Abstract: There has been extensive research in the field of KSHV/HHV8 virus, which has led to the development in the understanding of KSHV/HHV8 transmission, viral pathogenesis, how the virus drives neoplastic lesions, and how we can combat these processes. On extensive review of literature, only two true KSHV/HHV8 positive lymphoid neoplasms are described: Primary effusion lymphoma (PEL), which can also present as solid or extra-cavitary primary effusion lymphoma (EC-PEL) and diffuse large B-cell lymphoma (DLBCL). Two lymphoproliferative disorders have also been described, and while they are not true monotypic neoplasms, these lesions can transform into neoplasms: KSHV/HHV8 positive germinotropic lymphoproliferative disorder (GLPD) and Multicentric Castleman's disease (MCD). This review provides a somewhat concise overview of information related to KSHV/HHV8 positive lymphoid neoplasms and pertinent associated lymphoproliferative lesions.

Abstract: Peripheral artery disease (PAD) is a chronic progressive accumulation of atherosclerotic lesions with varying degrees of arterial obstruction determining ischemic symptoms of the involved extremities. PAD is associated with decreased bioavailable nitric oxide due to endothelial cell dysfunction and the development and progression of vascular arterial stiffening (VAS). Atherosclerosis also plays an essential role in the development and progression of vascular arterial stiffening (VAS), which associates with endothelial cell activation and dysfunction that results in a proinflammatory endothelium with a decreased ability to produce bioavailable nitric oxide (NO). NO is one of three gasotransmitters along with carbon monoxide and hydrogen sulfide that promotes vasodilation. NO plays a crucial role in the regulation of PAD and a deficiency in its bioavailability is strongly linked to the development of atherosclerosis, VAS, and PAD. A decreased arterial patency may also occur due to a reduction in the elasticity or diameter of the vessel wall due to the progressive nature of VAS and atherosclerosis in PAD. Progressive atherosclerosis and VAS promote narrowing over time, which lead to impairment of vasorelaxation and extremity blood flow. This narrative review examines how atherosclerosis, aging and hypertension, metabolic syndrome and type 2 diabetes, tobacco smoking, endothelial cell activation and dysfunction with decreased NO, VAS with its increased damaging pulsatile pulse pressure results in microvessel remodeling. Further, the role of ischemia and ischemia reperfusion injury is discussed and how it contributes to ischemic skeletal muscle remodeling, ischemic neuropathy, and pain perception in PAD.

Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract characterized by the deregulation of immuno-oncology markers. IBD includes ulcerative colitis and Chron disease. Chronic active inflammation is a risk factor for the development of colorectal cancer (CRC). Deep learning is a form of machine learning that is applicable to computer vision, and it includes algorithms and workflows used for image processing, analysis, visualization, and algorithm development. This technical note of data descriptor and methods type describes a dataset of histological images of ulcerative colitis, CRC (adenocarcinoma), and colon control. The samples were stained with hematoxylin and eosin (H&E), and immunohistochemically analyzed for LAIR1 and TOX2 markers. The methods used for collecting, processing, and analyzing scientific data using convolutional neural networks (CNNs), where the dataset can be found, and information about its use is also described. This note is a companion to the DOI: 10.3390/cancers16244230.

Abstract: This study aimed to elucidate the pathological features of thrombus-associated amyloid deposition. Thes features were validated by immunohistochemistry combined with proteomic analyses using liquid chromatography–tandem mass spectrometry with laser microdissection. Our findings revealed that thrombus-associated amyloid deposits within the thrombus and vessel wall primarily comprised apolipoprotein A-I, with a mixture of amyloid fibrils derived from amyloidogenic proteins, including transthyretin and lactoferrin. Given that these proteins are present in the blood, our results support a previous hypothesis that is, proteins denatured during thrombus aging are a source of amyloid. Furthermore, phagocytes were infiltrated around the intramural and extravascular deposits rather than around the amyloid deposits within the thrombus. Therefore, amyloid deposits generated within the thrombus may be transported from regions with limited blood flow to the vessel wall and surrounding tissues, where blood flow is present, during thrombus processing. These deposits were primarily removed by phagocytic cells. Our results suggest that a facilitative effect on deposition occurs via a cross-seeding mechanism between amyloid fibrils and that phagocytes can remove amyloid deposits. These findings help elucidate the pathogenesis of localized amyloidosis.

Abstract: Introduction: Pancreatic adenocarcinoma has a poor prognosis, underscoring the need for accurate staging systems. The 8th edition of the AJCC TNM classification introduced key changes, including size-based T staging and the N2 category for ≥4 positive lymph nodes. This study compares the prognostic value of the 7th and 8th editions. Methods: A retrospective cohort of 214 patients with resected pancreatic adenocarcinoma was analyzed. TNM staging was applied using both editions. Associations with disease progression and overall survival were assessed using chi-square tests and Kaplan-Meier survival analysis. Results: The 8th edition led to significant reclassification, especially within Stage II and Stage III. Both editions showed significant association with disease recurrence. However, only the 7th edition was significantly associated with overall survival. Conclusions: The 8th edition improves disease progression stratification through refined T and N criteria but shows limited ability to predict overall survival compared to the 7th edition. These findings support the use of updated TNM staging while highlighting the need for complementary prognostic tools.

Abstract: Homologous recombination deficiency (HRD) is a pivotal biomarker in oncology, influencing treatment strategies and prognostic assessments. HRD impairs DNA repair mechanisms, leading to genomic instability and heightened sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, particularly in ovarian and breast cancers. This review examines the molecular basis of HRD, current methodologies for its detection, and its clinical relevance in precision oncology. We address challenges in standardizing HRD assessment, including variability in testing approaches and interpretation thresholds. Additionally, emerging strategies for optimizing HRD-targeted therapies are discussed, emphasizing novel biomarkers and therapeutic combinations. By consolidating current knowledge and advancements, this review provides insights into HRD’s role in cancer biology and its potential for refining personalized treatment approaches.

Abstract: Periodontal disease is the most common chronic inflammatory condition with a polymicrobial origin, particularly among the elderly. Numerous risk factors can independently or synergistically contribute to immune suppression and inflammation in the periodontium. This leads to microbial dysbiosis in the periodontal pockets and the supra gingival biofilm, resulting in the elevation of patho bionts or opportunistic pathogens that are considered potential contributors to periodontal disease. The progression from gingivitis to chronic periodontitis typically follows an ecological succession, starting with the facultative anaerobes of the yellow complex and advancing to the strict anaerobes of the red complex of periodontal pathogens. Additionally, there has been an observed increase in sulfate-reducing bacteria (SRB) within the oral cavities, which are part of the human oral microbiome. SRB is a diverse group of naturally occurring microorganisms known for their capability of dissimilatory sulfate reduction to hydrogen sulfide (H2S). Methanogenic archaea are a minority within the SRB group, known for their hydrogenotrophic metabolism and cooperative growth alongside other species in the periodontal pockets. However, these methanogenic archaea are not typically recognized as contributors to the development of periodontal disease. Investigating the role of methanogenic archaea in the context of periodontal disease enhances our understanding of the dynamics within the supragingival biofilm associated with chronic periodontitis.

Abstract: Understanding the diagnostic landscape prior to developing novel diagnostic strategies is key to managing expectations and authenticating results. In considering the possibility of developing alternate diagnostic approaches for coeliac disease based on duodenal biopsies, we audited 18 months’ worth of duodenal biopsies received in our centre to determine the exact proportions of different diagnoses. A total of 6245 duodenal biopsies were audited, of which 73.76% were normal and 8.84% fell within the spectrum of coeliac disease. Additionally, 6.47% were classified as showing non-specific inflammation, 1.86% were adenomas, 0.42% were carcinomas, and 0.06% were neuroendocrine tumours. Rarer diagnoses included ulceration, Helicobacter pylori infection, Giardiasis, lymphangiectasia, transplant rejection, and lymphoma. Furthermore, 227 biopsies (3.63%) showed isolated intraepithelial lymphocytosis, of which 24 cases eventually received a definitive diagnosis of coeliac disease. We present the first long-term audit of all endoscopic duodenal biopsies received by the histopathology department of a tertiary care facility. The results indicate that a fully automated system that could identify normal duodenal biopsies and biopsies within the spectrum of coeliac disease-associated enteropathy could decrease pathologists’ endoscopic duodenal biopsy workload by up to 80%.

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an abnormal inflammatory response in the airways and alveoli due to prolonged exposure to harmful particles or gases. Despite treatments like bronchodilators and corticosteroids, challenges remain due to the disease’s heterogeneity and medication side effects, such as pulmonary infections. Recent studies suggest that blocking IL-17 could reduce inflammation in lung injury models. This study evaluated the effects of an IL-17 neutralizing antibody in a cigarette smoke-induced COPD mouse model. Mice were exposed to cigarette smoke for 6 months, and treatment with the antibody was initiated in the 5th month. Three experimental groups were formed: control, COPD, and COPD + anti-IL-17. Results showed an increase in the mean linear intercept (Lm) in the COPD group, while treatment with the neutralizing antibody reversed the structural changes. Additionally, the expression of inflammatory cytokines and the RORγt gene was higher in the COPD group. The study concludes that IL-17 neutralizing antibody treatment can reverse functional and structural lung alterations in COPD.

Abstract: Shock is a life-threatening condition characterized by inadequate tissue perfusion, leading to systemic hypoxia and metabolic failure. Ischemia-reperfusion (I/R) injury exacerbates shock progression through oxidative stress and immune dysregulation, contributing to multi-organ dysfunction. This narrative review synthesizes current evidence on the interplay between I/R injury, oxidative stress, and immune modulation in shock states. We analyze the classification of shock, its progression, and the molecular pathways involved in ischemic adaptation, inflammatory responses, and oxidative injury. Shock pathophysiology is driven by systemic ischemia, triggering adaptive responses such as hypoxia-inducible factor (HIF) signaling and metabolic reprogramming. However, prolonged hypoxia leads to mitochondrial dysfunction, increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and immune activation. The transition from systemic inflammatory response syndrome (SIRS) to compensatory anti-inflammatory response syndrome (CARS) contributes to immune imbalance, further aggravating tissue damage. Dysregulated immune checkpoint pathways, including CTLA-4 and PD-1, fail to suppress excessive inflammation, exacerbating oxidative injury and immune exhaustion. The intricate relationship between oxidative stress, ischemia-reperfusion injury, and immune dysregulation in shock states highlights potential therapeutic targets. Strategies aimed at modulating redox homeostasis, controlling immune responses, and mitigating I/R damage may improve patient outcomes. Future research should focus on novel interventions that restore immune balance while preventing excessive oxidative injury.

Abstract: Background/Objectives: Elevated human epididymis protein 4 (HE4) expression has been observed in breast cancer and is linked to cancer progression; however, its role in ductal carcinoma in situ (DCIS) remains unclear. This study evaluated HE4 levels in DCIS serum and tissue and their correlation with clinicopathological features. Methods: Preoperative serum HE4 levels were measured in 59 DCIS patients. HE4 mRNA and protein expression were assessed in DCIS and adjacent normal tissues via RNAscope in situ hybridization and immunohistochemistry. An independent tissue microarray of 41 DCIS cases was also analyzed, and the BreastMark database was applied to explore the prognostic relevance of HE4. Results: Serum HE4 levels (mean ± SD: 39.4 ± 11.9 pmol/L) were within the normal range and did not significantly correlate to clinicopathological parameters except menopause status. HE4 expression was significantly higher in DCIS tissues than in adjacent normal tissues, with mRNA and protein levels positively correlated (r = 0.771, p < 0.001). High HE4 mRNA and protein expression was associated with ER positivity, HER2 negativity, low stromal tumor-infiltrating lymphocyte density, and HR+/HER2- subtypes but did not predict DCIS recurrence. High HE4 expression in breast cancer patients correlated with better survival outcomes. Conclusions: While serum HE4 is not elevated in DCIS, high HE4 expression in tissues is linked to favorable clinicopathological characteristics; thus, further research is warranted on its potential prognostic role.

Abstract: The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the diverse cellular landscape, and the interconnected vascular and nervous networks, highlighting their roles in preserving bone function and responding to pathological changes. Recent studies reveal regulatory mechanisms involving oxygen tension, ionic balance, signaling molecules, and mechanotransduction pathways that shape bone metabolism and its adaptation to mechanical forces. Insights into the bone microenvironment’s metabolic shifts in cancer and its interaction with inflammation underscore its pivotal role in disease progression and therapeutic innovation. Additionally, advances in imaging techniques and biomaterials fuel progress in bone regeneration and understanding its microenvironment. Exploring the intricate physiochemical dynamics and regulatory networks within the intraosseous system unlocks potential clinical applications in bone diseases, tissue engineering, and systemic metabolic disorders. This comprehensive review bridges fundamental science with translational research, offering insights into the complex yet essential intraosseous environment.

Abstract: Background/Objectives: The global burden caused by high body mass index (BMI) particularly in postmenopausal (PMP) women is increasing significantly and is expected to be increasing in geographical and socioeconomic perspectives. Serum vitamin D (vitD) and pro-inflammatory factors influence the development and progression of T2DM particularly in overweight (OW)/obese PMP women. However, since there are controversies about the impact and interactive association of vitD with some of the pro-inflammatory biomarkers (interleukin-6 (IL-6), homocysteine (Hcy) and others) and therapeutic significance of vitD in OW women in PMP with T2DM, we planned to carry out study in NW and OW women with/ without T2DM in PMP. Methods: The normal weight (NW, BMI: 18.5 to 24.9 kg/m2) and OW (n: BMI: 25.0 to29.9 kg/m2) nondiabetic (ND, n: 199) and T2DM (n: 197) women in PMP (age range: 51-60 years) were consulted. The women subjects (n: 396) were categorized into NW-ND (n: 101), OW-ND (n:98), NW-DM (n:101) and OW-DM (n:96). Fasting blood samples were collected for the determination of serum levels of vitD, IL-6, Hcy, hemoglobin (HB) and hepcidin (Hp). Results: The present report in PMP women with and without T2DM showed significant difference of serum vitD for NW-ND vs. OW-ND, NW-DM vs. OW-DM, and NW-ND vs. NW-DM, Hcy for OW-ND vs. OW-DM and NW-DM vs. OW-DM and IL-6 for OW-ND vs. OW-DM and NW-DM vs. OW-DM. Among-groups comparison showed significant variation of serum vitD, Hcy and IL-6. A significant negative linear correlation of BMI was obtained against vitD for OW-ND and OW-DM. A significant positive linear correlation of BMI was found against Hcy as well as IL-6 for OW-ND and OW-DM. A significant inverse linear correlation of vitD was obtained against Hcy for OW-DM, and against IL-6 for NW-ND, NW-DM and OW-DM. Hcy plot with IL-6 levels showed significant positive linear correlation for NW-DM, OW-ND and OW-DM. Conclusions: The results obtained for the alterations noted for serum vitD, proinflammatory biomarkers (Hcy and IL-6) and other variables in the present investigation in PMP women (NW and OW) with T2DM, and associations among these factors are quite convincing to introduce a novel therapeutic approach based on vitD and proinflammatory markers for T2DM patients of high BMI levels.

Abstract: Although various factors contribute to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD), no clinically effective pharmacological treatment has been established. We investigated whether chymase inhibition is effective in preventing renal fibrosis, a key process in the transition from AKI to CKD. Male BALB/c mice were subjected to unilateral ischemia-reperfusion (I/R) injury, and TY-51469, a chymase-specific inhibitor, was administered intraperitoneally at a dose of 10 mg/kg/day for 6 weeks. The 45-minute ischemic period followed by 6 weeks of reperfusion resulted in severe renal atrophy. Renal fibrosis was particularly pronounced at the transition region between the cortex and medulla in placebo-treated mice. Expression of mouse mast cell protease 4 (MMCP-4, a mouse chymase) mRNA, number of chymase-positive mast cells, and fibrosis-related factors, such as transforming growth factor (TGF)-β1 and collagen I were all significantly increased in I/R-injured kidneys. However, treatment with TY-51469 significantly suppressed fibrosis formation, along with inhibition of renal chymase and TGF-β1 expression. These findings suggest that chymase inhibition may be a potential therapeutic strategy for preventing the transition from AKI to CKD by reducing fibrosis.

Abstract: Strumal carcinoid tumors of the ovary are rare neoplasms composed of an intimate mixture of thyroid and carcinoid tissues. While various theories regarding their histogenesis have been proposed, direct evidence confirming the origin of the carcinoid component has been lacking. We report a case of a 40-year-old female with a left ovarian strumal carcinoid arising in a mature cystic teratoma. Morphological and immunohistochemical findings provide convincing evidence that the carcinoid component originates from thyroid follicular epithelium undergoing neuroendocrine differentiation. A single-cell invasion pattern was also identified, expanding the known histological spectrum of strumal carcinoids. Our case provides definitive immunohistochemical evidence for the histogenetic origin of strumal carcinoids, offering new insights into their pathogenesis. Recognizing these distinct staining and invasive patterns are critical for accurate diagnosis and differentiation from metastatic disease.

Abstract: Cancer remains a global health issue, with early detection, correct diagnosis, and exact prognosis playing critical roles in improving patient outcomes. Recent developments in image processing and pattern recognition have significantly enhanced cancer detection, prediction, diagnosis, and prognosis, bridging the gap between conventional radiological methods and state-of-the-art artificial intelligence (AI)-based analytics. The abstract provides an in-depth introduction of the concepts behind, developing methods, and practical applications of image processing and pattern recognition in oncology. Image preprocessing algorithms, tumor segmentation algorithms, feature extraction, and pattern recognition methods based on artificial intelligence such as machine learning and deep learning models (e.g., CNNs, RNNs, and transformers) are all significant areas. We study cancer prediction using radiomics and radio genomics, artificial intelligence-based histopathological diagnosis, and fusion of multimodal data from imaging, genomics, and clinical history for personalized prognosis. The impact of explainable AI, 3D/4D imaging, nanotechnology-facilitated imaging, and cloud-based AI solutions is also discussed, including precision oncology and remote diagnosis. Even with these developments, significant clinical use limitations remain, such as poor annotated datasets, lack of interpretability, ethical considerations, and regulatory issues. The abstract proceeds with focusing on emerging trends, including federated learning, quantum computing, and real-time AI applications, that can potentially revolutionize cancer imaging and management. Image processing and pattern recognition, if integrated with interdisciplinary research, have the potential to develop more precise, equitable, and egalitarian cancer care in the future.

Abstract: The aim of this work was a detailed radiological and histopathological evaluation of a solid tumour, presumably cancerous in nature, diagnosed in a 2-year-old goose (Anser domesticus). The radiograph examination showed an osseous change with the involvement of cervical vertebrae. A tumour measuring 15x10x9 cm was dense and had well-defined borders, suggesting the presence of calcified bone tissue. Histopathology revealed a well-defined benign neoplasm derived from bone and consisted large area of irregular, disorganized bone trabeculae, surrounded by a layer of osteoblasts. The tumour has been classified as an osteoma, which originates from the body of the vertebrae. Osteoma is a benign, well-differentiated tumour with a structure that resembles bone tissue. It presents as a well-demarcated, hard, single tumour that can grow to a considerable size. The aetiology of osteomas in birds remains unclear, because of the small number of cases described. Therefore, the influence of factors such as age, breed or sex, trauma, embryonic malformation, infection, developmental disorders, genetic factors on the development of this type of tumour has not been established. Trauma seems to be the most obvious cause of growth in this case. This work provides valuable information about osteomas in birds, important for understanding these neoplasms.

Abstract: Carbon monoxide (CO) poisoning is a significant public health issue, with diagnosis often complicated by nonspecific symptoms and limited access to specialized tools. Early detection is vital for preventing long-term complications. The review examines diagnostic challenges, prognostic factors, management strategies, and future ad-vancements in CO poisoning. It highlights the limitations of current diagnostic tech-niques such as blood carboxyhemoglobin levels and pulse CO-oximetry, while explor-ing emerging methods for rapid detection. Prognosis is influenced by exposure severity and delayed treatment, which increases the risk of neurological damage. Hyperbaric oxygen therapy (HBOT) remains the primary treatment but is not always accessible. Advances in portable CO-oximeters and biomarkers offer potential for improved early diagnosis and monitoring. Addressing resource limitations and refining treatment protocols are crucial for better patient outcomes. Future research should focus on per-sonalized management strategies and the integration of modern technologies to en-hance care.

Abstract: Background/Objective Epstein-Barr Virus (EBV) infection can be associated with lymphocytic hematological malignancies, including Systemic Epstein-Barr Virus-Positive T-Cell Lymphoma of Childhood (SEBVTCL). A common complication of EBV infection, hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune activation that is present in virtually all cases of SEBVTCL, which requires urgent treatment as this malignancy can be rapidly fatal. Abnormal karyotypes have been strongly associated with SEBVTCL as a distinguishing feature from HLH in the literature. Here, we discuss the diagnostic challenges and social complications in a case of an unaccompanied minor immigrant patient with a highly complex karyotype diagnosed with SEBVTCL with associated HLH. Methods Laboratory testing confirmed the presence of EBV+ HLH and cytogenetic analysis was performed to investigate a neoplastic process in this patient, confirming SEBVTCL. Chromosomal microarray (CMA) was performed to try to clarify the complex findings by chromosome analysis but demonstrated normal results. Results: Chromosome analysis demonstrated a highly complex hypertriploid clone that confirmed a diagnosis SEBVTCL. After declining treatment, the patient was discharged to his guardian against medical advice and succumbed to his disease shortly after. Conclusions: SEBVTCL can be challenging to diagnose due to the similarity in clinical and pathological presentations. In virtually all cases reported in the literature, an abnormal karyotype has been reported to be the most important prognostic factor. We proposed that in cases with diagnostic ambiguity, an abnormal karyotype can help favor SEBVTCL over EBV+ HLH.

Abstract: Background: The emergency of carbapenem-resistant Enterobacterales is prevalent and poses a significant threat to health systems worldwide. This study aimed to conduct a molecular analysis of tigecycline resistance in 100 CRE in hospital isolates from Mthatha and surrounding hospitals. Methods: A retrospective study among patients who attended Nelson Mandela Academic Hospital (NMAH) and Mthatha Regional Hospital (MRH), Eastern Cape, South Africa. Enterobacterales isolates were identified using the Vitek2® system (bioMérieux), E-test was performed in 100 CRE hospital isolates according to manufacturer’s instructions, A multiplex SYBR green-based PCR assay for rapid detection of tet(X) and its variants, including tet(X1), tet(X2), and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5) were developed. Results: The results show a notable high prevalence of CRE infections in neonatal, male surgical, and maternal and pediatric wards, predominantly driven by Klebsiella spp. (53.4%), followed by Enterobacter spp. (20.5 %), then Escherichia coli (6.7%), 7.2% of CRE were resistant to Tigecycline (E-TEST), Tet(X) genes were Not responsible for tigecycline resistance in this setting. The risk factors associated with tigecycline resistance in CRE include age, pre-exposure to antibiotics, prolonged hospitalization, and undergoing invasive procedures indicated by strong r2 =0.9501. Conclusion: CRE gradually evolves, posing a significant threat to patients of all ages; early detection of carbapenemase production in clinical infections, carriage states, or both is essential to prevent hospital-based outbreaks.