Hyperplastic nodules (HNs) are benign polypoid lesions of the colorectal mucosa reportedly caused by hyperplasia of the crypt epithelial cells. They differ from hyperplastic polyps because the crypts do not have histologically serrated changes. HNs often occur in the rectal mucosa and tend to be multifocal. We have proposed a new colitis nucleomigrans (CN) concept as the third type of microscopic colitis. Our histopathological criteria of CN include: i) chained nuclear migration to the middle part of the surface-lining columnar epithelium, ii) apoptotic nuclear debris scattered in the eosinophilic cytoplasm underneath the nuclei, and iii) mild to moderate chronic inflammation in the lamina propria. Immunostaining for cleaved-caspase 3 revealed apoptotic bodies. In this study, we report that most HN lesions share the histological features with CN, representing polypoid CN. We evaluated 108 lesions of HN in total, and 94 (87%) were reclassified as polypoid CN. In the polypoid CN, the lamina propria mucosae were uniformly edematous, suggesting that accelerated apoptosis of the mucosal surface epithelium may cause osmotic dysregulation to form localized mucosal elevations.

Breast cancer is the second cause of fatality among all cancers for women. Automatic classification of breast cancer lesions in mammograms is a challenging task due to the irregularity and complexity of the location, size, shape, and texture of these lesions. The intensity dissimilarity has been found between breast cancer tissues and normal tissues, when a multi-spectral anatomical mammographic screening scans have been done. In this work, two approaches have been evaluated to classify the breast tumor lesions. The first one is through Gabor wavelet features and the second one is Statistical features. Subsequently, support vector machine, Multilayer Perceptron and KNN classifiers have been used with computer based method for breast tumor classification.

Objective: The aim of this study was to evaluate the clinical outcome of patients suffering from chronic limb threatening ischemia (CLTI) and tissue loss treated with primary isolated femoral bifurcation endarterectomy (FBE) or with FBE combined with bypass surgery. Methods: This retrospective study was performed in a tertiary university based care center. Between January 2008 and December 2019 a prospectively collected database of patients suffering from CLTI and tissue loss and undergoing either primary FBE (group A) or FBE in combination with bypass surgery (group B) was analysed. Study endpoints were ulcer healing, primary and secondary patency rate, limb salvage and survival. Results: In total, FBE was performed in 73 and FBE with bypass in 60 patients. Between both groups there were no significant differences regarding demographic data or the Global Limb Anatomic Staging System (GLASS) grade III and IV of femoropopliteal lesions. After 3 years, ulcer healing could be achieved in 72% of FBE and in 75% of FBE with bypass patients. The primary patency rate was 95% and 91% for FBE and 83% and 80% for FBE with bypass after one and three years, respectively. The 3-year limb salvage rate was 78% for FBE and 84% for FBE with bypass. The secondary patency rate after one and three years was 99% and 97% for FBE and 93% and 88% for FBE with bypass. Conclusion: FBE and FBE with bypass are equally effective for ulcer healing in cases of combined CFA and superficial femoral artery lesions. There was no significant difference between both groups regarding primary and secondary patency

Objectives. Optimal treatment strategy for ischemic stroke in patients presenting with tandem occlusions the internal carotid artery remains controversial. Several studies have demonstrated better clinical outcomes after eptifibatide, which is a short half-life antiplatelet agent. This retrospective analysis was focused at safety and efficacy of administration of low-dose eptifibatide in stroke patients with tandem lesions. Methods. We evaluated results of endovascular treatment in 148 stroke patients with tandem lesions. Patients in whom balloon angioplasty alone resulted in satisfactory cerebral flow did not receive eptifibatide (33 patients); others received this drug together with stent implantation (115 patients). Eptifibatide was given in as intravenous bolus 180 g/kg, and then in modified low dose of 1 g/kg/min for 24 hours. Results. There were no statistically significant differences between both groups regarding 30-day mortality, frequency of thrombotic events and hemorrhagic complications. Analysis of clinical status at 30-day follow-up revealed that administration of eptifibatide was associated with statistically significant better outcome: a higher rate of either no neurological symptoms or only mild symptoms (4 NIHSS points maximally). Conclusions. Administration of eptifibatide in stroke patients presenting with tandem lesions is relatively safe. Moreover, treatment with this drug can improve clinical outcomes in these challenging patients.

Premalignant lesions in the bronchial epithelium represent early stages of squamous cell lung carcinoma, challenging to detect with conventional methods. While previous studies have focused on gene expression, here we examine transcriptomic alterations associated with lesion development with the emphasis on protein-coding transcripts. We reanalyzed publicly available RNAseq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript abundances were quantified using kallisto, and differential expression and transcript usage analysis was conducted using the sleuth and RATs packages. Functional characterization included overrepresentation analysis (clusterProfiler), weighted co-expression network analysis (WGCNA), and network analysis (Enrichr-KG). We detected 5,906 differentially expressed transcripts, with significant enrichment in pathways related to oxidative phosphorylation and mitochondrial function. Transcript-level WGCNA identified single module correlated with dysplasia status, enriched in cilium-related biological processes. Analysis of hubs within this module highlighted key genes including RABL2B, DNAH1, EFHC1 and VWA3A, and revealed transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant lesion biology. By examining transcripts rather than genes, we identified potential biomarkers associated with early lung carcinogenesis.

Background: To assess effectiveness, safety of computed tomography (CT)-guided cryoablation for treating adrenal metastases (AMs). Materials and Methods: This study involved 12 patients treated with 13 CT-guided cryoablation procedures for AMs between 2016 and 2020. Patients’ ineligible for surgery, with tumors ≤5 cm, and no significant health risks were included. The procedures, conducted by expert radiologists, included initial non-contrast CT scans to determine lesion morphology, followed by cryoablation with monitoring for complications. Post-treatment, patients underwent regular physical and laboratory checks, including hormonal analysis, and CT scans at specified intervals to assess the treatment's effectiveness and detect disease recurrence or progression. Results: In this study, 12 patients with AMs successfully underwent cryoablation, achieving a primary technical success rate of 91.7% and a secondary rate of 100% after a repeat procedure for one patient. All cryoablation sessions were completed without major complications, with ice ball formations extending 1 cm beyond tumor margins to ensure safety. Over an 8–24-month follow-up (average 16.3 months), six patients required further systemic therapy, with three developing extra-adrenal tumors. Local progression was noted in two patients (16.7%), one of whom underwent a repeat cryoablation. Systemic progression was observed in five patients, involving renal and NSCLC cancer recurrences and bone metastasis. The study reported five deaths due to tumor progression and heart failure, with an average overall survival duration of 32.4 ± 7.6 months.

Breast cancer (BC) affects millions of women; it is the leading cause of death by neoplasia in wom-en worldwide, with at least 500 thousand deaths each year, 70% of which occur in developing countries. Elastography evaluates tissue stiffness, making this a promising non-invasive real-time technique. BI-RADS is recognized as a standard and helpful technique for establishing BC risk. This study aimed to determine, by strain elastography (SE), the fat-to-lesion index (F/L index), sen-sitivity, specificity, and optimal cut-off to diagnose BC. This prospective study included 216 wom-en who underwent SE, ultrasound, mammography, and breast biopsy; according to mammogra-phy, we recruited BI-RADS category 2 (n= 5), category 3 (n=29), category 4 (n= 94), category 5 (n= 71) and category 6 (n=17); after biopsy, 108 women were classified as negative, and 108 were pos-itive for BC. Three expert BC radiologists performed all imaging interpretations and biopsies. Our results show mean values of the F/L index for negative biopsies of 3.70±2.57 and positive biopsies of 18.10±17.01; we developed two models for the prediction of BC, a logistic regression model with an AUC of 0.893 and a neural network with an AUC of 0.902. The Youden index yielded a F/L index cut-off >5.76, with a sensitivity and specificity of 84.26%. Positive Spearman's Rho cor-relation coefficient was observed between the F/L index and BI-RADS, r=.073 (p< 0.001). ANOVA test showed a difference between F/L index vs. molecular subtypes (p=0.002). SE is helpful as a di-agnostic complement to mammography, or in cases where the latter is contraindicated, elas-tography has an adequate predictive capacity and is a fast and minimally invasive procedure.

Oral pyogenic granuloma (PG) is generally a solitary benign connective tissue proliferation of unknown etiology. It is the most common type of oral inflammatory hyperplasia histologically characterized by proliferation of granulation tissue with inflammatory infiltrates and high angiogenic capacity. Vascular neoformations of different diameters are usually present. Due to their structural characteristics, tendency to bleed, and rapid and alarming growth rate, these neoformations may have serious consequences. Sometimes, it is complex to make an accurate diagnosis. Therefore, adequate management and treatment are based on the characteristics and systemic conditions of each patient. This review was carried out to provide an overview of the factors involved in, or attributed to the etiopathogenesis of oral PG. It describes the different forms of presentation and clinical evolution, as well as the most frequent signs and symptoms that characterize this disease, while incorporating recent radiographic and microscopic findings. In addition, it describes the different modalities for the management of oral pyogenic granuloma depending on the particular characteristics of each patient.

The red fox, found on all continents except Antarctica, occupies diverse habitats. In Croatia it is an indigenous wild species with a population density of 0.7 animals per square kilometer. While tumors in wild animals from the Canidae family are scarce, the true prevalence and diversity of tumors are likely underestimated due to limited research. So far, a limited number of tumors were observed among the red fox population, either in their natural habitat or in captivity. As part of the National rabies control program, we examined 1,890 red fox carcasses over a four-year period. Our focus was on identifying abnormalities on the skin and internal organs that suggest potential neoplastic proliferation. Five red foxes, three males and two females, were found to have growths resembling potential tumors. Their age distribution spanned from 2 to 7 years. Microscopic investigation revealed two collagenous hamartomas, two Meibomian gland adenomas and one intra-abdominal teratoma within a cryptorchid testis. This retrospective study aims to provide a comprehensive description of tumor and tumor-like lesions observed in free-range red foxes from Croatia, marking the first research of its kind in Croatia.

Management of Sclerotinia stem rot (SSR) disease in Brassica napus is heavily reliant on prophylactic fungicide applications at flowering, which often provides inconsistent control depending on timing of ascospore release in the field and environmental conditions. Understanding host response to Sclerotinia sclerotiorum infection is essential for sustainable disease management in the future. This study determined the host response of nine B. napus varieties to four aggressive S. sclerotiorum isolates across two years by measuring four disease variables; area under the disease progress stairs (AUDPS), seed production, sclerotia number and average sclerotia weight. Brassica napus varieties varied greatly in their response to the four measured variables, with varieties producing the highest AUDPS not the same varieties that had the lowest seed production, the highest numbers of sclerotia or heaviest sclerotia. Repeating the experiment over two years using the same varieties and isolates identified the impact of environment as the most influential factor on measured disease variables, highlighting the complexity of disease responses to diverse isolates and host genotypes under different environments. It was recommended that both long-term (such as inoculum production) and short-term (such as seed production) disease outcomes be combined with lesion length measurement (i.e. AUDPS) for future host screening studies.

Plant-parasitic nematodes are a major constraint for agricultural production. They significantly impede crop yield. To complete their parasitism, they need to locate, disguise, and interact with plant signals exuded in the rhizosphere of the host plant. A specific subset of the soil microbiome can attach to the surface of nematodes in a specific manner. We hypothesized that host plants recruit species of microbes as helpers against attacking nematode species, and that these helpers differ among plant species. We investigated to what extend the attached microbial species are determined by plant species, their root exudates, and how these microbes affect nematodes. We conditioned the soil microbiome in the rhizosphere of different plant species, then employed culture-independent and culture-dependent methods to study the microbial attachment to the cuticle of the phytonematode Pratylenchus penetrans. Community fingerprints of nematode-attached fungi and bacteria showed that the plant species govern the microbiome associated with nematode cuticle. Bacteria isolated from the cuticle belonged to Actinobacteria, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Sphingobacteria, and Firmicutes. The isolates Microbacterium sp. i.14, Lysobacter capsici i.17, and Alcaligenes sp. i.37 showed the highest attachment rates to the cuticle. The isolates Bacillus cereus i.24 and L. capsici i.17 significantly antagonized P. penetrans after attachment. Significantly more bacteria attached to P. penetrans in microbiome suspensions from bulk soil or oat rhizosphere compared to Ethiopian mustard rhizosphere. However, the latter caused a better suppression of the nematode. Conditioning the cuticle of P. penetrans with root exudates significantly decreased the number of Microbacterium sp. i.14 attaching to the cuticle, suggesting induced changes of the cuticle structure. These findings will lead to a more knowledge-driven exploitation of microbial antagonists of plant-parasitic nematodes for plant protection.

Introduction: PP, also called plantar ligament, is a fibrocartilaginous structure found in the metatarsophalangeal (MP) and interphalangeal (IP) joints. The aim of our study is to evaluate the role of MRI, both in standard position and with joint hyperextension, “stress test” (ST), in the study of the plantar plate (PP) disease that involves metatarsophalangeal joints. Material and methods: 25 patients were recruited into our study over a two-year period, 15 positive for metatarsal pain and 10 controls. All symptomatic patients were evaluated before treatment (surgery). Hence, the imaging features were reflective of the natural and true state of the lesions. Results:25 patients were recruited into our study over a two-year period, 15 positive for metatarsal pain and 10 controls. In symptomatic patients: 11/15 demonstrated plantar plate tear/dysfunction on both standard position and stress test, 2/15 had plantar plate tear on stress test (tear not showed on standard position), and 2/12 had no plantar plate tear on both standard position and stress test. The latter two patients showed dorsal subluxation on stress test due to micro-instability for plantar plate failure. In asymptomatic patients, 9/10 were negative for plantar plate dysfunction, and 1/10 was positive for plantar plate dysfunction (dorsal subluxation demonstrated only on stress test), without plantar plate tear. Conclusion:Standard MRI reported, in asymptomatic patients, a specificity of 100% and high NPV (90%), incremented by the ST (NPV and specificity 100%). In symptomatic patients, PP evaluation on standard MRI reported sensitivity of 80%, while stress test increased sensitivity to 100%; in the evaluation of dorsal subluxation of the metatarsophalangeal joint, the sensitivity was 60% (standard MRI) but reached 100% with ST. "Stress test" is an easy task to perform and even affordable in terms of time-consuming (requiring only one additional T2-weighted MRI sequence) for both patients and operators.

(1) Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the standard method for treating early-stage cancer or precancerous lesions in the upper gastrointestinal tract, however it may be difficult in patients with liver cirrhosis due to coagulation dysfunction or presence of gastroesophageal varices. We aimed to demonstrate the safety and efficacy of ESD in these population. (2) Methods: We retrospectively collected the clinical data and analyzed. Patients inclusion criteria: 1) patients with liver cirrhosis; 2) patients who underwent ESD; 3) patients diagnosed of early-stage cancer or precancerous lesions in the upper gastrointestinal tract. (3) Results: Eight patients were enrolled from April 2019 to April 2023, of whom 3 were male and 5 female, with age ranging from 43 to 70 years old. Seven lesions were located in the stomach, and the other one lesion in the esophagus. ESD was performed successfully in all patients, and the resected lesion size ranged from 2 to 6 cm. Only one patient encountered postoperative complication, chest pain and fever. No recurrence of noticed during a follow-up of 6 to 36 months. (4) Conclusions: ESD is safe and effective for treating upper gastrointestinal early-stage cancer or precancerous lesions in patients with liver cirrhosis.

Pratylenchus loosi is an important root-lesion nematode that cause damage to tea plantations in Iran and all over the world. The present study reports on the characterization and evolution of three ß-1,4-engoglucanase genes Pl-eng-2, Pl-eng-3 and Pl-eng-4. The gene structure of Pl-eng-2 was fully determined with the predicted signal peptide and devoid of the linker domain and carbohydrate-binding domain, while Pl-eng-3 and Pl-eng-4 were only partially sequenced. The transcription of Pl-eng-2 was localized in the secretory esophageal glands of all life stages, but it was upregulated in male and females stages. Exon/intron structures of Pl-eng-2, Pl-eng-3 and Pl-eng-4 confirmed that they resulted from gene duplication followed by sequence and gene structure diversification with loss of linker domain and carbohydrate-binding domain during evolution. Phylogenetic analysis further confirmed that nematode endoglucanases resulted from horizontal gene transfer of a bacterial gene as Pl-eng-3 showed sister relationships with CelB cellulase of Bacillus subtilis. Silencing Pl-eng-2 by in vitro RNA interference, produced a 60% decrease of the transcript level. The reproductive ability of silenced P. loosi showed a 35% reduction of eggs and larval stages compared to untreated nematodes suggesting that this gene is involved in the early steps of invasion.

Epidemiologic studies suggest an inverse correlation between coffee consumption and the occurrence of neurodegenerative diseases, but the role of caffeine and roasting degree are still matter of debate. The objective of this work was to evaluate the effects of caffeinated (light, medium, and dark roast) and decaffeinated instant coffee samples in acetylcholinesterase inhibition and antioxidant assays, as well as in animal models of Parkinson’s disease. Caffeinated coffees inhibited the acetylcholinesterase in much smaller concentrations than decaffeinated coffee. All coffee samples showed antioxidant capacity without relation with the caffeine content. Dopaminergic-like activity in the haloperidol-induced catalepsy test was observed with caffeinated coffee, but not in the decaffeinated sample. The medium roast coffee reduced the number of rotations of rats after methamphetamine administration on the 6-hydroxydopamine unilateral lesion of the medial forebrain bundle. However, the coffee treatment did not avoid the loss of dopaminergic neurons on substantia nigra pars compact and only the smallest dose of coffee was able to avoid the decrease of dopamine levels in the lesioned side of the striatum. Altogether, these results suggest that coffee exerts moderate pro-cholinergic and pro-dopaminergic effects and caffeine seems to be the main responsible for these effects.

Automated skin lesion analysis is one of the trending fields that has gained attention among the dermatologists and healthcare practitioners. Skin lesion restoration is an essential preprocessing step for lesion enhancements for accurate automated analysis and diagnosis. Digital hair removal is a non-invasive method for image enhancement by solving the hair-occlusion artefact in previously captured images. Several hair removal methods were proposed for skin delineation and removal. However, manual annotation is one of the main challenges that hinder the validation of these proposed methods on a large number of images or using benchmarking datasets for comparison purposes. In the presented work, we propose a realistic hair simulator based on context-aware image synthesis using image-to-image translation techniques via conditional adversarial generative networks for generation of different hair occlusions in skin images, along with the ground-truth mask for hair location. Besides, we explored using three loss functions including L1-norm, L2-norm and structural similarity index (SSIM) to maximise the synthesis quality. For quantitatively evaluate the realism of image synthesis, the t-SNE feature mapping and Bland-Altman test are employed as objective metrics. Experimental results show the superior performance of our proposed method compared to previous methods for hair synthesis with plausible colours and preserving the integrity of the lesion texture.

White spot lesions (WSLs), a side effect of orthodontic treatment, can result in reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass (BAG) mixture(BAG@GO) was added to Low Viscosity Transbond XT(LV) in a ratio of 1, 3, 5%. The composite’s characterization and its physical and biological properties were verified with scanning electron microscopy(SEM) and X-ray diffraction(XRD); its microhardness, shear bond stress (SBS), cell viability, and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL was evaluated using antibacterial activity of S. mutans. Anti-demineralization was analyzed using a cycle of the acid-base solution. Adhesives with 3 or 5 wt.% of BAG@GO showed significant increase in microhardness compared with LV. The sample and LV groups showed no significant differences in SBS or ARI. The cell viability test confirmed that none of the sample groups showed higher toxicity compared to the LV group. Antibacterial activity was higher in the 48-hour group than in the 24-hour group; the 48-hour test showed that BAG@GO had a high antibacterial effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO concentration, the higher the anti-demineralization effect.

A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.

Lesion studies are crucial in establishing brain-behavior relationships, and accurately segmenting the lesion represents the first step in achieving this. Manual lesion segmentation is the gold standard for chronic strokes. However, it is labor-intensive, subject to bias, and limits sample size. Therefore, our objective is to develop an automatic segmentation algorithm for chronic stroke lesions on T1-weighted MR images. Methods: To train our model, we utilized an open-source dataset: ATLAS v2.0 (Anatomical Tracings of Lesions After Stroke). We partitioned the dataset of 655 T1 images with manual segmentation labels into five subsets and performed a 5-fold cross-validation to avoid overfitting of the model. We used a deep neural network (DNN) architecture for model training. Results: To evaluate the model performance, we used three metrics that pertain to diverse aspects of volumetric segmentation including shape, location, and size. The Dice similarity coefficient (DSC) compares the spatial overlap between manual and machine segmentation. The average DSC was 0.65 (0.61- 0.67; 95% bootstrapped CI). Average symmetric surface distance (ASSD) measures contour distances between the two segmentations. ASSD between manual and automatic segmentation was 12mm. Finally, we compared the total lesion volumes and the Pearson correlation coefficient (ρ) between the manual and automatically segmented lesion volumes, which was 0.97(p-value &lt; 0.001). Conclusions: We present the first automated segmentation model trained on a large multicentric dataset. This model will enable automated on-demand processing of MRI scans and quantitative chronic stroke lesion assessment.

The anarchic hand syndrome refers to an inability to control the movements of one’s own hand which acts as if it had a will of its own. The symptoms may differ depending on whether the brain lesion is anterior, posterior, callosal or subcortical, but the relative classifications are not conclusive. This study investigates the role of white matter disconnections in a patient whose symptoms are inconsistent with the mapping of the lesion site. A repeated neuropsychological investigation was associated with a review of the literature on the topic to identify the frequency of various different symptoms relating to this syndrome. Furthermore, an analysis of the neuroimaging regarding structural connectivity allowed us to investigate the grey matter lesions and white matter disconnections. The results indicated that some of the patient’s symptoms were associated with structures that, although not directly damaged, were dysfunctional due to a disconnection in their networks. This suggests that the anarchic hand may be considered as a disconnection syndrome involving the integration of multiple antero-posterior, insular and interhemispheric networks. In order to comprehend this rare syndrome better, the clinical and neuroimaging data need to be integrated with the clinical reports available in the literature on the topic.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Melanoma is widely recognized as one of the most lethal forms of skin cancer, with its incidence showing an upward trend in recent years. Nonetheless, the timely detection of this malignancy substantially enhances the likelihood of patients’ long-term survival. Several computer-based methods have recently been proposed in the pursuit of diagnosing skin lesions at their early stages. Despite achieving some level of success, there still remains a margin of error that the machine learning community considers to be an unresolved research challenge. This study presents a novel framework for the classification of skin lesions. The framework incorporates deep features to generate a highly discriminant feature vector, while also maintaining the integrity of the original feature space. Recent deep models including Darknet53, DenseNet201, InceptionV3, and InceptionResNetV2 are employed in our study for the purpose of feature extraction. Additionally, transfer learning is leveraged to enhance the performance of our approach. In the subsequent phase, the extracted feature information from the chosen pre-existing models is combined, with the aim of preserving maximum information, prior to undergoing the process of feature selection using a novel entropy-controlled grey wolf optimization (ECGWO) algorithm. The integration of fusion and selection techniques is employed to initially incorporate the feature vector with a high level of information and subsequently eliminate redundant and irrelevant feature information. The efficacy of our design is substantiated through the evaluation on three benchmark dermoscopic datasets, namely PH2, ISIC-MSK, and ISIC-UDA. In order to validate the proposed methodology, a comprehensive evaluation is conducted, including a rigorous comparison with established techniques in the field.

Increasingly small, non-palpable testicular incidentalomas <1cm are discovered in the clinical practice. The ESUR Scrotal and Penile Imaging Working Group suggests active surveillance with US, and surgery only for nodules that grow. This approach, however, requires validation. A consecutive series of 127 incidentalomas were initially followed-up and operated if they were growing (n=28), or because of preference of the patient and of the referring urologist (n=11). For the lesions that were growing specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential grow. Also, the velocity of increase of the average diameter (∆Dav) and of the maximum diameter (∆Dmax) were calculated. Of the 127 nodules which were initially followed-up, 6 disappeared, 8 reduced in size, 85 were stable, and 28 increased in size. All 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47x10-3 %volume/day, ≤179 days, >10x10-3 mm/day, and >5x10-3 mm/day for SGR, DT, ∆Dmax, ∆Dav, respectively. A conservative approach of non-growing small incidentalomas is safe. Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though superimposition exists.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Objective: Radiomics and deep transfer learning are two popular technologies used to develop computer-aided detection and diadnosis (CAD) schemes of medical images. This study aims to investigate and compare advantages and potential limitations of applying these two technologies in developing CAD schemes. Methods: A relatively large and diverse retrospective dataset including 3,000 digital mammograms is assembled in which 1,496 images depict malignant lesions and 1,054 images depict benign lesions. Two CAD schemes are developed to classify breast lesions. The first scheme is developed using four steps namely, applying an adaptive multi-layer topographic region growing algorithm to segment lesions, computing initial radiomics features, applying a principal component algorithm to generate an optimal feature vector, and building a support vector machine classifier. The second CAD scheme is built based a pre-trained residual net architecture (ResNet50) as a transfer learning model to classify breast lesions. Both CAD schemes are trained and tested using a 10-fold cross-validation method. Several score fusion methods are also investigated to classify breast lesions. CAD classification performance is evaluated by the area under ROC curve (AUC). Results: ResNet50 model-based CAD scheme yields AUC = 0.85±0.02, which is significantly higher than radiomics feature-based CAD scheme with AUC = 0.77±0.02 (p < 0.01). Additionally, fusion of classification scores generated by two CAD schemes does not further improve classification performance. Conclusion: This study indicates that using deep transfer learning is more efficient to develop CAD schemes and enables to yield higher lesion classification performance than CAD schemes developed using radiomics-based technology.

Treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone by block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (7 horses per group) and 18 months (7 MSC- and 5 control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation-, lameness- and ultrasonography scores improved more over time in the MSC-group. The lameness score difference significantly improved in the MSC- compared to the control-group after 6 months. In the MSC-group, 5 out of 7 horses were free of re-injuries and back to training until 12 and 18 months. In the control-group, 3 out of 7 horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for treatment of early phase tendon disease and provide a basis for a larger controlled study.

The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

It is one of the central goals of cognitive neuroscience to understand how structure and function relate in the brain. We review how cognitive function characterization has been approached in the past. In addition, we examine the ongoing efforts, as well as the implications for the future. Clinical studies on patients with lesions have provided key insights into the relationship between brain areas and behavior over the past century. We describe cognitive function according to localization considering these early efforts for characterization. We chose a perceptual-cognitive function, namely body perception, to describe our current efforts. Using body perception as an example, we summarize contemporary techniques. Finally, we outline the trajectory of current progress into the future and discuss the implications for clinical and basic neuroscience.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.