tbuckley/cabot-search huggingface dataset:
Effects of Aerobic and Resistance Exercise on Metabolic Syndrome, Sarcopenic Obesity, and Circulating Biomarkers in Overweight or Obese Survivors of Breast Cancer: A Randomized Controlled Trial
Authors: Christina M. Dieli-Conwright, Kerry S. Courneya, Wendy Demark-Wahnefried, Nathalie Sami, Kyuwan Lee, Thomas A. Buchanan, Darcy V. Spicer, Debu Tripathy, Leslie Bernstein, Joanne E. Mortimer
Journal: Journal of Clinical Oncology (2018)

Purpose Metabolic syndrome is associated with an increased risk of cardiovascular disease, type 2 diabetes, and breast cancer recurrence in survivors of breast cancer. This randomized controlled trial assessed the effects of a 16-week combined aerobic and resistance exercise intervention on metabolic syndrome, sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary, overweight, or obese survivors of breast cancer. Methods Eligible survivors of breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care (n = 50). The exercise group participated in supervised moderate-to-vigorous—65% to 85% of heart rate maximum—aerobic and resistance exercise three times per week for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity, and serum biomarkers were measured at baseline, postintervention (4 months), and 3-month follow-up (exercise only). Results Participants were age 53 ± 10.4 years, 46% were obese, and 74% were ethnic minorities. Adherence to the intervention was 95%, and postintervention assessments were available in 91% of participants. Postintervention metabolic syndrome z-score was significantly improved in exercise versus usual care (between-group difference, −4.4; 95% CI, −5.9 to −2.7; P &lt; .001). Sarcopenic obesity (appendicular skeletal mass index, P = .001; body mass index, P = .001) and circulating biomarkers, including insulin ( P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001), were significantly improved postintervention compared with usual care. At 3-month follow-up, all metabolic syndrome variables remained significantly improved compared with baseline in the exercise group ( P &lt; .01). Conclusion Combined resistance and aerobic exercise effectively attenuated metabolic syndrome, sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of sedentary, overweight, or obese survivors of breast cancer. Our findings suggest a targeted exercise prescription for improving metabolic syndrome in survivors of breast cancer and support the incorporation of supervised clinical exercise programs into breast cancer treatment and survivorship care plans.
Abstract 434: Sirt4 Accelerates Ang II-induced Pathological Cardiac Hypertrophy by Inhibiting Mnsod Activity
Authors: Depei Liu, Yu-Xuan Luo, Xiaoqiang Tang, Xi-Zhou An, Xue-Min Xie, Xiao-Feng Chen, Xiang Zhao, De-Long Hao, Hou-Zao Chen
Journal: Circulation Research (2016)

Aims: Oxidative stress contributes to the development of cardiac hypertrophy and heart failure. One of the mitochondrial sirtuins, Sirt4, is highly expressed in the heart, but its function remains unknown. The aim of the present study was to investigate the role of Sirt4 in the pathogenesis of pathological cardiac hypertrophy and the molecular mechanism by which Sirt4 regulates mitochondrial oxidative stress. Methods and results: Male C57BL/6 Sirt4 knockout mice, transgenic mice exhibiting cardiac-specific overexpression of Sirt4 (Sirt4-Tg) and their respective controls were treated with angiotensin II (Ang II). At 4 weeks, hypertrophic growth of cardiomyocytes, fibrosis and cardiac function were analyzed. Sirt4 deficiency conferred resistance to Ang II infusion by significantly suppressing hypertrophic growth, and the deposition of fibrosis. In Sirt4-Tg mice, aggravated hypertrophy and reduced cardiac function were observed compared with non-transgenic mice following Ang II treatment. Mechanistically, Sirt4 inhibited the binding of manganese superoxide dismutase (MnSOD) to Sirt3, another member of the mitochondrial sirtuins, and increased MnSOD acetylation levels to reduce its activity, resulting in elevated reactive oxygen species (ROS) accumulation upon Ang II stimulation. Furthermore, inhibition of ROS with MnTBAP, a mimetic of SOD, blocked the Sirt4-mediated aggravation of the hypertrophic response in Ang II-treated Sirt4-Tg mice. Conclusions: Sirt4 promotes hypertrophic growth and cardiac dysfunction by increasing ROS levels upon pathological stimulation. These findings reveal a role of Sirt4 in pathological cardiac hypertrophy, providing a new potential therapeutic strategy for this disease.
Epidemiology, Clinical Features, and Outcome of HTLV-1 Related Adult T-Cell Leukemia-Lymphoma in a Prevalent Area in the United States
Authors: Luis E Malpica Castillo, Agustin Pimentel, Isildinha M Reis, Eduardo Gotuzzo, Lazaros J. Lekakis, Krishna Komanduri, Thomas J. Harrington, Glen N. Barber, Juan Carlos Ramos
Journal: Blood (2017)
The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study
Authors: Thuy-Nhien Nguyen, Lorenz von Seidlein, Tuong-Vy Nguyen, Phuc-Nhi Truong, Son Do Hung, Huong-Thu Pham, Tam-Uyen Nguyen, Thanh Dong Le, Van Hue Dao, Mavuto Mukaka, Nicholas PJ Day, Nicholas J White, Arjen M Dondorp, Guy E Thwaites, Tran Tinh Hien
Journal: The Lancet Infectious Diseases (2018)

BackgroundA substantial proportion of Plasmodium species infections are asymptomatic with densities too low to be detectable with standard diagnostic techniques. The importance of such asymptomatic plasmodium infections in malaria transmission is probably related to their duration and density. To explore the duration of asymptomatic plasmodium infections and changes in parasite densities over time, a cohort of participants who were infected with Plasmodium parasites was observed over a 2-year follow-up period.MethodsIn this open cohort study, inhabitants of four villages in Vietnam were invited to participate in baseline and subsequent 3-monthly surveys up to 24 months, which included the collection of venous blood samples. Samples were batch-screened using ultra-sensitive (u)PCR (lower limit of detection of 22 parasites per mL). Participants found to be infected by uPCR during any of these surveys were invited to join a prospective cohort and provide monthly blood samples. We estimated the persistence of Plasmodium falciparum and Plasmodium vivax infections and changes in parasite densities over a study period of 24 months.FindingsBetween Dec 1, 2013, and Jan 8, 2016, 356 villagers participated in between one and 22 surveys. These study participants underwent 4248 uPCR evaluations (11·9 tests per participant). 1874 (32%) of 4248 uPCR tests indicated a plasmodium infection; 679 (36%) of 1874 tests were P falciparum monoinfections, 507 (27%) were P vivax monoinfections, 463 (25%) were co-infections with P falciparum and P vivax, and 225 (12%) were indeterminate species of Plasmodium. The median duration of P falciparum infection was 2 months (IQR 1–3); after accounting for censoring, participants had a 20% chance of having parasitaemia for 4 months or longer. The median duration of P vivax infection was 6 months (3–9), and participants had a 59% chance of having parasitaemia for 4 months or longer. The parasite densities of persistent infections oscillated; following ultralow-density infections, high-density infections developed frequently.InterpretationPersistent largely asymptomatic P vivax and P falciparum infections are common in this area of low seasonal malaria transmission. Infections with low-density parasitaemias can develop into much higher density infections at a later time, which are likely to sustain malaria endemicity.FundingThe Wellcome Trust, Bill & Melinda Gates Foundation.
Application of cell sheet technology for regenerative medicine: therapeutic angiogenesis and beyond
Authors: P. Makarevich, Boldyreva, K.V. Dergilev, P.P. Nimiritskiy, E.K. Shevchenko, O.A. Makarevich, E.Y. Efimenko, N.A. Alexandrushkina, V.A. Tkachuk, H. Yu-Chen, E.V. Parfyonova
Journal: Molecular Therapy (2017)
The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial
Authors: Pleun Joppe van Duijn, Walter Verbrugghe, Philippe Germaine Jorens, Fabian Spöhr, Dirk Schedler, Maria Deja, Andreas Rothbart, Djillali Annane, Christine Lawrence, Jean-Claude Nguyen Van, Benoit Misset, Matjaz Jereb, Katja Seme, Franc Šifrer, Viktorija Tomiç, Francisco Estevez, Jandira Carneiro, Stephan Harbarth, Marinus Johannes Cornelis Eijkemans, Marc Bonten, Herman Goossens, Surbhi Malhotra-Kumar, Christine Lammens, Jordi Vila, Ignaci Roca
Journal: The Lancet Infectious Diseases (2018)
Phenotypes of organ involvement in sarcoidosis
Authors: Jonas Christian Schupp, Sandra Freitag-Wolf, Elena Bargagli, Violeta Mihailović-Vučinić, Paola Rottoli, Aleksandar Grubanovic, Annegret Müller, Arne Jochens, Lukas Tittmann, Jasmin Schnerch, Carmela Olivieri, Annegret Fischer, Dragana Jovanovic, Snežana Filipovic, Jelica Videnovic-Ivanovic, Paul Bresser, René Jonkers, Kate O'Reilly, Ling-Pei Ho, Karoline I. Gaede, Peter Zabel, Anna Dubaniewicz, Ben Marshall, Robert Kieszko, Janusz Milanowski, Andreas Günther, Anette Weihrich, Martin Petrek, Vitezslav Kolek, Michael P. Keane, Sarah O'Beirne, Seamas Donnelly, Sigridur Olina Haraldsdottir, Kristin B. Jorundsdottir, Ulrich Costabel, Francesco Bonella, Benoît Wallaert, Christian Grah, Tatjana Peroš-Golubičić, Mauritio Luisetti, Zamir Kadija, Stefan Pabst, Christian Grohé, János Strausz, Martina Vašáková, Martina Sterclova, Ann Millar, Jiří Homolka, Alena Slováková, Yvonne Kendrick, Anjali Crawshaw, Wim Wuyts, Lisa Spencer, Michael Pfeifer, Dominique Valeyre, Venerino Poletti, Hubertus Wirtz, Antje Prasse, Stefan Schreiber, Michael Krawczak, Joachim Müller-Quernheim
Journal: European Respiratory Journal (2018)

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.
Inotuzumab Ozogamicin in Combination with Bosutinib for Patients with Relapsed or Refractory Ph+ ALL or CML in Lymphoid Blast Phase
Authors: Nitin Jain, Jorge E. Cortes, Farhad Ravandi, Marina Konopleva, Yesid Alvarado, Tapan Kadia, William G Wierda, Gautam Borthakur, Kiran Naqvi, Naveen Pemmaraju, Courtney D. DiNardo, Naval Daver, Musa Yilmaz, Keyur Patel, Debra Bull Linderman, Rebecca Garris, Elias J. Jabbour, Hagop M. Kantarjian
Journal: Blood (2017)
Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury
Authors: Alastair Proudfoot, Andrew Bayliffe, Cecilia M O’Kane, Tracey Wright, Adrian Serone, Philippe Jean Bareille, Vanessa Brown, Umar I Hamid, Younan Chen, Robert Wilson, Joanna Cordy, Peter Morley, Ruud de Wildt, Stuart Elborn, Matthew Hind, Edwin R Chilvers, Mark Griffiths, Charlotte Summers, Daniel Francis McAuley
Journal: Thorax (2018)

Background Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects. Methods We investigated the in vitro effects of GSK1995057 on human pulmonary microvascular endothelial cells (HMVEC-L) and then assessed the effects of pretreatment with nebulised GSK1995057 in a non-human primate model of acute lung injury. We then tested translation to humans by investigating the effects of a single nebulised dose of GSK1995057 in healthy humans (n=37) in a randomised controlled clinical trial in which subjects were subsequently exposed to inhaled endotoxin. Results Selective inhibition of TNFR1 signalling potently inhibited cytokine and neutrophil adhesion molecule expression in activated HMVEC-L monolayers in vitro (P&lt;0.01 and P&lt;0.001, respectively), and also significantly attenuated inflammation and signs of lung injury in non-human primates (P&lt;0.01 in all cases). In a randomised, placebo-controlled trial of nebulised GSK1995057 in 37 healthy humans challenged with a low dose of inhaled endotoxin, treatment with GSK1995057 attenuated pulmonary neutrophilia, inflammatory cytokine release (P&lt;0.01 in all cases) and signs of endothelial injury (P&lt;0.05) in bronchoalveolar lavage and serum samples. Conclusion These data support the potential for pulmonary delivery of a selective TNFR1 dAb as a novel therapeutic approach for the prevention of acute respiratory distress syndrome. Trial registration number ClinicalTrials.gov NCT01587807 .
Clinical implication of JAK2V167F-positive chronic myeloproliferative disorders: semi-quantitative Analysis of Mutated allele by sequence-specific primer-single molecule fluorescence detection assay
Authors: Kazuma Ohyashiki, Yasuo Aota, Akihiko Goto, Daigo Akahane, Junko Ohyashiki
Journal: Cancer Research (2007)

153  To ascertain the biological and clinical significance of JAK2V617F in chronic myeloprolifertive disorders (CMPD), we studied JAK2V617F in 211 individuals, including 94 patients with CMPD, using the sequence-specific primer-single molecule fluorescence detection (SSP-SMFD) assay. The JAK2V617F-positive PV patients with the WHO criteria (92.6%) had elevated leukocytes and platelets with a high incidence of chemotherapy requirement; patients with homozygous JAK2V617F frequently evolved into myelofibrosis and had palpable splenomegaly. Sixty-three percent of essential thrombocythemia (ET) patients had JAK2V617F, and they had higher leukocyte count and hemoglobin levels, and thrombosis history, compared to those with wild-type JAK2. The risk factors of associated-myelofibrosis in PV patients were homozygous JAK2V617F, presence of splenomegaly and chromosome abnormality at PV diagnosis, while the risk factors of thrombosis in ET patients are the presence of JAK2V617F and high platelet counts. These data indicate that an increase of mutated allele may closely linked to some risk factor in CMPD, therefore semi-quantification of mutated allele by SSP-SMPD is useful to manage patients. The current study demonstrates a common proliferative nature of JAK2V617F-positive CMPD. Moreover, JAK2V617F-negative clone in CMPD patients might exist and there is a possibility that primary and different pathogenesis may exist in each CMPD subtype.
Clinical Impact of the Immune Reconstitution Status on 100 Day after Allogeneic Stem Cell Transplantation with Fludarabine Based Conditioning
Authors: Jin Park, Se Hyung Kim, Sung Hee Lim, Jina Yun, Chan Kyu Kim, Kyoung Ha Kim, Jong-Ho Won, Dae-Sik Hong, Seong Kyu Park
Journal: Blood (2017)
Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves
Authors: Danny Dvir, Thierry Bourguignon, Catherine M. Otto, Rebecca T. Hahn, Raphael Rosenhek, John G. Webb, Hendrik Treede, Maurice E. Sarano, Ted Feldman, Harindra C. Wijeysundera, Yan Topilsky, Michel Aupart, Michael J. Reardon, G. Burkhard Mackensen, Wilson Y. Szeto, Ran Kornowski, James S. Gammie, Ajit P. Yoganathan, Yaron Arbel, Michael A. Borger, Matheus Simonato, Mark Reisman, Raj R. Makkar, Alexandre Abizaid, James M. McCabe, Gry Dahle, Gabriel S. Aldea, Jonathon Leipsic, Philippe Pibarot, Neil E. Moat, Michael J. Mack, A. Pieter Kappetein, Martin B. Leon
Journal: Circulation (2018)

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.
Abstract 200: Afebrile Kawasaki Disease Beyond Diagnostic Guideline Evolving Coronary Artery Complication
Authors: Sun Hwa Lee, Na Yeon Kim
Journal: Circulation (2015)

Kawasaki disease (KD) is diagnosed with clinical features. Presence of at least five days of fever is major criteria. Herein we report a 7 month -old boy diagnosed as afebrile kawasaki disease who initially presented with inflammation at the Bacille Calmette-Guerin (BCG) inoculation site (BCGitis) with multiple erythematous papular rash, followed by desquamation of finger tips at 11 day of illness. Laboratory test showed elevated ALT (110 U/L) and otherwise showed no specific finding. Clinical feature disappeared spontaneously except BCGitis. The patient did not fulfill the diagnostic criteria but progressive coronary arterial dilatation was noticed. Left coronary artery (LMCA) was dilated from Z-score 1.6 (3 day of illness) to 2.8 (11 day of illness). After treated with intravenous immunoglobulin (2g/kg), BCGitis disappeared and follow up echocardiogram showed normalized LMCA lesion (Z-score 1.0 at 17 day of illness). BCGitis was considered to be pathognomonic feature of this patient. Diagnostic algorithm and guidelines are useful tool for the incomplete KD patients but clinicians should also be cautious for the patient with BCGitis even they are excluded by diagnostic guideline.
Nivolumab Treatment Beyond Investigator-Assessed Progression: Outcomes in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 Checkmate 205 Study
Authors: Jonathon B Cohen, Andreas Engert, Stephen M Ansell, Anas Younes, Marek Trneny, Kerry J Savage, Radhakrishnan Ramchandren, Graham Collins, Michelle A. Fanale, Philippe Armand, Pier Luigi Zinzani, Jan Paul De Boer, Margaret A. Shipp, Armando Santoro, John M Timmerman, Mariana Sacchi, Oumar Sy, John Kuruvilla
Journal: Blood (2017)
Pre-clinical toxicology evaluation of STA-4783 alone or in combination with paclitaxel in rats, mice, and dogs.
Authors: Dan Zhou, Marie E. McKeon, Thomas A. Dahl, Eita Kitayama, Noriaki Tastuta, Lijun Sun, Mitsunori Ono, Long Li, James Barsoum, Shelley Mendenhall, Keizo Koya
Journal: Cancer Research (2004)

2112  STA-4783 is a novel compound that enhances anti-cancer activity of paclitaxel in animal models, and is currently in a Phase I clinical trial. The objectives for pre-clinical toxicology were to profile acute toxicity induced by STA-4783 alone and in combination with paclitaxel in rats, mice, and dogs. The pivotal studies were conducted in compliance with GLP guidelines and included STA-4783 alone and in combination with paclitaxel by bolus intravenous (i.v.) administration into rats or three hours i.v. infusion into dogs. Assessment of toxicity was based on mortality, clinical observations, body weight changes, clinical chemistry and hematology, and anatomic pathology. The LD50 of STA-4783 in rats and mice after a bolus i.v. injection was >200 mg/kg, although this dose level did cause some mortality in both rodent species. An LD50 could not be determined in dogs, as the highest dose of 37.5 mg/kg, determined by the solubility limits, did not produce mortality. Overall, rats and dogs tolerated STA-4783 at the dose of 125 mg/kg and 30 mg/kg, respectively. Throughout most of the dose ranges tested, the toxicity of the STA-4783/paclitaxel drug combination was similar to that of paclitaxel administered alone or attributed to paclitaxel based on clinical observations and macroscopic findings at necropsy consistent with paclitaxel toxicity. In summary, the studies suggest that there was no additional significant toxicity as a result of STA-4783 treatment in combination with paclitaxel in acute toxicity assessment in rats and dogs.
Early Life Indoor Inflammatory Exposures And Asthma Risk At Three Years Of Age In The Canadian Healthy Infant Longitudinal Development (child) Birth Cohort
Authors: T. K. Takaro, Y. Joffres, Huan Shu, J. Brook, A. B. Becker, K. McLean, A. J. Wheeler, J. A. Scott, D. L. Lefebvre, H. Sbihi, P. J. Mandhane, P. Subbarao, S. E. Turvey, M. R. Sears
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Early Life Indoor Inflammatory Exposures And Asthma Risk At Three Years Of Age In The Canadian Healthy Infant Longitudinal Development (child) Birth Cohort
Partisan elites shape citizens' economic beliefs
Authors: Martin Bisgaard, Rune Slothuus
Journal: Behavioral and Brain Sciences (2018)

Abstract Competition between political parties is a fundamental feature of democratic politics, but it is underplayed in the target article. We argue that a more comprehensive understanding of “folk-economic beliefs” (FEBs) must consider the ability of partisan elites to both shape citizens' economic beliefs and connect them to political choices. We review recent empirical findings supporting this theoretical perspective.
Good general care may offer as much benefit as cognitive behaviour therapy
Authors: C. Shepherd
Journal: BMJ (1996)

The initial evidence supporting the prone position in non-ventilated awake patients with COVID-19 infection was anecdotal and theoretical. However, several early studies support the potential role of this practice to improve oxygenation, improve clinical outcomes, and reduce the need for intensive care admission. Although there is not a set amount of time that has been proven to be optimal for awake proning, we recommend sessions of 2 to 3 hours for at least a total 4 to 5 hours a day as tolerated based on the existing data and our anecdotal experience. Despite the low-risk and low-cost nature of proning awake patients, there are still logistical concerns that may prevent adequate proning, the most significant of which is patient comfort and compliance.
Minimal Residual Disease in the Maintenance Setting in Myeloma: Prognostic Significance and Impact of Lenalidomide
Authors: Ruth M de Tute, David Cairns, Andy Rawstron, Charlotte Pawlyn, Faith E. Davies, John R Jones, Martin F Kaiser, Anna Hockaday, Alina Striha, Rowena Henderson, Gordon Cook, Nigel H. Russell, Mark T Drayson, Matthew W Jenner, Walter M Gregory, Graham Jackson, Gareth J. Morgan, Roger G. Owen
Journal: Blood (2017)