Ovarian tumors in mares are not common in comparison to other neoplasms and are divided into three categories: gonadal stromal tumors, coelomic epithelium surface tumors, and germinative cell tumors [12]. Some ovarian neo-plasms histologically show a mixture of multiple cell types in the same tumor, such as fibrothecoma, therefore the dif-ferentiation between fibroma and thecoma is often difficult [1]. According to World Health Organization, fibrothecoma is classified as sex cords stromal tumor (pure stromal tumor) [13]. Neoplasms, such as fibrothecoma have a very scarce morphology, clinical signs, ultrasonographic view and endocrine profile. To diagnose this type of tumor, a broad clini-cal examination is needed, but histopathology remains the most accurate. Herein, we report a case of incidentally found ovarian fibrothecoma during diagnostic laparotomy in 6-year-old KWPN mare which was presented to the clinic with colic symptoms. After unilateral ovariectomy, the altered right ovary, based on histopathological features was diag-nosed as fibrothecoma.

The giant anteater (Myrmecophaga tridactyla) is a vulnerable specie from Central and South America and is considered extinct in Belize, Guatemala, El Salvador, and Uruguay. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of their female reproductive tissues. We collected tissue samples from six female giant anteaters, and performed gross, morphological, and histochemical analyses. Five adult and one young subjects were enrolled in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

Environmental pollution is one of today's main ecological and social concerns. Among these pollutants are the heavy metals present in the burning of fossil fuels, mining, smelting of metallic minerals, fertilizers and pesticides. Billions of tons of heavy metals are emitted every year from industrial chimneys and sewers, contaminating the hydrosphere and polluting rivers, lakes and seas. In this context, freshwater fish are the most affected due to their proximity to the source of contamination and are therefore used as bioindicators in assessing environmental impact following exposure to metals. However, our understanding of the effects of heavy metals on detoxification organs - such as the liver and gills - in freshwater fish in situ is still limited. Therefore, we conducted a systematic review to determine the main changes and mechanisms involved in morphological modifications in the liver and gills of cichlid fish following exposure to heavy metals in situ. Based on a structured search, 36 original articles were selected from the PubMed and SCOPUS databases. The selection of studies and the identification of duplicates were identified by Rayyan, and the study selection process was presented in the PRISMA statement diagram. Bias analysis was carried out using the Software Review Mananger (RevMan) 5.3, from the Cochrane Collaboration. Thirty-six studies were selected which showed negative effects attributed to environmental contamination by heavy metals, ranging from bioaccumulation to morphophysiological alterations. Almost all the heavy metals analyzed were found in the liver and gill tissues, especially cadmium, copper, lead, zinc, iron and manganese. In view of the continuous morphophysiological changes identified in the liver and gill studies, it is possible to state that bioaccumulation analyses, combined with these configurations, are emerging as crucial tools for assessing and guiding environmental monitoring. This approach aims not only to preserve but also to strengthen the integrity of the aquatic ecosystem and the ichthyofauna.

Lichen Amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm or thigh. It is associated with itching and Atopic Dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids and phototherapy, but in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in LA related to AD and led to clinical and quality of life improvement in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in skin lesions after discontinuation, and the safety of long-term application.

Pesticides are among the most widely used synthetic chemicals worldwide to protect crops, but besides being beneficial, they pose several environmental and health issues. The present study evaluates toxic effects of acetamiprid (ACMP) in rat liver and kidney tissues. Rats were exposed to ACMP (21.7 mg/kg b.wt; 1/10th LD50) for 21 days. Oxidative stress generation, apoptotic progression, and structural changes were evaluated via biochemical assays, semi-quantitative PCR, western blotting, and histopathology. ACMP exposure significantly decreased body weight and altered relative organ weight in hepato-renal tissues. Significant oxidative stress was evident by increased oxidative injuries to lipids and proteins and alterations of endogenous anti-oxidative enzymes. The administration of ACMP upregulated mRNA expression of Bax and caspase-3, while downregulated the mRNA expression of Bcl-2 and released cytochrome c into the cytosol of the liver and kidney tissues. Likewise, exposure to ACMP caused severe degenerative changes in the histo-architecture of hepato-renal tissues. The results of the present study confirmed the toxicity of ACMP in rats’ liver and kidney tissues and emphasized the need for strict regulation and more mechanistic understanding to delineate the toxicity of ACMP in mammals.

“Severe acute respiratory syndrome” (SARS) due to Coronavirus (SARS-CoV) infection is a known cause of death. Sometimes demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flue-like symptoms. In this dobtfull cases the forensic pathologist could be requested to define cause of death occurred outside hospital. In this report the authors describe two thorough autopsied cases of SARS-CoV-2 related deaths occurred suddenly at home and not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.

Introduction: The aim of this study is to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. Material and Methods: Prospective case-control study. Data collection period was between May 2020-2022. 80 tracheostomies on patients with long intubation were performed and the resected tracheal ring was examined by standard microscopy. 40 consecutive tracheotomies in COVID-19 patients and 40 in patients without COVID-19 disease were carried out. Results: The mean age was 68.18 years in the COVID group and 56.1 years in the NO COVID group. The male/female ratio was 32/8 versus 29/11 respectively. No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented vasculitis (2,5%) and one case thrombotic microangiopathy (1,2%), all cases in the COVID group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2=0.779) no significant indices for measuring association (Rho= 0.1316) and no significant risk indices (RR = 1.8, OR=2.032, PAR= 44%). Conclusion: There is no evidence of increased risk of histopathological findings of the resected tracheal ring in patients with long intubation and COVID-19 disease.

Bifenthrin is a synthetic pyrethroid insecticide. It is used worldwide against different agricultural pests. Nervous system (NS) is the primary target organ for the pyrethroid group of insecticide which causes hyper excitation. The aim of this study to determine the effects of bifenthrin on the brain of rabbits. The animals were treated for 14 days with three different doses (1/5th, 1/10th and 1/15th of LD50) of bifenthrin. Neurotransmitters and Histopathological alterations were observed at the end of the experiments. Neurochemical parameters were checked 24 hours after the last dose. Significant changes in the level of biogenic amines were observed. The levels of epinephrine (EPN), dopamine (DA), 3, 4 dihydroxyphenylacetic acid (DOPAC) were decreased as compared to controls group with the increase in insecticide. However, norepinephrine (NE) and homovanillic acid (HVA) levels were found to be significantly higher than those of the controls. A significant reduction in the activity of the acetyl cholinesterase enzyme was found in the frontal cortex’s erythrocyte, plasma and brain of rabbit with the increase in administered bifenthrin. The oxidative stress showed significantly decrease in the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione S- transferase (GST) with the increase in dose of bifenthrin. Histopathological study of brain tissues showed normal GC (glial cells) and NC (neuronal cells) in the frontal cortex of brain tissue of control groups while the treated groups showed evacuation (odema), elongation of pyramidal nucleus, glial cell damage and brain haemorrhage.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analyzed, among the arboviruses studied, the hepatic involvement in cases of YF showed greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis and apoptosis were classified as degree of tissue damage from severe to very severe. The pathological abnormalities associated with infection by YFV, DENV, and CHIKV showed predominance of changes in the midzonal area. We also noted that in among of the arboviruses studied, liver involvement in cases of YFV infection was more intense.

In the present study, fish were exposed to sub-lethal doses of CuONPs (68.92 ± 3.49 nm) (10, 20, and 50 mg/L) for a long exposure period (25 days). Compared to the control group (0.0 mg/L CuONPs), a significant dose-dependent elevation in blood urea and creatinine values, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase enzyme activities were evident in CuONPs-exposed groups (P < 0.05). Fish exposure to 50 mg/L CuONPs significantly upregulated the transcription of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin 12, and interleukin 8), heat shock protein 70, apoptosis-related gene (caspase 3), and oxidative stress-related (superoxide dismutase, catalase, and glutathione peroxidase) genes in liver and gills of the exposed fish in comparison with those in the control group (P < 0.05). Moreover, varying histopathological injuries were noticed in the hepatopancreatic tissues, posterior kidneys, and gills of fish groups correlated to the examined exposure dose of CuONPs. In summary, our results provide new insights and helpful information for better understanding the mechanisms of CuONPs toxicity in Nile tilapia at hematological, molecular levels, and tissue levels.

Background: Lung cancer is one of the common causes of death worldwide. Although the incidence rate of lung cancer in Western countries is decreasing, it presents a growing trend in developed countries. Since there is no accurate enough information about the epidemiological and Histopathologic features of lung cancer in central Iran, Isfahan, we were motivated to conduct this research. Materials and Methods: This was a descriptive, cross-sectional study carried out in central Iran, Isfahan. All demographic, histopathological and clinical data of the lung cancer patients registered in MACSA, a referral charity-based cancer center in central Iran, was analyzed within 2012-2018 using SPSS v.22 software. Results: Altogether 260 patients with lung cancer were included in this study from 6127 cancer patients registered within 2012-2018 (4.2%). Out of them, 66.2% were men, and 18.8 % of the patients were alive at the time of the study. The mean age of the patients at diagnosis was 61.56 (SD=14.11, range: 9-93). Altogether, 63.1% of patients had metastasis of whom 57.6% were in stage IV at diagnosis. The Frequency of different types of lung cancer was 36.9% adenocarcinomas, 14.2% squamous cell carcinoma, 9.6% bronchogenic carcinoma and 8.1% small cell lung cancer, respectively. Altogether, 128 cases were smokers with an average 35.45 ± 14 pack- years. Only in 36.2% of the patients, the diagnostic and therapeutic biomarkers had been checked, and CK7 was positive in 88.9% of the cases in which the biomarker had been checked. Conclusion: Despite to similar Iranian studies, the most common histopathologic type of lung cancer among the patients was adenocarcinoma that it may be attributed to the lower consumption of smoking in our population and their different genetic context. Molecular biomarkers had been checked in a small portion of the patients. More education of the clinicians along with the development of cancer molecular testing may lead to promote the personalized-based approach.

Generalised Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria that can be used to design affordable subunit vaccines. GMMA are highly immunogenic and capable to induce an optimal antigen-specific humoral immune response both in animals and humans. Despite their potent immunogenicity, GMMA are usually formulated with aluminum salts (Alum) to reduce their potential systemic reactogenicity. GMMA, in fact, contain agonists of Toll-Like Receptor 4 (TLR4) and TLR2 that possess pro-inflammatory activity. The adsorption of GMMA onto Alum is believed to reduce their systemic exposure. However, it has been found that GMMA formulated without Alum did not induce concerning signs of systemic reactogenicity in the rabbit model. Here we asked whether GMMA promote local reactogenicity. We immunized mice intramuscularly with GMMA alone or formulated with Alum and we analyzed the injection site during 7 days after treatment. We found that GMMA alone promoted only mild inflammation within the muscle, whereas Alum induced severe muscle inflammation, as expected. Thus, in the mouse model, GMMA demonstrated to possess mild reactogenic potential locally, while Alum is confirmed a major driver of local reactogenicity. Our results further support the idea to investigate the reactogenicity of GMMA formulated without Alum in clinical studies.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

African Swine Fever (ASF) poses a significant threat to domestic pig populations worldwide. This study investigates the histopathological alterations in confirmed ASF-positive domestic pigs, focusing on over 100 cases from 2018 to 2021. Biological material from 118 pigs, confirmed ASF-positive via PCR examination, was histopathologically examined. Tissue samples from various organs were processed, embedded, and analyzed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was employed to detect the major capsid protein (p72) of the ASF virus.Histological examination revealed characteristic ASF lesions, including severe hemorrhages, lymphoid depletion, and inflammatory infiltrates. Vascular anomalies leading to hemorrhagic events were widespread. Microthromboses were prevalent in lymph nodes and kidneys. IHC detected p72 in various organs, with tonsils consistently showing the highest viral presence.This comprehensive study underscores the pivotal role of lymph nodes, spleen, and kidneys in ASF pathogenesis, highlighting prominent vascular involvement and hemorrhagic manifestations. The study establishes the efficacy of IHC in detecting ASF virus, even in autolyzed tissue samples. Tonsils emerge as a consistent epicenter of viral presence, shedding light on the intricate pathogenesis of ASFV.

Preeclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) in later life. Postpartum cardiovascular risk screening could identify patients who would benefit most from lifestyle interventions. However, there are no readily available methods to identify these high-risk women. We propose that placental lesions may be useful in this regard. Here, we sought to determine the association between placental lesions and lifetime CVD risk. Placentas from 85 PE women were evaluated for histopathological lesions. At 6 months postpartum, a lifetime cardiovascular risk score was calculated. Placental lesions were compared between CVD risk groups and the association was assessed using odds ratios. Multivariable logistic regression was used to develop prediction models for CVD risk with placental pathology. Placentas from high-risk women had more severe lesions of maternal vascular malperfusion (MVM) and resulted in a 3-fold increased risk of screening high-risk for CVD (OR 3.10[1.20-7.92]) compared to women without these lesions. MVM lesion severity was moderately predictive of high-risk screening (AUC 0.63[0.51,0.75]; sensitivity 71.8%[54.6,84.4]; specificity 54.7%[41.5,67.3]. When clinical parameters were added, the model’s predictive performance improved (AUC 0.73[0.62,0.84]; sensitivity 78.4%[65.4,87.5]; specificity 51.6%[34.8,68.0]. The results suggest that placenta pathology may provide a unique modality to identify women for cardiovascular screening.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND). ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease egg productions, mortality, and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading to overall decreased growth rate. In this study, we report the damage caused by the NDV infection in the pancreatic tissues of vaccinated as well as specific pathogen free chickens. The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

Gastric cancer has become a serious worldwide health concern, emphasizing the cru-cial importance of early diagnosis measures to improve patient outcomes. While tradi-tional histological image analysis is regarded as the clinical gold standard, it is la-bor-intensive and manual. Recognizing this problem, there has been a rise in interest in using computer-aided diagnostics tools to help pathologists with their diagnostic ef-forts. 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 exten-sive visual characteristics for correct categorization. To tackle this limitation, this study proposes the use of ensemble models, which incorporate the capabilities of sev-eral deep learning architectures and use aggregate knowledge of many models to im-prove classification performance, allowing for more accurate and efficient gastric cancer detection. To see how well these proposed models performed, this study com-pared them to other works, all of which were based on the Gastric Histopathology Sub-size Images Database, a publicly available dataset for gastric cancer. This research demonstrated that the ensemble models achieved 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%, high-lighting 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 showed that ensemble models may successfully detect criti-cal 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.

Background: Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. Methods: it is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (from February 2020 to February 2024). Results: We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12 – 70 years) with a slight female predominance (sex ratio = 1.16). Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4 – 8 cm). All cases were well-circumscribed solid (7/13 cases, 53.8%) or solido-cystic whitish nodules (6/13 cases, 46.2%). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Conclusions: Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms. Also, PN are often diagnosed as malignant tumors by clinicians before histopathological analysis.

Cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a Thoracic Pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and 15 culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, p=0.19), a history of hematopoietic cell transplant (80% vs. 53%, p=0.31), severe lymphopenia (absolute lymphocyte count ≤500/µL, 100% vs. 73%, p=0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, p=0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, p=0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.

Histological evidence of active prosthetic valve endocarditis (PVE) in cardiac valve tissue is widely regarded as a criterion established by Duke to confirm the presence of this condition, although the histological characteristics of mechanical prosthetic valve endocarditis have not yet been definitively established. The primary objective of this study was to determine the histologic differences in mechanical PVE in individuals with either early- or late-onset PVE, with the aim of distinguishing the unique aspects of this rare condition. Histological analysis of mechanical cardiac valve tissue was conducted in 27 patients who underwent surgical valve removal, comprising individuals with early onset and late-onset PVE. The findings were compared between the two groups. Histopathologically, PVE in individuals with mechanical heart valves is typically associated with the formation of vegetation and considerable neutrophil-rich infiltrates. In cases of early onset PVE, the affected valve tissue displays intense inflammation predominantly consisting of lymphocytes. In contrast, valve tissue samples from patients with late-onset PVE exhibit extensive fibrosis and inflammation, comprising macrophages, which are specialized immune cells and calcifications.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2. In a separate study, we reported that these compounds were non-toxic to Balb/C mice at 50 mg/kg suggesting their utility in in vivo studies. In the present study, we aimed to determine the therapeutic potential of these compounds by testing them in A375 cell-line derived xenograft in nu/nu mice. Animals were randomized into four groups (n=12/group) to receive subcutaneous administration of vehicle, 10 mg/kg vemurafenib, and 25 mg/kg 2155-14 and 2155-18 three times per week for 15 days along with a control group. The results revealed that both 2155-14 and 2155-18 significantly decreased the growth of A375 tumors, which was comparable to vemurafenib. These results were confirmed by tumor volume, weight, and histopathological examination. In conclusion, these results suggest a therapeutic potential of targeting spliceosomal proteins hnRNPH1 and H2.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

Breast cancer is among the most common and fatal diseases for women, and no permanent treatment has been discovered. Thus, early detection is a crucial step to control and cure breast cancer that can save the lives of millions of women. For example, in 2020, more than 65% of breast cancer patients were diagnosed in early-stage of cancer, from whom all survived cancer. Although early detection is the most effective approach for cancer treatment, breast cancer screening conducted by radiologists is very expensive and time-consuming. More importantly, conventional methods of analyzing breast cancer images suffer from high false detection rates. Different breast cancer imaging modalities are used to extract and analyze the key features affecting diagnosis and treatment of breast cancer. These imaging modalities can be divided into subgroups such as mammograms, ultrasound, magnetic resonance imaging, histopathological images, or any combination of them. Radiologists or pathologists analyze images produced by these methods manually that leads to increase the risk of wrong decisions for cancer detection. Thus, utilization of new automatic methods to analyze all kinds of breast screening images to assist radiologists to interpret images is required. Recently, artificial intelligence (AI) has been widely utilized to automatically improve the early detection and treatment of different types of cancer, specifically breast cancer, thereby enhancing the survival chance of patients. Advances in AI algorithms, such as deep learning, and availability of datasets obtained from various imaging modalities have opened an opportunity to surpass limitations of current breast cancer analysis methods. In this article, we first review breast cancer imaging modalities, and their strengths and limitations. Then, we explore and summarize the most recent studies that employed AI in breast cancer detection using various breast imaging modalities. In addition, we report available datasets on the breast cancer imaging modalities which are important in developing AI-based algorithms and training deep learning models. In conclusion, this review paper tries to provide a comprehensive resource to help researchers working in breast cancer imaging analysis.

Studies have shown that STK11 mutation plays a critical role in affecting the lung adenocarcinoma (LUAD) tumor immune environment. By training an Inception-Resnet-v2 deep convolutional neural network model, we were able to classify STK11-mutated and wild type LUAD tumor histopathology images with a promising accuracy (per slide AUROC=0.795). Dimensional reduction of the activation maps before the output layer of the test set images revealed that fewer immune cells were accumulated around cancer cells in STK11-mutation cases. Our study demonstrated that deep convolutional network model can automatically identify STK11 mutations based on histopathology slides and confirmed that the immune cell density was the main feature used by the model to distinguish STK11-mutated cases.

African swine fever (ASF) has evolved from an exotic animal disease to a threat to global pig production. An important avenue for wide-spread transmission of animal diseases is the dissemination of viruses through boar semen used for artificial insemination (AI). In this context, we investigated the role of male reproductive organs in ASF. Mature domestic boars and adolescent wild boar inoculated with different ASF virus strains were investigated by means of virological and pathological methods. Additionally, electron microscopy was employed to investigate in vitro inoculated sperm. Viral genome, antigen and infectious virus could be found in all gonadal tissues and accessory sex glands. The viral antigen and viral mRNAs were mainly found in mononuclear cells of the respective tissues. However, some other cell types, including Leydig, endothelial and stromal cells were also found positive. Using RNAScope, p72 mRNA could be found in scattered halo cells of the epididymal duct epithelium which could point to disruption of the barrier. No direct infection of spermatozoa was observed by immunohistochemistry or electron microscopy. Taken together, our results strengthen the assumption that ASFV can be transmitted via boar semen. Future studies are needed to explore excretion dynamics and transmission efficiency.

Deep learning techniques, such as convolutional neural networks (CNN), generative adversarial networks (GAN), and graph neural networks (GNN), have over the past decade changed the ac-curacy of prediction in many diverse fields. In recent years, the application of deep learning tech-niques in computer vision tasks in pathology demonstrated extraordinary potential in assisting clinicians, automating diagnosis, and reducing costs for patients. Formerly unknown pathologi-cal evidence, such as morphological features related to specific biomarkers, copy number varia-tions, and other molecular features, were also able to be captured by deep learning models. In this paper, we review popular deep learning methods and some recent publications about their appli-cations in pathology.

Endemically infected European wild boar are considered a major reservoir of African swine fever virus in Europe. While high lethality was observed in the majority of field cases, strains of moderate virulence occurred in the Baltic States. One of these, “Estonia 2014”, led to a higher number of clinically healthy, antibody-positive animals in the hunting bag of North-Eastern Estonia. Experimental characterization showed high virulence in wild boar but moderate virulence in domestic pigs. Putative pathogenic differences between wild boar and domestic pigs are unresolved and comparative pathological studies are limited. We here report on a kinetic experiment in both subspecies. Three animals each were euthanized at 4, 7 and 10 days post infection (dpi). Clinical data confirmed higher virulence in wild boar although macroscopy and viral genome load in blood and tissues were comparable in both subspecies. The percentage of viral antigen positive myeloid cells tested by flow cytometry did not differ significantly in most tissues. Only immunohistochemistry revealed consistently higher viral antigen loads in wild boar tissues in particular 7 dpi, whereas domestic pigs already eliminated the virus. The moderate virulence in domestic pigs could be explained by a more effective viral clearance.

Diabetic cardiac autonomic neuropathy (DCAN) is a severe complication of type 1 diabetes mellitus (T1DM) characterized by autonomic nerve fiber dysfunction in the heart and blood vessels. This study aimed to elucidate the histopathological mechanisms underlying DCAN and evaluate the therapeutic potential of MCC950, an NLRP3 inflammasome inhibitor, in a Wistar rat model. Male Wistar rats were divided into control and T1DM groups, with diabetes induced by streptozotocin (STZ) injection. Following confirmation of DCAN through elevated serum noradrenaline levels, diabetic rats were subdivided into positive control (insulin-treated), treatment (MCC950), and untreated groups. The stellate ganglia, thoracic aorta, and left ventricle were dissected for histological examination using Haematoxylin and Eosin (H&E) and Masson Trichrome staining. STZ-induced hyperglycemia was evident by Week 2 and sustained throughout the study. Serum noradrenaline levels significantly increased by Week 14 in diabetic rats, indicating DCAN onset. Histological analysis revealed atrophy in stellate ganglia, endothelial damage in the thoracic aorta, and myocardial fibrosis in untreated diabetic rats. MCC950 treatment preserved ganglionic structure, mitigated vascular damage, and reduced myocardial fibrosis, demonstrating its potential in attenuating DCAN progression. These findings highlight MCC950 as a promising therapeutic agent for DCAN by targeting inflammation and preserving autonomic and cardiovascular function. Further investigations are warranted to validate MCC950’s efficacy in human trials, with the potential to improve clinical outcomes for T1DM patients at risk of DCAN.

Macrobrachium rosenbergii is a valuable freshwater prawn in Asian aquaculture. In recent years, a new symptom that was generally called as ‘white head’ caused high mortality in M. rosenbergii farms in China. Samples of M. rosenbergii, M. nipponense, Procambarus clarkii, M. superbum, Penaeus vannamei, and Cladocera from a farm suffering from ‘white head’ in Jiangsu Province were collected and analyzed in this study. Pathogen detection showed that all samples were positive for Shrimp hemocyte iridescent virus (SHIV). Histopathological examination revealed dark eosinophilic inclusions and pyknosis in hematopoietic tissue, hepatopancreas and gills of M. rosenbergii and M. nipponense. Blue signals of in situ DIG-labeled LAMP (ISDL) appeared in hematopoietic tissue, hemocytes, hepatopancreatic sinus, and antennal gland. TEM of ultrathin sections showed a large number of SHIV particles with a mean diameter about 157.9 nm. The virogenic stromata and budding virions were observed in hematopoietic cells. Quantitative detection by TaqMan probe based real-time PCR of different tissues in natural infected M. rosenbergii showed that hematopoietic tissue contained the highest SHIV load with a relative abundance of (25.4±16.9)%. Hepatopancreas and muscle contained the lowest SHIV load with a relative abundance at (2.44±1.24)% and (2.44±2.16)%, respectively. Above results verified that SHIV is the pathogen causing ‘white head’ in M. rosenbergii, and M. nipponense and Pr. clarkii are also the susceptible species of SHIV.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas, the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). We, for the first time, have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Lung cancer is a prevalent malignancy that impacts individuals of all genders and is often diagnosed late due to delayed symptoms. To catch it early, researchers are developing algorithms to study lung cancer images. One such method uses computer aided detection to classify as benign or malignant from the histopathological images. Standard histopathological images were used from a Lung and Colon Cancer Histopathological Image Dataset (LC25000) which contains two classes of benign and malignant of 5000 each. Images were preprocessed and features extracted using Particle Swarm Optimization (PSO) and Grey Wolf Optimization (GWO). Feature selection methods used are KL Divergence and Invasive Weed Optimization (IWO). Seven different classifiers like SVM, KNN, Random Forest, Decision Tree, Softmax Discriminant, Multilayer Perceptron, and BLDC were used to analyze and classify the images as benign or malignant. Results were compared using standard metrics, and kappa analysis assessed classifier agreement. The Decision Tree Classifier with GWO feature extraction achieved good accuracy of 85.01% without Feature selection and Hyperparameter Tuning approaches. Furthermore, we present a methodology to enhance the accuracy of the classifiers by employing hyperparameter tuning algorithms based on Adam and RAdam. By combining features from GWO and IWO, and using the RAdam algorithm, the Decision Tree classifier achieves the commendable accuracy of 91.57%

Pigeon paramyxovirus serotype 1 (PPMV-1), primarily originating from racing pigeons, has become a global panzootic, spreading to poultry and wild birds, thus posing a threat to the poultry industry. Egypt uses both inactivated pigeon paramyxovirus (PPMV-1) and conventional Newcastle disease virus (NDV) vaccines to protect pigeons. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 isolated from vaccinated pigeons in Sharkia, Egypt (Pigeon/ Egypt/Sharkia-19/2015/KX580988). Ten-day-old specific-pathogen-free embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4±5.88 hours. The intracerebral pathogenicity index (ICPI) in day-old chicks was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection with this PPMV-1 strain at 106 EID50/0.1 ml resulted in a 62.5% mortality rate in pigeons, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while a single NDV LaSota vaccine provided 62.5% protection. The PPMV alone or combined with NDV LaSota induced protective levels of hemagglutination inhibition antibody titers and reduced virus shedding from buccal and cloacal cavities. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission.

Accurately diagnosing specific variants of alopecia remains challenging for pathologists, potentially delaying appropriate therapeutic decisions by dermatologists. Issues such as limited knowledge on optimal biopsy types and processing methods add complexity. Understanding the normal histology of hair follicles and their changes throughout the follicular cycle further complicates microscopic evaluation. This paper aims to summarize these characteristics and highlight essential diagnostic clues for pathologists to confidently suggest a diagnosis, therefore playing a key role in alopecia diagnosis. Ongoing education, collaboration with dermatologists, and staying updated on advancements is crucial for accurate diagnosis and effective management of different types of alopecia.

Work from the last years indicate that the extracellular matrix (ECM) plays a direct role in vari-ous cellular processes including proliferation, migration and differentiation. Besides homeostat-ic processes, its regulatory function in inflammation becomes more and more evident. In in-flammation like inflammatory bowel disease, the ECM composition is constantly remodeled which can result in a structuring of fistulizing disease course. Thus, tracking early ECM changes might bear the potential to predict the disease course. In this review, we will provide an over-view of relevant diagnostic methods focusing on ECM changes.

Prolonged ethanol (EtOH) consumption is associated with male infertility with a decreased spermatogenesis rate as one cause. Defective maturation and development of sperm during their storage in the cauda epididymis and transit in the seminal vesicle can be another cause, possibly occurring before the drastic spermatogenesis disruption. Herein, we demonstrated that the cauda epididymis and seminal vesicle of rats, orally fed with EtOH under a regimen that spermatogenesis was still ongoing, showed histological damage, including lesion and decreased height of the epithelial cells, and increased collagen fibers in the muscle layer, which implicated fibrosis. Lipid peroxidation (shown by malondialdehyde (MDA) levels) was observed, indicating that reactive oxygen species (ROS) was produced along with acetaldehyde during EtOH metabolism by CYP2E1. MDA, acetaldehyde and other lipid peroxidation products could further damage cellular components of the cauda epididymis and seminal vesicle and this was supported by increased apoptosis (shown by TUNEL assay and caspase 9/caspase 3 expression) in these two tissues of EtOH-treated rats. Consequently, functionality of the cauda epididymis and seminal vesicle in EtOH-treated rats was impaired, as demonstrated by decreases in 1H NMR-analyzed metabolites (e.g., carnitine, fructose), which were important for sperm development, metabolism and survival in their lumen.

Malignant lymphomas, encompassing Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), represent a significant category of hematological malignancies with diverse presentations and prognoses. This review synthesizes current understanding of malignant lymphomas, focusing on their classification, incidence, epidemiology, staging, histopathology, and evolving treatment strategies. Malignant lymphomas are broadly classified into HL and NHL, with NHL further subdivided into B-cell, T-cell, and NK-cell neoplasms. The emergence of grey zone lymphomas, which exhibit overlapping features and heightened aggressiveness, underscores the complexity of diagnosis and treatment. Epidemiologically, HL predominantly affects younger individuals, while NHL incidence increases with age, reflecting a global rise in both incidence and mortality rates. Advances in diagnostic techniques and treatments have led to improved outcomes, yet challenges persist, particularly in distinguishing between overlapping lymphoma types and managing increasing incidence rates. The management of HL and NHL involves a variety of treatment options tailored to the disease stage and individual patient characteristics. After diagnosis and staging, treatment regimens may include radiotherapy, chemotherapy (either alone or in combination), and immunotherapy. Monitoring patient response is crucial, with adjustments made in cases of therapeutic failure. Achieving remission—either partial or complete—depends on the normalization of biomarkers and imaging results, reduction of lymphoid organ size, and resolution of symptoms. Despite therapeutic advances, treatment complications, including short-term effects like myelosuppression and long-term issues such as cardiomyopathy and secondary cancers, remain significant. The future of HL and NHL treatment lies in refining these approaches, minimizing adverse effects, and enhancing efficacy through innovative therapies and personalized medicine strategies.