Socioeconomic and Demographic Disparities in Keratoconus Treatment.

Purpose: To investigate healthcare disparities associated with keratoconus (KCN) patients receiving treatment (corneal cross-linking [CXL] and keratoplasty), as well as comorbidities associated with KCN.

Design: Retrospective clinical cohort study.

Methods: A total of 3224 patients from the University of Illinois Hospital & Health Sciences System (UI-Health) database from 2020 to 2024 were examined, including 1612 patients with an International Classification of Diseases, Tenth Revision diagnosis of KCN, and 1612 ophthalmology patients as a control group.

Spatiotemporal modeling of molecular holograms.

Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo (https://github.com/aristoteleo/spateo-release), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.

Investigating the regulatory basis of C and C photosynthesis in grasses at single-cell resolution.

While considerable knowledge exists about the enzymes pivotal for C photosynthesis, much less is known about the regulation important for specifying their expression in distinct cell types. Here, we use single-cell-indexed ATAC-seq to identify cell-type-specific accessible chromatin regions (ACRs) associated with C enzymes for five different grass species. This study spans four C species, covering three distinct photosynthetic subtypes: and (NADP-dependent malic enzyme), (NAD-dependent malic enzyme), (phosphoenolpyruvate carboxykinase), along with the C outgroup .

Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy.

Microglia replacement strategies are increasingly being considered for the treatment of primary microgliopathies like adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). However, available mouse models fail to recapitulate the diverse neuropathologies and reduced microglia numbers observed in patients. In this study, we generated a xenotolerant mouse model lacking the fms-intronic regulatory element (FIRE) enhancer within Csf1r, which develops nearly all the hallmark pathologies associated with ALSP.

Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer.

Background: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking.

Methods: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion).

Association of Neighborhood-Level Marginalization With Health Care Use and Clinical Outcomes Following Hospital Discharge in Patients Who Underwent Coronary Catheterization for Acute Myocardial Infarction in a Single-Payer Health Care System.

Background: Canadian data suggest that patients of lower socioeconomic status with acute myocardial infarction receive less beneficial therapy and have worse clinical outcomes, raising questions regarding care disparities even in universal health care systems. We assessed the contemporary association of marginalization with clinical outcomes and health services use.

Methods: Using clinical and administrative databases in Ontario, Canada, we conducted a population-based study of patients aged ≥65 years hospitalized for their first acute myocardial infarction between April 1, 2010 and March 1, 2019.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

Background: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care.

Methods: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age.

Novel Variations in the Gene Causing X-Linked Intellectual Disability.

Background And Objectives: To investigate the pathogenicity of 2 novel variations, report the clinical and neuroimaging findings, and review the available literature.

Methods: Physical examinations, structural neuroimaging studies, and exome sequence analysis were performed. KDM5C constructs were used to study the effect of the variations in transfected cells.

Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment.

LGR4-6 (leucine-rich repeat-containing G-protein-coupled receptors 4, 5, and 6) are three related receptors with an upregulated expression in gastrointestinal cancers to various extents, and LGR5 is enriched in cancer stem cells. Antibody-drug conjugates (ADCs) targeting LGR5 showed a robust antitumor effect in vivo but could not eradicate tumors due to plasticity of LGR5-positive cancer cells. As LGR5-negative cancer cells often express LGR4 or LGR6 or both, we reasoned that simultaneous targeting of all three LGRs may provide a more effective approach.

LncRNA-SNHG6 promotes the progression of hepatocellular carcinoma by targeting miR-6509-5p and HIF1A.

Background: Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied.

Methods: In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels.

CircSOD2 induced epigenetic alteration drives hepatocellular carcinoma progression through activating JAK2/STAT3 signaling pathway.

Background: Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown.

Methods: The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR).

Oxysophocarpine suppresses FGFR1-overexpressed hepatocellular carcinoma growth and sensitizes the therapeutic effect of lenvatinib.

Aims: Hepatocellular carcinoma (HCC) is an aggressive solid tumor with restricted therapeutics. Lenvatinib is the second approved frontline drug for advanced HCC, however lenvatinib-resistant cases have been reported in clinical. Overexpression of fibroblast growth factor receptor (FGFR1) has been found to be associated with advanced HCC.

Piplartine suppresses proliferation and invasion of hepatocellular carcinoma by LINC01391-modulated Wnt/β-catenin pathway inactivation through ICAT.

Although piplartine is regarded as an anticancer agent, the relationship between long noncoding RNAs (lncRNAs), which are involved in various diseases (e.g., tumors) and piplartine in hepatocellular carcinoma (HCC) remains unclear.

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.

Background: Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.

Methods: In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group).

Prospective Validation of the Emergency Heart Failure Mortality Risk Grade for Acute Heart Failure.

Background: Improved risk stratification of acute heart failure in the emergency department may inform physicians' decisions regarding patient admission or early discharge disposition. We aimed to validate the previously-derived Emergency Heart failure Mortality Risk Grade for 7-day (EHMRG7) and 30-day (EHMRG30-ST) mortality.

Methods: We conducted a multicenter, prospective validation study of patients with acute heart failure at 9 hospitals.

Emergency Department Volume and Outcomes for Patients After Chest Pain Assessment.

Background: Chest pain is one of the most common reasons for emergency department (ED) visits in developed countries. Whether higher volume EDs have better outcomes, specifically for patients with chest pain, is unknown and pertinent.

Methods And Results: We conducted a study using population-based data on 498 291 patients ≥40 years old, presenting to ED in Ontario, Canada from 2008 to 2014, with chest pain and were discharged after assessment.

Vaccinols J-S, ten new salicyloid derivatives from the marine mangrove-derived endophytic fungus Pestalotiopsis vaccinii.

Ten new salicyloid derivatives, namely vaccinols J-S (1-10), along with five known compounds (11-15) were isolated from Pestalotiopsis vaccinii (cgmcc3.9199) endogenous with the mangrove plant Kandelia candel (L.) Druce (Rhizophoraceae).

Increased Stroke Burdens Among the Low-Income Young and Middle Aged in Rural China.

Background And Purpose: Although stroke in the young and middle aged accounts for 31% of all strokes in China, the disease burden is unknown. We aimed to determine the secular trends in stroke incidence and the transition of subtypes in rural China over a 24-year period.

Methods: In 1992, 14 920 residents were recruited to participate in the Tianjin Brain Study.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.

Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.

Methods: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years.

Preoperative Laboratory Investigations: Rates and Variability Prior to Low-risk Surgical Procedures.

Background: Increasing attention has been focused on low-value healthcare services. Through Choosing Wisely campaigns, routine laboratory testing before low-risk surgery has been discouraged in the absence of clinical indications. The authors investigated rates, determinants, and institutional variation in laboratory testing before low-risk procedures.

Clinical Risk Stratification for Primary Prevention Implantable Cardioverter Defibrillators.

Background: A conceptualized model may be useful for understanding risk stratification of primary prevention implantable cardioverter defibrillators considering the competing risks of appropriate implantable cardioverter defibrillator shock versus mortality.

Methods And Results: In a prospective, multicenter, population-based cohort with left ventricular ejection fraction ≤35% referred for primary prevention implantable cardioverter defibrillator, we developed dual risk stratification models to determine the competing risks of appropriate defibrillator shock versus mortality using a Fine-Gray subdistribution hazard model. Among 7020 patients referred, 3445 underwent defibrillator implant (79.

Phase II study of PX-866 in recurrent glioblastoma.

Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system in adults. Increased activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway is common. We performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM.

Neofunctionalization of duplicated Tic40 genes caused a gain-of-function variation related to male fertility in Brassica oleracea lineages.

Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp.