tbuckley/cabot-search huggingface dataset:
Diurnal rhythms (DR) in gene expression in human oral mucosa: Implications for gender differences in toxicity, response and survival and optimal timing of targeted therapy (Rx)
Authors: G. A. Bjarnason, A. Seth, Z. Wang, N. Blanas, M. Straume, T. A. Martino
Journal: Journal of Clinical Oncology (2007)

2507 Background: DR in processes relevant to oncology, including cell cycle, apoptosis, and angiogenesis, have been demonstrated (Nat Rev Cancer 3:350, Cancer Res 63:7277). In rodents, 10–20% of the genome has a 24-hour (h) rhythm in RNA expression (Cell 109:307). A molecular clock consisting of transcription/translation feedback loops of clock-genes controls this rhythmicity (Nat Rev Neurosci 4:649). We studied, for the first time, daily whole genome RNA expression patterning in healthy human volunteers. Methods: RNA samples extracted from oral mucosa biopsies (bx) obtained every 4h over 24h (6 bx) from 5 males (M) and 5 females (F) were subjected to microarray analysis (Affymetrix HG_U133_Plus2 chip, 54,679 transcripts). COSOPT, designed for circadian microarray time series analysis (Methods Enzymol 383: 149) was used to detect genes with significant rhythms (pMMC-Beta = 0.1). Expression patterns were visualized in GeneSpring GX7.3 (Agilent) and validated by real-time PCR and ANOVA. Results: There were 801 and 810 rhythmic genes in M and F respectively, with most genes peaking at 4AM or 4PM in M but at 6AM or 11AM in F. Only 90 rhythmic genes (including core clock-genes and clock controlled genes) were common to M and F, with over 700 genes only rhythmic in M and not in F and vice versa. The profiles of clock- genes and clock-controlled genes were inverted relative to the nocturnal rodent data. There were 75 and 67 rhythmic transcription factor genes in M and F respectively, with 28 common to both M and F. There were 71 rhythmic human cancer genes (Nat Rev Cancer 4:177) with significant gender differences. This group includes rhythmic gene products involved in signaling pathways currently targeted for cancer Rx. Conclusions: We show for the first time a significant gender specific DR in gene expression involving multiple genes of interest in oncology. This may contribute to the documented gender differences in toxicity, response and survival (J Clin Onc 24: 3562, NEJM 353:133), and can inform future trials of optimal timing of antisense Rx and other targeted Rx. The inverted DR in rodents vs. humans has implications for translating rodent data to human Rx trials. No significant financial relationships to disclose.
Association Between Genetic Variation in <i>FOXO3</i> and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis
Authors: Sebastien Viatte, James C. Lee, Bo Fu, Marion Espéli, Mark Lunt, Jack N. E. De Wolf, Lily Wheeler, John A. Reynolds, Madhura Castelino, Deborah P. M. Symmons, Paul A. Lyons, Anne Barton, Kenneth G. C. Smith
Journal: Arthritis & Rheumatology (2016)

Objective Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte‐driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. Methods Collagen‐induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss‐of‐function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C‐reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. Results Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin‐6 in the blood. Similarly, rs12212067 (a single‐nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. Conclusion Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage.
TCT-14 Specialist Chronic Total Occlusion (CTO) Programmes and Outcomes after CTO Percutaneous Coronary Interventions: An observational study of 5,496 patients from the Pan-London CTO Cohort
Authors: Daniel Jones, Krishnaraj Rathod, Roshan Weerackody, Andrew Wragg, Elliot Smith
Journal: Journal of the American College of Cardiology (2016)
Clonal Evolution and Clinical Significance of Copy Number Neutral Loss of Heterozygosity of Chromosome Arm 6p in Acquired Aplastic Anemia
Authors: Marisol Betensky, Daria V. Babushok, Jacquelyn J. Roth, Philip J Mason, Jaclyn A. Biegel, Curt Lind, Dimitrios Monos, Monica Bessler, Timothy S. Olson
Journal: Blood (2014)
Phase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2+ breast cancer.
Authors: Otto Metzger-Filho, William Thomas Barry, Ian E. Krop, W. Jerry Younger, Elizabeth S Lawler, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2014)

TPS660 Background: Central nervous system (CNS) metastases remain an important cause of morbidity and death for patients diagnosed with HER2+ breast cancer (BC). ONT-380 is an orally active reversible and selective HER2 inhibitor. In pre-clinical studies ONT-380 showed superior CNS penetration and improved overall survival (OS) when compared with lapatinib. In a previous phase I study, ONT-380 demonstrated an acceptable safety profile, with a low incidence and severity of diarrhea and rash. Dose limiting toxicity was represented by transient and reversible transaminases elevation. Clinical activity was observed. We therefore designed a Phase I clinical trial combining ONT-380 with trastuzumab for patients diagnosed with HER2+ BC and CNS metastases. Methods: This is an open-label, dose finding phase I study. The primary objectives are to determine the maximum-tolerated dose and schedule of ONT-380 in combination with trastuzumab in patients with HER2+ BC and CNS metastases. Secondary objectives include CNS objective response rate by RECIST and volumetric criteria, progression-free survival and OS. Correlative science analysis includes collection of circulating tumor cells at baseline and time of progression for molecular characterization, including FISH studies for EGFR, HER2, Met, and Myc. The study has two parallel arms with two dose regimens of ONT-380, either twice-daily or once-daily, in combination with standard dose trastuzumab. The dose level of ARRY-380 in the initial and subsequent dose escalation cohorts will be 450 and 600mg for the BID regimen and 750, 900, 1200mg for the QD regimen. Eligibility criteria include measurable disease in the CNS, ECOG performance status 0 to 2, and no limit on prior therapies. We utilize a 3+3 dose escalation design with an expansion phase of 16 participants per arm, which will provide additional information on the safety and biologic activity of the treatment combination. In addition, 16 participants per arm at the MTD will give an 89% probability of selecting the best regimen under a “pick the winner” selection design if true probabilities of clinical benefit are 10% and 30% respectively. Clinical trial information: NCT01921335.
Non-Dynamic Association of Depressive and Anxiety Disorders With Leukocyte Telomere Length?
Authors: Ezra Susser, Simon Verhulst, Jeremy D. Kark, Pam R. Factor-Litvak, Katherine Keyes, Per Magnus, Abraham Aviv
Journal: American Journal of Psychiatry (2016)

TO THE EDITOR: We applaud the attempt of Verhoeven and colleagues (1) to examine the relationship over time between depressive and anxiety disorders and leukocyte telomere length (LTL) shortening.We propose, however, that the absence of a relationship in their data may be due to measurement error.For the following reasons, measurement precision in their study was low relative to the effect that was assessed; that is, the variation related to depression or anxiety in the LTL shortening slope, which was on average 13.3 base pairs (bp) per year:
TCT-427 Comparison of Neointimal Coverage Patterns between Biodegradable Vascular Stents and Drug Eluting Stents using Optical Coherence tomography: A Meta-Analysis
Authors: Pradyumna Agasthi, Sivakanth Aloor, Vivek Menon, Kwan Lee, Gautam Kumar, Rajesh Sachdeva
Journal: Journal of the American College of Cardiology (2016)
An Unusually Wide QRS Complex Tachycardia in a Patient With Hemodynamic Instability
Authors: Yue-Chun Li, Jia-Feng Lin, Peng Chen
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
TCT-221 Predictors of optimal medical therapy on discharge after percutaneous coronary intervention for acute coronary syndrome: An analysis of the PROMETHEUS registry
Authors: Serdar Farhan, Usman Baber, Jaya Chandrasekhar, Samantha Sartori, Melissa Aquino, Gennaro Giustino, Annapoorna Kini, William Weintraub, Sunil Rao, Samir Kapadia, Sandra Weiss, Craig Strauss, Catalin Toma, J. Brent Muhlestein, Anthony DeFranco, Mark Effron, Stuart Keller, Brian Baker, Stuart Pocock, Timothy Henry, Roxana Mehran
Journal: Journal of the American College of Cardiology (2016)
AOP2014, a Novel Peg-Proline-Interferon Alpha-2b with Improved Pharmacokinetic Properties, Is Safe and Well Tolerated and Shows Promising Efficacy in Patients with Polycythemia Vera (PV)
Authors: Heinz Gisslinger, Robert Kralovics, Bettina Gisslinger, Daniel Lechner, Veronika Buxhofer-Ausch, Karin Strecker, Guenther Gastl, Ella Willenbacher, Richard Greil, Alexander Egle, Thomas Melchardt, Sonja Burgstaller, Ernst Schloegl, Franz-Josef Tarmann, Michael Zoerer, Christoph Klade, Oleh Zahriychuk, Josef Thaler
Journal: Blood (2012)
TCT-473 A Randomized Comparison of Biodegradable Polymer- and Permanent Polymer-coated Platinum Chromium Everolimus-Eluting Coronary Stents in China: EVOLVE China Study
Authors: Yaling Han, Yuejin Yang, Guosheng Fu, Xi Su, Tiemin Jiang, Wenyue Pang, Jiyan Chen, Zuyi Yuan, Hui Li, Haichang Wang, Tao Hong, Huiliang Liu, Fucheng Sun, Dominic J. Allocco, Mingdong Zhang, Keith Dawkins
Journal: Journal of the American College of Cardiology (2016)
Mammalian target of rapamycin (mTOR)-induced pneumonitis: Single-institution experience and treatment.
Authors: D. Y. Kahn, A. C. Mita, B. J. George, K. K. Sankhala, D. Mahalingam, K. R. Kelly, A. B. Karnad, J. Sarantopoulos, M. M. Mita
Journal: Journal of Clinical Oncology (2010)

e13520 Background: Pulmonary toxicity is a class-effect associated with mTOR inhibitors. The aim of this assessment was to review the Cancer Therapy and Research Center (CTRC) experience with pulmonary toxicity of temsirolimus (T) and ridaforolimus (R), to characterize the drug-induced pneumonitis (DIP) associated with these agents, and to propose a management algorithm. Methods: A retrospective analysis of patients (pts) enrolled in any clinical trial using T or R at CTRC from 2001 to 2008 was performed. Pts were allowed to receive any formulation (IV/oral), dose or schedule of either drug. Pts from phase I studies whose endpoint was maximum tolerated dose were also included. Demographics, clinical and radiographic manifestation compatible with interstitial pneumonitis, DIP treatment, and response for each pt were recorded. Results: 199 pts were reviewed, 77 treated with T and 122 with R. 4 pts (5%) on T and 13 pts (11%) on R had findings compatible with DIP by CT imaging and pulmonology evaluation. These were described as interstitial infiltrates and/or ground glass opacities. Pathologic documentation in 3 pts was consistent with lymphocytic alveolitis/interstitial infiltrates. Two pts developed DIP after successive treatment with either drug, thus supporting the hypothesis of a class-effect. DIP resolved with drug interruption and a prednisone taper regimen 40mg qd ×7 days, then 20mg qd ×7 days, then 10mg qd ×14 days. No DIP-related death was recorded. Full-dose treatment with mTOR inhibitors was successfully resumed after resolution of radiologic and clinical abnormalities in 5 pts who had documented clinical benefit (CB= PR or SD>6mo). CB was documented in 2/4 pts (50%) and 9/13 pts (69%) with suspected T-and R-induced pulmonary toxicity, respectively. One pt had 3 episodes of reversible DIP while treated with R over 5+ years. Conclusions: This large, single institution, retrospective assessment demonstrates that mTOR induced pneumonitis is a class-effect, reversible with drug interruption and brief corticosteroid treatment. Therapy can usually be resumed following treatment of DIP. A better understanding of mTOR induced pneumonitis will be derived from randomized, controlled trials. No significant financial relationships to disclose.
İrritable Bağırsak Sendromu ve Fonksiyonel Şişkinlikte Kolonik Distansiyon Algısında Kolonik Fermentasyonun Rolü
Authors: Michele Di Stefano, Emanuela Miceli, Antonio Missanelli, Samanta Mazzocchi, Paola Tana ve Gino Roberto Corazza
Journal: Clinical Gastroenterology and Hepatology (2006)
Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial
Authors: D. Torfoss, T. Fladhagen, H. Holte, L. Brinch, F.H. Schjesvold, Y. Fløisand, E. Nyquist, J. Dalgaard, P. Meyer, A.K. Lehmann, J. Hammerstrøm, T. Skjelbakken, E.A. Høiby, L. Sandvik, S. Kvaløy
Journal: Clinical Microbiology and Infection (2016)
Change in commute mode and body-mass index: prospective, longitudinal evidence from UK Biobank
Authors: Ellen Flint, Elizabeth Webb, Steven Cummins
Journal: The Lancet Public Health (2016)

Insufficient physical activity is a determinant of obesity and cardiovascular disease. Active travel to work has declined in high-income countries in recent decades. We aimed to determine which socioeconomic and demographic characteristics predicted switching to or from active commuting, whether switching from passive to active commuting (or the reverse) independently predicts change in objectively measured body-mass index (BMI), and to ascertain whether any association is attenuated by socioeconomic, demographic, or behavioural factors.This study used longitudinal data from UK Biobank. Baseline data collection occurred at 22 centres between March, 2006, and July, 2010, with a repeat assessment at one centre (Stockport) between August, 2012, and June, 2013, for a subset of these participants. Height and weight were objectively measured at both timepoints. We included individuals present at both timepoints with complete data in the analytic sample. Participants were aged 40-69 years and commuted from home to a workplace on a regular basis at both baseline and follow-up. Two exposures were investigated: transition from car commuting to active or public transport commuting and transition from active or public transport to car commuting. Change in BMI between baseline and repeat assessment was the outcome of interest, assessed with bivariate and multivariate logistic regression models.502 656 individuals provided baseline data, with 20 346 participating in the repeat assessment after a median of 4·4 years (IQR 3·7-4·9). 5861 individuals were present at both timepoints and had complete data for all analytic variables. Individuals who transitioned from car commuting at baseline to active or public transportation modes at follow-up had a decrease in BMI of -0·30 kg/m2 (95% CI -0·47 to -0·13; p=0·0005). Conversely, individuals who transitioned from active commuting at baseline to car commuting at follow-up had a BMI increase of 0·32 kg/m2 (0·13 to 0·50; p=0·008). These effects were not attenuated by adjustment for hypothesised confounders. Change in household income emerged as a determinant of commute mode transitions.Incorporation of increased levels of physical activity as part of the commute to work could reduce obesity among middle-aged adults in the UK.UK Medical Research Council.
Platelet Responsiveness to Aspirin Loading in Patients with ST Elevation MI Undergoing Primary Percutaneous Intervention Is Associated with Myocardial Reperfusion and Clinical Outcome.
Authors: Davi d Varon, Shlomi Matetzky, Paul Fefer, Boris Shenkman, Michael Shechter, Nitza Levi, Naphtali Savion, Hanoch Hod
Journal: Blood (2008)
Clinical Experience of Bendamustine Treatment for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Spanish Registry.
Authors: Blanca Sanchez-Gonzalez, Francisco Javier Peñalver, Helga Guillen, Marta Calleja, Raquel de Oña, Araceli Canovas, Mercedes Gironella, Reyes Arranz, Ignacio de la Fuente, Carlos Grande, Ricardo Perez, Juan Manuel Sancho, Eva Domingo, Jose Luis Lopez-Lorenzo, Elena Prieto, Inmaculada Perez, Carlos Panizo, Ana Gorosquieta, Miguel Marin, Jose Manuel Cervera, Antonio Salar
Journal: Blood (2009)
Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes
Authors: Kazuhiro Suzuki, Yuki Hayano, Akiko Nakai, Fumika Furuta, Masaki Noda
Journal: The Journal of Experimental Medicine (2016)

Various aspects of the immune system display circadian rhythms. Although lymphocyte trafficking has been suggested to show diurnal variations, the mechanisms and influences on immune responses are unclear. Here, we show in mice that inputs from adrenergic nerves contribute to the diurnal variation of lymphocyte recirculation through lymph nodes (LNs), which is reflected in the magnitude of the adaptive immune response. Neural inputs to β2-adrenergic receptors (β2ARs) expressed on lymphocytes reduced the frequency of lymphocyte egress from LNs at night, which was accompanied by an increase of lymphocyte numbers in LNs. Immunization during the period of lymphocyte accumulation in LNs enhanced antibody responses. The diurnal variation of the humoral immune response was dependent on β2AR-mediated neural signals and was diminished when lymphocyte recirculation through LNs was stopped. This study reveals the physiological role of adrenergic control of lymphocyte trafficking in adaptive immunity and establishes a novel mechanism that generates diurnal rhythmicity in the immune system.
DISECCIÓN SUBMUCOSA ENDOSCÓPICA COLORRECTAL EN DOS CENTROS ESPAÑOLES. UNA CURVA DE APRENDIZAJE PROMETEDORA EN UNA SERIE DE 98 CASOS
Authors: M López Gómez, M Hernández Conde, J Santiago García, C González Lois, P Matallanos, E Blazquez, JC Fernández Rial, JL Calleja Panero, L Abreu García, A Herreros De Tejada
Journal: Endoscopy (2016)

Introducción: La disección submucosa endoscópica (DSE) es la técnica de elección para el manejo de neoplasias colorrectales precoces de gran tamaño, sospecha de fibrosis submucosa y/o con adenocarcinoma focal o mínimamente invasivo.
Perioperative chemotherapy with bevacizumab (BV) for liver metastases (LM) in colorectal cancer (CRC): McGill University pilot study
Authors: N. Bouganim, P. Kavan, M. Eid, P. Metrakos, P. Chaudhury, G. Batist
Journal: Journal of Clinical Oncology (2009)

e15027 Background: Colorectal liver metastases treated with perioperative chemotherapy were previously shown to increase progression free survival. Given the survival benefit of bevacizumab in metastatic CRC, the aim of this study was to assess the efficacy and safety of bevacizumab based chemotherapy in the perioperative setting. Methods: In this single arm prospective pilot study, patients with resectable LM eligible to receive perioperative BV and chemotherapy were included. Kaplan Meier survival analysis was used to calculate overall survival and progression free survival. Results: A total of 60 patients were recruited, 41 male, with an average age of 55. Forty-three patients had synchronous LM. All but seven patients received pre and post-operative BV-based chemotherapy (34/60 oxaliplatin based, 22/60 CPT-11 based and 4/60 CPT-11 and oxaliplatin based). All patients underwent hepatectomy 6–8 weeks post last dose of BV. Overall response rate was 80% (48/60), 4pt with stable diseaase; 10% had a complete pathological response and 27% had no evidence of disease post hepatectomy with a median follow up of 33 months.8 patients progressed prior to surgery. Overall survival (OS) rates at 12, 24, 36 and 48 months were: 100%, 86%, 74% and 66% respectively and 5 year median survival of 55%. Progression free survival (PFS) was 14 months. Subgroup analysis of the data according to the chemotherapy pts received showed that PFS in the CPT-11 and the oxaliplatin arm were 13 and 15 months respectively. Most of the adverse events recorded were associated with the post-operative period and included wound healing (8pts), infections (2pts) and thromboemblic (6pts) disease. No sudden deaths or bowel perforations were reported. Conclusions: Bevacizumab-containing chemotherapy regimens in the peri-operative setting is effective in patients with colorectal liver metastases. Our 80% response rate and 10% complete pathological response is one of the highest reported and warrants further investigation in phase III trials. [Table: see text]
Successful Salvage Therapy By Idelalisib Followed By Haploidentical Allogenic Transplantation of an Alemtuzumab-Refractory T-Cell Prolymphocytic Leukemia
Authors: Julien Lenglet, Amélie Trinquand, Ludovic Lhermitte, Ali Bazarbachi, Laurent Frenzel, Olivier Tournilhac, Olivier Hermine
Journal: Blood (2015)
Abstract 3462: Pre-hospital 12 Lead ECG with Activation of Catheterization Lab Team Significantly Reduces Door to Balloon Time in STEMI
Authors: Jason P Brown, Ehtisham Mahmud, Ori Ben-Yehuda
Journal: Circulation (2006)

Background: Reducing door to balloon time in primary PCI for ST Elevation MI is a quality priority. Paramedic performed pre-hospital 12 lead ECG and activation of the cath lab may allow for signifi...
Luspatercept (ACE-536) Reduces Disease Burden, Including Anemia, Iron Overload, and Leg Ulcers, in Adults with Beta-Thalassemia: Results from a Phase 2 Study
Authors: Antonio Piga, Silverio Perrotta, M.Rita Gamberini, Ersi Voskaridou, Angela Melpignano, Aldo Filosa, Antonello Pietrangelo, Vincenzo Caruso, Gian Luca Forni, Xiaosha Zhang, Ashley Bellevue, Dawn Wilson, Abderrahmane Laadem, Matthew L. Sherman, Kenneth M. Attie
Journal: Blood (2015)