Midterm Survivorship and Clinical Outcomes in Fresh Osteochondral Allograft Transplantation for the Treatment of Large Bipolar Lesions of the Knee.

Background: Fresh osteochondral allograft (OCA) transplantation is an established treatment option for patients with chondral or osteochondral lesions of the knee. Predictably positive outcomes are seen in situations of focal or isolated cartilage defects. However, OCA transplantation may also be performed in more complex joint salvage situations in young patients.

Value of multi-parameter I-MIBG scintigraphy in the differential diagnosis of Parkinson's disease.

Background: I-MIBG scintigraphy plays a significant role in diagnosing Parkinson's disease (PD), with most studies primarily targeting cardiac uptake and relying on traditional ratio-based parameters for assessment. However, due to variations in scanning conditions and image processing methodologies, the clinical utility of different parameters remains a subject of debate. This study aims to evaluate the diagnostic accuracy of multi-parameter I-3-Iodobenzylguanidine (MIBG) scintigraphy and to identify the most reliable metrics for distinguishing PD from Parkinson-plus syndromes.

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Differential Connectivity Patterns of Mild Cognitive Impairment in Alzheimer's and Parkinson's Disease: A Large-scale Brain Network Study.

Rationale And Objectives: Cognitive disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), significantly impact the quality of life in older adults. Mild cognitive impairment (MCI) is a critical stage for intervention and can predict the development of dementia. The causes of these two diseases are not fully understood, but there is an overlap in their neuropathology.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Analyzing the Effect of Surgical and Corneal Parameters on the Postoperative Refractive Outcomes of Smile in Myopic Eyes Based on Machine Learning.

Purpose: To analyze the influence of individual parameters on the postoperative refractive outcomes of small incision lenticule extraction (SMILE) in myopic eyes using machine learning.

Design: Retrospective Clinical Cohort Study METHODS: This study included 477 patients (922 eyes) of SMILE and divided them into two groups based on postoperative spherical equivalent (SE) ≤ -0.50D to analyze the factors influencing postoperative refractive outcomes.

Association of Glymphatic Function With Clinical Characteristics in Patients With Clinical and Asymptomatic Creutzfeldt-Jakob Disease.

Background And Objectives: Abnormal glymphatic system-related proteins have been identified in a small-scale pathologic study of patients with Creutzfeldt-Jakob disease (CJD). However, it remains unclear whether glymphatic dysfunction occurs in vivo in patients with CJD and whether this decline begins during the preclinical stage. This study aimed to investigate the relationship between glymphatic dysfunction and clinical characteristics in patients with CJD, as well as potential glymphatic impairment in preclinical CJD.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Molecular Profiling of Mouse Models of Loss or Gain of Function of the KCNT1 (Slack) Potassium Channel and Antisense Oligonucleotide Treatment.

The potassium sodium-activated channel subtype T member 1 () gene encodes the Slack channel K1.1, which is expressed in neurons throughout the brain. Gain-of-function variants in are associated with a spectrum of epilepsy syndromes, and mice carrying those variants exhibit a robust phenotype similar to that observed in patients.

Immunotherapy that improves response to chemotherapy in high-grade serous ovarian cancer.

Single-cell RNA sequencing (scRNAseq) of tumour-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies reveals potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identifies NACT-induced overexpression of stabilin-1 (clever-1) on macrophages and FOXP3 in Tregs that is confirmed at the protein level. STAB1 inhibition in vitro induces anti-tumour macrophages.

[Bioinformatics analysis of pathogenesis-associated protein Rv2387 in Mycobacterium tuberculosis].

Objective To predict and analyze the structure and function of the protein encoding the Mycobacterium tuberculosis (Mtb) Rv2387 gene by bioinformatics methods. Methods Basic information about the Rv2387 gene and the protein it encodes was obtained from the National Center for Biological Information (NCBI) database. Physicochemical properties and the hydrophilicity/hydrophobicity of proteins were predicted using ProtParam and ProtScale tools; TMHMM-2.

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.

Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013-2019.

Aims/hypothesis: The aim of this study was to investigate racial and ethnic disparities in the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) among older adults with type 2 diabetes and cardiorenal conditions.

Methods: Using Medicare fee-for-service data (2013-2019), this retrospective cohort study identified older adults (≥65 years) with type 2 diabetes initiating second-line therapies (SGLT2is, GLP1-RAs, dipeptidyl peptidase-4 inhibitors [DPP4is] and sulfonylureas [SUs]) with (1) heart failure (HF), (2) atherosclerotic cardiovascular disease (ASCVD), (3) chronic kidney disease (CKD) and (4) no recorded cardiorenal conditions. Participants were classified as non-Hispanic White, non-Hispanic Black and Hispanic.

Site-Specific Histidine Aza-Michael Addition in Proteins Enabled by a Ferritin-Based Metalloenzyme.

Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine's moderately nucleophilic imidazole side chain. While recent studies have demonstrated chemoselective, histidine-specific modifications by further exploiting imidazole's electrophilic reactivity to overcome interference from the more nucleophilic lysine and cysteine, achieving site-specific histidine modifications remains a major challenge due to the absence of spatial control over chemical processes. Herein, through X-ray crystallography and cryo-electron microscopy structural studies, we describe the rational design of a nature-inspired, noncanonical amino-acid-incorporated, human ferritin-based metalloenzyme that is capable of introducing site-specific post-translational modifications (PTMs) to histidine in peptides and proteins.

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Study Question: Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?

Summary Answer: In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.

What Is Known Already: The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies.

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).

BAFF overexpression in triple-negative breast cancer promotes tumor growth by inducing IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses.

Purpose: Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment.

Methods: BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion.

β-GaO Nanoribbon with Ultra-High Solar-Blind Ultraviolet Polarization Ratio.

Solar-blind ultraviolet (UV) detection plays a critical role in imaging and communication due to its low-noise background, high signal-to-noise ratio, and strong anti-interference capabilities. Detecting the polarization state of UV light can enhance image information and expand the communication dimension. Although polarization detection is explored in visible and infrared light, and applied in fields such as astrophysics and submarine seismic wave detection, solar-blind UV polarization detection remains largely unreported.