Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

Ferguson Plot Analysis of Chaperone ClpB from Moderate Halophile.

The Ferguson plot is a simple method for determining the molecular weight of native proteins and their complexes. In this study, we tested the validity of the Ferguson plot based on agarose native gel electrophoresis using multimeric chaperone protein, ClpB, derived from a moderate halophile that forms a native hexamer. The Ferguson plot showed a single band with a molecular weight of 1,500 kDa, approximately twice the size of the native hexamer.

Demographic and clinical trends of young breast cancer patients from the national cancer database: disproportionate effect on minority populations.

Purpose: There is an increasing incidence of young breast cancer (YBC) patients with uncertainty surrounding the factors and patterns that are contributing.

Methods: We obtained characteristics and survival data from 206,156 YBC patients (≤ 40 years of age) diagnosed between 2005 and 2019 from the National Cancer Database (NCDB). Patients were subdivided into two comparison groups based on year of diagnosis (2005-2009, Old vs.

Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights.

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs.

Nonopioid vs opioid analgesics after impacted third-molar extractions: The Opioid Analgesic Reduction Study randomized clinical trial.

Background: Opioids are still being prescribed to manage acute postsurgical pain. Unnecessary opioid prescriptions can lead to addiction and death, as unused tablets are easily diverted.

Methods: To determine whether combination nonopioid analgesics are at least as good as opioid analgesics, a multisite, double-blind, randomized, stratified, noninferiority comparative effectiveness trial was conducted, which examined patient-centered outcomes after impacted mandibular third-molar extraction surgery.

A Randomized, Controlled Trial of In-Hospital Use of Virtual Reality to Reduce Preoperative Anxiety Prior to Cardiac Surgery.

Objective: To study the effectiveness of virtual reality (VR) in reducing anxiety levels in patients undergoing first-time sternotomy for cardiac surgery.

Patients And Methods: A total of 100 adult patients scheduled for cardiac surgery at Mayo Clinic in Rochester, Minnesota, USA, was recruited from April 19, 2022, to October 12, 2022. Before surgery, patients wore a physiological monitor to record vital signs.

Intrathecal Drug Delivery for Intractable Pain: Identified Patient Satisfaction Survey Study Comparing Intrathecal Dose With Satisfaction, Pain Relief, and Side Effects.

Objectives: Past studies have shown the efficacy of spinal targeted drug delivery (TDD) in pain relief, reduction in opioid use, and cost-effectiveness in long-term management of complex chronic pain. We conducted a survey to determine treatment variables associated with patient satisfaction.

Materials And Methods: Patients in a single pain clinic who were implanted with Medtronic pain pumps to relieve intractable pain were identified from our electronic health record.

No Association Between Donor Variables and Clinically Significant Outcomes, Reoperations, and Failure After Osteochondral Allograft Transplantation.

Background: Mismatch between osteochondral allograft (OCA) donor and recipient sex has been shown to negatively affect outcomes. This study accounts for additional donor variables and clinically relevant outcomes.

Purpose: To evaluate whether donor sex, age, donor-recipient sex mismatch, and duration of graft storage affect clinical outcomes and failure rates after knee OCA transplantation.

Fixation Methods, Complications, and Outcomes After Primary Fixation of Isolated Chondral Fragments in the Knee: A Systematic Review.

Background: Knee injuries resulting in purely cartilaginous defects are rare, and controversy remains regarding the reliability of chondral-only fixation.

Purpose: To systematically review the literature for fixation methods and outcomes after primary fixation of chondral-only defects within the knee.

Study Design: Systematic review; Level of evidence, 5.

Exploring the Relationship Between Combined, Acetabular, and Femoral Version on Postoperative Outcomes 2 Years After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Background: Many studies have examined the prevalence of acetabular version (AV) and femoral version (FV) abnormalities and their effect on patient-reported outcomes (PROs) after hip arthroscopy for femoroacetabular impingement syndrome (FAIS), but few have explored the prevalence and influence of combined version (CV) abnormalities.

Purpose: To (1) describe the distribution of AV, FV, and CV in the largest cohort to date and (2) determine the relationship between AV, FV, and CV and PROs after hip arthroscopy for FAIS.

Study Design: Cohort study; Level of evidence, 3.

Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review.

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

Leishmania mexicana N-Acetyltransferease 10 Is Important for Polysome Formation and Cell Cycle Progression.

Leishmania presents a complex life cycle that involves both invertebrate and vertebrate hosts. By regulating gene expression, protein synthesis, and metabolism, the parasite can adapt to various environmental conditions. This regulation occurs mainly at the post-transcriptional level and may involve epitranscriptomic modifications of RNAs.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

3D reconstruction of shoulder muscles in hominoid primates: Correlating scapular attachment areas with muscle volume.

Digital muscle reconstructions have gained attraction in recent years, serving as powerful tools in both educational and research contexts. These reconstructions can be derived from various 2D and 3D data sources, enabling detailed anatomical analyses. In this study, we evaluate the efficacy of surface scans in accurately reconstructing the volumes of the rotator cuff and teres major muscles across a diverse sample of hominoids.

Identification of Cannabis Product Characteristics and Pricing on Dark Web Markets.

Growing cannabis use has made it the most widely cultivated and trafficked illicit drug globally according to the World Health Organization, with 147 million people consuming cannabis-derived products (CDPs) in various product forms and constituency. Despite restrictions in certain countries, unregulated access can still be found on the dark web which specializes in trafficking of illicit goods. The objective was to systematically collect data from multiple marketplaces to identify types of cannabis products offered for sale.

Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited.

Retrospective Cohort Study on the Predictive Value of Primary Non-response to Initial Biologic for Future Biologic Use in Patients with Inflammatory Bowel Disease.

Background: The armamentarium of medical therapies to treat inflammatory bowel disease (IBD) continues to grow, which has expanded treatment options, particularly after first biologic failure. Currently, there are limited studies investigating the predictive value of first biologic primary non-response (PNR) on subsequent biologic success. Our objective was to determine if PNR to the first biologic for IBD is predictive of response to subsequent biologic therapy.

Optimized methods for scRNA-seq and snRNA-seq of skeletal muscle stored in nucleic acid stabilizing preservative.

Single cell studies have transformed our understanding of cellular heterogeneity in disease but the need for fresh starting material can be an obstacle, especially in the context of international multicenter studies and archived tissue. We developed a protocol to obtain high-quality cells and nuclei from dissected human skeletal muscle archived in the preservative Allprotect® Tissue Reagent. After fluorescent imaging microscopy confirmed intact nuclei, we performed four protocol variations that compared sequencing metrics between cells and nuclei enriched by either filtering or flow cytometry sorting.

Grouping of chemicals for safety assessment: the importance of toxicokinetic properties of salicylate esters.

Grouping of chemicals has been proposed as a strategy to speed up the screening and identification of potential substances of concern among the broad chemical universe under REACH. Such grouping is usually based on shared structural features and should only be used for the prioritization objectives. However, additional considerations (as well as structural similarity) are needed, e.

Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.

Introduction: Atogepant is a calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults in the USA, EU, and several other countries. The objectives of this study were to evaluate the pharmacokinetics (PK) and dose proportionality of atogepant in healthy Japanese participants, evaluate the safety and tolerability of atogepant in Japanese participants, and explore the differences in the PK and safety of atogepant in Japanese vs white participants.

Methods: A total of 50 participants (40 Japanese and 10 white) were enrolled into five cohorts; Japanese cohorts were randomized in a 4:1 ratio to atogepant (10 mg, 30 mg, or 60 mg daily dosing and 60 mg twice daily) or placebo.

Short-term Patient-Reported Outcomes Following Bilateral Risk-Reducing Mastectomy for Patients at a High Risk for Breast Cancer: A Systematic Review.

Background: Bilateral risk-reducing mastectomies (RRMs) have been proven to decrease the risk of breast cancer in patients at high risk owing to family history or having pathogenic genetic mutations. However, few resources with consolidated data have detailed the patient experience following surgery. This systematic review features patient-reported outcomes for patients with no breast cancer history in the year after their bilateral RRM.