tbuckley/cabot-search huggingface dataset:
Abstract 16214: Intracoronary Optical Coherence Tomography-Derived Virtual Fractional Flow Reserve for the Assessment of Coronary Artery Disease With Computational Fluid Dynamics Simulation
Authors: Fumiyasu Seike, Teruyoshi Uetani, Kazuhisa Nishimura, Hiroshi Kawakami, Haruhiko Higashi, Akira Fujii, Jun Aono, Takayuki Nagai, Katsuji Inoue, Jun Suzuki, Takafumi Okura, Kazunori Yasuda, Jitsuo Higaki, Shuntaro Ikeda
Journal: Circulation (2017)

Introduction:  Fractional flow reserve (FFR) and optical coherence tomography (OCT) are widely used for the assessment of morphology and myocardial ischemia in catheter laboratory. Computational fluid dynamics (CFD) has proven to be the method of choice for obtaining accurate readings of flow in subject specific arterial geometries.   Hypothesis:  We assessed the hypothesis that FFR value is accurately calculated with OCT imaging, CFD and novel original algorithm.   Methods:  We retrospectively analyzed 20 lesions in 20 patients with moderate -severe coronary stenosis, who underwent OCT and FFR measurements simultaneously. OCT-derived FFR (FFR OCT ) was calculated by the OCT, CFD and novel original algorithm.   Results:  The representative calculation was shown in Figure A (Streak line in the lesion) and B (Pressure distribution in the lesion). Mean values of percent diameter stenosis by quantitative coronary angiography (QCA) and FFR were 53.7 ± 10.7 and 0.71 ± 0.11, respectively. FFR OCT  showed a robust linear correlation with FFR measurements (r = 0.85, p    Conclusions:  The computation of FFR OCT  enables assessment not only of anatomic information, but also of the myocardial ischemia. FFR OCT has the potential to become an alternative method to conventional anatomical information for the assessment of functional myocardial ischemia.
Attention Deficit Hyperactivity Disorder (ADHD): Controversy, Developmental Mechanisms, and Multiple Levels of Analysis
Authors: Stephen P. Hinshaw
Journal: Annual Review of Clinical Psychology (2017)

Controversy abounds regarding the symptom dimensions of attention problems, impulsivity, and hyperactivity, developmentally extreme and impairing levels of which compose the diagnostic category of attention deficit hyperactivity disorder (ADHD). I highlight causal factors, underlying mechanisms, developmental trajectories, and female manifestations of ADHD, integrating the psychobiological underpinnings of this syndrome with contextual factors related to its clinical presentation, impairments, and soaring increases in diagnosed prevalence. Indeed, despite strong heritability, ADHD is expressed via transactional patterns of influence linked to family-, school-, peer-, neighborhood-, and policy-related factors. Moreover, intervention strategies must take into account both pharmacologic and behavioral modalities if the goal is to enhance competencies, rather than symptom reduction per se. A comprehensive understanding of ADHD mandates multiple levels of analysis—spanning genes, neurotransmission, brain pathways, individual skill levels, family socialization, peer relationships, and educational and cultural forces—which must be integrated and synthesized to surpass reductionist accounts, reduce stigma, and maximize the impact of prevention- and intervention-related efforts.
Prognostic Implication of Bone Marrow Abnormality of Appendicular Skeletons Detected By Low-Dose Multidetector Computed Tomography in Patients with Myelodysplastic Syndrome
Authors: Yoshiaki Abe, Tomotaka Ugai, Manabu Fujisawa, Kentaro Narita, Akihiro Kitadate, Hiroki Kobayashi, Masami Takeuchi, Kosei Matsue
Journal: Blood (2017)
Results of a phase I study of RX-5902: An orally bioavailable inhibitor of phosphorylated P68, targeting solid tumors.
Authors: S. Gail Eckhardt, William Larry Gluck, Martin Gutierrez, Christine Peterson, Reza Mazhari, Ely Benaim
Journal: Journal of Clinical Oncology (2016)

2554 Background: RX-5902 is a novel compound that targets phosphorylated p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. Phosphorylated p68 may play a vital role in cell proliferation and tumor/cancer progression. As a single agent, RX-5902 inhibits tumor growth, alters cell migration and enhances survival in a variety of in vivo animal xenograft tumor models (e.g., breast, ovarian, renal, pancreatic). We report the data from the first clinical study of RX-5902 as a single agent to treat solid tumors. Methods: This is a Phase 1 study (NCT02003092) designed to evaluate safety, tolerability and pharmacokinetics following increasing doses of RX-5902 at varying schedules. Primary objectives include safety, tolerability and dose limiting toxicities to identify the maximum tolerated dose and a recommended phase 2 dose and schedule (RP2D). Secondary objectives were pharmacokinetics (PK) and antitumor activity (RECIST v1.1). Eligible subjects (aged ≥ 18 years) with relapsed/refractory solid tumors received oral RX-5902 at 1, 3, 5 or 7 times per week for 3 weeks followed by 1 week of rest or for 4 weeks without a rest. Plasma concentrations were measured using a validated LC-MS/MS assay, and noncompartmental pharmacokinetic parameters were calculated using WinNonlin, Version 6.4. Results: As of January 2016, 18 subjects have been enrolled (8 Females, 10 males). No dose limiting toxicities or treatment related SAEs have been reported. Six subjects have experienced stable disease; three subjects are currently receiving treatment for > 1 year. The most common side effects were grade 1 related adverse events: nausea, vomiting and fatigue; no grade 2 related events have been reported. RX-5902 was orally bioavailable with median Tmax of 2 hours and median elimination half-life of 12 hours. Conclusions: Data from this study support that RX-5902 is safe and well tolerated at the doses and schedules tested. Early anti-tumor activity has been observed. A recommended phase 2 dose for RX-5902 for the treatment of triple negative breast cancer and advanced ovarian cancer will be presented. Clinical trial information: NCT02003092.
Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty‐Two–Week Randomized, Double‐Blind, Placebo‐Controlled Study
Authors: William Stohl, Andreas Schwarting, Masato Okada, Morton Scheinberg, Andrea Doria, Anne E. Hammer, Christi Kleoudis, James Groark, Damon Bass, Norma Lynn Fox, David Roth, David Gordon
Journal: Arthritis & Rheumatology (2017)

To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).Patients with moderate-to-severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Secondary end points were reduction in the corticosteroid dosage and time to severe flare. Safety was assessed according to the adverse events (AEs) reported and the laboratory test results.Of 839 patients randomized, 836 (556 in the belimumab group and 280 in the placebo group) received treatment. A total of 159 patients withdrew before the end of the study. At entry, mean SELENA-SLEDAI scores were 10.5 in the belimumab group and 10.3 in the placebo group. More patients who received belimumab were SRI4 responders than those who received placebo (61.4% versus 48.4%; odds ratio [OR] 1.68 [95% confidence interval (95% CI) 1.25-2.25]; P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171.0 days versus 118.0 days; hazard ratio 0.51 [95% CI 0.35-0.74]; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40-52 (18.2% versus 11.9%; OR 1.65 [95% CI 0.95-2.84]; P = 0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported by 10.8% of patients taking belimumab and 15.7% of those taking placebo. A worsening of IgG hypoglobulinemia by ≥2 grades occurred in 0.9% of patients taking belimumab and 1.4% of those taking placebo.In patients with moderate-to-severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.
Paroxysmal bradyarrhythmias are frequent among heart transplant recipients with unexplained syncope: a study based on implantable loop recorders
Authors: Emilse Martínez‐Paz, Eduardo Barge‐Caballero, Laura Álvarez‐Roy, Gonzalo Barge‐Caballero, David Couto‐Mallón, María J. Paniagua‐Martín, Ignacio Mosquera‐Pérez, Luisa Pérez‐Álvarez, Javier Muñiz, José J. Cuenca‐Castillo, José Manuel Vázquez‐Rodríguez, María G. Crespo‐Leiro
Journal: European Journal of Heart Failure (2017)
Targeting Mcl-1 enhances DNA replication stress sensitivity to cancer therapy
Authors: Guo Chen, Andrew T. Magis, Ke Xu, Dongkyoo Park, David S. Yu, Taofeek K. Owonikoko, Gabriel L. Sica, Sarah W. Satola, Suresh S. Ramalingam, Walter J. Curran, Paul W. Doetsch, Xingming Deng
Journal: Journal of Clinical Investigation (2017)

DNA double-strand breaks (DSBs) are mainly repaired either by homologous recombination (HR) or by nonhomologous end-joining (NHEJ) pathways. Here, we showed that myeloid cell leukemia sequence 1 (Mcl-1) acts as a functional switch in selecting between HR and NHEJ pathways. Mcl-1 was cell cycle-regulated during HR, with its expression peaking in S/G2 phase. While endogenous Mcl-1 depletion reduced HR and enhanced NHEJ, Mcl-1 overexpression resulted in a net increase in HR over NHEJ. Mcl-1 directly interacted with the dimeric Ku protein complex via its Bcl-2 homology 1 and 3 (BH1 and BH3) domains, which are required for Mcl-1 to inhibit Ku-mediated NHEJ. Mcl-1 also promoted DNA resection mediated by the Mre11 complex and HR-dependent DSB repair. Using the Mcl-1 BH1 domain as a docking site, we identified a small molecule, MI-223, that directly bound to BH1 and blocked Mcl-1-stimulated HR DNA repair, leading to sensitization of cancer cells to hydroxyurea- or olaparib-induced DNA replication stress. Combined treatment with MI-223 and hydroxyurea or olaparib exhibited a strong synergy against lung cancer in vivo. This mechanism-driven combination of agents provides a highly attractive therapeutic strategy to improve lung cancer outcomes.
PANOVA: A phase II study of TTFields (150 kHz) concomitant with standard chemotherapy for front-line therapy of advanced pancreatic adenocarcinoma—Updated efficacy results.
Authors: Manuel Benavides, Carmen Guillen, Fernando Rivera, Javier Gallego, Jose A. Lopez-Martin, Marc Küng
Journal: Journal of Clinical Oncology (2017)

e15790 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269). Methods: Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events. Results: The median age was 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72% (62.5% in metastatic disease and 87.5% in locally advanced disease). Conclusions: TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Clinical trial information: NCT01971281.
Riesgos de infecciones asociadas al agua en ambientes naturales o artificiales
Authors: G Nichols
Journal: Eurosurveillance (2006)

Tanto los ambientes naturales como los artificiales contaminados por heces humanas o animales pueden ser responsables de una enfermedad con diarrea. Los ninos son particularmente sensibles a tales exposiciones y a ser afectados por los agentes patogenos. Algunas enfermedades entericas producidas en la ninez pueden ser relativamente benignas y proporcionar una cierta proteccion en la edad adulta, mientras que otras pueden ser mas graves. En este contexto, los dos articulos presentados en esta edicion de Eurosurveillance describen pequenos brotes: el primero, escrito por Chikwe Ihekweazu y colaboradores, esta asociado a la exposicion a un riachuelo contaminado por Escherichia coli procedente de heces animales [1]; y el segundo, escrito por Melanie Jones y colaboradores, describe la exposicion a una atraccion acuatica contaminada por Cryptosporidium parvum procedente de heces humanas o animales [2].
Plant–Soil Feedback: Bridging Natural and Agricultural Sciences
Authors: Pierre Mariotte, Zia Mehrabi, T. Martijn Bezemer, Gerlinde B. De Deyn, Andrew Kulmatiski, Barbara Drigo, G.F. (Ciska) Veen, Marcel G.A. van der Heijden, Paul Kardol
Journal: Trends in Ecology & Evolution (2017)
Advances in Stimulus‐Responsive Polymeric Materials for Systemic Delivery of Nucleic Acids
Authors: Minjie Sun, Kaikai Wang, David Oupický
Journal: Advanced Healthcare Materials (2017)

Abstract Polymeric materials that respond to a variety of endogenous and external stimuli are actively developed to overcome the main barriers to successful systemic delivery of therapeutic nucleic acids. Here, an overview of viable stimuli that are proved to improve systemic delivery of nucleic acids is provided. The main focus is placed on nucleic acid delivery systems (NADS) based on polymers that respond to pathological or physiological changes in pH, redox state, enzyme levels, hypoxia, and reactive oxygen species levels. Additional discussion is focused on NADS suitable for applications that use external stimuli, such as light, ultrasound, and local hyperthermia.
Abstract 20062: Remodeling of Repolarization and Arrhythmia Susceptibility in a Myosin Binding Protein C Knockout Mouse Model
Authors: Amir Toib, Sadia Mohsin, Giulia Borghetti Borghetti, Xiaoxiao Zhang, Chen Zhang, Markus Wallner, Yijun Yang, Constantine D Troupes, Hajime Kubo, Thomas E Sharp, Eric Feldsott, Remus M Berretta, Danielle M Trappanese, Polina Gross, Xiongwen Chen, Steven R Houser
Journal: Circulation (2016)

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease (1:500 in the general population) and amongst the leading causes of sudden cardiac death (SCD) in the young....
Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited
Authors: K. Samitas, A. Carter, H. H. Kariyawasam, G. Xanthou
Journal: Allergy (2017)

Abstract Allergic rhinitis ( AR ), chronic rhinosinusitis ( CRS ) and asthma often co‐exist. The one airway model proposes that disease mechanisms occurring in the upper airway may mirror lower airway events. Airway remodelling is the term used to describe tissue structural changes that occur in a disease setting and reflect the dynamic process of tissue restructuring during wound repair. Remodelling has been long identified in the lower airways in asthma and is characterized by epithelial shedding, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, airway smooth muscle hyperplasia and increased angiogenesis. The concept of upper airway remodelling has only recently been introduced, and data so far are limited and often conflicting, an indication that more detailed studies are needed. Whilst remodelling changes in AR are limited, CRS phenotypes demonstrate epithelial hyperplasia, increased matrix deposition and degradation along with accumulation of plasma proteins. Despite extensive research over the past years, the precise cellular and molecular mechanisms involved in airway remodelling remain incompletely defined. This review describes our current rather limited understanding of airway remodelling processes in AR , CRS and asthma and presents mechanisms both shared and distinct between the upper and lower airways. Delineation of shared and disease‐specific pathogenic mechanisms of remodelling between the sinonasal system and the lung may guide the rational design of more effective therapeutic strategies targeting upper and lower airways concomitantly and improving the health of individuals with inflammatory airway diseases.
Annual Review of Biomedical Engineering
Authors: Martin L. Yarmush, Kenneth R. Diller, Mehmet Toner
Journal: Annual Review of Biomedical Engineering (2017)

The central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. As key intermediaries and modifiers, RNAs undergo various forms of modifications such as methylation, deamination, and hydroxylation. These ... Read More
Improving the diagnosis of invasive aspergillosis by the detection of Aspergillus in broncho-alveolar lavage fluid: Comparison of non-culture-based assays
Authors: Hélène Guegan, Florence Robert-Gangneux, Christophe Camus, Sorya Belaz, Tony Marchand, Marion Baldeyrou, Jean-Pierre Gangneux
Journal: Journal of Infection (2017)
Valoración de dificultad subjetiva y mediante puntuación SMSA de la RME de lesiones colo-rectales no pediculadas de gran tamaño
Authors: E Albéniz, F Ramos, A Elosua, J Espinós, C Guarner, D Martínez, A Herreros De Tejada, E Valdivielso, JG Martínez, MA Álvarez
Journal: Endoscopy (2017)

El sistema de puntuación “SMSA” basado en el tamaño, morfología, localización y acceso (size, morphology, site and access) se ha desarrollado para determinar la complejidad de la RME.
Optical coherence tomography angiography
Authors: Richard F. Spaide, James G. Fujimoto, Nadia K. Waheed, Srinivas R. Sadda, Giovanni Staurenghi
Journal: Progress in Retinal and Eye Research (2017)

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.
Monongahela Passing the Great Western, 1841
Authors: Frederick Butzen
Journal: JAMA (1980)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Protein Homeostatic Modulators, a Novel Class of Cereblon-Targeting Small Molecules As Potential Clinical Candidates in Multiple Myeloma
Authors: Jianxuan Zou, Richard J. Jones, Janet E. Mertz, Hua Wang, Isere Kuiatse, Bob Sullivan, Leah Fung, Normand Richard, Paul Erdman, Eduardo Torres, Aparajita Hoskote Chourasia, Kyle Wh Chan, Frank Mercurio, David I Stirling, Robert Z. Orlowski
Journal: Blood (2017)
Joseph Goldberger—Public Health Champion and Investigator of Pellagra
Authors: Kishore L. Jayakumar, Robert G. Micheletti
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal