tbuckley/cabot-search huggingface dataset:
Lessons to Be Learned From the UK Junior Doctors’ Strike
Authors: Andrew F. Goddard
Journal: JAMA (2016)

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
The Correlation Of Hepatic Iron Loading Determined By Magnetic Resonance Image and Serum Ferritin In Patients With Beta-Thalassemia Intermedia
Authors: Ampaiwan Chuansumrit, Jiraporn Laothamathat, Nongnuch Sirachainan, Pakawan Wongwerawattanakoon, Praguywan Kadekasem, Werasak Sasanakul
Journal: Blood (2013)
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney
Authors: Rohit Mehra, Pankaj Vats, Marcin Cieslik, Xuhong Cao, Fengyun Su, Sudhanshu Shukla, Aaron M. Udager, Rui Wang, Jincheng Pan, Katayoon Kasaian, Robert Lonigro, Javed Siddiqui, Kumpati Premkumar, Ganesh Palapattu, Alon Weizer, Khaled S. Hafez, J. Stuart Wolf, Ankur R. Sangoi, Kiril Trpkov, Adeboye O. Osunkoya, Ming Zhou, Giovanna Giannico, Jesse K. McKenney, Saravana M. Dhanasekaran, Arul M. Chinnaiyan
Journal: Cancer Discovery (2016)

Abstract Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. Significance: MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258–66. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 1197
Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension
Authors: Thomas Bertero, William M. Oldham, Katherine A. Cottrill, Sabrina Pisano, Rebecca R. Vanderpool, Qiujun Yu, Jingsi Zhao, Yiyin Tai, Ying Tang, Ying-Yi Zhang, Sofiya Rehman, Masataka Sugahara, Zhi Qi, John Gorcsan, Sara O. Vargas, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Kathleen J. Haley, Aaron B. Waxman, Victoria N. Parikh, Teresa De Marco, Priscilla Y. Hsue, Alison Morris, Marc A. Simon, Karen A. Norris, Cedric Gaggioli, Joseph Loscalzo, Joshua Fessel, Stephen Y. Chan
Journal: Journal of Clinical Investigation (2016)

Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus–infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ–GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH.
Drug Antisubstitution Laws
Authors: Russell E. Johnson
Journal: JAMA (1972)

<h3>To the Editor.—</h3> I am writing in regard to my most recent issue of the<i>American Pharmaceutical Association Newsletter</i>dated June 17,1972 in which there was a reprint of a letter from the APHA Board of Trustees Executive Committee to you. Speaking on behalf of myself and many of my fellow pharmacists, I completely disagree with the recommendation of the APHA Board of Trustees Executive Committee that the antisubstitution laws be amended to permit the pharmacist to exercise drug product selection. If a physician has specified a particular brand product, whatever the reason might be, this is what the pharmacist should dispense. If a physician prescribes generically, it is the responsibility of the pharmacist to select his choice of product. I honestly believe that most pharmacists disagree with the position taken by the APHA Board of Trustees Executive Committee on this issue.
Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways
Authors: Jongchan Kim, Ashley N. Siverly, Dahu Chen, Min Wang, Yuan Yuan, Yumeng Wang, Hyemin Lee, Jinsong Zhang, William J. Muller, Han Liang, Boyi Gan, Xianbin Yang, Yutong Sun, M. James You, Li Ma
Journal: Cancer Research (2016)

The invasive and metastatic properties of many human tumors have been associated with upregulation of the miRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here, we report the generation of miR-10b-deficient mice, in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial-mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer. Among the target genes of miR-10b, the tumor suppressor genes Tbx5 and Pten and the metastasis suppressor gene Hoxd10 are significantly upregulated by miR-10b deletion. Mechanistically, miR-10b promotes breast cancer cell proliferation, migration, and invasion through inhibition of the expression of the transcription factor TBX5, leading to repression of the tumor suppressor genes DYRK1A and PTEN In clinical specimens of breast cancer, the expression of TBX5, HOXD10, and DYRK1A correlates with relapse-free survival and overall survival outcomes in patients. Our results establish miR-10b as an oncomiR that drives metastasis, termed a metastamiR, and define the set of critical tumor suppressor mechanisms it overcomes to drive breast cancer progression. Cancer Res; 76(21); 6424-35. ©2016 AACR.
Coagulopathy in Cirrhosis: A Prospective Study to Correlate Conventional Tests of Coagulation and Bleeding Following Invasive Procedures in Cirrhotics
Authors: Apurva Shah, Deepak Amarapurkar, Mrudul Dharod, Madhuri Chandnani, Rajiv Baijal, Praveen Kumar, Mayank Jain, Nikhil Patel, Praful Kamani, Sonali Gautam, Nimish Shah, Sandeep Kulkarni, Soham Doshi
Journal: Clinical Gastroenterology and Hepatology (2015)
Keeping the fistula open: paradigm shift in the management of leaks after bariatric surgery?
Authors: Vivek Kumbhari, Barham Abu Dayyeh
Journal: Endoscopy (2016)

Leaks associated with bariatric surgery occur in 1 % – 3 % of patients [1] [2]. In sleeve gastrectomy, over 90 % of leaks occur at the proximal margin of the staple line [3]. The pathomechanism behind leak formation in this location is thought to relate to ischemia secondary to take down of the short gastric arteries, mismatch in staple height selection due to the thinner wall of the gastric fundus, high intraluminal pressures resulting from a poorly complaint sleeve, or gastric stenosis at the incisura angularis. The management of leaks after bariatric surgery lacks a standard management algorithm owing to a paucity of prospective randomized trials. Regardless, it is universally accepted that endoscopy plays a pivotal role in the management of both acute and chronic leaks.
CD19+,CD27+, IgM+ B Cells of Patients with Persistent Polyclonal B Cell (PPBL) Proliferate in a Low Intensity CD40-CD154 Interaction and Show Evidence of Immunoglobulin Isotype Switching
Authors: Robert Delage, Emmanuelle Dugas-Bourdages, Annie Roy, Sonia Neron, Andre Darveau
Journal: Blood (2008)
Early PET analysis to identify responders to erlotinib treatment of advanced NSCLC.
Authors: T. Zander, M. Scheffler, L. Nogova, S. Querings, M. Dietlein, B. Neumaier, C. Kobe, E. Stoelben, R. K. Thomas, J. Wolf
Journal: Journal of Clinical Oncology (2010)

e18092 Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, identification of EGFR mutations is not always possible due to lack of adequate tissue. We therefore investigated whether early PET might be a suitable tool to identify EGFR mutation positive responders. Methods: Six patients with NSCLC stage IIIB/IV showing partial remission according to RECIST criteria to first-line erlotinib treatment were analyzed and compared to 31 patients without response to first-line treatment with erlotinib. All patients were examined by [18F] FLT-PET and [18F] FDG-PET at baseline and after 1 week of treatment with erlotinib. The change in the sum of the maximum standard uptake value (sSUVmax) was calculated. Mutational status in each patient was analyzed by conventional Sanger sequencing. In case of negative results parallel sequencing using 454 technology was performed (EudraCT number 2005-005393-73; NCT00568841). Results: The median PFS for the 6 responding patients was 412 days. The mean reduction in the sSUV max was 37% (16-61) for [18F] FDG and 33% (0-55) for [18F] FLT after 1 week of treatment. Sanger sequencing of tissue available for molecular analyses revealed a sensitizing EGFR mutation in 3 of these 6 patients. Using the highly sensitve 454 technology an EGFR mutation could be demonstrated in 1 further patient. In the remaining two patients there was no diagnostic material allowing further molecular analyses. By comparison, the mean change in sSUVmax in patients not responding to erlotinib (n=31) was + 3% for [18F] FLT and -3% for [18F] FDG (p<0.005, T test). In the ROC analysis the AUC was calculated with 0.88 (0.73-1.00, p=0.004) for detection of response. Conclusions: Early [18F] FLT-PET and [18F] FDG-PET might be a suitable tool to detect patients with sensitizing EGFR mutations when treated with erlotinib. This might circumvent EGFR mutational analyses in patients with insufficient diagnostic material and enable early prediction of clinical response. Pat ID Histology Sanger 454 Change in sSUVmax LT-PET Change in sSUVmax FDPET 01-08 Adeno 0 del exon 19 -30 -44 01-18 Adeno del exon 19 N/A -44 -16 01-27 Adeno 0 N/A -55 -61 01-31 Adeno 0 N/A -39 -45 01-28 Adeno del exon 19 N/A 0 -38 01-25 Adeno L858R N/A -30 -22 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
P0309 : Gene expression profiling of hepatocellular carcinoma biopsies reveals three molecular classes with distinct clinical and biological properties
Authors: Z. Makowska, T. Boldanova, D. Adametz, L. Quagliata, J.E. Vogt, M.T. Dill, M.S. Matter, V. Roth, L. Terracciano, M.H. Heim
Journal: Journal of Hepatology (2015)
Assessment of Minimal Residual Disease in Standard-Risk AML
Authors: Megan Othus, Elihu Estey, Robert P Gale
Journal: New England Journal of Medicine (2016)

To the Editor: Ivey et al. report that the persistence of NPM1-mutated transcripts in blood samples after two cycles of chemotherapy was associated with an increase by a factor of 6.8 in the risk of relapse (P<0.001) in patients with standardrisk newly diagnosed AML.These findings and others 1,2 suggest a potential role for monitoring measurable residual disease in patients with AML.However, to make these analyses useful to the physician for patient-level decision making, the data should be supplemented by a measure evaluating patient-level prediction, such as a C-statistic.Our experience suggests that even for models that have several covariates with large hazard ratios that are independently significant (at P<0.01), C-statistics often range from 0.75 to 0.80. 3,4
Role of CEBPA-Mutations in AML with Prognostically Intermediate Cytogenetics: Data of the AMLCG Study Group and Gene Expression Analyses.
Authors: Susanne Schnittger, Viola Conrad, Alexander Kohlmann, Martin Dugas, Sylvia Merk, Wolfgang Kern, Thomas Buechner, Wolfgang Hiddemann, Claudia Schoch, Torsten Haferlach
Journal: Blood (2004)
Intravenous iron therapy in blood management of patients with breast cancer in Calabar, Nigeria.
Authors: N. I. Usoro, I. A. Ibanga, G. A. Ebughe, I. U. Ilori
Journal: Journal of Clinical Oncology (2011)

e19717 Background: Breast cancer patients, like all cancer patients, are prone to anemia arising from the disease, from chemotherapy, and from surgery. Repeated blood transfusion is hazardous, especially in a resource-poor setting, and is associated with a poor prognosis. EPO is effective but expensive in our setting. We aimed to carry out total breast cancer care without blood transfusion using pre-emptive and therapeutic iron therapy, and blood conservation methods during surgery. Methods: Fifteen female breast cancer patients had initial hemogram done and were placed on oral iron therapy with vitamin adjuncts (minus folate) from the first outpatient visit. Patients with HCT <27% also received intravenous iron dextran using the formula: [normal Hb – actual Hb] x 200 + 500 mg. All patients received 250mg of IV iron dextran with each cycle of chemotherapy. Patients on chemotherapy had a hemogram before each cycle and 3 weeks after the last cycle. Patients for surgery were assessed for blood conservation methods tailored to each patient. Postoperative hemograms were done on the third day and after 3 weeks. Results: Six patients successfully completed 6 cycles of chemotherapy, and 4 defaulted between the 1st and 5th cycles. Five patients died of non anemia–related complications of late-stage disease. One patient with early breast cancer and 3 patients with late breast cancer had modified radical mastectomy using blood conservation methods. All who had surgery recovered satisfactorily and 3 completed 6 cycles of chemotherapy. One patient reacted to iron dextran with pruritus which was relieved with intravenous hydrocortisone. All patients maintained a hematocrit >30% throughout chemotherapy and none received blood transfusion. Conclusions: Intravenous iron is practical, safe and effective in blood management of breast cancer patients in a resource-poor environment. Avoiding the hazards and cost of blood transfusion is desirable, and enhanced survival may also be achieved.
Lack of evidence for germline <i>RNF43</i> mutations in patients with serrated polyposis syndrome from a large multinational study
Authors: Daniel D Buchanan, Mark Clendenning, Li Zhuoer, Jenna R Stewart, Sharelle Joseland, Sonja Woodall, Julie Arnold, Kara Semotiuk, Melyssa Aronson, Spring Holter, Steven Gallinger, Mark A Jenkins, Kevin Sweet, Finlay A Macrae, Ingrid M Winship, Susan Parry, Christophe Rosty
Journal: Gut (2016)

Serrated polyposis syndrome (SPS) is characterised by the occurrence of multiple serrated polyps in the large bowel. Defined clinically by the 2010 revised WHO, SPS is associated with an increased risk of colorectal cancer (CRC) for affected individuals and their first-degree relatives. Yan et al 1 recently reported their findings from whole-exome sequencing (WES) of six individuals with SPS from four families, identifying a single family carrying a germline likely pathogenic variant in RNF43 (c.953-1 G>A, c.953_954delAG, p.E318fs). In this family, six carriers were identified, five of whom met the WHO criteria for SPS. This adds to two previous reports of germline mutations within RNF43 in individuals with SPS or who developed multiple serrated polyps.2 ,3 The current study by Yan et al 1 also importantly showed loss of second wildtype allele in 16 serrated polyps, five adenomatous polyps, and in the rectal adenocarcinoma from carriers through somatic single nucleotide variants or loss of heterozygosity, adding further weight to a potential role of RNF43 in the development of colonic serrated neoplasia.

We present …
Loss Of Tumor Suppressor BTG1 Enhances ATF4 Function and Promotes Cell Survival
Authors: Laurens T. van der Meer, Laurensia Yuniati, Esther J.H. Tijchon, Liesbeth van Emst, Manon Alkema, Caroline Rodenbach, Blanca Scheijen, Peter M. Hoogerbrugge, Frank N. van Leeuwen
Journal: Blood (2013)
Publication of CDC Surveillance Summaries
Authors: Jane Schulman
Journal: JAMA (1993)

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
Rexinoid therapy for poorly differentiated thyroid cancer: A pilot clinical phase II trial and correlation to retinoid and peroxisome-proliferator activated receptor gamma receptors expression.
Authors: L. P. De Oliveira, B. Haugen, M. Kane, A. Jimeno, J. Klopper
Journal: Journal of Clinical Oncology (2010)

TPS269 Background: Thyroid cancer causes over 1,600 deaths annually, mostly from poorly differentiated tumors that are radioiodine resistant. Cytotoxic chemotherapy has limited efficacy so alternative therapies are warranted. Retinoids are vitamin A derivatives that bind to retinoic acid and retinoid × receptors (RARs and RXRs), each with α, β, and γ isotypes. Retinoid receptors are present in thyroid tissue and the RXRγ isotype has been shown to be higher in thyroid cancer than matched normal tissue. RXRs can form a heterodimer partnership with PPARγ to enhance transcriptional activity upon DNA binding. Bexarotene is a selective RXR agonist approved for the treatment of cutaneous T-cell lymphoma. Preclinical in vitro and in vivo studies show that bexarotene reduces growth in RXRg expressing cells and xenograft tumor size, and this effect is enhanced when PPARγ is present. Additionally, bexarotene has been shown to increase radioiodine uptake in some patients with previously radioiodine-resistant thyroid cancer. Methods: Adult patients with radioiodine-resistant follicular-derived thyroid cancer and RECIST criteria disease progression and/or PET positive lesions will be enrolled. Eligible patients will receive open-label bexarotene at a dose of 300 mg/m2/day. Concomitant omega-3 fatty acids will be started two weeks before bexarotene. We propose a two-part, standard phase II trial where we will study 19 patients and if we see one response we will enroll 12 more for a total of 26 patients. With an anticipated 10-30% drop out this will allow for 14 initial patients and if a responder is found 23 patients total. Study drug will be given for one year and the primary end points are tumor response by RECIST criteria and correlation with primary thyroid cancer tissue expression of RXR and PPARy receptors. The secondary endpoint is radioiodine uptake at 6 months and 1 year. At weeks 8, 18, 24, 30, 38, 46, and 52 TSH, Free T4, total T4, total T3, thyroglobulin and thyroglobulin antibodies will be obtained. Neck ultrasound, PET-CT scan, and rhTSH-stimulated radioactive iodine whole body scan will be obtained on weeks 24 and 52. No significant financial relationships to disclose.