A nonequilibrium kinetic model of high-resolution vibrational energy transfer in RDX from selective IR excitation.

In this paper, we develop a model based on a second quantization-with anharmonic phonon scattering and the phonon Boltzmann transport equation-to study precise high-resolution nonequilibrium vibrational energy transfer (VET) under selective phonon excitation in cyclotrimethylene trinitramine. We simulate mid-infrared pump-probe spectroscopy and observe a prompt appearance (<1 ps) of broad-spectrum intensity, which agrees well with experimental data in the literature. The selective excitation of phonons at different frequencies reveals distinct VET pathways and the kinetic evolution of mode occupations as the system reaches a new equilibrium temperature.

Anterior-to-Central Cartilage Defects of Arthritic Knee Showed Better Cartilage Regeneration Than Posterior Cartilage Defects Using Mesenchymal Stem Cell Implantation.

Purpose: To analyze cartilage regeneration and clinical outcomes after human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSCs) implantation on the basis of the distribution and location of medial femoral condyle (MFC) cartilage defects.

Methods: Patients who underwent hUCB-MSC implantation for MFC cartilage defects involved in isolated medial compartment osteoarthritis were included. The patients were divided into 2 groups, those with MFC defects located within the anterior-central portion (group A) and those with MFC defects extending to the posterior portion (group P).

Deep learning-based algorithm for automatic quantification of nigrosome-1 and Parkinsonism classification using susceptibility map-weighted MRI.

Background And Purpose: To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI).

Materials And Methods: We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE.

Automated Idiopathic Normal Pressure Hydrocephalus Diagnosis via Artificial Intelligence-Based 3D T1 MRI Volumetric Analysis.

Background And Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan.

Materials And Methods: We quantified iNPH, Parkinson disease, Alzheimer disease, and healthy controls on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing.

Catalyst-free reactions of anilines with β-chloroenones: synthesis of α-chloroenaminones and 1,4-benzodiazepines.

The Michael addition of anilines to β-chloroenones gives enaminones by the elimination of hydrochloric acid (HCl). These enaminones are transformed into α-chloroenaminones sp C-H functionalization. Anilines that are attached to an electron-donating group react more readily with β-chloroenone to give the corresponding products in excellent yields.

Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages.

A wide variety of electrophilic derivatives of itaconate, the Kreb's cycle-derived metabolite, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production.

Endothelial Dysfunction in Youth-Onset Type 2 Diabetes: A Clinical Translational Study.

Background: Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers.

Deep Learning Model Using Stool Pictures for Predicting Endoscopic Mucosal Inflammation in Patients With Ulcerative Colitis.

Introduction: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation.

Methods: This was a prospective multicenter study conducted in 6 tertiary referral hospitals.

Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites.

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples).

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Background And Objectives: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

Background And Objectives: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population.

Methods: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study.

Aims: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting.

Methods And Results: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death.

HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant.

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection.

Polylactide Degradation Activates Immune Cells by Metabolic Reprogramming.

Polylactide (PLA) is the most widely utilized biopolymer in medicine. However, chronic inflammation and excessive fibrosis resulting from its degradation remain significant obstacles to extended clinical use. Immune cell activation has been correlated to the acidity of breakdown products, yet methods to neutralize the pH have not significantly reduced adverse responses.

Ocular Manifestations and Outcomes in Children With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Comparison With Adult Patients.

Purpose: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Design: Retrospective comparative case series.

Methods: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020.

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.

KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer.

"At the End I Have a Say": Engaging the Chinese Community in Advance Care Planning.

Context: Despite the association of advance care planning (ACP) with improved patient and caregiver outcomes, Chinese American elders have low rates of ACP.

Objectives: Assess ACP facilitators/barriers in the San Francisco (SF) Chinese community and codesign, implement, and test community-based ACP-promoting pilot events.

Methods: A Chinese Community Committee (N = 19 community-based organization leaders, health system representatives, community members) conducted focus groups in Cantonese and English with Chinese older adults (age ≥55), caregivers, and community leaders.