tbuckley/cabot-search huggingface dataset:
Abstract #4575: Determination of mechanisms of chemotherapy synergy in small cell lung cancer cell lines
Authors: Shadia Jalal, Sarah Shuck, John Turchi
Journal: Cancer Research (2009)

We have developed an  in vitro  model system using NCI H146 small cell lung cancer (SCLC) cells to study the interactions between potential therapeutic agents. We have validated with our model using cisplatin and etoposide, which is the standard of care for SCLC. NCI H146 SCLC cell lines were treated at different times with varying concentrations of cisplatin, etoposide and the combination. Viability assays were performed including assessment of metabolic activity using a modified MTT-based assay (CCK-8), cell cycle analysis assessed by propidium iodide staining and determination of apoptosis via annexin V/PI staining. IC 50  values were obtained for each agent individually and combination treatment performed at a constant ratio of IC 50  values. The combination index was then calculated from these analyses to assess the potential interaction of the 2 drugs. While the combination of platinum and etoposide is a standard regimen for treatment of SCLC, the poor overall survival necessitates the development of more effective therapies. Amrubicin is a synthetic anthracycline developed in Japan that has shown promise and significant activity in SCLC in clinical trials. Amrubicin has been studied in combination with a small number of other agents including topotecan, cisplatin and carboplatin, yet no studies have evaluated Amrubicin in conjunction with cyclophosphamide. Considering that combination treatment regimens containing anthracyclines with cyclophosphamide are the backbone of treatment for a variety of cancers, we have undertaken the evaluation of this combination treatment regimen in SCLC. Results will be presented using this H146 model system to determine the drug-drug interactions of Amrubicin and cyclophosphamide in an  in vitro  model of SCLC.      Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4575.
Nystagmus and Platinum Hair
Authors: Maria Fernanda Abalem, P. Kumar Rao, Rajesh C. Rao
Journal: JAMA (2018)

A 25-year-old woman of European ethnic ancestry with poor vision and photophobia since childhood and a history of pendular nystagmus had hypopigmented hair and lashes, fair skin, and reddish-pink irides on examination, with visual acuity 20/60 bilaterally. What would you do next?
The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study
Authors: Shu-Ying Liu, Daryl J Wile, Jessie Fanglu Fu, Jason Valerio, Elham Shahinfard, Siobhan McCormick, Rostom Mabrouk, Nasim Vafai, Jess McKenzie, Nicole Neilson, Alexandra Perez-Soriano, Julieta E Arena, Mariya Cherkasova, Piu Chan, Jing Zhang, Cyrus P Zabetian, Jan O Aasly, Zbigniew K Wszolek, Martin J McKeown, Michael J Adam, Thomas J Ruth, Michael Schulzer, Vesna Sossi, A Jon Stoessl
Journal: The Lancet Neurology (2018)
Novel Insights into the Clinical Phenotype and Pathophysiology Underlying Low VWF Levels: The Low Von Willebrand Factor in Ireland Cohort (LoVIC) Study
Authors: Michelle Lavin, Sonia Aguila, Sonja Schneppenheim, Niall Dalton, Jamie M O'Sullivan, Niamh M O'Connell, Kevin M. Ryan, Mary Byrne, Margaret Nolan, Roger Preston, Ulrich Budde, Paula D. James, Jorge Di Paola, James S O'Donnell
Journal: Blood (2016)
Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III
Authors: Eric B. Suhler, Alfredo Adán, Antoine P. Brézin, Eric Fortin, Hiroshi Goto, Glenn J. Jaffe, Toshikatsu Kaburaki, Michal Kramer, Lyndell L. Lim, Cristina Muccioli, Quan Dong Nguyen, Joachim Van Calster, Luca Cimino, Martina Kron, Alexandra P. Song, Jianzhong Liu, Sophia Pathai, Anne Camez, Ariel Schlaen, Mirjam E.J. van Velthoven, Albert T. Vitale, Manfred Zierhut, Samir Tari, Andrew D. Dick
Journal: Ophthalmology (2018)

To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.Phase 3, open-label, multicenter clinical trial extension (VISUAL III).Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF.Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78.Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff.Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials.Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors)
Authors: G. Redelman-Sidi, O. Michielin, C. Cervera, C. Ribi, J.M. Aguado, M. Fernández-Ruiz, O. Manuel
Journal: Clinical Microbiology and Infection (2018)
Randomised phase 3 trial of enzalutamide in first-line androgen deprivation therapy for metastatic prostate cancer: The ANZUP ENZAMET Trial (ANZUP 1304).
Authors: Ian D. Davis, Martin R. Stockler, Andrew James Martin, Wendy Hague, Xanthi Coskinas, Sonia Yip, Emily Tu, Nicola Jane Lawrence, Howard Chan, Ray McDermott, Simon Chowdhury, Vittorio Marchesin, Olwyn Deignan, Francisco Vera-Badillo, Scott A. North, Alexander Montenegro, Christopher Sweeney
Journal: Journal of Clinical Oncology (2016)

TPS5090 Background: Androgen deprivation therapy (ADT) is widely used as initial treatment for hormone-naive, metastatic prostate cancer (PC). Meta-analysis of RCTs showed a 3% absolute improvement in 5 year survival with the addition of non-steroidal anti androgen (NSAA) to ADT. Residual, low level androgen receptor (AR) signalling or agonist activity from conventional NSAA may provide a stimulatory signal to hormone-sensitive PC cells. We hypothesize that the early use of enzalutamide, a more potent and effective AR blocker, will reduce residual AR signalling and improve survival. The aim is to determine whether ADT + enzalutamide improves overall survival (OS) compared to ADT + conventional NSAA in M1 castrate-naïve PC. Methods: DESIGN: open label, randomised, phase 3 trial including ANZ, Canada, UK, Ireland and USA. ELIGIBILITY: metastatic PC starting first line ADT. STRATIFICATION: volume of disease, anti-resorptive therapy, comorbidities, planned early docetaxel use, study site. ENDPOINTS: OS (primary), PSA and clinical progression free survival (PFS), health related quality of life, adverse events and cost-effectiveness. Tertiary correlative objectives: identification of prognostic/predictive biomarkers from archival tumour tissue and fasting bloods collected at baseline, week 24 and progression. 1100 target participants + 3.5 years minimum follow-up for 80% power to detect a 25% reduction in the hazard of death assuming an OS rate at 3 years of 65% in control group. TREATMENT: medical or surgical castration plus either enzalutamide 160mg daily orally, or conventional oral NSAA until disease progression or prohibitive toxicity. Early docetaxel at investigator discretion. ASSESSMENTS: baseline, days 29 and 85 then 12 weekly until clinical progression; imaging prior to randomisation and on progression (PSA and clinical). 70 sites open with total accrual of 444 participants on 19th January 2016. ENZAMET is an international investigator-initiated cooperative group trial led by ANZUP Cancer Trials Group with funding from Astellas. ANZCTR: ACTRN12614000110684 Clinical trial information: NCT02446405.
Macitentan in pulmonary hypertension due to left ventricular dysfunction
Authors: Jean-Luc Vachiéry, Marion Delcroix, Hikmet Al-Hiti, Michela Efficace, Martin Hutyra, Gabriela Lack, Kelly Papadakis, Lewis J. Rubin
Journal: European Respiratory Journal (2018)

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12, versus placebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1-0.7) L·min-1·m-2) and decrease in NT-proBNP (0.77 (0.55-1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentan versus placebo.Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo. Macitentan resulted in no significant changes in any exploratory end-points.
Common measure of quality of life for people with systemic sclerosis across seven European countries: a cross-sectional study
Authors: Mwidimi Ndosi, Begonya Alcacer-Pitarch, Yannick Allanore, Francesco del Galdo, Marc Frerix, Sílvia García-Díaz, Roger Hesselstrand, Christine Kendall, Marco Matucci-Cerinic, Ulf Mueller-Ladner, Gunnel Sandqvist, Vicenç Torrente-Segarra, Tim Schmeiser, Matylda Sierakowska, Justyna Sierakowska, Stanslaw Sierakowski, Anthony Redmond
Journal: Annals of the Rheumatic Diseases (2018)

The aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc).This was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward-backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence.The adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale.The individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment.
Abstract 11738: Migraine With Aura, an Undescribed Complication of Catheter Ablation of Atrial Fibrillation
Authors: Volker Kuehlkamp, Matthias Gass, Bogdan Stanciu, Bernd Eigenberger
Journal: Circulation (2016)

Catheter ablation (CAbl), requiring transseptal puncture, has emerged to a standard procedure in patients (Pts) with symptomatic atrial fibrillation (AF). Frequently a small right to left shunt can be observed with Valsalva maneuvers after the procedure. A recent meta-analysis suggests that migraineurs with aura are more than 4x more likely to have a PFO than the general population. We describe a hitherto unrecognized phenomenon following CAbl of AF (439 consecutive Pts, 1/2015 to 3/2016, mean age 63±11 years, 66.5% male gender). CAbl was performed using radio frequency current (RF, n=260, Navistar Thermocool TM , settings 20watt to 40watt, 43°C) or cryo-energy (CRYO, n=179 paroxysmal AF only, Arctic Front Advance TM , &lt;-40°C to ≥-60°C). CAbl was performed during uninterrupted oral anticoagulation (OAC) with a vitamin K antagonists (n=128, INR &gt;2) or with direct OAC (Dabigatran n=89, Rivaroxaban n=148, Apixaban n=73, Edoxaban n=1). After CAbl Pts underwent continuous ECG-monitoring, a neurologic evaluation followed the procedure immediately and was repeated after 24h. Pts were encouraged to report any complaints. Eight Pts (1.8%) had short lasting neurologic complaints and received, as part of the work-up, cerebral magnetic resonance imaging (MRI). Two Pts with transient neurologic deficits (vertigo n=1, Phenprocoumon, INR 2.4, speech disorders n=1, Rivaroxaban 20mg) had new small ischemic cerebral lesions. All 6 Pts (Dabigatran n=3, Rivaroxaban n=2, Phenprocoumon n=1, INR 2,1, RF n=2, Cryo n=4) with negative MRI had visual disturbances, followed by headache, as typically reported by migraineurs. One patient had a history of migraine with aura, five Pts never before had similar complaints. Pts with visual disturbances and headache continued to have similar complaints during the following 2 weeks. Follow-up of both patients with new ischemic lesions was inconspicuous. Conclusion: Recurrent migraine with visual disturbances occurred after CAbl of AF in about 1.5% of Pts with uninterrupted OAC who never had migraine before. It seems likely that the mechanism of visual disturbances followed by headache after CAbl of AF resembles the mechanism of migraine in patients with PFO. It is unknown whether migraine may become a chronic condition after CAbl of AF.
New mechanism underlying IL-31–induced atopic dermatitis
Authors: Jianghui Meng, Masaki Moriyama, Micha Feld, Joerg Buddenkotte, Timo Buhl, Attila Szöllösi, Jingming Zhang, Paul Miller, Andre Ghetti, Michael Fischer, Peter W. Reeh, Chunxu Shan, Jiafu Wang, Martin Steinhoff
Journal: Journal of Allergy and Clinical Immunology (2018)
Reactive Oxygen Species and Metabolic Gene Expression Profiling Further Differentiate CXCR4/CD5 Fractions in Chronic Lymphocytic Leukemia
Authors: Eric Sturgill, Xiao J. Yan, Florencia Palacios, Kanti Rai, Jacqueline C. Barrientos, Steven L. Allen, Jonathan E. Kolitz, Nicholas Chiorazzi
Journal: Blood (2017)
Group 2 innate lymphoid cells promote airway hyperresponsiveness through production of VEGFA
Authors: Xiaofei Shen, Muhammad Asghar Pasha, Kelsi Hidde, Adil Khan, Mingwei Liang, Wenxian Guan, Yitao Ding, Angela Haczku, Qi Yang
Journal: Journal of Allergy and Clinical Immunology (2018)
Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer
Authors: J. Adam, N. Le Stang, I. Rouquette, A. Cazes, C. Badoual, H. Pinot-Roussel, L. Tixier, C. Danel, F. Damiola, D. Damotte, F. Penault-Llorca, S. Lantuéjoul
Journal: Annals of Oncology (2018)
Innate immunity-related Gene Expression Profiling Reveals Two Distinct Endotypes in PFAPA Syndrome
Authors: Mariko Hara, Noriko Morimoto, Kae Fujii, Sota Yamaguchi, Mayumi Tsunoda, Keisuke Yoshihama, Hideaki Morita, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2018)
Identification and analysis of peanut-specific effector T and regulatory T cells in children allergic and tolerant to peanut
Authors: Katherine A. Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R. Neeland, Mimi L.K. Tang, Thanh D. Dang, Katrina J. Allen, Pamela A. Frischmeyer-Guerrerio
Journal: Journal of Allergy and Clinical Immunology (2018)
Excess Mucin Impairs Subglottic Epithelial Host Defense in Mechanically Ventilated Patients
Authors: Jason Powell, James P. Garnett, Michael W. Mather, Faye A. H. Cooles, Andrew Nelson, Bernard Verdon, Jon Scott, Kasim Jiwa, Marie-Hélène Ruchaud-Sparagano, Stephen P. Cummings, John D. Perry, Stephen E. Wright, Janet A. Wilson, Jeffrey Pearson, Chris Ward, A. John Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP.Objectives: To characterize subglottic host defense dysfunction in mechanically ventilated patients in the ICU; to determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth.Methods: Prospective subglottic sampling in mechanically ventilated patients (intubated for four or more days), and newly intubated control patients (intubated for less than 30 min); isolation and culture of primary subglottic epithelial cells from control patients; laboratory analysis of host innate immune defenses.Measurements and Main Results: Twenty-four patients in the ICU and 27 newly intubated control patients were studied. Subglottic ICU samples had significantly reduced microbiological diversity and contained potential respiratory pathogens. The subglottic microenvironment in the ICU was characterized by neutrophilic inflammation, significantly increased proinflammatory cytokines and neutrophil proteases, and altered physical properties of subglottic secretions, including accumulation of mucins. Subglottic mucin from ICU patients impaired the capacity of neutrophils to phagocytose and kill bacteria. Phagocytic impairment was reversible on treatment with a mucolytic agent. Subglottic mucus promoted growth and invasion of bacterial pathogens in a novel air–liquid interface model of primary human subglottic epithelium.Conclusions: Mechanical ventilation in the ICU is characterized by substantial mucin secretion and neutrophilic inflammation. Mucin impairs neutrophil function and promotes bacterial growth. Mucolytic agents reverse mucin-mediated neutrophil dysfunction. Enhanced mucus disruption and removal has potential to augment preventive benefits of subglottic drainage.
Abstract 18485: Runx2 Haploinsufficiency Attenuates Angiotensin II-mediated Fibrosis and Proliferation in Mouse Mitral Valves
Authors: Nassir M Thalji, Michael A Hagler, Grace Casaclang-Verzosa, Bin Zhang, Rakesh M Suri, Jordan D Miller
Journal: Circulation (2015)

We recently reported activation of TGF-β superfamily pathways and activation of Wnt/β-catenin signaling in the pathogenesis of myxomatous mitral valve disease (MMVD), which may converge upon increased Runx2 expression. We also demonstrated that chronic in vivo administration of angiotensin II (AngII) recaptures various molecular aberrations characteristic of human disease -including increased TGF-β signaling and activation of Runx2- in mouse mitral valves. Here, we sought to determine whether Runx2 haploinsufficiency can attenuate molecular and/or phenotypic effects of AngII infusion in mouse mitral valves. We implanted littermate matched Runx2+/+ and Runx2+/- mice with osmotic minipumps delivering AngII (1000ng/kg/min) or saline for 2 weeks. We measured changes in mRNA (qRT-PCR) and protein (immunohistochemistry) levels in mitral valves, and assessed mitral valve function by echocardiography. In Runx2+/+ mice, AngII elicited increased mRNA levels of TGF-β3 and the TGF-β target COL3A1, and increased staining for canonical (p-SMAD2/3) and non-canonical (p-AKT) TGF-β signaling proteins. Runx2 haploinsufficiency attenuated AngII-induced changes in COL3A1 expression and p-AKT staining, without impacting AngII-mediated alterations in TGF-β3 and p-SMAD2/3. Evaluating collagen thickness by picrosirius red staining and visualization under circularly polarized light, AngII infusion in Runx2+/+ mice was associated with increased collagen density at the base of posterior mitral valve leaflets, a change that was abrogated by Runx2 haploinsufficiency. Similarly, Runx2-haploinsufficiency was again protective when examining mRNA and protein levels of the proliferation marker KI67 in response to AngII. Echocardiography identified a trend towards increased mitral valve regurgitation following AngII infusion that was unaltered by Runx2 haploinsuffiency. Collectively, these data suggest that increases in Runx2 expression in the mitral valve may serve to orchestrate tissue fibrosis and cellular proliferation that are hallmarks of MMVD, and that future pharmacological strategies aimed at reducing activity of Runx2 in the mitral valve may yield viable non-surgical alternatives for the management of this condition.