tbuckley/cabot-search huggingface dataset:
AB1034 The urate-lowering effect of febuxostat 80 mg and 40 mg (80 MG FILM-COATED TABLETS SPLIT IN HALF) in gout patients in daily clinical practice
Authors: M. Flendrie, B. van den Bemt, V. Huiskes, M. Hoefnagels, F. van den Hoogen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In Europe, the urate-lowering drug febuxostat for gout is registered in two strenghts, 80 mg and 120 mg, but not 40 mg. Starting 40 mg can sometimes be considered desirable, for instance for safety reasons. Splitting an 80 mg film-coated tablet in half is an option, but is off-label and might violate coating function and influence effectiveness and safety. <h3>Objectives</h3> To investigate the urate-lowering effect and safety of starting febuxostat at 40 mg once daily (80 mg film-coated tablet split in half) in gout patients compared to 80 mg once daily. <h3>Methods</h3> Single-centre retrospective study on all gout patients starting febuxostat 80 mg or 40 mg (80 mg film-coated tablets split in half). Patients characteristics were collected, as well as starting dose and starting date of febuxostat, follow-up time, adverse events (AEs), stop date and reason, serum urate (sU) and creatinin (sCreat) over time and relevant comorbidity. Patient characteristics were compared by Chi-square or T-test. Mean sU, percentual change from baseline and percentage of patients reaching targets (sU &lt;0.36 or 0.30 mmol/L) were tested using the appropriate t-test. <h3>Results</h3> 36 gout patients started febuxostat between April 1st 2012 and July 1st 2017. Twenty-three started on 80 mg and 13 on 40 mg once daily. Patient characteristics are shown in table 1. Table 2 shows mean sU at baseline and after start, percentage change in sU and percentage of patients reaching targets. Median follow-up time was 1.6 years (range 0–6.7); 1.4 y (0–6.7) resp. 1.9 (0.4–5.5) for 80 mg resp. 40 mg group. Figure 3 shows mean sU per group in the first year. 5 of 36 (14%) stopped during follow-up, all within 8 weeks after start and all because of AEs: diarrhoea (n=2, 40 mg and 80 mg), coronary syndrome (n=1, 80 mg), erectile dysfunction (n=1, 40 mg) and gout attacks (n=1, 40 mg). Other possible related AEs were dry mouth (n=1, 80 mg), elevated liver enzymes (n=1, 40 mg) and flushing (n=1, 40 mg). <h3>Conclusions</h3> Both daily dosages febuxostat of 80 and 40 mg (80 mg film-coated tablets split in half) result in significant decline in sU levels within 12 weeks. A starting dose of 80 mg febuxostat appears more effective in reducing sU levels. Selection bias may be a problem. <h3>Disclosure of Interest</h3> None declared
MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells
Authors: Zhigang Xie, Jing Yuan Chooi, Sabrina Hui Min Toh, Dongxiao Yang, Nurhidayah Binte Basri, Ying Swan Ho, Wee Joo Chng
Journal: Leukemia (2018)
Suppression of active CREB induces apoptosis and inhibition of cell growth in human non-small-cell Lung cancer cells
Authors: Sita Aggarwal, Seung Wook Kim, Ja Seok Koo
Journal: Cancer Research (2006)

2625  Genes that are regulated by cyclicAMP response element binding (CREB) protein suppress apoptosis, induce cell proliferation, and mediate inflammation, angiogenesis and tumor metastasis. It was not known whether CREB is involved in lung cancer. We hypothesized that constitutively active CREB is an important target in the treatment of non-small cell lung cancer (NSCLC) and that its inhibition should block cell proliferation and induce apoptosis in NSCLC cells. We found that the NSCLC cell lines we examined overexpressed constitutively active CREB, two of its upstream kinases, phospho- ribosomal s6-kinase (Rsk), phospho-extracellular signal kinase(Erk1/2) and cell survival genes such as Bcl-2 and Bcl-XL. Ectopic expression of a dominant-repressor CREB (KCREB), mutant CREB (CREB133, Ser133Ala), and small interfering (si) RNA against CREB (siCREB) suppressed the cell proliferation of NSCLC (H1734) cells. Furthermore, treatment of H1734 cells with a Protein Kinase C inhibitor (Ro-31-8220) inhibited CREB activation by abrogating phospho-Erks and phospho-Rsk. Consequently, the expression of anti-apoptotic genes such as Bcl-2 and Bcl-XL was suppressed. There was decreased cell proliferation because the cell cycle was arrested in the G2/M phase; this resulted in apoptosis, as indicated by upstream caspase-9 and downstream caspase-3 activation, poly (ADP-ribose)polymerase cleavage and terminal transferase dUTP nick end labeling staining in H1734 cells. In summary, suppression of CREB by KCREB, CREB133, siCREB, or Ro-31-8220 induced apoptosis in NSCLC cells. Thus, our results indicate that CREB plays an important role in NSCLC cell survival and its suppression inhibits NSCLC cell growth. Thus, agents that suppress CREB activation could have potential therapeutic value for NSCLC.
A More Balanced Approach to Dietary Supplement Data
Authors: Erica M. S. Sibinga, Claudia R. Morris
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
19 G nitinol needle versus 22 G needle for transduodenal endoscopic ultrasound-guided sampling of pancreatic solid masses: a randomized study
Authors: Arthur Laquière, Christine Lefort, Frédérique Maire, Alain Aubert, Rodica Gincul, Frédéric Prat, Philippe Grandval, Olivier Croizet, James Boulant, Geoffroy Vanbiervliet, Guillaume Pénaranda, Laurence Lecomte, Bertrand Napoléon, Christian Boustière
Journal: Endoscopy (2018)

Abstract Background The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. Methods Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. Results 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % – 80.8 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % – 90.2 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % – 100 %) vs. 86.4 % (95 %CI 75.0 % – 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 – 0.97). Conclusion The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.
The Role of Immunohistochemistry and Molecular Analysis of Succinate Dehydrogenase in the Diagnosis of Endocrine and Non-Endocrine Tumors and Related Syndromes
Authors: Lindsey Oudijk, José Gaal, Ronald R. de Krijger
Journal: Endocrine Pathology (2018)

Succinate dehydrogenase (SDH) is an enzyme complex, composed of four protein subunits, that plays a role in both the citric acid cycle and the electron transport chain. The genes for SDHA, SDHB, SDHC, and SDHD are located in the nuclear DNA, and mutations in these genes have initially been described in paragangliomas (PGL) and pheochromocytomas (PCC), which are relatively rare tumors derived from the autonomic nervous system and the adrenal medulla, respectively. Patients with SDH mutations, that are almost exclusively in the germline, are frequently affected by multiple PGL and/or PCC. In addition, other tumors have been associated with SDH mutations as well, including gastrointestinal stromal tumors, SDH-deficient renal cell carcinoma, and pituitary adenomas. Immunohistochemistry for SDHB and SDHA has been shown to be a valuable additional tool in the histopathological analysis of these tumors, and can be considered as a surrogate marker for molecular analysis. In addition, SDHB immunohistochemistry is relevant in the decision-making whether a genetic sequence variant represents a pathogenic mutation or not. In this review, we highlight the current knowledge of the physiologic and pathologic role of the SDH enzyme complex and its involvement in endocrine and non-endocrine tumors, with an emphasis on the applicability of immunohistochemistry.
Challenges in the introduction of next-generation sequencing (NGS) for diagnostics of myeloid malignancies into clinical routine use
Authors: Ulrike Bacher, Evgenii Shumilov, Johanna Flach, Naomi Porret, Raphael Joncourt, Gertrud Wiedemann, Martin Fiedler, Urban Novak, Ursula Amstutz, Thomas Pabst
Journal: Blood Cancer Journal (2018)

Abstract Given the vast phenotypic and genetic heterogeneity of acute and chronic myeloid malignancies, hematologists have eagerly awaited the introduction of next-generation sequencing (NGS) into the routine diagnostic armamentarium to enable a more differentiated disease classification, risk stratification, and improved therapeutic decisions. At present, an increasing number of hematologic laboratories are in the process of integrating NGS procedures into the diagnostic algorithms of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Inevitably accompanying such developments, physicians and molecular biologists are facing unexpected challenges regarding the interpretation and implementation of molecular genetic results derived from NGS in myeloid malignancies. This article summarizes typical challenges that may arise in the context of NGS-based analyses at diagnosis and during follow-up of myeloid malignancies.
Regression of Peripheral Subclinical Enthesopathy in Therapy‐Naive Patients Treated With Ustekinumab for Moderate‐to‐Severe Chronic Plaque Psoriasis: A Fifty‐Two–Week, Prospective, Open‐Label Feasibility Study
Authors: Laura Savage, Mark Goodfield, Laura Horton, Abdulla Watad, Elizabeth Hensor, Paul Emery, Richard Wakefield, Miriam Wittmann, Dennis McGonagle
Journal: Arthritis & Rheumatology (2018)

Objective To investigate whether sonographically determined subclinical enthesopathy in patients with moderate‐to‐severe psoriasis regresses with the use of ustekinumab therapy for skin disease. Methods Seventy‐three patients with moderate‐to‐severe psoriasis, who were not treated with systemic therapy and did not have symptoms of psoriatic arthritis (PsA), and 23 healthy volunteers were screened by ultrasound for subclinical enthesitis. Subsequently, 23 patients with psoriasis whose ultrasound results showed inflammatory changes were treated with ustekinumab for 52 weeks. The evolution of sonographic abnormalities of the upper and lower limb entheses was assessed using an extensive gray‐scale and power Doppler ( PD ) ultrasound protocol at weeks 0, 12, 24, and 52. For each parameter, a gray‐scale or PD ultrasound score of &gt;0 was determined to be abnormal, and a summative score based on the Glasgow Ultrasound Enthesitis Scoring System was calculated. Results Of all the patients with psoriasis screened using ultrasound, 49.3% had at least 1 inflammatory entheseal abnormality. Mean ± SD inflammation scores were higher in the patients with psoriasis compared with the healthy volunteers (9.9 ± 6.6 versus 1.0 ± 1.4). With treatment, the mean inflammation scores decreased significantly by 42.2% from week 0 to week 24 (–4.2 [95% confidence interval –6.3, –2.1]; P &lt; 0.001) and by 47.5% by week 42 (–4.7 [95% confidence interval –7.1, –2.3]; P = 0.001). Entheseal structural abnormalities did not change significantly during treatment. Conclusion Within 12 weeks of treatment, interleukin‐12 ( IL ‐12)/ IL ‐23 inhibition for psoriasis appears to suppress subclinical enthesopathy, and the suppression is maintained through week 52. Further longitudinal studies are needed to determine whether therapy initiated for skin disease may prevent the development of PsA.
Monitoring Jet Engines and the Health of People
Authors: Lionel Tarassenko, Eric J. Topol
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 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
Reply to Jeremy Y.C. Teoh, Thomas R.W. Herrmann, and Marek Babjuk's Letter to the Editor re: Valeria Panebianco, Yoshifumi Narumi, Ersan Altun, et al. Multiparametric Magnetic Resonance Imaging for Bladder Cancer: Development of VI-RADS (Vesical Imaging-Reporting and Data System). Eur Urol 2018;74:294–306
Authors: Valeria Panebianco, Jelle Barentsz, Yoshifumi Narumi, James W.F. Catto
Journal: European Urology (2018)
Abstract 11797: A Systematic Review and Meta-Analysis to Test the 'Timing Hypothesis' of Hormone Replacement Therapy and Cardiovascular Disease
Authors: Matthew Nudy, Andrew J Foy
Journal: Circulation (2017)

Introduction: The ‘Timing Hypothesis’ states that the benefits and harms of hormone replacement therapy (HRT) are related to the proximity with which it is begun following the onset of menopause. W...
The use of machine learning to understand the relationship between IgE to specific allergens and asthma
Authors: Thomas A. E. Platts-Mills, Matthew Perzanowski
Journal: PLoS Medicine (2018)

Thomas Platts-Mills and Matthew Perzanowski provide their expert Perspective on a translational study from Custovic and colleagues that identifies pairings of IgE that show value in estimating risk of concurrent asthma.
Abortion: US global gag rule is having “chilling effect” on sexual health service providers
Authors: Sophie Cousins
Journal: BMJ (2018)

Fear and confusion over the United States’ “global gag rule” on abortion has led to self censorship and over-implementation of the policy, experts on sexual and reproductive health and rights have warned.

The “global gag rule”—also known as the Mexico City Policy—prohibits foreign non-governmental organisations that receive US global health funding from providing legal abortion services or referrals and also bars advocacy for abortion law reform. The policy was reinstated and expanded by President Donald Trump when he took office.

Under previous Republican administrations the restrictions applied specifically to US family planning funds, but Trump’s expansion extended restrictions to an estimated $8.8bn (£6.84bn; €7.72bn) in US global health assistance, including funding for HIV, maternal and child …
Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer—Reply
Authors: Chelain R. Goodman, Jonathan B. Strauss
Journal: JAMA Oncology (2018)

In Reply We thank Drs Tsoutsou and Vozenin for their insightful comments regarding our recent article detailing the potential for using circulating tumor cell (CTC) status as a predictive biomarker for benefit of radiotherapy among patients with early-stage breast cancer.1
Association of Obesity With Mortality Over 24 Years of Weight History
Authors: Hanfei Xu, L. Adrienne Cupples, Andrew Stokes, Ching-Ti Liu
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Many studies of the association between obesity and mortality rely on weight status at a single point in time, making it difficult to adequately address bias associated with reverse causality. <h3>Objective</h3> To investigate the association between maximum body mass index (BMI) and all-cause mortality without the consequences of reverse causality. <h3>Design, Setting, and Participants</h3> Prospective cohort studies for the original and offspring cohorts of the Framingham Heart Study. The follow-up period started from baseline examination 13 for the original cohort and from baseline examination 6 for the offspring cohort and ended December 31, 2014. The analyses were conducted in 2017. Participants were 6197 individuals with 3478 deaths during a mean of 17 years of follow-up. <h3>Main Outcomes and Measures</h3> Maximum BMI over 24 years of weight history before the beginning of follow-up for all-cause mortality and cause-specific mortality. All-cause mortality and cause-specific mortality (deaths due to cardiovascular disease, cancer, or other causes). <h3>Results</h3> Among 6197 participants (mean [SD] age at baseline, 62.79 [8.98] years; 55.5% female), 3478 (56.1%) died during the follow-up. A monotonic association was observed between maximum BMI and mortality, with increasing risks observed across obese I (BMI of 30 to &lt;35; hazard ratio [HR], 1.27; 95% CI, 1.14-1.41) and obese II (BMI of 35 to &lt;40; HR, 1.93; 95% CI, 1.68-2.20) categories. A significant association was not observed for the overweight category (BMI of 25 to &lt;30; HR, 1.08; 95% CI, 0.99-1.18). Among never smokers, the risks increased, with a significant association emerging for individuals with maximum BMI in the overweight range (HR, 1.31; 95% CI, 1.13-1.51). The mortality rates of normal-weight individuals who were formerly overweight or obese were 47.48 and 66.67 per 1000 person-years, respectively, while individuals who never exceeded normal weight had a mortality rate of 27.93 per 1000 person-years. <h3>Conclusions and Relevance</h3> A monotonic association was found between maximum BMI over 24 years of weight history and subsequent all-cause mortality. Maximum BMI in the normal-weight range was associated with the lowest risk of mortality in this cohort, highlighting the importance of obesity prevention.
Moving Precision Oncology Forward Amid Myths and Misconceptions
Authors: Balkees Abderrahman, V. Craig Jordan
Journal: JAMA Oncology (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 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
Practice patterns, radiologic tumor response, and deterioration of liver function after transarterial chemoembolization (TACE): Final analysis of OPTIMIS in Korea and other regions
Authors: J. Heo, A.-L. Cheng, J.-L. Raoul, M. Peck-Radosavljevic, M. Kudo, K. Nakajima, I. Bayh, S.-M. Lin, H.C. Lee
Journal: Annals of Oncology (2018)
Abstract 12985: Addition of Smoking Status Improves Risk Prediction of Ischemic Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Younghoon Kwon, Faye L Lopez, Sunil K Agarwal, Elsayed Z Soliman, Gregory Y Lip, Alvaro Alonso, Lin Y Chen
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) is associated with increased risk of ischemic stroke and death. Current risk scores for stroke in AF do not include modifiable lifestyle risk factors. We studie...
Surviving Cancer in the Midst of a Treatment Revolution
Authors: Adam Philip Stern
Journal: JAMA Oncology (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 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
Diagnostic and Prognostic Utility of Cardiac Magnetic Resonance Imaging in Aortic Regurgitation
Authors: Andreas A Kammerlander, Matthias Wiesinger, Franz Duca, Stefan Aschauer, Christina Binder, Caroline Zotter Tufaro, Christian Nitsche, Roza Badre-Eslam, Robert Schönbauer, Philipp Bartko, Dietrich Beitzke, Christian Loewe, Christian Hengstenberg, Diana Bonderman, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2018)