Mariana Bisarro Dos Reis, Monise Tadin Reis, Marcus Matsushita, Gustavo Noriz Berardinelli, Tatiana Camacho Cheregatto, Welinton Hirai, Valiana Teodoro, Denise Peixoto Guimarães, Rui Manuel Reis
{"title":"Tumor-Associated Fusobacterium nucleatum and Aggressive Architectural Features in Stage II Colorectal Cancer.","authors":"Mariana Bisarro Dos Reis, Monise Tadin Reis, Marcus Matsushita, Gustavo Noriz Berardinelli, Tatiana Camacho Cheregatto, Welinton Hirai, Valiana Teodoro, Denise Peixoto Guimarães, Rui Manuel Reis","doi":"10.1111/apm.70225","DOIUrl":"10.1111/apm.70225","url":null,"abstract":"<p><p>Tumor budding (TB) and poorly differentiated clusters (PDCs) are histopathological indicators of invasive potential in colorectal cancer (CRC). Concurrently, Fusobacterium nucleatum (F. nucleatum) has emerged as a modulator of CRC progression. The relationship between intratumoral F. nucleatum and aggressive tumor architecture remains unknown. We evaluated 257 stage II primary CRCs. TB and PDC were assessed at the invasive front. Intratumoral F. nucleatum DNA was quantified from FFPE samples using droplet digital PCR. Associations between F. nucleatum load and molecular and clinicopathological features were analyzed. F. nucleatum was detected in 44.4% of tumors, with 19.8% classified as high bacterial load. Tumors with high F. nucleatum had a significantly higher frequency of intermediate- and high-grade PDCs (p = 0.047), with a specific enrichment for high-grade PDCs (p = 0.019). High F. nucleatum load was also associated with microsatellite instability (MSI-H). No significant associations were observed between F. nucleatum presence or load and 10-year overall, disease-free, and cancer-specific survival. A high F. nucleatum intratumoral burden was associated with aggressive tumor architecture characterized by PDC in stage II CRC. Nevertheless, no impact on long-term clinical outcomes was observed, indicating that F. nucleatum had limited prognostic value.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70225"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic Value of miR-517c-3p in Lung Cancer and Its Regulatory Effect on Tumor Progression.","authors":"Jia Chen, Qiu Ren, Bowen Sun, Yong Sun, Hongjie Jiang, Junwen Wang","doi":"10.1111/apm.70206","DOIUrl":"10.1111/apm.70206","url":null,"abstract":"<p><p>This study investigated the prognostic value and molecular mechanisms of miR-517c-3p in lung cancer. miR-517c-3p in 112 lung cancer tissues was detected using qRT-PCR. Kaplan-Meier survival analysis and Cox regression were used to assess its prognostic significance. Functional experiments, including cell proliferation, migration, and invasion, were conducted in lung cancer cell lines (H1229, A549) after miR-517c-3p overexpression. Target gene prediction and validation were performed using bioinformatics tools and dual-luciferase reporter assays. The regulatory effects of miR-517c-3p on ARNTL2 were further explored through gene overexpression and rescue experiments. miR-517c-3p was significantly downregulated in lung cancer tissues (p < 0.001) and correlated with advanced TNM stage, lymph node metastasis, and larger tumor size. Patients with low miR-517c-3p expression exhibited poorer overall survival (p < 0.001), and Cox regression identified miR-517c-3p as an independent prognostic factor (HR = 0.110, 95% CI = 0.047-0.256). Functional assays demonstrated that miR-517c-3p overexpression inhibited lung cancer cell proliferation, migration, and invasion. Dual-luciferase reporter assays confirmed ARNTL2 as a direct target of miR-517c-3p, and ARNTL2 restoration reversed the suppressive effects of miR-517c-3p on tumor progression. miR-517c-3p is significantly downregulated in lung cancer and associated with poor patient prognosis. Furthermore, miR-517c-3p suppresses tumor progression by directly targeting ARNTL2.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70206"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos A Rubio, Daniel Firmbach, Christian Matek, Michael Vieth, Corinna Lang-Schwarz
{"title":"Additional Crypt Phenotypes Lined With High-Grade Cellular Dysplasia in Protruding Growths in Ulcerative Colitis.","authors":"Carlos A Rubio, Daniel Firmbach, Christian Matek, Michael Vieth, Corinna Lang-Schwarz","doi":"10.1111/apm.70216","DOIUrl":"10.1111/apm.70216","url":null,"abstract":"<p><p>Two crypt phenotypes (ACP): crypt rings in tandem (CRT) and crypts with lateral budding's (CLB's) were recently found interpolated amidst generally accepted crypt phenotypes (GACP, i.e., tubular, tubulovillous, villous and serrated). The frequency of cases with UC-PDG, with CRT and with CLB's in GACP and in UC-associated sporadic adenomas (UC-aspa) was recorded. The possibility that the presence of ACP could increase histological discrimination between UC-PDG and UC-aspa was also explored. Two hundred digitalized biopsy-cases were investigated: 100 with UC-PDG and 100 with UC-aspa. Six GACP and two types of cellular dysplasia: low-grade (LGD) and high-grade dysplasia (HGD) were found. CRT and CLB's were present in 66% of the 200 cases. A significantly higher number of cases with villous phenotype wihout or with HGD, with CLB's phenotype without or with HGD, and with tubulovillous phenotype with HGD were found in UC-PDG than in UC-asta. Several authors found no significant difference in the histological characteristics between UC-protruding dysplastic lesions and US-aspa. This work reveals, however, that the different number of cases with the above-mentioned histological parameters present in each group permitted to discriminate between UC-PDG and UC-asta.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70216"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional Stability of Tetracycline: Practical Information for Its Use in Bacterial Selection.","authors":"Adrián Salazar-Sánchez, Ilargi Martínez-Ballesteros, Irati Martinez-Malaxetxebarria","doi":"10.1111/apm.70222","DOIUrl":"10.1111/apm.70222","url":null,"abstract":"<p><p>Genetic manipulation is widely employed in laboratories for purposes such as gene function characterization, the development of novel traits in transformed microorganisms, and the production of biotechnologically relevant compounds. A key step in this process is the selection of mutant strains, often facilitated by antibiotics. Tetracyclines are commonly used; however, their aqueous solutions tend to precipitate and turn brown over time, potentially compromising stability and efficacy. This necessitates frequent in situ preparation. The present study aimed to evaluate the functional stability of tetracycline hydrochloride for selecting transformed tetracycline-resistant bacterial strains in both liquid and solid media. A tetracycline stock solution and supplemented agar plates were prepared and used to cultivate resistant and non-resistant strains of Escherichia coli and Arcobacter butzleri. This allowed for assessment of antibiotic stability and utility over a 200-day period. Additionally, the minimal inhibitory concentration (MIC) of tetracycline was determined for each strain. Results indicated that the tetracycline-containing materials maintained functional stability for at least 175 days post-preparation, effectively supporting the selection of resistant strains in genetic manipulation experiments. These findings obviate the need for the continual and time-consuming preparation of tetracycline-supplemented culture media, thereby enhancing the practicality of employing this antibiotic in genetic modification studies.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70222"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147961876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luís Henrique Nunes de Souza, Guilherme Ferreira da Silva, Márcia Cibele Andrade Dos Santos Ferreira, Priscila Luiza Mello, Luiz Eduardo Nunes Ferreira
{"title":"Candida albicans, HIV And Immune System in a Holobiont Perspective.","authors":"Luís Henrique Nunes de Souza, Guilherme Ferreira da Silva, Márcia Cibele Andrade Dos Santos Ferreira, Priscila Luiza Mello, Luiz Eduardo Nunes Ferreira","doi":"10.1111/apm.70224","DOIUrl":"10.1111/apm.70224","url":null,"abstract":"<p><p>Holobiont describes all types of relationships between hosts and their associated microbial communities, which can also attenuate the virulence of pathogens by the host microbiome. The cross-kingdom interactions between HIV, Candida albicans, and the human immune system have presented intriguing biological aspects. The human immunodeficiency 1 (HIV-1) virus is responsible for causing the acquired immune deficiency syndrome (AIDS) by infecting CD4<sup>+</sup> cells. HIV-1 internalization also depends on binding to coreceptors in the cell membrane, such as CCR5 and CXCR4. The expression of these chemokine receptors, as well as their ligands, can be modulated by the presence of Candida albicans PAMPs. Thus, this review discusses the inflammatory response mechanism activated by the commensal fungi Candida albicans that can modify the rate of immune cell infection by HIV-1. Despite the possibility of this crosstalk modulation, future research must validate the clinical significance of this holobiont interaction.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70224"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing Placental Pathology With Artificial Intelligence: Toward Reproducible and Predictive Diagnostics.","authors":"Negar Taheri, Sahussapont J Sirintrapun","doi":"10.1111/apm.70219","DOIUrl":"10.1111/apm.70219","url":null,"abstract":"<p><p>Placental pathology remains underdeveloped in its application of artificial intelligence (AI) and digital pathology, despite established diagnostic guidelines and increasing clinical demand. Determining which placentas require histologic examination continues to strain staffing and resources, while histologic interpretation is limited by high interobserver variability and a lack of scalable analytic tools. This review synthesizes current applications and future opportunities for AI in placental pathology across multiple domains, including gross examination, villous maturation, lesion detection, and inflammation. We examine challenges related to data scarcity, reproducibility, and interpretability, and discuss potential solutions such as human-in-the-loop workflows. Recent studies demonstrate strong performance of AI models in automated placental gross image analysis, villous maturation assessment, and lesion detection, with inflammatory lesion analysis and cell classification further highlighting AI's ability to quantify complex, traditionally subjective features. Collectively, these findings show that placental morphology is machine-recognizable and quantifiable. AI-driven placental pathology has the potential to improve diagnostic reproducibility, uncover novel disease mechanisms, and enable earlier prediction of adverse maternal-fetal outcomes. Clinical translation will require addressing dataset diversity, tissue-processing variability, and model interpretability, as well as strategic investment in digital infrastructure, standardization, and interdisciplinary collaboration.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70219"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ingrid Pontoppidan Føh, Thomas Leineweber Kristensen, Ann Sofie Olesen, Thomas Bruun Rasmussen, Louise Lohse, Uffe Vest Schneider, Bo Bødker Jensen
{"title":"The Human Threat From West Nile Virus and Usutu Virus in a Changing Climate.","authors":"Ingrid Pontoppidan Føh, Thomas Leineweber Kristensen, Ann Sofie Olesen, Thomas Bruun Rasmussen, Louise Lohse, Uffe Vest Schneider, Bo Bødker Jensen","doi":"10.1111/apm.70218","DOIUrl":"10.1111/apm.70218","url":null,"abstract":"<p><p>In recent years, the closely related arboviruses West Nile virus (WNV) and Usutu virus (USUV) have spread farther north in Europe. The viruses often co-circulate and are maintained in a natural cycle between ornithophilic mosquitoes and birds. Humans and other mammals can become infected with these viruses, but are considered dead-end hosts. Both viruses can cause fever and encephalitis and may potentially be fatal to humans, birds, and horses. Usutu virus was discovered in blackbirds in Denmark for the first time in the fall of 2024 and again in 2025. Denmark is currently a European border country of WNV and the recent emergence of USUV may precede establishment of WNV. With ongoing climate change, increasing temperatures and precipitation levels are expected. Both factors affect virus transmission and vector season length, thereby increasing the risk of these viruses moving northwards. The risk calls for enhanced surveillance of both viruses to ensure timely interventions and optimal control from a One Health perspective. This review describes the similarities and differences between the viruses, the epidemiology and surveillance strategies implemented in Denmark and Europe and discusses the aspects in relation to ongoing climate changes.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70218"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biofilms in Disease and Control Strategies.","authors":"Y V Nancharaiah, Alwar Ramanujam Padmavathi","doi":"10.1111/apm.70220","DOIUrl":"10.1111/apm.70220","url":null,"abstract":"","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70220"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristiane Barington, Christof Albert Bertram, Katharina Breininger, Henrik Elvang Jensen
{"title":"Computational Quantification of Collagen Density and Ki67-Positive Cells in a Forensic Porcine Wound Model.","authors":"Kristiane Barington, Christof Albert Bertram, Katharina Breininger, Henrik Elvang Jensen","doi":"10.1111/apm.70217","DOIUrl":"10.1111/apm.70217","url":null,"abstract":"<p><p>Obtaining an accurate age of skin wounds is a diagnostic challenge in forensic pathology. This study aimed to quantify collagen density and proliferation activity in porcine experimental wounds over time using machine learning-based segmentation to provide an objective method for wound age estimation. Tissue sections from porcine experimental wounds (n = 68) were stained with Masson's trichrome stain or immunohistochemically labeled for proliferation activity by Ki67. The experimental wounds were located on the back and 5-35 days old. Collagen and proliferation activity in the wounds were quantified by training and application of neural network pixel and random trees object classifiers. The relative collagen fraction and the collagen ratio between lower and upper wound regions displayed significant time-dependent patterns. The proliferative activity, assessed by the percentage of Ki67-positive cells, was not suitable for age assessment. In conclusion, the application of a neural network pixel classifier trained to differentiate between collagen and cellular components is an objective method for forensic wound age assessment. However, to obtain a higher precision, the method should be used as a supportive tool in combination with other time-dependent markers.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"134 5","pages":"e70217"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}