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John B. Welsh

Bio: John B. Welsh is an academic researcher from Medtronic plc. The author has contributed to research in topics: Hypoglycemia & Insulin pump. The author has an hindex of 30, co-authored 73 publications receiving 6824 citations. Previous affiliations of John B. Welsh include University of California, San Francisco & Genomics Institute of the Novartis Research Foundation.


Papers
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Journal Article
TL;DR: Primary prostate cancer was characterized by monitoring expression levels of more than 8900 genes in normal and malignant tissues, and a striking group of about 400 genes were identified that were overexpressed in tumor tissues.
Abstract: Detection, treatment, and prediction of outcome for men with prostate cancer increasingly depend on a molecular understanding of tumor development and behavior. We characterized primary prostate cancer by monitoring expression levels of more than 8900 genes in normal and malignant tissues. Patterns of gene expression across tissues revealed a precise distinction between normal and tumor samples, and revealed a striking group of about 400 genes that were overexpressed in tumor tissues. We ranked these genes according to their differential expression in normal and cancer tissues by selecting for highly and specifically overexpressed genes in the majority of cancers with correspondingly low or absent expression in normal tissues. Several such genes were identified that act within a variety of biochemical pathways and encode secreted molecules with diagnostic potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other genes, such as fatty acid synthase, encode enzymes known as drug targets in other contexts, which suggests new therapeutic approaches.

919 citations

Journal ArticleDOI
TL;DR: In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy.
Abstract: At 1 year, the baseline mean glycated hemoglobin level (8.3% in the two study groups) had decreased to 7.5% in the pump-therapy group, as compared with 8.1% in the injection-therapy group (P<0.001). The proportion of patients who reached the glycated hemoglobin target (<7%) was greater in the pump-therapy group than in the injection-therapy group. The rate of severe hypoglycemia in the pump-therapy group (13.31 cases per 100 person-years) did not differ significantly from that in the injection-therapy group (13.48 per 100 person-years, P = 0.58). There was no significant weight gain in either group. Conclusions In both adults and children with inadequately controlled type 1 diabetes, sensoraugmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (ClinicalTrials.gov number, NCT00417989.)

806 citations

Journal Article
TL;DR: This study demonstrates the feasibility of predicting the tissue origin of a carcinoma in the context of multiple cancer classes by accurately and confidently predicting the anatomical site of tumor origin for 90% of 175 carcinomas, including 9 of 12 metastatic lesions.
Abstract: Classification of human tumors according to their primary anatomical site of origin is fundamental for the optimal treatment of patients with cancer. Here we describe the use of large-scale RNA profiling and supervised machine learning algorithms to construct a first-generation molecular classification scheme for carcinomas of the prostate, breast, lung, ovary, colorectum, kidney, liver, pancreas, bladder/ureter, and gastroesophagus, which collectively account for ∼70% of all cancer-related deaths in the United States. The classification scheme was based on identifying gene subsets whose expression typifies each cancer class, and we quantified the extent to which these genes are characteristic of a specific tumor type by accurately and confidently predicting the anatomical site of tumor origin for 90% of 175 carcinomas, including 9 of 12 metastatic lesions. The predictor gene subsets include those whose expression is typical of specific types of normal epithelial differentiation, as well as other genes whose expression is elevated in cancer. This study demonstrates the feasibility of predicting the tissue origin of a carcinoma in the context of multiple cancer classes.

726 citations

Journal ArticleDOI
TL;DR: This study uses oligonucleotide microarrays with probe sets complementary to >6,000 human genes to identify genes whose expression correlated with epithelial ovarian cancer and demonstrates the rapidity with which large amounts of expression data can be generated.
Abstract: Epithelial ovarian cancer is the leading cause of death from gynecologic cancer, in part because of the lack of effective early detection methods. Although alterations of several genes, such as c-erb-B2, c-myc, and p53, have been identified in a significant fraction of ovarian cancers, none of these mutations are diagnostic of malignancy or predictive of tumor behavior over time. Here, we used oligonucleotide microarrays with probe sets complementary to >6,000 human genes to identify genes whose expression correlated with epithelial ovarian cancer. We extended current microarray technology by simultaneously hybridizing ovarian RNA samples in a highly parallel manner to a single glass wafer containing 49 individual oligonucleotide arrays separated by gaskets within a custom-built chamber (termed “array-of-arrays”). Hierarchical clustering of the expression data revealed distinct groups of samples. Normal tissues were readily distinguished from tumor tissues, and tumors could be further subdivided into major groupings that correlated both to histological and clinical observations, as well as cell type-specific gene expression. A metric was devised to identify genes whose expression could be considered ideal for molecular determination of epithelial ovarian malignancies. The list of genes generated by this method was highly enriched for known markers of several epithelial malignancies, including ovarian cancer. This study demonstrates the rapidity with which large amounts of expression data can be generated. The results highlight important molecular features of human ovarian cancer and identify new genes as candidate molecular markers.

688 citations

Journal ArticleDOI
TL;DR: This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values.
Abstract: BackgroundThe threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. MethodsWe randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. ResultsA total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insuli...

541 citations


Cited by
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Journal ArticleDOI
Zefang Tang1, Chenwei Li1, Boxi Kang1, Ge Gao1, Cheng Li1, Zemin Zhang 
TL;DR: GEPIA (Gene Expression Profiling Interactive Analysis) fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources.
Abstract: Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.

5,980 citations

Journal ArticleDOI
20 Apr 1990-Cell
TL;DR: Cet article synthese montre comment des recepteurs membranaires a activite tyrosine kinase peuvent etre impliques dans la transduction and notamment jouent le role de signal de the transduction.

5,536 citations

Journal ArticleDOI
TL;DR: These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care.
Abstract: D iabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. Specifically titled sections of the standards address children with diabetes, pregnant women, and people with prediabetes. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A large number of these interventions have been shown to be cost-effective (4). A grading system (Table 1), developed by the American Diabetes Association (ADA) andmodeled after existingmethods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence. For the current revision, committee members systematically searched Medline for human studies related to each subsection and published since 1 January 2010. Recommendations (bulleted at the beginning of each subsection and also listed in the “Executive Summary: Standards of Medical Care in Diabetesd2012”) were revised based on new evidence or, in some cases, to clarify the prior recommendation or match the strength of the wording to the strength of the evidence. A table linking the changes in recommendations to new evidence can be reviewed at http:// professional.diabetes.org/CPR_Search. aspx. Subsequently, as is the case for all Position Statements, the standards of care were reviewed and approved by the ExecutiveCommittee of ADA’s Board ofDirectors, which includes health care professionals, scientists, and lay people. Feedback from the larger clinical community was valuable for the 2012 revision of the standards. Readers who wish to comment on the “Standards of Medical Care in Diabetesd2012” are invited to do so at http://professional.diabetes.org/ CPR_Search.aspx. Members of the Professional Practice Committee disclose all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the standards revisionmeeting. Members of the committee, their employer, and their disclosed conflicts of interest are listed in the “Professional PracticeCommitteeMembers” table (see pg. S109). The AmericanDiabetes Association funds development of the standards and all its position statements out of its general revenues and does not utilize industry support for these purposes.

4,266 citations

Journal ArticleDOI
28 Oct 2005-Science
TL;DR: In this article, the authors used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression and identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1.
Abstract: Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.

3,543 citations

Journal ArticleDOI
TL;DR: In this paper, high-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale, and the authors have designed custom arrays that interrogate the expression of the vast majority of proteinencoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues.
Abstract: The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.

3,513 citations