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
• Ataxia Telangiectasia Mutated Proteins genetics   MeSH
• Adult MeSH
• ErbB Receptors genetics   MeSH
• Papillomavirus Infections MeSH
• Cyclin-Dependent Kinase Inhibitor p16 genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Biomarkers, Tumor * genetics   analysis   MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Penile Neoplasms * genetics   mortality   pathology   virology   MeSH
• Prognosis MeSH
• Telomere-Binding Proteins MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Shelterin Complex MeSH
• Carcinoma, Squamous Cell * genetics   mortality   pathology   virology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

• MeSH
• Adult MeSH
• Forkhead Box Protein O1 * genetics   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * genetics   MeSH
• Mutation * MeSH
• Granulosa Cell Tumor * genetics   pathology   MeSH
• Ovarian Neoplasms * genetics   pathology   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Forkhead Box Protein L2 genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Telomerase genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Precise localization of peripheral nerve injuries and evaluation of their prognosis based on clinical and electrodiagnostic examinations are particularly challenging in the acute phase. High-resolution ultrasound (HRUS) may offer a viable and cost-effective imaging option for assessing the morphology of nerve injuries. Consequently, a systematic review and meta-analysis of studies on the use of ultrasound for diagnosing traumatic nerve injuries were conducted. A total of 15 studies were included, reporting the most recent findings on using HRUS in the diagnosis of traumatic nerve injury. These studies assessed the diagnostic test accuracy of ultrasound for the detection of traumatic nerve injury in 272 participants, with the cross-sectional area at the site of traumatic nerve injury also reported in 1,249 participants. The pooled sensitivity and specificity of the included studies were 92% confidence interval (CI) (0.89-0.95) and 86% CI (0.82-0.89), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 13.76 CI (1.41-134.34), 0.08 CI (0.03-0.18), and 286.23 CI (21.22-3,860.40), respectively. In the summary of the receiver operating characteristic curve, the area under the curve was 0.986, and the Q* index was 0.949. Based on the current literature, HRUS has shown promising results in addition to its availability and feasibility. HRUS can serve as a valuable complement to clinical and electrodiagnostic examinations for diagnosing traumatic peripheral nerve injuries. Further research is recommended to better understand the ultrasound characteristics of these injuries.

• MeSH
• Humans MeSH
• Peripheral Nerve Injuries * diagnostic imaging   diagnosis   MeSH
• Ultrasonography * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

• Publication type
• Journal Article MeSH

A tubular microdialysis probe is made from polysulfone hollow fibre for human haemodialysis, which has an inner diameter of 200 μm and a thickness of 20 μm. Milk is deposited to the outer surface of the hollow fibre and allowed to dry to form a dry sample. The tubular probe is then connected to the syringe pump and microdialysis of the dry sample into 0.5 mol/L HCl as acceptor is performed. 2.5 μL of microdialysate is obtained and analyzed for inorganic cations by capillary electrophoresis with contactless conductivity detection. Baseline separation of NH4+, K+, Ca2+, Na+, Mg2+, Li+ is achieved in 5.5 mol/L acetic acid as background electrolyte using a fused silica capillary with inner diameter of 25 μm and length of 31.5 cm. The reproducibility of dry sample microdialysis including CE analysis for peak area ranges from 2.4 to 3.9 % after normalization to Li+ as internal standard.

• MeSH
• Electrophoresis, Capillary * instrumentation   methods   MeSH
• Cations * analysis   MeSH
• Microdialysis * instrumentation   methods   MeSH
• Milk * chemistry   MeSH
• Cattle MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH

OBJECTIVE: This scoping review aims to identify, catalogue, and characterize previously reported tools, techniques, methods, and processes that have been recommended or used by evidence synthesizers to detect fraudulent or erroneous data and mitigate its impact. INTRODUCTION: Decision-making for policy and practice should always be underpinned by the best available evidence-typically peer-reviewed scientific literature. Evidence synthesis literature should be collated and organized using the appropriate evidence synthesis methodology, best exemplified by the role systematic reviews play in evidence-based health care. However, with the rise of "predatory journals," fraudulent or erroneous data may be invading this literature, which may negatively affect evidence syntheses that use this data. This, in turn, may compromise decision-making processes. INCLUSION CRITERIA: This review will include peer-reviewed articles, commentaries, books, and editorials that describe at least 1 tool, technique, method, or process with the explicit purpose of identifying or mitigating the impact of fraudulent or erroneous data for any evidence synthesis, in any topic area. Manuals, handbooks, and guidance from major organizations, universities, and libraries will also be considered. METHODS: This review will be conducted using the JBI methodology for scoping reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Databases and relevant organizational websites will be searched for eligible studies. Title and abstract, and, subsequently, full-text screening will be conducted in duplicate. Data from identified full texts will be extracted using a pre-determined checklist, while the findings will be summarized descriptively and presented in tables. REVIEW REGISTRATION: Open Science Framework https://osf.io/u8yrn.

• MeSH
• Humans MeSH
• Fraud prevention & control   MeSH
• Systematic Reviews as Topic MeSH
• Scientific Misconduct * MeSH
• Research Design standards   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

One of the main challenges in analyzing chemical messengers in the brain is the optimization of tissue sampling and preparation protocols. Limiting postmortem time and terminating enzyme activity is critical to identify low-abundance neurotransmitters and neuropeptides. Here, we used a rapid and uniform conductive heat transfer stabilization method that was compared with a conventional fresh freezing protocol. Together with a selective chemical derivatization method and an optimized quantitation approach using deuterated internal standards, we spatially mapped neurotransmitters and their related metabolites by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in rat brain tissue sections. Although the heat stabilization did not show differences in the levels of dopamine, norepinephrine, and serotonin, their related metabolites 3,4-dihydroxyphenylacetaldehyde, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylacetaldehyde, dihydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid were all significantly lower, indicating reduced neurotransmitter postmortem turnover ratios. Heat stabilization enabled detection of an increased number and higher levels of prodynorphin, proenkephalin, and tachykinin-derived bioactive neuropeptides. The low-abundant C-terminal flanking peptide, neuropeptide-γ, and nociceptin remained intact and were exclusively imaged in heat-stabilized brains. Without heat stabilization, degradation fragments of full-length peptides occurred in the fresh frozen tissues. The sample preparation protocols were furthermore tested on rat brains affected by acute anesthesia induced by isoflurane and medetomidine, showing comparable results to non-anesthetized animals on the neurotransmitters level without significant changes. Our data provide evidence for the potential use of heat stabilization prior to MALDI-MSI analyses to improve the examination of the in vivo state of neuronal chemical messengers in brain tissues not impacted by prior acute anesthesia.

• MeSH
• Rats MeSH
• Brain Chemistry * physiology   MeSH
• Brain * metabolism   MeSH
• Neurons * metabolism   chemistry   MeSH
• Neurotransmitter Agents * metabolism   analysis   MeSH
• Rats, Sprague-Dawley MeSH
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization * methods   MeSH
• Hot Temperature * MeSH
• Freezing MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Severe combined immunodeficiency (SCID) is a fatal but treatable inborn error of immunity (IEI). Newborn screening (NBS) using T-cell receptor excision circles (TREC) has been adopted globally, with very few countries incorporating kappa recombination excision circles (KREC) to also detect early B-cell development disorders, such as X-linked agammaglobulinemia (XLA). OBJECTIVE: To evaluate the effectiveness of a 2-year pilot SCID NBS program in the Czech Republic, emphasising the utility of combined TREC/KREC screening. METHODS: Between January 2022 and December 2023, a dual TREC/KREC NBS pilot was conducted across the Czech Republic, alongside spinal muscular atrophy (SMA) screening. Approximately 200,000 newborns were screened using quantitative real-time PCR on dried blood spots collected 48-72 h after birth. RESULTS: The pilot referred 58 newborns, identifying 21 cases of IEI, including two SCID cases, with an overall incidence of TREC/KREC screenable IEI of 10.5/100,000 newborns. SCID incidence was 1/100,000. KREC screening proved invaluable, detecting 10 cases of congenital agammaglobulinemia including novel non-XLA forms, which increased the estimated incidence of agammaglobulinemia in the Czech Republic sixfold. Over one-third of low KREC results were linked to maternal immunosuppression. CONCLUSION: The Czech pilot demonstrated the effectiveness of integrated TREC/KREC NBS in detecting both T- and B-cell immunodeficiencies. As of 2024, SCID and SMA screening are included in the nationwide NBS, with KREC screening significantly improving early detection of B-cell disorders.

• MeSH
• Agammaglobulinemia diagnosis   MeSH
• B-Lymphocytes immunology   MeSH
• Genetic Diseases, X-Linked MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening * methods   MeSH
• Pilot Projects MeSH
• Receptors, Antigen, T-Cell * genetics   MeSH
• Severe Combined Immunodeficiency * diagnosis   genetics   epidemiology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

INTRODUCTION: In developed countries, urologic fistulas arise mainly from malignancies, radiotherapy, or surgical trauma. Hysterectomy and radiation therapy are both critical components of the treatment of women with cancers. Urologic fistulas significantly reduce the quality of life of cancer patients, and may result in delays or even refusal of adjuvant treatment by these patients, thereby negatively impacting both short- and long-term cancer survival. MATERIALS AND METHODS: A 10-year retrospective study of urologic fistulas associated with gynaecologic malignancies at the University hospital Hradec Kralove, Czech Republic was conducted. Descriptive statistics of the fistula and treatment characteristics of women with malignant fistulas were conducted using the NCSS 22 statistical software program (NCSS, Keysville, Utah). RESULTS: Cervical cancer was mostly commonly associated with urologic fistulas (36, 76.8%). Most of the malignant fistulas were complex (41, 87.2%) vesicovaginal (23, 48.9%) fistulas (VVFs). More than two-thirds (33, 70.2%) of the fistulas were diagnosed following radiotherapy, with a time interval from radiotherapy to fistula diagnosis of between 3.00 and 14.50 years. Primary fistuloraphy was performed for all the six cases with simple VVFs and seven (41.2%) of the 17 patients with complex VVFs. Treatment success rate was 83.33% and 14.3% for simple and complex fistulas, respectively. All the failed complex fistula repairs recurred. CONCLUSION: Malignant fistulas predominantly follow radiotherapy for cervical cancers, and are usually detected up to 15 years post-radiotherapy. Most are complex VVFs, which are difficult to treat, with a high rate of recurrence.

• MeSH
• Adult MeSH
• Hysterectomy adverse effects   MeSH
• Quality of Life MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Fistula * etiology   epidemiology   MeSH
• Uterine Cervical Neoplasms * complications   MeSH
• Genital Neoplasms, Female * complications   therapy   pathology   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Vesicovaginal Fistula * etiology   epidemiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Umělá inteligence (AI) se stále častěji uplatňuje v radiologii, kde nabízí potenciál zlepšit přesnost a efektivitu diagnostiky, zejména při hodnocení běžných zobrazovacích metod, jako jsou rtg snímky hrudníku. Tato studie analyzuje přesnost komerčního softwaru využívajícího strojové učení, respektive metody umělé inteligence, při detekci abnormalit na rtg snímcích hrudníku ve srovnání s nezávislými hodnoceními 3 juniorních radiologů. Výzkum byl proveden ve spolupráci s Nemocnicí Tábor, která poskytla dataset 207 anonymizovaných rtg snímků, z nichž 196 bylo vyhodnoceno jako relevantní. Senzitivita a specificita AI byla porovnána s lidským hodnocením v 5 kategoriích abnormalit: atelektáza (ATE), konsolidace (CON), zvětšení srdečního stínu (CMG), pleurální výpotek (EFF) a plicní léze (LES). Software Carebot AI CXR dosáhl vysoké senzitivity ve všech hodnocených kategoriích (např. ATE: 0,909; CMG: 0,889; EFF: 0,951), přičemž jeho přesnost byla konzistentní napříč všemi nálezy. Naopak specificita AI byla v některých kategoriích nižší (např. EFF: 0,792; CON 0,895), zatímco u radiologů dosahovala ve většině případů hodnot blížících se 1,000 (např. RAD 1 a RAD 2 EFF: 1,000). AI vykazovala konzistentně vyšší senzitivitu než méně zkušení radiologové (např. RAD 1 ATE: 0,087; CMG: 0,327) a v některých případech i než zkušenější hodnotitelé, avšak za cenu mírného snížení specificity. Studie zahrnuje také kazuistiky, včetně falešně pozitivních a falešně negativních nálezů, které přispívají k hlubšímu pochopení přesnosti AI v klinické praxi. Výsledky naznačují, že AI může efektivně doplňovat práci radiologů, zejména u méně zkušených lékařů, a zlepšit senzitivitu diagnostiky na rtg snímcích hrudníku.

Artificial intelligence (AI) has been increasingly applied in radiology, where it offers the potential to improve the accuracy and efficiency of diagnosis, particularly in the evaluation of conventional imaging modalities such as chest X-rays. This study analyzes the performance of commercial software using machine learning and, respectively, artificial intelligence approaches (Carebot AI CXR; Carebot s.r.o.) in detecting abnormalities in chest radiographs compared with independent evaluations by 3 radiologists of different levels of experience. The study was conducted in collaboration with Hospital Tabor, which provided a dataset of 207 anonymised radiographs, out of which 196 were assessed as relevant. The sensitivity and specificity of AI were compared with human assessment in 5 categories of abnormalities: atelectasis (ATE), consolidation (CON), cardiac shadow enlargement (CMG), pleural effusion (EFF) and pulmonary lesions (LES). Carebot AI CXR software achieved high sensitivity in all evaluated categories (e.g., ATE: 0.909, CMG: 0.889, EFF: 0.951), and its performance was consistent across all findings. In contrast, AI specificity was lower in some categories (e.g., EFF: 0.792, CON: 0.895), while radiologists achieved performance values approaching 1.000 in most cases (e.g., RAD 1 and RAD 2 EFF: 1.000). AI demonstrated consistently higher sensitivity than less experienced radiologists (e.g., RAD 1 ATE: 0.087, CMG: 0.327) and in some cases than more experienced assessors, but at a modest decrease in specificity. The study also includes case reports, including false-positive and false-negative findings, which contribute to a deeper understanding of AI performance in clinical practice. The results suggest that AI can effectively complement the work of radiologists, especially for less experienced doctors, and improve the sensitivity of diagnosis on chest radiographs.