Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.

Design and performance of a magnetic bottle electron spectrometer for high-energy photoelectron spectroscopy.

We describe the design and performance of a magnetic bottle electron spectrometer (MBES) for high-energy electron spectroscopy. Our design features a 2 m long electron drift tube and electrostatic retardation lens, achieving sub-electronvolt (eV) electron kinetic energy resolution for high energy (several hundred eV) electrons with a close to 4π collection solid angle. A segmented anode electron detector enables the simultaneous collection of photoelectron spectra in high resolution and high collection efficiency modes.

Antibiotic Use and Subsequent Cognitive Decline and Dementia Risk in Healthy Older Adults.

Background And Objectives: Antibiotics rapidly reduce intestinal bacterial diversity, leading to dysbiosis that persists for months to years. Although emerging evidence from retrospective and claims-based studies has linked dysbiosis to cognitive function, prospective data are lacking. We aim to examine the prospective association of antibiotics with cognitive aging among initially healthy older adults.

ACKR1ECs Promote Aortic Dissection Through Adjusting Macrophage Behavior.

Background: Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development.

Methods And Results: Single-cell transcriptomic analysis of human aortic tissues revealed increased populations of endothelial cells exhibiting high ACKR1 expression and proinflammatory macrophages in TAAD samples.

Heteroaryl Glutarimides and Dihydrouracils as Cereblon Ligand Scaffolds for Molecular Glue Degrader Discovery.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds.

Ultrafast structural dynamics of UV photoexcited ,-1,3-cyclooctadiene observed with time-resolved electron diffraction.

Conjugated diene molecules are highly reactive upon photoexcitation and can relax through multiple reaction channels that depend on the position of the double bonds and the degree of molecular rigidity. Understanding the photoinduced dynamics of these molecules is crucial for establishing general rules governing the relaxation and product formation. Here, we investigate the femtosecond time-resolved photoinduced excited-state structural dynamics of ,-1,3-cyclooctadiene, a large-flexible cyclic conjugated diene molecule, upon excitation with 200 nm using mega-electron-volt ultrafast electron diffraction and trajectory surface hopping dynamics simulations.

GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders.

Background: Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported.

Methods: GSK3β-floxed and GSK3α-floxed mice were crossed with adiponectin-Cre mice to generate GSK3β or GSK3α adipocyte-specific knockout mice (GSK3β and GSK3α).

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients.

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients And Methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed.

MR1 presents vitamin B6-related compounds for recognition by MR1-reactive T cells.

The major histocompatibility complex class I related protein (MR1) presents microbially derived vitamin B2 precursors to mucosal-associated invariant T (MAIT) cells. MR1 can also present other metabolites to activate MR1-restricted T cells expressing more diverse T cell receptors (TCRs), some with anti-tumor reactivity. However, knowledge of the range of the antigen(s) that can activate diverse MR1-reactive T cells remains incomplete.

[18F]-Fluorodeoxyglucose Uptake as a Marker of Residual Anaplastic and Poorly Differentiated Thyroid Carcinoma Following BRAF-Targeted Therapy.

Background And Purpose: Neoadjuvant BRAF-directed therapy and immunotherapy followed by surgery improves survival in patients with BRAF-mutant anaplastic thyroid carcinoma (ATC), more so in those who have complete ATC pathologic response. This study assesses the ability of FDG-PET to non-invasively detect residual high-risk pathologies including ATC and poorly differentiated thyroid carcinoma (PDTC) in the preoperative setting.

Materials And Methods: This retrospective, single-center study included consecutive BRAF-mutant ATC patients treated with at least 30 days of neoadjuvant BRAF-directed therapy and who underwent FDG-PET/CT within 30 days prior to surgery.

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

Comparative Effectiveness of Abaloparatide and Teriparatide in Women 50 Years of Age and Older: Update of a Real-World Retrospective Analysis.

Background: Abaloparatide and teriparatide are osteoanabolic treatments indicated for postmenopausal women and men with osteoporosis at high risk of fracture. In the Abaloparatide Comparator Trial In Vertebral Endpoints study, bone mineral density improvements were significantly greater with abaloparatide compared to teriparatide at the total hip and femoral neck. We conducted a retrospective claims study to examine the incidences of hip and nonvertebral fractures and cardiovascular events in women aged ≥50 years initiating abaloparatide or teriparatide therapy, expanding on a previous retrospective claims study.

All-Suture Anchor Techniques for Biceps Tenodesis Are Noninferior in End-Cycle Stiffness to an Interference Screw Technique; However, Secondary Outcomes, Such as Ultimate Failure Load, Yield Load, Creep, and Load-to-Failure Stiffness, Are Inferior in an Ovine Model.

Purpose: To assess the biomechanical performance of 2 simplified loop-and-tack biceps tenodesis techniques, all-suture anchor and all-suture anchor with a button, compared with the interference screw technique in an ovine model.

Methods: Twenty-one biceps tenodesis procedures were executed on the humeri and flexor digitorum profundus tendons of skeletally mature, female sheep. Limbs were evenly randomized into 2 experimental groups (all-suture anchor with or without button) and 1 control group (interference screw).

Pan-cancer γδ TCR analysis uncovers clonotype diversity and prognostic potential.

Gamma-delta T cells (γδ T cells) play a crucial role in both innate and adaptive immunity within tumors, yet their presence and prognostic value in cancer remain underexplored. This study presents a large-scale analysis of γδ T cell receptor (γδ TCR) reads from 11,000 tumor samples spanning 33 cancer types, utilizing the TRUST4 algorithm. Our findings reveal extensive diversity in γδ TCR clonality and gene expression, underscoring the potential of γδ T cells as prognostic biomarkers in various cancers.

Oral Microbiome: A Review of Its Impact on Oral and Systemic Health.

Purpose Of Review: This review investigates the oral microbiome's composition, functions, influencing factors, connections to oral and systemic diseases, and personalized oral care strategies.

Recent Findings: The oral microbiome is a complex ecosystem consisting of bacteria, fungi, archaea, and viruses that contribute to oral health. Various factors, such as diet, smoking, alcohol consumption, lifestyle choices, and medical conditions, can affect the balance of the oral microbiome and lead to dysbiosis, which can result in oral health issues like dental caries, gingivitis, periodontitis, oral candidiasis, and halitosis.