Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the World Health Organization distinguishes between human papillomavirus (HPV)-related and HPV-independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 expression, as well as clusters of genes associated with HPV status. In this study, we conducted comprehensive next-generation sequencing DNA profiling of 146 pSCC samples using a panel consisting of 355 genes associated with tumors. This profiling was correlated with immunohistochemical markers and prognostic clinical data. A survival analysis of recurrent genomic events (found in ≥10 cases) was performed. TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR alterations were associated with significantly shortened overall survival in univariate and multivariate analysis. HPV positivity, diagnosed through both p16 immunohistochemistry and HPV DNA analysis, displayed no impact on survival but was associated with high-grade, lymphatic invasion, programmed death ligand-1 negativity/weak expression, and low TMB. FAT1, TP53, CDKN2A, CASP8, and HRAS were more often mutated in HPV-independent pSCC. In contrast, HPV-associated pSCCs were enriched by EPHA7, ATM, GRIN2A, and CHEK1 mutations. PIK3CA, FAT1, FBXW7, and KMT2D mutations were associated with high TMB. NOTCH1, TP53, CDKN2A, POT1, KMT2D, ATM, CHEK1, EPHA3, and EGFR alterations were related to adverse clinicopathologic signs, such as advanced stage, high tumor budding, and lymphovascular invasion. We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination repair pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular pathologic, clinical, and prognostic analysis correlating with prognosis.

• MeSH
• ATM protein genetika   MeSH
• dospělí MeSH
• erbB receptory genetika   MeSH
• infekce papilomavirem MeSH
• inhibitor p16 cyklin-dependentní kinasy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory penisu * genetika   mortalita   patologie   virologie   MeSH
• prognóza MeSH
• proteiny vázající telomery MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shelterinový komplex MeSH
• spinocelulární karcinom * genetika   mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.

• MeSH
• 2. světová válka * MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychický stres MeSH
• socioekonomické faktory MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH

BACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

• MeSH
• chromozomální proteiny, nehistonové * genetika   metabolismus   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   metabolismus   genetika   MeSH
• lymfatické metastázy MeSH
• nádorové biomarkery * genetika   metabolismus   MeSH
• nádory prostaty rezistentní na kastraci patologie   genetika   metabolismus   MeSH
• nádory prostaty * patologie   metabolismus   genetika   MeSH
• prognóza MeSH
• senioři MeSH
• stupeň nádoru MeSH
• transkripční faktory genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Escherichia coli is a significant pathogen in extraintestinal infections, and ESBL-producing E. coli poses a major clinical challenge due to its antibiotic resistance. This study comprehensively analyzed E. coli isolates from urine and blood samples of patients with urinary tract and bloodstream infections at three major tertiary hospitals in South Korea. The goal was to provide insights into the distribution, antibiotic resistance, and virulence factors of these strains. Our analysis identified CTX-M and TEM as the dominant ESBL types, found in 71.7% and 61.7% of isolates, respectively, with 46.7% showing co-occurrence. Multilocus sequence typing (MLST) revealed the predominance of high-risk clones such as ST131, ST69, ST73, and ST95, with rare sequence types like ST410 and ST405 also identified. The high prevalence of virulence factors, including iutA (80.8%) and kpsMII (74.2%), further highlights the complexity of these strains. In addition, 38.3% of clinical isolates contained a combination of siderophore, adhesin, protectin, and toxin-related genes. There was no significant difference between urinary tract and bloodstream infections or regional differentiation in Korea. This study highlights the importance of controlling ESBL-producing E. coli infections, especially given the increasing incidence among patients with underlying medical conditions and older adults who are more susceptible to urinary tract infections. These findings serve as valuable indicators for pathogen analysis, especially those harboring antibiotic resistance and toxin genes. The insights gained are expected to contribute significantly to the development of infectious disease prevention and control strategies.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriemie * mikrobiologie   epidemiologie   MeSH
• beta-laktamasy * genetika   metabolismus   MeSH
• dospělí MeSH
• Escherichia coli * genetika   izolace a purifikace   patogenita   enzymologie   účinky léků   klasifikace   MeSH
• faktory virulence genetika   MeSH
• infekce močového ústrojí * mikrobiologie   epidemiologie   MeSH
• infekce vyvolané Escherichia coli * mikrobiologie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mladý dospělý MeSH
• multilokusová sekvenční typizace MeSH
• prevalence MeSH
• proteiny z Escherichia coli genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• virulence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Korejská republika MeSH

Super-resolution (SR) microscopy is a cutting-edge method that can provide detailed structural information with high resolution. However, the thickness of the specimen has been a major limitation for SR methods, and large biological structures have posed a challenge. To overcome this, the key step is to optimise sample preparation to ensure optical homogeneity and clarity, which can enhance the capabilities of SR methods for the acquisition of thicker structures. Oocytes are the largest cells in the mammalian body and are crucial objects in reproductive biology. They are especially useful for studying membrane proteins. However, oocytes are extremely fragile and sensitive to mechanical manipulation and osmotic shocks, making sample preparation a critical and challenging step. We present an innovative, simple and sensitive approach to oocyte sample preparation for 3D STED acquisition. This involves alcohol dehydration and mounting into a high refractive index medium. This extended preparation procedure allowed us to successfully obtain a unique two-channel 3D STED SR image of an entire mouse oocyte. By optimising sample preparation, it is possible to overcome current limitations of SR methods and obtain high-resolution images of large biological structures, such as oocytes, in order to study fundamental biological processes. Lay Abstract: Super-resolution (SR) microscopy is a cutting-edge tool that allows scientists to view incredibly fine details in biological samples. However, it struggles with larger, thicker specimens, as they need to be optically clear and uniform for the best imaging results. In this study, we refined the sample preparation process to make it more suitable for SR microscopy. Our method includes carefully dehydrating biological samples with alcohol and then transferring them into a mounting medium that enhances optical clarity. This improved protocol enables high-resolution imaging of thick biological structures, which was previously challenging. By optimizing this preparation method, we hope to expand the use of SR microscopy for studying large biological samples, helping scientists better understand complex biological structures.

• MeSH
• alkoholy MeSH
• fluorescenční mikroskopie metody   MeSH
• myši MeSH
• odběr biologického vzorku metody   MeSH
• oocyty * MeSH
• refraktometrie metody   MeSH
• zobrazování trojrozměrné * metody   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The intertumoral and intratumoral heterogeneity of colorectal adenocarcinoma (CRC) at the morphologic level is poorly understood. Previously, we identified morphological patterns associated with CRC molecular subtypes and their distinct molecular motifs. Here we aimed to evaluate the heterogeneity of these patterns across CRC. Three pathologists evaluated dominant, secondary, and tertiary morphology on four sections from four different FFPE blocks per tumor in a pilot set of 22 CRCs. An AI-based image analysis tool was trained on these tumors to evaluate the morphologic heterogeneity on an extended set of 161 stage I-IV primary CRCs (n = 644 H&E sections). We found that most tumors had two or three different dominant morphotypes and the complex tubular (CT) morphotype was the most common. The CT morphotype showed no combinatorial preferences. Desmoplastic (DE) morphotype was rarely dominant and rarely combined with other dominant morphotypes. Mucinous (MU) morphotype was mostly combined with solid/trabecular (TB) and papillary (PP) morphotypes. Most tumors showed medium or high heterogeneity, but no associations were found between heterogeneity and clinical parameters. A higher proportion of DE morphotype was associated with higher T-stage, N-stage, distant metastases, AJCC stage, and shorter overall survival (OS) and relapse-free survival (RFS). A higher proportion of MU morphotype was associated with higher grade, right side, and microsatellite instability (MSI). PP morphotype was associated with earlier T- and N-stage, absence of metastases, and improved OS and RFS. CT was linked to left side, lower grade, and better survival in stage I-III patients. MSI tumors showed higher proportions of MU and TB, and lower CT and PP morphotypes. These findings suggest that morphological shifts accompany tumor progression and highlight the need for extensive sampling and AI-based analysis. In conclusion, we observed unexpectedly high intratumoral morphological heterogeneity of CRC and found that it is not heterogeneity per se, but the proportions of morphologies that are associated with clinical outcomes.

• MeSH
• adenokarcinom * patologie   genetika   mortalita   MeSH
• dospělí MeSH
• kolorektální nádory * patologie   genetika   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Neuromuscular diseases (NMDs) are rare disorders characterized by progressive muscle fibre loss, leading to replacement by fibrotic and fatty tissue, muscle weakness and disability. Early diagnosis is critical for therapeutic decisions, care planning and genetic counselling. Muscle magnetic resonance imaging (MRI) has emerged as a valuable diagnostic tool by identifying characteristic patterns of muscle involvement. However, the increasing complexity of these patterns complicates their interpretation, limiting their clinical utility. Additionally, multi-study data aggregation introduces heterogeneity challenges. This study presents a novel multi-study harmonization pipeline for muscle MRI and an AI-driven diagnostic tool to assist clinicians in identifying disease-specific muscle involvement patterns. METHODS: We developed a preprocessing pipeline to standardize MRI fat content across datasets, minimizing source bias. An ensemble of XGBoost models was trained to classify patients based on intramuscular fat replacement, age at MRI and sex. The SHapley Additive exPlanations (SHAP) framework was adapted to analyse model predictions and identify disease-specific muscle involvement patterns. To address class imbalance, training and evaluation were conducted using class-balanced metrics. The model's performance was compared against four expert clinicians using 14 previously unseen MRI scans. RESULTS: Using our harmonization approach, we curated a dataset of 2961 MRI samples from genetically confirmed cases of 20 paediatric and adult NMDs. The model achieved a balanced accuracy of 64.8% ± 3.4%, with a weighted top-3 accuracy of 84.7% ± 1.8% and top-5 accuracy of 90.2% ± 2.4%. It also identified key features relevant for differential diagnosis, aiding clinical decision-making. Compared to four expert clinicians, the model obtained the highest top-3 accuracy (75.0% ± 4.8%). The diagnostic tool has been implemented as a free web platform, providing global access to the medical community. CONCLUSIONS: The application of AI in muscle MRI for NMD diagnosis remains underexplored due to data scarcity. This study introduces a framework for dataset harmonization, enabling advanced computational techniques. Our findings demonstrate the potential of AI-based approaches to enhance differential diagnosis by identifying disease-specific muscle involvement patterns. The developed tool surpasses expert performance in diagnostic ranking and is accessible to clinicians worldwide via the Myo-Guide online platform.

• MeSH
• dospělí MeSH
• internet MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• neuromuskulární nemoci * diagnóza   diagnostické zobrazování   MeSH
• strojové učení * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hyaluronan and hyaluronidases are critical in tissue remodeling, inflammation, and tumor progression. This chapter provides a comprehensive guide to hyaluronan zymography, a powerful technique for detecting and quantifying hyaluronidase activity in complex biological samples. The method involves separating proteins by polyacrylamide gel electrophoresis with hyaluronan incorporated into the gel matrix. Following electrophoresis, the gel is incubated to allow hyaluronidases to degrade the hyaluronan substrate, resulting in clear digestion zones. Detailed protocols for sample preparation and the zymographic process are included, offering researchers a robust tool for studying hyaluronidase activity and regulation in various biological contexts.

• MeSH
• elektroforéza v polyakrylamidovém gelu * metody   MeSH
• enzymatické testy * metody   MeSH
• hyaluronoglukosaminidasa * metabolismus   MeSH
• kyselina hyaluronová * metabolismus   chemie   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cellular processes such as tissue regeneration, inflammation, and migration require the proteolysis of the extracellular matrix and the proteolytic activation of signaling molecules. A widely used and accessible technique for studying these processes is gelatin zymography, particularly for investigating matrix metalloproteinases (MMPs), though it is not limited to them. This method is favored for its simplicity, low cost, and robustness. Despite certain limitations, it remains a preferred approach for the initial investigation of complex samples.Here, we present a protocol applicable to various sample sources, including proteases from human cell lines and bacteria isolated from chronic wounds. We also explore changes in protease activity within exudates from human chronic wounds, a challenging analysis for more complex techniques. Additionally, we emphasize the potential to extend the basic protocol to study the conditions under which proteases are active.

• MeSH
• chronická nemoc MeSH
• elektroforéza MeSH
• enzymatické testy * metody   MeSH
• lidé MeSH
• matrixové metaloproteinasy * metabolismus   MeSH
• rány a poranění * enzymologie   MeSH
• želatina * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Febrilné kŕče (FK) postihujú približne 2-5% detí. Podľa väčšiny guidelines je indikáciou k hospitalizácii a diagnostike podskupina komplikovaných resp. rekurentných simplexných FK. V prípade stabilného stavu u dieťaťa (nad 18 mesiacov) po simplexných FK nie je dôvod hospitalizovať ani rozširovať diagnostiku, u detí do 18 mesiacov sa odporúča observácia do vylúčenia neuroinfekcie. Cieľom bolo porovnať publikované odporúčania s realitou praxe. Materiál a metódy: Súbor tvorilo 66 detí s FK hospitalizovaných počas 12 mesiacov na Klinike detí a dorastu UPJŠ LF a DFN Košice. Pacienti boli rozdelení podľa klinického stavu a priebehu. Manažment bol porovnaný s medzinárodnými odporúčaniami s cieľom preveriť opodstatnenosť vyšetrení (elektroencefalografia, EEG) a samotnej hospitalizácie. Výsledky: V 14 prípadoch bola dôvodom prijatia opodstatnená neurologická indikácia (komplikované FK n = 5 resp. recidivujúce simplexné kŕče n = 9). V prípadoch prvovýskytu simplexného charakteru bolo v 11 prípadoch (16% z celého súboru) hospitalizované aj stabilné dieťa s nízkym rizikom komplikácií. Počas hospitalizácie bolo EEG realizované až u 75% detí (n = 39) zo skupiny prvého výskytu simplexných FK, pričom žiadne nemalo abnormálny nález. Záver: Štúdia konštatuje nadužívanie EEG vyšetrenia, ktoré v prípade jednoduchých FK nemá opodstatnenie. EEG a neuropediatrické vyšetrenie sa odporúča realizovať len v prípadoch komplikovaných a rekurentných jednoduchých FK. Dáta potvrdzujú benígny charakter FK a podčiarkujú význam nasledovania medicínskych postupov založených na dôkazoch s cieľom racionalizácie a optimalizácie zdravotnej starostlivosti. Hospitalizácia detí s nekomplikovanými FK je opodstatnená len v prípade potreby diagnostiky a liečby pridruženej komorbidity (signifikantná dehydratácia apod.), alebo ak neuroinfekciu nie je možné klinicky vylúčiť z dôvodu nízkeho veku.

Introduction: Febrile seizures (FS) cumulatively affect approximately 2-5% of children. According to most guidelines, complicated and recurrent simplex FS are indicated for hospitalization and further diagnostic workup. In the case of a stable condition in a child (over 18 months) after simple FK, there is no reason to hospitalize or extend the diagnosis, in children under 18 months observation is recommended until neuroinfection is ruled out. The aim was to compare published recommendations with the reality of practice. Material and methods: Studied sample consisted of 66 children with FS hospitalized over 12 months at the Department of Paediatrics and Adolescent Medicine of P. J. Safarik University and Children Teaching Hospital in Košice. Patients were divided according to clinical status and course. The management was compared with international recommendations in order to verify the validity of examinations (electroencephalography, EEG) and hospitalization itself. Results: In 14 cases, the reason for admission was a justified neurological indication (complicated FS n=5 or recurrent simplex convulsions n=9). In cases of first simple FS 11 cases were identified (16% of the entire set) where a stable child with a low risk of complications was also hospitalized. During hospitalization, EEG was carried out in up to 75% of children (n=39) from the subgroup of first simple FS. None of them had abnormal EEG findings. Conclusions: The study shows the overuse of the EEG examination, which is not justified in the case of simple FS. Electroencephalographic and neuropediatric examination is recommended only in cases of complicated and recurrent simple FS. The data confirm the benign nature of FS and underline the importance of following evidence-based medical practices to rationalize and optimize health care. Hospitalization of children with uncomplicated FS is justified only if diagnosis and treatment of associated comorbidity is necessary (significant dehydration, etc.) or if neuroinfection cannot be clinically excluded due to young age.

• MeSH
• benzodiazepiny farmakologie   terapeutické užití   MeSH
• diferenciální diagnóza MeSH
• elektroencefalografie metody   MeSH
• febrilní křeče * diagnóza   etiologie   klasifikace   komplikace   MeSH
• infekce centrálního nervového systému diagnóza   komplikace   MeSH
• kojenec MeSH
• lidé MeSH
• nemoci nervového systému diagnóza   klasifikace   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• Geografické názvy
• Slovenská republika MeSH