tbuckley/cabot-search huggingface dataset:
Abstract A83: Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study
Authors: Tabatha Gutierrez Prieto, Vanessa Karen de Sá, Eloisa Helena Ribeiro Olivieri, Eduardo Caetano Albino da Silva, Rui Manuel Reis, Dirce Maria Carraro, Vera Luiza Capelozzi
Journal: Clinical Cancer Research (2018)

Abstract Background: Metastasis are responsible for the death of 90% of patients with lung cancer, indicating the need to know the multiple signaling pathways involved. Neuroendocrine lung carcinomas (NELC) encompass a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and atypical carcinoid (AC), to the high-grade large cell neuroendocrine carcinoma (LCNEC) and the small-cell lung carcinoma (SCLC). Low-grade NELC are indolent, while high-grade NELC invade and metastasize rapidly. Biomarkers of NELC aggressiveness remain to be determined. Epithelial to mesenchymal transition (EMT) genes profile show promise as indicator of invasion and metastasis. Our aim was to evaluate: (1) EMT gene expression in NELC, (2) its relationship with the histologic subtypes, and (3) its impact on behavior of the tumors. Methods: Patients with SCLC (n = 10), LCNEC (n=5), AC (n=2) and TC (n=7) were included. EMT gene expression was quantified with a quantitative real-time (RT)-PCR carried out on StepOnePlus™ Real-Time PCR System (Applied Biosystems) with RT2 Profiler PCR Array System (Qiagen, Dusseldorf, Germany). Associations of the gene signature and clinicopathologic features, as well as prognostic factors were evaluated. Results: A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGF-beta 1, TGF-beta 2, TGF-beta 3, and VIM) that was related to EMT was upregulated in tumor-tissue from all NELC patients, mainly in those with high-grade NELC. An increased expression of DSP, TCF3, and TGF-beta 2 genes were shown in high-grade when compared to low-grade NELC and associated with lymph node metastasis with statistical significance respectively for DSP (p&amp;lt;0.05), TGF-beta 3 (p&amp;lt;0.05), and marginal significance for TCF3 (p=0.08). TCF3 was also associated with tobacco history (p=0.04). Conclusion: The EMT analysis identified genes involved in cell proliferation, motility, invasion, and metastasis of NELC. We further inferred DSP, TCF3, and TGF-beta 3 as target against lung cancer metastasis and invasion, thus arising as a promising therapeutic agent. Citation Format: Tabatha Gutierrez Prieto, Vanessa Karen de Sá, Eloisa Helena Ribeiro Olivieri, Eduardo Caetano Albino da Silva, Rui Manuel Reis, Dirce Maria Carraro, Vera Luiza Capelozzi. Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A83.
Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA
Authors: Jens Klotsche, Kirsten Minden, Martina Niewerth, Gerd Horneff
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To determine the reasons of methotrexate (MTX) discontinuation, frequency of adverse events (AE) and whether the time in inactive disease before MTX withdrawal disease is associated with the risk of disease flare. Methods Patients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX were prospectively observed in the national JIA biologic register Biologika in der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up register Juvenile arthritis Methotrexate/Biologics long-term Observation. Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, flare after MTX discontinuation by reoccurrence of at least moderate disease activity or restart of treatment with a disease-modifying antirheumatic drug . Results MTX treatment was initiated in 1514 patients after a mean disease duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness (36.9%) and achieving inactive disease (32.1%) were the most common reasons. Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up. The likelihood of a flare was a function of time in inactive disease prior to MTX discontinuation (HR 0.95; 95% CI 0.92 to 0.97). Patients with inactive disease for longer than 12 months had a significantly lower flare rate (58 of 119, 48.7%; HR 0.48; 95% CI 0.34 to 0.69). The most frequently reported AE was MTX intolerance, including nausea, aversion and vomiting, accounting for 441 events (13.0 events/100 exposure years) in 307 (20.3%) patients. Conclusions Patients who spent at least 12 months in inactive disease before MTX discontinuation had a significantly lower flare rate.
Transplantation of Human Embryonic Stem Cell–Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction
Authors: Philippe Menasché, Valérie Vanneaux, Albert Hagège, Alain Bel, Bernard Cholley, Alexandre Parouchev, Isabelle Cacciapuoti, Reem Al-Daccak, Nadine Benhamouda, Hélène Blons, Onnik Agbulut, Lucie Tosca, Jean-Hugues Trouvin, Jean-Roch Fabreguettes, Valérie Bellamy, Dominique Charron, Eric Tartour, Gérard Tachdjian, Michel Desnos, Jérôme Larghero
Journal: Journal of the American College of Cardiology (2018)
Association of Early-Life Factors With Life-Course Trajectories of Resting Heart Rate
Authors: Celia O’Hare, Diana Kuh, Rebecca Hardy
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Higher resting heart rate (RHR) is associated with increased risk of cardiovascular and all-cause mortality. Limited attention has been paid to early-life determinants of life-course RHR. <h3>Objective</h3> To describe trajectories of RHR in the same individuals from age 6 to 69 years. <h3>Design, Setting, and Participants</h3> Data were from the Medical Research Council National Survey of Health and Development population-based cohort of individuals who were followed up from birth in 1946 until 2015. Analysis was conducted between September 2016 and June 2017. Multilevel models were used to estimate life-course mean RHR trajectory by sex and to investigate associations with early childhood factors. The maximal sample included participants who had at least 1 measure of RHR since study entry and a measure of birth weight (N = 4779; observations = 26 182). <h3>Exposures</h3> Information on early-life factors was ascertained prospectively: childhood socioeconomic position, birth weight, body mass index (calculated as weight in kilograms divided by height in meters squared) change from age 2 to 6 years (conditioned on body mass index at age 2 years), duration of breastfeeding, and markers of neurodevelopment (age at first walking independently and cognitive ability at age 8 years). <h3>Main Outcomes and Measures</h3> Resting heart rate measured on 8 occasions between age 6 and 69 years (3 occasions in childhood and 5 in adulthood). <h3>Results</h3> Of 4779 participants, 2492 (52.1%) were women, and 2287 (47.9%) were men. Mean estimated RHR decreased with increasing age and plateaued in adulthood. In sex-adjusted analyses, higher birth weight and conditional body mass index change were associated with lower RHR at age 6 years and across the life course (–0.56 bpm [95% CI, –0.95 to –0.17] per 1 kg higher birth weight and –0.30 bpm [95% CI, –0.48 to –0.13] per 1 kg/m<sup>2</sup>change in body mass index). Associations between socioeconomic position and breastfeeding on RHR trajectory emerged in adulthood such that by age 69 years, RHR was 1.48 bpm (95% CI, 0.45 to 2.51) higher in participants from a disadvantaged vs advantaged background and –1.34 bpm (95% CI, –2.39 to –0.29) lower for those who were breastfed for 8 months or longer vs never. A later age at first walking was associated with higher RHR at age 6 years (1.49 bpm [95% CI, 0.39 to 2.59] higher for those 18 months or older vs those younger than 12 months) but with lower RHR in adulthood (–1.18 bpm [95% CI, –2.75 to 0.39] at age 69 years). <h3>Conclusions and Relevance</h3> Early life is a key period in determining future RHR trajectories with associations with potentially modifiable factors persisting into the seventh decade of life.
Ingestion accidentelle d'aiguilles: nouvelle circonstance de survenue
Authors: N Elleuch, A Sabbek, A Ben Slama, A Hammami, H Jaziri, A Braham, S Ajmi, M Ksiaa, A Jmaa
Journal: Endoscopy (2018)

Le plus souvent accidentelles, les ingestions de corps étrangers (CE) surviennent dans la majorité des cas avant l'âge de 5 ans. Chez l'adulte, l'ingestion de CE est beaucoup plus rare que chez l'enfant, et se voit sur des terrains prédisposés ou des situations propices. L'épingle à foulard est un CE particulier de plus en plus fréquent chez les femmes qui portent le voile.
Nasopharyngeal Microbiome During Health and Illness in Early Life
Authors: Anna Lang, Kathryn E. Holt, Michael Inouye, Patrick G. Holt, Shu Mei Teo, Howard H.F. Tang, Louise M. Judd, Robert F. Lemanske, Michael D. Evans, Daniel J. Jackson, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact de l'obésité sur la préparation colique: A propos d'une cohorte nord-africaine
Authors: B Bouchabou, L Hamzaoui, K Agar, M Medhioub, K Amal, MM Azouz
Journal: Endoscopy (2018)

Une mauvaise préparation colique peut être responsable de méconnaissance diagnostique, des procédures répétitives, une augmentation du coût et un risque accru de complications. Le lien de l'obésité avec la néoplasie colorectal a été bien établi. Par conséquent, la qualité de la préparation colique chez les personnes en surcharge pondérale est intéressante. Le but de cette étude est d'étudier l'impact de l'indice de masse corporelle (IMC) sur la qualité de préparation de la muqueuse colique.
Endophthalmitis after Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors
Authors: Kunyong Xu, Eric K. Chin, Steven R. Bennett, David F. Williams, Edwin H. Ryan, Sundeep Dev, Robert A. Mittra, Polly A. Quiram, John B. Davies, D. Wilkin Parke, Jill B. Johnson, Herbert L. Cantrill, David R.P. Almeida
Journal: Ophthalmology (2018)
Modalités thérapeutiques des sténoses ulcéreuses bulbaires: A propos de 115 patients
Authors: S Ben Amor, M Medhioub, L Hamzaoui, A Ben Mohamed, K Amal, O Gharbi, MM Azouz
Journal: Endoscopy (2018)

La maladie ulcéreuse du bulbe est une pathologie bénigne dont les complications les plus fréquentes sont l'hémorragie et la sténose. Au fil des années, le traitement endoscopique et médical a largement remplacé la chirurgie dans le traitement de la sténose bulbaire. Le but de notre travail est de décrire l'évolution des modalités thérapeutiques de ces sténoses au fil du temps.
Traitement endoscopique des complications biliaires du kyste hydatique du foie: A propos de 19 cas
Authors: I Ghribi, B Ben Slimane, K Boughoula, S Bizid, AH Ben, MR Bouali, N Abdelli
Journal: Endoscopy (2018)

L'hydatidose hépatique est une pathologie fréquente sous nos cieux, où elle sévit sur le mode endémique et constitue un véritable problème de santé publique. C'est une maladie bénigne mais risque d'entraîner des complications biliaires, pour lesquelles le drainage biliaire par voie endoscopique est très efficace. Le but de notre étude était d'évaluer l'efficacité du traitement endoscopique dans la prise en charge des complications biliaires du kyste hydatique du foie (KHF).
Podoplanin expression is an independent predictor of survival in malignant gliomas
Authors: Erik Sulman, Christopher Pelloski, J. McDonald, Clarissa De La Cruz, Lihong Long, Sonya Popoff, Susan McGovern, Howard Colman, Kenneth Aldape
Journal: Cancer Research (2007)

2438   Despite aggressive clinical care, glioblastoma (GBM) is a near uniformly fatal disease with median survival of 10 to 12 months. Few molecular markers exist that are prognostic for overall survival. Data from multiple expression profiling experiments suggested that the mucin-type transmembrane glycoprotein podoplanin may be a significant marker of survival. We sought to validate this finding in an independent cohort of GBM patients. Cases of GBM (WHO grade IV) or low and intermediate grade astrocytoma (WHO grade II and III) who underwent surgical resection from 11/1985 to 6/2005 with available medical records and archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue were selected for this study. Podoplanin expression was detected by immunohistochemical (IHC) staining and scored as negative, intermediate, or high expression. Radiation response was previously determined in patients without a gross-total resection by evaluation of magnetic resonance imaging. Quantitative real-time PCR (QPCR) of  PDPN  cDNA was performed following reverse transcription of total RNA derived from FFPE tissue. A total of 113 GBMs were initially examined for podoplanin expression by IHC using the D2-40 antibody. Median survival in the podoplanin expressing group was 60 wks vs. 148 wks in the non-expressing group (p=0.008, log-rank test). This result was validated using an independent set of 95 GBMs with a 2 year survival of 52% vs. 10% (p=0.017). Median and 2-year survival among all GBMs (median follow-up of 55 weeks) for podoplanin expression vs. non-expression was 54 wks vs. 148 wks and 15% vs. 56%, respectively (p
There is too much traffic for Alex to walk to school, so we drive: a call to action based on a 42-year trend
Authors: Christopher William Oliver, Paul Kelly, Graham Baker, Dave du Feu, Adrian Davis
Journal: British Journal of Sports Medicine (2018)

In 1971, a study of children’s travel to and from school focused on five English primary schools.1 The schools’ locations ranged from inner-urban London to a village primary school (ages 4–11). In 1990, the Policy Studies Institute published a follow-up study with the same schools and added linked secondary schools (ages 11–16).2 The results were alarming. Independent active travel was declining steeply—on average, a child in 1990 had to be 2.5 years older than in 1971 to be allowed permissions such as to cross local roads and to travel the school journey without an adult.1 2 A further study in 2013 reported further significant shrinkage.3 We are concerned about the effects this will have for Alex and all young people (figure 1).



Figure 1 
The school journey.



The drivers of children being kept on a leash are multifaceted, but implicated above all is the dominance of the ‘windscreen perspective’—politicians and highway engineers have a driver’s perspective. Travel by car, and provision for that, becomes the default choice. Public …
Traitement des tumeurs kystiques et neuroendocrines pancréatiques par Radio fréquence guidée sous échoendoscopie: première étude prospective multicentrique
Authors: M Barthet, N Lesavre, M Giovannini, C Boustière, B Napoléon, S Koch, E Bories, M Gasmi, JM Gonzalez, G Vanbiervliet
Journal: Endoscopy (2018)

Les tumeurs neuroendocrines et TIPMP avec signes inquiétants sont généralement traitées par résection chirurgicale. Les traitements antitumoraux guidés sous échoendoscopie ont été récemment développés mais ils sont principalement basés sur l'injection d'alcool dont la diffusion incontrôlée entraîne des complications graves. Le but de cette étude était d'évaluer prospectivement le rôle de la radiofréquence guidée sous échoendoscopie pour détruire ces tumeurs in situ: l'objectif premier était d'évaluer la morbidité et le second d'apprécier l'efficacité.
Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery
Authors: Tobias Atkin, Stefano Comai, Gabriella Gobbi
Journal: Pharmacological Reviews (2018)

Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs. We analyzed the melatonergic agonist drugs, agomelatine, prolonged-release melatonin, ramelteon, and tasimelteon; the dual orexin receptor antagonist suvorexant; the modulators of the <i>α</i><sub>2</sub><i>δ</i> subunit of voltage-sensitive calcium channels, gabapentin and pregabalin; the H<sub>1</sub> antagonist, low-dose doxepin; and the histamine and serotonin receptor antagonists, amitriptyline, mirtazapine, trazodone, olanzapine, and quetiapine. The pharmacology and mechanism of action of these treatments and the evidence-base for the use of these drugs in clinical practice is outlined along with novel pipelines. There is evidence to recommend suvorexant and low-dose doxepin for sleep maintenance insomnia; there is also sufficient evidence to recommend ramelteon for sleep onset insomnia. Although there is limited evidence for the use of the quetiapine, trazodone, mirtazapine, amitriptyline, pregabalin, gabapentin, agomelatine, and olanzapine as treatments for insomnia disorder, these drugs may improve sleep while successfully treating comorbid disorders, with a different side effect profile than the BZDs and Z-drugs. The unique mechanism of action of each drug allows for a more personalized and targeted medical management of insomnia.
Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?
Authors: Barbara J Jefferis, Tessa J Parsons, Claudio Sartini, Sarah Ash, Lucy T Lennon, Olia Papacosta, Richard W Morris, S Goya Wannamethee, I-Min Lee, Peter H Whincup
Journal: British Journal of Sports Medicine (2018)

To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour.Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-1980. In 2010-2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71-92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016.After median 5.0 years' follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality.In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults.
North American public health schools decline funding from tobacco funded foundation
Authors: Owen Dyer
Journal: BMJ (2018)

The deans of 19 schools of public health from prominent universities in the US and Canada have signed a joint statement1 declining offers of research funding from the Foundation for a Smoke-Free World (FSFW), an organisation set up with money from tobacco giant Philip Morris International.

The deans wrote that “both the tobacco industry and Philip Morris International have a long history of funding ‘research’ in ways meant to purposely confuse the public and advance their own interests, aggressively market cigarettes globally, including to children, and persist in their relentless opposition to evidence based tobacco control interventions.”

The World Health Organization has declined to work with FSFW, the deans noted, and they cite the WHO Framework Convention on Tobacco Control, the world’s …
Pediatric Participation in Medical Decision Making: Optimized or Personalized?
Authors: Maya Sabatello, Annie Janvier, Eduard Verhagen, Wynne Morrison, John Lantos
Journal: The American Journal of Bioethics (2018)

Olszewski and Goldkind (2018) argue that children's participation in medical decision making should be “the default position” and that a stepwise approach is needed to ensure that children are rout...
Ventilatory support or respiratory muscle training as adjuncts to exercise in obese CPAP-treated patients with obstructive sleep apnoea: a randomised controlled trial
Authors: Isabelle Vivodtzev, Renaud Tamisier, Marilie Croteau, Jean-Christian Borel, Angélique Grangier, Bernard Wuyam, Patrick Lévy, Caroline Minville, Frédéric Sériès, François Maltais, Jean-Louis Pépin
Journal: Thorax (2018)

Background Obstructive sleep apnoea (OSA) and obesity are interdependent chronic diseases sharing reduced exercise tolerance and high cardiovascular risk. Intervention A 3-month intervention with innovative training modalities would further improve functional capacity and cardiovascular health than usual cycle exercise training in already continuous positive airway pressure (CPAP)-treated obese patients with OSA. Methods Fifty three patients (35&lt;body mass index (BMI) &lt;45 kg/m 2 ) were randomly allocated to exercise training on a cycle ergometer, either alone (ERGO) or with respiratory muscle training (ERGO+RMT) or non-invasive ventilation (ERGO+NIV). Changes in 6 min walking distance (primary outcome), aerobic capacity (VO 2peak ), cardiovascular parameters, body composition and sleep quality were evaluated. Measurements and main results All training modalities increased 6 min walking distance without differences between groups (P=0.97). ERGO+NIV and ERGO+RMT led to significantly higher improvement in VO 2peak compared with ERGO (3.1 (95% CI 1.6 to 4.6) vs 2.3 (0.8 to 3.7) vs 0.5(−1.0 to 1.9) mL/min/kg, respectively, P=0.04) and ERGO+NIV significantly reduced self-measured blood pressure compared with ERGO+RMT and ERGO (systolic: −9.5 (95% CI −14.1 to −4.9) vs −13 (−5.8 to 3.1) vs −0.7 (−5.1 to 3.8) mm Hg, respectively, P=0.01). Waist and neck circumferences were reduced after ERGO+NIV compared with ERGO+RMT and ERGO (P=0.01). Conclusions Combining RMT or NIV with cycling exercise training failed to provide further improvement in functional capacity as compared with cycling exercise training alone. However, the combination of NIV and exercise training demonstrated superiority for improving cardiometabolic risk factors in obese CPAP-treated patients with OAS. TRIAL REGISTRATION NUMBER Results, NCT01155271 .
Improving access to eating disorder services
Authors: Antony Natt
Journal: BMJ (2018)

This timely article on eating disorders in children and young people reminds us that the interval between onset of illness and access to specialist interventions predicts outcome.12 Early intervention (specialist treatment within 6 months of onset) predicts good outcomes, whereas late intervention (after 36 months) predicts poorer outcomes.3 The estimated delay from onset to accessing specialist services is 42 months—patients present after about 36 months, and service …