tbuckley/cabot-search huggingface dataset:
Validation of Electronic Health Record Phenotyping of Bipolar Disorder Cases and Controls
Authors: Victor M. Castro, Jessica Minnier, Shawn N. Murphy, Isaac Kohane, Susanne E. Churchill, Vivian Gainer, Tianxi Cai, Alison G. Hoffnagle, Yael Dai, Stefanie Block, Sydney R. Weill, Mireya Nadal-Vicens, Alisha R. Pollastri, J. Niels Rosenquist, Sergey Goryachev, Dost Ongur, Pamela Sklar, Roy H. Perlis, Jordan W. Smoller, Jordan W. Smoller, Roy H. Perlis, Phil Hyoun Lee, Victor M. Castro, Alison G. Hoffnagle, Pamela Sklar, Eli A. Stahl, Shaun M. Purcell, Douglas M. Ruderfer, Alexander W. Charney, Panos Roussos, Carlos Pato, Michele Pato, Helen Medeiros, Janet Sobel, Nick Craddock, Ian Jones, Liz Forty, Arianna DiFlorio, Elaine Green, Lisa Jones, Katherine Dunjewski, Mikael Landén, Christina Hultman, Anders Juréus, Sarah Bergen, Oscar Svantesson, Steven McCarroll, Jennifer Moran, Jordan W. Smoller, Kimberly Chambert, Richard A. Belliveau
Journal: American Journal of Psychiatry (2014)

Objective: The study was designed to validate use of electronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects. Method: EHR data were obtained from a health care system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype diagnoses was calculated against diagnoses from direct semistructured interviews of 190 patients by trained clinicians blind to EHR diagnosis. Results: The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR-classified control subject received a diagnosis of bipolar disorder on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based classifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses. Conclusions: Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.
Evolutionary Analysis of Amino Acid Repeats across the Genomes of 12 Drosophila Species
Authors: Melanie A. Huntley, Andrew G. Clark
Journal: Molecular Biology and Evolution (2007)

Repeated motifs of amino acids within proteins are an abundant feature of eukaryotic sequences and may catalyze the rapid production of genetic and even phenotypic variation among organisms. The completion of the genome sequencing projects of 12 distinct Drosophila species provides a unique dataset to study these intriguing sequence features on a phylogeny with a variety of timescales. We show that there is a higher percentage of proteins containing repeats within the Drosophila genus than most other eukaryotes, including non-Drosphila insects, which makes this collection of species particularly useful for the study of protein repeats. We also find that proteins containing repeats are overrepresented in functional categories involving developmental processes, signaling, and gene regulation. Using the set of 1-to-1 ortholog alignments for the 12 Drosophila species, we test the ability of repeats to act as reliable phylogenetic signals and find that they resolve the generally accepted phylogeny despite the noise caused by their accelerated rate of evolution. We also determine that in general the position of repeats within a protein sequence is non-random, with repeats more often being absent from the middle regions of sequences. Finally we find evidence to suggest that the presence of repeats is associated with an increase in evolutionary rate upon the entire sequence in which they are embedded. With additional evidence to suggest a corresponding elevation in positive selection we propose that some repeats may be inducing compensatory substitutions in their surrounding sequence.
Widespread intradermal accumulation of mononuclear leukocytes in lepromatous leprosy patients treated systemically with recombinant interferon gamma.
Authors: C Nathan, K Squires, W Griffo, W Levis, M Varghese, C K Job, A R Nusrat, S Sherwin, S Rappoport, E Sanchez
Journal: The Journal of Experimental Medicine (1990)

Intradermal administration of recombinant interferon gamma (rIFN-gamma) to lepromatous leprosy patients has converted the local histology toward a tuberculoid pattern. However, such changes have been confined to the site of injection. In contrast, in the present study, marked, intradermal accumulation of CD3+, CD4+, CD8+, and CD1a+ T cells and Leu-M5+ mononuclear phagocytes was induced at a distance from the sites of administration, in a dose-dependent manner, by 10 daily intramuscular injections of 10-30 micrograms rIFN-gamma/m2. Mononuclear cell infiltration began within 3 d of onset of rIFN-gamma therapy and persisted at least 8 wk. Intramuscular administration of rIFN-gamma to lepromatous patients receiving concurrent chemotherapy can safely induce widespread histologic features of an upgrading reaction.
Words in "In A Word"
Authors: Byron A. Myhre
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Identification of Ny-Eso-1 Epitopes Presented by Human Histocompatibility Antigen (Hla)-Drb4*0101–0103 and Recognized by Cd4+T Lymphocytes of Patients with Ny-Eso-1–Expressing Melanoma
Authors: Elke Jäger, Dirk Jäger, Julia Karbach, Yao-Tseng Chen, Gerd Ritter, Yasuhiro Nagata, Sacha Gnjatic, Elisabeth Stockert, Michael Arand, Lloyd J. Old, Alexander Knuth
Journal: The Journal of Experimental Medicine (2000)

NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1–expressing cancers. Since CD4+ T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and antibody responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1–specific CD4+ T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4+ T lymphocytes in autologous settings. We identified three NY-ESO-1–derived peptides presented by DRB4*0101–0103 and recognized by CD4+ T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II–restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I–restricted peptides may be improved by adding HLA class II–presented epitopes.
Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells
Authors: Mu Hao, Li Zhang, Gang An, Weiwei Sui, Zhen Yu, Dehui Zou, Yan Xu, Hong Chang, Lugui Qiu
Journal: Journal of Hematology & Oncology (2011)

Abstract The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM) cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6) produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.
Physicians' Attitudes About Multiplex Tumor Genomic Testing
Authors: Stacy W. Gray, Katherine Hicks-Courant, Angel Cronin, Barrett J. Rollins, Jane C. Weeks
Journal: Journal of Clinical Oncology (2014)

Although predictive multiplex somatic genomic tests hold the potential to transform care by identifying targetable alterations in multiple cancer genes, little is known about how physicians will use such tests in practice.Before the initiation of enterprise-wide multiplex testing at a major cancer center, we surveyed all clinically active adult cancer physicians to assess their current use of somatic testing, their attitudes about multiplex testing, and their genomic confidence.A total of 160 physicians participated (response rate, 61%): 57% were medical oncologists; 29%, surgeons; 14% radiation oncologists; 37%, women; and 83%, research principal investigators. Twenty-two percent of physicians reported low confidence in their genomic knowledge. Eighteen percent of physicians anticipated testing patients infrequently (≤ 10%), whereas 25% anticipate testing most patients (≥ 90%). Higher genomic confidence was associated with wanting to test a majority of patients (adjusted odds ratio [OR], 6.09; 95% CI, 2.1 to 17.5) and anticipating using actionable (adjusted OR, 2.46; 95% CI, 1.2 to 5.2) or potentially actionable (adjusted OR, 2.89; 95% CI, 1.1 to 7.9) test results to inform treatment recommendations. Forty-two percent of physicians endorsed disclosure of uncertain genomic findings to patients.Physicians at a tertiary-care National Cancer Institute-designated comprehensive cancer center varied considerably in how they planned to incorporate predictive multiplex somatic genomic tests into practice and in their attitudes about the disclosure of genomic information of uncertain significance. Given that many physicians reported low genomic confidence, evidence-based guidelines and enhanced physician genomic education efforts may be needed to ensure that genomically guided cancer care is adequately delivered.
Status of Surgical Margins and Prognosis in Adult Soft Tissue Sarcomas of the Extremities: A Series of Patients Treated at a Single Institution
Authors: A. Gronchi, P.G. Casali, L. Mariani, R. Miceli, M. Fiore, S. Lo Vullo, R. Bertulli, P. Collini, L. Lozza, P. Olmi, J. Rosai
Journal: Journal of Clinical Oncology (2004)

To explore the prognostic effect of microscopic marginal status after surgery for extremity soft tissue sarcomas.We analyzed 911 consecutive patients surgically treated throughout a 20-year span at a single referral center. Six hundred forty-two were first seen with a primary tumor, and 269, with a locally recurrent tumor. All patients underwent macroscopically complete resection. Microscopic marginal status was negative (tumor size > 1 mm) in 748 patients and positive (</= 1 mm) in 163 patients. Median follow-up was 107 months.Patients with primary disease had a lower disease-specific mortality in comparison to those first examined for recurrence (25% v 37%, respectively, at 10 years). Size, malignancy grade, depth, histotype, and local recurrence had a statistically significant prognostic effect at multivariable analysis, while microscopically positive surgical margins had not, though a trend in favor of negative margins was observed. However, an extra risk was observed for patients with positive margins after 3 to 5 years (hazard ratio, 1.8 after 5 years v 0.8 before 5 years). In patients treated for a local recurrence, the prognostic impact of positive margins was higher (hazard ratio, 1.6).Positive surgical margins had a weak adverse prognostic effect, which was more pronounced for those patients escaping an early relapse. This would seem to justify a policy of surgical adequacy in adult soft tissue sarcomas, though clinical decision making in borderline presentations for conservative surgery might be reasonably flexible and shared with the patient. Once a local relapse has occurred, the impact of local treatments seems more critical.
INFECTION, INFLAMMATION, AND GASTROINTESTINAL CANCER
Authors: C R Boland
Journal: Gut (2005)

The struggle to understand the origins of human cancers has captured the imagination of many investigators. The epidemiology of human cancers and the availability of many laboratory models of cancer could give the casual observer the impression that all cancers are a result of exposures to chemical carcinogens in the environment. This is only part of the story, and in most instances environmental exposures are very different in scale from what is required in laboratory animals to induce tumours. Actually, most laboratory models have been carefully developed to match the carcinogen with the host. For example, several alkylating agents can induce intestinal cancers in rodents.1 However, the distribution of the neoplasms throughout the gut varies from one mouse strain to another, and in some instances the carcinogens induce tumours only outside the gut. Lower doses—perhaps those more relevant for human cancers—may be tolerated, and not induce cancer at all. The mechanisms for tumour development in the human gastrointestinal tract appear to be a much more complicated issue.

This review of recent advances in basic science will focus on newly discovered mechanisms involved in the development of colorectal cancer (CRC). This is potentially a very broad topic, and therefore we have selected two novel mechanisms for emphasis. Firstly, a virus carried by most healthy individuals has been implicated as a possible cause for chromosomal instability (CIN), the process that leads to aneuploidy. Chromosomal aberrations and this form of genomic instability play a major role in the development and progression of multistep carcinogenesis, such as occurs in CRC.2 Secondly, it is abundantly clear that inflammation is carcinogenic, and furthermore, endogenous processes that can modify the ability of the host to cope with inflammation appear to modify the risk of cancer to the host. There is growing evidence that this may …
A Population-Based Assessment of Specialty Physician Involvement in Cancer Clinical Trials
Authors: C. N. Klabunde, N. L. Keating, A. L. Potosky, A. Ambs, Y. He, M. C. Hornbrook, P. A. Ganz
Journal: JNCI Journal of the National Cancer Institute (2011)

Clinical trials are critical for evaluating new cancer therapies, but few adult patients participate in them. Physicians have an important role in facilitating patient participation in clinical trials. We examined the characteristics of specialty physicians who participate in clinical trials by enrolling or referring patients, the types of trials in which they participate, and factors associated with physicians who report greater involvement in clinical trials. We analyzed data from the Cancer Care Outcomes Research and Surveillance Consortium. The study included 1533 specialty physicians who cared for colorectal and lung cancer patients (496 medical oncologists, 228 radiation oncologists, and 809 surgeons) and completed a survey conducted during 2005–2006 (response rate = 61.0%). Descriptive statistics were used to characterize physicians' personal and practice characteristics, and regression models were used to examine associations between these characteristics and physician participation in clinical trials. All statistical tests were two-sided. A total of 87.8% of medical oncologists, 66.1% of radiation oncologists, and 35.0% of surgeons reported referring or enrolling one or more patients in clinical trials during the previous 12 months. The mean number of patients referred or enrolled by these physicians was 17.2 (95% confidence interval [CI] = 15.5 to 18.9) for medical oncologists, 9.5 (95% CI = 7.7 to 11.3) for radiation oncologists, and 12.2 (95% CI = 9.8 to 14.6) for surgeons ( P < .001). Specialty type, involvement in teaching, and affiliation with a Community Clinical Oncology Program (CCOP) and/or a National Cancer Institute–designated cancer center were associated with physician trial participation and enrolling more patients (all P s < .05). Two-thirds of physicians with a CCOP or National Cancer Institute–designated cancer center affiliation reported participating in trials. Features of specialty physicians' practice environments are associated with their trial participation, but many physicians at CCOPs and cancer centers do not participate.
PTU-183 Dysphagia With Normal Endoscopic Appearances – Could We Do Better?
Authors: V Sehgal, M Abayalingam, H Alexander, A Mitra, I Ahmed, B Krishnan, NV Someren, K Besherdas
Journal: Gut (2014)

<h3>Introduction</h3> Dysphagia is an ‘alarm symptom’ that merits prompt investigation by gastroscopy to exclude cancer. Cases in whom cancer is diagnosed at endoscopy in the UK are ‘fast tracked’ for multidisciplinary team discussion to plan future management. If endoscopy shows no cancer or intrinsic lesion (peptic stricture, oesophageal ring or web), the cause is usually secondary to oesophageal dysmotility. It is recommended that this group of patients should receive a trial of anti-reflux therapy to exclude reflux-related dysmotility. If no improvement in symptoms is seen patients should be referred for oesophageal physiology studies. <h3>Methods</h3> To assess the number of patients who underwent a gastroscopy for dysphagia that had no intrinsic cause found and to evaluate if these patients were managed in line with recommendations. A retrospective analysis of all patients who underwent a gastroscopy for an indication that included dysphagia at Chase Farm Hospital over a 3-month period (April–June 2012) was performed. Data was obtained from endoscopy reports via the Unisoft GI Reporting Tool (Middlesex) and clinic outcome letters. Intrinsic oesophageal causes for dysphagia were said to be cancer, benign oesophageal stricture and eosinophillic oesophagitis (EE). <h3>Results</h3> 106 patients (37 male, 69 female), median age 66 years, were investigated. 28 (26.4%) had an intrinsic cause for dysphagia - benign oesophageal stricture 18 (17%), cancer 8 (7.5%) and EE 2 (1.9%). 78 (73.5%) patients had no intrinsic cause – reflux oesophagitis 26 (32.5%), Barrett’s oesophagus 2 (2.5%), hiatus hernia 28 (35%), gastritis/duodenitis 39 (48.8%), normal 22 (27.5%) and other 13 (16.3%). 55 (70%) of these patients had no follow-up organised after endoscopy. The remaining had clinic review 20 (25.6%), repeat endoscopy 4 (5%) or referral for oesophageal physiology studies 1 (1.3%). 30 (38.5%) patients with no intrinsic cause were prescribed anti-reflux medication after endoscopy. 19 (63.3%) of these patients had no further follow-up. The remaining had clinic review 9 (30%) or a repeat endoscopy 2 (6.7%); none were sent for oesophageal physiology studies. <h3>Conclusion</h3> In this study, 75% of patients with dysphagia had no intrinsic cause identified. The majority of patients are discharged from the service without an accurate diagnosis or management recommendation. Our study highlights important shortcomings in the management of patients with a benign cause of dysphagia. We recommend that patients presenting with dysphagia who at endoscopy have no intrinsic cause, be prescribed acid suppression therapy followed by clinical review, and if symptoms persist be considered for oesophageal physiological studies. <h3>Disclosure of Interest</h3> None Declared.
Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese infants aged 16-24 months: the Osaka Maternal and Child Health Study
Authors: Y Miyake, S Sasaki, K Tanaka, S Ohfuji, Y Hirota
Journal: Thorax (2009)

<h3>Background:</h3> One factor capable of modulating antenatal immune responses is diet. This prospective study examined the association between maternal intake of specific types of fatty acids, cholesterol, fish and meat during pregnancy and the risk of wheeze and eczema in the offspring. <h3>Methods:</h3> Subjects were 763 mother-child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Data on wheeze and eczema based on criteria of the International Study of Asthma and Allergies in Childhood were obtained from a questionnaire completed by mothers 16–24 months postpartum. <h3>Results:</h3> Higher maternal intake of α-linolenic acid and docosahexaenoic acid during pregnancy was independently associated with a reduced risk of wheeze, but not eczema, in the offspring (adjusted odds ratios (ORs) between extreme quartiles 0.52 (95% CI 0.28 to 0.97) and 0.37 (95% CI 0.15 to 0.91), respectively). Higher maternal intake of n-6 polyunsaturated fatty acids and linoleic acid during pregnancy was independently related to an increased risk of infantile eczema but not wheeze (adjusted ORs 2.25 (95% CI 1.13 to 4.54) and 2.11 (95% CI 1.06 to 4.26), respectively). No significant exposure-response relationships were observed between maternal consumption of total fat, saturated fatty acids, monounsaturated fatty acids, eicosapentaenoic acid, arachidonic acid, cholesterol, meat and fish and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption during pregnancy and infantile wheeze or eczema. <h3>Conclusions:</h3> Maternal intake of α-linolenic acid and docosahexaenoic acid during pregnancy may be preventive against infantile wheeze. Maternal intake of n-6 polyunsaturated fatty acids, especially linoleic acid, during pregnancy may increase the risk of childhood eczema.