Carbonic anhydrase 2-derived drug-responsive domain regulates membrane-bound cytokine expression and function in engineered T cells.

Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).

Gender-Affirming Voice Therapy Duration and Satisfaction: Experiences from a Single Institution.

Objective: Current literature involving gender-affirming voice therapy (GAVT) for transgender and nonbinary (TGNB) individuals is limited. This study describes treatment duration and satisfaction at a single institution.

Study Design: Retrospective cohort.

10-Fold Increase in Hydrogen Atom Transfer Reactivity for a Series of = 1 Fe═O Complexes Over the = 2 [(TQA)Fe═O] Complex via Entropic Lowering of Reaction Barriers by Secondary Sphere Cycloalkyl Substitution.

Nonheme iron enzymes utilize = 2 iron(IV)-oxo intermediates as oxidants in biological oxygenations. In contrast, corresponding synthetic nonheme Fe═O complexes characterized to date favor the = 1 ground state that generally shows much poorer oxidative reactivity than their = 2 counterparts. However, one intriguing exception found by Nam a decade ago is the = 1 [Fe(O)(MeNTB)] complex (MeNTB = [tris((-methyl-benzimidazol-2-yl)methyl)amine], ) with a hydrogen atom transfer (HAT) reactivity that is 70% that of the = 2 [Fe(O)(TQA)] complex (TQA = tris(2-quinolylmethyl)amine, ).

Long Sleep Duration, Cognitive Performance, and the Moderating Role of Depression: A Cross-Sectional Analysis in the Framingham Heart Study.

Introduction: We investigated whether depression modified the associations between sleep duration and cognitive performance.

Methods: Multivariable linear regression models examined the associations between sleep duration and cognition in 1,853 dementia- and stroke-free participants from the Framingham Heart Study. Participants were categorized in four groups: no depressive symptoms, no antidepressants; depressive symptoms without antidepressants use; antidepressant use without depressive symptoms; both depressive symptoms and antidepressant use.

Neutrophil prime unique transcriptional responses in intestinal organoids during infection with nontyphoidal serovars.

Nontyphoidal strains of are a major cause of foodborne illnesses, and infection with these bacteria results in inflammatory gastroenteritis. Polymorphonuclear leukocytes (PMNs), also known as neutrophils, are a dominant immune cell type found at the site of infection in infected individuals, but how they regulate infection outcome is not well understood. Here, we used a co-culture model of primary human PMNs and human intestinal organoids to probe the role of PMNs during infection with two of the most prevalent serovars: serovar Enteritidis and Typhimurium.

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.

Prospective Assessment of Safety, Tolerance, and Perceptions of Awake Airway and Esophageal Dilation.

Objective: An increasing number of laryngeal and esophageal procedures are being performed as "awake" procedures (non-general anesthesia), with some under local anesthesia, including in clinic. While high tolerance and safety profiles have been reported for various laryngeal procedures, few studies directly assess tolerability of awake dilation procedures of the upper esophagus (UE) and laryngotracheal airway (LTA).

Study Design: Prospective, open-label.

Follow-up Trends in Patients Undergoing Modified Wendler Glottoplasty.

Objectives: After modified Wendler glottoplasty (mWG), close follow-up with laryngologist and speech-language pathologist (SLP) is thought to be essential to achieve best outcomes. This study presents a case series of patients undergoing mWG at a single institution to identify factors associated with trends in post-operative follow-up.

Methods: Retrospective review of trans women patients who underwent mWG between March 2018 and July 2023 was performed.

Impact of Age in Single-Level Versus Multilevel Airway Compromise: A Multi-Institutional Review.

Objective: Examine the association between age and treatment outcomes in conditions causing single- versus multilevel airway restriction.

Study Design: Multi-institutional retrospective cohort study.

Setting: Tertiary laryngology centers.

Development of the "LAser Surgical skills Evaluation for Residents" (LASER) Scale Through a Modified Delphi Method.

Background: The CO laser is frequently used during microlaryngeal surgery (MLS) for a variety of pathology including laryngeal malignancy and stenosis. Learning how to use the laser safely is part of the curriculum for every otolaryngology resident. However, assessment of laryngoscopy technical skills can be challenging for supervisors, making it difficult to adequately provide feedback to trainees.

Flagellar switch inverted repeat impacts flagellar invertibility and varies RT027/MLST1 virulence.

RT027 strains cause infections that vary in severity from asymptomatic to lethal, but the molecular basis for this variability is poorly understood. Through comparative analyses of RT027 clinical isolates, we determined that isolates that exhibit greater variability in their flagellar gene expression exhibit greater virulence . flagellar genes are phase-variably expressed due to the site-specific inversion of the 5'UTR region, which reversibly generates ON vs.

Singing Voice Handicap Index-10 Minimal Clinically Important Difference: A Prospective Determination.

Background/objectives: The Singing Voice Handicap Index-10 (SVHI-10) is a validated patient-reported outcome measure (PROM) that assesses patients' perception of handicap related to singing voice. A normative value has been established with a score ≥20 being abnormal. However, there is no defined minimal clinically important difference (MCID).

Efficacy of Posterior Pharyngeal Wall Injection for Velopharyngeal Dysfunction in Adults.

Objective(s): Posterior pharyngeal wall (PPW) injection is often employed to treat velopharyngeal deficiency (VPD). We sought to analyze the impact of PPW injection on severity of dysphagia and dysphonia.

Methods: Retrospective chart review was conducted of patients undergoing PPW injection from 2018 to 2023 at a tertiary laryngology center.

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( ) vs. without persistent GI symptoms ( ).

The Disorderly Nature of Caliciviruses.

An intrinsically disordered protein (IDP) or region (IDR) lacks or has little protein structure but still maintains function. This lack of structure creates flexibility and fluidity, allowing multiple protein conformations and potentially transient interactions with more than one partner. Caliciviruses are positive-sense ssRNA viruses, containing a relatively small genome of 7.

Venous Compressive Disorders.

Venous compressive disorders are a heterogenous group of vascular syndromes characterized by extrinsic venous compression that can lead to complications of venous hypertension or venous thrombosis. Endovascular damage secondary to deep venous thrombosis (DVT) can result in post-thrombotic syndrome (PTS), a potentially debilitating condition that can be associated with significant morbidity in the pediatric population. Here we discuss 4 venous compressive disorders: iliac vein compression (May-Thurner syndrome [MTS]); subclavian vein compression at the venous thoracic inlet (Paget-Schroetter syndrome); left renal vein compression (nutcracker syndrome); and popliteal vein compression (popliteal entrapment syndrome) with a focus on clinical evaluation and diagnostic methods.

Idiopathic Subglottic Stenosis in Non-Caucasian Women.

Objective: To characterize presentation, disease course, and treatment of idiopathic subglottic stenosis (iSGS) in non-Caucasian women and compare this cohort to the predominantly female, Caucasian patient cohorts identified in the literature.

Study Design: Retrospective review. Results are compared to systematic review of demographics.

The Microbiome in Quiescent Crohn's Disease With Persistent Symptoms Show Disruptions in Microbial Sulfur and Tryptophan Pathways.

Background And Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and worsen quality of life. Amongst patients without inflammation (quiescent CD), we hypothesized that microbial community structure and function, including tryptophan metabolism, would differ between patients with persistent symptoms () and without persistent symptoms ().

Methods: We performed a multicenter observational study nested within the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease.

Public health case for microbiome-sparing antibiotics and new opportunities for drug development.

Although antibiotics remain a cornerstone of modern medicine, the issues of widespread antibiotic resistance and collateral damage to the microbiome from antibiotic use are driving a need for drug developers to consider more tailored, patient-directed products to avoid antibiotic-induced perturbations of the structure and function of the indigenous microbiota. This perspective summarizes a cascade of microbiome health effects that is initiated by antibiotic-mediated microbiome disruption at an individual level and ultimately leads to infection and transmission of multidrug-resistant pathogens across patient populations. The scientific evidence behind each of the key steps of this cascade is presented.

Bisphosphonium Benzene Diimides.

The incorporation of cationic groups onto electron-poor compounds is a viable strategy for achieving potent electron acceptors, as evidenced by reports of air-stable radical forms of large aromatic diimides such as naphthalene and perylene diimides. These ions have also been observed to exhibit anion-π interaction tendencies of interest in molecular recognition applications. The benefits of phosphonium incorporation, however, have not yet been extended to the smallest benzene diimides.