tbuckley/cabot-search huggingface dataset:
Abstract MP026: Effects of Substituting Sedentary Behavior With Light and Moderate-to-vigorous Physical Activity on Obesity Indices in Adults
Authors: Bárbara B Gonze, Evandro F Sperandio, Antônio R Gagliardi, Marcello Romiti, Rodolfo L Arantes, Victor Z Dourado
Journal: Circulation (2017)

Sedentary behavior (SB) has emerged as an independent risk factor for the occurrence of cardiovascular problems and all-cause mortality. However, the deleterious effect of SB may be a consequence of replacing time spent in light and moderate-to-vigorous (MVPA) physical activities. Few studies have explored this topic, especially in prospective follow-up studies with adults. We hypothesized that substituting SB with light and MVPA may be associated with 1-year change in body weight, body mass index (BMI) and fat body mass (FBM) in asymptomatic adults. We aimed to use isotemporal substitution modeling to investigate cross-sectional and longitudinal effects of reallocating SB with light and MVPA on obesity indices in asymptomatic adults. Also, we examined the correlations between 1-year changes in physical activity intensity categories (i.e., sedentary, light, moderate, vigorous, very vigorous, and MVPA) and changes in FBM. We included 780 participants over the age of 20-yr. Body weight, BMI, and FBM (bioelectrical impedance), as well as its 1-year changes, were the outcomes. We objectively measured physical activity using triaxial accelerometers (ActiGraph GT3X) worn above the dominant hip during waking hours for at least four consecutive days (4-7 days). After 1-year follow-up, 242 completed all the assessments. We reallocated time spent in SB by light or MVPA and assessed the cross-sectional and prospective associations with the outcomes. The cross-sectional isotemporal substitution analysis showed that substituting 10-min blocks of SB with MVPA was significantly related to decreases of 1.23 kg in body weight, 0.30 kg/m2 in BMI and 0.38% in FBM. Substituting 10-min blocks of SB with light physical activity produced significant lower values of body weight (1 kg) and BMI (0.1 kg/m2). We found no effects of substituting SB with light physical activity on FBM. As for the longitudinal analysis, we observed that reallocating SB with MVPA was only associated with a significant decline in FBM (-0.31%). We found no other significant effects of substituting SB with light or MVPA. We observed significant correlations between change in FBM and changes in sedentary (r = 0.147), light (r = -0.290) and vigorous (r = -0.277) physical activity. After stepwise multiple regressions adjusted for all physical activity intensities and covariates, change in vigorous physical activity was the only intensity selected as a significant predictor for 1-year absolute change in FBM (β = -0.312; ΔR 2 = 0.102). We may conclude that SB presents non-consistent influence on obesity indices in asymptomatic adults and its substitution with MVPA is associated with significant improvement in body composition over a short-term follow-up. Our results suggest that vigorous physical activities play the most important role in obesity in adults.
Comprehensive Multi-Omics Analysis of Gene Fusions in a Large Multiple Myeloma Cohort
Authors: Steven M. Foltz, Qingsong Gao, Christopher J. Yoon, Amila Weerasinghe, Hua Sun, Lijun Yao, Mark A. Fiala, Daniel R. Kohnen, Justin King, Yeong Seok Ju, John F. DiPersio, Ravi Vij, Li Ding
Journal: Blood (2018)
High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients
Authors: Silje Halvorsen Sveaas, Annelie Bilberg, Inger Jorid Berg, Sella Arrestad Provan, Silvia Rollefstad, Anne Grete Semb, Kåre Birger Hagen, Melissa Woll Johansen, Elisabeth Pedersen, Hanne Dagfinrud
Journal: British Journal of Sports Medicine (2019)

Background Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown. Objective To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA). Method Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0–10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study. Results 97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: −0.6 [–0.8 to –0.3], p&lt;0.001 and BASDAI: −1.2 [–1.8 to –0.7], p&lt;0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health. Conclusion High intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients’ function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA. Trial registration number NCT02356874 .
Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment
Authors: Ana C. Garrido-Castro, Nancy U. Lin, Kornelia Polyak
Journal: Cancer Discovery (2019)

Abstract Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. To date, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in outcomes of patients with TNBC, and chemotherapy remains the standard of care. Here, we seek to review the most recent efforts to classify TNBC based on the comprehensive profiling of tumors for cellular composition and molecular features. Technologic advances allow for tumor characterization at ever-increasing depth, generating data that, if integrated with clinical–pathologic features, may help improve risk stratification of patients, guide treatment decisions and surveillance, and help identify new targets for drug development. Significance: TNBC is characterized by higher rates of relapse, greater metastatic potential, and shorter overall survival compared with other major breast cancer subtypes. The identification of biomarkers that can help guide treatment decisions in TNBC remains a clinically unmet need. Understanding the mechanisms that drive resistance is key to the design of novel therapeutic strategies to help prevent the development of metastatic disease and, ultimately, to improve survival in this patient population.
Abstract A17: Metronomic topotecan causes MYCN inactivation and impedes tumor growth selectively in MYCN-amplified neuroblastoma cells in vitro and in vivo by therapy-induced senescence
Authors: Sabine Taschner-Mandl, Teresa Gerber, Magdalena Schwarz, Johanna Blaha, Maximilian Kauer, Florian Kromp, Nelli Frank, Fikret Rifatbegovic, Tamara Weiss, Ruth Ladenstein, Martin Hohenegger, Inge M. Ambros, Peter F. Ambros
Journal: Cancer Research (2018)

Abstract Background: Poor prognosis and frequent relapses are major challenges for patients with high-risk neuroblastoma (NB), especially when tumors show MYCN amplification. High-dose chemotherapy triggers apoptosis, necrosis, and senescence, a cellular stress response leading to permanent proliferative arrest and a typical senescence-associated secretome (SASP). SASP components reinforce growth arrest and act in an immune-stimulatory fashion, while others are tumor promoting. Studies on low-dose long-term, i.e., metronomic, treatment schedules have demonstrated effects on the tumor microenvironment, but have not comprehensively analyzed cellular responses in tumor cells. Methods and Results: We evaluated efficacy and mode of action of low-dose metronomic treatment schedules in in vitro and in vivo NB models. Importantly, by using the secretome as a discriminator for beneficial versus adverse effects of senescence, drugs with a tumor-inhibiting SASP were identified. Our preclinical work has demonstrated that low-dose long-term topotecan (TPT) treatment (0.1 mg/kg/d, i.p., daily over 15 weeks) improves survival in mouse NB xenografts and leads to long-term cure in 40% of mice. TPT induces a tumor-inhibiting type of senescence, accompanied by changes in the tumor transcriptome and secretome, specifically in MYCN-amplified NB cells. As senescent NB cells showed a reduced MYCN copy number and strongly downregulated MYCN expression, we investigated the mechanism of MYCN inactivation. This showed that upon senescence MYCN is epigenetically silenced and gene copies are recruited to the nuclear periphery where changes in the nuclear lamina composition take place. Conclusion: This new mode of action of metronomic TPT treatment, i.e., promoting a tumor-inhibiting type of senescence selectively in MYCN-amplified neuroblastoma, is clinically relevant as metronomic regimens are increasingly implemented in therapy protocols of various cancer entities and are considered as a feasible maintenance treatment option with moderate adverse event profiles. Citation Format: Sabine Taschner-Mandl, Teresa Gerber, Magdalena Schwarz, Johanna Blaha, Maximilian Kauer, Florian Kromp, Nelli Frank, Fikret Rifatbegovic, Tamara Weiss, Ruth Ladenstein, Martin Hohenegger, Inge M. Ambros, Peter F. Ambros. Metronomic topotecan causes MYCN inactivation and impedes tumor growth selectively in MYCN-amplified neuroblastoma cells in vitro and in vivo by therapy-induced senescence [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A17.
Comprehensive Integrated Genomic Perturbations Reveal Molecular Mechanisms of Red Blood Cell Trait Associations
Authors: Yuxuan Wu, Mitchel A. Cole, Abdou Mousas, Jing Zeng, Qiuming Yao, Divya Vinjamur, Ryo Kurita, Yukio Nakamura, Luca Pinello, Guillame Lettre, Daniel E. Bauer
Journal: Blood (2018)
Abstract 14022: Associations Between Testosterone Levels and Mortality in Male Patients With Heart Failure
Authors: Satoshi Suzuki, Akiomi Yoshihisa, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Shunsuke Watanabe, Yuki Kanno, Makiko Tatsumi, Satoshi Abe, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: The age-related decline of circulating anabolic hormones in male is associated with increased morbidity and mortality. It has been reported that anabolic deficiency is associated with cachexia in patients with heart failure (HF). Thus, we aimed to investigate the impact of testosterone on prognosis of HF and underlying cardiac function, cardiac damage and exercise capacity. Methods and Results: We analyzed consecutive 618 male patients with HF (age 65.9 years), who admitted to our hospital. These patients were divided into 4 groups based on the serum levels of total testosterone (TT): 1st (TT >631 ng/dl, n=154), 2nd (462< TT ≤631 ng/dl, n=155), 3rd (300< TT ≤462 ng/dl, n=156) and 4th (TT ≤300 ng/dl, n=153) quartiles. Although age did not differ among the groups, in the Kaplan-Meier analysis (mean 1281 days), all-cause mortality progressively increased from 1st to 2nd, 3rd and 4th groups (Figure). In the Cox proportional hazard analysis, after adjusting for other potential confounding factors, ...
Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity
Authors: Maria J. Pereira, Jan W. Eriksson
Journal: Drugs (2019)

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.
PTH-034 Do faecal calprotectin levels influence colonoscopy rates?
Authors: Hesham Khalil, Paul Sherwood
Journal: Endoscopy (2018)

<h3>Introduction</h3> Faecal Calprotectin (FC) often helps clinicians to decide the need for colonoscopy in patient with variety of bowel symptoms. Many clinicians are uncomfortable with intermediately raised FC and tend to opt for colonoscopies to avoid the risk of missing an organic disease. The aim of this audit is to assess the influence the FC level on the rate colonoscopies and pathology found. <h3>Methods</h3> Data were collected from Northampton General Hospital database for all FC specimens tested between April 2015 and March 2016. We excluded all IBD patients and patients aged 18 and under. We compared patients who had an intermediately raised FC (IRFC) results (51–150), patients with significantly raised FC (SRFC) results (≥151) and a selected manageable sample with negative FC (≤50). <h3>Results</h3> 2169 patients were tested for FC. 501 had raised FCs. 79 known IBD patients were excluded. The remaining were 217 patient with IRFC and 205 with SRFC. 111 of the FC negative group from August 2015 were studied. Colonoscopies were done in 91 patients (42%) of the IRFC group, compared to 119 patients (58%) of SRFC. 24 patients (22%) with negative FC had colonoscopy. Age and gender had no influence on the colonoscopy rate, but FC significantly influenced the rate of colonoscopy referral (χ<sup>2</sup> test, p&lt;0.0001). 96% of the patients scoped with FC ≤50 had normal colonic mucosa; one patient aged 66 had an adenoma. 78/91 (86%) patients with IRFC, had normal colons, 6 patients were newly diagnosed with IBD and 7 patients were found to have other colonic pathologies. This included 2 cancers seen in patients aged 42 and 55 who had weight loss or rectal bleeding. In the SRFC group, 70/121 (58%) had normal colons. 30 patients (25%) were newly diagnosed with IBD and 21 patients were found to have other colonic pathologies including 6 cancers. <h3>Conclusions</h3> Faecal calprotectin significantly influences the rate of colonoscopy referral and outcome. There was good evidence to support colonoscopy in patients with FC &gt;150, but 86% of patients had normal colons with FC of 51–150 and a repeat FC in the absence of warning symptoms would be reasonable, particularly in younger patients.
Cost and Outcomes Information Should Be Part of Shared Decision Making—Reply
Authors: Margaret L. Schwarze, David Urbach, Kimberly E. Kopecky
Journal: JAMA Surgery (2019)

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
A Randomized Phase 3 Study, Sinus-52, Evaluating the Efficacy and Safety of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps
Authors: Claus Bachert, Martin Desrosiers, Joaquim Mullol, Peter W. Hellings, Anders Cervin, Lawrence Sher, John V. Bosso, Stella E. Lee, Jorge F. Maspero, Shigeharu Fujieda, Shoji Matsune, Xin Lu, Chunpeng Fan, Steven Draikiwicz, Nikhil Amin, Siddhesh Kamat, Asif Khan, Gianluca Pirozzi, Neil M.H. Graham, Marcella Ruddy, Heribert Staudinger, Leda P. Mannent
Journal: Journal of Allergy and Clinical Immunology (2019)
Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems
Authors: Kanghee Jo, Hyeongmin Kim, Prakash Khadka, Taejun Jang, Soo Jin Kim, Seong-Ha Hwang, Jaehwi Lee
Journal: Asian Journal of Pharmaceutical Sciences (2019)

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus (HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated self-microemulsifying drug delivery system (S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS. Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper self-microemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS. Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.
Elective Colonoscopy in Older Adults—Minimizing Risks
Authors: Kartik Sampath, Sameer D. Saini, Audrey H. Calderwood
Journal: JAMA Internal Medicine (2019)

This Teachable Moment describes the case of an elderly man who chose to undergo elective colonoscopy and polypectomy, possibly without a clear understanding of the risk-benefit imbalance of such a procedure.
Abstract 19131: The Advanced Life Support Termination of Resuscitation Rule: A Local Evaluation of the Impact on Termination Rates
Authors: Joris Nas, Judith L Bonnes, Dominique V Verhaert, Wessel Keuper, Pierre van Grunsven, Menko-Jan de Boer, Joep L Smeets, Marc A Brouwer
Journal: Circulation (2015)

Introduction: Termination of Resuscitation (TOR) rules have been designed to guide in-field termination decisions and reduce futile hospital transportations. The impact of such a rule may depend on regional infrastructure, arrest characteristics and pre-existent termination rates. Our region is characterized by high rates of bystander cardiopulmonary resuscitation (CPR), and Advanced Life Support (ALS) trained rescuers authorized to make termination decisions. We aim to investigate the actual in-field termination rates and the termination rates as recommended by the ALS-TOR rule. Furthermore, we studied factors associated with the actual termination decisions. Methods: Cohort of out-of-hospital cardiac arrest patients who were resuscitated in the Nijmegen area, the Netherlands (2008-2011). The ALS-TOR rule recommends termination in case all following criteria are met: unwitnessed arrest, no bystander CPR, no shock delivery, no return of spontaneous circulation (ROSC). Results: The observed percentage of in-field termination was 46% (275/598), while the ALS-TOR rule recommended termination in only 6% (35/588), owing to high percentages of witnessed arrests (73%) and bystander CPR (54%) in our region. Factors independently associated with the actual decisions to terminate resuscitation were absence of ROSC [aOR 35.6 (95% CI 18.3-69.3)], non-shockable initial rhythm [aOR 6.0 (95% CI 3.2-11.0)], unwitnessed arrest [aOR 2.7 (95% CI 1.4-5.2)], non-public arrest [aOR 2.5 (95% CI 1.2-5.0)] and longer EMS-response times [aOR 1.1 per minute increase (95% CI 1.0-1.2)]. Conclusions: Contrary to previous studies, implementation of the ALS-TOR rule in our region would have decreased termination rates from almost half to less than 10% due to the favourable arrest characteristics. In light of the prognosis after OHCA, this finding suggests that adherence to this set of criteria does not contribute to efficient triage in our population. Therefore it seems prudent to locally evaluate the utility of the ALS-TOR rule prior to implementation.