tbuckley/cabot-search huggingface dataset:
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA
Authors: Kasmintan A. Schrader, Donavan T. Cheng, Vijai Joseph, Meera Prasad, Michael Walsh, Ahmet Zehir, Ai Ni, Tinu Thomas, Ryma Benayed, Asad Ashraf, Annie Lincoln, Maria Arcila, Zsofia Stadler, David Solit, David M. Hyman, Liying Zhang, David Klimstra, Marc Ladanyi, Kenneth Offit, Michael Berger, Mark Robson
Journal: JAMA Oncology (2015)

Tumor genetic sequencing identifies potentially targetable genetic alterations with therapeutic implications. Analysis has concentrated on detecting tumor-specific variants, but recognition of germline variants may prove valuable as well.To estimate the burden of germline variants identified through routine clinical tumor sequencing.Patients with advanced cancer diagnoses eligible for studies of targeted agents at Memorial Sloan Kettering Cancer Center are offered tumor-normal sequencing with MSK-IMPACT, a 341-gene panel. We surveyed the germline variants seen in 187 overlapping genes with Mendelian disease associations in 1566 patients who had undergone tumor profiling between March and October 2014.The number of presumed pathogenic germline variants (PPGVs) and variants of uncertain significance per person in 187 genes associated with single-gene disorders and the proportions of individuals with PPGVs in clinically relevant gene subsets, in genes consistent with known tumor phenotypes, and in genes with evidence of second somatic hits in their tumors.The mean age of the 1566 patients was 58 years, and 54% were women. Presumed pathogenic germline variants in known Mendelian disease-associated genes were identified in 246 of 1566 patients (15.7%; 95% CI, 14.0%-17.6%), including 198 individuals with mutations in genes associated with cancer susceptibility. Germline findings in cancer susceptibility genes were concordant with the individual's cancer type in only 81 of 198 cases (40.9%; 95% CI, 34.3%-47.9%). In individuals with PPGVs retained in the tumor, somatic alteration of the other allele was seen in 39 of 182 cases (21.4%; 95% CI, 16.1%-28.0%), of which 13 cases did not show a known correlation of the germline mutation and a known syndrome. Mutations in non-cancer-related Mendelian disease genes were seen in 55 of 1566 cases (3.5%; 95% CI, 27.1%-45.4%). Almost every individual had more than 1 variant of uncertain significance (1565 of 1566 patients; 99.9%; 95% CI, 99.6%-99.9%).Germline variants are common in individuals undergoing tumor-normal sequencing and may reveal otherwise unsuspected syndromic associations.
Achilles’ Lead: Will Pacemakers Break Free?
Authors: Mark S. Link
Journal: New England Journal of Medicine (2015)

Pacemaker leads, which connect the chest-wall generator of a pacemaker to the pacing electrode in the heart, are the “Achilles’ heel” of pacing and defibrillation systems. Over time, they wear out, which often necessitates their risky removal and replacement. In addition, transvenous leads provide a portal into the vascular space, which increases the risk of infection. Patients with traditional pacemakers and defibrillators are also susceptible to hematomas and pocket infections in the chest wall where the generators lie. Thus, a self-contained leadless pacemaker that can be placed directly into the heart is an appealing prospect.Reports of two recent nonrandomized, . . .
Calr Mutations in Essential Thrombocythemia: Frequency, Clinical Correlation and Screening By High-Resolution Melting Analysis
Authors: Ken-Hong Lim, Huan-Chau Lin, Yi-Hao Chiang, Wei-Ting Wang, Ching-Sung Lin, Yu-Cheng Chang, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Ruey-Kuen Hsieh, Ming-Chih Chang, Yi-Fang Chang, Yuan-Yeh Kuo, Wen-Chien Chou
Journal: Blood (2014)
Initial Interventions for Out-of-Hospital Cardiac Arrest—Reply
Authors: Carolina Malta Hansen, James G. Jollis, Christopher B. Granger
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 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
LNK mutations and myeloproliferative disorders
Authors: Mary Frances McMullin, Holger Cario
Journal: American Journal of Hematology (2015)

The lymphocyte adaptor protein (LNK) is one of a family of adaptor proteins involved cell signaling and control of B cell populations. It has a critical role in regulation of signaling in hematopoiesis. Lnk negatively regulates cytokine initiated cell signaling and it functions as a negative regulator of the mutant protein in myeloproliferative neoplasms JAK2V617F. A number of mutations in LNK have been described in a variety of myeloproliferative neoplasms some of which have been demonstrated to cause increased cellular proliferation. The majority of mutations occur in exon 2. In a small number of cases idiopathic erythrocytosis with subnormal erythropoietin levels LNK mutations have been found which may account for the clinical phenotype. Thus investigation for LNK mutations should be considered in the investigation of idiopathic erythrocytosis and perhaps other myeloproliferative neoplasms.
Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD
Authors: Kristoffer Ostridge, Nicholas Williams, Viktoriya Kim, Michael Bennett, Stephen Harden, Lindsay Welch, Simon Bourne, Ngaire A Coombs, Paul T Elkington, Karl J Staples, Tom MA Wilkinson
Journal: Thorax (2015)

<h3>Background</h3> Matrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised. <h3>Objectives</h3> We investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls. <h3>Methods</h3> We analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease. <h3>Results</h3> Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways. <h3>Conclusions</h3> Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD. <h3>Trial registration number</h3> NCT01701869
<i>In Vivo</i> Detection of Succinate by Magnetic Resonance Spectroscopy as a Hallmark of <i>SDH</i>x Mutations in Paraganglioma
Authors: Charlotte Lussey-Lepoutre, Alexandre Bellucci, Aurélie Morin, Alexandre Buffet, Laurence Amar, Maxime Janin, Chris Ottolenghi, Franck Zinzindohoué, Gwennhael Autret, Nelly Burnichon, Estelle Robidel, Benjamin Banting, Sébastien Fontaine, Charles-André Cuenod, Paule Benit, Pierre Rustin, Philippe Halimi, Laure Fournier, Anne-Paule Gimenez-Roqueplo, Judith Favier, Bertrand Tavitian
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Germline mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. Experimental Design: A pulsed proton magnetic resonance spectroscopy (1H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb−/− or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n = 5) or not (n = 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, and SDH protein expression was assessed by immunohistochemistry in resected tumors. Results: A succinate peak was observed at 2.44 ppm by 1H-MRS in all Sdhb−/−-derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wild-type mouse tumors nor in patients exempt of SDHx mutation. In one patient, 1H-MRS results led to the identification of an unsuspected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. Conclusions: Detection of succinate by 1H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This noninvasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors. Clin Cancer Res; 22(5); 1120–9. ©2015 AACR.
Timeliness in Breast Cancer Treatment—The Sooner, the Better
Authors: Adrienne G. Waks, Tari A. King, Eric P. Winer
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal
Comparing once weekly GLP-1 receptor agonists for type 2 diabetes finds no clear winner
Authors: Michael McCarthy
Journal: BMJ (2015)

A systematic review comparing the safety and efficacy of five once weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) has found no clear winner for treating type 2 diabetes.

The findings, published in the Annals of Internal Medicine ,1 emphasised the need for trials that directly compare these drugs to identify their relative benefits and harms, the researchers wrote.

GLP-1RAs are relatively new injectable drugs that stimulate insulin secretion, inhibit glucagon secretion, slow gastric emptying, and reduce food intake. They have been shown to improve glucose control and reduce body weight and are currently recommended by the American Diabetes Association and the European Association for the Study of …
Food Restriction Ameliorates the Development of Polycystic Kidney Disease
Authors: Gina Warner, Kyaw Zaw Hein, Veronica Nin, Marika Edwards, Claudia C.S. Chini, Katharina Hopp, Peter C. Harris, Vicente E. Torres, Eduardo N. Chini
Journal: Journal of the American Society of Nephrology (2015)

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%-40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD.
Integrating pharmacy into the primary care team
Authors: G Crowe, C J Harris, G E Forster, B T Goh
Journal: BMJ (1995)

“One stop clinic” has advantages for patients

EDITOR,--We agree with Steven Ford and Kevin Jones that the policy of integrating pharmacy into the primary care team has much to recommend it.1 Genitourinary medicine clinics have pioneered the concept of “one stop care,” with on site medical, nursing, laboratory, pharmacy, counselling, psychology, and social work facilities. With the ever increasing numbers of patients with HIV infection attending, these in house services have …
Did inappropriate delivery systems hamper therapeutic efficacy of di-sodium-cromo-glycate (DSCG)? Time for a reappraisal
Authors: Manfred Keller, Oliver Denk, Albert Bucholski, Martin Knoch
Journal: European Respiratory Journal (2011)

Chymase-positive mast cells located in distal airways play a crucial role in asthma (Balzar 2005 & 2010). A review on inhaled DSCG by Keller & Schierholz (2011) provided evidence that poor efficacy of DSCG is most probably linked with sub-therapeutic lung doses. The hygroscopic nature of DSCG causes particle growth associated with reduced lung deposition (Hiller 1980) which may explain insufficient therapeutic efficacy. Significantly higher in-vitro respirable doses were found by aerodynamic particle size assessments in a next generation impactor operated at 50% and 95% rel. humid., respectively using small droplet nebulisers compared to Intal® MDI and DPI (Keller 2007). Nebulised isotonic solutions provided better tolerability and efficacy than hypotonic Intal solution (Weiner 1988, Soferman 1990). Higher Cmax and AUC values were obtained for nebulisers compared to MDIs and DPIs (Patel 1986 & Kato 1999). Above mentioned aspects and critisism on earlier meta-analyses by Stevens 2007 were still ignored in the latest Cochrane meta-analysis by van der Wouden 2009. Recent data from a clinical trial in 48 asthmatic children (10.3±2.8 yrs, 19 girls) inhaling for 6 months either 3× daily 20 mg isotonic DSCG via an investigational eFlow® electronic nebuliser or twice daily inhaled steroids via MDI with spacer showed comparable efficacy to inhaled steroids (Basek 2010). In conclusion, in-vivo data suggest that DSCG is a safe and effective asthma controller when a highly efficient, small droplet size generating nebuliser is used. Impactor data obtained at 50% and 95% rel. humidity show that therapeutic efficacy of DSCG is strongly affected by the delivery system.
John Templeton Bowen
Authors: Harleen Arora, Simran Arora, Vidhi Shah, Keyvan Nouri
Journal: JAMA Dermatology (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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 2024 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 Dermatology journal
Co-delivery of doxorubicin and 131I by thermosensitive micellar-hydrogel for enhanced in situ synergetic chemoradiotherapy
Authors: Pingsheng Huang, Yumin Zhang, Weiwei Wang, Junhui Zhou, Yu Sun, Jinjian Liu, Deling Kong, Jianfeng Liu, Anjie Dong
Journal: Journal of Controlled Release (2015)
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Authors: Hirohide Asai, Seiko Ikezu, Satoshi Tsunoda, Maria Medalla, Jennifer Luebke, Tarik Haydar, Benjamin Wolozin, Oleg Butovsky, Sebastian Kügler, Tsuneya Ikezu
Journal: Nature Neuroscience (2015)
Effects of a rapid infusion of 20 % human serum albumin solution on acid–base status and electrolytes in critically ill patients
Authors: Jihad Mallat, Mehdi Meddour, Malcolm Lemyze, Emmanuelle Durville, Florent Pepy, Johanna Temime, Nicolas Vangrunderbeeck, Laurent Tronchon, Didier Thevenin
Journal: Intensive Care Medicine (2015)
Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes
Authors: Ji-Ann Lee, Andrey Damianov, Chia-Ho Lin, Mariana Fontes, Neelroop N. Parikshak, Erik S. Anderson, Daniel H. Geschwind, Douglas L. Black, Kelsey C. Martin
Journal: Neuron (2015)
LP11 : Warfarin anticoagulation for liver fibrosis in patients transplanted for hepatitis C (WAFT-C): results at one year
Authors: A. Dhar, E. Tschotazis, R. Brown, P. Manousou, C. Millson, M. Aldersley, S. Forbes, K. Aggarwal, A. Gera, M. Cramp, A. Holt, D. Mutimer, S. McPherson, A. Burroughs, Q. Anstee, R. Goldin, M.R. Thursz
Journal: Journal of Hepatology (2015)
A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism
Authors: Josep M. Cruzado, Pablo Moreno, José V. Torregrosa, Omar Taco, Richard Mast, Carmen Gómez-Vaquero, Carolina Polo, Ignacio Revuelta, José Francos, Joan Torras, Arantxa García-Barrasa, Oriol Bestard, Josep M. Grinyó
Journal: Journal of the American Society of Nephrology (2015)

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open–label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR&gt;30 ml/min per 1.73 m 2 . The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet ( n =15) or subtotal parathyroidectomy ( n =15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group ( P =0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.
Network Adequacy Standards and Health Insurance—Reply
Authors: Simon F. Haeder, David L. Weimer, Dana B. Mukamel
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 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
Associations Between Industry Sponsorship and Results of Cost-effectiveness Analyses of Drugs Used in Breast Cancer Treatment
Authors: Jordan D. Lane, Mark W. Friedberg, Charles L. Bennett
Journal: JAMA Oncology (2015)

A 1999 investigation1 found that industry sponsorship of cost-effectiveness analyses (CEAs) for oncology drugs was associated with lower likelihood of reporting unfavorable conclusions relative to CEAs with other sponsorship. Over the past 15 years, the CEA literature for oncology drugs has expanded dramatically, and oncology now accounts for the largest single pharmaceutical sales area worldwide.2 We sought to determine whether the association between industry sponsorship and CEA results has persisted.