TNF-α-Driven Changes in Polarized EGF Receptor Trafficking Facilitate Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling from the Apical Surface of MDCK Epithelial Cells

This manuscript describes a novel unconventional secretory pathway that facilitates EGF receptor (EGFR) signaling from apical membranes in polarized epithelial cells responding to immune cell mediators. Epithelial tissues provide a physical barrier between our bodies and the external environment and share an intimate relationship with circulating and local immune cells. Our studies describe an unexpected connection between the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and EGFR typically localized to basolateral membranes in polarized epithelial cells. These two molecules sit atop complex biological networks with a long history of shared investigative interest from the vantage point of signaling pathway interactions. We have discovered that TNF-α alters the functional landscape of fully polarized epithelial cells by changing the speed and direction of EGFR secretion. Our results show apical EGFR delivery occurs within minutes of de novo synthesis likely via a direct route from the endoplasmic reticulum without passage through the Golgi complex. Additionally, our studies have revealed that apical cellular compartmentalization constitutes an important mechanism to specify EGFR signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase/protein-kinase-B pathways. Our study paves the way for a better understanding of how inflammatory cytokines fine-tune local homeostatic and inflammatory responses by altering the spatial organization of epithelial cell signaling systems

Disparities in Dysphagia Care Among Head and Neck Cancer Patients: A Retrospective Cohort Study

Objective: To investigate the incidence of dysphagia among head and neck cancer (HNC) patients and assess disparities in utilization of speech-language pathology (SLP) services across different demographic groups. Study Design: Retrospective cohort study. Setting: Analysis of data from the TriNetX global health network, comprising over 125 million deidentified electronic health records worldwide. Methods: HNC patients diagnosed with oral, oropharyngeal, laryngeal, or nasopharyngeal cancer with and without dysphagia between January 1, 2004 and October 30, 2024 were identified. Patients were divided into two cohorts for comparison: those who received SLP services after dysphagia diagnosis and those who did not. The association of demographic characteristics (sex, ethnicity, and race) with SLP services were analyzed. Results: Of 269,629 HNC patients, 28.8% (n = 77,562) were diagnosed with dysphagia. Significant disparities were found: female and non-White patients were less likely to be diagnosed with dysphagia. Once diagnosed, female, Hispanic/Latino, and non-White patients were also significantly less likely to receive SLP services compared to female, Hispanic/Latino, and non-White patients. Overall, only 38.8% of patients with dysphagia received SLP services. Conclusion: This study highlights significant sex, ethnic, and racial disparities in dysphagia diagnosis and SLP service utilization among HNC patients. Furthermore, SLP services are underutilized. There is a need for targeted interventions to increase dysphagia prevention and surveillance and ensure equitable access to dysphagia care, improving outcomes for all HNC survivors

Behavior of Rio Sao Francisco Piranhas in Response to Changes in Space and Density

Previous observations of Rio Sao Francisco piranhas (Pygocentrus piraya) at Cleveland Metroparks Zoo revealed frequent aggressive interactions, which were associated with the injury and death of some individuals. Fishes are known to increase aggressive behavior when available space is limited. We compared the behavior of the piranhas longitudinally across three different space/density conditions: (1) in a group held in a small aquarium before the death of one individual, (2) in the same group after the death of one individual, (3) and in one individual of the group after it was later moved into a larger, multispecies aquarium. In the smaller aquarium, individuals maintained stable positions in the tank and remained inactive except to behave aggressively toward each other, retreat, or feed when food was offered. After the death of one individual, aggression decreased significantly but so did overall activity, including swimming behavior. After one individual was moved to a larger aquarium, it exhibited a striking increase in the amount of time spent swimming. Our data suggest that the well-being of P. piraya, and possibly other species of piranhas, might be better in large aquariums than in the small single-species exhibits often used in zoos and public aquariums. This study takes an important step in addressing the psychological and social well-being of bony fishes, an underrepresented area of research in zoos and aquariums

Elevation in White Blood Cell Count After Corticosteroid Use in Noninfected Hospitalized Patients

Background: It is widely accepted that corticosteroids cause leukocytosis. Clinicians must decide whether a rise in white blood cell (WBC) count is due to steroids versus other processes like developing infection. Objective: The objective of this study is to measure the increase in white blood cell count after corticosteroid administration in hospitalized patients without malignancy, infection, or immune dysfunction. Methods: This is a retrospective cohort study from 2017 to 2018 in a single large healthcare system. We analyzed the trajectory of WBC count stratified by steroid dose. The study included nonsurgical patients admitted with at least two complete blood count measurements. Patients were excluded if they had immunosuppression, infection, malignancy, or steroid use within 2 weeks before admission. The main outcome was mean WBC count by day following corticosteroid administration. Results: Our sample included 28,425 patients with at least two WBC measurements, 1608 (5.7%) of which received steroids. WBC response peaked at 48 h after steroid administration with a mean increase of 2.4 × 10⁹/L WBCs. In all patients on steroids, across doses, the mean increase was 0.3 × 10⁹/L WBCs, 1.7 × 10⁹/L WBCs, and 4.84 × 10⁹/L WBCs in low, medium, and high dose groups, respectively. For patients not on steroids, the mean WBC count decreased during hospitalization. Conclusions: When interpreting WBC counts after initiating steroids, increases of up to 4.84 × 10⁹/L cells may be seen within 48 h after high-dose steroids. Larger increases, and any increase after low-dose steroids, suggest other causes of leukocytosis

Voclosporin‐Induced Gingival Enlargement: A Case Report

The gingiva (gums) is often a site in the mouth where changes or reactions can occur in response to certain systemic medications. Some drugs, particularly those used to treat autoimmune conditions or following organ transplants, can cause the gums to grow excessively, a condition known as drug-induced gingival enlargement (also known as gingival overgrowth). In this report, we document the case of a 27-year-old woman with lupus nephritis who developed gingival enlargement after starting a medication called voclosporin. This drug is a newer treatment option for lupus nephritis, but until now had not been linked to gingival enlargement. The patient experienced significant gum swelling, bleeding, and pain, making it difficult for her to eat. After trying nonsurgical treatments with limited success, and given her objection to surgical therapy, the medication was gradually stopped in consultation with her physician. The enlargement of the gums significantly improved once the drug was discontinued. This report highlights for the first time, to the authors\u27 knowledge, the development of gingival enlargement in response to voclosporin therapy and the significant improvement of the condition upon cessation of drug usage

Nerve Transfers for Median Nerve Injury

Due to its role in hand function, median nerve injuries can have a significant impact on patients’ lives. Nerve transfers can be performed alone or in conjunction with tendon transfers to restore critical functions supplied by the median nerve, with a particular emphasis on restoring grasp, pinch, and sensation. Continued study into possible nerve transfers for median nerve injury has led to multiple options that can be tailored to the patient\u27s demands, deficits, and injury pattern

A Continuous-Heat-Flux Phase Change Model for Simulating Realistic Two-Phase Unsaturated Evaporation Processes

Accurately modeling liquid-vapor mass transfer rates is essential for optimizing cryogenic fluid management processes critical to advancing future space missions. This study introduces a continuous-heat-flux phase change model proposed to simulate conditions observed in realistic two-phase unsaturated evaporation phenomena. The mass transfer rate across the two-phase interface is calculated directly based on the local interfacial continuous heat flux on both liquid and vapor phases, effectively accounting for superheated, saturated, and subcooled liquid effects without requiring any empirical tuning parameters. Moreover, phase change occurs exclusively within interfacial cells, ensuring the sharp representation of deformed evaporating interfaces with high accuracy. The proposed model is implemented using user-defined functions in ANSYS Fluent and evaluated against various benchmark evaporation problems, including Stefan and film boiling test cases with nonequilibrium (temperature other than saturation) in a single phase and in both phases. The numerical results, encompassing liquid-vapor interface evolution and temperature distributions, exhibit excellent agreement with published analytical and numerical solutions. Additionally, the model is applied to simulate the complex heat and mass transfer processes in cryogenic tank self-pressurization under two heating configurations: vapor heating and uniform heating. The results demonstrate good agreement with the tank pressure rise trends reported in the literature, validating the applicability of the model to practical evaporation scenarios

The Baryonic Tully-Fisher Relation. II. Stellar Mass Models

We present new color-ϒ* (mass-to-light ratio) models to convert Wide-field Infrared Survey Explorer W1 fluxes into stellar masses. We outline a range of possible star formation histories and chemical evolution scenarios to explore the confidence limits of stellar population models on the value of ϒ*. We conclude that the greatest uncertainties (around 0.1 dex in ϒ*) occur for the bluest galaxies with the strongest variation in recent star formation. For high-mass galaxies, the greatest uncertainty arises from the proper treatment of bulge-disk separation in which to apply different ϒ* relations appropriate for those differing underlying stellar populations. We compare our deduced stellar masses with those deduced from Spitzer Space Telescope 3.6 μm fluxes and stellar mass estimates in the literature using optical photometry and different ϒ* modeling. We find the correspondence to be excellent, arguing that rest-frame near-IR photometry is still more advantageous than other wavelengths