Polyfunctional IL-21 IFNG T follicular helper cells contribute to checkpoint inhibitor diabetes mellitus and can be targeted by JAK inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic beta-islet cell destruction leading to hyperglycemia and life-long insulin dependence.

Intake and Nutritional Adequacy in Patients With Cancer Diagnosed With Malignant Bowel Obstruction: A Secondary Analysis of a Randomized Trial.

Background: Malignant bowel obstruction (MBO) is experienced by many with advanced cancer. Patients with MBO cannot eat and may have reduced ability to eat once the acute process has resolved. Sparse data exist to describe oral intake capacity and adequacy of nutrition in patients with MBO.

Cost-effectiveness of antenatal fetal surveillance for medication-treated gestational diabetes.

Objective: To evaluate the relative cost-effectiveness of starting antenatal fetal surveillance at 32 vs. 36 weeks, in medication-treated gestational diabetes.

Methods: We performed a 2017-2022 retrospective cohort study of patients with medication-treated GDM who underwent BPPs.

No-Dose Photodynamic Therapy Against Half-Dose Photodynamic Therapy for Treatment of Central Serous Chorioretinopathy.

Introduction: This study aimed to describe the effects of no-dose full-fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC).

Methods: This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with HDFF PDT a minimum of 3 months before and were considered as the control group.

Isolated celiac artery avulsion from blunt abdominal trauma.

Trauma-related celiac artery injuries are a rare and life-threatening pathology that often requires urgent multidisciplinary care. Rarer still are cases of celiac artery avulsion in the setting of blunt trauma. There is little literature describing such injury patterns.

A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis.

Background: This study assessed the efficacy and safety of velusetrag-a 5-HT agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE).

Methods: In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).

Cortical Correlates of Increased Postural Task Difficulty in Young Adults: A Combined Pupillometry and EEG Study.

The pupillary response reflects mental effort (or cognitive workload) during cognitive and/or motor tasks including standing postural control. EEG has been shown to be a non-invasive measure to assess the cortical involvement of postural control. The purpose of this study was to understand the effect of increasing postural task difficulty on the pupillary response and EEG outcomes and their relationship in young adults.

A Novel Somatic Treatment for Post-traumatic Stress Disorder: A Case Report of Hydrodissection of the Cervical Plexus Using 5% Dextrose.

Despite years of standard treatments, a Marine veteran and former firefighter, disabled due to severe post-traumatic stress disorder (PTSD), worsened over ten weeks while receiving usual care. Bilateral injection of 10 mL of 5% dextrose in water using a 30-gauge needle just under the sternocleidomastoid muscle was performed at weeks 10, 12, 14, 16, and 18. Clinically important improvements were observed by 18 weeks on a 0-10 anxiety rating scale (57%), the PTSD checklist for civilians (41%), EuroQol overall quality of life scale (40%), and the Hospital Anxiety and Depression Scale (28%).

The Ethics of Procedural Education Under Pandemic Conditions.

Background: The COVID-19 pandemic significantly disrupted emergency medicine residents' education. Early in the pandemic, many facilities lacked adequate personal protective equipment (PPE), and intubation was considered particularly high risk for transmission to physicians, leading hospitals to limit the number of individuals present during the procedure. This posed difficulties for residents and academic faculty, as opportunities to perform endotracheal intubation during residency are limited, but patients with COVID-19 requiring intubation are unstable and have difficult airways.

The complete sequence of a human genome.

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding.

Complete genomic and epigenetic maps of human centromeres.

Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.

The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies.

Interest in the role of coagulation and fibrinolysis in the nervous system was active in several laboratories dating back before cloning of the functional thrombin receptor in 1991. As one of those, our attention was initially on thrombin and plasminogen activators in synapse formation and elimination in the neuromuscular system, with orientation towards diseases such as amyotrophic lateral sclerosis (ALS) and how clotting and fibrinolytic pathways fit into its pathogenesis. This perspective is on neuro-thromboinflammation, emphasizing this emerging concept from studies and reports over more than three decades.

Influence of ligand geometry on cholinesterase enzyme - A comparison of 1-isoindolinone based structural analog with Donepezil.

Donepezil (DNPZ) is one of the few FDA-approved widely used medication in the clinical care of Alzheimer's disease (AD) patients. To investigate the effect of geometry and to find the significance of an enol form if any in DNPZ on acetylcholinesterase (AChE) inhibition, we changed the tetrahedral geometry of DNPZ to planar trigonal pyramidal geometry by replacing the α-carbon atom next to ketone functionality with a nitrogen atom. To mimic 1-indanone in DNPZ, we selected 1-isoindolinone framework to synthesize 25 new DNPZ derivatives and characterized using H NMR, C NMR and ESI-MS spectroscopy methods.

Nicotine metabolite ratio: Comparison of the three urinary versions to the plasma version and nicotine clearance in three clinical studies.

Background: Variation in CYP2A6 activity influences tobacco smoking behaviors and smoking-related health outcomes. Plasma Nicotine Metabolite Ratio (NMR) is a robust phenotypic biomarker of CYP2A6 activity and nicotine clearance. In urine, the NMR has been calculated as a ratio of free trans-3'-hydroxycotinine to free cotinine (NMR), total trans-3'-hydroxycotinine to free cotinine (NMR), or total trans-3'-hydroxycotinine to total cotinine (NMR).

Incidence of Intracranial Melanoma Progression in the Setting of Positive Extracranial Response to Targeted Therapy and Immunotherapy: An Indication for More Frequent Screening in This Population?

Background and objective The incidence of intracranial metastases from melanoma is on the rise. In this study, we aimed to determine the incidence of intracranial disease progression in patients on BRAF/MEK targeted therapy and immunotherapy in the setting of controlled or improving extracranial disease. Methods This was a single-center, retrospective review that involved patients who underwent stereotactic radiosurgery (SRS) for intracranial metastatic melanoma between January 1, 2014, and December 31, 2018.

Clinician engagement in the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) trial.

Background: ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) is a pragmatic clinical trial examining high-dose versus low-dose aspirin among patients with cardiovascular disease. ADAPTABLE is leveraging novel approaches for clinical trial conduct to expedite study completion and reduce costs. One pivotal aspect of the trial conduct is maximizing clinician engagement.

Preclinical Evaluation of Gilteritinib on NPM1-ALK-Driven Anaplastic Large Cell Lymphoma Cells.

Anaplastic large cell lymphoma (ALCL) is an aggressive type of non-Hodgkin lymphoma. More than three-fourths of anaplastic lymphoma kinase (ALK)-positive ALCL cases express the () fusion gene as a result of t(2;5) chromosomal translocation. The homodimerization of NPM1-ALK fusion protein mediates constitutive activation of the chimeric tyrosine kinase activity and downstream signaling pathways responsible for lymphoma cell proliferation and survival.

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer.

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC.

Functional brain abnormalities associated with comorbid anxiety in autism spectrum disorder.

Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social-communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala-prefrontal and amygdala-striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD).

Social determinants of alcohol and cigarette use by race/ethnicity: Can we ignore measurement issues?

Psychometric critiques of cross-cultural research emphasize testing whether instruments measure the same construct across cultural groups. We tested for measurement invariance (by race/ethnicity) of instruments used to evaluate the relationship between alcohol and tobacco use with perceived discrimination and socioeconomic status (SES). Tests of psychometric equivalence across race/ethnicity focused on: the latent organization of constructs (configural invariance); if observed indicators have equal factor loadings or "true score" variance (metric invariance); and whether manifest indicators change uniformly contingent on change in the latent variable (scalar invariance).

A small molecule STAT3 inhibitor, LLL12, enhances cisplatin‑ and paclitaxel‑mediated inhibition of cell growth and migration in human ovarian cancer cells.

Ovarian cancer is one of the most lethal cancer types in American women. The platinum agent cisplatin, and/or paclitaxel, remains the first‑line chemotherapy for ovarian cancer, but the treatment success is severely limited by chemoresistance. As previously reported, persistent STAT3 signaling is associated with resistance to cisplatin and paclitaxel.

How Emergency Physicians Approach Refusal of Observation after Naloxone Resuscitation.

Background: Patients who are resuscitated with naloxone frequently refuse a period of observation, even though they may be suffering from a variety of medical and psychiatric comorbidities. Emergency physicians (EPs) are then confronted with the challenge of how best to serve patients' interests while respecting autonomy.

Objectives: We sought to characterize how EPs think about this kind of dilemma and the strategies they use to resolve them.