tbuckley/cabot-search huggingface dataset:
Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia
Authors: Sana M. Al-Khatib, Aysha Arshad, Ethan M. Balk, Sandeep R. Das, Jonathan C. Hsu, Josè A. Joglar, Richard L. Page
Journal: Circulation (2015)

Objective— To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes. Methods— PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English. Results— Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design—a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients—and 8 were uncontrolled prospective cohort studies (n=1594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and &lt;10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; P &lt;0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval &gt;250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case. Conclusions— The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.
Nanomedicine: In Vivo Gene-Silencing in Fibrotic Liver by siRNA-Loaded Cationic Nanohydrogel Particles (Adv. Healthcare Mater. 18/2015)
Authors: Leonard Kaps, Lutz Nuhn, Misbah Aslam, Alexander Brose, Friedrich Foerster, Sebastian Rosigkeit, Patricia Renz, Rosario Heck, Yong Ook Kim, Ingo Lieberwirth, Detlef Schuppan, Rudolf Zentel
Journal: Advanced Healthcare Materials (2015)

Knocking down collagen synthesis in liver fibrosis: On page 2809, D. Schuppan, R. Zentel, and co-workers show how systemically administered cationic nanohydrogel particles loaded with anti-Col1α1 siRNA target fibrogenic effector cells in the liver and thereby suppress collagen synthesis and attenuate fibrosis (Cover design: Cristina Sala).
Antiemetics in children receiving cancer chemotherapy: a double-blind prospective randomized study comparing metoclopramide with chlorpromazine.
Authors: J Graham-Pole, J Weare, S Engel, R Gardner, P Mehta, S Gross
Journal: Journal of Clinical Oncology (1986)

This is the first prospective randomized study comparing commonly used antiemetics in children receiving cancer chemotherapy. We compared metoclopramide (MCP) with chlorpromazine (CLP), both administered in conventional doses, in 50 cancer patients aged 6 to 18 years who were receiving emetic chemotherapy. CLP proved significantly better than MCP in reducing both the frequency of vomiting (P less than .05) and the duration of nausea and vomiting (P less than .025). Extrapyramidal reactions (EPRs) were more common in MCP-treated patients. We conclude that, in the standard doses used, CLP is a better overall antiemetic than MCP for children receiving intensive chemotherapy. However, further prospective pediatric studies of antiemetic combinations are needed.
Molecular and structural transition mechanisms in long‐term volume overload
Authors: Belal A. Mohamed, Moritz Schnelle, Sara Khadjeh, Dawid Lbik, Melissa Herwig, Wolfgang A. Linke, Gerd Hasenfuss, Karl Toischer
Journal: European Journal of Heart Failure (2015)

Abstract Aim We have previously reported that early phase (1 week) of experimental volume overload ( VO ) has an adaptive phenotype while wall stress‐matched pressure overload ( PO ) is maladaptive. Here we investigate the transition from adaptation to heart failure ( HF ) in long‐term VO . Methods and results FVB /N wild‐type mice were subjected to VO induced by aortocaval shunt, and were followed by serial echocardiography until in vivo left ventricular ejection fraction was below &lt;50% (135 ± 35 days). Heart failure was evident from increased lung and liver weight and increased mortality compared with sham. Maladaptive remodelling resulted in significantly reduced sarcomeric titin phosphorylation (causing increased sarcomeric stiffness), whereas interstitial fibrosis was not increased. This was paralleled by re‐expression of the fetal gene program, activation of calcium/calmodulin‐dependent protein kinase II ( CaMKII ), decreased protein kinase B (Akt) phosphorylation, high oxidative stress, and increased apoptosis. Consistently, development of HF and mortality were significantly aggravated in Akt ‐deficient mice. Conclusion Transition to HF in VO is associated with decreased Akt and increased CaMKII signalling pathways together with increased oxidative stress and apoptosis. Lack of interstitial fibrosis together with sarcomeric titin hypophosphorylation indicates an increased stiffness at the sarcomeric but not matrix level in VO ‐induced HF (in contrast to PO ). Transition to HF may result from myocyte loss and myocyte dysfunction owing to increased stiffness.
Long-term Results and Recurrence-Related Risk Factors for Crohn Disease in Patients Undergoing Side-to-Side Isoperistaltic Strictureplasty
Authors: Marilena Fazi, Francesco Giudici, Cristina Luceri, Micaela Pronestì, Francesco Tonelli
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Side-to-side isoperistaltic strictureplasty (SSIS) is useful in patients undergoing surgery for Crohn disease (CD) to avoid wide small-bowel resections. To our knowledge, there are no definitive data regarding its recurrence risk factors. <h3>Objective</h3> To evaluate the results obtained in a monocentric population of patients with CD who have undergone SSIS. <h3>Design, Setting, and Participants</h3> From August 1996 to March 2010, 91 patients with CD underwent SSIS in our center. In this prospective observational study, side-to-side isoperistaltic strictureplasty was according the Michelassi technique in 69 patients and the Tonelli technique in 22 patients. Factors relating to the patient and the CD, surgery, and pharmacological therapy during the preoperative and perioperative periods were evaluated in association with medical or surgical recurrence. <h3>Exposure</h3> Side-to-side isoperistaltic strictureplasty. <h3>Main Outcomes and Measures</h3> The recurrence-free curve was estimated using Kaplan-Meier analysis. Patients were stratified into cohorts in relation to the considered categorical variables and data were compared by using the Mantel-Cox log-rank test. Cox proportional hazard regression analysis was used to set up a predictive model simultaneously exploring the effects of all independent variables on a dichotomous outcome recurrence in relation to time. <h3>Results</h3> Among the 91 patients, the mean (SD) age was 39.5 (11.2) years and preoperative disease duration was 97.9 (85.8) months; 83 patients (91.2%) were followed up, of whom 37 (44.58%) experienced a recurrence at a mean (SD) of 55.46 (36.79) months after surgery (range, 9-140 months). The recurrence in the SSIS site at a mean (SD) of 48.25 (29.94) months after surgery affected 24 of 83 patients (28.9%), 9 being medical and 15 being surgical recurrence. Recurrence in the SSIS was statistically significantly associated with the time elapsed between diagnosis and surgery (<i>P</i> = .03). A borderline association between family history of CD and surgical recurrence (<i>P</i> = .054) was also found. Multivariate analysis identified the age at diagnosis (χ<sup>2</sup> = 5.56;<i>P</i> = .02) and at surgery (χ<sup>2</sup> = 7.77;<i>P</i> = .005), family history (χ<sup>2</sup> = 6.26;<i>P</i> = .01), and smoking habit (χ<sup>2</sup> = 10.06;<i>P</i> = .007) as independent risk factors for recurrence. <h3>Conclusions and Relevance</h3> In the short-term, SSIS leads to a resolution of symptoms in more than 90% of cases and the recurrence rate in the SSIS area is acceptable, even after long-term follow-up.
US lifts 30 year ban and allows some gay men to donate blood
Authors: Michael McCarthy
Journal: BMJ (2015)

The US will lift its three decade long ban on blood donations by men who have sex with men (MSM) and allow donations by those who have had no sexual contact with another man in the previous 12 months, the Food and Drug Administration announced on 21 December.

FDA officials said that the decision was based on a review of recent studies, US epidemiological data, and the experiences of other countries that have relaxed their policies on blood donations by MSM, such as Australia, Japan, Sweden, and the United Kingdom, which have adopted one year deferral policies.1 Published studies indicated that shifting to a 12 month deferral policy would not change risk to the blood supply, FDA officials said. Data on the safety of …
Abstract 15312: Genetic Deletion of Toll-like Receptor 9 Accelerates Blood Flow Recovery after Hindlimb Ischemia
Authors: Sachiko Nishimoto, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Hiroshi Sakaue, Michio Shimabukuro, Masataka Sata
Journal: Circulation (2014)

Background: Peripheral artery disease causes significant functional disability and results in impaired quality of life. Toll-like receptor (TLR)-2, 3 and 4 are suggested to participate in blood flow recovery in ischemic limb by modulating inflammation and angiogenesis, however, the role of TLR9 remains unknown. TLR9 recognizes bacterial unmethylated DNA and plays a role in innate defense, although it can also provoke inflammation in response to fragmented DNA released from regenerated mammalian cells. This study tested the hypothesis that genetic deletion of TLR9 accelerates blood flow recovery after femoral artery ligation by inhibiting inflammation and improving endothelial cell function. Methods and Results: Unilateral femoral artery ligation was performed in TLR9-deficient (TLR9KO) mice and wild type (WT) mice. Femoral artery ligation significantly increased RNA expression of TLR9 (20-times) in WT mice and plasma levels of single-stranded DNA and double-stranded DNA, endogenous ligands for TLR9, in both strains of mice compared with each sham-operated group (P&lt;0.05). Laser Doppler perfusion imaging demonstrated that TLR9KO mice significantly improved the ratio of the blood flow in the ischemic to non-ischemic limb compared with WT mice at 2 weeks after ligation (P&lt;0.05). TLR9KO mice showed less accumulation of macrophages and less expression of inflammatory molecules (e.g., TNF-α, MCP-1 and IL-1β in ischemic muscle compared with WT mice (P&lt;0.05, respectively). In vitro experiments using thioglycolate-stimulated peritoneal macrophages demonstrated that CpG ODN, agonistic oligonucleotide for TLR9, promoted the expression of pro-inflammatory molecules (e.g., MCP-1 and TNF-α) in WT macrophages (P&lt;0.05, respectively) but not in TLR9 KO macrophages. Furthermore, activation of TLR9 by CpG ODN inhibited migration and proliferation of endothelial cells as determined by scratch-wound assay and MTS assay, respectively (P&lt;0.05). Conclusion: Our results suggested that TLR9 enhances inflammation and affects migration and proliferation of endothelial cells, leading to impaired blood flow recovery in ischemic limb. TLR9 may serve as a potential therapeutic target for ischemic limb disease.
Clostridium difficile -related hospitalizations in Madrid (Spain) between 2003 and 2014, a rising trend
Authors: María D. Esteban-Vasallo, Salomé Naval Pellicer, Felicitas Domínguez-Berjón, Mireia Cantero Caballero, Ángel Asensio, Gabriela Saravia, Jenaro Astray-Mochales
Journal: Journal of Infection (2015)
Progress in Medicine: Experts Take Stock
Authors: Andrew Beck, Ewan Birney, Manuel Graeber, James Tumwine, Phillipa Hay, Hyeong Sik Ahn, Anushka Patel, Philipp du Cros, Lorenz von Seidlein, Nick Wareham, Nicola Low
Journal: PLoS Medicine (2015)

In the year-end editorial, the PLOS Medicine editors ask 11 researchers and clinicians about the most relevant challenges, promising research, and important initiatives in their fields as we head into 2016.
Cardiac Determinants of Heterogeneity in Fitness Change in Response to Moderate Intensity Aerobic Exercise Training
Authors: Ambarish Pandey, Colby Ayers, Steven N. Blair, Damon L. Swift, Conrad P. Earnest, Dalane W. Kitzman, Amit Khera, Timothy S. Church, Jarett D. Berry
Journal: Journal of the American College of Cardiology (2015)
Structural basis for collagen recognition by the immune receptor OSCAR
Authors: Long Zhou, Jennifer M. Hinerman, Michal Blaszczyk, Jeanette L. C. Miller, Deborah G. Conrady, Alexander D. Barrow, Dimitri Y. Chirgadze, Dominique Bihan, Richard W. Farndale, Andrew B. Herr
Journal: Blood (2015)
Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression
Authors: Guocan Wang, Xin Lu, Prasenjit Dey, Pingna Deng, Chia Chin Wu, Shan Jiang, Zhuangna Fang, Kun Zhao, Ramakrishna Konaparthi, Sujun Hua, Jianhua Zhang, Elsa M. Li-Ning-Tapia, Avnish Kapoor, Chang-Jiun Wu, Neelay Bhaskar Patel, Zhenglin Guo, Vandhana Ramamoorthy, Trang N. Tieu, Tim Heffernan, Di Zhao, Xiaoying Shang, Sunada Khadka, Pingping Hou, Baoli Hu, Eun-Jung Jin, Wantong Yao, Xiaolu Pan, Zhihu Ding, Yanxia Shi, Liren Li, Qing Chang, Patricia Troncoso, Christopher J. Logothetis, Mark J. McArthur, Lynda Chin, Y. Alan Wang, Ronald A. DePinho
Journal: Cancer Discovery (2015)

Abstract The signaling mechanisms between prostate cancer cells and infiltrating immune cells may illuminate novel therapeutic approaches. Here, utilizing a prostate adenocarcinoma model driven by loss of Pten and Smad4, we identify polymorphonuclear myeloid-derived suppressor cells (MDSC) as the major infiltrating immune cell type, and depletion of MDSCs blocks progression. Employing a novel dual reporter prostate cancer model, epithelial and stromal transcriptomic profiling identified CXCL5 as a cancer-secreted chemokine to attract CXCR2-expressing MDSCs, and, correspondingly, pharmacologic inhibition of CXCR2 impeded tumor progression. Integrated analyses identified hyperactivated Hippo–YAP signaling in driving CXCL5 upregulation in cancer cells through the YAP–TEAD complex and promoting MDSC recruitment. Clinicopathologic studies reveal upregulation and activation of YAP1 in a subset of human prostate tumors, and the YAP1 signature is enriched in primary prostate tumor samples with stronger expression of MDSC-relevant genes. Together, YAP-driven MDSC recruitment via heterotypic CXCL5–CXCR2 signaling reveals an effective therapeutic strategy for advanced prostate cancer. Significance: We demonstrate a critical role of MDSCs in prostate tumor progression and discover a cancer cell nonautonomous function of the Hippo–YAP pathway in regulation of CXCL5, a ligand for CXCR2-expressing MDSCs. Pharmacologic elimination of MDSCs or blocking the heterotypic CXCL5–CXCR2 signaling circuit elicits robust antitumor responses and prolongs survival. Cancer Discov; 6(1); 80–95. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1
Hypomethylation of TET2 Target Genes Identifies a Curable Subset of Acute Myeloid Leukemia
Authors: Jumpei Yamazaki, Rodolphe Taby, Jaroslav Jelinek, Noel J. M. Raynal, Matteo Cesaroni, Sherry A. Pierce, Steven M. Kornblau, Carlos E. Bueso-Ramos, Farhad Ravandi, Hagop M. Kantarjian, Jean-Pierre J. Issa
Journal: JNCI Journal of the National Cancer Institute (2015)

Acute myeloid leukemia (AML) is curable in a subset of cases. The DNA methylation regulator TET2 is frequently mutated in AML, and we hypothesized that studying TET2-specific differentially methylated CpGs (tet2-DMCs) improves AML classification.We used bisulfite pyrosequencing to analyze the methylation status of four tet2-DMCs (SP140, MCCC1, EHMT1, and MTSS1) in a test group of 94 consecutive patients and a validation group of 92 consecutive patients treated with cytarabine-based chemotherapy. Data were analyzed with hierarchical clustering, Cox proportional hazards regression, and Kaplan-Meier analyses. All statistical tests were two-sided.In the test cohort, hierarchical clustering analysis identified low levels of tet2-DMC methylation in 31 of 94 (33%) cases, and these had markedly longer overall survival (median survival 72+ vs 14 months, P = .002). Similar results were seen in the validation cohort. tet2-DMC-low status was shown to be an independent predictor of overall survival (hazard ratio = 0.29, P = .0002). In The Cancer Genome Atlas (TCGA) dataset where DNA methylation was analyzed by a different platform, tet2-DMC-low methylation was also associated with improved outcome (median survival = 55 vs 15 months, P = .0003) and was a better predictor of survival than mutations in TET2, IDH1, or IDH2, individually or combined.Low levels of tet2-DMC methylation define a subgroup of AML that is highly curable and cannot be identified solely by genetic and cytogenetic analyses.
Editorial
Authors: Levi, Marcel, Middeldorp, Saskia, Büller, Harry R.
Journal: Cardiovascular Research (1999)

This editorial in Cardiovascular Research presents data on the effect of postmenopausal estrogen replacement therapy on carotid artery stiffness.  It proposes a mechanism based on research that may explain the association between oral contraceptive (OC) use and other estrogen substitution with the enhanced risk of venous thromboembolism.  It is believed that the imbalance between activation of coagulation and fibrinolysis contribute to the increased incidence.  The estrogen content of OCs appears to cause alterations in the concentration of coagulation factors and the physiologic inhibitors.  Similarly estrogen induced a dose-dependent activation of endogenous fibrinolytic activity. Furthermore it is hypothesized that the progestagen content of OCs may modulate the estrogen-induced enhancement of fibrinolysis resulting in the imbalance of coagulation and fibrinolysis induced by estrogen.  Such mechanism may provide an explanation for the association of OCs with venous thromboembolism as well as for their differential effects on the incidence of venous thrombosis.
Using RNAi to identify modulators of the HIF pathway/hypoxia for cancer
Authors: Edyta Tyminski, Cole Liberator, Tom Rush, Theresa Zhang, Chris Winter, Alessandra Di Bacco, Marlene Artime, Brian Haines, Steve Bartz, Zhan Zhang, Aaron Chang, Bin Zhang, Jun Zhu, Marc Ferrer, Raul Lacson, Yaping Liu, Joleen Kajdas, David Ross, Smith Todd, Locco Lou, Ansu Bagchi, Eric Minch, Pam Carroll, Joe Marszalek
Journal: Cancer Research (2008)

2380   As a tumor expands, it outgrows its vasculature, depriving the cells of oxygen and nutrients needed for continued growth and survival. In response to the low oxygen levels, the HIF transcription factors are stabilized, altering the expression of 100’s of genes which coordinately enhance tumor growth. Cancer patients with high levels of tumor HIF expression have a poor prognosis for long-term survival. HIF is a particularly intriguing cancer target in that it is a central node upstream of many pro-cancerous pathways that are currently being individually targeted for cancer therapy. Accordingly, reducing HIF expression may be more efficacious than targeting these pathways individually. To identify genes that modulate the HIF pathway, we conducted a comprehensive genome-scale siRNA screen under hypoxic conditions using a cell-based HIF reporter assay. As part of hit follow-up, we developed several mRNA and protein based cellular and molecular assays to measure HIF pathway activity. From the siRNA screen, we identified ~450 genes that when inhibited decrease the HIF pathway activity to varying extents in a cell context dependent manner. Several of the hits are known HIF modulating genes, validating the method. Other hits appear to be novel HIF modulators. Combining the screening results with network-based analysis should reveal unique insights into how the HIF pathway is regulated.
Abstract 9597: Benefits of Nurse-Guided Cognitive Behavioral Therapy for Depression after Cardiac Surgery
Authors: Lynn V Doering, Belinda Chen, Rebecca Cross, Marise Magsarili, Adey Nyamathi, Michael R Irwin
Journal: Circulation (2011)

Background: Depression occurs in 15 to 40% of patients undergoing cardiac surgery, but studies of depression treatment after cardiac surgery have been limited. Objective: To evaluate nurse-guided cognitive behavioral therapy (CBT) in a home environment in patients recovering from cardiac surgery. Methods: We enrolled 808 cardiac surgery patients from five hospitals. They were screened for depressive symptoms with the Beck Depression Inventory (BDI) in the hospital and one month later and interviewed using the Structured Clinical Interview for DSM-IV (SCID-I); those who met criteria for clinical depression (n=81; 31% female, age 63 ± 9.8 years) were randomized to CBT (n=46) or usual care (UC; n=35). CBT patients received 8 weeks of nurse-guided therapy. UC patients received usual postop care plus biweekly phone calls to maintain contact. After 8 weeks, clinical depression in both groups was re-evaluated. Differences in symptom severity and depression status were determined by McNair-Bowker and Chi-Square tests, respectively. Clinical importance of change in BDI scores was evaluated by the Reliable Change Index method of Jacobson and Traux. Results: Intention-to-treat analyses showed greater reduction on the BDI in the CBT group compared to the UC group (mean BDI 9.7 [95% CI, 6.9-12.5] vs 17.6 [95% CI, 14.5-20.6], F=14.7, p&lt;.0001). CBT patients showed greater reduction in symptom severity than did UC patients (Figure). The CBT group was more likely to report remission in clinical depression (63% vs 23%; number need to treat, 2.5 [95% CI, 1.7-4.9]) than the UC group (p&lt;.0001). CBT reduced sleep disturbance (p = .01) and pain interference (, p=.001) and increased perceived control (p = .008). Conclusions: Nurse-guided CBT is an effective treatment option for depressed patients after cardiac surgery. Nurse-guided CBT also reduced negative aspects of other common postop complaints and increased patients' sense of control over their cardiac disease.
Delivery of siRNA targeting tumor metabolism using non-covalent PEGylated chitosan nanoparticles: Identification of an optimal combination of ligand structure, linker and grafting method
Authors: Cyril Corbet, Héloïse Ragelle, Vincent Pourcelle, Kévin Vanvarenberg, Jacqueline Marchand-Brynaert, Véronique Préat, Olivier Feron
Journal: Journal of Controlled Release (2015)