tbuckley/cabot-search huggingface dataset:
Concern Regarding Age Distribution of Breast Cancer—Reply
Authors: Tawakalitu O. Oseni, Sahael M. Stapleton, David C. Chang
Journal: JAMA Surgery (2018)

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 Surgery 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 Surgery journal
THU0207 Finding the optimal treatment strategy for disease activity-guided dose reduction of adalimumab and etanercept in rheumatoid arthritis: a modelling study
Authors: L.M. Verhoef, D.P. Bos, C.H. van den Ende, F.H. van den Hoogen, B. Fautrel, M.E. Hulscher, W. Kievit, A.A. den Broeder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several studies have shown that disease activity-guided dose reduction without deterioration of disease activity is possible, while saving costs in patients with stable and low disease activity.(<sup>1</sup> Despite these positive results, questions remain on the optimal tapering strategy. Different strategies are conceivable, with varying results regarding the balance between number of flares, utilities and costs. <h3>Objectives</h3> The objective of this study was to investigate the most cost-effective TNFi dose reduction strategy for RA patients using a modelling design. <h3>Methods</h3> In a cost-utility analysis using Markov modelling based on data from the DRESS study, STRASS study, and the RA Nijmegen cohort, the following strategies were tested against continuation: 1. Four-step DRESS tapering (figure 1: 100%–67%–50%–0%); 2. Tapering with an extra dosage step of 33%; 3. Tapering without withdrawal; 4. Use of a stricter flare criterion (DAS &gt;2.6); and 5. Use of a predictor (biomarker: 80% specific, 80% sensitive, €100 per test) for successful tapering. Scenario analyses with 30% and 50% drug price discount and no discounting were executed. Also, it was examined how well a biomarker should be able to predict to become cost-effective compared to the other strategies. <h3>Results</h3> All examined tapering strategies were found to be cost saving but yielded more short-lived flares compared to continuation (table 1). The change in utilities was minimal and not clinically relevant. Strategy 1 was cost-effective compared to all other strategies (highest incremental Net Monetary Benefit (iNMB)). However, there was a large overlap in credible intervals, especially between strategy 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it has a sensitivity and specificity of at least 86%. Data is mean values per patient over 1.5 years (95% credible intervals). *Stricter flare criterion (DAS28 &gt;2.6). ** NMB=QALYs * WTP/WTA – costs; iNMBs are given at a WTP/WTA of €80 000. <h3>Conclusions</h3> All dose reduction strategies dominated the continuation strategy regarding cost-effectiveness. Because our study showed a comparable iNMB for tapering in four or five steps, we recommend a choice between these strategies, based on shared decision making. <h3>Reference</h3> [1] Nam JL, et al. Ann Rheum Dis2017Jun;76(6):1113–1136. <h3>Disclosure of Interest</h3> L. Verhoef: None declared, D. Bos: None declared, C. van den Ende: None declared, F. van den Hoogen Consultant for: Biogen, Celltrion and Mundipharma, B. Fautrel: None declared, M. Hulscher: None declared, W. Kievit: None declared, A. den Broeder: None declared
Sorafenib Combined with 5-azacytidine in Older Patients with Untreated <i>FLT3</i> -ITD Mutated Acute Myeloid Leukemia
Authors: Maro Ohanian, Guillermo Garcia‐Manero, Mark Levis, Elias Jabbour, Naval Daver, Gautam Borthakur, Tapan Kadia, Sherry Pierce, Jan Burger, Mary Ann Richie, Keyur Patel, Michael Andreeff, Zeev Estrov, Jorge Cortes, Hagop Kantarjian, Farhad Ravandi
Journal: American Journal of Hematology (2018)

Based on our previous study of the combination of sorafenib with 5-azacytidine (AZA) in relapsed/refractory patients with FLT3 mutated acute myeloid leukemia (AML), we hypothesized that the combination would be efficacious and well tolerated in untreated patients with FLT3 mutated AML who are unsuitable for standard chemotherapy due to advanced age or lack of fitness. Newly diagnosed patients with untreated FLT3 mutated AML who underwent frontline therapy on 2 separate protocols of AZA plus sorafenib were analyzed. The clinical trials were registered at clinicaltrials.gov (NCT02196857 and NCT01254890). Overall, 27 patients with untreated FLT3 mutated AML (median age of 74 years, range, 61-86) were enrolled. The overall response rate was 78% (7 [26%] CR, 12 [44%] CRi/CRp, and 2 [7%] PR). Patients received a median of 3 treatment cycles (1-35). The median duration of CR/CRp/CRi is 14.5 months (1.1-28.7 months). Three (11%) responding patients (1 CR, 2 CRi) proceeded to allogeneic stem cell transplant. The median follow-up for surviving patients was 4.1 months (3.0-17.3 months). The median overall survival for the entire group was 8.3 months, and 9.2 months in the 19 responders. The regimen was well tolerated in elderly patients with untreated FLT3 mutated AML with no early deaths.
Frequency of tumour necrosis factor alpha receptor superfamily 1A multiple sclerosis-associated variants in patients with rheumatoid arthritis with anti-tumour necrosis factor therapy-related demyelinating complications
Authors: Samuel Bitoun, Corinne Miceli-Richard, Céline Verstuyft, Pierre Antoine Juge, Philippe Dieudé, Jean-Marie Berthelot, Christophe Richez, Cécile Cauquil, Christelle Sordet, Sylvie Melac-Ducamp, Laure Gossec, Beatrice Bouvard, Emmanuelle Dernis, Eric Houvenagel, Marie-Astrid Boutry-Bacle, Xavier Mariette, Raphaèle Seror
Journal: Annals of the Rheumatic Diseases (2018)

Tumour necrosis factor alpha (TNFα) is a key cytokine in inflammatory rheumatic diseases but is also implicated in multiple sclerosis (MS) where TNFα is elevated in demyelinating plaques. However, TNFα inhibitors (TNFi) have opposite effects: they have revolutionised the treatment of chronic rheumatic diseases but may cause flares of MS.1 Several studies have suggested an association between TNFi use and occurrence of demyelinating disorders.2 3 Their incidence is estimated up to 4% after 18 months of treatment in a recent prospective study with systematic neurological examination before and after treatment initiation.4 

In addition, two TNF receptor superfamily 1 ( TNFRSF1A ) single nucleotide polymorphisms, (SNPs) rs1800693 and rs4149584 (TNFRSF1A R92Q), have been shown to increase the risk of developing MS.5 The rs1800693*G allele leads to a dysfunctional TNFα soluble receptor that inhibits TNFα signalling.6 Rare variants of TNFRSF1A locus have also been implicated …
A Systematic Review And Meta-Analyses Of Airflow For The Relief Of Chronic Refractory Breathlessness In People With Advanced Cardio-Respiratory Diseases And Mild Hypoxaemia
Authors: F. Swan, A. Newey, M. Bland, C. Bausewein, S. Booth, M. Johnson, J. Yorke
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
FET PET in Primary Central Nervous System Vasculitis
Authors: Lothar Burghaus, Christoph Kabbasch, Martina Deckert, Maximilian I. Ruge, Gereon R. Fink, Karl-Josef Langen, Norbert Galldiks
Journal: Clinical Nuclear Medicine (2018)

Primary central nervous system vasculitis is confined to the brain and spinal cord. While serological markers of inflammation are usually normal, conventional angiography may confirm the diagnosis. The diagnostic method of choice is central nervous system biopsy. A 57-year-old man suffered from a first generalized epileptic seizure. MRI revealed a contrast-enhancing lesion, and O-(2-[F]fluoroethyl)-L-tyrosine amino acid PET displayed increased metabolic activity, both findings highly suggestive of a malignant glioma. Surprisingly, histology obtained following stereotactic biopsy revealed small-vessel vasculitis.
Cochrane’s reply to Shokraneh and colleagues
Authors: David Tovey
Journal: BMJ (2018)

I’m grateful to Shokraneh and colleagues for raising the subject of Cochrane’s leadership role in the area of open data.12 As they say, Cochrane supports initiatives aimed at encouraging clinical trial transparency and the AllTrials initiative and, as a community, is committed to moving towards the greatest possible transparency and openness. The debate over open access and open data is current and important within Cochrane, so this letter is a welcome addition to the conversation.

It is worth restating the progress that Cochrane has made regarding open data and open access, which reflects our commitment and is consistent with our mission to promote evidence informed health decision making by producing high quality, relevant, accessible systematic reviews. Readers of Cochrane reviews in the Cochrane Library have, for many years, been able to download …
MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage
Authors: Melanie J. Harriff, Curtis McMurtrey, Cara A. Froyd, Haihong Jin, Meghan Cansler, Megan Null, Aneta Worley, Erin W. Meermeier, Gwendolyn Swarbrick, Aaron Nilsen, Deborah A. Lewinsohn, William Hildebrand, Erin J. Adams, David M. Lewinsohn
Journal: Science Immunology (2018)

A diverse array of microbial metabolites binds to MR1 and selectively activates MR1-restricted T cells.
The Genetic Epidemiology of Treated Major Depression in Sweden
Authors: Kenneth S. Kendler, Henrik Ohlsson, Paul Lichtenstein, Jan Sundquist, Kristina Sundquist
Journal: American Journal of Psychiatry (2018)

Objective: The authors examined the heritability of treated major depression in a twin and full/half-sibling design, to describe key genetic epidemiological features of major depression and to determine which clinical indices of genetic liability optimally predict risk of depression in relatives. Method: The authors examined all treated cases of major depression in Sweden recorded in inpatient, specialist, and primary care registries and, using OpenMx, estimated the etiologic role of genetic and environmental factors from monozygotic and dizygotic twin pairs and full and half siblings reared together and apart (total N=1,718,863 pairs). Eight indices of genetic risk were examined in 875,010 proband-relative pairs. Results: The heritability of major depression in men and women was estimated at 0.41 (95% CI=0.21, 0.49) and 0.49 (95% CI=0.31, 0.56), respectively, in the twin design and 0.36 (95% CI=0.31, 0.38) and 0.51 (95% CI=0.51, 0.53), respectively, in the independent full/half-sibling design. The best estimate of the correlation in genetic effects across sexes was 0.89 (95% CI=0.87, 0.91). The results also showed evidence of modest shared environmental effects (0.02–0.05). Seven of the eight indices predicted risk for major depression in relatives, with stronger effects in those more closely related. The strongest indices were early age at onset, recurrence, comorbid anxiety disorder, and measures of clinical severity. Conclusions: In a large national sample, the heritability of major depression was similar when estimated from twin and full/half-sibling designs. The heritability of major depression was greater in women than in men, with the two sexes sharing most but not all genetic risk factors. In affected individuals, genetic risk for major depression could be meaningfully assessed from commonly available clinical indices.
Familial Scimitar Syndrome
Authors: KinyaAshida, AkiraItoh, TakahikoNaruko, MasatoOtsuka, YujiSakanoue, MakotoKobayashi, HajimeYamashita, MichitakaNagashima, TakuroShinsato, SyuichiroTakanashi, YoshihiroShimizu, KazuoHaze
Journal: Circulation (2001)
Gene Transfers of Vascular Endothelial Growth Factor-A, Vascular Endothelial Growth Factor-B, Vascular Endothelial Growth Factor-C, and Vascular Endothelial Growth Factor-D Have No Effects on Atherosclerosis in Hypercholesterolemic Low-Density Lipoprotein-Receptor/Apolipoprotein B48-Deficient Mice
Authors: PiaLeppänen, SuviKoota, IvanaKholová, JonnaKoponen, ChristinaFieber, UlfEriksson, KariAlitalo, SeppoYlä-Herttuala
Journal: Circulation (2005)

Background— The role of vascular endothelial growth factors (VEGFs) in large arteries has been proposed to be either vasculoprotective or proatherogenic. Because VEGF family members are used for human therapy, it is important to know whether they could enhance atherogenesis. We tested the effects of the members of the VEGF gene family on atherogenesis in LDL-receptor/apolipoprotein (apo) B48 double-knockout (LDLR/apoB48) mice using systemic adenoviral gene transfer. Methods and Results— Six groups of LDLR/apoB48-deficient mice (n=110) were kept 3 months on a Western-type diet. After 6 weeks of diet, mice were injected via tail vein with recombinant adenoviruses expressing VEGF-A, -B, -C, or -D or LacZ (1×109 PFU) or rhVEGF-A protein (2 μg/kg) and euthanized 6 weeks later. Also, older mice (n=36) were injected after 4 months on the diet and euthanized 6 weeks later (total time on the diet, 22 weeks) to evaluate the effects of gene transfers on the development of more mature lesions. Aortas were analyzed fo...
Improving social and behavioral science by making replication mainstream: A response to commentaries
Authors: Rolf A. Zwaan, Alexander Etz, Richard E. Lucas, M. Brent Donnellan
Journal: Behavioral and Brain Sciences (2018)

Abstract The commentaries on our target article are insightful and constructive. There were some critical notes, but many commentaries agreed with, or even amplified our message. The first section of our response addresses comments pertaining to specific parts of the target article. The second section provides a response to the commentaries' suggestions to make replication mainstream. The final section contains concluding remarks.
Clinical profile and outcomes in glioblastoma multiforme: Institutional experience.
Authors: Kesava Ramgopal Adavikolanu, Fayaz ahmed Syed, Monica Malik, Jagannathrao Naidu K, Suresh Pamidighantam, Venkataratnam Sunkavalli
Journal: Journal of Clinical Oncology (2012)

e12501 Background: The standard of care for glioblastoma is surgical resection followed by adjuvant RT (radiotherapy) with concurrent and adjuvant temozolomide. Methods: Between January 2006 to December 2010, patients of glioblastoma who underwent surgery and RT to a dose of 60 Gy were analysed retrospectively. Age, KPS, extent of surgery, RPA class were noted and patients were divided into two groups, RT alone (Group I) or RT with concurrent temozolomide 75mg/m 2 /day followed by adjuvant temozolomide 150 mg/m 2 /dayX5days q28days for 6 cycles(Group II). Results: A total of 62 patients were analysed, 23 patients in group I and 39 in group II. Median age in group I was 48 years (range 16-60, 19 male, 4 female), 8(34.8%) patients underwent gross total resection, 12 (52.2%) had partial resection and 3(13%) had stereotactic biopsy. The median overall survival (OS) was six months. Median age in group II was 50 years (range 13-76, 26 male, 13 female), 17(43.6%) patients underwent gross total resection, 19(48.7%) had partial resection and 3 (7.7%) had stereotactic biopsy. The median OS was nine months (p=0.018). Patients were analysed according to the RPA class (III-VI). Median OS and 1 yr survival for group I for RPA class III,IV,V/ VI were 12, 6 and 4 months and 50%,15.3%,0% respectively. Median OS and 1 yr survival rates for group II for RPA class III, IV,V / VI were 20, 8 and 5.5 months and 66.6%, 35%, 30% respectively. On multivariate analysis age(p=0.005), KPS(p=0.05), extent of surgery(p=0.043) were found to affect survival. Conclusions: Concurrent radiotherapy and temozolomide followed by adjuvant temozolomide results in improved survival in glioblastoma.
Potential Child Health Consequences of the Federal Policy Separating Immigrant Children From Their Parents
Authors: Howard A. Zucker, Danielle Greene
Journal: JAMA (2018)

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
Abstract B18: Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1
Authors: Valeria G. Antico Arciuch, Nicolas Anselmino, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez
Journal: Clinical Cancer Research (2018)

Abstract Prostate cancer (PCa) is the second leading cause of cancer-associated death in men, with bone metastases being the main cause of mortality. Energetic metabolism alterations have become a new hallmark of cancer, since variations in a single gene can orchestrate changes in metabolic pathways and confer an adaptive advantage. Heme-oxygenase 1 (HO-1) exerts an antitumoral role in PCa inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this work was to assess the role of HO-1 in the metabolic signature of PCa. Through RNA-Seq we found a set of metabolic genes deregulated under pharmacologic induction (hemin treatment) or genetic induction of HO-1 in PC3 cells. STAR and ATP5L2 were found upregulated, while HMGCS2, PRODH and ACOT12 were downregulated. These genes encode for steroid hormone metabolism, ATP synthesis, ketogenesis, proline and lipid metabolism. The analysis of the deregulated genes (2-fold) under HO-1 modulation by Gene Ontology revealed alterations in several metabolic pathways such as steroid, tyrosine and lipid metabolism, and ion transport. Bone is the only site of PCa progression, and bone cells are able to produce factors that increase the growth and survival of tumor cells favoring progression. However, the molecular nature of this interaction remains to be elucidated. Our preliminary results performed on cocultures of PC3 cells (treated or not with hemin) with Raw264.7 (pre-osteoclastic) or MC3T3 (preosteoblastic) cells demonstrate that HO-1 is able to direct the metabolic fate of bone precursor cells due to the deregulation of glycolytic genes. HO-1 induction in PC3 cells downregulated the expression of PKM2 and LDHA in cocultured Raw264.7 and MC3T3 cells (p&amp;lt; 0.05). Based on our results, we propose HO-1 as a key regulator of the metabolic status of PCa cells and a powerful mediator capable of redefining the metabolic signature of bone precursor cells, thus favoring the establishment of a less aggressive phenotype. Citation Format: Valeria G. Antico Arciuch, Nicolas Anselmino, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez. Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1 [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B18.
P2X7 Receptor Activation–Induced Contraction and Lysis in Human Saphenous Vein Smooth Muscle
Authors: ChrystelleCario-Toumaniantz, GervaiseLoirand, AnnieLadoux, PierrePacaud
Journal: Circulation Research (1998)

Abstract—In cutaneous veins where purinergic neurotransmission is more prominent compared with in deep vessels, physiological and pathological roles of nerve-released ATP have been described. Neuronally released ATP has been reported to act through activation of unidentified ionotropic P2X receptor(s). This study analyzed P2X receptor subtypes expressed in human saphenous vein smooth muscle and their physiological functions. Transcripts for both hP2X1 receptors, already identified in other smooth muscles, and, surprisingly, hP2X7 receptors known to be responsible for the cytotoxic effect of ATP in macrophages were detected by Northern blot analysis in total RNA from saphenous vein smooth muscle. ATP and other P2X receptor agonists [αβ-methylene-ATP, 2-methylthio-ATP, and 2′,3′-(4-benzoyl)benzoyl-ATP] dose-dependently contracted venous rings, but the contraction induced by 2-methylthio-ATP was more transient than that evoked by the other P2X agonists. The effect of hP2X1 agonists involved the activation of...
PTH-063 Fermentation capacity of gut microbiota in patients with inflammatory bowel disease compared to healthy controls
Authors: M Kokkorou, M McGowan, M Rebull, Y Koh, Gaya, R Hansen, RK Russell, K Gerasimidis
Journal: Gut (2017)

Introduction  Gut microbiota in the colon ferment undigested dietary fibre to produce short-chain fatty acids (SCFA). SCFA have beneficial effects on colonic health. Differences in microbiota composition and metabolic activity have been described between IBD patients and healthy controls. This project explored the capacity of the gut microbiota of IBD patients to breakdown dietary fibre.  Method  Fresh faecal samples were collected from IBD patients in clinical remission and healthy controls (HC). In vitro batch culture fermentations were carried out for 5 carbohydrate/fibres and for a mixture of these 5 fibres together (hi maize, pectin, raftilose, wheat bran, cellulose). Aliquots were taken at 0 and 48 hours. Faecal SCFA (butyrate, propionate and acetate) concentration (umol/g) and their proportional ratio (%) were measured with Gas Chromatography.  Results  25 IBD patients (13 CD and 12 UC) and 14 matched HC were recruited. Following 48 hour batch cultures, total SCFA from hi maize and raftilose in CD patients (median (IQR) HC; 51.76 (22.02) vs. CD; 41.12 (23.28) vs. UC; 41.94 (14.72) p=0.02) and from hi maize in UC patients were significantly lower than in heathy controls (median (IQR) HC; 58.87 (17.69) vs. UC; 44.92 (21.49) p=0.008). The proportional contribution of butyrate to total SCFA following fermentation with mixed fibre was also significantly higher for healthy controls compared to UC patients (median (IQR) HC; 10.76 (8.26) vs. CD; 8.75 (4.74) p=0.044). In no cases were there any significant differences between the SCFA concentration or relative contribution in CD or UC patients.  Conclusion  These data suggest that the microbiota of IBD patients has a lower capacity to break down fibre, compared to healthy people. The findings of this work should be complemented with changes in microbiota composition using next generation sequencing.  Disclosure of Interest  None Declared