Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022.

BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time. METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted. RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n = 225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services. CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members.

Agricultural practices and quality of environment: evidence for global perspective.

The study emphasizes to examine the causal relationship among CO2 emission, agricultural value added, industrial production, urbanization, nuclear energy consumption, and economic growth across the panel of 59 countries. The data is collected from World Bank database over the period of 1982-2015. For econometric estimations, we have divided the sample into different income groups: low income, lower middle income, upper middle income, and higher income. In case of higher income countries, empirical results have reported the unidirectional causality from agricultural value added to CO2 emission, whereas, bidirectional causality between nuclear energy consumption and CO2 emission. Upper-middle-income countries have confirmed the bidirectional causality between CO2 emissions and agricultural added; however, unidirectional causality runs from nuclear consumption to CO2 emission. According to Granger causality estimations, agricultural value added and nuclear energy consumption do not cause the CO2 emission in low income and lower-middle-income countries. Long-run estimations have mentioned that higher agricultural value added leads to increase the CO2 emission, in upper middle income and higher income countries. On contrary, in case of low-income and lower-middle-income countries, agricultural value added has inverse relationship with CO2 emission. Higher nuclear energy consumption tends to reduce the CO2 emission, except the upper-middle-income countries.

Testing EKC hypothesis with energy and sustainable development challenges: a fresh evidence from belt and road initiative economies.

Diverse impact of greenhouse gasses (GHGs) over the landscape of environment is generally believed in literature. As CO2 emission acutely leads to GHGs is a major contributor for global warming, it creates a serious pressure on natural resources and ecological settings. Similarly, low-carbon (CO2) economy, plenty of energy resources, and sustainable growth are a big ask for worldwide economies in this era of mechanization. This paper analyzes the Environmental Kuznets Curve (EKC) hypothesis, for Belt and Road Initiative (BRI) economies, to contend the role of mega projects in BRI as an attribute for ecological detriments. The on-hand study engages fresh data information ranging from 1981 to 2016 holding with heterogeneity and cross-sectional dependence as a special deliberation. The calculated outcomes expose that, mean group estimator provides strong evidence and favor the existence of EKC approximately in every region. The long-run influence is measured by pooled mean group estimators, which shows significant outcomes in every region; additionally, the EKC hypothesis affirmed in the long run especially for developed economies. Mega projects, i.e., BRI requisite immense energy sources to accomplishing the enclosed projects efficiently and effectively. The positive association between carbon emission and energy consumption troubled the governments to make policies for restraining the magnitude of carbon emission and controls energy usage for enduring environment to its original position. Next, the valuations depicted the dense recommendations for state administrations in capacity of rigorous level supremacy, trash managing campaigns, renewable energy reliance, and advance for desirable judgments to sterilize the atmosphere.

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort.

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US.  Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB).   Methods:  888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses data and associated biospecimens for over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier's method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal).  Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were younger than 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and having combination treatment of surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone.

Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues.

A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test and its properties was assessed under Clinical Laboratory Improvement Amendments-approved guidelines using FFPE tissue from an independent multicenter patient cohort. Concordance studies were performed using matched frozen and FFPE mesothelioma samples. The prognostic value of the test was evaluated in an independent validation cohort of 73 mesothelioma patients who underwent surgical resection. FFPE-based classification demonstrated overall high concordance (83%) with the matched frozen specimens, on removal of cases with low confidence scores, showing sensitivity and specificity in predicting type B classification (poor outcome) of 43% and 98%, respectively. Concordance between research and clinical methods increased to 87% on removal of low confidence cases. Median survival times in the validation cohort were 18 and 7 months in type A and type B cases, respectively (P = 0.002). Multivariate classification adding pathologic staging information to the gene expression score resulted in significant stratification of risk groups. The median survival times were 52 and 14 months in the low-risk (class 1) and intermediate-risk (class 2) groups, respectively. The prognostic molecular test for mesothelioma can be performed on FFPE tissues to predict survival, and can provide an orthogonal tool, in combination with established pathologic parameters, for risk evaluation.

PaTH: towards a learning health system in the Mid-Atlantic region.

The PaTH (University of Pittsburgh/UPMC, Penn State College of Medicine, Temple University Hospital, and Johns Hopkins University) clinical data research network initiative is a collaborative effort among four academic health centers in the Mid-Atlantic region. PaTH will provide robust infrastructure to conduct research, explore clinical outcomes, link with biospecimens, and improve methods for sharing and analyzing data across our diverse populations. Our disease foci are idiopathic pulmonary fibrosis, atrial fibrillation, and obesity. The four network sites have extensive experience in using data from electronic health records and have devised robust methods for patient outreach and recruitment. The network will adopt best practices by using the open-source data-sharing tool, Informatics for Integrating Biology and the Bedside (i2b2), at each site to enhance data sharing using centrally defined common data elements, and will use the Shared Health Research Information Network (SHRINE) for distributed queries across the network.

Use of automated image analysis in evaluation of Mesothelioma Tissue Microarray (TMA) from National Mesothelioma Virtual Bank.

The National Mesothelioma Virtual Bank (NMVB) was established to provide annotated biospecimens to the mesothelioma research community. The resource provides tissue microarrays (TMA) to evaluate the biomarkers along with a variety of other resected mesothelioma specimens. In this manuscript, we describe the immunohistochemical evaluation of the mesothelioma TMA with three key antibodies that are used in making the diagnosis of mesothelioma, and compared the immunohistochemical assessment between manual scoring and image analysis. The TMA was assessed for the immunohistochemical expression of calretinin (N=39), cytokeratin (CK) 5/6 (N=33), and D2-40 (N=37). Immunohistochemistry was evaluated by semi-quantitative (manual) scoring using light microscope (MS) and by automated image analysis (AS). Calretinin staining was seen in both cytoplasmic and nuclear locations. CK5/6 stain was localized to the cytoplasm. D2-40 stain showed only membranous expression in our cases. • Based on the pathologist's scores, calretinin was positive in 31 of the 39 cases (80%), CK 5/6 in 15 of the 33 cases (46%) and D2-40 in 18 of the 37 cases (49%). • The percent-positive agreement between manual scores and image analysis was 90% (35/39), 94% (31/33), and 95% (35/37) for calretinin, CK 5/6, and D2-40, respectively. There was a substantial agree-ment between manual and automated scores for calretinin (kappa = 0.614) and an almost perfect agreement for CK5/6 (kappa = 0.879) and D2-40 (kappa = 0.892). Our study confirms that the immunohistochemical staining pattern of mesotheliomas in the NMVB UPMC TMA is similar to other studies. Our findings also show that automated image analysis provides similar results to manual scoring by pathologists, and provides a reproducible, objective, and accurate platform for immunohistochemical assessment of biomarker expression.

National Mesothelioma Virtual Bank: A Platform for Collaborative Research and Mesothelioma Biobanking Resource to Support Translational Research.

The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New York University, University of Pennsylvania, University of Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).

Design and utilization of the colorectal and pancreatic neoplasm virtual biorepository: An early detection research network initiative.

BACKGROUND: The Early Detection Research Network (EDRN) colorectal and pancreatic neoplasm virtual biorepository is a bioinformatics-driven system that provides high-quality clinicopathology-rich information for clinical biospecimens. This NCI-sponsored EDRN resource supports translational cancer research. The information model of this biorepository is based on three components: (a) development of common data elements (CDE), (b) a robust data entry tool and (c) comprehensive data query tools. METHODS: The aim of the EDRN initiative is to develop and sustain a virtual biorepository for support of translational research. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. The data entry tool is a portable and flexible Oracle-based data entry application, which is an easily mastered, web-based tool. The data query tool facilitates investigators to search deidentified information within the warehouse through a "point and click" interface thus enabling only the selected data elements to be essentially copied into a data mart using a dimensional-modeled structure from the warehouse's relational structure. RESULTS: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository database contains multimodal datasets that are available to investigators via a web-based query tool. At present, the database holds 2,405 cases and 2,068 tumor accessions. The data disclosure is strictly regulated by user's authorization. The high-quality and well-characterized biospecimens have been used in different translational science research projects as well as to further various epidemiologic and genomics studies. CONCLUSIONS: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository with a tangible translational biomedical informatics infrastructure facilitates translational research. The data query tool acts as a central source and provides a mechanism for researchers to efficiently query clinically annotated datasets and biospecimens that are pertinent to their research areas. The tool ensures patient health information protection by disclosing only deidentified data with Institutional Review Board and Health Insurance Portability and Accountability Act protocols.

A decade of experience in the development and implementation of tissue banking informatics tools for intra and inter-institutional translational research.

CONTEXT: Tissue banking informatics deals with standardized annotation, collection and storage of biospecimens that can further be shared by researchers. Over the last decade, the Department of Biomedical Informatics (DBMI) at the University of Pittsburgh has developed various tissue banking informatics tools to expedite translational medicine research. In this review, we describe the technical approach and capabilities of these models. DESIGN: Clinical annotation of biospecimens requires data retrieval from various clinical information systems and the de-identification of the data by an honest broker. Based upon these requirements, DBMI, with its collaborators, has developed both Oracle-based organ-specific data marts and a more generic, model-driven architecture for biorepositories. The organ-specific models are developed utilizing Oracle 9.2.0.1 server tools and software applications and the model-driven architecture is implemented in a J2EE framework. RESULT: The organ-specific biorepositories implemented by DBMI include the Cooperative Prostate Cancer Tissue Resource (http://www.cpctr.info/), Pennsylvania Cancer Alliance Bioinformatics Consortium (http://pcabc.upmc.edu/main.cfm), EDRN Colorectal and Pancreatic Neoplasm Database (http://edrn.nci.nih.gov/) and Specialized Programs of Research Excellence (SPORE) Head and Neck Neoplasm Database (http://spores.nci.nih.gov/current/hn/index.htm). The model-based architecture is represented by the National Mesothelioma Virtual Bank (http://mesotissue.org/). These biorepositories provide thousands of well annotated biospecimens for the researchers that are searchable through query interfaces available via the Internet. CONCLUSION: These systems, developed and supported by our institute, serve to form a common platform for cancer research to accelerate progress in clinical and translational research. In addition, they provide a tangible infrastructure and resource for exposing research resources and biospecimen services in collaboration with the clinical anatomic pathology laboratory information system (APLIS) and the cancer registry information systems.

Nephrogenic adenoma.

Nephrogenic adenoma is an uncommon benign lesion. Its pathogenesis is as yet unclear although various theories have been proposed, including the embryological and inflammatory theory. The proposal that nephrogenic adenoma originates from the implantation of exfoliated renal tubular cells is lately gaining wider acceptance. Careful histological examination is essential to accurately identify this lesion and to differentiate it from other locally arising malignant lesions. The role of immunohistochemistry cannot be undermined in the diagnosis of nephrogenic adenoma, although histological diagnosis is usually conclusive. The possibility of nephrogenic adenoma should always be in the differential diagnosis when evaluating patients with predisposed urinary tract symptoms.

An informatics supported web-based data annotation and query tool to expedite translational research for head and neck malignancies.

BACKGROUND: The Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer neoplasm virtual biorepository is a bioinformatics-supported system to incorporate data from various clinical, pathological, and molecular systems into a single architecture based on a set of common data elements (CDEs) that provides semantic and syntactic interoperability of data sets. RESULTS: The various components of this annotation tool include the Development of Common Data Elements (CDEs) that are derived from College of American Pathologists (CAP) Checklist and North American Association of Central Cancer Registries (NAACR) standards. The Data Entry Tool is a portable and flexible Oracle-based data entry device, which is an easily mastered web-based tool. The Data Query Tool helps investigators and researchers to search de-identified information within the warehouse/resource through a "point and click" interface, thus enabling only the selected data elements to be essentially copied into a data mart using a multi dimensional model from the warehouse's relational structure.The SPORE Head and Neck Neoplasm Database contains multimodal datasets that are accessible to investigators via an easy to use query tool. The database currently holds 6553 cases and 10607 tumor accessions. Among these, there are 965 metastatic, 4227 primary, 1369 recurrent, and 483 new primary cases. The data disclosure is strictly regulated by user's authorization. CONCLUSION: The SPORE Head and Neck Neoplasm Virtual Biorepository is a robust translational biomedical informatics tool that can facilitate basic science, clinical, and translational research. The Data Query Tool acts as a central source providing a mechanism for researchers to efficiently find clinically annotated datasets and biospecimens that are relevant to their research areas. The tool protects patient privacy by revealing only de-identified data in accordance with regulations and approvals of the IRB and scientific review committee.

Usefulness of a synoptic data tool for reporting of head and neck neoplasms based on the College of American Pathologists cancer checklists.

The primary source of information that clinicians use when evaluating and managing patients with cancer is the surgical pathology report. Omission of critical information from the report is a recognized problem in pathology, especially considering the expanding amount of information, such as molecular diagnostics data, that is now routinely included in reports. To standardize surgical pathology reports, the College of American Pathologists (CAP) introduced the CAP checklists. In 2004, the American College of Surgeons Commission on Cancer mandated that 90% of pathology reports indicating a cancer diagnosis at participating centers contain all scientifically validated or regularly used data elements. The University of Pittsburgh Medical Center has implemented synoptic reporting based on the CAP checklists for all major tumor types. We report our experience with synoptic reporting on head and neck neoplasms, demonstrating, in particular, how this can be customized according to needs of each institution.

Adenomatoid tumor of testis.

Adenomatoid tumors are responsible for 30% of all paratesticular masses. These are usually asymptomatic, slow growing masses. They are benign tumors comprising of cords and tubules of cuboidal to columnar cells with vacuolated cytoplasm and fibrous stroma. They are considered to be of mesothelial origin supported by histochemical studies and genetic analysis of Wilms tumor 1 gene expression. Excision biopsy is both diagnostic and therapeutic procedure. The main clinical consideration is accurate diagnosis preventing unnecessary orchiectomy. Diagnostic studies include serum tumor markers (negative alpha fetoprotein, beta HCG, LDH) ultrasonography (hypoechoic and homogenous appearance) and frozen section.

National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research.

BACKGROUND: Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. METHODS: The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid (caBIG, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. RESULT: The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. CONCLUSION: The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer - an emerging standard based approach for the Mesothelioma Virtual Tissue Bank.

BACKGROUND: Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) - compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). METHODS: The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). RESULTS: Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions. CONCLUSION: The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.

Automated whole slide imaging.

BACKGROUND: Automated high-speed, high-resolution whole slide image (WSI) technology is being rapidly adopted in pathology owing to increased speed of computing, rapid networking, and high image quality and potential to reduce the overall turnaround time required for slide assessment. Method/objectives: This review presents the structure, functioning and performance of some of the WSI systems available in the market and highlights a few validation studies that have been performed to assess the overall utility of WSI systems. CONCLUSION: The automated WSI is a robotic microscope that digitizes the entire slide field by field and uses software to merge or stitch individual fields into a composite image. Commercially available systems provide many improved functions that are useful for editing the digital images and improving the image quality.