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The Delta Smelt is a largely zooplank­tivorous, endangered fish endemic to the San Francisco Estuary (the estuary). High flows increase the availability of fresh and brackish water habitat for Delta Smelt, but also may mobilize contaminants, potentially increasing toxicological stress. Here, we examine the association between contaminants and Delta Smelt health across contrasting water year types and flow-related management actions. Our study spanned the fall season of three years: 1 dry year (2018) bracketed by 2 wet years (2017 and 2019) and coincided with several management actions meant to benefit Delta Smelt. We collected field water from six sites in the estuary that encompass the freshwater and low-salinity habitat of Delta Smelt and analyzed the water for contaminant concentrations. After a 96-hour exposure to the field water, we assessed cultured Delta Smelt survival and the histopathological condition of the gill and liver. Insecticides, particularly fipronil metabolites, were the most prevalent contaminants detected in 2017 and 2018, and a variety of contaminants associated with the rice harvest were detected in 2019. No acute toxicity was observed during any exposure, but we observed negative effects in the livers of Delta Smelt exposed to agricultural water from the Toe Drain and Cache Slough during a 2019 pulse flow action, which coincided with elevated detections and concentrations of organic pesticides. Other noteworthy sub-lethal effects, likely occurring in response to contaminant mixtures, included severe gill lesions in Delta Smelt exposed to Decker Island water in 2019. In the drier year of 2018, lesions were generally mild or absent. Thus, the trade-offs between increased habitat availability and contaminant loading may provide one explanation for why Delta Smelt abundance does not consistently respond positively to outflow.

Background: The European Thyroid Association Thyroid Imaging Data and Reporting Systems (EU-TIRADS) is widely used in the risk stratification of thyroid nodule malignancy. However, data on the subject in Sub-Saharan Africa are limited. The objective of this study is to evaluate the clinical, sonographic and histopathological concordance of thyroid nodules in the diagnosis of thyroid cancer. Methods: This was an analytical cross-sectional study that examined the clinical, ultrasound and pathological data of 61 patients from 4 hospitals in the city province of Kinshasa over a period of 24 months, from June 01, 2020 to May 31, 2022. Results: Of the 61 patients, their mean age was 47.38 ± 8.8 years. The mean clinical score of the patients was 3.4 ± 0.84 with the extremes ranging from 1 to 5. The majority of the patients were classified as having an intermediate risk, ie 85.2% of the cases. It was noted that 41% of the nodules had a high risk according to the EU-TIRADS score and 8.2% of the nodules were malignant after histopathological analysis. The ROC curves reported at the diagnosis of malignancy show an area under the curve of 0.709 with 95% CI (0.486–0.931), a Youden index of 0.769 for the clinical score, and an area under the curve of 0.830 with 95% CI (0.605–0.995), a Youden index of 0.772 for the EU-TIRADS score. Conclusion: In a low-income country, a well-performed thyroid ultrasound and the well-applied clinical score could be an important tool in the selection of thyroid nodules suspected of malignancy and requiring histopathological examination to avoid excessive acts in the patient. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of primary Sjögren's syndrome (pSS) remains difficult due to its insidious onset. Objectives: To identify whether meibomian gland dropout (MGD) is a sensitive and noninvasive predictor of pSS by studying its association with histopathology in labial salivary gland biopsy in patients with clinically suspected pSS. Design: Prospective, randomized, multicenter, comparative effectiveness study. Methods: The study was conducted from July 2022 to July 2023. In all, 56 eligible participants with clinically suspected pSS were recruited from three combined ophthalmology medicine/rheumatology SS clinics. All participants with suspected pSS were evaluated and diagnosed by ophthalmology and rheumatology consultants and underwent infrared imaging of the meibomian glands using Keratograph 5M and histopathological evaluation of labial salivary gland biopsies. The length, width, and tortuosity of the meibomian glands were measured; the dropout rate in the nasal, temporal, and total eyelids was analyzed; and the dropout score was calculated using meibography grading scales. Results: Among the 56 participants, 34 were identified with pSS, and 22 were diagnosed with non-SS dry eye (NSSDE) and served as the control group. We recorded significant differences in the temporal and total MGD rates of the upper eyelids between the pSS and NSSDE groups (all p < 0.01). Improved prediction accuracy was achieved with the temporal and total MGD rates in the upper eyelids, with area under the curve values of 0.94 and 0.91, and optimal cutoff points of 0.78 and 0.75, respectively. Conclusion: MGD in the upper eyelids, especially in the temporal portion, is strongly associated with the histopathological outcome of labial salivary gland biopsy in pSS and is proposed as a highly predictive and noninvasive biomarker for the early diagnosis of pSS. Trial registration: ClinicalTrials.gov identifier: ChiCTR2000038911. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD–CLC (cSBD–CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD–CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment. [ABSTRACT FROM AUTHOR]

Objective(s): Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model. Materials and Methods: Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated. Results: Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and highdose groups regarding the immunohistochemical reactivity of αVβ3 integrin, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) (P<0.05). Conclusion: We demonstrated that chronic caffeine consumption in rats adversely affects the recovery process of wounds in a dose-dependent manner. This effect may occur through delayed wound healing via the molecules MMP-9, αVβ3 integrin, and VEGF. Treatment that modulates these molecules can lead to enhanced and quicker recovery of damaged skin in coffee lovers. [ABSTRACT FROM AUTHOR]

Background: Primary uterine alveolar soft part sarcoma (ASPS) is a rare, indolent mesenchymal malignancy with less than 40 patients documented in the literature. Case: We report an example of ASPS in a 61-year-old postmenopausal woman. Macroscopically, the uterus showed multiple nodular masses. Microscopic examination revealed tumor arranged in nests and alveolar pattern. The tumor cells were moderately to markedly pleomorphic, epithelioid to polygonal, with eccentrically placed nuclei, vesicular chromatin, prominent macro-nucleoli, and moderate to abundant eosinophilic cytoplasm. PAS-positive and diastase-resistant intracytoplasmic crystals were also seen in some tumor cells. On immunohistochemistry, the tumor cells showed diffuse positivity for vimentin and nuclear positivity for TFE3, a surrogate marker for ASPS. These were negative for SMA, desmin, CD10, h-caldesmon, cyclin D1, EMA, Melan A, and CD34. SMARCB1 expression was retained. Based on the histopathology and IHC, a final diagnosis of uterine ASPS was rendered. Conclusions: Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare tumors. Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare sarcoma in an uncommon site with an unusual age. [ABSTRACT FROM AUTHOR]

Study Design. Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study. Objective. The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and ß-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model. Summary of Background Data. ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases. However, pseudarthrosis associated with increased patient morbidity occurs in ~2.6% of the surgeries. SBG may enhance bony fusion and subsequently decrease the risk of pseudarthrosis. Recent studies on monetite-based SBGs for use in large cranial defects in humans have shown promising bone healing results, necessitating further investigation of their use in cervical spinal fusion. Materials and Methods. Four adult female Danish Göttingen minipigs received partial cervical anterior discectomy and intervertebral defects at an upper and lower level. One defect was filled with SBG, and the other was left empty. Bony fusion was evaluated using computed tomography (CT) at three-month intervals for 12 months. Fifteen months postsurgery, the animals were euthanized for further ex vivo qualitative histopathologic and micro-CT evaluations. Fusion rates were compared using the Fisher exact test at each time point. Results. Increased interbody bony fusion rates were observed at SBG levels (4/4) compared with control levels (0/4) evaluated by CT at 6 and 9 months postsurgery (P=0.029). Fusion was observed at all SBG levels 12 months postsurgery and at only one control level. Histopathologic evaluation confirmed high-quality interbody bony fusion at all SBG levels and fusion by spondylosis at one control level. Conclusion. This proof-of-concept study provides preliminary evidence of a novel, calcium pyrophosphate-containing, and ß-tricalcium phosphate-containing monetite SBG that promotes bony fusion compared with a negative control in a clinically relevant porcine model of ACDF. [ABSTRACT FROM AUTHOR]

The objective of this research was to assess the impact of 2-methyl-2-nitro-3-guanidine on mammalian species, otherwise not the intended targets, followed by one-time exposure and its adverse effects. Thirty-five Sprague Dawley rats of either male or female sex, aged four weeks, and with an average weight of 80±20g, were divided into three groups randomly: control E exposed and exposed and supplemented with vitamin C, and assigned the titles C,E, and V, respectively. Each group comprised fifteen rats. Both E and V groups were further divided into subgroups: E1, E2, and E3, exposed to LD10, LD25, and LD50 doses of Dinotefuran respectively, and V1, V2, and V3, exposed in the same manner but supplemented with a fixed dose of ascorbic acid (vitamin C). Ascorbic acid was administered in aqueous form 35mg/100mL of water and provided ad libitum. Eight hours after exposure to Dinotefuran, 5ml of blood was collected under sedation through the cardiac vein. After 48 hours, two rats randomly selected from each subgroup, including the control group, were anesthetized, euthanized, and dissected. Different body tissues, and the kidney, liver, bones, and heart, were isolated and preserved in formalin solution for subsequent analysis. CBC, liver, renal, and cardiac biomarkers were evaluated. In addition, histopathology and bone characteristics of soft tissues were also conducted. Mortality and morbidity were recorded. The result showed significant disruptions in CBC and other biomarkers related to kidney, liver, and heart in a dose-dependent pattern. Although vitamin supplementation improved the overall outcome, the improvement was not statistically significant. Histopathological examination displayed changes in the exposed (E) group, with no observable improvements with vitamin supplementation. Moreover, the bone-related parameters exhibited similar trends. [ABSTRACT FROM AUTHOR]

This article presents the first recorded instance of Sphaerothecum destruens infection in a native North American fish species, the warpaint shiner. S. destruens is a pathogen that has been linked to disease in salmonids in North America and has spread to European cyprinids through the introduction of the invasive topmouth gudgeon. The parasite can have significant impacts, causing deaths in salmonids and leading to population declines in susceptible wild fish species. The article provides details on the microscopic characteristics of the infection in the warpaint shiner and raises concerns about the health of native cyprinid populations in North America. Further research is needed to understand the distribution and host range of S. destruens in freshwater fish in North America. [Extracted from the article]

A 4-year-old neutered male English bulldog was referred to the veterinary teaching hospital for presumed short bowel syndrome following an ileocecal resection to remove a tumor involving the caudal third of the jejunum, ileum, and proximal colon. Histopathology of the tumor revealed chronic transmural lipogranulomatous and necrotizing lymphangitis. After surgery, mixed-bowel diarrhea developed and the patient lost weight. When the diarrhea and weight loss did not respond to medical management, the patient was referred to the university nutrition service for nutritional management of presumed short bowel syndrome and lymphangitis. Diet modification in conjunction with medical management led to improved body weight and fecal consistency. [ABSTRACT FROM AUTHOR]

Abrus precatorius (AP) is a medicinal plant rarely studied for its beneficial effects against diabetes mellitus (DM) type-1. We estimated DM type-1 related parameters—total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days, followed by histopathological analysis of kidney and liver sections. AP leaf bioactives (ALPBs) were collected from GCMS fractions, database, and literature; common targets were intersected with annotated DM type-1 genes from the experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, and their protein–protein interaction network was analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, and Cytoscape, to provide insight into the potential molecular basis of APLBs in DM-type-1. 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p < 0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea and creatinine while hepatorenal photomicrographs indicated moderate safety. Erucic acid, oleic acid, phytol and stigmasterol interacted with 25 type-1 DM biomarkers enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction, and van der Waals forces from the docking study. Future interests may provide additional experimental data into the mechanisms by which APLBs elicit this remarkable ability. [ABSTRACT FROM AUTHOR]

Purpose: Undifferentiated carcinoma of the esophagus (UEC) is a rare malignancy. Deficiency in SMARCA genes, critical for chromatin regulation, has been observed in cases of UEC. Research in UEC is sparse, however, and we present a case series along with a comprehensive review of the literature. Case Series: Case 1 is a 49-year-old female with abdominal pain and dysphagia and esophagogastroduodenoscopy (EGD) showing a friable mass at the gastroesophageal (GE) junction. Biopsies showed a poorly differentiated neoplasm and immunohistochemistry showed loss for SMARCA4. With metastatic disease, she agreed to undergo palliative chemotherapy and radiation, passing away at 4 months. Case 2 is an 88-year-old male with dysphagia, nausea, vomiting, and distal esophageal mass with biopsy showing a malignancy with loss of SMARCA4 expression. Due to extensive metastases, he was counseled on hospice care. Case 3 is a 53-year-old male with extensive alcohol and smoking history presenting with hematemesis, passing away shortly. Posthumous histopathology consistent with undifferentiated SMARCA4-deficient carcinoma of the esophagus. Results of the literature review indicate a predilection towards males (75.0%) and a variable age range (39–88 years). Majority (76.2%) reported with a distal esophagus location. Metastatic disease was common at initial presentation. Median survival was 2.60 months. Some were managed with chemotherapy and radiation. Conclusions: Research in SMARCA-deficient UEC is very limited. It is more common in men, age is variable, and associated with Barret's esophagus. Further research is necessary to better understand it and to establish treatment guidelines; however, it is clear that SMARCA4-deficient UEC carries a significantly poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: Prototype cosmetic formulations containing short-chain acids and alcohols intended to be applied in the proximity of the eyes are sometimes evaluated for ocular irritation potential using the validated Bovine Corneal Opacity and Permeability Assay (OECD TG 437). We evaluated the eye irritation potential of nine experimental cosmetic formulations designed and prepared by Avon Global Reserach and Development to differ only in the concentrations of Ethanol, Glycolic Acid and Salicylic Acid. Methods: We analysed the data generated using the BCOP assay. The opacity and permeability values obtained following the exposure of bovine corneas to experimental cosmetic formulations were combined into a single In Vitro Irritancy Score used to rank eye irritation potential. Histopathological examination of treated corneas was used to provide additional information about the depth and degree of the injury and to support the prediction of eye irritation potential of each experimental cosmetic formulation. Results: The In Vitro Irritancy Scores and histopathological analysis showed that experimental formulations containing only Ethanol, Glycolic Acid, or Salicylic Acid alone had, at most, a mild ocular irritation potential. The experimental formulations containing both Ethanol and Glycolic Acid had a mild ocular irritation potential, while the experimental formulations containing both Ethanol and Salicylic Acid had a moderate ocular irritation potential. Severe ocular irritation potential was induced by an experimental formulation containing a combination of Glycolic Acid and Salicylic Acid and it was further accentuated by the addition of Ethanol to the formulation. Our data indicate a possible synergistic effect on eye irritation potential of Ethanol, Glycolic Acid and Salicylic Acid in at least some experimental cosmetic formulations. Further, our results provide insight on an apparent concentration-dependent ocular irritation potential effect of combinations of Glycolic Acid, Salicylic Acid and Ethanol in at least one experimental cosmetic formulation. Conclusions: The results presented herein emphasise the need to consider in vitro testing of prototype cosmetic formulations containing combinations of Ethanol, Glycolic Acid and Salicylic Acid rather than relying on any predicted additive effect on ocular irritation based solely on previously generated results of similar formulations containing Ethanol, Glycolic Acid or Salicylic Acid alone. Further work is required to understand the significance of these observations and to elucidate the mechanisms responsible for the apparent synergistic effects of Glycolic Acid, Salicylic Acid and Ethanol and eye irritation potential suggested by our results. [ABSTRACT FROM AUTHOR]

Background: Granular Cell Tumor (GCT) is an uncommon benign lesion in the oral cavity whose pathogenesis remains poorly understood. Due to their infrequent occurrence and similarity to other oral lesions, they are often forgotten during the initial clinical diagnosis. Therefore, understanding its prevalence, clinical and pathological characteristics is crucial for an accurate diagnosis and adequate management. Methods: All cases diagnosed as GCTs in six Brazilian and Argentinian oral diagnostic centers were re-evaluated by HE staining, and clinical, demographic, and histopathological data were collected and evaluated. Results: The series comprised 45 female (73.8%) and 16 male (26.2%), with a 2.8:1 female-to-male ratio and a mean age of 35.3 ± 16.9 years (range: 7–77 years). Most cases occurred on the tongue (n = 49; 81.6%) and presented clinically as asymptomatic papules or nodules (n = 50; 89.3%) with a normochromic (n = 25; 45.5%) or yellowish (n = 11; 20.0%) coloration and sizes ranging from 0.2 to 3.0 cm (mean ± SD: 1.40 ± 0.75 cm). Morphologically, most tumors were characterized by a poorly delimited proliferation (n = 52; 88.1%) of cells typically rounded to polygonal containing abundant, eosinophilic, finely granular cytoplasm. Pustulo-ovoid bodies of Milian were identified in all lesions (n = 61; 100%). Entrapment of skeletal striated muscle (n = 44; 72.1%) and nerve fibers (n = 42; 68.9%) were common findings. Pseudoepitheliomatous hyperplasia (PEH) was observed in 23 cases (39.0%). In only 27.7% of cases (n = 13) there was agreement between the clinical and histopathological diagnosis. Outcome information was available from 16 patients (26.2%), with clinical follow-up ranging from 4 to 36 months (mean 13.3 months), and none developed local recurrence. Conclusions: The clinical and histopathological features of GCTs were consistent with those described in previous studies. In general, these lesions have a predilection for the lateral region of the tongue in adult women. It is essential to consider GCTs in the differential diagnosis of yellow or normochromic papules and nodules in the oral cavity. Histopathological evaluation is essential for the definitive diagnosis and the prognosis is excellent. [ABSTRACT FROM AUTHOR]

Lake Burullus is an important source of fish production in Egypt; it produces 20.5% of the Egyptian fisheries' production. There is intense controversy about the heavy metal pollution in Burullus water and its effects on fish health and safety for human consumption. Heavy metals represent a major concern for aquatic life and could negatively affect fish health. Agricultural and industrial water drainage represents a considerable part of the lake water supply. The present work was conducted to determine heavy metal concentrations in lake water and blue tilapia Oreochromis aureus musculature. Water samples were collected from six locations to determine cadmium, copper, lead, zinc and iron. Sixty O. aureus fish samples were also collected from the same sampling points to assess the prevalent parasites infesting fish and to determine the heavy metal (Cd, Cu, Pb, Zn and Fe) concentrations in fish musculature then study the relationship between heavy metals concentration and prevailing fish parasites. Results indicated that 53.34% of the examined fish were infested with encysted metacercaria. Centrocestus formosanus, Prohemistomum vivax, and Euclinostomum heterostomum were retrieved from gills, musculature, hepatopancreas and the posterior kidney. The parasitic intensity in fish tissues was between 1 and 9 cyst g−1. Centrocestus formosanus was identified using the polymerase chain reaction in the gill tissues of 16 fish. The gill parasitic copepod Lamproglena monodi was identified in one fish. Degenerative changes such as thickening, corrugation, and destruction of gill filament are the most dominant pathological changes in infested fish gills. Heavy metal concentrations in water samples were at normal levels, except for copper and iron in the southern part of the lake. All heavy metals in fish musculature were below the permissible limits. The parasitic infestation was more dominant in the northern part of the lake than in the southern region; this could be due to elevated copper concentration in the southern part of the lake that could negatively affect the survival of the first intermediate host and parasite cercaria. In conclusion, captured fish from Lake Burullus were safe for human consumption, and heavy metal pollution in lake water does not represent a severe risk. [ABSTRACT FROM AUTHOR]

Objective: To comprehensively analyze reported cases of nasolacrimal squamous cell carcinoma (NLSCC), focusing on risk factors, treatment modalities, and outcomes. Additionally, investigate the impact of human Papillomavirus (HPV) status and histopathological subtypes' impact on prognosis. Data Sources: Pubmed, Embase. Review Methods: We conducted a systematic literature review to identify relevant studies reporting cases of NLSCC. The review methods adhered to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. The final update was performed on May 31, 2023. Results: The 72 studies included a total of 313 participants (mean age: 55; 60% male). Longer symptom duration (44.1 ± 59.2 months) correlated with recurrence (p = 0.004), and males exhibited higher mortality rates (19.6% vs. 2.4% in females, p = 0.01). The overall survival (OS) rate among all patients was 87.1%. Basaloid NLSCC had a worse death outcome (p ≤ 0.001). HPV‐positive cases showed comparable OS, recurrence, and metastasis rates to the general population (p = 0.917, 0.851, 0.07, respectively). Comparing treatment approaches (surgery, surgery with adjuvant radiation, chemoradiotherapy [CRT] followed by surgery), no significant differences in 5 and 10‐year OS rates or recurrence were observed (p = 0.4, 0.24, respectively), but 5‐year metastasis events were significant (p = 0.024). Eye exenteration rates were 31.1%, 20%, and 0% for the respective treatments (p = 0.089). Induction chemotherapy saved four cases from potential exenteration with favorable prognosis. Conclusion: Early detection and diagnosis are of utmost importance in the management of NLSCC. Regardless of the treatment approach, HPV‐related NLSCC demonstrated similar outcomes to the general population. Basaloid histology represents the worst subtype in terms of prognosis. Limited adjuvant CRT cases showed improved outcomes and induction chemotherapy's importance was emphasized in recent literature and our shared experience. Laryngoscope, 134:3892–3902, 2024 [ABSTRACT FROM AUTHOR]

Background: Pancreatic cystic lesions (PCLs) are frequent on MRI and are thought to be associated with pancreatic adenocarcinoma (PDAC) necessitating long‐term surveillance based on older studies suffering from selection bias. Purpose: To establish the percentage of patients with PCLs on MRI with a present or future PDAC. Study Type: Systematic review, meta‐analysis. Population: Adults with PCLs on MRI and a present or future diagnosis of PDAC were eligible. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus were searched to April 2022 (PROSPERO:CRD42022320502). Studies limited to PCLs not requiring surveillance, <100 patients, or those with a history/genetic risk of PDAC were excluded. Field Strength/Sequence: ≥1.5 T with ≥1 T2‐weighted sequence. Assessment: Two investigators extracted data, with discrepancies resolved by a third. QUADAS‐2 assessed bias. PDAC was diagnosed using a composite reference standard. Statistical Tests: A meta‐analysis of proportions was performed at the patient‐level with 95% confidence intervals (95% CI). Results: Eight studies with 1289 patients contributed to the percentage of patients with a present diagnosis of PDAC, and 10 studies with 3422 patients to the percentage with a future diagnosis. Of patients with PCLs on MRI, 14.8% (95% CI 2.4–34.9) had a PDAC at initial MRI, which decreased to 6.0% (2.2–11.3) for studies at low risk of bias. For patients without PDAC on initial MRI, 2.0% (1.1–3.2) developed PDAC during surveillance, similar for low risk of bias studies at 1.9% (0.7–3.6), with no clear trend of increased PDAC for longer surveillance durations. For patients without worrisome features or high‐risk stigmata, 0.9% (0.1–2.2) developed PDAC during surveillance. Of 10, eight studies had a median surveillance ≥3 years (range 3–157 months). Sources of bias included retrospectively limiting PCLs to those with histopathology and inconsistent surveillance protocols. Data Conclusion: A low percentage of patients with PCLs on MRI develop PDAC while on surveillance. The first MRI revealing a PCL should be scrutinized for PDAC. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

This study aimed to formulate diacerein (DCN)-loaded flexosomes for enhanced efficacy against osteoarthritis. A 23 D-optimal design was employed, investigating the impact of surfactant type (A), surfactant concentration (%w/v) (B), and oleylamine amount (mg) (C). Flexosomes were formulated using a rotary evaporator, and Design-Expert® software was utilized to statistically analyze entrapment efficiency (EE%), zeta potential (ZP), poly-dispersity index (PDI), and particle size (PS) to determine the optimum formula. The selection criteria prioritized increased ZP (as absolute value) and EE%, coupled with decreased PDI and PS. Rigorous physicochemical, in vivo, and ex vivo tests were conducted to validate the safety, stability, and activity of the optimal formula. Physicochemical assessments encompassed pH measurement, transmission electron microscopy, differential scanning calorimetry, release profiles, storage effects, and Fourier transform infrared spectroscopy. In vivo tests included permeation studies, histopathology, anti-inflammatory activity, and skin irritancy, while ex vivo tests focused on permeation parameters and skin deposition. The optimum formula demonstrated high desirability (0.931), along with favorable EE% (90.93%), ZP (− 40.4 mV), particle size (188.55 nm), and sustained behavior. Notably, improved in vivo permeation (132 µm), skin deposition (193.43 µg/cm2), and antinociceptive activity (66%) compared to DCN suspension (48 µm, 66.31 µg/cm2, and 26%, respectively) were observed. The optimal formula also exhibited excellent safety and storage characteristics. In conclusion, DCN-loaded flexosomes exhibit significant potential for effectively managing osteoarthritis. [ABSTRACT FROM AUTHOR]

Dimethoate (DMT) is one of the most harmful and commonly used organophosphate pesticides in agricultural lands to control different groups of parasitic insects. However, this pesticide is considered a dangerous pollutant for aquatic organisms following its infiltration in coastal ecosystems through leaching. Yet, our investigation aimed to gain new insights into the toxicity mechanism of DMT in the muscles of the green crab Carcinus aestuarii, regarding oxidative stress, neurotransmission impairment, histological aspects, and changes in lipid composition, assessed for the first time on the green crab's muscle. Specimens of C. aestuarii were exposed to 50, 100, and 200 µg DMT L−1 for 24 h. Compared to the negative control group, the higher the DMT concentration, the lower the saturated fatty acids (SFA), and the higher the monounsaturated fatty acids (MUFA). The significant increase in polyunsaturated fatty acid n-6 (PUFA n-6) was related to the high release, mainly, of linoleic acid (LA, C18: 2n6) and arachidonic acid (ARA, C20: 4n6) levels. Biochemical biomarkers showed that DMT exposure promoted oxidative stress, highlighted by increased levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), advanced oxidation protein product levels (AOPP), and protein carbonyl (PCO). Furthermore, the antioxidant defense system was activated, as demonstrated by the significant changes in the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels associated with an adaptation process of C. aestuarii to cope with the DMT exposure. This pesticide significantly impairs the neurotransmission process, as evidenced by the inhibition of acetylcholinesterase (AChE) activity. Finally, several histopathological changes were revealed in DMT-treated crabs, including vacuolation, and muscle bundle loss. This research offered new insights into the toxic mechanism of DMT, pointing to the usefulness of fatty acid (FA) composition as a sensitive biomarker in littoral crabs. [ABSTRACT FROM AUTHOR]

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Cold snare polypectomy (CSP) has the disadvantage of a lower histopathological complete resection rate (HCRR) because blunt resection using CSP‐dedicated snares (DSs) causes mucosal retraction into the sheath during capture/resection. In this study, attachments are designed to narrow the sheath tip's inner diameter from 1.8 to 1.3‒1.1 mm to prevent mucosal retraction. Eight prototype snares with different component characteristics are combined with these attachments. Additionally, product version DS with attachment (Smart Snare Cold) and existing DSs, such as Exacto Cold Snare, are prepared. For snare performance evaluation, the force required to resect (FRR) human colonic mucosa, mucosal retraction amount (MRA), and clinical data are obtained. The attachments that narrowed the inner diameter to 1.3 or 1.1 mm reduce the FRR to 74.9%−93.8% and 68.0%−84.9%, respectively, and reduce the MRA to 21.0%−35.3% and 15.1%−26.8%, respectively. Thus, the reduced inner diameter improves resection ability and prevents mucosal retraction. The clinical findings show that Smart Snare Cold has significantly higher muscularis mucosa resection rates and HCRRs than Exacto Cold Snare (P < 0.001 and P = 0.003, respectively). Thus, the novel DS with tip attachment improves the HCRR and overcomes the current CSP disadvantage by simultaneously improving resection ability and preventing mucosal retraction. [ABSTRACT FROM AUTHOR]

The quality assurance provided by preimplantation biopsy quantification of chronic damage may allow greater use of kidneys from expanded criteria donors, and thereby expand the deceased donor pool. Preimplantation biopsy may, however, identify additional acute or chronic pathologies not considered in the scoring of chronic damage, and these may influence the decision to implant or discard the kidney. This single-centre retrospective cohort study of a contemporary UK donor population systematically characterised the nature of additional findings in 1,046 preimplantation and implantation biopsies over an eight-year period. A diverse range of findings were identified in 111/1,046 (11%) organs; most frequently diabetic glomerulopathy, focal segmental glomerulosclerosis, (micro)thrombi, neutrophil casts, and immunoglobulin/ complement staining. Seventy (63%) of these were transplanted, with subsequent biopsy in 41 (58%) cases confirming that 80% of the initial acute changes had spontaneously resolved, while there was no progression of diabetic glomerulopathy, and the lesions of focal segmental glomerulosclerosis were not identified. Over 75% of assessable grafts with additional histological findings at the time of transplant showed adequate function at one-year following transplant. In conclusion, most histological abnormalities that may be identified in addition to chronic scarring in preimplantation kidney biopsies would not preclude transplantation nor predict poor graft function. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disorder in which patients suffer from inflammatory-erosive arthritis. Recent advances on histopathology heterogeneity of RA synovial tissue revealed three distinct phenotypes based on cellular composition (pauci-immune, diffuse and lymphoid), suggesting that distinct etiologies warrant specific targeted therapy which motivates a need for cost effective phenotyping tools in preclinical and clinical settings. To this end, we developed an automated multi-scale computational pathotyping (AMSCP) pipeline for both human and mouse synovial tissue with two distinct components that can be leveraged together or independently: (1) segmentation of different tissue types to characterize tissue-level changes, and (2) cell type classification within each tissue compartment that assesses change across disease states. Here, we demonstrate the efficacy, efficiency, and robustness of the AMSCP pipeline as well as the ability to discover novel phenotypes. Taken together, we find AMSCP to be a valuable cost-effective method for both pre-clinical and clinical research. Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Objective To understand the prognosis of patients with bone metastases from first-treatment non-small cell lung cancer （NSCLC） of different pathological types after different first-line treatment regimens， in order to provide clinical prediction of disease progression， guidance of treatment， and improvement of prognosis. Methods 403 NSCLC patients with bone metastases who received primary treatment with bone metastases from Chaohu Hospital of Anhui Medical University from 1 January 2019 to 31 December 2023 were selected for univariate analysis using survival analysis （Log-rank test） and multifactorial analysis with Cox regression， and it was found that histopathological subtyping was an independent factor affecting the prognosis of patients （P = 0.001， HR = 1.952）， after which the effect of this factor on prognosis was removed， and the total number of patients was divided into two groups according to histopathological classification: adenocarcinoma group （316） and squamous carcinoma group （87）， and then multifactorial analysis was performed again using Cox regression model to analyse the factors affecting survival prognosis. Results In this data analysis， patients with the pathological type of squamous carcinoma had a median overall survival （mOS） of 15 months （95% CI: 12.85 ~ 17.15） and a median progression-free survival （mPFS） of 9 months （95% CI: 7.34 ~ 10.67）， whereas patients in the adenocarcinoma group had a mOS of 25 months （95% CI: 23.26 ~ 26.74） and mPFS was 16 months （95% CI:14.43 ~ 17.57）， a statistically significant difference. The OS of the overall group was affected by multiple factors， including Eastern Cooperative Oncology Group （ECOG） score status （1/> 1） at the time of initial diagnosis， bone metastases to Trunk + limb bones + cranium， number of bone metastases ≥ 4， mutation of ALK target genes， and the use of chemotherapy+targeted therapy as the first line of treatment. therapy； similarly， PFS was also affected by the above factors. In addition， in the adenocarcinoma and squamous carcinoma models based on histopathological classification， chemotherapy + targeted therapy and chemotherapy + immunotherapy were found to be the protective factors for the two groups， and ALK target gene mutation was only a protective factor for the adenocarcinoma group. Conclusion This study further confirmed the prognostic factors influencing the prognosis of patients with bone metastases from primary NSCLC， which provides an important reference for clinical treatment. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD. Riboflavin attenuates alcoholic liver disease progression, regulates alcohol-induced changes in intestinal microbiota, and affects inflammatory cell infiltration suggesting that riboflavin may be a potentially effective agent for treating ALD [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) continues to be the most prevalent type of liver cancer worldwide. Diethylnitrosamine (DEN)‐induced HCC is an extensively used hepatic cancer model in experimental animals. Acetazolamide (AZA) is a carbonic anhydrase enzyme inhibitor. This study aimed to assess the therapeutic mechanism of AZA against DEN‐induced HCC. Thirty male Wistar albino rats were divided equally into three groups. Group I (C): control group, Group II (HCC): DEN‐induced HCC, and Group III (HCC/AZA): AZA‐treated HCC. Verification of the HCC induced by DEN was confirmed by elevated liver enzymes' activities, and increased α‐fetoprotein (AFP) levels, as well as distinct liver architecture changes. On the other hand, the AZA‐treated HCC group experienced decreases in the activities of serum liver enzymes and AFP levels, as well as, regulated liver architecture. Additionally, it downregulated p‐p38 MAPK/p‐JNK1/JNK2/p‐C‐Jun/p‐NF‐κB p65 protein expressions. Moreover, it ameliorated autophagy by controlling the expression of the p‐AMPK/p‐mTOR1/LC3 I/II proteins. Furthermore, it downregulated the relative gene expressions of carbonic anhydrase‐IX (CAIX) and hexokinase‐II (HKII). Histopathological examination of AZA‐treated HCC liver tissues supported these findings. Conclusion: AZA provides a new dimension in ameliorating experimentally induced HCC through regulation of hepatic biomarkers, antioxidant status, inflammatory markers, and autophagy, mediated by amelioration of CAIX and HKII gene expressions. [ABSTRACT FROM AUTHOR]

Introduction: Leucocytozoon is an intracellular blood parasite that affects various bird species globally and is transmitted by blackfly vectors. This parasite is responsible for leucocytozoonosis, a disease that results in significant economic losses due to reduced meat and egg production. There is limited knowledge about the epidemiological pattern of leucocytozoonosis and its causative species in Egypt, particularly in pigeons. Methods: The current study involved the collection of 203 blood samples from domestic pigeons from various household breeders and local markets across Qena Province, Upper Egypt. Samples were initially examined for potential Leucocytozoon infection using blood smears, followed by an evaluation of associated risk factors. Molecular identification of the parasite in selected samples (n = 11), which had initially tested positive via blood smears, was further refined through nested PCR and sequence analysis of the mitochondrial cytochrome b gene to ascertain the Leucocytozoon species present. Additionally, histopathological examination of the liver, spleen, and pancreas was conducted on animals that tested positive by blood smears. Results: Interestingly, 26 out of 203 samples (12.08%) had confirmed Leucocytozoon infections based on microscopic analysis. Additionally, all 11 samples that initially tested positive via blood smears were confirmed positive through nested PCR analysis, and their sequencing revealed the presence of Leucocytozoon sabrazesi, marking the first report of this parasite in Egypt. The study into potential risk factors unveiled the prevalence of Leucocytozoon spp. seems host gender-dependent, with males exhibiting a significantly higher infection rate (33.33%). Additionally, adult birds demonstrated a significantly higher infection prevalence than squabs, suggesting an age-dependent trend in prevalence. Seasonality played a significant role, with the highest occurrence observed during summer (37.25%). Histopathological examination revealed the presence of numerous megaloschizonts accompanied by lymphocytic infiltration and multiple focal areas of ischemic necrosis. Conclusion: To our knowledge, this is the first study to shed light on the epidemiological characteristics and molecular characterization of leucocytozoonosis in pigeons in Egypt. Further research endeavors are warranted to curb the resurgence of Leucocytozoon parasites in other avian species across Egypt, thereby refining the epidemiological understanding of the disease for more effective control and prevention measures. [ABSTRACT FROM AUTHOR]

Background: Myxofibrosarcoma is a myxoid soft tissue sarcoma showing T2 high intensity on magnetic resonance imaging. However, myxofibrosarcoma is a heterogeneous sarcoma with both myxoid and cellular portions. Magnetic resonance imaging findings were obtained MRI findings for comparison with histological and Ki-67 immunohistochemical features, in different portions of one myxofibrosarcoma. Case presentation: Magnetic resonance imaging observations were compared with gross pathological and microscopic findings of a myxofibrosarcoma from a 50-year-old Japanese female. The Ki-67 labeling indices of different portions of the tumor, that is, the myxoid, cellular, and histologically confirmed infiltrative margin portions (pathological tail sign), were compared. The T2 low intensity area was more cellular than the T2 high intensity area, while the cellular portion had a significantly higher Ki-67 index than the myxoid portion (p = 0.0313). The portions with the pathological tail sign had a significantly higher Ki-67 labeling index than those without this sign (p = 0.0313). Conclusions: More cellular portions of a myxofibrosarcoma correspond to more areas of the tumor showing aggressive features. Furthermore, our data also support the hypothesis of high aggressiveness being associated with the pathological tail sign in myxofibrosarcoma. To our knowledge, this is the first case report to describe comparisons among the imaging findings, histological features, and Ki-67 immunohistochemistry results for different portions of one myxofibrosarcoma. [ABSTRACT FROM AUTHOR]

The second most common type of malignant tumor worldwide is colorectal cancer. Histopathology image analysis offers crucial data for the clinical diagnosis of colorectal cancer. Currently, deep learning techniques are applied to enhance cancer classification and tumor localization in histopathological image analysis. Moreover, traditional deep learning techniques might loss integrated information in the image while evaluating thousands of patches recovered from whole slide images (WSIs). This research proposes a novel colorectal cancer detection network (CCDNet) that combines coordinate attention transformer with atrous convolution. CCDNet first denoises the input histopathological image using a Wiener based Midpoint weighted non-local means filter (WMW-NLM) for guaranteeing precise diagnoses and maintain image features. Also, a novel atrous convolution with coordinate attention transformer (AConvCAT) is introduced, which successfully combines the advantages of two networks to classify colorectal tissue at various scales by capturing local and global information. Further, coordinate attention model is integrated with a Cross-shaped window (CrSWin) transformer for capturing tiny changes in colorectal tissue from multiple angles. The proposed CCDNet achieved accuracy rates of 98.61% and 98.96%, on the colorectal histological image and NCT-CRC-HE-100 K datasets correspondingly. The comparison analysis demonstrates that the suggested framework performed better than the most advanced methods already in use. In hospitals, clinicians can use the proposed CCDNet to verify the diagnosis. [ABSTRACT FROM AUTHOR]

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer is a major worldwide health concern, underscoring the importance of early detection to enhance patient outcomes. Traditional histological analysis, while considered the gold standard, is labour intensive and manual. Deep learning (DL) is a potential approach, but existing models fail to extract all of the visual data required for successful categorization. This work overcomes these constraints by using ensemble models that mix different deep-learning architectures to improve classification performance for stomach cancer diagnosis. Using the Gastric Histopathology Sub-Size Images Database, the ensemble models obtained an average accuracy of more than 99% at various resolutions. ResNet50, VGGNet, and ResNet34 performed better than EfficientNet and VitNet, with the ensemble model continuously delivering higher accuracy. These findings show that ensemble models may accurately detect important characteristics from smaller picture patches, allowing pathologists to diagnose stomach cancer early and increasing patient survival rates. Gastric cancer has become a serious worldwide health concern, emphasizing the crucial importance of early diagnosis measures to improve patient outcomes. While traditional histological image analysis is regarded as the clinical gold standard, it is labour intensive and manual. In recognition of this problem, there has been a rise in interest in the use of computer-aided diagnostic tools to help pathologists with their diagnostic efforts. In particular, deep learning (DL) has emerged as a promising solution in this sector. However, current DL models are still restricted in their ability to extract extensive visual characteristics for correct categorization. To address this limitation, this study proposes the use of ensemble models, which incorporate the capabilities of several deep-learning architectures and use aggregate knowledge of many models to improve classification performance, allowing for more accurate and efficient gastric cancer detection. To determine how well these proposed models performed, this study compared them with other works, all of which were based on the Gastric Histopathology Sub-Size Images Database, a publicly available dataset for gastric cancer. This research demonstrates that the ensemble models achieved a high detection accuracy across all sub-databases, with an average accuracy exceeding 99%. Specifically, ResNet50, VGGNet, and ResNet34 performed better than EfficientNet and VitNet. For the 80 × 80-pixel sub-database, ResNet34 exhibited an accuracy of approximately 93%, VGGNet achieved 94%, and the ensemble model excelled with 99%. In the 120 × 120-pixel sub-database, the ensemble model showed 99% accuracy, VGGNet 97%, and ResNet50 approximately 97%. For the 160 × 160-pixel sub-database, the ensemble model again achieved 99% accuracy, VGGNet 98%, ResNet50 98%, and EfficientNet 92%, highlighting the ensemble model's superior performance across all resolutions. Overall, the ensemble model consistently provided an accuracy of 99% across the three sub-pixel categories. These findings show that ensemble models may successfully detect critical characteristics from smaller patches and achieve high performance. The findings will help pathologists diagnose gastric cancer using histopathological images, leading to earlier identification and higher patient survival rates. [ABSTRACT FROM AUTHOR]

Emerging Industry 5.0 designs promote artificial intelligence services and data-driven applications across multiple places with varying ownership that need special data protection and privacy considerations to prevent the disclosure of private information to outsiders. Due to this, federated learning offers a method for improving machine-learning models without accessing the train data at a single manufacturing facility. We provide a self-adaptive framework for federated machine learning of healthcare intelligent systems in this research. Our method takes into account the participating parties at various levels of healthcare ecosystem abstraction. Each hospital trains its local model internally in a self-adaptive style and transmits it to the centralized server for universal model optimization and communication cycle reduction. To represent a multi-task optimization issue, we split the dataset into as many subsets as devices. Each device selects the most advantageous subset for every local iteration of the model. On a training dataset, our initial study demonstrates the algorithm's ability to converge various hospital and device counts. By merging a federated machine-learning approach with advanced deep machine-learning models, we can simply and accurately predict multidisciplinary cancer diseases in the human body. Furthermore, in the smart healthcare industry 5.0, the results of federated machine learning approaches are used to validate multidisciplinary cancer disease prediction. The proposed adaptive federated machine learning methodology achieved 90.0%, while the conventional federated learning approach achieved 87.30%, both of which were higher than the previous state-of-the-art methodologies for cancer disease prediction in the smart healthcare industry 5.0. [ABSTRACT FROM AUTHOR]

AbstractAyurveda is one of the oldest systems of traditional medicine that provides treatments for a wide range of acute and chronic health problems. It is a common myth amongst people that Ayurvedic drugs have no side effects, whereas the fact is that these drugs can cause adverse effects. Despite their wide use, the safety data of many Ayurvedic formulations are still unavailable. Tapyadi loha is an Ayurvedic formulation traditionally claimed for iron deficiency anemia in pregnant and non-pregnant patients. However, no scientific study has been conducted to evaluate its oral toxicity. Hence, the present study evaluated the acute and subacute oral toxicity of the Tapyadi loha according to the OECD test guidelines 425 and 407, respectively. Tapyadi loha did not cause mortality nor any signs of toxicity when given once orally at a dose of 2000 mg/kg. Subacute toxicity study showed no mortality as well as no behavioral, hematological, biochemical and histopathological abnormalities in rats treated with Tapyadi loha formulation at 250, 500 and 1000 mg/kg for 28 days. It is concluded that the Tapyadi loha is safe at a single dose of 2000 mg/kg and 28 days repeated dose of 1000 mg/kg by oral route in rats. [ABSTRACT FROM AUTHOR]

In 2021, White Trevally or Striped Jack cultured in the western part of Japan exhibited mild, but chronic mortalities from late September through early October. The cumulative mortality rate was approximately 0.02% per a net pen containing approximately 50,000 fish. Although the cumulative mortality rate was not high, most of the fish in net pens showed characteristic gross signs and an abnormal swimming behaviour. The body of diseased fish became pale and the yellow lines on the lateral sides of fish body became darken. In addition, silver lines along the dorsal fin became apparent. Loss of schooling behaviour was noted during the mortality event. In addition, affected fish became lethargic and failed to swim against current, or frequently stopped swimming and sank to the bottom of net pens after feeding. The goal of this study was to identify the cause of the mortality event. To achieve the goal, we used histopathology and metatranscriptome analysis. Histopathological examination revealed that xenoma of microsporidian were frequently observed in the nerve axon in the brain and spinal cord. Spores observed in the sections were stained with a fluorescent dye, Uvitex 2B, indicating those spores are microsporidian. The data from metatranscriptome analysis indicated that the microsporidian is Spraguea sp. The microsporidian was frequently detected from diseased fish with similar symptoms collected in the same region, suggesting that the microsporidian was highly associated with abnormal swimming behaviour of fish. [ABSTRACT FROM AUTHOR]

Background: Stratipath Breast is a CE-IVD marked artificial intelligence-based solution for prognostic risk stratification of breast cancer patients into high- and low-risk groups, using haematoxylin and eosin (H&E)-stained histopathology whole slide images (WSIs). In this validation study, we assessed the prognostic performance of Stratipath Breast in two independent breast cancer cohorts. Methods: This retrospective multi-site validation study included 2719 patients with primary breast cancer from two Swedish hospitals. The Stratipath Breast tool was applied to stratify patients based on digitised WSIs of the diagnostic H&E-stained tissue sections from surgically resected tumours. The prognostic performance was evaluated using time-to-event analysis by multivariable Cox Proportional Hazards analysis with progression-free survival (PFS) as the primary endpoint. Results: In the clinically relevant oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patient subgroup, the estimated hazard ratio (HR) associated with PFS between low- and high-risk groups was 2.76 (95% CI: 1.63–4.66, p-value < 0.001) after adjusting for established risk factors. In the ER+/HER2- Nottingham histological grade (NHG) 2 subgroup, the HR was 2.20 (95% CI: 1.22–3.98, p-value = 0.009) between low- and high-risk groups. Conclusion: The results indicate an independent prognostic value of Stratipath Breast among all breast cancer patients, as well as in the clinically relevant ER+/HER2- subgroup and the NHG2/ER+/HER2- subgroup. Improved risk stratification of intermediate-risk ER+/HER2- breast cancers provides information relevant for treatment decisions of adjuvant chemotherapy and has the potential to reduce both under- and overtreatment. Image-based risk stratification provides the added benefit of short lead times and substantially lower cost compared to molecular diagnostics and therefore has the potential to reach broader patient groups. [ABSTRACT FROM AUTHOR]

Samples from the mesenteric lymph nodes (MS LNs) and ileocecal valves (ICV) of 105 goats, comprising 61 non-vaccinated and 44 vaccinated against Mycobacterium avium subspecies paratuberculosis (MAP), were collected at slaughter from a farm with a confirmed history of paratuberculosis (PTB). These goats had subclinical infections. PTB-compatible lesions in the MS LNs, ICV lamina propria (LP), and Peyer's patches (PPs) were graded separately. Furthermore, the load of acid-fast bacilli was quantified using Ziehl-Neelsen staining (ZN), MAP antigens by immunohistochemistry (IHC), and MAP DNA by PCR targeting the IS900 sequence. Gross PTB-compatible lesions were found in 39% of the goats, with 31.72% vaccinated (V) and 68.29% non-vaccinated (nV). Histopathological lesions inducedMAP were observed in 58% of the animals, with 36.07% vaccinated and 63.93% non-vaccinated. The inclusion of histopathology as a diagnostic tool led to a 28% increase in diagnosed cases in MS LNs and 86.05% in ICV. Grade IV granulomas with central mineralization and necrosis were the most common lesions in MS LNs. In the ICV, mild granulomatous enteritis with multifocal foci of epithelioid macrophages was predominant, occurring more frequently in the PPs than in the LP. Furthermore, statistical differences in the presence of histopathological lesions between vaccinated and non-vaccinated goats were noted in MS LNs, ICV LPs, and ICV PPs. Non- vaccinated animals showed higher positivity rates in ZN, IHC, and PCR tests, underscoring the benefits of anti-MAP vaccination in reducing PTB lesions and bacterial load in target organs. Our findings emphasize the necessity of integrating gross and histopathological assessments with various laboratory techniques for accurate morphological and etiological diagnosis of PTB in both vaccinated and non-vaccinated goats with subclinical disease. However, further studies are required to refine sampling protocols for subclinical PTB in goats to enhance the consistency of diagnostic tools. [ABSTRACT FROM AUTHOR]

The ability of algae to decolorize and remove synthetic dyes such as Congo red, methylene blue, rhodamine B, and remazol black dyes was investigated in this study. The tested algae showed increased efficiency for color degradation observed by UV spectral analysis. Chlorococcum sp. exhibited a very drastic reduction in absorbance on the 5th day, and the laccase enzyme production was also higher (533 U/ml) in Congo red treatment. The other tested dyes also showed limited degradation, but their absorbance dropped only after 10 days of treatment. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed a significant shift in functional groups of control and treated samples. Furthermore, the Clarias gariepinus fish was acclimatized and was preceded for dye treatment. In the toxicity assessment of Congo red, the mortality rate of 100% was observed on the 8th day, whereas the algae-treated dye at 2 ppm showed only 40% mortality on the 20th day. Histopathological observations of the liver and kidney from sacrificed fishes revealed intense cellular damage in higher concentrations. In the experimental studies, 6 ppm of the dye had the least toxicity to tested fish cells (kidney and liver). The uniqueness and significance of the present investigation was to evaluate the toxicity of various concentrations of Congo red dye on fish by performing histological studies of internal organs, which made Chlorococcum sp. a potential candidate for dye effluent treatment. From the present study, it is evident that the investigated microalgae may serve as a better tool for industrial applications in safe toxicant removal from aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Trace metal pollution of soils is a widespread consequence of anthropogenic activity. Land slugs can be used as bio-indicators of the metals' pollution in the soil, so the present study aimed to determine the metal in the soil and Laevicaulis stuhlmanni land slug tissues by studying its effects on different physiological parameters. Slugs and soil samples were collected from fields in Abu-Rawash, Giza, Egypt. Slugs were identified, and the metals were determined in slug tissues and soil samples. On the other hand, slugs were reared in the laboratory and the new generation was fed on lettuce dipped in 0.027 µg/ml lead (Pb) for 10 days. The results revealed that the soil and slug tissues contained copper, manganese, lead, and zinc; the lead metal bioaccumulation factor was the highest. Also, the results showed that the hemocytes' count, testosterone, and estradiol hormones were significantly decreased. At the same time, the phagocytic index was increased considerably, and some morphological alterations in the granulocytes and hyalinocytes were observed after treatment with 0.027 µg/ml lead compared to untreated slugs. On the other hand, all the oxidative stress parameters were significantly increased in the treated slugs compared with the control. Concerning the histopathological studies, lead caused a rupture, vacuolation, or degeneration in the digestive cells of treated slugs. Finally, it can be concluded that the land slugs were sensitive to lead which was reflected by endocrine disruption, immunotoxicity, and increased oxidative stress parameters with histopathological damages. Hence, Laevicaulis stuhlmanni can be used as a metal accumulation bio-indicator to reflect the metal pollution in the soil. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the effectiveness of ultrasound criteria, TI-RADS score, and elastography in distinguishing benign thyroid nodules from malignant ones, as a substitute for invasive diagnostic procedures. Although the minority of thyroid nodules is malignant, invasive diagnostic procedures are often necessary. Methods: In this prospective study, a total of 104 thyroid nodules were assessed using fine-needle aspiration cytology. The euthyroid state of the patients was ensured. Conventional ultrasound and shear wave elastography (SWE) were performed by a single experienced operator. Final postoperative histopathologic findings were compared to conventional ultrasound and elastography findings. Results: SWE elasticity indices (EIs) were found to be significantly higher in malignant nodules than benign ones (p < 0.05). Combined results of both TI-RADS and SWE increased the sensitivity of detection of malignant nodules. Conclusion: Combined SWE and TI-RADS could enhance the diagnostic accuracy in differentiating thyroid nodules by leveraging their complementary strengths. [ABSTRACT FROM AUTHOR]

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade = 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of = 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 = 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy. [ABSTRACT FROM AUTHOR]

Introduction: Net biofouling has a significant impact for the global salmon industry in the seawater grow-out stage in terms of its management. Current mitigation strategies occur primarily through the regular removal of biofouling using in situ cleaning. While in situ net cleaning is effective there is uncertainty as to whether the equipment or dispersed material has an impact upon the fish in the cages. Through direct contact with the environment, the significant surface area of the gill including its microbiome is directly exposed to the acute environmental changes generated by net cleaning. This study aimed to provide a detailed understanding of the impact of in situ net cleaning on Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) gill health. Methods: Three field trials were conducted on commercial fish farms in western Norway. Fouling organisms on net pens and flushed particles during in situ cleaning were identified and screened for major fish pathogens. Hydrographic profile measurements were performed to measure the impact on water quality. Gill samples were examined for histopathological changes, immune gene expression, and the prevalence of major pathogens. 16S rRNA amplicon sequencing was employed to explore the impact of net cleaning on gill microbiome. Results and discussion: Data obtained from these trials identified a diversity of fouling species including hydroids, algae, skeleton shrimps, and filter feeders on net pens, a direct impact on measured water quality indicators, a moderate change in gill inflammatory and antigen presentation activity at the level of mRNA, and a large significant change in gillmicrobiome. Observed changes in gill microbial community involved a decrease in bacterial richness coupled to an increase in identified bacterial genera related to negative health consequences. Parallel analyses for pathogens load in biofouling organisms and flushed particles highlighted the presence of several fish bacteria and parasites. However, minor changes were detected in salmon gill pathogen diversity and loading. Our results suggest that biofouling organisms may actas transient reservoirs for somefishpathogensbutnotvirusesandthatgillmicrobial dysbiosis could be related to the host stress response during and post net cleaning. [ABSTRACT FROM AUTHOR]

In the field of biomedical research, rats are widely used as experimental animals due to their short gestation period and strong reproductive ability. Accurate monitoring of the estrous cycle is crucial for the success of experiments. Traditional methods are time-consuming and rely on the subjective judgment of professionals, which limits the efficiency and accuracy of experiments. This study proposes an EfficientNetmodel to automate the recognition of the estrous cycle of female rats using deep learning techniques. The model optimizes performance through systematic scaling of the network depth, width, and image resolution. A large dataset of physiological data from female rats was used for training and validation. The improved EfficientNet model effectively recognized different stages of the estrous cycle. The model demonstrated high-precision feature capture and significantly improved recognition accuracy compared to conventional methods. The proposed technique enhances experimental efficiency and reduces human error in recognizing the estrous cycle. This study highlights the potential of deep learning to optimize data processing and achieve high-precision recognition in biomedical research. Future work should focus on further validation with larger datasets and integration into experimental workflows. [ABSTRACT FROM AUTHOR]

Background: Urolithiasis is a painful condition and current treatment doesn't assure the prevention of recurrence. This research aims to demonstrate the scientific reliability of Chloroform leaf extract of Flemingia Strobilifera R.Br. (CEFS) for antiurolithiatic activity using ethylene glycol-induced urolithiasis model. Results: Ethylene glycol (EG) was used to induce hyperoxaluria in male Wistar rats. The rats were grouped into 7-groups containing six each. Group I and II served as negative and positive control, group III received standard treatment, whereas Group IV to VII served as testing groups. CEFS of 30 mg/kg body-weight and 60 mg/kg body-weight was used as a preventive and curative regimen. The urine biochemistry was analysed for the presence of calcium, magnesium, phosphate, and oxalate. The rats were sacrificed for histopathological examination and LDH detection. The 24-hours urine volume was increased in both EG-treated groups as well as CEFS-treated groups, indicating the diuretic activity of plant. CEFS dose-dependently inhibited urine excretion of phosphate, calcium, and oxalate compared to the positive-control group. The histopathological examination of CEFS-treated rats' kidneys had reduced loss of renal structure and lessened deposition of calcium oxalate crystals. Conclusion: CEFS exhibited significant antiurolithiatic activity by reducing supersaturation of urine and excretion of stone forming components. [ABSTRACT FROM AUTHOR]

To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves. [ABSTRACT FROM AUTHOR]

Lung and colon cancers are leading contributors to cancer-related fatalities globally, distinguished by unique histopathological traits discernible through medical imaging. Effective classification of these cancers is critical for accurate diagnosis and treatment. This study addresses critical challenges in the diagnostic imaging of lung and colon cancers, which are among the leading causes of cancer-related deaths worldwide. Recognizing the limitations of existing diagnostic methods, which often suffer from overfitting and poor generalizability, our research introduces a novel deep learning framework that synergistically combines the Xception and MobileNet architectures. This innovative ensemble model aims to enhance feature extraction, improve model robustness, and reduce overfitting. Our methodology involves training the hybrid model on a comprehensive dataset of histopathological images, followed by validation against a balanced test set. The results demonstrate an impressive classification accuracy of 99.44%, with perfect precision and recall in identifying certain cancerous and non-cancerous tissues, marking a significant improvement over traditional approach. The practical implications of these findings are profound. By integrating Gradient-weighted Class Activation Mapping (Grad-CAM), the model offers enhanced interpretability, allowing clinicians to visualize the diagnostic reasoning process. This transparency is vital for clinical acceptance and enables more personalized, accurate treatment planning. Our study not only pushes the boundaries of medical imaging technology but also sets the stage for future research aimed at expanding these techniques to other types of cancer diagnostics. [ABSTRACT FROM AUTHOR]

Context Aims Materials and Methods Results Conclusion The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non‐proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories – inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system.The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters.All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated.Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non‐PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system.Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases. [ABSTRACT FROM AUTHOR]

Worldwide, particularly in developing nations, helminth infections are the leading causes of livestock illness and mortality. Parascaris (P.) equorum, a parasitic worm from the Ascarididae family, significantly impacts the production, health, and working performance of equines. This study aimed to investigate the impact of intraperitoneal sensitization of P. equorum on the immune system, oxidative stress, and histology in Wistar rats. After acclimatization for 7 days, we divided the rats into five groups, each consisting of six rats. Group I, serving as the control, was administered distilled water, followed by groups II (day 7), III (day 14), IV (day 21), and V (day 33). The rats were euthanized every day mentioned (Days 7–33). On day 0, a dosage of 1ml/100 gm rat (containing 500 μg/ml protein content) emulsified crude antigen extract with an incomplete Freund's adjuvant (1:1 volume), followed by a second dose of the same antigen concentration on day 7. To assess the allergenicity of this nematode, we measured a whole blood profile, serum levels of IFN-γ, IL-5, IL-10, IL-13, and IL-33, total immunoglobulins IgE and IgG, and oxidative stress markers. Also, we examined histological changes in the liver, kidney, and spleen. The results showed that values of total leukocyte count, granulocytes, monocytes, and lymphocytes were significantly (P < 0.05) increased on day 14 post-infection relative to other days of investigation. It was found that the levels of total immunoglobulins (IgE and IgG) and cytokines (INF-γ, IL-5, IL-13, and IL-33) on days 14 and 21 were significantly higher than in the control group. At all periods of the experiment, the injected group exhibited significantly higher concentrations of MDA and NO compared to the control group (P < 0.05). Conversely, GSH and CAT levels (P < 0.05) dropped significantly on days 7, 14, and 21. Different rat tissues showed alterations. Ultimately, this study described the detrimental effects of P. equorum crude antigen administration on the immune system, oxidative states, and histological changes of Wistar rats at various intervals. [ABSTRACT FROM AUTHOR]

Introduction: Vibrio alginolyticus is a Gram-negative, rod-shaped bacterium belonging to the family of Vibrionaceae, a common pathogen in aquaculture animals, However, studies on its impact on Scylla serrata (mud crabs) are limited. In this study, we isolated V. alginolyticus SWS from dead mud crab during a disease outbreak in a Hong Kong aquaculture farm, which caused up to 70% mortality during summer. Methods: Experimental infection and histopathology were used to investigate the pathogenicity of V. alginolyticus SWS in S. serrata and validate Koch's postulates. Comprehensive whole-genome analysis and phylogenetic analysis antimicrobial susceptibility testing, and biochemical characterization were also performed. Results: Our findings showed that V. alginolyticus SWS caused high mortality (75%) in S. serrata with infected individuals exhibiting inactivity, loss of appetite, decolored and darkened hepatopancreas, gills, and opaque muscle in the claw. Histopathological analysis revealed tissue damage and degeneration in the hepatopancreas, gills, and claw muscle suggesting direct and indirect impacts of V. alginolyticus SWS infection. Conclusions: This study provides a comprehensive characterization of V. alginolyticus SWS as an emerging pathogen in S. serrata aquaculture. Our findings underscore the importance of ongoing surveillance, early detection, and the development of targeted disease management strategies to mitigate the economic impact of vibriosis outbreaks in mud crab aquaculture. [ABSTRACT FROM AUTHOR]