Search Results (1,181)

Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future. Full article

In recent years, phylogenomic approaches have significantly deepened our understanding of moss diversity. These techniques have uncovered numerous previously overlooked species and provided greater clarity in resolving complex taxonomic relationships. In this context, the genus Rehubryum is particularly outstanding, because of its close morphological similarity to both Ulota and Atlantichella. The challenges posed by its segregation are addressed in this study, which integrates morphological and molecular data to reassess the circumscription of Rehubryum and its phylogenetic placement within the subtribe Lewinskyinae. Our results support the recognition of a new species, R. kiwi, and show that its inclusion within the genus further complicates the morphological delimitation of Rehubryum from Ulota, as both genera are distinguishable by only two consistent gametophytic characteristics: a submarginal leaf band of elongated cells, and the presence of geminate denticulations in the margins of the basal half of the leaf. Moreover, R. kiwi challenges the current morphological circumscription of Rehubryum itself, as it overlaps in key characteristics with its sister genus Atlantichella, rendering their morphological separation untenable. The striking interhemispheric disjunction between Rehubryum and Atlantichella raises new questions about long-distance dispersal and historical biogeography in mosses, despite these complexities at the generic level. Nevertheless, species-level distinctions remain well defined, especially in sporophytic traits and geographic distribution. These findings highlight the pervasive cryptic diversity within Orthotrichaceae, underscoring the need for integrative taxonomic frameworks that synthesize morphology, molecular phylogenetics, and biogeography to resolve evolutionary histories. Full article

Accounting for 15–30% of colorectal cancer cases, the serrated pathway remains poorly characterized compared to the adenoma–carcinoma sequence. It involves sessile serrated lesions as precursors and is characterized by BRAF mutations (BRAF^V600E), CpG island hypermethylation, and microsatellite instability (MSI). Using label-free proteomics, we compared normal tissue margins from patients with diverticular disease, sessile serrated lesions, low-grade adenomas, and high-grade adenomas. We identified S100A14 as significantly overexpressed in sessile serrated lesions compared to low-grade adenomas, high-grade adenomas, and normal tissues. This overexpression was confirmed by immunohistochemical scoring in an independent cohort. Gene expression analyses of public datasets showed higher S100A14 expression in BRAF^V600E-mutated and MSI-H colorectal cancers compared to microsatellite stable BRAF^wt tumors. This finding was confirmed by immunohistochemical scoring in an independent colorectal cancer cohort. Furthermore, single-cell RNA sequencing analysis from the Human Colon Cancer Atlas revealed that S100A14 expression in tumor cells positively correlated with the abundance of tumoral CD8⁺ cytotoxic T cells, particularly the CD8⁺ CXCL13⁺ subset, known for its association with a favorable response to immunotherapy. Collectively, our results demonstrate for the first time that S100A14 is a potential biomarker of serrated neoplasia and further suggests its potential role in predicting immunotherapy responses in colorectal cancer. Full article

Doxorubicin (DOX) is widely used for the treatment of several tumors, but considerable dose-dependent side effects on many normal tissues, including bones, have been reported. The aim of the present study was to follow for the first time the kinetics of DOX accumulation/clearance in the non-vascularized intervertebral disc (IVD), as well as to assess the drug’s biological action in the annulus fibrosus (AF) and nucleus pulposus (NP) IVD cells and tissues. DOX was administered intravenously to rabbits before the isolation of IVDs, in which DOX quantification was performed using a highly sensitive LC-HRMS/MS analytical method. The effect of the drug on IVD cells’ physiology was assessed in vitro, while IVD tissue quality post-DOX administration was studied in vivo through histological analysis. DOX delivery was found significantly lower in the IVD compared to the highly vascularized skin, declining from the outer AF to the inner NP. The low DOX concentrations reaching the IVDs had marginal effects on cells’ viability, intracellular redox status, and p38 MAPK activation, while they did not evoke cellular senescence. Most importantly, the drug did not negatively affect ECM integrity, as collagen and proteoglycan content remained stable in vitro and in vivo. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article

Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth decade of life, the first diagnosed with VIN 3 (carcinoma in situ) and the second with stage IA keratinizing squamous cell carcinoma. Both patients had HPV infection; immunohistochemistry confirmed HPV-dependent VIN3 in the first case, while the second patient had a pre-existing HPV high-risk 53 infection. Both patients underwent partial vulvectomy, with the second also having bilateral inguinal–femoral lymph node dissection, which showed no lymph node invasion. The first patient had a histopathological result of VIN 3 with clear margins. The second patient underwent adjuvant radiotherapy following restaging pathology. Both are showing favorable postoperative progress. Conclusions. The early diagnosis of vulvar neoplasms enables less radical but effective surgeries, balancing oncologic control with quality of life. A multidisciplinary approach is essential for adjusting treatments, improving both clinical outcomes and patient well-being. Full article

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article

Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract, characterized by high mortality rates and responsible for about one million new cases each year globally. Surgery is the main treatment, but achieving radical resection remains a relevant intraoperative challenge. Fluorescence-guided surgery offers clinicians greater capabilities for real-time detection of tumor nodules and visualization of tumor margins. In this field, the main challenge remains the development of fluorescent dyes that can selectively target tumor tissues. Methods: we examined the expression of the most suitable GC markers, including carcinoembryonic antigen cell adhesion molecule-5 (CEACAM5) and Claudin-4 (CLDN4), in GC cell lines. To further evaluate their expression, we performed immunohistochemistry (IHC) on tumor and healthy tissue samples from 30 GC patients who underwent partial gastrectomy at the Digestive System Surgery Unit, AOU Careggi, Florence. Additionally, we validated anti-CEACAM5 expression on patient-derived organoids. Furthermore, we developed a fluorescent molecule targeting CEACAM5 on the surface of GC cells and assessed its binding properties on patient tissue slices and fragments. Results: in this work, we first identified CEACAM5 as an optimal GC biomarker, and then we developed a fluorescent antibody specific for CEACAM5. We also evaluated its binding specificity for GC cell lines and patient-derived tumor tissue, achieving an optimal ability to discriminate tumor tissue from healthy mucosa. Conclusions: Overall, our results support the development of our fluorescent antibody as a promising tumor-specific imaging agent that, after further in vivo validation, could improve the accuracy of complete tumor resection. Full article

We performed a diagnostic disease investigation on a wild smallmouth bass (Micropterus dolomieu) with skin ulcers that was collected from Lake Oahe, South Dakota, following reports from anglers of multiple fish with similar lesions. Gross and histologic lesions of ulcerative dermatitis, myositis, and lymphocytolysis within the spleen and kidneys were consistent with largemouth bass virus (LMBV) infection. LMBV was detected by conventional PCR in samples of a skin ulcer, and the complete genome sequence of the LMBV (99,184 bp) was determined from a virus isolate obtained from a homogenized skin sample. A maximum likelihood (ML) phylogenetic analysis based on the major capsid protein (MCP) gene alignment supported the LMBV isolate (LMBV-SD-2023) as a member of the species Ranavirus micropterus1, branching within the subclade of LMBV isolates recovered from North American largemouth (Micropterus salmoides) and smallmouth bass. This is the first detection of LMBV in wild smallmouth bass from South Dakota. The ultrastructure of the LMBV isolate exhibited the expected icosahedral shape of virions budding from cellular membranes. Viral nucleic acid in infected cells was visualized via in situ hybridization (ISH) within dermal granulomas, localized predominantly at the margin of epithelioid macrophages and central necrosis. Further sampling is needed to determine the geographic distribution, affected populations, and evolutionary relationship between isolates of LMBV. Full article

Background: Medullary thyroid carcinoma (MTC) is a rare malignancy derived from parafollicular C-cells, with calcitonin (Ct) as its key biomarker. While basal Ct (bCt) levels above 100 pg/mL strongly suggest MTC, intermediate elevations (10–100 pg/mL) may reflect C-cell hyperplasia (CCH) or other benign conditions, making diagnostics challenging. Although calcium stimulation testing enhances sensitivity, the optimal cut-off values and comparative efficacy of calcium gluconate (CG) versus calcium chloride (CC) remain insufficiently researched. Methods: Data on 176 patients who underwent total thyroidectomy between 2009 and 2025 were retrospectively analyzed. BCt values ranged from 10 to 100 pg/mL, and stimulated Ct (sCt) values were above 100 pg/mL. CG was used from 2009 to 2019, and CC was used from 2020 to 2025. Definitive pathohistological findings divided patients into those with MTC, CCH, or no C-cell pathology. Receiver operating characteristic (ROC) analysis identified optimal Ct thresholds for predicting MTC for each stimulatory agent. Results: Of the 176 patients, 36 (20.5%) had confirmed MTC. A bCt threshold of 31.1 pg/mL yielded 69.4% sensitivity and 87.1% specificity. For sCt, optimal cut-offs were 810.8 pg/mL for CG and 1076 pg/mL for CC. Lower thresholds (388.4 pg/mL for CG and 431.5 pg/mL for CC) improved sensitivity (≥76.9%) and negative predictive value (>91%). Conclusions: Calcium stimulation testing improves MTC detection in patients with moderate bCt elevation. Although CG showed marginally better diagnostic performance, CC remains a practical and reliable alternative, especially when higher cut-off values are considered. Early surgical intervention should be considered when sensitivity-driven thresholds are met. Full article

Polyploidy in plants can enhance stress resistance and secondary metabolite production, offering potential benefits for Clausena lansium (L.) Skeel, a medicinally valuable species. However, systematic studies of polyploidy-induced morphological, anatomical, and metabolic changes in this species are lacking. This study aimed to induce and characterize polyploid C. lansium lines, assess ploidy-dependent variations, and evaluate their impact on bioactive metabolite accumulation. Three cultivars were hybridized, treated with colchicine, and bred, yielding 13 stable polyploid lines confirmed by flow cytometry and chromosome counting. The polyploids exhibited distinct traits, including larger pollen grains, altered leaf margins, increased leaflet numbers, enlarged guard cells with reduced stomatal density, and thicker leaf tissues. Metabolomic analysis revealed that tetraploids accumulated significantly higher levels of flavonoids, alkaloids, and phenolic acids compared to diploids, while triploids showed moderate increases. These findings demonstrate that polyploidization, particularly tetraploidy, enhances C. lansium’s medicinal potential by boosting pharmacologically active compounds. The study expands germplasm resources and supports the development of high-quality cultivars for pharmaceutical applications. Full article

Improving photovoltaic (PV) panel performance under extreme climatic conditions is critical for advancing sustainable energy systems. In hyper-arid regions, elevated operating temperatures significantly reduce panel efficiency. This study investigates and compares three cooling techniques—air cooling, water cooling, and porous media cooling—using thermal and electrical modeling based on CFD simulations in ANSYS. The numerical model replicates a PV system operating under peak solar irradiance (900 W/m²) and realistic ambient conditions in Adrar, Algeria. Simulation results show that air cooling leads to a modest temperature reduction of 6 °C and a marginal efficiency gain of 0.25%. Water cooling, employing a top-down laminar flow, reduces cell temperature by over 35 °C and improves net electrical output by 30.9%, despite pump energy consumption. Porous media cooling, leveraging passive evaporation through gravel, decreases panel temperature by around 30 °C and achieves a net output gain of 26.3%. Mesh sensitivity and validation against experimental data support the accuracy of the model. These findings highlight the significant potential of water and porous material cooling strategies to enhance PV performance in hyper-arid environments. The study also demonstrates that porous media can deliver high thermal effectiveness with minimal energy input, making it a suitable low-cost option for off-grid applications. Future work will integrate long-term climate data, real diffuser geometries, and experimental validation to further refine these models. Full article

Objectives: The aim of the study was to assess the utility of contrast-enhanced ultrasound (CEUS), using both qualitative and quantitative perfusion analysis, in differentiating subtypes of renal cell carcinoma (RCC). Methods: This prospective, single-center study includes 91 patients with histologically confirmed RCC. We performed a CEUS within one week prior to nephrectomy. Qualitative parameters (enhancement pattern, heterogeneity, pseudocapsule) and quantitative perfusion metrics were assessed. Logistic regression models were developed to evaluate the diagnostic performance of CEUS in differentiating high-grade (clear cell RCC) from low-grade RCC (papillary and chromophobe). Results: Qualitative CEUS findings showed that hyperenhancement and isoenhancement were significantly associated with high-grade RCC (OR = 38.3 and OR = 7.8, respectively; p < 0.001 and p = 0.014). Hypoenhancement was predominant in low-grade RCC (80.0%). Quantitative parameters, including peak enhancement and wash-in/wash-out area under the curve, significantly differed between tumor grades (p < 0.001). A model using qualitative parameters alone achieved an AUC of 0.847 and 81.9% accuracy. Adding quantitative metrics marginally improved performance (AUC 0.912, accuracy 86.2%), though not significantly. Conclusions: CEUS provides valuable diagnostic information in differentiating RCC subtypes, with qualitative parameters alone demonstrating strong predictive power. While quantitative analysis slightly enhances diagnostic accuracy, its added value may be limited by technical challenges. Full article

In this study, we investigated the expression of TIM-3 and Galectin-9 (Gal-9) in colorectal cancer (CRC) and their associations with oncogenic mutations, MSI status, cytokine profiles, and transcriptional data. TIM-3 and Gal-9 protein levels were significantly increased in CRC tissues compared to matched non-tumor margins (p < 0.05 and p < 0.001, respectively). TIM-3 protein concentration was notably higher in PIK3CA-mutated tumors (p < 0.05), while no associations were found with KRAS, NRAS, BRAF, AKT1, or MSI status. Multiplex cytokine profiling revealed strong correlations between TIM-3 and Gal-9 levels and key immunomodulatory pathways, including IL-10, IL-17, and chemokine signaling. We also observed significant associations with cytokine subsets involved in protumor activity and immune regulation. Gene set enrichment analysis (GSEA) demonstrated that high TIM-3 and Gal-9 expression was associated with upregulation of cell cycle-related pathways, and downregulation of immune signatures, such as interferon responses and TNF-α/NFκB signaling. These findings suggest that increased TIM-3 and Gal-9 expression reflects a shift toward proliferative activity and immune suppression in the CRC tumor microenvironment, highlighting their potential as biomarkers of immunoevasive tumor phenotypes, especially in PIK3CA-mutant CRC tumors. Full article

The attachment of the oral epithelium to the abutment surface is crucial for the long-term success of dental implants. This study aimed to evaluate the attachment of human epithelial cells to anodized titanium surfaces. Anodized titanium discs were used as the experimental group, while machined titanium discs served as the control. Surface roughness and wettability were first measured for each group. Next, human epithelial cells were seeded onto each disc at a density of 4.0 × 10⁴ cells/cm² and evaluated 3, 6, and 24 h later for cell proliferation, as well as mRNA expression and protein levels of laminin and integrin β₄. Surface roughness was comparable between the two groups; however, wettability was significantly higher in the experimental group. Cell proliferation increased over time in both groups and showed no significant difference. Notably, the expression levels of both laminin and integrin β₄ were significantly higher in the experimental group at 24 h. Furthermore, protein localization of laminin and integrin β₄ was observed along the cell margins on the anodized surface. These findings suggest that anodization enhances epithelial cell attachment by promoting the expression and peripheral organization of key adhesion molecules. Full article