The Impact of Medicaid Expansion on Stage at Diagnosis of Melanoma Patients: A Retrospective Study.

Background: This study addresses the lack of research on Medicaid expansion's impact on melanoma staging, treatment utilization, and outcomes by evaluating its effects under the Affordable Care Act (ACA), particularly focusing on staging at diagnosis, treatment use, and 3-year mortality outcomes. The objective is to determine whether Medicaid expansion led to earlier melanoma diagnosis and improved survival rates among non-elderly adults (ages 40-64) by analyzing data from the National Cancer Database (NCDB).

Methods: A total of 12,667 patients, aged 40-64, diagnosed with melanoma from 2010 to 2020 were identified using the NCDB.

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands.

Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available.

Validation of a Cancer-Focused Information Seeking Experience (ISEE) Scale.

Background: Searching for health information is critical for maintaining one's health and reducing risk of disease, including cancer. However, some people are more likely to experience challenges in finding and comprehending health information; therefore, it is important to measure health information-seeking behavior. In order to add to prior research conducted with the scale, this study provides the first formal evaluation of the validity and reliability of the four-item, cancer-focused Information Seeking Experience (ISEE) scale in a cross-sectional, nationally representative health survey of U.

Knowing is Half the Battle: The Factors Leading to Efficient Recruitment of Representative Samples in Schizophrenia Research.

Background And Objectives: Drug development in schizophrenia is limited by the differential scaling of the active treatment and placebo arms of a study, such that, as the number of sites increases, the magnitude of placebo response disproportionately increases. The objective of this article was to identify factors conducive to efficient recruitment as a step towards trial designs allowing recruitment of more participants per site, leading to reduced variability, and potentially a smaller placebo effect.

Patients And Methods: Using the information of 554 individuals, we calculated the percentage of individuals who were screened, consented, and retained in our research, along with rationale for nonconsent.

Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Beyond dyslipidemia, inflammation contributes to the development of atherosclerosis. However, intrinsic factors that counteract vascular inflammation and atherosclerosis remain scarce. Here we identify insulin-like growth factor binding protein 6 (IGFBP6) as a homeostasis-associated molecule that restrains endothelial inflammation and atherosclerosis.

Clinical trials for implantable neural prostheses: understanding the ethical and technical requirements.

Neuroprosthetics research has entered a stage in which animal models and proof-of-concept studies are translated into clinical applications, often combining implants with artificial intelligence techniques. This new phase raises the question of how clinical trials should be designed to scientifically and ethically address the unique features of neural prostheses. Neural prostheses are complex cyberbiological devices able to acquire and process data; hence, their assessment is not reducible to only third-party safety and efficacy evaluations as in pharmacological research.

Point-of-care ultrasound in Gastroenterology and Hepatology.

Point-of-care ultrasound (POCUS) is changing the practice of nearly all specialties and is increasingly being incorporated as a bedside tool by more gastroenterologists and hepatologists. POCUS is most often used to answer focused clinical questions, supplement the traditional physical examination, and guide performance of invasive bedside procedures. This review describes several common POCUS applications used in gastroenterology and hepatology, as well as some novel applications that warrant further investigation.

Thoracic Surgery Outcomes Research Network (ThORN) Consensus Document on Defining a High Quality Wedge Resection for Early Stage Lung Cancer.

With the publication of CALGB 140503, an increase in wedge resections for small, peripheral non-small cell lung cancer is expected; however, a relative paucity of data exists as to what defines a high quality oncologic wedge resection. The Thoracic Surgery Outcomes Research Network (ThORN), through expert discussion, guided by review of what limited data does exist, and through use of a modified Delphi process, provides these consensus statements defining an oncologically sound, high quality wedge resection. The statements are classified into five categories: 1) Preoperative Considerations 2) Technical Aspects 3) Lymph Node Assessment 4) Margin Assessment and 5) Tissue Handling by Pathology.

Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial.

Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.

Direct visualization of electric-field-stimulated ion conduction in a potassium channel.

Understanding protein function would be facilitated by direct, real-time observation of chemical kinetics in the atomic structure. The selectivity filter (SF) of the K channel provides an ideal model, catalyzing the dehydration and transport of K ions across the cell membrane through a narrow pore. We used a "pump-probe" method called electric-field-stimulated time-resolved X-ray crystallography (EFX) to initiate and observe K conduction in the NaK2K channel in both directions on the timescale of the transport process.

Cognitive restraint and body dissatisfaction are more strongly related to muscle building behaviors for men than women.

Muscle building behaviors are an understudied eating disorder (ED) symptom increasing in prevalence, especially among men. However, little is known about the cognitive ED correlates that may underlie muscle building behaviors and whether these associations differ by gender. We examined associations between cognitive ED symptoms and muscle building behaviors, and whether these associations differ between men and women.

Indications for tracheostomy placement in pediatric patients with cerebral palsy.

Background: Cerebral palsy (CP) is the most common neuromuscular disorder in children, and children with CP are at increased risk of respiratory distress potentially requiring tracheostomy placement. Previous studies have characterized indications for tracheostomy in neurologically compromised children, however no studies focus specifically on children with CP. The purpose of this study was to identify the indications for tracheostomy placement, sites of airway obstruction, and rate of decannulation in children with CP.

Orthopedic Resident Intern Foundations: A Cross-Institutional, Month-Long Skills Training Boot Camp for PGY-1 Residents.

Objective: Orthopedic residents are tasked with rapidly acquiring clinical and surgical skills, especially during their PGY-1 year. However, resource constraints and other factors frequently cause skills training to fall short of established guidelines. We aimed to design and evaluate a cross-institutional, month-long curriculum aimed at pooling resources to optimize training.

The unequal adoption of ChatGPT exacerbates existing inequalities among workers.

We study the adoption of ChatGPT, the icon of Generative AI, using a large-scale survey linked to comprehensive register data in Denmark. Surveying 18,000 workers from 11 exposed occupations, we document that ChatGPT is widespread, especially among younger and less-experienced workers. However, substantial inequalities have emerged.

Income inequality and the erosion of democracy in the twenty-first century.

Among the most pressing problems societies face today are economic inequality and the erosion of democratic norms and institutions. In fact the two problems-inequality and democratic erosion-are linked. In a large cross-national statistical study of risk factors for democratic erosion, we establish that economic inequality is one of the strongest predictors of where and when democracy erodes.

A hybrid meta on-top functional for multiconfiguration pair-density functional theory.

Multiconfiguration pair-density functional theory (MC-PDFT) was proposed a decade ago, but it is still in the early stage of density functional development. MC-PDFT uses functionals that are called on-top functionals; they depend on the density and the on-top pair density. Most MC-PDFT calculations to date have been unoptimized translations of generalized gradient approximations (GGAs) of Kohn-Sham density functional theory (KS-DFT).

Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.

The Association of Modified 5-Item Frailty Index on Perioperative Cochlear Implant Speech Perception.

Objective: This study aims to evaluate the potential association of perioperative hearing outcomes with frailty by Modified 5-Item Frailty Index (mFI-5).

Design: Retrospective cross-sectional study.

Setting: Single-institutional study conducted at a tertiary care hospital between January 2018 and January 2022.

ADELLE: A global testing method for trans-eQTL mapping.

Understanding the genetic regulatory mechanisms of gene expression is an ongoing challenge. Genetic variants that are associated with expression levels are readily identified when they are proximal to the gene (i.e.

Chromatin conformation, gene transcription, and nucleosome remodeling as an emergent system.

In single cells, variably sized nanoscale chromatin structures are observed, but it is unknown whether these form a cohesive framework that regulates RNA transcription. Here, we demonstrate that the human genome is an emergent, self-assembling, reinforcement learning system. Conformationally defined heterogeneous, nanoscopic packing domains form by the interplay of transcription, nucleosome remodeling, and loop extrusion.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Medicaid Policy and Hepatitis C Treatment Among Rural People Who Use Drugs.

Background: Restrictive Medicaid policies regarding hepatitis C virus (HCV) treatment may exacerbate rural health care disparities for people who use drugs (PWUD). We assessed associations between Medicaid restrictions and HCV treatment among rural PWUD.

Methods: We compiled state-specific Medicaid treatment policies across 8 US rural sites in 10 states and merged these with participant survey data.

DNTT-mediated DNA Damage Response Drives Inotuzumab Ozogamicin Resistance in B-cell Acute Lymphoblastic Leukemia.

Inotuzumab Ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide inter-patient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered the loss of DNTT as a primary driver of InO resistance.