tbuckley/cabot-search huggingface dataset:
Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America
Authors: J.L. Arredondo-García, S.R. Hadinegoro, H. Reynales, M.N. Chua, D.M. Rivera Medina, T. Chotpitayasunondh, N.H. Tran, C.C. Deseda, D.N. Wirawan, M. Cortés Supelano, C. Frago, E. Langevin, D. Coronel, T. Laot, A.P. Perroud, L. Sanchez, M. Bonaparte, K. Limkittikul, D. Chansinghakul, S. Gailhardou, F. Noriega, T.A. Wartel, A. Bouckenooghe, B. Zambrano
Journal: Clinical Microbiology and Infection (2018)

Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo.The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies.Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds.The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.
A comparison of cisplatin resistance in epithelial ovarian cancer cell lines overexpressed histone deacetylase(HDAC) isoforms
Authors: Jong-Hyeok Kim, Min-Gyun Kim, Yun-Hyun Cho, Min-Hyung Jung, Dae-Yeon Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
Journal: Cancer Research (2008)

751    Objective:  To investigate the relationship between cisplatin resistance and HDAC isoform expression in ovarian cancer cell lines.   Methods:  The survival rate of SKOV3 cells and OVCAR3 cells after cisplatin treatment were measured by CCK-8 assay. Expression of HDAC isoforms(HDAC 1, 2, 3 and HDAC 4) in ovarian cancer cell lines were examined by western blot analyses. Transfection of HDAC isoforms plasmid DNA in ovarian cancer cell lines was examined by culture with lipofectamine LTX. The overexpressed HDAC isoforms in ovarian cancer cell lines after tranfection was examined by wetern blot analyses and RT-PCR. The survival rate of SKOV3 cells and OVCAR3 cells with overexpressed HDAC isoforms after cisplatin treatment was measured by CCK-8 assay.   Results:  The decrease of the survival rate of ovarian cancer cell lines was observed through time after cisplatin treatment. But the more decrease of survival rate in SKOV3 cells was observed after 24 hours.The increase of the expression of histone3(H3) was seen in SKOV3 cells through time after cisplatin treatment. The overexpression of HDAC isoforms after transfection in ovarian cancer cell lines was observed by western blot and RT-PCR.  The survival rates of the overexpressed HDAC 1 and 3 more increased than control by 15% and 13% respectively in SKOV3 cells(P  Conclusion : These observations provide new information of the correlation between overexpressed HDACs and cisplatin resistance in ovarian cancer cell lines, and difference of HDAC isoform related to cisplatin resistance. So combination therapy of cisplatin and specific HDAC inhibitor may provide the effective treatment in cisplatin resistant-ovarian cancer.
Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): First report of a randomized expansion cohort from CheckMate 032.
Authors: Matthew David Hellmann, Patrick Alexander Ott, Jon Zugazagoitia, Neal E. Ready, Christine L. Hann, Filippo G. De Braud, Scott Joseph Antonia, Paolo Antonio Ascierto, Victor Moreno, Akin Atmaca, Stefania Salvagni, Matthew H. Taylor, Asim Amin, D. Ross Camidge, Leora Horn, Emiliano Calvo, Weiguo Cai, Justin P. Fairchild, Margaret K. Callahan, David R. Spigel
Journal: Journal of Clinical Oncology (2017)

8503 Background: Patients (pts) with advanced SCLC after first-line platinum-based chemotherapy (PLT-CT) have a poor prognosis and limited treatment options. CheckMate 032 is a phase I/II trial evaluating multiple regimens of nivo ± ipi in solid tumors, including advanced SCLC. Tolerability and efficacy of nivo ± ipi were demonstrated in early results from the initial treatment arms (Antonia, Lancet Oncol 2016), prompting long-term follow-up and the addition of a randomized expansion cohort to further evaluate nivo ± ipi in advanced SCLC. Methods: In the initial treatment arms, pts with advanced SCLC and disease progression after prior PLT-CT were assigned to nivo (3 mg/kg Q2W; n = 98) or nivo 1 + ipi 3 (1 mg/kg and 3 mg/kg Q3W x 4, then nivo 3 Q2W; n = 61); safety/efficacy was assessed with a follow-up of ~18 mo. In the subsequent SCLC expansion cohort, pts were randomized 3:2 to nivo vs nivo 1 + ipi 3 and stratified by number of prior therapies. The primary endpoint was objective response rate (ORR). Results: Updated efficacy/safety results from the initial (non-randomized) nivo and nivo 1 + ipi 3 arms are summarized in the table. Responses were durable and occurred regardless of PD-L1 expression or PLT-sensitivity; safety was consistent with prior nivo ± ipi studies. In the expansion cohort, 247 pts were randomized to nivo or nivo 1 + ipi 3. The presentation will contain the first report of efficacy/safety results and subgroup analyses from this randomized expansion cohort. Conclusions: Durable responses are observed with nivo and nivo + ipi in pts with previously treated SCLC. The expansion cohort represents the first randomized evaluation of combined immune checkpoint blockade in SCLC. Clinical trial information: NCT01928394. [Table: see text]
Status of Cardiovascular Health in US Adolescents
Authors: Christina M. Shay, Hongyan Ning, Stephen R. Daniels, Cherie R. Rooks, Samuel S. Gidding, Donald M. Lloyd-Jones
Journal: Circulation (2013)

The American Heart Association recently developed definitions and metrics for monitoring the spectrum of cardiovascular health in adolescents and children. Current nationally representative prevalence estimates according to sex and race/ethnicity are unavailable.We examined the components of cardiovascular health in 4673 participants aged 12 to 19 years (representing ≈33.2 million US adolescents) from the 2005-2010 National Health and Nutrition Examination Surveys. Population prevalence of individual cardiovascular health behaviors and factors was estimated according to American Heart Association criteria for poor, intermediate, and ideal levels. Ideal blood pressure was most prevalent (males, 78%; females, 90%), whereas a dramatically low prevalence of ideal Healthy Diet Score was observed (males, <1%; females, <1%). Females exhibited a lower prevalence of ideal total cholesterol (65% versus 72%, respectively) and ideal physical activity levels (44% versus 67%, respectively) yet a higher prevalence of ideal blood glucose (89% versus 74%, respectively) compared with males. Approximately two thirds of adolescents exhibited ideal body mass index (males, 66%; females, 67%) and ideal smoking status (males, 66%; females, 70%). Less than 50% of adolescents exhibited ≥5 ideal cardiovascular health components (45%, males; 50%, females). Prevalence estimates according to sex were consistent across race/ethnic groups.The low prevalence of ideal cardiovascular health behaviors in US adolescents, particularly physical activity and dietary intake, will likely contribute to a worsening prevalence of obesity, hypertension, hypercholesterolemia, and dysglycemia as the current US adolescent population reaches adulthood. Population-wide emphasis on establishment of ideal cardiovascular health behaviors early in life is essential for maintenance of ideal cardiovascular health throughout the lifespan.
<i>Helicobacter pylori</i> eradication treatment and the risk of gastric adenocarcinoma in a Western population
Authors: Eva Doorakkers, Jesper Lagergren, Lars Engstrand, Nele Brusselaers
Journal: Gut (2018)

Objective Gastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population. Design This was a nationwide, population-based cohort study in Sweden in 2005–2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs. Results During the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1–3 years, 2.02 (95% CI 1.25 to 3.09) for 3–5 years and 0.31 (95% CI 0.11 to 0.67) for 5–7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93). Conclusion Eradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.
HIF2 Inhibitor Joins the Kidney Cancer Armamentarium
Authors: William G. Kaelin
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. December 19, 2017 ARTICLE CITATION DOI: 10.1200/JCO.2017.77.5254 Journal of Clinical Oncology - published online before print January 31, 2018 PMID: 29384723 HIF2 Inhibitor Joins the Kidney Cancer Armamentarium William G. Kaelin JrxWilliam G. Kaelin JrSearch for articles by this author Show More William G. Kaelin Jr, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2017.77.5254 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma
Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming (vol 16, pg 123, 2010)
Authors: Mark J. Kwakkenbos, Sean A. Diehl, Etsuko Yasuda, Arjen Q. Bakker, Caroline M. M. van Geelen, Michaël V. Lukens, Grada M. van Bleek, Myra N. Widjojoatmodjo, Willy M. J. M. Bogers, Henrik Mei, Andreas Radbruch, Ferenc A. Scheeren, Hergen Spits, Tim Beaumont
Journal: Nature Medicine (2016)
Exceptional Responses to Epigenetic Based Therapy in Pediatric and Young Adult Monosomy 7 MDS/AML Patients with and without TP53 Mutations
Authors: LaQuita M Jones, Maureen M O'Brien, Erin H. Breese, Karen Burns, Jennifer Mangino, Michael J. Absalon, Javier A. El-Bietar, Michael Grimley, Benjamin Mizukawa, Lynn Lee, John Peter Perentesis, Christine L Phillips
Journal: Blood (2017)
Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine graft-versus-host disease
Authors: Shuichiro Takahashi, Daigo Hashimoto, Eiko Hayase, Reiki Ogasawara, Hiroyuki Ohigashi, Takahide Ara, Emi Yokoyama, Ko Ebata, Satomi Matsuoka, Geoffrey R. Hill, Junichi Sugita, Masahiro Onozawa, Takanori Teshima
Journal: Blood (2018)
Does <i>Akkermansia muciniphila</i> play a role in type 1 diabetes?
Authors: Gilles Mithieux
Journal: Gut (2018)

A field currently attracting increasing interest concerns the possible role that the intestinal microbiota might play in human health and disease. The fact that novel sequencing approaches applied to the microbiota genome are available has definitely favoured the rapid development of this field. The recent re-emergence in this area began with studies on obesity and metabolic diseases. Various associations between microbiota composition and metabolic diseases such as obesity and type 2 diabetes have been reported, in both rodents and humans, emphasising the key role of dietary habits in the composition of the bacterial population.1–3 However, experiments aimed at changing microbiota composition and transferring/exchanging the intestinal microbiota to alter the metabolism of the host have proved somewhat controversial and failed to unequivocally establish a causal role for the gut microbiota in metabolic diseases.4 Whatever the case, it is noteworthy that a specific bacterium, Akkermansia muciniphila , an abundant constituent of the gut microbiota in healthy humans, has been demonstrated to correct host metabolic disorders when given by gavage as a probiotic in obese insulin-resistant mice.2 Nowadays, interest in the role of intestinal microbiota in …
Abstract 19427: Cardiovascular Response to Exercise in Obesity Mimics Heart Failure With Preserved Ejection Fraction
Authors: James MacNamara, Christopher Hearon, Michinari Hieda, Norman Aiad, Margot Morris, Braden Everding, Mitchel Samels, Satyam Sarma
Journal: Circulation (2017)

Introduction:  Obesity is a known risk factor for HFpEF. This connection is thought to be driven by concentric ventricular remodeling, diastolic dysfunction, and low fitness. We investigated whether the mechanisms for low fitness were similar between “at risk” middle age obese subjects and HFpEF patients. We hypothesized obese subjects would have similar impairments in cardiovascular response to exercise as HFpEF.   Methods:  Cardiopulmonary exercise testing was performed on 49 middle aged, obese subjects (33% men; age 49 ± 6 yrs; BMI 38.8 kg/m2) who were deemed at risk for HFpEF by elevated cardiac biomarkers (NT-proBNP > 40 pg/ml; hs-cTnT > 3 pg/ml) and increased visceral adiposity (> 2.5 kg). Sixty one middle aged, healthy, non-obese (CON) subjects 48% men; age: 52 ± 5 yrs; BMI 26.0 kg/m2) and 25 HFpEF patients (38% men; age: 71 ± 7 yrs; BMI 34.4 kg/m2) were used as references for exercise performance. Peak VO2 (Douglas bags) and cardiac output (Qc; acetylene rebreather) were measured at rest, sub-max, and max exercise. AVO2 difference was calculated from VO2 and Qc. Stroke volume (SV) reserve was defined as change in SV from rest to sub-max exercise.   Results:  Peak VO2 was significantly different between all three groups (HFpEF: 13.1 OB: 17.2 CON: 29.3 ml/kg/min; p   Conclusions:  Mechanisms for low fitness are similar, albeit to a lesser degree, between “at risk” obese subjects and HFpEF despite a difference in age of two decades. An inability to augment stroke volume or peripheral extraction, characteristic features of HFpEF, contribute to poor exercise performance in obesity. Further sedentary aging and development of comorbid conditions may amplify these impairments leading to HFpEF.
The Impact of Underpowered Studies on Clinical Trial Results
Authors: Arif Khan, Kaysee Fahl Mar, Walter A. Brown
Journal: American Journal of Psychiatry (2018)

Are Innovative Drugs Failing in Phase III?" (1), brings up a critical topic: the frequent failure of phase III trials for CNS programs.The authors effectively summarized investigations into this issue.However, we believe that a possible explanation for phase III trial failure was minimized, as noted in the commentary: "that the phase II results were misleading" (1, p. 829).It is perhaps an underappreciated truism that statistically underpowered studies with small sample sizes (often earlyphase studies) are highly likely to both under-and overestimate treatment effect sizes (2, 3).By considering large effects from small studies to be true effects rather than overestimation errors, some researchers have concluded that smaller trials are more advantageous.Take, for example, the citation of Undurraga and Baldessarini, who suggest limiting phase III antidepressant trials to 30-75 patients (4, p. 860).Testing this suggestion using data from Food and Drug Administration (FDA) antidepressant phase III trials, we found that treatment arms with Ns of #75 had both the highest (0.75) and lowest (20.29) effect sizes of the entire group of 115 arms and that they achieved statistical significance only 50% of the time.In contrast, the largest treatment arms (with Ns of $350) had a 100% rate of statistical significance and little variation in effect size (from 0.24 to 0.33).These smaller trials empirically demonstrate the chance findings of underpowering-they are no more reliable than tossing a coin.These findings are unsurprising, given that a two-arm trial with Ns of #75 would be powered only at 50% for an effect size of 0.5 (2).Underreporting negative studies in published research may mask the downside of the underpowering coin, which can be seen in the FDA data; that is, those "unlucky" underpowered trials resulting in failure and underestimations of drug effect.The increase in size of phase III trials should not be viewed as a design flaw because this rejects the statistical principles of the scientific method.If phase II results are a reflection of the true magnitude of treatment effects, by rule they should be replicated in a larger sample.If they are not, then the phase II results were likely misleading.Seeking to replicate such lucky results from underpowered studies by underpowering future studies only perpetuates scientifically unsound methods and high failure rates.
Autophagic dysfunction in patients with Papillon-Lefèvre syndrome is restored by recombinant cathepsin C treatment
Authors: Pedro Bullón, Beatriz Castejón-Vega, Lourdes Román-Malo, María Paz Jimenez-Guerrero, David Cotán, Tamara Y. Forbes-Hernandez, Alfonso Varela-López, Antonio J. Pérez-Pulido, Francesca Giampieri, José L. Quiles, Maurizio Battino, José A. Sánchez-Alcázar, Mario D. Cordero
Journal: Journal of Allergy and Clinical Immunology (2018)
Symptoms Do Not Correlate With Findings From Colonoscopy in Children With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
Authors: Amanda Ricciuto, Jennifer Fish, Nicholas Carman, Thomas D. Walters, Peter C. Church, Bettina E. Hansen, Eileen Crowley, Iram Siddiqui, Geoffrey C. Nguyen, Binita M. Kamath, Anne M. Griffiths
Journal: Clinical Gastroenterology and Hepatology (2018)
Initial Results of Ibrutinib Plus Venetoclax in Relapsed, Refractory CLL (Bloodwise TAP CLARITY Study): High Rates of Overall Response, Complete Remission and MRD Eradication after 6 Months of Combination Therapy
Authors: Peter Hillmen, Talha Munir, Andy Rawstron, Kristian Brock, Samuel Munoz Vicente, Francesca Yates, Rebecca Bishop, Christopher Fegan, Donald Macdonald, Alison McCaig, Anna Schuh, Andrew Pettitt, John G. Gribben, Stephen Devereux, Adrian Bloor, Christopher P Fox, Francesco Forconi
Journal: Blood (2017)
Social Media Intervention Improves Vaccine Acceptance
Authors: Anita Slomski
Journal: JAMA (2018)

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US’s $2bn annual spend on dry eye disease “brings tears to your eyes,” say critics
Authors: Nigel Hawkes
Journal: BMJ (2018)

The US spends over $2bn (£1.4bn; €1.6bn) a year on a marginally effective drug for a condition many people would not consider to be a disease, a viewpoint article in JAMA Internal Medicine has claimed.1

Lisa Schwartz and Stephen Woloshin, of the Institute for Health Policy at Dartmouth, New Hampshire, say that Restasis—a drug manufactured by Allergan to treat dry eye disease—was approved by the US Food and Drug Administration on scant evidence and that sales have been driven by an aggressive marketing campaign.

“Think about all the good that could have been done with the billions spent in the US on Restasis,” they conclude. “It should bring tears to your eyes. Which is what Restasis is supposed to do—just not like this.”

The manufacturer, headquartered in Dublin, Ireland, denies …
Research Priorities in Pathophysiology for Sleep-disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Research Statement
Authors: Atul Malhotra, Alan R. Schwartz, Hartmut Schneider, Robert L. Owens, Pamela DeYoung, MeiLan K. Han, Jadwiga A. Wedzicha, Nadia N. Hansel, Michelle R. Zeidler, Kevin C. Wilson, M. Safwan Badr
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are common conditions; the co-occurrence of these diseases, called the overlap syndrome (OVS), has been associated with poor health outcomes.The purpose of this Official American Thoracic Society Research Statement is to describe pathophysiology, epidemiology, outcomes, diagnostic metrics, and treatment of OVS, as well as to identify important gaps in knowledge and make recommendations for future research.Clinicians and researchers with expertise in sleep medicine, pulmonary medicine, or both were invited to participate. Topics were divided among the participants according to their interest and expertise. A literature search was conducted; the search was not a formal systematic review. Evidence was considered and supplemented with the panelists' nonsystematic clinical observations. Important knowledge gaps were identified.Recommendations for research to fill existing knowledge gaps were made. The recommendations were formulated by discussion and consensus.Many important questions about OVS exist. This American Thoracic Society Research Statement highlights the types of research that leading clinicians and researchers believe will have the greatest impact on better understanding the spectrum of disease, improving diagnosis, and optimizing therapy.