Brobergpeele0918

We propose the name of Acral FibroChondroMyxoid Tumors for this new entity.Sarcoma is a rare disease affecting both bone and connective tissue and with over 100 pathologic entities, differential diagnosis can be difficult. Complementing immune-histological diagnosis with current ancillary diagnostic techniques, including FISH and RT-PCR, can lead to inconclusive results in a significant number of cases. We describe here the design and validation of a novel sequencing tool to improve sarcoma diagnosis. A NGS DNA capture panel containing probes for 87 fusion genes and 7 genes with frequent copy number changes was designed and optimized. A cohort of 113 DNA samples extracted from soft-tissue and bone sarcoma FFPE material with clinical FISH and/or RT-PCR results positive for either a translocation or gene amplification was used for validation of the NGS method. Sarcoma-specific translocations or gene amplifications were confirmed in 110 out of 113 cases using FISH and/or RT-PCR as gold-standard. MDM2/CDK4 amplification and a total of 25 distinct fusion genes were identified in this cohort of patients using the NGS approach. Overall, the sensitivity of the NGS panel is 97% with a specificity of 100 and 0% failure rate. Targeted NGS appears to be a feasible and cost-effective approach to improve sarcoma subtype diagnosis with the ability to screen for a wide range of genetic aberrations in one test.Mucinous colorectal adenocarcinoma (CRC) is conventionally defined by extracellular mucin comprising >50% of the tumour area, while tumours with ≤50% mucin are designated as having a mucinous component. However, these definitions are largely arbitrary and comparisons of clinico-molecular features and outcomes by proportion of mucinous component are limited. A cohort of 1643 patients with stage II/III cancer was examined for tumour mucinous component, DNA mismatch repair (MMR) status, BRAF mutation and tumour infiltrating lymphocytes (TILs). Tumours with ≤50% mucinous component exhibited similar characteristics as mucinous tumours, including association with female gender, proximal location, high grade, TIL-high, defective MMR (dMMR) and BRAF mutation. Proportion of mucinous component did not stratify disease-free survival (DFS). In univariate analysis dMMR status, but not histological grade, stratified survival for mucinous and mucinous component tumours; however, in multivariate analysis dMMR status was not an independent predictor. BRAF mutation prognostic value depended on mucinous differentiation and MMR status, with poor prognosis limited to non-mucinous pMMR tumours (HR 2.61, 95% CI 1.69-4.03; p  less then  0.001). TIL status was a strong independent predictor of DFS in mucinous/mucinous component tumours (HR 0.40, 95% CI 0.23-0.67; p  less then  0.001), and a superior predictor of prognosis compared with histological grade, MMR and BRAF mutation. Mucinous component and mucinous stage II/III CRCs exhibit clinico-molecular resemblances, with histological grade and BRAF mutation lacking prognostic value. Prognosis for these tumours was instead strongly associated with TIL status, with the most favourable outcomes in TIL-high dMMR tumours, whilst TIL-low tumours had poor outcomes irrespective of MMR status.BK polyomavirus (BKPyV) causes major complications in solid organ transplant recipients but little is known about its role in the development of urothelial carcinoma (UC) during immunosuppression. Immunohistochemistry (IHC) screening for polyomavirus large T antigen (LTag) was performed in 94 micropapillary UC (MPUC), 480 unselected UC, 199 muscle invasive UC (including 83 UC with variant differentiation), 76 cases of plasmocytoid, nested and large nested UC and 15 posttransplant UC. LTag expressing UC were reevaluated regarding their histomorphological features and characterized by IHC for p53 and HER2, chromogenic in situ hybridization for HER2 and SNaPshot analysis of the TERT promoter and HRAS. Real-time PCR and next generation sequencing (NGS) were performed to search for BKPyV-DNA and for variants in the tumor and viral genomes. We detected five LTag expressing UC which were diagnosed between 2 and 18 years after kidney (n = 4) or heart (n = 1) transplantation. 89 MPUC without history of organ transplantation and overall 755 UC (including cases with variant histology) were LTag negative. Of the five LTag expressing UC, three were MPUC, one showed extensive divergent differentiation with Mullerian type clear cell carcinoma, and one displayed focal villoglandular differentiation. All five tumors had aberrant nuclear p53 expression, 2/5 were HER2-amplified, and 3/5 had TERT promoter mutations. Within the 50 most common cancer related genes altered in UC we detected very few alterations and no TP53 mutations. BKPyV-DNA was present in 5/5 UC, chromosomal integration of the BKPyV genome was detectable in 4/5 UC. Two UC with BKPyV integration showed small deletions in the BKPyV noncoding control region (NCCR). The only UC without detectable BKPyV integration had a high viral load of human herpesvirus 6 (HHV-6). Our results suggest that LTag expression of integrated BKPyV genomes and resulting p53 inactivation lead to aggressive high-grade UC with unusual, often micropapillary morphology.We describe a morphologically distinct pattern of tumor infarction and associated sarcoma-like changes, mimicking focal anaplasia, in otherwise WHO grade I meningiomas. The described cases (n = 9) all demonstrated a discrete spindle-cell (pseudosarcomatous) component with brisk mitotic activity (12-14 mitoses/10 HPF), elevated Ki-67 (mean 75.5 ± 25.0%, quantified), absence of PR, SSTR2A, or EMA expression, and potential SMA expression (50%). Despite these high-grade features, all nine patients remained free of progression or recurrence post resection (follow-up mean 49.8 months). In contrast, among a comparison (control) cohort of consecutive WHO grade II and III meningiomas (n = 16), as expected, progression rate was high (68.8%, P = 0.002, Fisher's exact, average time to progression = 25 months, follow-up mean 39.8 months). While necrosis was a frequent feature among atypical/anaplastic meningiomas (12/16, 75%), and elevated mitoses and proliferative index were present consistent with histologic grade, a weic counterparts.Computer-assisted 3D planning has overcome the limitations of conventional 2D planning-guided orthognathic surgery (OGS), but difference for facial contour asymmetry outcome has not been verified to date. This comparative study assessed the facial contour asymmetry outcome of consecutive patients with unilateral cleft lip and palate who underwent 2D planning (n = 37)- or 3D simulation (n = 38)-guided OGS treatment for correction of maxillary hypoplasia and skeletal Class III malocclusion between 2010 and 2018. Normal age-, gender-, and ethnicity-matched individuals (n = 60) were enrolled for comparative analyses. 2D (n = 60, with 30 images for each group) and 3D (n = 43, with 18 and 25 images for 2D planning and 3D simulation groups, respectively) photogrammetric-based facial contour asymmetry-related measurements were collected from patients and normal individuals. The facial asymmetry was further verified by using subjective perception of a panel composed of 6 blinded raters. On average, the facial contour asymmetry was significantly (all p  less then  0.05) reduced after 3D virtual surgery planning for all tested parameters, with no significant differences between post-OGS 3D simulation-related values and normal individuals. No significant differences were observed for pre- and post-OGS values in conventional 2D planning-based treatment, with significant (all p  less then  0.05) differences for all normal individuals-related comparisons. This study suggests that 3D planning presents superior facial contour asymmetry outcome than 2D planning.Gafchromic films are widely used in radiotherapy using photons, electrons and protons. Dosimetric characteristics of the films in terms of beam-quality is of great importance for a better evaluation of the absorbed-dose in the clinic. In proton-therapy, film's response has been reported in terms of track-average, LΔ,T, or dose-average, LΔ,D, linear energy transfer (LET), concluding that LΔ,D is a more reliable parameter than LΔ,T. Nonetheless, in photon-beams, the film's response is generally scrutinised in terms of photon-energy. This work aimed at investigating, the total (TEF) and secondary (SE) electron fluence produced in EBT3 and MD-V3 films exposed to 20 kV-160 kV x-ray and 60Co beams and their corresponding LΔ,T and LΔ,D to determine their influence on the film's relative-efficiency, REFilm. Regardless the film-model, at energies below 100 keV, LΔ,D for TEF are about 1.7 to 2.5 times those of LΔ,T while for SE they are relatively similar (8-29%). CL-82198 mw For 60Co-gamma, LΔ,D for TEF and SE are approximately 9 and 4 times LΔ,T, respectively, which implies that LΔ,D is more important for high-photon energies. Independent of the electron-fluence and film-model, REFilm is almost constant at low average-LET, rapidly increases and thereafter steadily rises with average-LET. The REFilm-LET curve indicated that LΔ,D is more sensitive to small change than LΔ,T and if it is evaluated for SE, it would even be more appropriate to better describing the dosimeter response induced by photons in terms of ionization-density instead of LΔ,T for TEF, as generally done. Based on these results, once can conclude that the effect of the average-LET on the film's response should be considered when use for clinical-dosimetry using photons and not only the energy.High pressure below 100 MPa interferes inter-molecular interactions without causing pressure denaturation of proteins. In Escherichia coli, the binding of the chemotaxis signaling protein CheY to the flagellar motor protein FliM induces reversal of the motor rotation. Using molecular dynamics (MD) simulations and parallel cascade selection MD (PaCS-MD), we show that high pressure increases the water density in the first hydration shell of CheY and considerably induces water penetration into the CheY-FliM interface. PaCS-MD enabled us to observe pressure-induced dissociation of the CheY-FliM complex at atomic resolution. Pressure dependence of binding free energy indicates that the increase of pressure from 0.1 to 100 MPa significantly weakens the binding. Using high-pressure microscopy, we observed that high hydrostatic pressure fixes the motor rotation to the counter-clockwise direction. In conclusion, the application of pressure enhances hydration of the proteins and weakens the binding of CheY to FliM, preventing reversal of the flagellar motor.Apart from some model organisms, the interactome of most organisms is largely unidentified. High-throughput experimental techniques to determine protein-protein interactions (PPIs) are resource intensive and highly susceptible to noise. Computational methods of PPI determination can accelerate biological discovery by identifying the most promising interacting pairs of proteins and by assessing the reliability of identified PPIs. Here we present a first in-depth study describing a global view of the ant Camponotus floridanus interactome. Although several ant genomes have been sequenced in the last eight years, studies exploring and investigating PPIs in ants are lacking. Our study attempts to fill this gap and the presented interactome will also serve as a template for determining PPIs in other ants in future. Our C. floridanus interactome covers 51,866 non-redundant PPIs among 6,274 proteins, including 20,544 interactions supported by domain-domain interactions (DDIs), 13,640 interactions supported by DDIs and subcellular localization, and 10,834 high confidence interactions mediated by 3,289 proteins.