https://hdl.handle.net/20.500.14178/904 2026-09-09T20:56:29Z 2026-09-09T20:56:29Z Dvořák, Pavel Tonar, Zbyněk https://hdl.handle.net/20.500.14178/3924 2026-09-08T01:00:24Z 2026-01-01T00:00:00Z

Estimating clinical manifestations in cell biology teaching is a suitable active element for teaching beginning medical students Dvořák, Pavel; Tonar, Zbyněk Objective: Cell biology courses in medical education often emphasize molecular detail without sufficient clinical integration, which can reduce student motivation and hinder application of knowledge. Embedding diagnostic reasoning into basic science teaching may enhance engagement and relevance. We developed short, task-based exercises in which students are actively encouraged to infer potential clinical symptoms of genetically determined diseases from cellular mechanisms. Methods: Each task followed three steps: (1) introduction to a specific cellular process, (2) guided prediction of clinical manifestations resulting from dysfunction of key proteins, and (3) verification of hypotheses through published literature. Tasks were implemented into first-year medical student seminars of Medical Biology in both face-to-face and online formats. Evaluation was based on assessments by experienced teachers and a student questionnaire at the end of the course. Results: Two illustrative tasks were presented: role of adhesion proteins in leukocyte extravasation, linked to leukocyte adhesion deficiency syndromes, and sarcolemma-cytoskeleton interactions, associated with various muscular dystrophies. Teachers as well as students consistently rated the tasks positively in surveys conducted. Better understanding of the connection between cellular mechanisms and clinical symptoms, greater confidence in diagnostic reasoning, and an increased ability to search and interpret scientific literature were reported. Based on the evaluation, modifications to the learning outcomes were proposed to place greater emphasis on the ability to draw conclusions from cellular processes. Conclusion: Integrating short, clinically anchored exercises into cell biology teaching provides an effective means of activating student learning and fostering early diagnostic reasoning. This approach strengthens the perceived relevance of basic science, supports critical thinking, and offers a scalable model for enhancing preclinical medical curricula.

2026-01-01T00:00:00Z D'Mellow, Matthew Wang, Huanwei Palmer, Jane M Hemminki, Kari Jussi Cebulla, Colleen M Beasley, Aaron B Bechrakis, Nikolaos E Pritchard, Antonia L Wadt, Karin W Johansson, Peter A Mobuchon, Lenha Barlow, Samantha Brooks, Kelly Beckman, Timothy Olsen, Catherine M Warrier, Sunil K Byrne, Lindsey Kalirai, Helen Mustard, Colette Ingold, Nathan Försti, Asta Isaacs, Timothy Jayasinghe, G J M Shanika R Glasson, William J Williamson, Gayle McGrath, Lindsay A Le, Ngoc-Quynh Chadha, Vikas Gray, Elin S Brown, Kevin M Cauchi, Paul Thomsen, Hauke Connolly, Julie MacGregor, Stuart Whiteman, David C Kiilgaard, Jens F Stern, Marc-Henri Coupland, Sarah E Abdel-Rahman, Mohamed H Zeschnigk, Michael Hayward, Nick Law, Matthew H https://hdl.handle.net/20.500.14178/3912 2026-09-03T01:00:41Z 2026-01-01T00:00:00Z

GWAS meta-analysis provides new insights into uveal melanoma risk D'Mellow, Matthew; Wang, Huanwei; Palmer, Jane M; Hemminki, Kari Jussi; Cebulla, Colleen M; Beasley, Aaron B; Bechrakis, Nikolaos E; Pritchard, Antonia L; Wadt, Karin W; Johansson, Peter A; Mobuchon, Lenha; Barlow, Samantha; Brooks, Kelly; Beckman, Timothy; Olsen, Catherine M; Warrier, Sunil K; Byrne, Lindsey; Kalirai, Helen; Mustard, Colette; Ingold, Nathan; Försti, Asta; Isaacs, Timothy; Jayasinghe, G J M Shanika R; Glasson, William J; Williamson, Gayle; McGrath, Lindsay A; Le, Ngoc-Quynh; Chadha, Vikas; Gray, Elin S; Brown, Kevin M; Cauchi, Paul; Thomsen, Hauke; Connolly, Julie; MacGregor, Stuart; Whiteman, David C; Kiilgaard, Jens F; Stern, Marc-Henri; Coupland, Sarah E; Abdel-Rahman, Mohamed H; Zeschnigk, Michael; Hayward, Nick; Law, Matthew H OBJECTIVE: The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls. METHODS: Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM's genetic architecture. RESULTS: We identify nine linkage disequilibrium (LD)-independent loci (three novel) with an IVW P value of less than 5 x 10(-8). TWAS analysis indicates five potential target genes, including MOB3B, RBAK, and MTSS1, which have established links to multiple cancer types. We note a significant genetic correlation (rg = 0.31, P = 0.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg = 0.25, P = 0.08). CONCLUSIONS: This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation.

2026-01-01T00:00:00Z Klubíčková, Natálie Dermawan, Josephine K Ameline, Baptiste Martínek, Petr Vaněček, Tomáš Hájková, Veronika Ptáková, Nikola Grossmann, Petr Šteiner, Petr Kormunda, Stanislav Perret, Raul E Le Loarer, François Dehner, Carina Torres-Mora, Jorge Gross, John M Chrisinger, John S A Charville, Gregory Kosemehmetoglu, Kemal Wangsiricharoen, Sintawat Meis, Jeanne Špůrková, Zuzana Zámečník, Michal Zambo, Iva Staniczková Klinger, Tomáš Švajdler, Marián Kinkor, Zdeněk Michalová, Květoslava Baumhoer, Daniel Michal, Michal Antonescu, Cristina R Michal, Michael https://hdl.handle.net/20.500.14178/3887 2026-07-30T01:00:13Z 2026-01-01T00:00:00Z

Clinicopathological, Molecular, and DNA Methylation Analysis of Ossifying Fibromyxoid Tumors Delineates the ZC3H7B::BCOR Subset as a Distinct Entity Klubíčková, Natálie; Dermawan, Josephine K; Ameline, Baptiste; Martínek, Petr; Vaněček, Tomáš; Hájková, Veronika; Ptáková, Nikola; Grossmann, Petr; Šteiner, Petr; Kormunda, Stanislav; Perret, Raul E; Le Loarer, François; Dehner, Carina; Torres-Mora, Jorge; Gross, John M; Chrisinger, John S A; Charville, Gregory; Kosemehmetoglu, Kemal; Wangsiricharoen, Sintawat; Meis, Jeanne; Špůrková, Zuzana; Zámečník, Michal; Zambo, Iva Staniczková; Klinger, Tomáš; Švajdler, Marián; Kinkor, Zdeněk; Michalová, Květoslava; Baumhoer, Daniel; Michal, Michal; Antonescu, Cristina R; Michal, Michael Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm of uncertain lineage of differentiation driven by a broad spectrum of gene fusions. It manifests primarily in soft tissues of the extremities. In this study, we performed a comprehensive clinicopathological, molecular-genetic, and epigenetic analysis of 70 cases of OFMT, with a specific focus on rare fusion subtypes, particularly ZC3H7B::BCOR, PHF1::TFE3 and MEAF6::PHF1. In addition, we included seven tumors with novel fusions, namely AFF3::PHF1, PHF1::KLF15, PHF1::PRKAG1, CREBBP::PHF1, EPC1::BMI1, MEAF6::BCOR, and EP300::BCORL1. The clinicopathological characteristics revealed a correlation between specific fusions and aggressive clinical behavior; notably, tumors with ZC3H7B::BCOR fusions were always classified as morphologically atypical or malignant and were associated with significantly higher recurrence and metastatic rates compared to other fusion groups, particularly EP400::PHF1. Immunohistochemical analysis further revealed a distinct immunophenotype in the ZC3H7B::BCOR group. While immunopositivity for cytokeratins and myogenic markers was observed in approximately one-quarter and more than one-third of OFMT cases overall, respectively, ZC3H7B::BCOR-rearranged tumors were negative for both. In contrast, the majority showed immunopositivity for pan-Trk. Additionally, DNA methylation profiling distinguished ZC3H7B::BCOR-rearranged cases from other fusion-positive OFMT, whereas the former clustered closely with a subset of high-grade endometrial stromal sarcomas. This study supports the recognition of ZC3H7B::BCOR-positive tumors as a distinct clinicopathological entity, contributing to the refined molecular taxonomy of this neoplasm.

2026-01-01T00:00:00Z Hemminki, Kari Jussi Zitrický, František Försti, Asta Hemminki, Akseli https://hdl.handle.net/20.500.14178/3885 2026-07-28T01:00:38Z 2026-01-01T00:00:00Z

Recent survival trends in the most fatal cancers in the Nordic countries: gains in some but not in all Hemminki, Kari Jussi; Zitrický, František; Försti, Asta; Hemminki, Akseli Background Global survival studies distinguish a group of solid cancers with especially poor survival, which in the Nordic countries are cancers of the hypopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung and pleura, each with a 5-year overall survival ranging between 15 to 30%. These cancers need extra attention. Methods We analyze here 1- and 5- year relative survival in the above cancers in Denmark, Finland, Norway and Sweden comparing periods 2013-18 and 2019-23 using the NORDCAN database. Results Survival improvement was significant for lung cancer in each country, more for women than for men. For females, 1- and 5-year lung cancer survival improvements were about 5 and 6 % units between the two periods, compared to all cancer of 1.5 and 2 % units, respectively. Regarding other individual sites, Norway and Sweden demonstrated significant survival improvements in stomach cancer, and Norway also in pancreatic cancer. However, non-significant survival improvements were observed for most cancers. No positive evidence was found for esophageal cancer in Finland and gallbladder cancer in Norway. More significant improvements were found for 1- than for 5-year survival. Conclusions Survival in lung cancer increased in all countries well over improvements for all cancers. Survival increased also significantly for stomach and pancreatic cancers in some countries, and improvements were seen for other cancers. Although the results show success in fight against the most fatal cancers, continuous efforts are needed in early detection, facile clinical handling and novel therapeutics. However, for these fatal cancers primary prevention would be highly rewarding.

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