tbuckley/cabot-search huggingface dataset:
Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients
Authors: Ayalew Tefferi, Emnet A. Wassie, Paola Guglielmelli, Naseema Gangat, Alem A. Belachew, Terra L. Lasho, Christy Finke, Rhett P. Ketterling, Curtis A. Hanson, Animesh Pardanani, Alexandra P. Wolanskyj, Margherita Maffioli, Rosario Casalone, Annalisa Pacilli, Alessandro M. Vannucchi, Francesco Passamonti
Journal: American Journal of Hematology (2014)

CALR (calreticulin) trails JAK2 as the second most mutated gene in essential thrombocythemia (ET). Mutant CALR in ET is a result of frameshift mutations, caused by exon 9 deletions or insertions; type-1, 52-bp deletion (p.L367fs*46), and type-2, 5-bp TTGTC insertion (p.K385fs*47) variants constitute more than 80% of these mutations. The current study includes a total of 1027 patients divided into test (n = 402) and validation (n = 625) cohorts. Among the 402 ET patients in the test cohort, 227 (57%) harbored JAK2, 11 (3%) Myeloproliferative leukemia virus oncogene (MPL), and 114 (28%) CALR mutations; 12% were wild-type for all three mutations (i.e., triple-negative). Among the 114 patients with CALR mutations, 51 (45%) displayed type-1 and 44 (39%) type-2 variants; compared to mutant JAK2, both variants were associated with higher platelet and lower hemoglobin and leukocyte counts. However, male sex was associated with only type-1 (P = 0.005) and younger age with type-2 (P = 0.001) variants. Notably, platelet count was significantly higher in type-2 vs. type-1 CALR-mutated patients (P = 0.03) and the particular observation was validated in the validation cohort that included 111 CALR-mutated ET patients (P = 0.002). These findings, coupled with the recent demonstration of preferential expression of mutant and wild-type CALR in megakaryocytes, suggest differential effects of CALR variants on thrombopoiesis.
Atrial Fibrillation and Risk of Postoperative Complications
Authors: Johann Auer, Thomas Weber, Bernd Eber
Journal: JAMA (2004)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Increased Measles Risk Possible in African Countries Affected by Ebola
Authors: M.J. Friedrich
Journal: JAMA (2015)

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
Abstract P388: Which Obesity-related Indicator is Better for Predicting Incident Hypertension? Results from the population-based cohort study of Japan
Authors: Michikazu Nakai, Makoto Watanabe, Kunihiro Nishimura, Misa Takegami, Yoshihiro Kokubo, Aya Higashiyama, Tomonori Okamura, Yoshihiro Miyamoto
Journal: Circulation (2014)

Objective: Obesity is an established risk factor for hypertension (HT), but it is still controversial which obesity-related indicator is superior in predictability. This study compared the predictability among three indicators, body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR), in the population-based prospective cohort study of Japan, the Suita study. Methods: Participants who had no HT at baseline (1,591 men and 1,973 women) aged 30-84 years were included in this study. The Cox proportional hazard model was used to estimate hazard ratios (HRs) of each indicator for incident HT with the adjustment for age, cigarette smoking and alcohol drinking. Harrell’s C statistics were also estimated for comparison of indicators’ accuracy. Results: During median follow-up of 7.2 years, 1,325 participants (640 men and 685 women) developed HT. HR (95% CI) of BMI, WC and WHtR for incident HT corresponding to a 1 SD increase was 1.25 (1.15-1.35), 1.21 (1.12-1.31) and 1.23 (1.14-1.34) in men while 1.32 (1.22-1.42), 1.27 (1.18-1.37) and 1.32 (1.21-1.44) in women, respectively. Also, C-statistic (95% CI) of BMI, WC and WHtR was 0.64 (0.62-0.66), 0.63 (0.61-0.65) and 0.63 (0.61-0.66) in men while 0.69 (0.67-0.71), 0.69 (0.67-0.71) and 0.69 (0.67-0.71) in women, respectively. Using 95% CI of each C-statistics, there were no statistical differences among three indicators in both men and women. Conclusion: In this study, we showed that all three indicators (BMI, WC and WHtR) were estimated similarly to predict the risk of developing HT in both Japanese men and women.
Markers of β-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes
Authors: Angus G. Jones, Timothy J. McDonald, Beverley M. Shields, Anita V. Hill, Christopher J. Hyde, Bridget A. Knight, Andrew T. Hattersley
Journal: Diabetes Care (2015)

To assess whether clinical characteristics and simple biomarkers of β-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes.
Abstract 856: Combination of crizotinib and radiation in the treatment of ALK-positive and cetuximab-resistant lung cancer
Authors: Chunrong Li, Shyhmin Huang, Noah Walters, Eric A. Armstrong, Paul M. Harari
Journal: Cancer Research (2014)

Abstract Approximately 4% of patients with non-small cell lung carcinoma (NSCLC) carry the EML4-ALK chromosomal rearrangement. Crizotinib, a c-MET and ALK inhibitor, has shown significant therapeutic benefit as a single agent with FDA approval for the treatment of patients with ALK-positive NSCLC. Since radiation commonly plays a key role in lung cancer treatment, we sought to evaluate the potential of crizotinib as a radiation sensitizer and the role of ALK in cellular radiation sensitivity. We examined the effect of crizotinib in combination with radiation on ALK signaling, cell proliferation, cell cycle distribution and radiosensitivity in ALK-positive NSCLC cell lines H3122 and H2228 in vitro. We also examined the in-vivo effects of crizotinib in combination with radiation in H3122 and H2228 xenograft models. Crizotinib blocked phosphorylation of ALK and its downstream effectors and inhibited cell proliferation in a dose-dependent manner. The combination of crizotinib and radiation resulted in increased inhibition of cell growth. Although cells were sensitized to radiation by crizotinib, molecular knockdown of ALK by siRNA had only modest impact on cell radiosensitivity. Cell cycle analysis by flow cytometry showed that ALK-siRNA induced G1 arrest. Interestingly, low dose crizotinib induced G1 arrest, while doses above 2µM induced G2 arrest. Combination treatment induced arrest in G1 and G2 phases and decreased the cell population in S-phase. Moreover, in xenograft tumor models, we observed combined treatment to produce additive tumor growth inhibition over that observed with either drug or radiation alone. We further examined the capacity of crizotinib overcome cetuximab resistance in our established in vitro resistance models. Compared with parental cells, cetuximab-resistant cells showed cross-resistance to radiation. Crizotinib inhibited the growth of cetuximab-resistant cells and resensitized cells to radiation. Compared with single-agent treatment, the combination of crizotinib and erlotinib resulted in increased growth inhibition and further re-sensitization to radiation. These data suggest that crizotinib in combination with radiation can enhance the inhibitory effect on ALK-positive tumor cell growth in vitro and in-vivo and also suggest the potential value of using crizotinib in combination with other EGFR-targeting therapeutics. Ultimately however, the potential value of crizotinib as a radiation sensitizer requires systematic clinical investigation. Citation Format: Chunrong Li, Shyhmin Huang, Noah Walters, Eric A. Armstrong, Paul M. Harari. Combination of crizotinib and radiation in the treatment of ALK-positive and cetuximab-resistant lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 856. doi:10.1158/1538-7445.AM2014-856
Abstract B51: Image-based classification of cancer drug combination response surfaces
Authors: Manway Liu, Thomas Horn, Matthew Greene, Joseph Lehar
Journal: Clinical Cancer Research (2015)

Abstract Recent advances in targeted chemotherapy have dramatically improved the survival odds of patients suffering from specific molecular subtypes of cancer. Nonetheless, while a fortunate few enjoy a durable and lasting response to treatment, the majority will eventually relapse after some grace period in remission due to the emergence of drug-resistant cancer cells. Acquired resistance is a complex phenomenon that likely involves intra-tumoral heterogeneity, tumor-stromal interactions, and natural selection due to the pressure of chemotherapy. One promising approach to overcome resistance involves utilization of two or more drug compounds in combination, where each compound targets a different member of a signaling pathway important in the disease. By targeting more proteins, the hope is that the probability of any particular cancer cell failing to respond will decrease as the barrier to survival increases. While drug combinations are an exciting and promising direction for chemotherapeutic research, such studies present additional challenges and opportunities. Interpretation of synergistic and efficacious drug combinations is not always straightforward and pairs of drugs may interact in surprising ways that deviate from expectation based on the molecular pathway relationships between their targets. Moreover, the question of which drugs to prioritize for testing in combination is an important one to which there is currently no standard solution. The brute force approach is not cost-effective due to the factorial growth in the number of possible higher-order drug combinations. In this work, we present and describe an algorithmic approach to (1) predict synergistic and efficacious drug combinations based on pathway relationships between their targets and (2) classify drug combination response surfaces into canonical archetypes of greatest pharmaceutical interest. Our approach borrows from classical work in image analysis and recognition. We trained and tested our algorithm on two publicly available datasets of drug combinations. We further trained on a private dataset of cancer drug combination data and made predictions that were later experimentally validated in vitro. To our knowledge, our approach is the first proof-of-concept algorithm that utilizes the actual shapes of response surfaces to categorize and prioritize drug combinations for further testing. Citation Format: Manway Liu, Thomas Horn, Matthew Greene, Joseph Lehar. Image-based classification of cancer drug combination response surfaces. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B51.
Tissue Uptake of Circulating Thrombopoietin Is Increased in Immune-Mediated Compared With Irradiated Thrombocytopenic Mice
Authors: Mei Chang, John X. Qian, Sun min Lee, John Joubran, George Fernandez, Jacqueline Nichols, Annika Knoppel, Jeffrey S. Buzby
Journal: Blood (1999)
GASTROINTESTINAL ALLERGY IN CHILDREN
Authors: Horton Casparis
Journal: Annals of Internal Medicine (1933)

Article1 November 1933GASTROINTESTINAL ALLERGY IN CHILDRENHORTON CASPARIS, M.D., F.A.C.P.HORTON CASPARIS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-5-625 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this discussion is to consider some of the gastrointestinal allergic manifestations in children and to suggest their relationship and similarity to certain symptoms which occur in adults and which are not generally considered as having an allergic basis. In this brief discussion no attempt will be made to consider extra-gastrointestinal allergic signs and symptoms, such as angioneurotic edema, urticaria, eczema, migraine, allergic rhinitis, asthma, and so forth, any one of which may result from the ingestion of food to which the individual is over sensitive; but, only evidences of local allergic irritation to the gastrointestinal tract will...Bibliography1. LEWISHAYDEN JHHC: Effect of heat on antigenic properties of milk, Am. Jr. Dis. Child., 1932, xliv, 1211-1220. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Nashville, Tennessee*Read at the Montreal Meeting of the American College of Physicians, February 7, 1933.From The Department of Pediatrics, Vanderbilt University Medical School, Nashville, Tennessee. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGastro-Intestinal AllergyRecurrent vomiting in children 1 November 1933Volume 7, Issue 5Page: 625-629KeywordsAllergic rhinitisChildrenEdemaFoodGastrointestinal tractIngestionMigrainePediatricsSigns and symptomsUrticaria ePublished: 1 December 2008 Issue Published: 1 November 1933 PDF downloadLoading ...
Progression of Barrett's Metaplasia to Adenocarcinoma Is Associated with the Suppression of the Transcriptional Programs of Epidermal Differentiation
Authors: Erik T. Kimchi, Mitchell C. Posner, James O. Park, Thomas E. Darga, Masha Kocherginsky, Theodore Karrison, John Hart, Kerrington D. Smith, James J. Mezhir, Ralph R. Weichselbaum, Nikolai N. Khodarev
Journal: Cancer Research (2005)

Abstract We did expressional profiling on 24 paired samples of normal esophageal epithelium, Barrett's metaplasia, and esophageal adenocarcinomas. Matching tissue samples representing the three different histologic types were obtained from each patient undergoing esophagectomy for adenocarcinoma. Our analysis compared the molecular changes accompanying the transformation of normal squamous epithelium with Barrett's esophagus and adenocarcinoma in individual patients rather than in a random cohort. We tested the hypothesis that expressional profiling may reveal gene sets that can be used as molecular markers of progression from normal esophageal epithelium to Barrett's esophagus and adenocarcinoma. Expressional profiling was done using U133A GeneChip (Affymetrix), which represent approximately two thirds of the human genome. The final selection of 214 genes permitted the discrimination of differential gene expression of normal esophageal squamous epithelium, Barrett's esophagus, and adenocarcinoma using two-dimensional hierarchical clustering of selected genes. These data indicate that transformation of Barrett's esophagus to adenocarcinoma is associated with suppression of the genes involved in epidermal differentiation, including genes in 1q21 loci and corresponding to the epidermal differentiation complex. Correlation analysis of genes concordantly expressed in Barrett's esophagus and adenocarcinoma revealed 21 genes that represent potential genetic markers of disease progression and pharmacologic targets for treatment intervention. PCR analysis of genes selected based on DNA array experiments revealed that estimation of the ratios of GATA6 to SPRR3 allows discrimination among normal esophageal epithelium, Barrett's dysplasia, and adenocarcinoma.
Abstract 13387: Highly Sensitive Troponin I and Coronary Computed Tomography Angiography Assessment of Stenosis and High-risk Plaque Permit Rapid Classification of Acute Coronary Syndrome Risk in Chest Pain Patients: Results from the ROMICAT II Trial
Authors: Maros Ferencik, Ting Liu, Thomas Mayrhofer, Stefan B Puchner, Michael T Lu, Pal Maurovich-Horvat, J. Hector Pope, Quynh A Truong, James E Udelson, W. Frank Peacock, Charles S White, Pamela K Woodard, Jerome L Fleg, John T Nagurney, James L Januzzi, Udo Hoffmann
Journal: Circulation (2014)

Introduction: Highly sensitive troponin (hsTn) and coronary computed tomography angiography (CCTA) are promising diagnostic tools for triage of acute chest pain patients in the emergency department (ED). We determined whether a diagnostic strategy of initial hsTn I followed by early CCTA improves classification of ACS risk. Methods: We included ED patients with acute chest pain, negative electrocardiogram and conventional troponin who were enrolled in the ROMICAT II trial, randomized to CCTA and had hsTn I (hsVista, Siemens Diagnostics) measured at the time of presentation. The patients were categorized as having hsTn I &lt; the limit of detection (&lt;0.5 pg/mL), &gt; 99th percentile (&gt;49 pg/mL), or intermediate. Core lab readers assessed CCTA for the presence of ≥50% stenosis and high-risk plaque features (positive remodeling, low CT attenuation &lt;30 HU, napkin ring sign, spotty calcium). Results: Overall, 160 patients met inclusion criteria (mean age 53±8 years, 40% women, ACS during index hospitalization 10.6%, n=19). The ACS rate was 0% (n=0/9) for patients with HsTn I &lt; the limit of detection 8.6% (n=12/139) for patients with intermediate HsTn I and 53.8% (n=7/12) for patients with hsTnI &gt; 99th percentile. No coronary plaque was present in 68 (42.5%), non-obstructive CAD in 70 (43.8%), ≥50% stenosis in 22 (13.8%), and high-risk plaque in 61 (38.1%) patients. The figure shows ACS risk stratification based on hsTn I followed by CCTA. The addition of CCTA increased the number of patients categorized as low risk from 9 to 96 and high risk from 12 to 25 and re-classified 63% of patients (n=100). The net gain in reclassification proportion was 0.47 (95%CI 0.16-0.78; p=0.003) for patients with ACS and 0.59 (95%CI 0.46-0.72; p &lt;0.001) for patients without ACS, and net reclassification index was 1.06 (95%CI 0.73-1.40; p &lt;0.001). Conclusions: A strategy of initial hsTn I at the time of ED presentation followed by early CCTA improved classification of ACS risk in patients with acute chest pain.
Abstract 17512: Stress Myocardial Perfusion Computed Tomography versus Fractional Flow Reserve for Guiding Percutaneous Coronary Intervention in Intermediate Coronary Artery Disease
Authors: Shiro Nakamori, Kakuya Kitagawa, Kaoru Dohi, Masaki Ishida, Yasutaka Ichikawa, Motonori Nagata, Toshiki Sawai, Jun Masuda, Naoki Fujimoto, katsuya Onishi, Mashio Nakamura, Hajime Sakuma, Masaaki Ito
Journal: Circulation (2014)

Introduction: Percutaneous coronary intervention (PCI) based on invasively determined fractional flow reserve (FFR) has demonstrated improved event free survival. Stress myocardial computed tomography perfusion (CTP) permits the detection of haemodynamically relevant coronary artery disease (CAD) defined by FFR and has a potential to become a non-invasive test for replacing invasive FFR assessment. We sought to determine the clinical outcomes of stress CTP guided PCI compared with FFR-guided PCI. Methods: We studied 206 patients (149 men, age 69 ± 10 years) who had angiographic luminal narrowing of 50-90% in the proximal or mid part of a major coronary artery. CT-guided PCI was performed in 88 patients and FFR-guided PCI in 118 patients. In FFR-guided group, FFR of less than 0.8 was considered significant and revascularization was indicated, while CT-guided PCI was guided by the ischemic territories identified on CT images in combination with the results of angiogram. Patients were followed up for the occ...
Reproductive Genetic Testing and Human Genetic Variation in the Era of Genomic Medicine
Authors: Chelsea Lowther, Gregory Costain, Anne S. Bassett
Journal: The American Journal of Bioethics (2015)

New genetic technologies are increasingly being used in the clinical setting, necessitating an open and pragmatic discourse on their ethical use. The greatest urgency applies to preimplantation and prenatal genetic testing, particularly with the commercialization and expanding scope of noninvasive prenatal testing (NIPT) (Hayden 2014). Sparrow (2015) has made another important contribution to the ongoing debate about the value of, and possible threats to, disability and genetic diversity. Often missing from this debate are clinicians and researchers with expertise in genetics. Although Sparrow (2015) acknowledges the “dangers of oversimplification” in his hypothetical scenarios, we have a social responsibility to address herein common misconceptions about the human genome and about the capabilities of some reproductive genetic technologies (Scully 2008).