 281 RRMS patients (Dataset-1, male/female = 101/180, median age [range] = 35.0 [17.

A Multi-Institutional Study on Ultrasound Image Analysis for Staging HBV-Derived Liver Fibrosis: A Potential Noninvasive Alternative to Liver Stiffness Measurement.

Introduction: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI).

Methods: Texture features were extracted from ultrasound images.

JAK2/mTOR inhibition fails to prevent acute GVHD despite reduced Th1/Th17 cells: final phase 2 trial results.

Our phase 1 graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib (PAC; recommended phase 2 dose: 100 mg orally twice a day on day 0 to +70) plus sirolimus and tacrolimus (SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). PAC inhibits interleukin 6 (IL-6) receptor activity and pathogenic T helper cell 1 (Th1)/Th17 differentiation in preclinical models and the phase 1 trial. Herein, we report on our completed phase 2 trial of PAC/SIR/TAC after 8/8 human leukocyte antigen matched alloHCT.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

Background: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored.

Innovative Formulation Platform: Paving the Way for Superior Protein Therapeutics with Enhanced Efficacy and Broadened Applications.

Protein therapeutics offer high therapeutic potency and specificity; the broader adoptions and development of protein therapeutics, however, have been constricted by their intrinsic limitations such as inadequate stability, immunogenicity, suboptimal pharmacokinetics and biodistribution, and off-target effects. This review describes a platform technology that formulates individual protein molecules with a thin formulation layer of crosslinked polymers, which confers the protein therapeutics with high activity, enhanced stability, controlled release capability, reduced immunogenicity, improved pharmacokinetics and biodistribution, and ability to cross the blood brain barriers. Based on currently approved protein therapeutics, this formulating platform affords the development of a vast family of superior protein therapeutics with improved efficacy and broadened indications at significantly reduced cost.

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

Background: Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

Background: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated.

Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult.

Methods: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls.

AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease.

Background: Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and promotes CAVD progression.

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

Background: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

Background: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing.

Objective: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control.

Design: A multicenter, randomized, sham-controlled trial.

Cereblon influences the timing of muscle differentiation in tadpoles.

Thalidomide has a dark history as a teratogen, but in recent years, its derivates have been shown to function as potent chemotherapeutic agents. These drugs bind cereblon (CRBN), the substrate receptor of an E3 ubiquitin ligase complex, and modify its degradation targets. Despite these insights, remarkably little is known about the normal function of cereblon in development.

Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy.

Cancer immunotherapy has reshaped the landscape of cancer treatment. However, its efficacy is still limited by tumor immunosuppression associated with the excessive production of lactate by cancer cells. Although extensive efforts have been made to reduce lactate concentrations through inhibition of lactate dehydrogenase, such inhibitors disrupt the metabolism of healthy cells, causing severe nonspecific toxicity.

Therapy-associated remodeling of pancreatic cancer revealed by single-cell spatial transcriptomics and optimal transport analysis.

In combination with cell intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged high-plex single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with specific malignant subtypes and neoadjuvant chemotherapy/radiotherapy. We developed Spatially Constrained Optimal Transport Interaction Analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression.

Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease.

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029).