Eosinophilic Cells Research Articles

Insights into the toxic impact of long-term exposure to diethyl phthalate on commercially important species Catla (Labeo catla)

BackgroundDiethyl phthalate (DEP), used as a plasticizer, is more prevalent in the aquatic environment due to its widespread usage in plastics, cosmetics, and numerous pharmaceutical industries. It is a potential endocrine disruptor, but the underlying mechanism in fish needs to be investigated. The present study evaluated the toxic impacts of DEP exposure for 30 days on commercially important fish Labeo catla (Catla). Alterations at multiple level endpoints of the hypothalamic–pituitary–gonadal axis (HPG axis) were assessed. DEP-induced changes in oxidative stress, histopathological changes (liver, kidney and brain) and bioaccumulation in fish muscle were also evaluated.ResultsDEP exposure to 1/10th (1.62 mg/L) and 1/50th (0.32 mg/L) LC50 dose for 30 days to Catla revealed that it stimulated the expression of kisspeptin (Kiss 1 and Kiss 2) genes in the hypothalamus, leading to an increased GnRH concentration (36.75%) in the higher dose. The brain FSH levels increased by 11.24 and 55.42% times than control in both the doses. This led to an increase in circulating sex steroids E2 (41.62%) and 11 KT (24.59%) and eventually triggered hepatic Vtg production (23.90%) in a dose-dependent manner. DEP exposure lowered the concentration of antioxidants superoxide dismutase (SOD) and catalase (CAT), the effect being more pronounced in the higher dose. The histopathological alterations, such as hepatocyte vacuolization, sinusoidal congestion, loss of brush border, degeneration of lumen, infiltration of eosinophilic cells in liver, kidney and brain, respectively, were noted.ConclusionsThis pioneering study could provide detailed insight into the endocrine disruptive potential of DEP in fish, as evidenced by its impact at multiple endpoints, even at low doses after 30 days of exposure. The output of this investigation thus emphasized the need for regular monitoring of DEP for ecological risk assessment.

White Blood Cell Classification Using SMOTE-SVM Method with Hybrid Feature Extraction and Image Segmentation Using Gaussian Mixture Model

White blood cells are crucial to the immune system. The irregular structure of white blood cells, along with the fact that each type has its unique structure, makes manual identification challenging. Manual identification is prone to errors due to medical personnel's subjectivity and fatigue from time and effort demands. A fast and accurate method for classifying white blood cells is needed, but challenges remain regarding the quality and quantity of samples for each cell type. This study proposes the use of SMOTE and SVMSMOTE to address the issue of data imbalance, as well as a combination of shape features (size, circularity, convexity, solidity) and convolutional autoencoder (CAE) for feature extraction, along with a Gaussian mixture model for nucleus segmentation. The study finds that, without using SMOTE or SVMSMOTE for data balancing, the proposed features are already sufficient to represent each cell type except eosinophils, achieving an accuracy of 92.4%, precision of 91.9%, recall of 92.3%, F1-Score of 92%, MCC of 0.862, and CEN of 0.1376 using a polynomial kernel. The worst results were obtained with the sigmoid kernel. The combined feature extraction (shape and CAE) outperformed individual methods. Shape alone achieved 86.8% accuracy, CAE alone 87.8%. Recall for eosinophil cells improved using SMOTE and SVMSMOTE.

Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED

RationaleKnowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.ObjectivesTo assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.MethodsData of 421 patients with severe asthma (62% female; mean age 51.9 ± 13.4 years; mean FEV1 67.5 ± 21.3%pred) from the U-BIOPRED cohort were analyzed. The included PROMs were: Asthma Control Questionnaire (ACQ5); Asthma Quality of Life Questionnaire (AQLQ); Hospital Anxiety and Depression scale (HADS); Epworth Sleepiness Scale (ESS); Medication Adherence Report Scale (MARS); Sino-Nasal Outcomes Test (SNOT20). Participants were assessed at baseline and after 12–18 months of usual care.ResultsPROMs showed very weak to weak correlations with clinical characteristics such as age, body mass index, FEV1, FeNO and eosinophilic cell count. Patients presenting no exacerbations during follow-up showed a statistically significant improvement in all PROMs (except for MARS), whereas individuals experiencing > 2 exacerbations showed a deterioration. Baseline ACQ5 was a predictor of exacerbations with an AUC of 0.590 (95%CI 0.514–0.666).ConclusionsThe association of PROMs with clinical measures was poor in severe asthmatics. Moreover, PROMs were prone to changes in usual care, with exacerbations playing a key role. PROMs need to be systematically evaluated in severe asthma to improve clinical care based on specific patient’s needs.

Causal relationship between 41 inflammatory factors, circulating white blood cells, and pruritus: A 2-sample bidirectional Mendelian randomization study.

The influence of circulating white blood cells and inflammatory factors on pruritus is gradually recognized by the public, but the specific causal relationship is still unknown. In this study, we included inflammatory cytokine profiles from 8293 healthy subjects, genetic data on blood cells from various ethnic and ancestry backgrounds, including 746,667 individuals, and 1370 patients of European descent with pruritus for a bidirectional 2-sample Mendelian randomization (MR) analysis. We employed several robust statistical methods, including the inverse variance weighted, weighted median, and the MR-Egger method. We further refined our analysis through a meticulous sensitivity assessment using the leave-one-out strategy, evaluated the heterogeneity of our findings using Cochran's Q test, and addressed potential pleiotropic effects through the MR-Egger intercept test. Ultimately, a reverse MR analysis was conducted to assess the potential for reverse causation. Genetic prediction data indicate a positive correlation between eosinophil cell count and the risk of developing pruritus (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.09-1.55, P = .003). Furthermore, elevated levels of stromal-cell-derived factor 1 alpha (OR = 1.80, 95% CI: 1.15-2.77, P = .009), monokine induced by gamma interferon (OR = 1.23, 95% CI: 1.04-1.46, P = .015), and cutaneous T-cell-attracting chemokine (OR = 1.24, 95% CI: 1.01-1.53, P = .043) are all associated with an increased risk of pruritus occurrence, respectively. No evidence of horizontal pleiotropy or heterogeneity was observed among the genetic variants (P > .05), and the leave-one-out analysis confirmed the stability and robustness of this association. The reverse MR analysis demonstrated the absence of reverse causality. Our research delineates the causal links between eosinophil cell count, stromal-cell-derived factor 1 alpha, monokine induced by gamma interferon, cutaneous T-cell-attracting chemokine levels, and pruritus susceptibility. These insights may present promising avenues for enhancing the management and therapeutic strategies for patients suffering from pruritus.

Clinical Characteristics and Outcomes of Acute Myocarditis: An Analysis of Korean Multicenter Registry.

Data are limited on the clinical manifestations and outcomes of acute myocarditis from a large-scale registry. We investigated acute myocarditis's clinical characteristics and prognosis from a large-scale, multi-center registry in the Republic of Korea. We collected data from seven hospitals between 2001 and 2021. Clinical variables and outcomes during the index hospitalization and follow-up periods were analyzed. We also evaluated inter-center and temporal differences in diagnostic and treatment patterns. Eight hundred forty-one patients diagnosed with acute myocarditis were included. Common symptoms included chest pain (60.4%), followed by fever or myalgia (46.3%), and dyspnea (45.7%). Fulminant myocarditis occurred in 421 (50.1%), with 217 requiring extracorporeal membrane oxygenation (ECMO) support. Endomyocardial biopsy (EMB) was performed in 276 (32.8%) patients, and biopsy-proven diagnosis was made in 234 (27.8%). Based on the EMB results, lymphocytic myocarditis was the predominant form (69.6%), followed by eosinophilic (13.8%) and giant cell myocarditis (1.4%). Eighty-three in-hospital (9.9%) and 16 (1.9%) additional mortality during the follow-up occurred. An increase in the use of EMB, cardiac imaging, and immunosuppressive therapy was noted over time, but in-hospital mortality remained unchanged. Remarkable variations in diagnosis and treatment were observed across different centers. This study unveiled clinical features of acute myocarditis in the Republic of Korea, including a high incidence of fulminant myocarditis and complex cases requiring ECMO. Given the considerable inter-center variation in diagnostic and treatment patterns and prognosis, protocolized future trials are needed to clarify diagnosis and treatment in patients with acute myocarditis. ClinicalTrials.gov Identifier: NCT05933902.

Basophils may as a risk factor for upper gastrointestinal cancer: a Mendelian randomization (MR) study.

Upper gastrointestinal (UGI) cancers, including esophageal (EC) and gastric (GC) cancers, pose a significant global health challenge. Previous studies have indicated a fundamental correlation between basophil count and the risk of UGI cancer. However, confirming a causal relationship demands further investigation. Mendelian randomization (MR) provides a critical method for evaluating the possible causal connections between peripheral circulating blood cells (PCBCs) and UGI cancer. Our study comprehensively employed a two-sample MR analysis. We used publicly available genetic data to survey the causal association between PCBC and UGI cancer. We used inverse variance weighting and weighted median for MR analyses and sensitivity analyses to assess heterogeneity and pleiotropy. In terms of the association between PCBCs and UGI cancer, we found that basophils count (EC: OR = 1.416, 95% CI = 1.125-1.783, p = 0.003; GC: OR = 1.623, 95% CI = 1.052-2.505, p = 0.029) were all strongly correlated with both EC and GC. Interestingly, Basophil count was a risk factor for both EC and GC. However, no significant correlations were seen between eosinophil, monocyte, lymphocyte or white blood cell count and UGI cancer. The findings of this research corroborate the idea that basophils might serve as a fundamental risk factor for UGI cancer. Further exploration of the underlying mechanisms driving this relationship could provide crucial understanding helpful in creating prospective preventive and treatment methods for UGI cancer.

High RRM2 Correlates with Mitochondrial and Immune Responses in the Eosinophilic Subtype of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC), the predominant subtype of RCC, is distinguished by unique biological characteristics and heterogeneity, including eosinophilic and clear subtypes. Notwithstanding progress in therapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs), the prognosis for individuals with metastatic ccRCC remains poor, presumably owing to metabolic alterations leading to mitochondrial dysfunction, which affects treatment response variability. We analyzed histological and immunohistochemical data from a cohort at Dalian Medical University's First Affiliated Hospital alongside RNA-sequencing transcriptome data from the TCGA database. Histologically, eosinophilic and clear ccRCC subtypes were evaluated using Kaplan-Meier and Cox proportional hazards models for survival analysis and prognosis. Differential gene expression (DEG) analysis and Gene Set Enrichment Analysis were performed to explore transcriptomic differences and relevant pathways. The study discovered substantial histological and molecular differences between the eosinophilic and clear cell subtypes of ccRCC. The eosinophilic subtype linked with frequent high-grade tumors (69.05% eosinophil vs 35.35% clear) and a poorer prognosis (HR=2.659, 95% CI:1.437-4.919, P=0.002). DEG analysis revealed distinct expression patterns among subtypes and identified a risk score signature that remained significant even after adjusting for clinical variables (HR=3.967, 95% CI: 1.665-9.449, P=0.002), showing less favorable survival in the high-risk group (P < 0.0001). RRM2 emerged as the most prognostic gene from this risk score, particularly in the eosinophilic subtype, alongside other clinical variables. By IHC, RRM2 shows high IHC score in eosinophilic compared to clear subtype (P=0.019). In addition, highly expressed RRM2 correlates with poor outcomes and is linked to mitochondrial genes, immunological pathways, and ICIs treatment. These findings show significant differences in prognosis between subtypes. RRM2 was the most prognostic gene from the discovered novel risk score signature associated with subtypes. Future research is essential to validate these insights and their therapeutic implications for ccRCC management.

Antioxidative and Anti-Atopic Dermatitis Effects of Peptides Derived from Hydrolyzed Sebastes schlegelii Tail By-Products.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with significant morbidity, including pruritus, recurrent skin lesions, and immune dysregulation. This study aimed to investigate the antioxidative and anti-AD effects of peptides derived from hydrolyzed Sebastes schlegelii (Korea rockfish) tail by-products. Hydrolysates were prepared using various enzymes, including Alcalase, Flavourzyme, Neutrase, and Protamex. Among them, Protamex hydrolysates demonstrated the highest ABTS radical scavenging activity with an RC50 value of 69.69 ± 0.41 µg/mL. Peptides were further isolated from the Protamex hydrolysate using dialysis, fast protein liquid chromatography (FPLC), and high-performance liquid chromatography (HPLC). The most active peptide, STPO-B-II, exhibited a single peak and was identified as a sequence of Glu-Leu-Ala-Lys-Thr-Trp-His-Asp-Met-Lys, designated as MP003. In vivo experiments were conducted using a 2,4-dinitrochlorbenzene (DNCB)-induced AD model in NC/Nga mice. The isolated peptide, MP003, showed significantly reduced AD symptoms, including erythema, lichenification, and collagen deposition. Additionally, MP003 decreased epidermal and dermal thickness, eosinophil, and mast cell infiltration and downregulated the expression of pro-inflammatory cytokines IL-1β, IL-6, and IgE in serum and skin tissues. These findings suggest that peptides derived from Sebastes schlegelii tail by-products may serve as potential therapeutic agents for AD.

Optimizing Siglec-8-Directed Immunotherapy for Eosinophilic and Mast Cell Disorders

Background/Objective: Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells. Methods: Here, we used transgenic mice to raise a diverse panel of fully human mAbs that either recognize the V-set domain, membrane-distal C2-set domain, or membrane-proximal C2-set domain of full-length Siglec-8 as a basis for novel therapeutics. Results: All mAbs were efficiently internalized into Siglec-8-expressing cells, suggesting their potential to deliver cytotoxic payloads. Tool T cell-engaging bispecific antibodies (BiAbs) and chimeric antigen receptor (CAR)-modified natural killer (NK) cells using single-chain variable fragments from Siglec-8 mAbs showed highly potent cytolytic activity against Siglec-8-positive cells even in cases of very low target antigen abundance, whereas they elicited no cytolytic activity against Siglec-8-negative target cells. Siglec-8V-set-directed T cell-engaging BiAbs and Siglec-8V-set-directed CAR-modified NK cells induced substantially greater cytotoxicity against cells expressing an artificial smaller Siglec-8 variant containing only the V-set domain than cells expressing full-length Siglec-8, consistent with the notion that targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, unconjugated Siglec-8C2-set mAbs, Siglec-8C2-set-directed T cell-engaging BiAbs, and Siglec-8C2-set-directed CAR-modified NK cells showed high antigen-specific cytolytic activity against Siglec-8-positive human cell lines and primary patient eosinophils. Conclusions: Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

12526 Acromegaly Secondary to Sparsely Granulated Adenoma

Abstract Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None. The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol &amp;gt;16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (&amp;gt;400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors. Presentation: 6/3/2024

Unveiling the influence of circulating immune cells count on type 1 diabetes: Insight from bidirectional Mendelian randomization.

Observational studies have demonstrated an association between circulating immune cell and type 1 diabetes (T1D) risk. However, it is unknown whether this relationship is causal. Herein, we adopted a 2-sample bidirectional Mendelian randomization study to figure out whether circulating immune cell profiles causally impact T1D liability. Summary statistical data were obtained from genome-wide association study (GWAS) to investigate the causal relationship between white cell (WBC) count, 5 specific WBC count, and lymphocyte subtypes cell count and T1D risk. After false discovery rate (FDR) correction, the results indicated that lower lymphocyte cell count (odds ratio [OR] per 1 standard deviation [SD] decrease = 0.746, 95% confidence interval (CI): 0.673-0.828, PFDR = 0.036), and basophil cell count (OR per 1 SD decrease = 0.808, 95% CI: 0.700-0.932, PFDR = 0.010) were causally associated with T1D susceptibility. However, the absolute count of WBC, monocyte, neutrophil, eosinophil, and lymphocyte subtypes cell had no statistically significant effect on T1D risk. Taken together, this study indicates suggestive association between circulating immune cell count and T1D. Moreover, lower numbers of circulating lymphocyte and basophil cell were associated with the increased risk of T1D, which confirmed the immunity predisposition for T1D.

Functional Role of Piezo1 in the Human Eosinophil Cell Line AML14.3D10: Implications for the Immune and Sensory Nervous Systems.

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.

Crack lung: a difficult differential diagnosis of ground glass opacities in the emergency setting

BackgroundThe term 'Crack lung' refers to an acute syndrome of diffuse alveolar damage and hemorrhagic alveolitis that occurs within 48 hours of smoking freebase cocaine. Crack lung induces a variety of pulmonary complications, both acute and chronic, including pulmonary edema, alveolar hemorrhage, eosinophilic pneumonia, pneumothorax, and pulmonary thromboembolism. Ischaemia of pneumocytes because of crack use is induced by the following phenomena: thermal damage to the airways, direct toxicity, inflammatory damage, barotrauma and vasospasm. Diffuse alveolar damage and alveolar hemorrhage with eosinophilic cell infiltration and IgE deposits are found in the lung tissue.PurposeWe present two clinical cases of patients admitted to the emergency department of our university hospital with respiratory failure. HRCT scans showed bilaterally, subpleural, and peri-hilar lung parenchyma, extensive areas of parenchymal ground-glass hyperdensity, crazy paving aspects, and relative sparing of the apices. The temporal relationship between the appearance of the bilateral opacities, the history documenting drug use, and the onset of hypoxemia suggests the diagnosis of "Crack lung".ConclusionsIt is important to include drug abuse and crack lung in the differential diagnosis of acute respiratory symptoms with ground-glass opacities, as they are not uncommon in emergency departments and may rapidly progress to ARDS. CT findings are not specific, but it is important to accurately collect anamnestic data and collaborate with the clinician to achieve a diagnosis and establish proper therapy.

Enhanced machine learning models for predicting one-year mortality in individuals suffering from type A aortic dissection

ObjectiveThe study objective was to develop and validate an interpretable machine learning model to predict 1-year mortality in patients with type A aortic dissection, improving risk classification and aiding clinical decision-making. MethodsWe enrolled 289 patients with type A aortic dissection, dividing them into a training cohort (202 patients) and a validation cohort (87 patients). The Least Absolute Shrinkage and Selection Operator method with 10-fold cross-validation identified 8 key factors related to 1-year mortality. The Treebag model's performance was assessed using accuracy, F1-Score, Brier score, area under the curve, and area under the precision-recall curve with calibration and clinical utility evaluated through decision curves. Shapley Additive Explanations analysis determined the most influential predictors. ResultsThe Treebag model outperformed others, achieving a Brier score of 0.128 and an area under the curve of 0.91. Key risk factors included older age and elevated white blood cell count, whereas higher systolic blood pressure, lymphocyte, carbon dioxide combining power, eosinophil, β-receptor blocker use, and surgical intervention were protective. A web-based application, TAAD One-Year Prognostic Risk Assessment Web, was developed for clinical use (available at https://taad-1year-mortality-predictor.streamlit.app/). This platform allows for the prediction of 1-year mortality in patients with type A aortic dissection based on the identified predictive factors, facilitating clinical decision-making and patient management. ConclusionsThe Treebag machine learning model effectively predicts 1-year mortality in patients with type A aortic dissection, stratifying risk profiles. Key factors for enhancing survival include surgical intervention, β-blocker administration, and management of systolic blood pressure, lymphocyte, carbon dioxide combining power, eosinophil, and white blood cell levels, offering a valuable tool for improving patient outcomes.

Sebaceous gland epithelioma with potential malignancy in a dog

Sebaceous gland tumors consist of neoplastic proliferations of sebaceous gland cells located around hair follicles in the dermis. These tumors are subclassified as sebaceous epithelioma, sebaceous adenoma, sebaceous adenocarcinoma and nodular hyperplasia. In this case report, a nodular growth in the sacral region of an eight-year-old male Belgian Malinois dog was presented. Macroscopically, the nodular mass had a slightly soft consistency, grayish-white, and dark red-black appearance. The mass was measured in the dimension of 2x1x1 cm. Histopathologically, the tumor was observed to have a multilobular structure shaped by neoplastic cell islands. The tumor consisted mainly of eosinophilic cells with small cytoplasm resembling epithelial basaloid cells and to a lesser extent differentiated sebocytes. The parenchyma of the tumor consisted of irregular islets containing a small number of mature sebocytes. Their nuclei are oval with one to three small nucleoli. Immunohistochemically, tumor cells for Ki67 antibody showed strongly positive immunoreactivity. Based on the histopathological and immunohistochemical features, the tumor was diagnosed as sebaceous epithelioma having, a potential malignancy. Since no case of sebaceous epithelioma with malignant potential has been reported in our country, we aimed to present the case with histopathological and immunohistochemical features.

Time to resolution of airway inflammation caused by bronchoalveolar lavage in healthy horses.

Bronchoalveolar lavage (BAL) is a common procedure for evaluation of the equine lower airways. Time to resolution of post-BAL inflammation has not been clearly defined. Residual inflammation, evident by changes in immune cell populations and inflammatory cytokines, will resolve by 72 hours after BAL. Six adult, healthy, institution-owned horses. Randomized, complete cross-over design. Each horse underwent 3 paired BALs, including a baseline and then 48, 72, and 96 hours later, with a 7-day washout between paired BALs. Each sample underwent cytological evaluation and cytokine concentrations were determined by a commercially available multiplex bead immunoassay. Statistical analysis was performed by multilevel mixed-effects Poisson regression analysis. Data are reported as marginal means and 95% confidence interval (CI). Neutrophil, eosinophil and mast cell percentages were not significantly different at any time points. Macrophage percentages were higher at 72 hours (45.0 [95% CI, 41.6-48.4]%) and 96 hours (45.3 [95% CI, 42.9-47.7]%) vs baseline (37.4 [95% CI, 33.5-41.4]%; P < .001 and P = .01, respectively), and at 72 hours and 96 hours vs 48 hours (31.9 [95% CI, 28.1-35.6]%; P < .001). Neutrophil percentage was not significantly increased at 48 hours (P = .11). Interleukin (IL)-6 concentration was increased at 72 hours (5.22 [95% CI, 3.44-6.99] pg/mL) vs 48 hours (4.38 [95% CI, 2.99-5.78] pg/mL; P < .001). Significant lung inflammation was not detected at 72 and 96 hours, suggesting that repeating BAL at 72 hours or more can be done without concern of residual inflammation.

Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study

BackgroundHuman aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined.MethodsThis study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration.ResultsIn the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E−03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E−07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E−06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E−04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E−03 < 0.01).ConclusionThese findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.

Changes in respiratory tract and gut microbiota in AR mice and their relationship with Th1/Th2/Treg

BackgroundThe etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. ObjectiveThe aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. MethodsStandardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. ResultsIn the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. ConclusionOur results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.

Chondroid Synoviocytic Neoplasm: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of a Distinctive Tumor of Synoviocytes

Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix are rare and most often involve the temporomandibular joint (TMJ). We studied 21 tumors consisting of synoviocytes (large, eosinophilic mononuclear cells containing hemosiderin) and chondroid matrix to better understand these unusual neoplasms. The tumors occurred in 10 males and 11 females, in the age group of 31 to 80 years (median, 50 years) and involved the TMJ region (16), extremities (4), and spine (1). As in conventional TGCT, all were composed of synoviocytes, small histiocytes, foamy macrophages, siderophages, and osteoclast-like giant cells in variably hyalinized background. Expansile nodules of large, moderately atypical synoviocytes were present, in addition to “chondroblastoma-like,” “chondroma-like,” or “phosphaturic mesenchymal tumor-like” calcified matrix. The synoviocytes expressed clusterin (17/19) and less often desmin (3/15). The tumors were frequently CSF1 positive by chromogenic in situ hybridization (8/13) but at best weakly positive for CSF1 by immunohistochemistry (0/3). Background small histiocytes were CD163 positive (12/12). All were FGF23 negative (0/10). Cells within lacunae showed a synoviocytic phenotype (clusterin positive; S100 protein and ERG negative). RNA-Seq was successful in 13 cases; fusions were present in 7 tumors, including FN1::TEK (5 cases); FN1::PRG4 (2 cases); and MALAT1::FN1, PDGFRA::USP35, and TIMP3::ZCCHC7 (1 case each). Three tumors contained more than 1 fusion (FN1::PRG4 with TIMP3::ZCCHC7, FN1::TEK with FN1::PRG4, and FN1::TEK with MALAT1::FN1). Clinical follow-up (17 patients; median follow-up duration 38 months; range 4-173 months) showed 13 (76%) to be alive without evidence of disease and 4 (24%) to be alive with persistent/recurrent local disease. No metastases or deaths from disease were observed. We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term “chondroid synoviocytic neoplasm,” rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.