Operationalizing flow-centric air traffic management with granular cells and dynamic handover times

The vomeronasal system consists of a vomeronasal organ (VNO) and an accessory olfactory bulb (AOB) that act together to detect specific substances such as pheromones. The degree to which this system has developed varies among carnivorans. Raccoon dogs (Nyctereutes viverrinus) communicate using feces and urine, suggesting a significant role of the vomeronasal system. Here, we histologically detail the VNO and AOB of raccoon dogs. The VNO had a J-shaped cartilage and opened anteriorly into the incisive duct. Numerous blood vessels surrounded the vomeronasal lumen, which was medially lined by sensory epithelium. The VNO contained secretory vomeronasal glands in the submucosa, multicellular intraepithelial glands in non-sensory epithelium, and goblet cells. Submucosal glands were periodic acid-Schiff (PAS) positive and negative for Alcian blue (pH 2.5). Multicellular intraepithelial glands positive for PAS were observed in three of the six raccoon dogs analyzed herein; the glands were AB-negative and positive in one and two, respectively. The vomeronasal nerve and glomerular layers were histologically distinguishable in the AOB, but deeper layers comprised a single plexiform-granule layer with intermingled mitral/tufted and granular cells. These characteristics of raccoon dog AOBs resembled those of domesticated dogs rather than wild red foxes and gray wolves. The vomeronasal nerve and glomerular layers were positive for anti-Gαi2 and negative for anti-Gαo, suggesting that vomeronasal type 1 receptors are functionally expressed in the vomeronasal system of raccoon dogs. Overall, our findings morphologically indicated that raccoon dogs communicate using the vomeronasal system.

Granular cell dermatofibroma (GCDF) is a unique histopathological variant of dermatofibroma, characterized by a portion of the lesion composed of cells with abundant granular cytoplasm, resembling granular cell tumors (GCT). GCTs are associated with mutations in V-ATPase component genes; however, the pathogenesis and molecular alterations in GCDF remain uncharacterized. We performed whole exome sequencing on six GCDF cases. Comparative whole exome sequencing analysis of lesional and paired control tissues was conducted to identify genetic mutations in GCDF. Three of the six cases (50%) of GCDF harbored mutations in V-ATPase component genes, including ATP6AP1, ATP6V0C, and ATP6AP2. These findings expand the spectrum of tumors associated with V-ATPase mutations. It is important for dermatopathologists to be aware of clinical, histopathological, and molecular findings in GCDF, and to differentiate these from atypical or malignant GCT, as GCDF are benign and do not need aggressive surgical management.

Objective The present investigation is designed to assess the synergistic impact of endoscopic ultrasonography (EUS)paired with endoscopic therapy in addressing upper gastrointestinal (GI) lesions that protrude. Methods Our approach involved retrospectively reviewing medical records to analyze 106 instances of upper GI protruding lesions identified via EUS at our institution, all of which were treated with either endoscopic techniques or surgery. Sample size was determined based on a prior pilot study, where the diagnostic concordance rate of EUS for upper GI protruding lesions was approximately75%. Using a margin of error of 5% and a confidence level of 95%, the calculated minimum sample size was83cases;106 patients were ultimately included to account for potential loss to follow-up. Comprehensive clinical and pathological information was systematically documented for each patient. Results Among the106cases, endoscopic treatment was successful in101cases,2 cases were transferred to surgical treatment midway, and 3 cases were directly treated with surgery. The most common pathological types included polyps in 26 cases (24.53%), inflammatory changes in 25 cases (23.58%), leiomyomas in 22 cases (20.75%), gastrointestinal stromal tumors (GIST)in 11 cases (10.38%), and cysts in 10 cases (9.43%). The diagnostic concordance rate between EUS and pathological diagnosis was 81.13% (86/106; 95% confidence interval [CI]: 73.25–87.46%). For common lesion subtypes, the concordance rates were as follows: polyps (89.66%,26/29;95%CI:73.78–97.23%), leiomyomas (86.36%, 22/25; 95% CI: 68.17–95.84%), and GIST (73.33%, 11/15; 95% CI: 45.30–91.15%). Additionally, EUS showed favorable diagnostic performance for these lesions: sensitivity and specificity were 92.86%/98.04% for polyps,88.00%/97.06% for leiomyomas, and 73.33%/98.99% for GIST, respectively. Polyps are more common in the stomach and mostly originate from the mucosal layer; leiomyomas are more common in the esophagus and originate from the muscularis mucosae and the muscularis propria; GIST are more common in the stomach and mostly originate from the muscularis propria. Conclusion The study’s conclusions highlight the remarkable precision of EUS in determining the intricacies of upper GI protrusions. Moreover, endoscopic treatments predicated on EUS assessments were found to be clinically safe, with a low incidence of postoperative adverse effects. Nonetheless, for rarer GI pathologies, such as schwannomas and granular cell tumors, there is an evident need for enhanced clinical acumen to mitigate the risk of misdiagnosis. The limitations of this single-center, retrospective study (e.g., small sample size, lack of long-term follow-up) should be considered when interpreting these findings.

Investigation of the role of HSP70 immunohistochemical staining method to the diagnosis of sudden unexpected death in epilepsy in autopsies.

Renal juxtaglomerular renin-producing cells and preglomerular vascular smooth muscle cells (VSMCs) are specialized pericytes with notable plasticity. Preglomerular VSMCs can convert to renin-producing cells during severe hypotension or salt depletion, and renin cells can transform into erythropoietin (EPO)-producing cells when hypoxia‑inducible factor (HIF)-2α is stabilized through deletion of prolyl-4-hydroxylases (PHD) 2 and 3. These findings raise the question of whether PHD2 and PHD3 likewise regulate the endocrine plasticity of preglomerular VSMCs. To investigate the role of PHD2 and/or PHD3 in (preglomerular) contractile pericytes, inducible mouse models with smooth muscle myosin heavy chain (SMMHC)-specific deletion of PHD2 and/or PHD3 were examined under basal conditions or after stimulation of renin production by treating the mice with a low-salt diet and angiotensin converting enzyme inhibitor enalapril (LSE). At baseline, none of the deletions altered renin production or induced EPO expression in preglomerular pericyte-like VSMCs, despite HIF-2α stabilization in PHD2/PHD3-deficient mice. However, HIF-2α stabilization resulting from PHD2 or PHD2/PHD3 deletion triggered EPO production in interstitial SMMHC+ contractile pericytes. LSE treatment induced renin in VSMCs and extraglomerular mesangial cells of control, SMMHCCreERT2 PHD2ff and SMMHCCreERT2 PHD3ff mice. In contrast, VSMCs of PHD2/PHD3-deficient mice produced EPO rather than renin, while renin induction persisted only in mesangial cells. Notably, this LSE-induced EPO production was reversible despite ongoing HIF-2α stabilization. Transcriptional changes indicated a shift in PHD2/PHD3-deficient VSMCs from a contractile/renin cell-like to a contractile/EPO cell-like signature. These findings indicate that HIF-2α stabilization determines the endocrine product of preglomerular VSMCs and interstitial pericytes. Notably, loss of PHD2/PHD3 does not compromise the plasticity of VSMCs to reversibly adopt endocrine functions. KEY POINTS: Smooth muscle myosin heavy chain (SMMHC)-specific deletion of the prolyl‑4‑hydroxylases PHD2 and PHD3stabilized hypoxia‑inducible factor (HIF)‑2α in preglomerular pericyte‑like vascular smooth muscle cells (VSMCs), prompting a transcriptional shift from a contractile/renin cell‑like toward a more contractile/EPO cell‑like signature without activating erythropoietin (EPO) transcription. A reduction in systolic blood pressure through treatment with low-salt diet and angiotensin converting enzyme inhibitor enalapril induced EPO synthesis instead of renin in preglomerular PHD2/PHD3-deficient VSMCs. Transformation of preglomerular VSMCs into EPO-producing cells was reversible despite persistent HIF-2α stabilization. SMMHC cell-specific deletion of PHD2 and PHD2/PHD3 activated EPO production in interstitial contractile pericytes independent of systolic blood pressure. Short‑term HIF‑2α stabilization was insufficient to induce EPO production in preglomerular VSMCs or contractile pericytes. Τaken together these findings demonstrate that HIF-2α stabilization governs the endocrine output of preglomerular VSMCs and interstitial pericytes. Notably, the loss of PHD2/PHD3 does not impair the capacity of VSMCs to reversibly assume endocrine functions.

Central Role of MITF/TFE Family Transcription Factors in Diverse Clear and Granular Cell Tumors.

Congenital granular cell epulis (CGCE) is a rare benign tumor of the neonatal gingiva, with fewer than 250 cases reported worldwide. It presents most commonly as a pedunculated mass arising from the maxillary alveolar ridge and may interfere with feeding or, rarely, respiration. Early recognition is essential, particularly in resource-limited settings where diagnostic tools may be restricted. We report the case of a 7-day-old female neonate born at term with a 2 × 1.5 cm smooth, pedunculated intraoral mass originating from the anterior maxillary alveolar ridge. The lesion did not impair respiration or feeding. Baseline laboratory investigations were normal, and the mass was electively excised under general anesthesia on day 7 of life. Histopathology revealed large polygonal cells with granular eosinophilic cytoplasm and atrophic overlying epithelium, confirming the diagnosis of congenital granular cell epulis. Immunohistochemical studies were not available. Postoperative recovery was uneventful, with complete resolution and no recurrence at the one-month follow-up. CGCE can be effectively managed with simple surgical excision, even in low-resource environments. Increased awareness among clinicians is essential to ensure timely diagnosis and avoid unnecessary interventions.

Granular cell tumor is a rare mesenchymal neoplasm of neurogenic origin. The clinical course of GCT is mostly asymptomatic. In the gastrointestinal tract, it usually presents as a submucosal lesion detected during routine endoscopic examination. The article presents the experience of managing patients at the GBUZ Moscow Clinical Scientific Center named after Loginov MHD from 2017 to 2025.

Submucosal lesions of the esophagus and stomach are commonly discovered as incidental findings during routine endoscopy. These lesions arise from varying layers of the gastrointestinal wall, primarily from the submucosa or the muscularis propria, and can range from benign to malignant. This review provides an overview of common submucosal lesions including gastrointestinal stromal tumors (GIST), leiomyomas, duplication cysts, varices, glomus tumors, lipomas, granular cell tumors, neuroendocrine tumors, pancreatic rest, and schwannomas. We focus on their clinical presentation, endoscopic characteristics, radiologic features, and histopathologic findings to aid in diagnosis.

Diagnostic puzzle—a case of an axillary soft tissue granular cell tumor mimicking a breast cancer lymphadenopathy: diagnostic challenge and surgical treatment

JC virus encephalopathy (JCE) includes progressive multifocal leukoencephalopathy (PML), a demyelinating disease, and granular cell neuronopathy (GCN), a less frequent disease that affects the neurons of the cerebellar granular cells [1].

Glucocorticoid-induced hypertension affects over 30% of treated patients, yet its underlying mechanisms remain unclear, particularly how glucocorticoids regulate renin within the renin-angiotensin-aldosterone system (RAAS). Modeling these dynamics is difficult because only four dose-response measurements are available at a single 24-h timepoint (36 observations total), while the system depends on roughly eleven biochemical parameters spanning minutes-long receptor interactions to days-long protein secretion. Classical parameter estimation becomes unreliable in this extremely underdetermined setting, and purely data-driven methods offer limited biological interpretability. In this paper, we introduce a physics-informed neural network (PINN) framework that integrates ELISA measurements from As4.1 juxtaglomerular cells, ordinary differential equations describing glucocorticoid receptor signaling and renin transcription, and automatic differentiation to enforce mechanistic constraints. By systematically tuning synthetic-data weights (SW in {0.2, 0.3, 0.5}), we identify an intermediate value of SW = 0.3 that provides the best overall balance between predictive accuracy, accepted ensemble size, and biologically plausible parameter estimates among the tested configurations. The framework uses adaptive constraint scheduling with a plateau ramp to reduce premature convergence and introduces calibrated plausibility thresholds reflecting experimental noise. The accepted PINN ensemble (n = 5, 50% success rate) achieved R2 = 0.803, compared with 0.759 for the SW = 0.5 baseline and −0.220 for the ODE-only baseline, with RMSE = 0.024. Key learned parameters (IC50 = 2.925 ± 0.012 mg/dL, Hill = 1.950 ± 0.009) are biologically plausible within the model assumptions, and the best single accepted model attained R2 = 0.891. Information criteria favored the PINN over the ODE model, with improvements of approximately 77× (AIC) and 5.9× (BIC). Despite training on a single timepoint, the PINN also infers full 48-h trajectories and reproduces non-monotonic dose-response behavior. This work presents, to our knowledge, the first PINN framework for glucocorticoid-mediated renin regulation and should be interpreted as a proof-of-concept approach for integrating sparse biomedical data with mechanistic constraints. The inferred parameters and temporal dynamics are best viewed as model-dependent, hypothesis-generating estimates rather than validated biological quantities.

A21-year-old female presented with a1 cm red, polypoid cutaneous tumor near the axilla that was surgically excised. Histomorphology revealed asubepithelial tumor with features suggestive of agranular cell tumor; however, immunohistochemistry for S100 and SOX10 was negative. Further analysis showed immunohistochemical ALK positivity, and Archer-based molecular testing identified aKLC1-ALK fusion (KLC1 exon 3-ALK exon20). These findings supported the diagnosis of acutaneous non-neural granular cell tumor, arare cutaneous neoplasm that mimics conventional granular cell tumors histomorphologically but lacks their typical immunophenotype and commonly harbors ALK fusions.

Microscopy-based analysis of red blood cell (RBC) morphology is widely used to study phenotypes in sickle cell disease (SCD). Although AI models have been developed to automate classification, most are trained on pre-cropped single-cell images and thus struggle with full-scope microscopic images containing densely packed cells and diverse morphologies, which require both accurate detection and fine-grained classification. We propose an end-to-end computational framework to identify individual RBCs in full-scope microscopy images and classify them into five morphological categories: discocytes (DO), echinocytes (E), elongated and sickle-shaped cells (ES), granular cells (G), and reticulocytes (R). We first evaluate advanced detection-classification models, including You Only Look Once (YOLO) and Detection Transformers (DETR), and demonstrate that while these models effectively detect cells, their classification performance falls short of specialized classifiers trained on single-cell images, particularly for minority phenotypes. To address this limitation, we introduce a two-step framework in which a YOLO-based detector localizes and crops individual cells from full-scope images, followed by a fine-tuned DenseNet121 ensemble classifier that assigns each cell to one of the five morphological categories. The proposed framework achieves a detection-level F1-score of 0.9661 and a weighted-average classification F1-score of 0.9708, with an overall classification accuracy of 97.06%. Compared with the single-step YOLO26n baseline, the two-step pipeline yields a macro-average F1-score improvement of +0.1675, with particularly substantial gains for minority classes (E: +0.1623; G: +0.2774; R: +0.2603). Overall, this hybrid framework demonstrates a practical strategy for adapting fast, general-purpose detection models to domain-specific biomedical tasks by combining them with specialized classifiers, delivering both efficiency and high accuracy for scientific and clinical image analysis.

Acute heat stress frequently causes mass mortality in farmed red swamp crayfish (Procambarus clarkii), yet the mechanisms underlying immune collapse remain poorly understood. We established an acute heat stress model (37 °C, 6 h) and performed an integrative analysis combining hemocyte profiling, redox and immune assays, RNA-seq, and qRT-PCR. Heat stress significantly increased mortality and disrupted the hemocyte system, with a ~25% reduction in total hemocyte count and a selective decline in granular cells. This was associated with severe redox imbalance, evidenced by ROS/H2O2 accumulation, suppressed SOD and CAT activities, and lipid peroxidation damage. Transcriptomic analysis revealed 1446 differentially expressed genes, indicating concurrent activation of ER stress and autophagy alongside suppression of energy metabolism. Key gene validation confirmed upregulation of pro-apoptotic factors (CASP3, P53) and ER stress markers (GRP78, XBP1), consistent with hemocyte depletion. These findings provide multi-level evidence that acute heat stress triggers a redox crisis ("oxidative burst-defense suppression"), which in turn activates ER stress and apoptosis, leading to selective loss of granular cells and systemic immune compromise. This study establishes a mechanistic framework for understanding heat-induced mortality in crustaceans and offers a theoretical basis for developing targeted interventions to enhance thermal resilience in crayfish aquaculture.

First morphological description of hemocyte subtypes in the freshwater bivalve Corbicula largillierti.

Novel RUNX1/2 fusions in unclassified cystic squamous salivary gland tumors: Possible expansion of the keratocystoma family.

Introduction: Laryngeal granular cell tumors (GCTs) are rare, typically submucosal lesions that hinder early diagnosis; involvement of the laryngeal ventricle is exceptional.Aim: To report a ventricular laryngeal GCT, review diagnostic and surgical management, and propose a practical decision-making algorithm.Case report: A 33-year-old woman presented with months-long hoarseness and globus sensation. Videolaryngoscopy revealed a well-circumscribed mass in the right laryngeal ventricle bulging the vestibular fold and causing glottic asymmetry. Neck CT showed an ~9-mm contrast-enhancing lesion without cartilage destruction or lymphadenopathy. Under general anesthesia, direct microlaryngoscopy enabled complete excision with clear margins. Histopathology confirmed GCT: S-100(+), SOX10(+), CD68(+), focal NSE(+), Ki-67 ~1%; negative for cytokeratins, desmin, SMA, and MyoD1. Recovery was uneventful; 3-monthly follow-up for ≥2 years was advised.Discussion: Laryngeal GCTs may mimic fibroma, cyst, or papilloma. The S-100/SOX10/CD68 profile supports neuroectodermal origin and facilitates differentiation from myogenic or epithelial tumors. The treatment of choice is endoscopic resection (often CO₂ laser) with margin control and preservation of phonatory function; ventricular location requires a high index of suspicion and meticulous preoperative assessment.Conclusions: (1) GCT should be considered in the differential of submucosal laryngeal lesions; (2) diagnosis relies on histology and S-100/SOX10/CD68 expression; (3) complete endoscopic excision provides excellent functional outcomes; (4) scheduled surveillance is recommended due to rare recurrences and potential malignant transformation.

Recently, glucagon-like peptide 1 (GLP-1) and its new blockbuster class of analogs have emerged as powerful therapeutics to combat obesity and diabetes, with growing evidence for potential efficacy in addiction, depression, and other psychiatric conditions. Although metabolic diseases are common in both women and men, certain pathological and clinical features exhibit sex-specific differences, as do psychiatric disorders. Importantly, as part of a broader network of peptides and hormones regulating ingestive and reward-related behaviors, GLP-1 appears to have stronger effects on appetite suppression, glycemic regulation, and body weight loss in females compared with males-though sex differences in its psychiatric effects remain underexplored. We utilized RNAscope to create a comprehensive atlas of sex-specific (n = 3 per sex) GLP-1 expressing sites in the murine brain. Notably, in the hindbrain, Glp1 densities and total numbers of Glp1-expressing neurons in the raphe obscurus nucleus, ventral and ventrolateral parts of the solitary nucleus were higher in females compared with males. In the olfactory bulb, Glp1 densities were greater in the granular cell layer of males in comparison with females. Collectively, this atlas should serve as a resource to advance our understanding of GLP-1's central functions in both metabolic and psychiatric contexts.