The Angiosarcoma Project: Generating the genomic landscape of a rare cancer through a direct-to-patient initiative.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1519-1519 ◽  
Author(s):  
Corrie Painter ◽  
Michael Dunphy ◽  
Elana Anastasio ◽  
Mary McGillicuddy ◽  
Kristin Anderka ◽  
...  
Keyword(s):  
Medical Records ◽  
Large Scale ◽  
Dna Analysis ◽  
Genomic Analysis ◽  
Clinical Information ◽  
Rapid Identification ◽  
Blood Draw ◽  
Tissue Samples ◽  
The Usa ◽  
Reported Data

1519 Background: Angiosarcoma (AS) is a rare soft tissue sarcoma, with an incidence of 300/yr and a 5-year DSS of 30%. The low incidence has impeded large-scale research efforts that may lead to improved clinical outcomes. To address this, we launched a nationwide study, which seeks to empower patients (pts) to accelerate research by sharing their samples and clinical information remotely. Methods: With pts and advocacy groups we developed a website to allow AS pts to participate across the US. Pts are mailed a saliva and blood draw kit for germline and cell free (cf) DNA analysis. We then obtain medical records and stored tumor samples. Whole exome sequencing will be performed on tumor, cfDNA and saliva samples. Transcriptome analysis will be performed on tumor samples. A clinically annotated genomic database will be generated and shared widely to identify genomic drivers and mechanisms of response and resistance to therapies. Study updates will be shared with pts regularly. Results: We conducted a 3-week pilot study to test the feasibility of enrolling geographically dispersed AS pts through a direct-to-patient (DTP) approach. Through social media, we identified 100+ pts willing to participate, 90 within the first day of outreach. We enrolled 15 pts from 10 states to test our ability to remotely obtain pt reported data, online consent, and samples. The average age of pts is 48, ranging 23-71 yrs. Primary locations of AS are breast 6 pts (40%), cardiac 4 pts (27%), scalp 2 pts (13%), liver 1 pt (6%), bladder 1 pt (6%), forehead 1 pt (6%). 9 pts (60%) reported being disease free, 4 pts (27%) reported having AS spread to lung, lymph, bone, and hip. Requests for medical records and tissue samples are underway, and initial saliva samples have been received. We are now opening this study to all AS pts in the USA. Conclusions: A DTP approach enabled rapid identification of an initial cohort of AS pts willing to share tumors, saliva, blood and medical records. We were able to obtain detailed clinical experiences and samples to perform genomic analysis. This study serves as proof of principle that DTP genomics efforts can democratize cancer research for exceedingly rare cancers, which to date have been disproportionately understudied.

The Metastatic Breast Cancer (MBC) project: Accelerating translational research through direct patient engagement.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1076-1076 ◽  
Author(s):  
Nikhil Wagle ◽  
Corrie Painter ◽  
Elana Anastasio ◽  
Michael Dunphy ◽  
Mary McGillicuddy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Medical Records ◽  
De Novo ◽  
Metastatic Breast ◽  
Genomic Analysis ◽  
Clinical Information ◽  
Rapid Identification ◽  
Cancer Treatments ◽  
Whole Exome

1076 Background: The Metastatic Breast Cancer Project is a nationwide research study, launched in Oct 2015 in collaboration with patients (pts) and advocacy groups, that directly engages pts through social media and seeks to empower them to share their experiences, clinical information, and samples to accelerate research. Methods: MBC pts enroll by providing their information at mbcproject.org. Pts are sent a saliva kit and asked to mail back a sample which is used to extract germline DNA. We contact pts medical providers and obtain medical records (MRs) and stored tumor samples. Pts may also submit a blood sample, used to extract cell free DNA (cfDNA). Whole exome sequencing (WES) is performed on tumor, germline, and cfDNA; transcriptome sequencing is performed on tumor. Clinical and genomic data are used to generate genomic landscapes in pt subgroups and to identify mechanisms of response and resistance to therapies. Data are shared widely through public databases. Pts receive regular study updates. Results: In 12 months, 2908 MBC pts from 50 states enrolled. 95% completed the 16-question survey about their cancer, treatments, and demographics. 1730 (60%) completed the online consent form. 100-200 pts continue to enroll monthly. To date, 1539 saliva kits were mailed and 1120 samples were received (73%). 992 unique treating institutions were reported by pts, including 733 institutions reported by only 1 pt each and 5 institutions reported by more than 40 pts each. We have obtained MRs from 253 patients (67% yield) and tumor samples from 85 pts (67% yield). WES was successfully completed for 79 tumors of 88 attempted (90%). WES has been performed on initial cfDNA samples. Conclusions: A direct-to-patient approach enabled rapid identification of thousands of MBC pts willing to share MRs, saliva, and tumor samples, including many with rare phenotypes. Remote acquisition of MRs, saliva, tumor, and blood for pts located throughout the US is feasible. We estimate that for ~33% of consenting patients, we can obtain medical records, saliva, and tumor tissue. Genomic analysis of tumor and cfDNA from subgroups including young pts, pts with extraordinary responses, and pts with de novo MBC will be presented.

scholarly journals GENVISAGE: Rapid Identification of Discriminative and Explainable Feature Pairs for Genomic Analysis

2020 ◽  
Author(s):  
Silu Huang ◽  
Charles Blatti ◽  
Saurabh Sinha ◽  
Aditya Parameswaran
Keyword(s):  
Large Scale ◽  
Genomic Analysis ◽  
Rapid Identification ◽  
Biological Data ◽  
Data Sets ◽  
Chemotherapy Drugs ◽  
Link Type ◽  
Discriminative Feature ◽  
Exploration Tool ◽  
High Dimensional Datasets

AbstractMotivationA common but critical task in genomic data analysis is finding features that separate and thereby help explain differences between two classes of biological objects, e.g., genes that explain the differences between healthy and diseased patients. As lower-cost, high-throughput experimental methods greatly increase the number of samples that are assayed as objects for analysis, computational methods are needed to quickly provide insights into high-dimensional datasets with tens of thousands of objects and features.ResultsWe develop an interactive exploration tool called Genvisage that rapidly discovers the most discriminative feature pairs that best separate two classes in a dataset, and displays the corresponding visualizations. Since quickly finding top feature pairs is computationally challenging, especially when the numbers of objects and features are large, we propose a suite of optimizations to make Genvisage more responsive and demonstrate that our optimizations lead to a 400X speedup over competitive baselines for multiple biological data sets. With this speedup, Genvisage enables the exploration of more large-scale datasets and alternate hypotheses in an interactive and interpretable fashion. We apply Genvisage to uncover pairs of genes whose transcriptomic responses significantly discriminate treatments of several chemotherapy drugs.AvailabilityFree webserver at http://genvisage.knoweng.org:443/ with source code at https://github.com/KnowEnG/Genvisage

Familial nonsyndromic craniosynostosis with specific deformity of the cranium

2012 ◽  
Vol 10 (6) ◽  
pp. 560-564 ◽  
Author(s):  
Azusa Shimizu ◽  
Yuzo Komuro ◽  
Masakazu Miyajima ◽  
Hajime Arai
Keyword(s):  
Large Scale ◽  
Dna Analysis ◽  
Genomic Analysis ◽  
Male Infant ◽  
Copy Number Polymorphism ◽  
Syndromic Craniosynostosis ◽  
Frontoorbital Advancement ◽  
Metopic Suture ◽  
Long Term Observation

An otherwise healthy, developmentally normal 3-week-old male infant presented with complex multisuture craniosynostosis involving the metopic suture and bilateral coronal sutures with frontal prominence and hypotelorism. Frontal craniectomy and bilateral frontoorbital advancement remodeling were performed at the age of 5 months. The postoperative course was uneventful. The child's development was normal up to 8 months after the operation. His father and grandfather had similar specific deformities of the cranium, but no anomaly of the extremities was found, and conversation suggested that their intelligence was normal, excluding the possibility of syndromic craniosynostosis. A DNA analysis revealed large-scale copy number polymorphism of chromosome 4 in the patient and his family, which may include the phenotype of the cranium. Neither FGFR mutation nor absence of a TWIST1 mutation in the sequence from 291 to 1087, which includes DNA binding, Helix1, Loop, and Helix2, was identified. The patient apparently had a rare case of familial nonsyndromic craniosynostosis. The authors plan further genomic analysis of this family and long-term observation of the craniofacial deformity of this patient.

Screening for the FV: Q506 Mutation – Evaluation of Thirteen Plasma-based Methods for their Diagnostic Efficacy in Comparison with DNA Analysis

1997 ◽  
Vol 77 (03) ◽  
pp. 436-439 ◽  
Author(s):  
Armando Tripodi ◽  
Barbara Negri ◽  
Rogier M Bertina ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thrombosis ◽  
Large Scale ◽  
Dna Analysis ◽  
Genetic Defect ◽  
Laboratory Diagnosis ◽  
Economic Benefits ◽  
Factor V ◽  
Factor X ◽  
Diagnostic Efficacy ◽  
Dna Test

SummaryThe factor V (FV) mutation Q506 that causes resistance to activated protein C (APC) is the genetic defect associated most frequently with venous thrombosis. The laboratory diagnosis can be made by DNA analysis or by clotting tests that measure the degree of prolongation of plasma clotting time upon addition of APC. Home-made and commercial methods are available but no comparative evaluation of their diagnostic efficacy has so far been reported. Eighty frozen coded plasma samples from carriers and non-carriers of the FV: Q506 mutation, diagnosed by DNA analysis, were sent to 8 experienced laboratories that were asked to analyze these samples in blind with their own APC resistance tests. The APTT methods were highly variable in their capacity to discriminate between carriers and non-carriers but this capacity increased dramatically when samples were diluted with FV-deficient plasma before analysis, bringing the sensitivity and specificity of these tests to 100%. The best discrimination was obtained with methods in which fibrin formation is triggered by the addition of activated factor X or Russell viper venom. In conclusion, this study provides evidence that some coagulation tests are able to distinguish carriers of the FV: Q506 mutation from non-carriers as well as the DNA test. They are inexpensive and easy to perform. Their use in large-scale clinical trials should be of help to determine the medical and economic benefits of screening healthy individuals for the mutation before they are exposed to such risk factors for venous thrombosis as surgery, pregnancy and oral contraceptives.

Bedside Cardiac Pocus in Emergency Setting: A Practice Review

2020 ◽  
Vol 15 ◽  
Author(s):  
Christian Zanza ◽  
Yaroslava Longhitano ◽  
Marco Artico ◽  
Gianmaria Cammarota ◽  
Andrea Barbanera ◽  
...  
Keyword(s):  
Emergency Medicine ◽  
Core Curriculum ◽  
Case Reports ◽  
Short Review ◽  
Rapid Identification ◽  
Cochrane Library ◽  
Emergency Setting ◽  
Holistic View ◽  
Questions And Answers ◽  
The Usa

Background: in the last years, ultrasound technology has entered in clinical practice as a tank and today, it has also allowed to no-cardiologists to extend and to deep their medical examination without the needing to call the consultant and having a good profile of diagnostic accuracy. The ultrasound bedside does not replace the consultant but it allows not to perform inappropriate consultations with more savings for hospitals. Objective: The aim was to review recently published literature to inform the clinician about the most up to date management of use bedside echography in emergency setting. In this short review we focused on two types of syndromes, no traumatichypotension and dyspnea, common to the three holistic disciplines of medicine, showing the main and basic questions and answers that ultrasound can give us for rapid identification of the problem Methods: We conducted a systematic review using Pubmed/Medline, Ovid/Willey and Cochrane Library, combining key terms such as “cardiac ultrasound, “cardiac diseases”,“emergency medicine”,“pocus”, “dyspnea”,“ hypotension”. We selected the most relevant clinical trials and review articles (excluding case reports) published in the last 19 years and in our opinion 59 publications appeared the best choice according to the PRISMA statement. In additional papers identified from individual article reference lists were also included. Conclusion: Recent studies have shown promise in establishing best practices for evaluation of heart, lung abdomen and deep vessels At the moment bedside US is widely used in an integrated ultrasound vision just like the holistic view have internal medicine, intensive care and emergency medicine and many medical schools in Europe and the USA are inserting ultrasonography into the core curriculum but we still have to find a standard method for the training program for minimum competence acquisition.

scholarly journals Large-Scale, High-Throughput Validation of Short Hairpin RNA Sequences for RNA Interference

2006 ◽  
Vol 11 (3) ◽  
pp. 236-246 ◽  
Author(s):  
Laurence H. Lamarcq ◽  
Bradley J. Scherer ◽  
Michael L. Phelan ◽  
Nikolai N. Kalnine ◽  
Yen H. Nguyen ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Strong Support ◽  
Gc Content ◽  
Rapid Identification ◽  
Hairpin Rna ◽  
Rna Sequences ◽  
Short Hairpin ◽  
Short Hairpin Rnas ◽  
Interfering Rna

A method for high-throughput cloning and analysis of short hairpin RNAs (shRNAs) is described. Using this approach, 464 shRNAs against 116 different genes were screened for knockdown efficacy, enabling rapid identification of effective shRNAs against 74 genes. Statistical analysis of the effects of various criteria on the activity of the shRNAs confirmed that some of the rules thought to govern small interfering RNA (siRNA) activity also apply to shRNAs. These include moderate GC content, absence of internal hairpins, and asymmetric thermal stability. However, the authors did not find strong support for positionspecific rules. In addition, analysis of the data suggests that not all genes are equally susceptible to RNAinterference (RNAi).

scholarly journals Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuxuan Li ◽  
Yang Jie ◽  
Xiaofei Wang ◽  
Jing Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Medical Records ◽  
Clinical Information ◽  
Serum Cytokines ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Ifn Γ ◽  
Quantitative Changes ◽  
Anti Inflammatory Cytokine

Abstract Background Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. Results The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. Conclusions Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

scholarly journals Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Yan ◽  
Zuotian Huang ◽  
Tong Mou ◽  
Yunhai Luo ◽  
Yanyao Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Clinical Information ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Competing Endogenous Rna ◽  
Tissue Samples ◽  
Potential Biomarkers

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.

scholarly journals Implementing an Integrated Large-Scale Clinical Information System for ISSSTE’s Hospital Network in Mexico

2021 ◽  
Vol 3 (2) ◽  
pp. 444-453
Author(s):  
Arturo Cervantes Trejo ◽  
Sophie Domenge Treuille ◽  
Isaac Castañeda Alcántara
Keyword(s):  
Health Care ◽  
Information System ◽  
Health Care Services ◽  
Large Scale ◽  
Clinical Information System ◽  
Clinical Information ◽  
Public Hospitals ◽  
Care Services ◽  
Cost Reductions

AbstractThe Institute for Security and Social Services for State Workers (ISSSTE) is a large public provider of health care services that serve around 13.2 million Mexican government workers and their families. To attain process efficiencies, cost reductions, and improvement of the quality of diagnostic and imaging services, ISSSTE was set out in 2019 to create a digital filmless medical image and report management system. A large-scale clinical information system (CIS), including radiology information system (RIS), picture archiving and communication system (PACS), and clinical data warehouse (CDW) components, was implemented at ISSSTE’s network of forty secondary- and tertiary-level public hospitals, applying global HL-7 and Digital Imaging and Communications in Medicine (DICOM) standards. In just 5 months, 40 hospitals had their endoscopy, radiology, and pathology services functionally interconnected within a national CIS and RIS/PACS on secure private local area networks (LANs) and a secure national wide area network (WAN). More than 2 million yearly studies and reports are now in digital form in a CDW, securely stored and always available. Benefits include increased productivity, reduced turnaround times, reduced need for duplicate exams, and reduced costs. Functional IT solutions allow ISSSTE hospitals to leave behind the use of radiographic film and printed medical reports with important cost reductions, as well as social and environmental impacts, leading to direct improvement in the quality of health care services rendered.

scholarly journals Correcting Citizens’ Misperceptions about non-Western Immigrants: Corrective Information, Interpretations, and Policy Opinions

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Frederik Juhl Jørgensen ◽  
Mathias Osmundsen
Keyword(s):  
Immigration Policy ◽  
Large Scale ◽  
Total Population ◽  
Survey Experiment ◽  
Correct Information ◽  
The Usa ◽  
Large Scale Survey ◽  
Nationally Representative ◽  
Information Change ◽  
Corrective Information

Abstract Can corrective information change citizens’ misperceptions about immigrants and subsequently lead to favorable immigration opinions? While prior studies from the USA document how corrections about the size of minority populations fail to change citizens’ immigration-related opinions, they do not examine how other facts that speak to immigrants’ cultural or economic dependency rates can influence immigration policy opinions. To extend earlier work, we conducted a large-scale survey experiment fielded to a nationally representative sample of Danes. We randomly expose participants to information about non-Western immigrants’ (1) welfare dependency rate, (2) crime rate, and (3) proportion of the total population. We find that participants update their factual beliefs in light of correct information, but reinterpret the information in a highly selective fashion, ultimately failing to change their policy preferences.

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