N-Acyl Homoserine Lactone Production by the Marine Isolate, Dasania marina.

Dasania marina (isolate SD1D, with 98.5% sequence similarity to Dasania marina DMS 21967 KOPRI 20902) is a marine bacterium that was isolated from ballast tank fluids as part of a biofilm study in 2014. Our previous work indicated that although this strain produced no detectable biofilm, it was the only isolate to produce N-acyl homoserine lactones (AHLs) in assays using the broad-range reporter strain, Agrobacterium tumefaciens KYC55. The goal of the current study was to determine the types of AHL molecules produced by the D. marina isolate using gas chromatography-mass spectroscopy (GCMS) and C4- to C14-AHL as standards. A time course assay indicated that the D. marina strain produced the highest level of AHLs at 20 h of growth. When extracts were subjected to GCMS, detectable levels of C8- and C10-AHL and higher levels of C12-AHL were observed. Interestingly, several biofilm-forming isolates obtained from the same source also produced detectable amounts of several AHLs. Of the isolates tested, a strain designated SD5, with 99.83% sequence similarity to Alteromonas tagae BCRC 17571, produced unstable biofilms, yet detectable levels of C6-, C8-, C10- and C12-AHL, and isolate SD8, an Alteromonas oceani S35 strain (98.85% sequence similarity), produced robust and stable biofilms accompanied by detectable levels of C8- and C12-AHL. All isolates tested produced C12-AHL at higher levels than the other AHLs. Results from this study suggest that quorum sensing and biofilm formation are uncoupled in D. marina. Whether the suite of AHLs produced by this isolate could modulate biofilm formation in other strains requires further study.

Descriptive and functional anatomy of the Heschl Gyrus: historical review, manual labelling and current perspectives.

PURPOSE: The Heschl Gyrus (HG), which includes the Primary Auditory Cortex (PAC), lies on the upper surface of the superior temporal gyrus (T1). It has been the subject of growing interest in the fields of neuroscience over the past decade. Given the considerable interhemispheric and interindividual variability of its morphology, manual labelling remains the gold standard for its radio-anatomical study. The aim of this study was to revisit the original work of Richard L. Heschl, to provide a broad overview of the available anatomical knowledge and to propose a manually labelled 3D digital model. METHODS: We reviewed existing works on the HG, from Heschl's original publication of 1878, Dejerine neuroanatomical atlas of 1895 to the most recent digital atlases (Julich-Brain Cytoarchitectonic Atlas, the Human Connectome Project). Our segmentation work was based on data from the BigBrain Project and used the MRIcron 2019 software. RESULTS: The original publication by Heschl has been translated into French and English. We propose a correspondence of previous nomenclatures with the most recent ones, including the Terminologia Neuroanatomica. Finally, despite the notable anatomical variability of the HG, clear and coherent segmentation criteria allowed us to generate a 3D digital model of the HG. DISCUSSION AND CONCLUSION: Heschl's work is still relevant and could impulse further anatomical and functional studies. The segmentation criteria could serve as a reference for manual labelling of the HG. Furthermore, a thorough, and historically based understanding of the morphological, microstructural and functional characteristics of the HG could be useful for manual segmentation.

Uncovering potential interspecies signaling factors in plant-derived mixed microbial culture.

Microbes use signaling factors for intraspecies and interspecies communications. While many intraspecies signaling factors have been found and characterized, discovery of factors for interspecies communication is lagging behind. To facilitate the discovery of such factors, we explored the potential of a mixed microbial culture (MMC) derived from wheatgrass, in which heterogeneity of this microbial community might elicit signaling factors for interspecies communication. The stability of Wheatgrass MMC in terms of community structure and metabolic output was first characterized by 16S ribosomal RNA amplicon sequencing and liquid chromatography/mass spectrometry (LC/MS), respectively. In addition, detailed MS analyses led to the identification of 12-hydroxystearic acid (12-HSA) as one of the major metabolites produced by Wheatgrass MMC. Stereochemical analysis revealed that Wheatgrass MMC produces mostly the (R)-isomer, although a small amount of the (S)-isomer was also observed. Furthermore, 12-HSA was found to modulate planktonic growth and biofilm formation of various marine bacterial strains. The current study suggests that naturally derived MMCs could serve as a simple and reproducible platform to discover potential signaling factors for interspecies communication. In addition, the study indicates that hydroxylated long-chain fatty acids, such as 12-HSA, may constitute a new class of interspecies signaling factors.

Malignant mesothelioma in situ: diagnostic and clinical considerations.

In situ stages of malignancy have been characterised in various neoplasms. Mesothelioma in situ (MIS) has been a controversial diagnosis, lacking clear diagnostic criteria and understanding as to whether it is truly a premalignant lesion in the progression of malignant mesothelioma (MM). Originally understood as a concept and defined as atypical mesothelial proliferation in the presence of invasion, it has now been suggested that loss of nuclear labelling for BRCA1-associated protein-1 (BAP1) in flat, non-invasive mesothelial lesions can define MIS. This study aimed to characterise BAP1 expression in a cohort of 19 patients diagnosed with MIS (either pure MIS, n=3, or MIS-predominant invasive MM, n=16) and to compare survival between MIS, MIS-predominant MM and MM (n=114) in order to gain insight into the characteristics of MIS. We defined pure MIS as any architectural pattern of surface mesothelial cells with loss of BAP1 in the absence of invasion, but in specimens with superficial stromal invasion we also accepted the original definition of cytologically and architecturally atypical mesothelial proliferation, in the absence of inflammatory features, with or without loss of BAP1. We observed that MIS associated with minimal invasion was associated with significantly improved survival compared to MM (8 months vs 22 months). This suggests that MIS is indeed a precursor to MM and that these cases represent earlier stage disease. Loss of BAP1 was present in 60% of mesotheliomas with invasion, so not all early cases can be detected by BAP1 loss, but our study provides evidence that BAP1 loss may be an early molecular alteration in MM pathogenesis in patients that have loss of BAP1. We confirm that BAP1 loss can be useful for diagnosis of pure MIS in surgical specimens, permitting earlier diagnosis. However, identification of a predominant MIS component with minimal invasion has prognostic and conceptual implications. Whilst no approved therapy is available for MIS, close follow up of patients with BAP1 mutation in mesothelial cells and/or diagnosis of MIS is required to monitor for disease progression and potentially investigate earlier treatment interventions.

Temperature dependence of differential capacitance in the electric double layer.Symmetric valency 1:1 electrolytes.

The differential capacitance of an electric double layer formed by an aqueous solution of KNO3 on a glassy carbon electrode is measured by impedance analysis at constant frequency. Results are obtained at electrolyte concentrations of 0.1 mol/dm3, 0.5 mol/dm3, and 1.0 mol/dm3, and at a series of temperatures, viz., 288 K, 298 K, 308 K, 318 K, and 328 K. The differential capacitance envelopes reveal a rich, complex pattern of maxima, minima, and local minima, whose magnitude and position change with a change in solution concentration. At the two lower concentrations, the temperature dependence of the capacitance, for example, at zero electrode potential, shows an alternating positive-negative behavior, while at the highest concentration of 1.0 mol/dm3, the slope of the differential capacitance-electrode potential curve is always positive. The experimental results are supplemented by a numerical grand canonical Monte Carlo simulation study of a restricted primitive model double layer but with an off-center cationic charge achieved by displacing the charge center from the ion sphere center toward its surface. The simulations, performed at the electrolyte concentration of 1.0 mol/dm3 and constant cation charge center displacement, and at varying electrode potentials and temperatures, show, in general, a negative temperature dependence of the differential capacitance. However, this temperature dependence can also be positive for a negative electrode charge and for a sufficiently large gradient of the cation charge center displacement with temperature. This feature is seen to be associated with an increase in the entropy of formation of the double layer.

The Incidence of Labelling of Non-Lung Adenocarcinomas With Antibodies Against TTF-1 and Diagnostic Implications.

Thyroid transcription factor 1 (TTF-1) is an immunohistochemical marker in the identification of lung and thyroid tumors. However, positive labelling for TTF-1 can occur in tumors from other sites, and this can result in misdiagnosis if only a limited panel of antibodies is used. We assessed the frequency of expression of 3 TTF-1 antibody clones, namely, 8G7G3/1, SPT24, and SP141 on a tissue microarray of 104 colorectal cancer (CRC), and whole-tumor sections of 165 CRC with known microsatellite instability (MSI) status. We also analyzed the expression of TTF-1 in a tissue microarray of 112 prostatic adenocarcinomas. The association of TTF-1 expression with clinicopathologic parameters and patient survival was analyzed. Six of 104 (5.7%) primary colorectal carcinomas expressed TTF-1 with SPT24 and SP141 clones, whereas only 2 (2%) of these tumors labeled positive for TTF-1 with clone 8G7G3/1. A significant association of TTF-1 expression with younger age at diagnosis (P=0.001) was found, but not with stage, or survival. The SP141 clone also labelled 24/165 (14.5%) of 165 CRC with known MSI status. There was an association with younger age (P<0.001), but not with MSI status or survival. TTF-1 expression was found in 39/112 (34%) prostate adenocarcinomas with 6/112 (5.3%) labelling with clone 8G7G3/1, 26/112 (23%) with clone SP141, and 31/112 (28%) with clone SPT24. TTF-1 expression appeared to be associated with extracapsular extension (P=0.022) and with higher stage (P=0.039). Here too TTF-1 expression was not associated with survival. The mRNA expression of TTF-1 in these tumors was confirmed by RTPCR, indicating that this is not false-positive labelling. Depending on the clone used, TTF-1 expression can vary with the SP141 and SPT24 clones exhibiting higher incidence of labelling. Pathologists should be aware of the differences in performance profiles of the different TTF-1 clones in diagnostic practice.

Asbestos, Smoking and Lung Cancer: An Update.

This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.

Implications of the diagnostic criteria of idiopathic pulmonary fibrosis in clinical practice: Analysis from the Australian Idiopathic Pulmonary Fibrosis Registry.

BACKGROUND AND OBJECTIVE: Current guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) provide specific criteria for diagnosis in the setting of multidisciplinary discussion (MDD). We evaluate the utility and reproducibility of these diagnostic guidelines, using clinical data from the Australian IPF Registry. METHODS: All patients enrolled in the registry undergo a diagnostic review whereby international IPF guidelines are applied via a registry MDD. We investigated the clinical applicability of these guidelines with regard to: (i) adherence to guidelines, (ii) Natural history of IPF diagnostic categories and (iii) Concordance for diagnostic features. RESULTS: A total of 417 participants (69% male, 70.6 ± 8.0 years) with a clinical diagnosis of IPF underwent MDD. The 23% of participants who did not meet IPF diagnostic criteria displayed identical disease behaviour to those with confirmed IPF. Honeycombing on radiology was associated with a worse prognosis and this translated into poorer prognosis in the 'definite' IPF group. While there was moderate agreement for IPF diagnostic categories, agreement for specific radiological features, other than honeycombing, was poor. CONCLUSION: In clinical practice, physicians do not always follow IPF diagnostic guidelines. We demonstrate a cohort of IPF patients who do not meet IPF diagnostic guideline criteria, based largely on their radiology and lack of lung biopsy, but who have outcomes identical to those with IPF.

Off-center charge model revisited: Electrical double layer with multivalent cations.

The off-center charge model of ions is a relatively simple model for introducing asymmetry in Coulomb interaction while retaining the simplicity and convenience of the spherical hard core geometry. A Monte Carlo simulation analysis of the planar electric double layer formed by this ionic model for 1+:1- valence systems [S. Lamperski et al., Langmuir 33, 11554-11560 (2017)] is extended to include solutions of multivalent (2+, 3+) hard spherical cations and single valence (1-) hard spherical anions near a uniformly charged, planar electrode. The solvent is modelled as a uniform dielectric continuum with a dielectric constant equal to that of the pure solvent, viz., the primitive model. Results are reported for the ion density, the cation charge profile, and the electrostatic potential profile at 1 mol/dm3 salt concentration. Additionally, the double layer potential drop, that is, the electrode potential, and the integral and the differential capacitances are computed as functions of the electrode surface charge density. The latter two quantities show an expected asymmetry as long as the cation valence is not too great and the charge of the off-center ion cannot approach too close to the electrode surface. It is unusual that the integral and differential capacitances are negative for high valence cations and a negatively charged electrode when the off-center charge is large and can be very near the surface of the electrode. The corresponding electrode potential versus surface charge density curve becomes non-monotonic and shows a change of slope, and thus the resultant integral and differential capacitances can become negative. This nonphysical result is the result of an incipient singularity when a large positive charge is too near a negatively charged electrode. Overall, the off-center charge model suggests a useful recipe to model electrical asymmetry within the broader context of the primitive model provided that the off-center charge is not too near the surface of the electrode.

Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data.

The aim of this study was to carry out a comparative analysis by transducin-like enhancer of split 1 (TLE1) immunohistochemistry and molecular analysis of SYT-SSX, for 16 pleural predominantly sarcomatoid mesotheliomas and six cases of pleuropulmonary synovial sarcoma (five pleural in distribution only, with one case of a predominantly subpleural upper lobe synovial sarcoma), all of which were solely or predominantly monophasic. Our comparison included survival and some clinical data. We consider that the following points emerged from this study.

Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis?

Malignant mesothelioma (MM) is an aggressive malignancy of the serosal membranes. Early diagnosis and accurate prognostication remain problematic. BAP1 is a tumour suppressor gene commonly mutated in MM. Germline BAP1 mutation has been associated with early onset and less aggressive disease compared with sporadic MM. Sporadic BAP1 mutations are common and are associated with improved survival in MM, contrary to other malignancies. This study investigated the prognostic role of BAP1 in matched cytology and surgical specimens and aimed to investigate the association between BAP1 and the established prognostic marker VEGFA from a cohort of 81 patients. BAP1 mutation was found in 58% of histology and 59% of cytology specimens. Loss of BAP1 expression in both surgical and cytology specimens was significantly associated with poorer survival in a multivariate analysis when controlling for known prognostic indicators. Increased levels of VEGFA in pleural effusions were associated with poor survival. We conclude that the prognostic significance of BAP1 mutations in MM cannot be determined in isolation of other prognostic factors, which may vary between patients. Pathologists should employ caution when commenting on prognostic implications of BAP1 status of MM patients in diagnostic pathology reports, but it may be useful for early diagnosis.

The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center.

Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostat, Englewood, NJ). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin and mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.

Monte Carlo Study of a Planar Electric Double Layer Formed by Ions with Off-Center Charge.

Grand canonical Monte Carlo simulation results are reported for an electric double layer (EDL) modeled by a planar charged hard wall, hard sphere cations with an off-center charge, and spherical anions with a charge at the center of the sphere. The ion charge numbers are Z+ = +1 and Z- = -1, and the diameter, d, of a hard sphere is the same for anions and cations. The ions are immersed in a solvent mimicked by a continuum dielectric medium at standard temperature. The results are obtained for three values of charge displacement, s+0 = d/16, d/4, 7d/16 from the center of the sphere and the following electrolyte concentrations: 0.5, 1.0, 2.0, and 3.0 M. The profiles of electrode-ion singlet distributions, cation reduced charge density, angular function, and mean electrostatic potential are reported for an electrode surface charge density σ = -0.30 C m-2, whereas the electrode potential and the differential capacitance of EDL are shown as functions of the electrode charge density varying from -1.00 to +1.00 C m-2. At negative electrode charges and with increasing values of the charge separation, the differential capacitance curve rises. As the electrolyte concentration increases, the shape of the differential capacitance curve changes from that of a minimum surrounded by two maxima into that of a distorted single maximum.

On the capacitance of narrow nanotubes.

The storage of ions in narrow nanotubes is investigated by grand-canonical Monte Carlo simulations. The interaction between the ions is screened by the image charge on the wall of the tube, but at close distances it is still much larger than the thermal energy. Depending on the electrochemical potential imposed by the contact with an electrolyte solution, two different regimes can be distinguished at the potential of zero charge: for low values corresponding to an ionophobic pore the tube is almost empty; for high values - ionophilic pore - a one dimensional salt is formed. The two regions are separated by a narrow transition zone marked by strong fluctuations. Depending on the regime and on the value assumed for the dielectric constant, the interfacial capacity shows four, two, or in rare cases three maxima. The results are compared to a reference system of non-interacting ions, and discussed with respect to recent calculations within classical density functional theory.

Ion distribution and selectivity of ionic liquids in microporous electrodes.

The energy density of an electric double layer capacitor, also known as supercapacitor, depends on ion distributions in the micropores of its electrodes. Herein we study ion selectivity and partitioning of symmetric, asymmetric, and mixed ionic liquids among different pores using the classical density functional theory. We find that a charged micropore in contact with mixed ions of the same valence is always selective to the smaller ions, and the ion selectivity, which is strongest when the pore size is comparable to the ion diameters, drastically falls as the pore size increases. The partitioning behavior in ionic liquids is fundamentally different from those corresponding to ion distributions in aqueous systems whereby the ion selectivity is dominated by the surface energy and entropic effects insensitive to the degree of confinement.

Vasculogenic mimicry in malignant mesothelioma: an experimental and immunohistochemical analysis.

Vasculogenic mimicry, the process in which cancer cells form angiomatoid structures independent of or in addition to host angiogenesis has been recorded in several otherwise non-endothelial malignant neoplasms. This study describes evidence of routine vascular mimicry by human mesothelioma cell lines in vitro, when the cell lines are cultured alone or co-cultured with human umbilical vascular endothelial cells, with the formation of angiomatoid tubular networks. Vasculogenic mimicry is also supported by immunohistochemical demonstration of human-specific anti-mitochondria antibody labelling of tumour-associated vasculature of human mesothelioma cells xenotransplanted into nude mice, and by evidence of vascular mimicry in some biopsy samples of human malignant mesotheliomas. These studies show mosaic interlacing of cells that co-label or label individually for immunohistochemical markers of endothelial and mesothelial differentiation. If vascular mimicry in mesothelioma can be characterised more fully, this may facilitate identification of more specific and targeted therapeutic approaches such as anti-angiogenesis in combination with chemotherapy and immunotherapy or other therapeutic approaches.

Can ionophobic nanopores enhance the energy storage capacity of electric-double-layer capacitors containing nonaqueous electrolytes?

The ionophobicity effect of nanoporous electrodes on the capacitance and the energy storage capacity of nonaqueous-electrolyte supercapacitors is studied by means of the classical density functional theory (DFT). It has been hypothesized that ionophobic nanopores may create obstacles in charging, but they store energy much more efficiently than ionophilic pores. In this study, we find that, for both ionic liquids and organic electrolytes, an ionophobic pore exhibits a charging behavior different from that of an ionophilic pore, and that the capacitance-voltage curve changes from a bell shape to a two-hump camel shape when the pore ionophobicity increases. For electric-double-layer capacitors containing organic electrolytes, an increase in the ionophobicity of the nanopores leads to a higher capacity for energy storage. Without taking into account the effects of background screening, the DFT predicts that an ionophobic pore containing an ionic liquid does not enhance the supercapacitor performance within the practical voltage ranges. However, by using an effective dielectric constant to account for ion polarizability, the DFT predicts that, like an organic electrolyte, an ionophobic pore with an ionic liquid is also able to increase the energy stored when the electrode voltage is beyond a certain value. We find that the critical voltage for an enhanced capacitance in an ionic liquid is larger than that in an organic electrolyte. Our theoretical predictions provide further understanding of how chemical modification of porous electrodes affects the performance of supercapacitors.

Usefulness of Aquaporin 1 as a Prognostic Marker in a Prospective Cohort of Malignant Mesotheliomas.

(1) BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumour of the serosal membranes, associated with exposure to asbestos. Survival is generally poor, but prognostication for individual patients is difficult. We recently described Aquaporin 1 (AQP1) as independent prognostic factor in two separate retrospective cohorts of MM patients. Here we assess the usefulness of AQP1 prospectively, and determine the inter-observer agreement in assessing AQP1 scores; (2) METHODS: A total of 104 consecutive cases of MM were included. Sufficient tissue for immunohistochemistry was available for 100 cases, and these cases were labelled for AQP1. Labelling was assessed by two pathologists. Complete clinical information and follow up was available for 91 cases; (3) RESULTS: Labelling of ≥50% of tumour cells for AQP indicated improved prognosis in a univariate model (median survival 13 versus 8 months, p = 0.008), but the significance was decreased in a multivariate analysis. Scoring for AQP1 was robust, with an inter-observer kappa value of 0.722, indicating substantial agreement between observers; (4) CONCLUSION: AQP1 is a useful prognostic marker that can be easily incorporated in existing diagnostic immunohistochemical panels and which can be reliably interpreted by different pathologists.

Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

CONTEXT: -The International Collaboration on Cancer Reporting is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom; the College of American Pathologists; the Canadian Association of Pathologists-Association Canadienne des Pathologists, in association with the Canadian Partnership Against Cancer; and the European Society of Pathology. Its goal is to produce common, internationally agreed upon, evidence-based datasets for use throughout the world. OBJECTIVE: -To describe a dataset developed by the Expert Panel of the International Collaboration on Cancer Reporting for reporting malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of "required" (mandatory) and "recommended" (nonmandatory) elements. DESIGN: -Based on a review of the most recent evidence and supported by explanatory commentary. RESULTS: -Eight required elements and 7 recommended elements were agreed upon by the Expert Panel to represent the essential information for reporting malignant mesothelioma of the pleura and peritoneum. CONCLUSIONS: -In time, the widespread use of an internationally agreed upon, structured, pathology dataset for mesothelioma will lead not only to improved patient management but also provide valuable data for research and international benchmarks.