tbuckley/cabot-search huggingface dataset:
Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink
Authors: Zhiwei Liu, Rotana Alsaggaf, Katherine A McGlynn, Lesley A Anderson, Huei-Ting Tsai, Bin Zhu, Yue Zhu, Sam M Mbulaiteye, Shahinaz M Gadalla, Jill Koshiol
Journal: Gut (2018)

To evaluate the association between statin use and risk of biliary tract cancers (BTC).This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.
Abstract 11499: Asymptomatic Peripheral Arterial Disease is an Independent Limiting Factor for a Delay in Recovery From Reduced Exercise Capacity After Hospital Discharge in Patients With Chronic Heart Failure
Authors: Shinya Tanaka, Takashi Masuda, Kentaro Kamiya, Nobuaki Hamazaki, Ryota Matsuzawa, Kohei Nozaki, Ryosuke Shimizu, Yumi Kamada, Akihiro Aoyama, Chiharu Noda, Emi Maekawa, Minako Yamaoka-Tojo, Junya Ako
Journal: Circulation (2014)

Background:Reduced exercise capacity is well known to increase mortality in patients with chronic heart failure (CHF). Although a symptomatic peripheral arterial disease (PAD) decreases exercise capacity in CHF patients, the relation of an asymptomatic PAD to its reduction is still unknown. The purpose of this study was to investigate whether an asymptomatic PAD contributed to a delay in recovery from reduced exercise capacity after hospital discharge in CHF patients. Methods: We studied 231 CHF patients (73 females) aged 65 ± 13 years who underwent a cardiac rehabilitation, after excluding patients with PAD of Fontaine stage 2 or more, patients on hemodialysis, or those who needed any assistance for walking. Patients were diagnosed to have an asymptomatic PAD of Fontaine stage 1, if their ankle-brachial index (ABI) measured at hospital discharge showed ≦0.90. They were divided into two groups based on 0.90 of ABI: PAD(+) and PAD(-) groups. We assessed patients’ characteristics including estimated glomeru...
Spindle Cell Nuclear in Testis Carcinoma of the Lung: A Challenging Tumor
Authors: Giuseppe Pelosi, Maria Cannone, Emanuela Balladore, Daoud Rahal, Paola Bossi, Pierluigi Novellis, Edoardo Bottoni, Luca Toschi, Massimo Roncalli, Christopher A. French, Giulia Veronesi
Journal: Journal of Thoracic Oncology (2018)
Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial
Authors: Sachin Shinde, Helen A Weiss, Beena Varghese, Prachi Khandeparkar, Bernadette Pereira, Amit Sharma, Rajesh Gupta, David A Ross, George Patton, Vikram Patel
Journal: The Lancet (2018)
Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer
Authors: E.S. Sokol, Y.X. Feng, D.X. Jin, A. Basudan, A.V. Lee, J.M. Atkinson, J. Chen, P.J. Stephens, G.M. Frampton, P.B. Gupta, J.S. Ross, J.H. Chung, S. Oesterreich, S.M. Ali, R.J. Hartmaier
Journal: Annals of Oncology (2018)

BackgroundInvasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed.Patients and methodsTissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes.ResultsWhereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P<0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P<0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%).ConclusionsThis study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.
Improved Survival of Patients with AML By Addition of Cladribine to Standard DA3+7 Induction Chemotherapy (DAC) - Single Center Experience at University Medical Centre Ljubljana, Slovenia
Authors: Sasa Anzej Doma, Matjaz Sever, Uros Mlakar, Luka Cemazar, Matevz Skerget, Samo Zver
Journal: Blood (2018)
Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo
Authors: Jose L. Garrido, Joseph Prescott, Mario Calvo, Felipe Bravo, Raymond Alvarez, Alexis Salas, Raul Riquelme, Maria L. Rioseco, Brandi N. Williamson, Elaine Haddock, Heinz Feldmann, Maria I. Barria
Journal: Science Translational Medicine (2018)

Post-exposure highly potent human monoclonal antibodies target Andes hantavirus glycoprotein in a hamster hantavirus cardiopulmonary syndrome model.
Abstract 20680: Correlation of Geomagnetic Activity With Life-Threatening Arrhythmias and Sudden Cardiac Death
Authors: Nikhil Singh, Jan Belohlavek, Ondrej Franek, Jaroslav Valasek, Jiri Danda, Petr Kolouch, Akash Rusia, Samuel H Cho, Jonathan Nattiv, Rahul Doshi, Tomas Konecny
Journal: Circulation (2017)

Background: Previous studies have demonstrated a modest inverse relationship between defibrillator therapies for ventricular tachyarrhythmias and geomagnetic activity (GMA) which is primarily affec...
Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection
Authors: Valerie J. Kinchen, Muhammad N. Zahid, Andrew I. Flyak, Mary G. Soliman, Gerald H. Learn, Shuyi Wang, Edgar Davidson, Benjamin J. Doranz, Stuart C. Ray, Andrea L. Cox, James E. Crowe, Pamela J. Bjorkman, George M. Shaw, Justin R. Bailey
Journal: Cell Host & Microbe (2018)
Response to: ‘Metering the METEOR in methotrexate failure: is propensity score a falling star?’ by Ahmed <i>et al</i>
Authors: Sytske Anne Bergstra, Cornelia F Allaart, Robert B M Landewé
Journal: Annals of the Rheumatic Diseases (2018)

We thank Dr Ahmed for his response to our article and for his interest in the methodology we used.1 The aim of our study was twofold: to compare, in daily practice, treatment options after failure of initial methotrexate (MTX) in rheumatoid arthritis (RA) patients, but also to introduce the multiple propensity score (PS) in rheumatology.

As Dr Ahmed mentioned, previous research has been performed into treatment options after MTX failure, including the mentioned network meta-analysis based on clinical trials.2 These trials mostly included a selected population and reported response to one or at most two treatment options, either including a biologic disease modifying anti-rheumatic drug (bDMARD) or conventional synthetic (cs) DMARD triple therapy. But in daily practice, there are many scenarios in which rheumatologists consider multiple treatment options aimed to specifically benefit their individual patient, rather than following predefined study protocols. In our large, international daily practice database, we were able to compare three treatment …
Abstract LB-139: Efficacy, safety, and changes in blood markers following sunitinib monotherapy in patients with advanced hepatocellular carcinoma: Experience from a multidisciplinary Phase II study
Authors: Petra Pavlickova, Peter K. Vogt
Journal: Cancer Research (2008)

Abstract Patients with advanced hepatocellular carcinoma (HCC) have a very poor prognosis. HCC is a highly vascular tumor with increased levels of angiogenic factors, including VEGF and VEGFR2. Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with activity against VEGFR2, PDGFRβ, and c-KIT. We performed a multidisciplinary Phase II study to evaluate the efficacy, toxicity, and changes in angiogenic parameters following sunitinib administration in patients with advanced HCC. Eligibility criteria included unresectable or metastatic measurable HCC. Patients were treated with sunitinib at 37.5 mg po qd on a standard 4 weeks on, 2 weeks off regimen (6 weeks/cycle). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to assess changes in tumor permeability. Plasma markers were assayed by multiplex protein array. In a subset of patients, viable circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) were evaluated by flow cytometry in fresh whole blood samples at days 1, 15, 29, 57, 85, and 133. The primary endpoint of the study was progression-free survival (PFS). The targeted 34 patients have been enrolled: median age=63 (range 30-81); M/F=29/5; ECOG 0/1=15/19; CLIP 1/2/3=13/12/9. The treatment was generally well tolerated. Grade 3/4 toxicities included SGOT/SGPT (18/9%), neutropenia (12%), lymphopenia (15%), thrombocytopenia (12%), fatigue (9%), hand-foot syndrome (6%), rash (6%), hyperbilirubinemia (6%), and ataxia/disequilibrium (3%). One patient had a partial response and 10 patients had stable disease of at least 12 weeks. The median PFS was 4.0 months (95% CI: 2.8-7.0) and the median overall survival was 10 months (95% CI: 7.5-not estimable). Following 2 weeks of sunitinib administration, the mean tumor permeability (Ktrans) decreased by an average of 40% from the baseline. Sunitinib decreased sVEGFR2 levels and increased PlGF and VEGF levels in most patients. Interim analyses suggested that sunitinib treatment increase the number of CECs at day 15. The number of CPCs was significantly decreased by sunitinib at days 15, 29, and 57 compared to baseline (P&amp;lt;0.01). Sunitinib administered in the current dose schedule can be safely given with close monitoring in the majority of HCC patients. Preliminary evidence of antitumor activity was observed. Changes in functional parameters on DCE-MRI were seen following sunitinib administration. Complete data on VEGF, PlGF, bFGF, and sVEGFR2 in plasma, CECs, and CPCs– and their correlation with changes in DCE-MRI and clinical response– will be presented.
Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations
Authors: Wei-Chih Chang, Jan Kudlacek, Jaroslav Hlinka, Jan Chvojka, Michal Hadrava, Vojtech Kumpost, Andrew D. Powell, Radek Janca, Matias I. Maturana, Philippa J. Karoly, Dean R. Freestone, Mark J. Cook, Milan Palus, Jakub Otahal, John G. R. Jefferys, Premysl Jiruska
Journal: Nature Neuroscience (2018)
The lonely driver or the orchestra of mutations? How next generation sequencing datasets contradict the concept of single driver checkpoint mutations in solid tumours – NSCLC as a scholarly example
Authors: Verena Schildgen, Oliver Schildgen
Journal: Seminars in Cancer Biology (2018)

Driver mutations are considered to be responsible for the majority of cancers and several of those mutations provide targets in order to set up personalized therapies. So far the generally accepted opinion had been that driver mutations occur as stand-alone factors, but novel sequencing technologies induced an essential rethink. Next generation sequencing approaches have shown that double, triple or multiple concurrent mutations could occur within the same tumour and may by interaction influence sensitivity to anticancer drugs and therapy success. This review focusses on this novel concept and discusses the challenges for molecular pathology and laboratory diagnostics while providing putative solutions to overcome the present pitfalls, thereby taking NSCLC as an example.
Conferring DNA virus resistance with high specificity in plants using virus-inducible genome-editing system
Authors: Xiang Ji, Xiaomin Si, Yi Zhang, Huawei Zhang, Feng Zhang, Caixia Gao
Journal: Genome biology (2018)

The CRISPR/Cas9 system has recently been engineered to confer resistance to geminiviruses in plants. However, we show here that the usefulness of this antiviral strategy is undermined by off-target effects identified by deep sequencing in Arabidopsis. We construct two virus-inducible CRISPR/Cas9 vectors that efficiently inhibit beet severe curly top virus (BSCTV) accumulation in both transient assays (Nicotiana benthamiana) and transgenic lines (Arabidopsis). Deep sequencing detects no off-target effect in candidate sites of the transgenic Arabidopsis. This kind of virus-inducible genome-editing system should be widely applicable for generating virus-resistant plants without off-target costs.
Wearable sensors for Parkinson’s disease: which data are worth collecting for training symptom detection models
Authors: Luca Lonini, Andrew Dai, Nicholas Shawen, Tanya Simuni, Cynthia Poon, Leo Shimanovich, Margaret Daeschler, Roozbeh Ghaffari, John A. Rogers, Arun Jayaraman
Journal: npj Digital Medicine (2018)

Machine learning algorithms that use data streams captured from soft wearable sensors have the potential to automatically detect PD symptoms and inform clinicians about the progression of disease. However, these algorithms must be trained with annotated data from clinical experts who can recognize symptoms, and collecting such data are costly. Understanding how many sensors and how much labeled data are required is key to successfully deploying these models outside of the clinic. Here we recorded movement data using 6 flexible wearable sensors in 20 individuals with PD over the course of multiple clinical assessments conducted on 1 day and repeated 2 weeks later. Participants performed 13 common tasks, such as walking or typing, and a clinician rated the severity of symptoms (bradykinesia and tremor). We then trained convolutional neural networks and statistical ensembles to detect whether a segment of movement showed signs of bradykinesia or tremor based on data from tasks performed by other individuals. Our results show that a single wearable sensor on the back of the hand is sufficient for detecting bradykinesia and tremor in the upper extremities, whereas using sensors on both sides does not improve performance. Increasing the amount of training data by adding other individuals can lead to improved performance, but repeating assessments with the same individuals-even at different medication states-does not substantially improve detection across days. Our results suggest that PD symptoms can be detected during a variety of activities and are best modeled by a dataset incorporating many individuals.
miR-146a Controls Immune Response in the Melanoma Microenvironment
Authors: Justin Mastroianni, Natalie Stickel, Hana Andrlova, Kathrin Hanke, Wolfgang Melchinger, Sandra Duquesne, Dominik Schmidt, Martina Falk, Geoffroy Andrieux, Dietmar Pfeifer, Heide Dierbach, Annette Schmitt-Graeff, Frank Meiss, Melanie Boerries, Robert Zeiser
Journal: Cancer Research (2018)

Abstract MicroRNAs (miR) are small noncoding RNAs that regulate gene expression, posttranscription, and manipulate immune responses in different types of cancers. In this study, we identify miR-146a as a negative regulator of immune activation, comparable to immune-checkpoint molecules. miR-146a levels were increased in melanoma microenvironmental tissue, and miR-146a−/− mice survived longer and developed less metastases in comparison with wild-type melanoma-bearing mice. T cells isolated from miR-146a−/− mice revealed higher expression levels of the miR-146a target gene Stat1 and the Stat1-regulated cytokine IFNγ. Neutralization of IFNγ in miR-146a−/− mice decreased survival and increased melanoma metastasis patterns to those of wild-type mice. In vitro, IFNγ reduced melanoma cell migration, cell-cycle activity, and basal metabolic rate. Conversely, IFNγ also increased PD-L1 levels on the melanoma cells, which may counterbalance some of the beneficial effects increasing immune escape in vivo. Combined treatment with a miR-146a antagomiR and anti–PD-1 resulted in improved survival over isotype control or anti–PD-1 treatment alone. In summary, these data show that miR-146a plays a central role within the STAT1/IFNγ axis in the melanoma microenvironment, affecting melanoma migration, proliferation, and mitochondrial fitness as well as PD-L1 levels. Additionally, combined inhibition of PD-1 and miR-146a could be a novel strategy to enhance antitumor immune response elicited by checkpoint therapy. Significance: These findings identify a microRNA–based mechanism by which melanoma cells escape the immune system, providing a new therapeutic strategy to improve the current management of patients with melanoma.
Abstract 11908: Organizational Structure, Resources, and Educational Initiatives in Cardiac Intensive Care Units: A National Cross-sectional Survey on Behalf of the American Heart Association Acute Cardiac Care Committee
Authors: Christopher B Fordyce, Zachary Wegermann, Christopher B Granger, Amanda Stebbins, David A Morrow, Timothy D Henry, Ian C Gilchrist, Jason N Katz, Mauricio G Cohen, L. K Newby, Sean Van Diepen
Journal: Circulation (2016)

Introduction: The acuity and medical complexity of patients admitted to cardiac intensive care units (CICUs) is increasing; yet, little is known about contemporary CICU organizational structures, staffing, resources, and educational activities in the United States Methods: A cross-sectional, 16-question web-based survey was distributed electronically (October 2015) to AHA Mission: Lifeline coordinators at 542 registered hospitals with a request for completion by the CICU director or unit manager. Non-responders were contacted by email and phone. Results: A total of 138 hospitals (25.5% response rate) had completed the survey by May 1, 2016 (17.4% academic, 20.3% tertiary non-academic, and 62.3% community hospitals). Most CICUs were open units (76.8%) with multiple simultaneous responsible attending physicians. The Figure shows variation in CICU patient populations, organizational structure, medical leadership and role of intensivists. Overall, 61% of centers participated in clinical training of housestaff and/or advanced practice providers, while only 8.5% of centers had a dedicated Cardiac Critical Care subspecialty training program. 12.3% of all CICUs had the organizational structure and on-site resources to be classified as a Level 1 CICU by 2012 American Heart Association Scientific Statement on CICU medical staffing and training models. Conclusions: Among US hospitals, there was substantial variability in CICU organizational structure, practice, and educational activities. Approximately 1 in 10 CCUs had on-site resources necessary matching a Level 1 CICU classification. These data inform the current CICU landscape and may help to identify potential areas for organizational improvement and resource allocation.
Abstract 15783: Cardiac Fusion Imaging With Computed Tomography and Doppler Echocardiography in the Assessment of Right Ventricular Outflow Tract Obstruction in Oatients With Adult Congenital Heart Disease
Authors: Hiroki Oe, Nobuhisa Watanabe, Toru Miyoshi, Sho Takahashi, Yuko Ohno, Yuji Koide, Takashi Miki, Koji Nakagawa, Nobuhiro Nishii, Teiji Akagi, Hiroshi Ito
Journal: Circulation (2016)

Backgrounds: Echocardiographic visualization of right ventricular outflow tract (RVOT) in patients with adult congenital heart disease (ACHD) is sometimes difficult and misleading because of the po...
Review: Long-chain ω-3 fatty acids have no effect on mortality or overall cardiovascular events
Authors: Donald A. Smith
Journal: Annals of Internal Medicine (2018)

Source Citation Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;7:CD003177. 30019766
A pilot study of single pegfilgrastim compared with intermittent every other days of 5 shot-filgrastim in breast cancer patients receiving adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy (G-CSF 105 trial: NCT02685111)
Authors: J. Jeong, B.S. Sohn, J.-H. Ahn, K.H. Jung, J.E. Kim, J. Oh, H. Lee, J.H. Sohn, S.-J. Koh, J.H. Seo, K.S. Lee, S.-B. Kim
Journal: Annals of Oncology (2018)
Diagnostic Pitfalls and Treatment Challenges in Interstitial Pneumonia With Autoimmune Features: Comment on the Article by Wilfong et al
Authors: Pavel Novikov, Elena Shchegoleva, Larisa Akulkina, Nikolai Bulanov, Ekaterina Vinogradova, Sergey Moiseev
Journal: Arthritis & Rheumatology (2018)