Search Results (927)

Neurolymphomatosis (NL), a rare manifestation of non-Hodgkin’s lymphoma affecting the peripheral nervous system, remains a diagnostic challenge. This study aimed to define an optimal diagnostic approach for timely and effective identification of NL. We analyzed 559 NL cases from 231 articles published from 1951 to 2022, examining how patient outcomes correlated with various diagnostic modalities, including magnetic resonance imaging (MRI), computed tomography (CT), [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET), electromyography-nerve conduction studies (EMG-NCS), ultrasound, and tissue biopsy when used individually or in combination. Separate analyses were performed in a mutually exclusive fashion to minimize confounding effects from multiple modalities. The results of this investigation revealed that patients with biopsies had a longer time interval from first treatment to progression (Kruskal–Wallis p < 0.0001), survival from diagnosis (overall survival) (p < 0.0001), and survival from symptom onset (p < 0.0001), but not symptom onset to diagnosis (p = 0.2134). Pairwise comparisons of biopsy plus 2, 3, or 4 diagnostic modalities revealed a positive trend for the combination of biopsy + PET + MRI + EMG-NCS. A majority of patients without biopsy had secondary NL. In this non-biopsied population, no diagnostic modality had a significant correlation with outcome. The data collectively indicate that histological confirmation of NL from biopsy was associated with a positive patient outcome. Management of NL patients requires timely testing using PET, MRI, and EMG-NCS to quickly identify a site for image-guided nerve biopsy. Full article

Maternal exposure to airborne particulate matter smaller than $2.5$ μm (${\mathrm{PM}}_{2.5}$) has been associated with adverse fetal outcomes, although its effects on intramembranous ossification remain poorly understood. This study evaluated the impact of gestational and pregestational exposure to wood-smoke-derived ${\mathrm{PM}}_{2.5}$ on fetal neurocranial ossification in Sprague–Dawley rats. Females were allocated to four exposure conditions combining filtered air (FA) and non-filtered air (NFA): FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Fetuses were collected at gestational day 21 and analyzed using fetal morphometry, radiography, micro-computed tomography, whole-mount alizarin red skeletal staining, histology, and immunohistochemistry for HIF-1$\alpha$, COL-1, BMP-2, FGF-R1, and TGF-$\beta$. Continuous exposure (NFA/NFA) was associated with reduced fetal weight, shorter crown–rump length, impaired craniofacial mineralization, widened cranial sutural regions, and reduced mineral density, particularly in the occipital and interparietal bones. Histologically, exposed fetuses exhibited abundant osteoid, reduced osteocyte incorporation, and diffuse osteoblastic distribution, consistent with delayed osteogenic maturation. Immunohistochemistry showed increased HIF-1$\alpha$ immunoreactivity, altered TGF-$\beta$ regulation, and reduced COL-1 expression in continuously exposed fetuses, whereas BMP-2 and FGF-R1 showed no significant changes. These findings suggest that maternal exposure to wood-smoke-derived PM_2.5 is associated with delayed fetal neurocranial intramembranous ossification, particularly under continuous exposure. The observed immunohistochemical profile, elevated HIF-1$\alpha$, reduced COL-I, and altered TGF-$\beta$, is consistent with a hypoxia-associated imbalance between extracellular matrix deposition and mineral maturation; however, the underlying mechanistic pathway was not directly functionally tested and should be regarded as a biologically plausible inferential model requiring further experimental validation. Full article

Background: Thymic epithelial tumors (TETs) are rare mediastinal malignancies whose prognosis is largely determined by histology. Current predictive models rely on clinical variables and subjective imaging interpretation, with unsatisfied performance. Non-invasive pre-treatment risk stratification could guide surgical planning and perioperative management in patients with TETs. The role of fluorine-18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) in identifying aggressive disease is increasingly recognized. In this bicentric study, we aimed to evaluate a machine learning-based radiomics model using PET and CT images to differentiate between low-risk and high-risk TETs. Methods: Seventy-five patients who underwent PET/CT to evaluate the suspected anterior mediastinal mass and histopathologically diagnosed with TETs were included. On PET/CT images, the tumor was manually segmented by two experienced clinicians. First-order, shape, and texture features were extracted using the PyRadiomics library, resulting in 200 radiomics features (186 intensity/texture features and 14 shape features). In addition, rPET (i.e., tumor SUVmax/Liver SUVmax) parameter was included, yielding a grand total of 201 features. The feature set was reduced to 20 variables using ANOVA, with both selection and model evaluation performed via stratified 5-fold cross-validation. Results: The proposed approach achieved an average balanced accuracy of 0.58 ± 0.07 and an average AUC of 0.71 ± 0.04. Average sensitivity and specificity were 0.48 and 0.68, respectively. The model obtained an average Gmean of 0.57, indicating balanced and stable classification performance. Conclusions: Our ML models trained on PET/CT radiomic features showed moderate discriminatory performance for TET risk stratification. Full article

Background/Objectives: Intranasal tumors are common malignancies in dogs, characterized by locally aggressive behavior and clinical signs such as epistaxis, nasal discharge, and facial deformity. Radiotherapy (RT) is considered the treatment of choice due to anatomical limitations to surgical resection. This study aimed to evaluate clinical outcomes, toxicity, and prognostic factors in dogs with primary malignant intranasal tumors treated with cobalt-60–based megavoltage radiotherapy. Methods: This retrospective study included 40 dogs with histopathologically confirmed primary malignant intranasal tumors treated between September 2018 and February 2025 at a veterinary radiotherapy clinic in Rio de Janeiro, Brazil. Medical records were reviewed for patient demographics, tumor characteristics, treatment protocols, response, toxicity, and survival outcomes. Tumors were staged using modified Adams criteria based on computed tomography. Definitive-intent protocols (n = 32) delivered 48–54 Gy in 10–13 fractions administered three to five times weekly, while palliative protocols consisted of either four fractions of 8 Gy delivered once weekly or five fractions of 4 Gy delivered daily. Results: Adenocarcinoma was the most common histologic subtype (42.5%), and 82.5% of dogs had stage III–IV disease. The objective response rate was 82.5% (CR: 17.5%; PR: 65.0%), with clinical benefit observed in 92.5% of cases. Acute toxicity was frequent but manageable, primarily affecting skin, oral mucosa, and eyes. Overall median progression-free interval (PFI) and survival time (MST) were 382 days and 430 days, respectively. Stage IV disease was significantly associated with shorter survival when compared to stage I-III (MST 345 vs. 1063 days, respectively; p = 0.016). Treatment response was significantly associated with PFI in univariate analysis (p < 0.05). Conclusions: Radiotherapy provided high response rates and meaningful clinical benefit with acceptable toxicity in dogs with malignant intranasal tumors, highlighting the importance of early diagnosis and treatment. Further prospective studies with standardized protocols are warranted. Full article

Methods of ridge preservation following tooth extraction, aiming to maintain alveolar bone volume and support tissue regeneration, have been extensively researched. Continuously, new approaches and materials are being explored in this context. To scientifically evaluate outcomes, the pre-implant situation is usually assessed radiologically, histologically, and/or clinically. However, the influence of ridge preservation on implant placement itself is rarely examined in depth, and if at all, the focus has been on implant stability or survival rates. Based on the assumption that preoperative radiological assessment, including cone beam computed tomography, provides only an indirect and inherently limited approximation of actual intraoperative bone condition, undetected factors such as insufficient bone density, mechanically unfavorable trabecular structure, or incompletely resorbed residual biomaterial may necessitate a shift of the implant from the preferred position originally occupied by the tooth root. We therefore established a method that evaluates and categorizes implant position in three dimensions based on radiological data post-implantation. Our data, derived from a multicenter randomized clinical trial (RCT), demonstrate that the greatest positional deviations are observed without preservation, whereas the combination of biomaterial and PRF most frequently allowed for central implant placement. The proposed method proves well suited for evaluating the outcome of ridge preservation procedures. The findings demonstrate that both the absence and presence, and further the type, of preservation have a measurable influence on the final implant positioning. Full article

Background/Objectives: Given rising lung cancer incidence and limited data on pulmonologist-performed ultrasound-guided transthoracic core biopsy (US-TTCB), in this study, we evaluated diagnostic yield and safety for pleural or pulmonary lung masses, using Clavien–Dindo classification to standardize complication reporting. Methods: We retrospectively reviewed single-center pulmonologist-performed US-TTCB using a MEDONE biopsy gun with a 16 G/18 G Tru-Cut needle between January 2019 and December 2025. The primary endpoints were diagnostic yield, defined as specific malignant or benign histology, and complication rate. Non-diagnostic results were assessed using available clinical/imaging follow-up. Univariate analyses screened candidate correlates, and a prespecified computer tomography (CT)-completed subanalysis (n = 67) used multivariable logistic regression and receiver operating characteristic (ROC) analysis to assess CT lesion size discrimination. Results: Diagnostic yield was 84.2% (202/240); complications occurred in 12.1% (29/240), including one Clavien–Dindo Grade III event (0.4%). In the CT-completed subset (n = 67), diagnostic yield was independently associated with CT lesion size (aOR 1.03/mm, 95% CI 1.00–1.05; p = 0.022) and Chronic Obstructive Pulmonary Disease (COPD) (aOR 2.30, 95% CI 1.06–4.96; p = 0.034); CT lesion size showed an area under the curve (AUC) of 0.717 for predicting yield. Diagnostic yield remained stable over time (84.2% in first vs. second half; p = 1.00), with no association between case order and yield (OR 0.999; p = 0.64). Conclusions: US-TTCB of pleural/pulmonary masses achieved a high diagnostic yield with minimal major complications. Large CT dimension and COPD were associated with higher diagnostic success, and CT size provided fair discrimination for predicting yield; findings should be interpreted in the context of the retrospective single-center design and the restricted CT-completed subset. Full article

Whole-slide imaging has transformed histopathology into a data-rich domain; however, many computational pathology models encode tissue morphology within latent representations, limiting interpretability, reproducibility, and generalization. This review positions histomics as an intermediate phenotype representation layer linking histological images with downstream clinical inference through structured descriptors of tissue morphology, spatial organization, and tissue architecture. Unlike prior reviews focused primarily on feature extraction or predictive performance, the study adopts a representation-centric perspective of histomics. A taxonomy of histomic features across biological scales is presented, and artificial intelligence frameworks, including machine learning, deep learning, weakly supervised learning, and multimodal approaches, are systematically examined. Key challenges, including segmentation dependence, feature instability, aggregation variability, and domain shift, are critically analyzed alongside emerging developments in foundation models, representation learning, and multimodal pathology. The review provides a unified framework for understanding histomic representations and identifies future directions for developing robust, interpretable, and generalizable computational pathology systems. Full article

Breast cancer is a highly prevalent malignancy among women globally and arises from the uncontrolled proliferation of abnormal cells in breast tissue. Timely and precise diagnosis is critical for effective treatment and enhanced survival. Histopathological image analysis is considered the gold standard; nevertheless, manual assessment is labor-intensive and prone to variability. Existing deep learning and transformer-based approaches demonstrate strong effectiveness; however, they incur significant computational complexity and limited efficiency in capturing multi-scale features. To address these challenges, this research presents a framework that integrates ConvMixer, multi-scale patch learning, and an Adaptive Combined Runge–Kutta–Harris Hawks Optimization (AC-RUNHHO) algorithm. The model effectively captures both fine-grained cellular patterns and global tissue structures, while adaptive optimization improves convergence and hyperparameter tuning. The framework is evaluated on a breast cancer histology dataset comprising 4000 histopathological images across four classes. Experimental results demonstrate robust performance under the evaluated experimental conditions, achieving 98.63% accuracy, 98.63% precision, 98.62% recall, and 98.62% F1-score. Ablation and cross-validation analyses further confirm the generalization capability of the model. Overall, the developed framework demonstrates promising performance in computer-aided breast histopathological image classification, achieving high predictive accuracy and providing interpretable visual explanations. Full article

Morus alba L. fruit extract (MFE), which is rich in cyanidin 3-glucoside (C3G), demonstrates antioxidant properties and pharmacological effects, but its reproductive safety remains poorly understood. Polyphenols modulate steroidogenesis, spermatogenesis, and sperm acrosome integrity; therefore, toxicity assessment is needed for use. This study aimed to evaluate the antioxidant profiles and subchronic reproductive effects of MFE. MFE was standardized using high-performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Male rats were administered MFE (250 or 500 mg/kg BW) for 56 days. Assessments included computer-assisted sperm analysis (CASA), testosterone, seminal fructosamine, and testicular CYP11A1 and androgen receptor (AR) expression. Acrosomal status was determined using PNA lectin staining. The results showed that MFE contained C3G (119.42 mg/g), antioxidant capacity (DPPH IC₅₀: 0.101 mg/mL; FRAP: 465.01 µmol Fe (II)/g), and total contents (phenolics: 41.15 mg GAE/g; flavonoids: 3.15 mg CE/g; anthocyanidins: 11.04 mg C3G/g). MFE did not alter testicular histology and seminiferous stages VII-IX. High doses significantly increased sperm concentration, while both doses reduced sperm beat cross frequency. Testosterone, fructosamine, and CYP11A1/AR expressions showed increasing trends. Significantly, high doses induced a precocious acrosome reaction. In conclusion, MFE has no reproductive toxicity and pro-fertility effects on sperm quantity or androgenic markers, supporting safe subchronic use. Full article

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterised by elevated serum levels of IgG4 and multiorgan damage. Its diagnosis is challenging and requires a careful integration of clinical, radiological, serological and histological data. Pancreatic and biliary involvement is one of the most common manifestations of IgG4-RD, presenting as type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC), two entities that often occur synchronously and may mimic malignancy in the form of pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma, respectively. The main objective of this article is to illustrate the key imaging features of AIP and IgG4-SC on computed tomography (CT) and magnetic resonance imaging (MRI), providing a comprehensive review of their current diagnostic criteria and discussing their differential diagnosis with other benign and malignant conditions. Full article

Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg/kg) mitigates cadmium-induced toxicity (5 mg/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (−30.8%), elevated transaminases (AST, ALT; p < 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p < 0.01). Sperm concentration dropped from 75.2 to 21.8 × 10⁶/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 × 10⁶/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver/kidney biomarkers showed significant but incomplete recovery (p < 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (−8.4 kcal/mol), CAT (−8.3 kcal/mol), and SOD (−6.4 kcal/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery. Full article

Background/Objectives: Pleura-based pulmonary nodules in soft-tissue sarcoma (STS) patients remain diagnostically challenging, and entity-specific contrast-enhanced ultrasound (CEUS) data are scarce. We aimed to characterize CEUS perfusion patterns of pleura-based STS pulmonary metastases in a pilot cohort. Methods: We investigated a single-center retrospective cohort at a tertiary STS referral center (Dec 2024–Dec 2025). Of 51 consecutive STS patients with suspected pulmonary metastases screened, 32 lacked pleural contact and 6 were excluded for logistical reasons; the remaining 13 underwent standardized CEUS of a pleura-contacting lesion (≥5 mm) visible on B-mode lung ultrasound (B-LUS), with 1 excluded on biopsy (anaplastic lymphoma). The reference standard combined histology, therapy-related size reduction of the index lesion, and/or documented distant metastatic STS. Two readers rated all examinations independently, with adjudication by a third senior reader. Wilson 95% confidence intervals (CIs) and Cohen’s κ were computed. Results: In the 12 analyzed patients (mean age 58.8 ± 17.8 years; 7 male), the index lesion was histologically confirmed in 4 (33.3%). On CEUS, bronchial-arterial (BA) enhancement predominated (10/12; 83.3%, 95% CI 55.2–95.3%) and pulmonary-arterial timing occurred in 2/12 (16.7%). Marked enhancement was present in 9/12 (75.0%), homogeneous in 8/12 (66.7%), and rapid washout (<120 s) in all lesions (12/12; 100%, 95% CI 75.8–100%). Inter-reader agreement was substantial to almost perfect for the diagnostically relevant CEUS perfusion variables (enhancement κ = 0.75; EE κ = 0.80; HE κ = 0.82) and moderate for the descriptive shape variable (Form κ = 0.47). Conclusions: In this selected pilot cohort, pleura-based STS lung metastases most commonly showed BA-dominant enhancement with universal rapid washout. The findings are hypothesis-generating and require validation in larger, prospective multicenter cohorts. Full article

In situ hybridization (ISH) has undergone a rapid evolution from a low-throughput histological staining technique to a diverse family of modern methods for sensitive, specific and multiplexed molecular detection in intact cells and tissues, and to a cornerstone technology for image-based spatial transcriptomics. This transformation has been driven by advances in probe design, signal amplification, cyclic imaging, combinatorial barcoding, automated fluidics and computational decoding, which together allow RNA molecules to be measured within preserved cellular and tissue architecture. In this review, we examine the molecular and engineering principles that underlie modern ISH methods and their extension into ISH-based spatial profiling, with emphasis on hybridization chain reaction, branched-DNA amplification, SABER-FISH, rolling-circle-amplification-based approaches, seqFISH, MERFISH, RAEFISH and selected commercial implementations. We discuss how sensitivity, specificity, tissue compatibility, optical crowding, imaging burden, cost, reproducibility and computational uncertainty shape the practical use of each method. Sequencing-based spatial capture platforms are not reviewed comprehensively, but are considered where comparative benchmarks help clarify trade-offs in spatial resolution, transcriptome breadth, tissue area or analytical interpretation. We also consider how recent benchmarking and standardization efforts are beginning to define quantitative criteria for comparing platforms, and how advances in segmentation, barcode decoding, spatial integration and cell–cell communication analysis convert raw images into biological insight. Finally, we highlight applications in targeted transcript detection, tissue-based validation, neuroscience, cancer, developmental biology, non-model organisms and spatial functional genomics, where modern ISH methods and ISH-based spatial profiling provide information that bulk and dissociated single-cell approaches cannot capture. Together, these developments trace how ISH has expanded from targeted molecular visualization into a broad methodological framework for in situ detection and spatially resolved transcriptomic analysis. Full article

Background: Acetamiprid (ACMP) exposure mediates a variety of pathological complications, including testicular toxicity. Berberine (BBR) is a plant-derived alkaloid with potential pharmacological properties. This study sought to evaluate the ameliorative effects of BBR against ACMP-induced testicular toxicity. Methods: Male Wistar rats were divided into four groups: control, BBR-treated, ACMP-exposed, and BBR+ACMP co-treated, and were administered with BBR (150 mg/kg b.wt) and ACMP (21.7 mg/kg b.wt) for 21 days. Biochemical and FTIR analyses, RT-PCR, computational analyses, and histopathological examination were conducted to assess alterations in lipid and protein profiles, as well as apoptotic and structural changes. Results: ACMP exposure was associated with oxidative injury, functional alterations (stretching of -OH, -CH₂, -NH, C=O, C-N, -COO-, -PO₂⁻), and compositional changes in proteins and lipids. Pre-treatment of BBR (2 h prior) was associated with attenuation of the functional and compositional alterations in proteins and lipids in co-treated rats. RT-PCR and computational analysis showed increased Bax and caspase-3 and decreased Bcl-2 mRNA expression, suggesting a potential modulation of ACMP-induced apoptosis by BBR. Histological examination showed that pre-treatment with BBR prevented ACMP-induced structural alterations, including cellular disorganization and alteration in seminiferous tubules. Conclusions: The study suggested that the BBR may exert ameliorative effects against ACMP-induced testicular toxicity by modulating lipid and protein changes and the anti-apoptotic pathway. Thus, BBR could be used as a potential ameliorative agent against oxidative stress. However, more mechanistic studies are needed for broader biological relevance and validity. Full article

Objectives: Cone-beam computed tomography (CBCT) is central to three-dimensional assessment in oral surgery and implant dentistry; however, CBCT-derived gray values expressed as HU-like units are not equivalent to true CT-derived Hounsfield Units (HU). This brief methodological secondary analysis evaluated the reliability and practical limitations of such values in assessing radiographic changes after peri-implantitis surgery. Methods: The analysis used the imaging protocol and group-level radiological data from a previously published prospective clinical cohort, conducted under the same protocol and ethical approval of the Institutional Ethics Committee of the Medical University of Lublin (KE-0254/248/11/2023; 23 November 2023). The source cohort included 57 patients treated after implant removal for severe peri-implantitis with small-particle dentin (n = 22), Bio-Oss (n = 15), or spontaneous healing without grafting (n = 20). CBCT scans were analyzed in OnDemand3D (version 1.0.11.1007) using manually selected square regions of interest (ROI; 30 × 30 pixels). No external phantom calibration, cross-device normalization, or formal intra-/inter-observer reproducibility assessment was available in the secondary dataset. Results: The previously reported mean study-site values were 779.62 ± 325.92 gray-value units for small-particle dentin, 910.51 ± 155.03 gray-value units for Bio-Oss, and 206.04 ± 174.21 gray-value units for controls. These findings are presented as protocol-dependent attenuation patterns, not as direct material rankings, bone-density thresholds, or proof of regeneration. Variability remained substantial, with study-site coefficients of variation of 41.8%, 17.0%, and 84.6%, respectively, and high adjacent-site variability. Interpretation was constrained by manual ROI placement, lack of calibration, absence of observer-agreement metrics, unequal follow-up timing, and CBCT sensitivity to scatter, beam hardening, field of view, reconstruction settings, and metal-related artifacts. Conclusions: CBCT-derived gray values may be useful as relative indicators of local radiographic attenuation change within a standardized protocol, but they should not be interpreted as absolute measures of bone density. Future regenerative oral surgery studies should combine standardized acquisition, explicit ROI methodology, repeated measurements, observer-agreement analysis, and complementary clinical, radiographic, or histological outcomes. Full article