https://hdl.handle.net/20.500.14178/904 2026-07-11T16:31:43Z 2026-07-11T16:31:43Z Molano, Leidy-Alejandra G Hirsch, Pascal Keller, Andreas Dolejská, Monika Palkovičová, Jana https://hdl.handle.net/20.500.14178/3866 2026-07-10T01:00:31Z 2026-01-01T00:00:00Z

HERA: a web server for host element reference-based aligner Molano, Leidy-Alejandra G; Hirsch, Pascal; Keller, Andreas; Dolejská, Monika; Palkovičová, Jana Plasmids play a central role in bacterial adaptation and in the dissemination of antimicrobial resistance, driving a growing need for accessible tools that support their comparative analysis without requiring local computational infrastructure. Although several circular genome visualization platforms exist, most are designed for general bacterial genome analysis rather than focused on plasmid comparison. Host element reference-based aligner (HERA) is a web server for intuitive visualization and comparison of plasmids and other circular molecules through BLAST alignment against reference sequences. Built on interactive circular genome visualization, HERA simplifies comparative genomics by providing an accessible interface for exploring sequence similarity, identifying conserved regions, and analyzing genetic elements without the complexity of traditional local tools. HERA includes a plasmid-oriented annotation pipeline covering replicon and mobility typing, antimicrobial resistance detection, mobile element identification, and homology search against the PLSDB plasmid database. HERA also provides an automatic selection of the reference which is the most appropriate from the uploaded sequences. The web server is available without login or any restriction at https://web.ccb.uni-saarland.de/hera/.

2026-01-01T00:00:00Z Gagaletsios, Lazaros A Sourenian, Tsolaire Karpouzas, Dimitrios Bitar, Ibrahim Papagiannitsis, Costas https://hdl.handle.net/20.500.14178/3865 2026-07-10T01:00:40Z 2026-01-01T00:00:00Z

Comparison of microbial profiles between hospital wastewater and river water Gagaletsios, Lazaros A; Sourenian, Tsolaire; Karpouzas, Dimitrios; Bitar, Ibrahim; Papagiannitsis, Costas This study aimed to compare the microbial profiles between hospital wastewater and river water to assess the dissemination of clinical isolates into the environment. Two types of water samples were collected from sampling sites which were geographically close (wastewater from the University Hospital of Larissa and river water from the Pineios River). Gram-negative bacteria isolated from both sample types were identified using MALDI-TOF. Furthermore, the minimum inhibitory concentration (MIC) of antibiotics were evaluated. A total of 54 Gram-negative isolates, belonging to diverse species, were collected from wastewater sample and river sample. All isolates were classified as MDR, exhibiting resistance to at least one agent from more than three different antibiotic classes. Based on species identification and susceptibility profiles, 27 isolates (19 from wastewater and 8 from river-water) were selected to be further characterized by whole-genome sequencing (WGS). Analysis of WGS data, revealed the presence of different STs, even in isolates belonging to the same bacterial species. Additionally, WGS data showed that carbapenemase-encoding genes were identified in the majority of isolates. PlasmidFinder identified a huge variety of plasmid replicons among the isolates studied. In conclusion, both hospital wastewater and river water contained isolates carrying clinically relevant resistance determinants, such as carbapenemase-encoding genes. The presence of these pathogenic bacteria in the river poses a significant public health concern. Although we could not identify the origin of MDR bacteria in the river sample, these findings highlight the growing threat of antimicrobial resistance in the environment and underscore the urgent need for improved treatment methods and stricter surveillance to control its spread.

2026-01-01T00:00:00Z Zitrický, František Sundquist, Kristina Sundquist, Jan Hemminki, Akseli Försti, Asta Hemminki, Kari Jussi https://hdl.handle.net/20.500.14178/3863 2026-07-04T01:00:16Z 2026-01-01T00:00:00Z

Familial cancers associated with cancers of the breast, prostate, colorectum and lung in Sweden Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Hemminki, Akseli; Försti, Asta; Hemminki, Kari Jussi Available epidemiological evidence shows that many cancers share familial risks, and this is increasingly confirmed by data on shared pathogenic germline gene variants between cancers. We decided to harness the world's largest resource on familial cancer to assess discordant familial risks for female breast (BC), prostate (PC), colorectal (CRC) and lung (LC) cancers with any of 22 different cancers in first-degree relatives (proband cancers). Familial relative risk was calculated as standardized incidence ratio (SIR) when either one proband or 2 or more (2+) probands were found in a family to distinguish low- and high-risk associations. Discordant familial associations of BC were significant for 15 1-proband and 6 2+ proband cancers. For PC the numbers were 10 and 4, for CRC they were 9 and 3 and for LC they were 14 and 5. The results with large case numbers showed that BC, CRC and LC associated with each other but the familial association between PC and LC was negative. Many novel associations with possible genetic causes were found, including lobular BC with stomach cancer, PC with kidney cancer, CRC with squamous cell skin, brain and thyroid cancers, and LC with gallbladder and endocrine tumors, the most common of which were parathyroid adenomas. Also, LC associations with esophageal and cervical cancers were unlikely to be due to smoking alone and require additional explanations. In conclusion, 2/3 of discordant associations could suggest low-risk genetic and environmental causation and 1/3 high-risk genetic causation, both waiting for experimental proof.

2026-01-01T00:00:00Z Michal, Michael Dermawan, Josephine K. https://hdl.handle.net/20.500.14178/3845 2026-06-19T01:00:25Z 2026-01-01T00:00:00Z

An Updated Conceptual Framework for Myoepithelial Tumors of Soft tissues and Bone: Toward a Molecularly Informed Classification Michal, Michael; Dermawan, Josephine K. Myoepithelial tumors (MET) of soft tissue and bone comprise a rare group of neoplasms unified by partially overlapping morphology and so called myoepithelial immunophenotype. Historically, MET have long posed diagnostic and prognostic challenges. Grading and risk stratification have relied largely on the presence of cytologic atypia. Recent molecular and epigenetic studies have fundamentally revised this concept, demonstrating that MET represent a biologically heterogeneous family rather than a single disease entity. Soft tissue (mostly deep-seated) and osseous MET frequently harbor recurrent gene fusions, most commonly involving FET family genes (EWSR1 or less often FUS) with partners such as POU5F1, PBX1, PBX3, KLF15, KLF17 , and ZNF444 , and more rarely non-FET fusions including SS18::POU5F1 . These fusion types correlate with reproducible clinicopathologic patterns and, in emerging outcome datasets, with subtype-specific differences in behavior. In contrast, superficially located adnexal tumors with ductal differentiation - representing true cutaneous mixed tumors/myoepitheliomas - typically lack EWSR1/FUS rearrangements and instead show PLAG1 rearrangements, supporting a bona fide myoepithelial origin and close relationship to PLAG1 -driven salivary gland counterparts. Additional complexity arises from SMARCB1-deficient, fusion-negative tumors and a small subset lacking identifiable recurrent drivers, as well as substantial overlap in morphology and immunophenotype with multiple MET mimics, contributing to diagnostic misclassification when using morphology and immunohistochemistry alone. To address these issues, we synthesize clinicopathologic, molecular, methylomic and pooled outcome data across major MET subgroups from recent multi-institutional cohorts, highlighting pronounced epigenetic and clinical heterogeneity and providing practical diagnostic guidance for surgical pathologists. We propose a molecularly informed classification framework that improves diagnostic precision, clarifies terminology - particularly distinguishing PLAG1 -rearranged cutaneous salivary-gland analogs from fusion-associated soft tissue/bone sarcomas with myoepithelial-like phenotype - and lays a foundation for refined prognostic stratification and future therapeutic studies.

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