tbuckley/cabot-search huggingface dataset:
The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer
Authors: Yi-Chen Zhang, Qing Zhou, Yi-Long Wu
Journal: Journal of Hematology & Oncology (2017)

The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into oncogene-directed precision medicine. Identifying actionable genomic alterations is the initial step towards precision medicine. An important scientific progress in molecular profiling of NSCLC over the past decade is the shift from the traditional piecemeal fashion to massively parallel sequencing with the use of next-generation sequencing (NGS). Another technical advance is the development of liquid biopsy with great potential in providing a dynamic and comprehensive genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS with liquid biopsy has been demonstrated to play emerging roles in genomic profiling of NSCLC by increasing evidences. This review summarized the potential applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC including identifying actionable genomic alterations, tracking spatiotemporal tumor evolution, dynamically monitoring response and resistance to targeted therapies, and diagnostic value in early-stage NSCLC, and discussed emerging challenges to overcome in order to facilitate clinical translation in future.
Diagnosis and management of cystic fibrosis: summary of NICE guidance
Authors: Gemma Villanueva, Gemma Marceniuk, M Stephen Murphy, Martin Walshaw, Rami Cosulich
Journal: BMJ (2017)

#### What you need to know

Cystic fibrosis is a life limiting autosomal recessive disorder that affects up to one in 2500 babies born in the UK. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator protein, which acts at the cell surface in all mucus producing organs in the body. It is a multisystem disorder, affecting the lungs, pancreas, liver, and intestine. It is usually diagnosed in the UK through a neonatal screening programme, although diagnosis can be made later, and even in adult life.1 The median age at diagnosis is 2 months.1 In the past, when early death was common, cystic fibrosis was uncommon in adults, but with improved management this is no longer the case in more developed countries. However, in low income countries, mortality in childhood is still high.2 At present, more than 60% of people on the UK cystic fibrosis registry are aged over 16.1

This article summarises the recent National Institute for Health and Care Excellence (NICE) guidance on the diagnosis and management of cystic fibrosis in children, …
OA01.03 Attrition Rate in Community-Based Lung Cancer Screening: One and Done
Authors: A.S. Carlson, C.L. Wilshire, J.T. Fathi, J.R. Rayburn, C.R. Gilbert, S.C. Blanshan, B.E. Louie, R.W. Aye, A.S. Farivar, E. Vallieres, J.A. Gorden
Journal: Journal of Thoracic Oncology (2017)
TCT-708 Diagnostic Performance of Resting Distal to Aortic Coronary Pressure Using Instantaneous Wave-Free Ratio as a Reference Standard
Authors: Yuhei Kobayashi, Nils Johnson, Frederik Zimmermann, Nils Witt, Colin Berry, Allen Jeremias, Bon-Kwon Koo, Giovanni Esposito, Gilles Rioufol, Seung-Jung Park, Takeshi Nishi, Dong-Hyun Choi, Keith Oldroyd, Emanuele Barbato, Nico Pijls, Bernard De Bruyne, William Fearon
Journal: Journal of the American College of Cardiology (2017)
Vigilancia centinela de la infección por VIH en clínicas de detección de VIH en España, 1992-2002
Authors: A Barrasa, J Castilla, J del Romero, I Pueyo, C de Armas, J A Varela, J M Ureña, F J Bru, J R Ordoñana, L M Sáez de Vicuña
Journal: Eurosurveillance (2004)

Se ha monitorizado la infeccion por VIH en Espana en personas analizadas voluntariamente en diez centros centinela entre 1992 y 2002. Solo se consideraron los pacientes atendidos en primera visita. Su numero aumento desde 4426 en 1992 hasta 6649 en 2002, la mayoria referian exposiciones heterosexuales de riesgo, los usuarios de drogas inyectadas disminuyeron del 19% al 2% de los sujetos analizados, y las mujeres que ejercian la prostitucion aumentaron del 6% al 26%. El numero de personas diagnosticadas de infeccion por el VIH descendio desde 604 in 1992 hasta 153 in 2002 y la seroprevalencia de 13,6% a 2,3%. En todas las categorias de exposicion se observaron caidas en la seroprevalencia de VIH, mas pronunciados en los primeros anos, y con posterior tendencia a la estabilizacion. En 2002 las mayores seroprevalencias se observaron en UDI (14,2%), en hombres homo/bisexuales (7,5%) y en personas con pareja heterosexual diagnosticada de infeccion por el VIH (10,2%).
P2.03b-048 Access to Biomarker Testing in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Apar Ganti, Fred R. Hirsch, Murry Wynes, Arliene Ravelo, Suresh Ramalingam, Raluca Ionescu-Ittu, Irina Pivneva, Hossein Borghaei
Journal: Journal of Thoracic Oncology (2017)
Do sports medicine clinicians have credible alternatives to knee arthroscopy for the degenerative knee?
Authors: Kay M Crossley, Joanne L Kemp, Adam G Culvenor, Christian J Barton
Journal: British Journal of Sports Medicine (2017)

The evidence refuting arthroscopy to treat meniscal degeneration and knee osteoarthritis (OA) is clear and compelling.1–3 At least 10 randomised controlled trials and a systematic review attribute knee arthroscopy with a clinically insignificant benefit (approximately 2.4 mm out of 100 mm for improved pain).1 2 Furthermore, knee arthroscopy confers no benefit when compared head to head with a cost-effective, supervised exercise therapy programme.4

Sports medicine clinicians are key providers of care for middle-aged patients with painful knees. If we ‘abandon ship’, abandon arthroscopy as a treatment option for our patients,3 what can we offer them? What can we say when a patient walks into our practice/clinic hoping for an arthroscopic ‘clean up’? What alternatives do we have?

The answer should be simple, but sadly, it is not. Current evidence and clinical guidelines recommend supervised exercise therapy and education.5 However, our recent unpublished survey of 116 physiotherapists (Australia and Canada) who regularly treat knee …
TCT-341 Percutaneous coronary intervention in cardiac allograft vasculopathy: long term results from a single centre
Authors: Silvia Vilches-Soria, Juan Francisco Oteo Dominguez, Ebrey León Aliz, Carlos Arellano Flores, Javier Lopez-Pais, Jorge Manuel Solano López Morel, Arturo Garcia-Touchard, Jose Antonio Fernandez Diaz, Javier Goicolea, Javier Segovia-Cubero
Journal: Journal of the American College of Cardiology (2017)
IL-10, TGF-β, and glucocorticoid prevent the production of type 2 cytokines in human group 2 innate lymphoid cells
Authors: Noriko Ogasawara, Julie A. Poposki, Aiko I. Klingler, Bruce K. Tan, Ava R. Weibman, Kathryn E. Hulse, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Robert P. Schleimer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Joseph R. Raviv, Pejman Soroosh, Omid Akbari, Tetsuo Himi, Robert C. Kern, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2017)
Enterochromaffin cells in the gut: a distant regulator of brain function?
Authors: Chun Yang, Jie Gao, Jie Zhang, Ai-Lin Luo
Journal: Gut (2017)

We read with great interest the recent excellent work by Stevens et al ,1 in which the authors showed that zonulin and fatty acid-binding protein 2 have a relationship with the increase in lipopolysaccharide (LPS) and abnormal composition of gut microbiota in patients with anxiety or depression. We appreciate these findings and would like to discuss the role of enterochromaffin cells (ECs) in brain function in this context.

Accumulating evidence has shown that neuropsychiatric diseases are frequently associated with gut microbiota disorders.2 It has been widely recognised that toxins within the human body mainly stem from the gut.3 The opening of intercellular tight junctions in the gut allow many toxins into the bloodstream that then have a deleterious effect on the brain, finally resulting in a series of neuropsychiatric symptoms. …
Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy
Authors: Weiquan Zhu, Dallas S. Shi, Jacob M. Winter, Bianca E. Rich, Zongzhong Tong, Lise K. Sorensen, Helong Zhao, Yi Huang, Zhengfu Tai, Tara M. Mleynek, Jae Hyuk Yoo, Christine Dunn, Jing Ling, Jake A. Bergquist, Jackson R. Richards, Amanda Jiang, Lisa A. Lesniewski, M. Elizabeth Hartnett, Diane M. Ward, Alan L. Mueller, Kirill Ostanin, Kirk R. Thomas, Shannon J. Odelberg, Dean Y. Li
Journal: Journal of Clinical Investigation (2017)

The devastating sequelae of diabetes mellitus include microvascular permeability, which results in retinopathy. Despite clinical and scientific advances, there remains a need for new approaches to treat retinopathy. Here, we have presented a possible treatment strategy, whereby targeting the small GTPase ARF6 alters VEGFR2 trafficking and reverses signs of pathology in 4 animal models that represent features of diabetic retinopathy and in a fifth model of ocular pathological angiogenesis. Specifically, we determined that the same signaling pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs exert distinct but complementary effects on VEGFR2 trafficking and signal transduction. ARF6 activation was independently regulated by 2 different ARF GEFs — ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100 activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in either pathway inhibited VEGFR2 signal output. Finally, using a combination of in vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6 is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2 trafficking has potential as a therapeutic approach for retinal vascular diseases such as diabetic retinopathy.
Abstract 11893: The Impact of Statin Therapy on Survival Following Inpatient Cardiac Arrest
Authors: Rami Khoury Abdulla, Amr E Abbas
Journal: Circulation (2016)

Introduction: Over 200,000 hospitalized patients suffer cardiac arrest annually with a high morbidity and mortality following cardiopulmonary resuscitation (CPR). The aim of this study was to examine factors associated with survival post CPR in hospitalized patients. Hypothesis: Pre-arrest statin therapy is associated with improved survival. Methods: A retrospective analysis of consecutive hospitalized patients that underwent CPR between 4/2012 to 12/2013 at Beaumont Hospital. Patients with CPR perioperatively, in the setting of trauma, during pregnancy and postpartum were excluded, also patients or their surrogates who elected palliative care/hospice were excluded. Univariable and a step-down logistic regression multivariable analysis were performed. Results: Of 124 patients included in the study, 80 patients died, whereas 44 patients survived. Pre-arrest clinical factors and CPR characteristics associated with survival on univariable analysis were: History of PCI in 36.4% of survivors compared to 16.5% of those who did not survive (p=0.013). Hyperlipidemia was more common in survivors (68.2% versus 32.5%, p=0.001), as well as being on statins (76.7% versus 43%, p=0.0004). Those who did not survive were more likely to have active cancer (16.3% versus 2.3%, p=0.018), less likely to have a shockable rhythm (7.9% versus 27.9%, p=0.003), and more likely to have CPR ≥ 15 minutes (82.4% versus 19.5%, p&lt;0.0001). On multivariable analysis, CPR duration and statin therapy were the only factors associated with survival. Those who did not survive were more likely to have CPR ≥ 15 minutes (Adjusted OR 18.08, 95% CI 6.5-50.5, p&lt;0.001) and less likely to be on statin therapy before cardiac arrest ( Adjusted OR 0.29, 95% CI : 0.10-0.83 p= 0.021) with C-Statistic of 0.86. Conclusion: This study suggests that being on statin therapy is associated with high likelihood of survival following CPR. Further studies are needed to confirm this finding.
Adequate SIRT activity dose is as important as adequate chemotherapy dose – Authors' reply
Authors: Ricky A Sharma, Peter Gibbs, Navesh K Sharma, Jens Ricke, Julien Taieb, Joanna Moschandreas, Pradeep S Virdee, Peter Dutton, Guy van Hazel, Harpreet S Wasan
Journal: The Lancet Oncology (2017)
Extent of Dorsolateral Prefrontal Cortex Plasticity and Its Association With Working Memory in Patients With Alzheimer Disease
Authors: Sanjeev Kumar, Reza Zomorrodi, Zaid Ghazala, Michelle S. Goodman, Daniel M. Blumberger, Amay Cheam, Corinne Fischer, Zafiris J. Daskalakis, Benoit H. Mulsant, Bruce G. Pollock, Tarek K. Rajji
Journal: JAMA Psychiatry (2017)

<h3>Importance</h3> The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known. <h3>Objectives</h3> To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants. Participants were recruited from a university teaching hospital from May 2013 to October 2016. <h3>Main Outcomes and Measures</h3> Plasticity of the DLPFC measured as potentiation of cortical-evoked activity using paired associative stimulation (a combination of peripheral nerve electrical stimulation and transcranial magnetic stimulation) combined with electroencephalography. Working memory was assessed with the<i>n</i>-back task (1- and 2-back) and measured using the<i>A'</i>statistic. <h3>Results</h3> Among the 32 participants with AD, 17 were women and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with controls (mean [SD] potentiation, 1.40 [0.35];<i>F</i><sub>1,44</sub> = 5.90;<i>P</i> = .02; between-group comparison, Cohen<i>d</i> = 0.77;<i>P</i> = .01). Participants with AD also had impaired performances on the 1-back condition (mean [SD]<i>A</i>′ = 0.47 [0.30]) compared with controls (mean [SD]<i>A</i>′ = 0.96 [0.01]; Cohen<i>d</i> = 1.86;<i>P</i> &lt; .001), with similar findings for participants with AD on the 2-back condition (mean [SD]<i>A'</i> = 0.29 [0.2]) compared with controls (mean [SD],<i>A</i>′ = 0.85 [0.18]; Cohen<i>d</i> = 2.83;<i>P</i> &lt; .001). Plasticity of DLPFC was positively associated with working memory performance on the 1-back<i>A</i>′ (parameter estimate<i>B</i>[SE] = 0.32 [0.13]; standardized β = 0.29;<i>P</i> = .02) and 2-back<i>A</i>′ (<i>B</i> [SE] = 0.43 [0.15]; β = 0.39;<i>P</i> = .006) across both groups after controlling for age, education, and attention. <h3>Conclusions and Relevance</h3> This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD.
EGFRvIII vaccine in glioblastoma—InACT-IVe or not ReACTive enough?
Authors: Michael Platten
Journal: Neuro-Oncology (2017)

Variant III of the epidermal growth factor receptor (EGFRvIII) fulfills many criteria of a suitable target for a glioblastoma vaccine.Unlike many tumor-associated self antigens currently targeted in vaccine trials, it is specifically expressed by tumor cells but not in healthy tissue, thus representing a so-called neoantigen.The in-frame deletion of the extracellular domain in EGFRvIII results in the fusion of exons 1 and 8 and thus generates a peptide sequence encompassing the fusion point, which is foreign to the immune system.EGFRvIII is the most common gain-offunction mutation in glioblastoma shown to contribute to the malignant phenotype by complex cytokine network alterations. 1Preclinical studies have shown immunogenicity and efficacy in several tumor models. 2In the clinical development the vaccine (rindopepimut) has early on been tested in patients with newly diagnosed glioblastoma to ensure low tumor burden and a sufficient time window to achieve a meaningful immune response.The single-arm ACTIVATE, ACT II, and ACT III trials in patients with newly diagnosed, resected, EGFRvIII+ glioblastoma demonstrated a median survival of 20-22 months, comparing favorably to historical matched controls. 3ith these data at hand, the stage seemed to be set for the first successful registration trial of a glioblastoma immunotherapy.The double blind, phase III ACT-IV trial is an important study and randomized 745 patients with newly diagnosed, resected, EGFRvIII+ glioblastoma stable after radiochemotherapy to receive rindopepimut or control (keyhole limpet hemocyanin [KLH]) concurrent with standard temozolomide. 4he trial screened 4652 patients, reflecting the prevalence of EGFRvIII of 20%-25%.The primary endpoint was overall survival (OS) for patients with no or small enhancing tumors (<2 cm 2 ), operationally defined as minimal residual disease (MRD).This endpoint was chosen under the assumption that MRD improves the starting conditions for any immune intervention otherwise deemed to overcome the suppressive microenvironment of large residual tumors.The trial was negative with a median OS of 20.1 months in the rindopepimut group versus 20.0 months in the control group. 4o rationalize why ACT-IV was negative despite robust induction of humoral immune responses, it is imperative to go Overall survival
P3.02c-048 A Phase I/II Trial Evaluating the Combination of Stereotactic Body Radiotherapy and Pembrolizumab in Metastatic NSCLC
Authors: Roy Decker, Sarah Goldberg, Sameer Nath, Zain Husain, Rogerio Lilenbaum, Kurt Schalper, Anne Chiang, Mehmet Altan, Daniel Zelterman, Susan Kaech, Roy Herbst, Scott Gettinger
Journal: Journal of Thoracic Oncology (2017)
Tendencias recientes de las infecciones por Chlamydia trachomatis en el Reino Unido y perspectivas de un programa de detección nacional
Authors: Jeanne Pimenta, K. A. Fenton
Journal: Eurosurveillance (2001)

Se ha realizado un estudio piloto en el Reino Unido destinado a evaluar la viabilidad de un programa nacional de deteccion de infecciones genitales por clamidia. Los resultados preliminares muestran una alta tasa de aceptacion (70% de los candidatos) y una cobertura significativa de la poblacion diana (40% en un periodo de seis meses). Otros estudios estan en marcha para precisar los procedimientos de despistaje y las estrategias de notificacion de contactos sexuales mas adecuadas, asi como para evaluar el costo-efectividad de un programa nacional.
Abstract 12420: Ivabradine Effectiveness in Everyday Clinical Practice: Results From a Population With Stable Coronary Artery Disease and Coronary Stenosis (&gt;50%) Not Submitted for Revascularization
Authors: Ioannis Zarifis, Apostolos Katsivas
Journal: Circulation (2015)

Introduction: Angina pectoris is the most common manifestation of flow limited coronary stenosis, reflecting myocardial ischemia and limiting significantly ordinary activities of patients. Purpose: To evaluate Ivabradine’s anti-anginal effectiveness and effect on quality of life (QoL), when co-administered with a β-blocker, during a 4 month therapy of patients with coronary artery disease (CAD) and coronary stenosis (&gt;50%) not submitted for revascularization. Methods: This is a post hoc analysis (563 patients with documented coronary stenosis &gt;50%) of a Pan-Hellenic, prospective, non-interventional study including 2403 patients with CAD and stable angina. Follow-up visits were performed at baseline, at 1 and 4 months after inclusion, while patients’ QoL was assessed by EQ-5D questionnaire. Results: 9 patients (1.6%) out of 563 enrolled CAD patients with &gt;50% coronary stenosis, prematurely discontinued treatment. Mean heart rate decrease on study completion compared to baseline was -17.5 bpm (p&lt;0.001), while mean number of angina attacks and nitroglycerin consumption decrease was -1.8 and -1.4 times/week respectively (p&lt;0.001). The percentage of patients with angina CCS I (Canadian Cardiovascular Society classification), increased from 37% (baseline), to 87% (study completion) (p&lt;0.001). For all dimensions of EQ-5D, the improvement was significant leading to an overall amelioration of daily functioning at study completion (p&lt;0.001) At the 1st month of treatment, 52% of patients received 7.5 mg bid of Ivabradine, which was maintained throughout the study, while compliance to treatment was high; almost 97% of the population was taking their treatment “every day” or “quite often” throughout the study. Conclusions: Ivabradine administration presents a significant anti-anginal effect, while improving also QoL and restoring a level of satisfactory usual activity in patients with coronary stenosis &gt;50% not submitted for revascularization.
Heteromultivalent targeting of integrin αvβ3 and neuropilin 1 promotes cell survival via the activation of the IGF-1/insulin receptors
Authors: Tao Jia, Jungyoon Choi, Jéremy Ciccione, Maxime Henry, Ahmad Mehdi, Jean Martinez, Béatrice Eymin, Gilles Subra, Jean-Luc Coll
Journal: Biomaterials (2017)
Brief Report: Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthritis
Authors: Martijn H. van den Bosch, Arjen B. Blom, Fons A. van de Loo, Marije I. Koenders, Floris P. Lafeber, Wim B. van den Berg, Peter M. van der Kraan, Peter L. van Lent
Journal: Arthritis & Rheumatology (2017)

Increased Wnt signaling in chondrocytes is associated with development of osteoarthritis (OA). However, OA is considered a disease of the entire joint, where the synovium has been attributed an important role in disease pathogenesis and progression. This study was undertaken to determine whether Wnt signaling in synovial tissue could contribute to pathologic development of OA through the production of matrix metalloproteinases (MMPs), and to assess the relationship of synovial expression of Frizzled (FZD) receptors and the Wnt inhibitor FRZB to MMP expression and disease progression in patients with early OA in the Dutch Cohort Hip and Cohort Knee (CHECK) study cohort.In mouse knee joints, human WNT8A and mouse Wnt16 were overexpressed using adenoviral vectors, and expression of messenger RNA (mRNA) for MMPs in the synovium was determined by reverse transcription-polymerase chain reaction or Luminex assay. In human synovial tissue from a subgroup of patients with early OA with knee pain enrolled in the CHECK cohort, levels of Wnt family members were assessed for linkage to MMP expression and disease progression. In addition, MMP production in human synovium from patients with end-stage OA was determined after stimulation of Wnt signaling with WNT3A or inhibition with FRZB or DKK1 in the synovium.Overexpression of WNT8A and Wnt16 in mouse knee joints induced MMP expression in vivo. Expression of MMPs relevant to human OA in the synovium from CHECK study participants significantly correlated with expression of FZD1, FZD10, and FRZB mRNA. Moreover, increased FZD1 mRNA expression and decreased FRZB mRNA expression were observed in CHECK study patients who experienced disease progression compared to those who were nonprogressors. Stimulation of human OA synovium with WNT3A induced the production of various MMPs, whereas inhibition of Wnt signaling with FRZB or DKK1 reduced the production of MMPs.Wnt signaling in the synovium may potently induce progression of OA via increased production of MMPs.