AIMS: Ossifying fibromyxoid tumour is a rare mesenchymal neoplasm predominantly affecting adults characterised by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non-ossifying ossifying fibromyxoid tumour with lipomatous differentiation which caused diagnostic difficulty, we sought to further explore cases of ossifying fibromyxoid tumour with non-osseous heterologous elements. METHODS AND RESULTS: A search of our institutional and consultation archives revealed three additional cases that demonstrated lipomatous components and two cases with cartilaginous differentiation. RNA-sequencing revealed fusions involving PHF1 (n = 4) or EPC1 (n = 1) in all (five of five) cases tested, including EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been reported before in ossifying fibromyxoid tumour. CONCLUSION: These six cases expand the histomorphological spectrum of ossifying fibromyxoid tumour, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.

• MeSH
• Cell Differentiation MeSH
• Cartilage pathology   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipoma * pathology   diagnosis   genetics   MeSH
• Soft Tissue Neoplasms * pathology   diagnosis   genetics   MeSH
• Fibroma, Ossifying * pathology   diagnosis   genetics   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

A double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole-exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein-protein interaction and pathway analysis. A total of 150 missense, 19 stop-gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole-exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.

• MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Colorectal Neoplasms * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• DNA Repair genetics   MeSH
• Pedigree MeSH
• Exome Sequencing * methods   MeSH
• Aged MeSH
• Germ-Line Mutation * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.

• MeSH
• Action Potentials MeSH
• Bundle-Branch Block * physiopathology   therapy   diagnosis   MeSH
• Time Factors MeSH
• Cardiomyopathy, Dilated physiopathology   therapy   diagnosis   MeSH
• Electrocardiography * MeSH
• Ventricular Function, Left * MeSH
• Hemodynamics * MeSH
• Middle Aged MeSH
• Humans MeSH
• Predictive Value of Tests * MeSH
• Cardiac Resynchronization Therapy Devices MeSH
• Aged MeSH
• Heart Rate MeSH
• Cardiac Resynchronization Therapy * MeSH
• Heart Failure physiopathology   therapy   diagnosis   MeSH
• Stroke Volume MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups. RESULTS: Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 [0.82-0.92], specificity 0.84 [0.72-0.91]) but not in metastases (sensitivity 0.64 [0.38-0.84], specificity 0.56 [0.33-0.77]). APT-CEST combined with conventional/advanced MRI rendered 0.92 [0.86-0.96] and 0.88 [0.72-0.95] in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity (I2 = 62.25%; p < 0.01) and specificity (I2 = 66.31%; p < 0.001). CONCLUSION: A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases. CLINICAL RELEVANCE STATEMENT: This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome. KEY POINTS: Therapy-related changes mimicking progression complicate brain tumour treatment. Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes. Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases.

• MeSH
• Amides * MeSH
• Diagnosis, Differential MeSH
• Glioma * diagnostic imaging   pathology   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local diagnostic imaging   MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Neoplasms * diagnostic imaging   secondary   MeSH
• Disease Progression * MeSH
• Protons MeSH
• Sensitivity and Specificity MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

BACKGROUND: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis. METHODS: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions. RESULTS: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile. CONCLUSION: Our findings highlight that comprehensive analysis, considering morphological heterogeneity, is crucial for personalised CRC treatment strategies.

• MeSH
• Drug Resistance, Neoplasm * genetics   MeSH
• Adult MeSH
• ErbB Receptors antagonists & inhibitors   MeSH
• PTEN Phosphohydrolase genetics   MeSH
• GTP Phosphohydrolases genetics   MeSH
• Protein Kinase Inhibitors * therapeutic use   MeSH
• Colorectal Neoplasms * genetics   drug therapy   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation * MeSH
• DNA Mutational Analysis MeSH
• Pilot Projects MeSH
• Antineoplastic Agents * therapeutic use   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Proto-Oncogene Proteins p21(ras) genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Úvod: Shigelóza je vysoce nakažlivé průjmové onemocnění s potenciálně velmi závažným průběhem. I s ohledem na třetinový nárůst případů v roce 2023 ve srovnání s rokem předchozím jsme si stanovili za cíl podat přehled aktuálních informací o onemocnění a analyzovat data nahlášených případů shigelózy v České republice (ČR). Metody: Zpracovali jsme narativní rešerši odborné literatury v českém a anglickém jazyce, zejména cílenou na evropské studie od roku 2018. Dále jsme provedli analýzu dat hlášených pod kódem diagnózy A03 v národním systému pro hlášení infekčních nemocí (ISIN) v letech 2018–2023. Soustředili jsme se na hlavní epidemiologické ukazatele, zejména pohlaví, věk, geografickou distribuci, sezonnost a hospitalizace. Použity byly programy Excel (verze 2016), STATA (verze 17) a Datawrapper GmbH. Výsledky: Celkem bylo nahlášeno 681 případů onemocnění shigelózou s průměrnou roční incidencí 1/100 000 obyvatel: do roku 2021 byla incidence mírně vyšší u žen, od roku 2022 evidujeme trend opačný. V pandemických letech byl zaznamenán významný pokles případů. V letech 2022 a 2023 byl počet případů mírně vyšší než v období před pandemií. Nejvíce případů evidujeme v ČR každoročně v měsících srpen až prosinec. Ze všech sérotypů shigel byla nejčastěji detekována S. sonnei (80 %), následovaná S. flexneri (15 %). Incidence na 100 000 obyvatel byla nejvyšší u osob ve věku 5–9 let: 2,6 (chlapci 2,4 a dívky 2,8), dále 1–4 roky: 2,4 (chlapci 2,2, dívky 2,6) a osob ve věku 25–34 let: 1,8 (muži 1,8 a ženy 1,7). Podle krajů byla průměrná roční specifická incidence nejvyšší v krajích Moravskoslezském, Olomouckém a v hlavním městě Praze. Hospitalizováno bylo 27 % případů, nejvíce ve věkových skupinách 25–34 a 5–9 let (shodně 17,9 %). Proporce hospitalizovaných případů v rámci jednotlivých věkových skupin byla nejvyšší ve věkové skupině 75+ let (69 %), dále věkových skupinách 1–4 roky, 5–9 let a 65–74let (32–37 %). V souvislosti s onemocněním bylo vykázáno jedno úmrtí muže ve věku 52 let. V rámci epidemického výskytu bylo nahlášeno 11 % případů. Importováno bylo 39 % nahlášených případů. Závěr: V ČR je shigelóza spíše málo zastoupeným gastrointestinálním onemocněním, přičemž téměř 40 % případů tvoří importované nákazy. V současnosti je hrozbou pro veřejné zdraví především globální šíření multirezistentních kmenů podpořené narůstajícím cestovním ruchem a volnými sexuálními praktikami. Rizikovými skupinami zůstávají děti, imunokompromitované osoby (včetně seniorů) a muži mající sex s muži. Očkování není v Evropě dostupné. Stěžejním je nadále dodržování základních hygienických pravidel, zejména v kolektivech a při práci s potravinami. Důraz by měl být dále kladen na zdravotní edukaci osob, včetně poučení před vycestováním do zahraničí. Důkladná anamnéza, včasné trasování, dohled a racionální volba eventuální antibiotické terapie jsou zásadní. V ČR musí být všechny suspektní kmeny zaslány do NRL ke konfirmaci. Celogenomovou sekvenaci a testy citlivosti na antibiotika je vhodné provádět u všech izolátů.

Introduction: Shigellosis is a highly contagious diarrheal disease, which could potentially be very serious. Considering the onethird increase in cases in 2023 compared to the previous year, we aimed to provide an update on the disease and to analyse data on reported cases of shigellosis in the Czech Republic (CZ). Methods: We conducted a narrative search of the literature in Czech and English, particularly targeting European studies from 2018 onwards. We also analysed data reported under the diagnosis code A03 to the National Infectious Disease Reporting System (ISIN) in 2018–2023. We focused on the main epidemiological indicators, i.e. gender, age, geographical distribution, seasonality, and hospitalizations. Excel (version 2016), STATA (version 17), and Datawrapper GmbH were used. Results: A total of 681 shigellosis cases were reported with an average annual incidence of 1/100,000 population: until 2021, the incidence was slightly higher in women, while from 2022 onwards, the trend was reversed. A significant decrease in cases was recorded in the pandemic years. In 2022 and 2023, the number of cases was slightly higher than in the pre-pandemic period. Most cases were detected in CZ in August and December each year. Of all shigella serotypes, S. sonnei was the most frequently detected (80%), followed by S. flexneri (15%). The incidence per 100.000 population was highest among children aged 5–9 years: 2.6 (boys 2.4 and girls 2.8), followed by 1–4-year-olds: 2.4 (2.2 and 2.6, respectively) and persons aged 25–34 years: 1.8 (males 1.8 and females 1.7). Within individual age group, the average annual specific incidence rates were highest in the Moravian-Silesian and Olomouc regions and the capital city Prague. Hospitalizations accounted for 27% of cases, with the highest numbers in the 25–34 and 5–9 age groups (both 17.9%). The proportion of hospitalized cases was highest in the age groups 75+ (69%), 1–4, 5–9, and 65–74 (32–37%). A 52-year-old man was reported to have die in relation to the disease. Eleven percent of cases were reported in outbreak settings. Thirty-nine percent of reported cases were imported. Conclusions: In CZ, shigellosis is a relatively rare gastrointestinal disease, with nearly 40% of cases being imported. At present, the threat to public health is posed mainly by the global spread of multi-resistant strains linked to increasing tourism and free sexual practices. Children, immunocompromised persons (including the elderly), and men who have sex with men remain risk groups. Vaccination is not available in Europe. Compliance with basic hygiene rules, especially in collectives and when working with food, is still a key concern. Emphasis should also be placed on the health education, including instructions before traveling abroad. A thorough medical history, early tracing, surveillance, and rational choice of antibiotic therapy if appropriate are essential. In CZ, all suspected strains shall be sent to the NRL for confirmation. Whole genome sequencing and antibiotic susceptibility testing should be performed on all isolates.

• MeSH
• Dysentery, Bacillary * epidemiology   transmission   MeSH
• Travel MeSH
• Disease Notification statistics & numerical data   MeSH
• Clinical Studies as Topic methods   MeSH
• Humans MeSH
• Data Collection statistics & numerical data   MeSH
• Sexual Behavior MeSH
• Shigella pathogenicity   MeSH
• Check Tag
• Humans MeSH

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB , or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors' registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB ; ACTB::MYB; ESRRG::DNM3 , and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases) , NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1 , PDGFRA , each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.

• MeSH
• Carcinoma, Adenoid Cystic * genetics   pathology   MeSH
• Adult MeSH
• Phenotype MeSH
• Gene Fusion MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• Genetic Predisposition to Disease MeSH
• In Situ Hybridization, Fluorescence * MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation * MeSH
• DNA Mutational Analysis MeSH
• Biomarkers, Tumor * genetics   MeSH
• Paranasal Sinus Neoplasms * genetics   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• NFI Transcription Factors genetics   MeSH
• High-Throughput Nucleotide Sequencing * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

AIMS: Spindle-cell/sclerosing rhabdomyosarcomas (SS-RMS) are clinically and genetically heterogeneous. They include three well-defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS-RMS and to perform a clinicopathological and statistical analysis of all TFCP2-rearranged SS-RMS described in the English literature to more comprehensively characterize this rare tumour type. METHODS AND RESULTS: Cases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break-apart probes, next-generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan-Cancer Panel). The PubMed database was searched for relevant peer-reviewed English reports. Five cases of SS-RMS were found. Three cases were TFCP2 rearranged SS-RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle-round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18-24 years were negatively correlated to overall survival. CONCLUSION: EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%).

• MeSH
• Child MeSH
• DNA-Binding Proteins genetics   MeSH
• Adult MeSH
• Gene Fusion MeSH
• In Situ Hybridization, Fluorescence MeSH
• Middle Aged MeSH
• Humans MeSH
• Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase genetics   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Biomarkers, Tumor genetics   MeSH
• RNA-Binding Protein EWS genetics   MeSH
• RNA-Binding Proteins genetics   MeSH
• Retrospective Studies MeSH
• Rhabdomyosarcoma * genetics   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcription Factors * genetics   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.

• MeSH
• Cognition physiology   MeSH
• Humans MeSH
• Molecular Mimicry * MeSH
• Models, Molecular MeSH
• Amino Acid Sequence MeSH
• Protein Binding MeSH
• Viral Proteins metabolism   chemistry   MeSH
• Computational Biology methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name "PLAG1-rearranged uterine sarcoma."

• MeSH
• DNA-Binding Proteins * genetics   MeSH
• Adult MeSH
• Phenotype MeSH
• Gene Rearrangement * MeSH
• Immunohistochemistry MeSH
• Leiomyosarcoma * genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Uterine Neoplasms * genetics   pathology   MeSH
• Sarcoma * genetics   pathology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH