tbuckley/cabot-search huggingface dataset:
Brief Behavioral Therapy for Pediatric Anxiety and Depression in Primary Care
Authors: V. Robin Weersing, David A. Brent, Michelle S. Rozenman, Araceli Gonzalez, Megan Jeffreys, John F. Dickerson, Frances L. Lynch, Giovanna Porta, Satish Iyengar
Journal: JAMA Psychiatry (2017)

Anxiety and depression affect 30% of youth but are markedly undertreated compared with other mental disorders, especially in Hispanic populations.To examine whether a pediatrics-based behavioral intervention targeting anxiety and depression improves clinical outcome compared with referral to outpatient community mental health care.This 2-center randomized clinical trial with masked outcome assessment conducted between brief behavioral therapy (BBT) and assisted referral to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6, 2010, through December 5, 2014. Youths who met DSM-IV criteria for full or probable diagnoses of separation anxiety disorder, generalized anxiety disorder, social phobia, major depression, dysthymic disorder, and/or minor depression; lived with a consenting legal guardian for at least 6 months; and spoke English were included in the study. Exclusions included receipt of alternate treatment for anxiety or depression, presence of a suicidal plan, bipolar disorder, psychosis, posttraumatic stress disorder, substance dependence, current abuse, intellectual disability, or unstable serious physical illness.The BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy delivered in pediatric clinics by master's-level clinicians. The ARC families received personalized referrals to mental health care and check-in calls to support accessing care from master's-level coordinators.The primary outcome was clinically significant improvement on the Clinical Global Impression-Improvement scale (score ≤2). Secondary outcomes included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale-Revised, and functioning.A total of 185 patients were enrolled in the study (mean [SD] age, 11.3 [2.6] years; 107 [57.8%] female; 144 [77.8%] white; and 38 [20.7%] Hispanic). Youths in the BBT group (n = 95), compared with those in the ARC group (n = 90), had significantly higher rates of clinical improvement (56.8% vs 28.2%; χ21 = 13.09, P < .001; number needed to treat, 4), greater reductions in symptoms (F2,146 = 5.72; P = .004; Cohen f = 0.28), and better functioning (mean [SD], 68.5 [10.7] vs 61.9 [11.9]; t156 = 3.64; P < .001; Cohen d = 0.58). Ethnicity moderated outcomes, with Hispanic youth having substantially stronger response to BBT (76.5%) than ARC (7.1%) (χ21 = 14.90; P < .001; number needed to treat, 2). Effects were robust across sites.A pediatric-based brief behavioral intervention for anxiety and depression is associated with benefits superior to those of assisted referral to outpatient mental health care. Effects were especially strong for Hispanic participants, suggesting that the protocol may be a useful tool in addressing ethnic disparities in care.clinicaltrials.gov Identifier: NCT01147614.
Effects of gold nanoparticle-based vaccine size on lymph node delivery and cytotoxic T-lymphocyte responses
Authors: Sukmo Kang, Sukyung Ahn, Jeewon Lee, Jin Yong Kim, Minsuk Choi, Vipul Gujrati, Hyungjun Kim, Jinjoo Kim, Eui-Cheol Shin, Sangyong Jon
Journal: Journal of Controlled Release (2017)
Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis
Authors: David R.W. Jayne, Annette N. Bruchfeld, Lorraine Harper, Matthias Schaier, Michael C. Venning, Patrick Hamilton, Volker Burst, Franziska Grundmann, Michel Jadoul, István Szombati, Vladimír Tesař, Mårten Segelmark, Antonia Potarca, Thomas J. Schall, Pirow Bekker
Journal: Journal of the American Society of Nephrology (2017)

Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P =0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P =0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.
Surgeon who operated on wrong vertebrae has no action taken against him
Authors: Clare Dyer
Journal: BMJ (2017)

A consultant neurosurgeon who operated on the wrong vertebrae in a patient’s spine then kept his mistake hidden from the patient and his NHS trust has been spared any sanction by a medical practitioners tribunal, despite its finding that his practice was impaired on the grounds of dishonesty.

Nicholas Brooke’s efforts to remediate his error led to the introduction of new consent and preoperative procedures that had improved patient safety where he worked, the tribunal heard.

The main charge against Brooke involved a 2012 spinal operation on an NHS patient at the private Spire …
Health Related Quality of Life Results from the Open-Label, Randomized, Phase III Endeavor Trial Evaluating Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma
Authors: Heinz Ludwig, Philippe Moreau, Meletios A Dimopoulos, Maria-Victoria Mateos, Martin F Kaiser, Shibao Feng, Kim Cocks, Jacqueline Buchanan, Katja Weisel
Journal: Blood (2016)
TCTAP C-281 Double Perclose ProGlide Devices Method with a Balloon for Removal of Arterial Cannula of Extracorporeal Membrane Oxygenation Support
Authors: Tomohiro Nakamura, Ken Tsuboi, Yoshimasa Tsurumaki, Yusuke Tamanaha, Mitsunari Matsumoto
Journal: Journal of the American College of Cardiology (2017)
Clinical effectiveness of Everolimus and Exemestane in advanced breast cancer patients from Asia and Africa: First efficacy and updated safety results from the phase IIIb EVEREXES study.
Authors: Young-Hyuck Im, Ruchan Uslu, Keun Seok Lee, Rajnish Vasant Nagarkar, Joohyuk Sohn, Alper Sevinc, Kadri Altundag, Yuan-Ching Chang, Hikmat Abdel-Razeq, Seock-Ah Im, Joon Jeong, Ho Yong Park, Wichit Arpornwirat, Patricia A. Bastick, Tuan Anh Le, Ozlem Ocak Arikan, Hong-Ling Xue, Aycin Canatar, Roberta Valenti, Sung-Bae Kim
Journal: Journal of Clinical Oncology (2015)

e11579 Background: BOLERO-2 phase III trial clearly demonstrated the efficacy of everolimus (EVE) plus exemestane (EXE) for the treatment of postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer (aBC). However, in this study only a minority ( < 10%) of patients were recruited from African and Asia Pacific countries (except Japan). Considering the potential effects of ethnic and cultural differences on treatment effectiveness, it remains compelling to confirm the safety and efficacy profile of EVE+EXE in these populations. Methods: EVEREXES is an open-label phase IIIb, single arm, multi-center trial, which enrolled 251 post-menopausal, HR-positive and HER2-negative, aBC patients who were treated with EVE+EXE across 13 Asia Pacific and African countries. Its primary objective was to investigate the safety and tolerability profile of EVE+EXE. Secondary objectives were the evaluation of efficacy (assessed by PFS, ORR, and CBR based on RECIST 1.1 criteria) and change in ECOG performance status. Results: From March 2013 to October 2014, 251 patients were enrolled across Asia Pacific, Middle East, North and South Africa. At data cut off of 30st of November 2014, a majority of grade 1/2 adverse events (AEs) was reported, with a small proportion ( < 10%) of ≥ grade (G) 3 AEs. In particular, 66% of patients developed stomatitis (9% G3), 53% skin toxicity (2% G3), 32% infections (4% ≥ G3), 26% hyperlipidemia (2% G3), 17% elevated liver enzymes (6% G3), 14% hyperglycemia (5% G3) and 10% noninfectious pneumonitis (with just 1 case ≥ G3). Overall, 47% of patients underwent dose adjustments/temporary interruptions and 7% permanently discontinued treatment due to AEs. Conclusions: These results are in line with those previously reported in BOLERO-2 trial, with EVE+EXE safety profile being predictable and manageable. Efficacy and safety data of EVE+EXE at January 31, 2015 data cut off will be presented for the first time in the above mentioned patient population with a median follow up of approximately 11 months, fostering further evaluation of the impact of ethnic and cultural differences on treatment outcomes.
Human Multipotent Mesenchymal Stromal Cells Inhibit Proliferation of PBMC in the Absence of Functional IFNγR1 and IDO Expression.
Authors: Friederike Gieseke, Susanne Viebahn, Sandra Kordowich, Ewa Koscielniak, Wilhelm Friedrich, Rupert Handgretinger, Ingo Müller
Journal: Blood (2006)
Anti-arrhythmic potential of the late sodium current inhibitor GS-458967 in murine Scn5a-1798insD+/− and human SCN5A-1795insD+/− iPSC-derived cardiomyocytes
Authors: Vincent Portero, Simona Casini, Maaike Hoekstra, Arie O. Verkerk, Isabella Mengarelli, Luiz Belardinelli, Sridharan Rajamani, Arthur A.M. Wilde, Connie R. Bezzina, Marieke W. Veldkamp, Carol Ann Remme
Journal: Cardiovascular Research (2017)

Selective inhibition of cardiac late sodium current (INaL) is an emerging target in the treatment of ventricular arrhythmias. We investigated the electrophysiological effects of GS-458967 (GS967), a potent, selective inhibitor of INaL, in an overlap syndrome model of both gain and loss of sodium channel function, comprising cardiomyocytes derived from both human SCN5A-1795insD+/− induced pluripotent stem cells (hiPSC-CMs) and mice carrying the homologous mutation Scn5a-1798insD+/−. On patch-clamp analysis, GS967 (300 nmol/l) reduced INaL and action potential (AP) duration in isolated ventricular myocytes from wild type and Scn5a-1798insD+/− mice, as well as in SCN5A-1795insD+/− hiPSC-CMs. GS967 did not affect the amplitude of peak INa, but slowed its recovery, and caused a negative shift in voltage-dependence of INa inactivation. GS967 reduced AP upstroke velocity in Scn5a-1798insD+/− myocytes and SCN5A-1795insD+/− hiPSC-CMs. However, the same concentration of GS967 did not affect conduction velocity in Scn5a-1798insD+/− mouse isolated hearts, as assessed by epicardial mapping. GS967 decreased the amplitude of delayed after depolarizations and prevented triggered activity in mouse Scn5a-1798insD+/− cardiomyocytes. The INaL inhibitor GS967 decreases repolarization abnormalities and has anti-arrhythmic effects in the absence of deleterious effects on cardiac conduction. Thus, selective inhibition of INaL constitutes a promising pharmacological treatment of cardiac channelopathies associated with enhanced INaL. Our findings furthermore implement hiPSC-CMs as a valuable tool for assessment of novel pharmacological approaches in inherited sodium channelopathies.
Curcumin prevents and reverses murine cardiac hypertrophy
Authors: Hong-Liang Li, Chen Liu, Geoffrey de Couto, Maral Ouzounian, Mei Sun, Ai-Bing Wang, Yue Huang, Cheng-Wei He, Yu Shi, Xin Chen, Mai P. Nghiem, Youan Liu, Manyin Chen, Fayez Dawood, Masahiro Fukuoka, Yuichiro Maekawa, Liyong Zhang, Andrew Leask, Asish K. Ghosh, Lorrie A. Kirshenbaum, Peter P. Liu
Journal: Journal of Clinical Investigation (2009)

During the preparation of the manuscript, different fields of the same sample for WGA immunofluorescence staining were mistakenly used to represent 2 distinct treatment groups on 2 occasions, in Figures 2 and7, and some of the raw data for the earlier experiments were lost due to poor record keeping.All authors have agreed to retract the article.
Pregnancy and fetal outcomes after paternal exposure to azathioprine, methotrexate or mycophenolic acid: a critically appraised topic
Authors: F.M. Garritsen, M.P.H. van den Broek, A.D. van Zuilen, H.H. Fidder, M.S. de Bruin-Weller, P.I. Spuls
Journal: British Journal of Dermatology (2017)

Linked Comment: Albrecht and Nast. Br J Dermatol 2017; 176:847–848
TCTAP A-014 Optimal Timing of Invasive Strategy in Stable Non-ST-segment Elevation Myocardial Infarction: Impact of Immediate Intervention
Authors: Doo Sun Sim, Myung-Ho Jeong, Youngkeun Ahn, Young Jo Kim, Shung Chull Chae, Taek Jong Hong, In-Whan Seong, Jei Keon Chae, Chong-Jin Kim, Myeong-Chan Cho, Seung-Woon Rha, Jang-Ho Bae, Ki-Bae Seung, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2017)
Homeobox B9 Mediates Resistance to Anti-VEGF Therapy in Colorectal Cancer Patients
Authors: Carmine Carbone, Geny Piro, Francesca Simionato, Francesca Ligorio, Chiara Cremolini, Fotios Loupakis, Greta Alì, Daniele Rossini, Valeria Merz, Raffaela Santoro, Camilla Zecchetto, Marco Zanotto, Federica Di Nicolantonio, Alberto Bardelli, Gabriella Fontanini, Giampaolo Tortora, Davide Melisi
Journal: Clinical Cancer Research (2017)

Purpose: The identification of predictive biomarkers for antiangiogenic therapies remains an unmeet need. We hypothesized that the transcription factor Homeobox B9 (HOXB9) could be responsible for the tumor resistance to the anti-VEGF agent bevacizumab.Experimental Design: HOXB9 expression and activation were measured in eight models of colorectal and pancreatic cancer with different resistance to bevacizumab. Serum levels of Angiopoietin-like Protein (Angptl)2, CXC receptor ligand (CXCL)1, IL8, and TGFβ1 in tumor-bearing mice were measured by multiplex xMAP technology. HOXB9 expression was measured by immunohistochemical analysis in 81 pretreatment specimens from metastatic colorectal cancer patients. Differences in progression-free survival (PFS) were determined using a log-rank test.Results: HOXB9-positive tumors were resistant to bevacizumab, whereas mice bearing HOXB9-negative tumors were cured by this agent. Silencing HOXB9 in bevacizumab-resistant models significantly (P < 0.05) reduced Angptl2, CXCL1, IL8, and TGFβ1 levels, reverted their mesenchymal phenotype, reduced CD11b+ cells infiltration, and restored, in turn, sensitivity to bevacizumab. HOXB9 had no prognostic value in patients treated with a first-line chemotherapeutic regimen noncontaining bevacizumab. However, patients affected by an HOXB9-negative tumor had a significantly longer PFS compared with those with an HOXB9-positive tumor if treated with a first-line regimen containing bevacizumab (18.0 months vs. 10.4 months; HR 2.037; 95% confidence interval, 1.006-4.125; P = 0.048).Conclusions: These findings integrate the complexity of numerous mechanisms of anti-VEGF resistance into the single transcription factor HOXB9. Silencing HOXB9 could be a promising approach to modulate this resistance. Our results candidate HOXB9 as predictive biomarker for selecting colorectal cancer patients for antiangiogenic therapy. Clin Cancer Res; 23(15); 4312-22. ©2017 AACR.
Lung volumes predict survival in patients with chronic lung allograft dysfunction
Authors: Nikolaus Kneidinger, Katrin Milger, Silke Janitza, Felix Ceelen, Gabriela Leuschner, Julien Dinkel, Melanie Königshoff, Thomas Weig, René Schramm, Hauke Winter, Jürgen Behr, Claus Neurohr
Journal: European Respiratory Journal (2017)

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD. A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95). Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p&lt;0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39–9.18; p=0.008; and HR 2.65, 95% CI 1.05–6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes. Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.
Pioglitazone for the treatment of NASH in patients with prediabetes or type 2 diabetes mellitus
Authors: Kenneth Cusi
Journal: Gut (2017)

I read with great interest the recent comprehensive review by Rotman and Sanyal.1 I would just like to point out an error in table 1 (row 1), where the authors inadvertently state that pioglitazone has shown histological benefit only in secondary analyses and not been studied in patients with diabetes and nonalcoholic fatty liver disease (NAFLD). Benefit with the thiazolidinedione has been reported for the primary histological outcome in two randomised controlled trials (RCTs) in patients with prediabetes or type 2 diabetes mellitus (T2DM). This is most likely an oversight as in the …
Review: In CAD without HF, RAS inhibitors reduce deaths more than placebo but not active control
Authors: Angela Lowenstern, L. Kristin Newby
Journal: Annals of Internal Medicine (2017)

Source Citation Bangalore S, Fakheri R, Wandel S, et al. Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials. BMJ. 2017;356:j4. 28104622
Quality of Life After Surgery or DES in Patients With 3-Vessel or Left Main Disease
Authors: Mouin S. Abdallah, Kaijun Wang, Elizabeth A. Magnuson, Ruben L. Osnabrugge, A. Pieter Kappetein, Marie-Claude Morice, Friedrich A. Mohr, Patrick W. Serruys, David J. Cohen
Journal: Journal of the American College of Cardiology (2017)
H2A monoubiquitination in Arabidopsis thaliana is generally independent of LHP1 and PRC2 activity
Authors: Yue Zhou, Francisco J. Romero-Campero, Ángeles Gómez-Zambrano, Franziska Turck, Myriam Calonje
Journal: Genome biology (2017)

Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets. By using genome-wide analyses, we show that H2AK121ub marks are surprisingly widespread in Arabidopsis thaliana, often co-localizing with H3K27me3 but also occupying a set of transcriptionally active genes devoid of H3K27me3. Furthermore, by profiling H2AK121ub and H3K27me3 marks in atbmi1a/b/c, clf/swn, and lhp1 mutants we found that PRC2 activity is not required for H2AK121ub marking at most genes. In contrast, loss of AtBMI1 function impacts the incorporation of H3K27me3 marks at most Polycomb group targets. Our findings show the relationship between H2AK121ub and H3K27me3 marks across the A. thaliana genome and unveil that ubiquitination by PRC1 is largely independent of PRC2 activity in plants, while the inverse is true for H3K27 trimethylation.
TCTAP A-002 Bioresorbable Vascular Scaffold in Real World Practice: Single Center Experiences
Authors: Yi-Chih Wang, Jing-Yi Jhang, Cho-Kai Wu, Jen-Kuang Lee, Chia-Ti Tsai, Lian-Yu Lin, Ching-Chang Huang, Chih-Fan Yeh, Ying-Hsien Chen, Mao-Shin Lin, Yen-Hung Lin, Po-Yuan Chang, Paul Hsien-Li Kao, Chii-Ming Lee, Fu-Tien Chiang, Juey-Jen Hwang
Journal: Journal of the American College of Cardiology (2017)
Abstract P257: Isoform-Specific Effects of the Transcription Factor Sister-of-Mammalian Grainyhead on Endothelial Cells and in Vivo
Authors: Arne Mlynek, Margarete Lukosz, Martin Graf, Christoph Winkler, Judith Haendeler, Joachim Altschmied
Journal: Circulation Research (2011)

Apoptosis and reduced migratory capacity of human endothelial cells (EC) are hallmarks for the development of atherosclerosis. TNFalpha has been described as one apoptotic stimulus, which is increased during cardiovascular disease. However, recent findings support the hypothesis that TNFalpha can induce survival genes before committing cells to apoptosis. In a screen for anti-apoptotic genes regulated by TNFalpha we have identified the transcription factor Sister-of-Mammalian Grainyhead/Grainyhead-like 3 (SOM/GRHL3). In humans two RNAs are transcribed from the gene, one of which is alternatively spliced, yielding the protein isoforms SOM1 and SOM3, the latter being an N-terminally truncated version. We have found that both isoforms are expressed in EC. Since nothing is known about the function of these proteins in EC, we investigated their functional properties and role in migration and apoptosis. To analyze their transcription factor activity we established a SOM-dependent reporter system by inserting tandem SOM binding sites and corresponding mutants upstream of a minimal promoter driving luciferase expression. To assess transcriptional activation by SOM1 and SOM3 we cotransfected these reporters with expression vectors for both proteins. In contrast to previously published work, in which isolated SOM domains fused to a Gal4 DNA binding domain were used, we found that both full length proteins are active transcription factors. We next investigated the influence of SOM1 and SOM3 on EC functions. Surprisingly, overexpression of isoform 1 induced migration and inhibited apoptosis, whereas isoform 3 had opposite effects. Along the same lines, SOM1, but not SOM3 activated endothelial nitric oxide synthase and Akt. To investigate whether these isoforms have different functions also in vivo, we overexpressed them in zebrafish embryos. SOM3 but not SOM1 overexpression led to increased lethality, a strong reduction in normal phenotype and a 10 fold higher frequency in heavy deformations. The effects observed on EC migration and apoptosis as well as on zebrafish development suggest that these isoforms activate different sets of target genes, which we are currently identifying by microarray analysis.
A novel antigen delivery system induces strong humoral and CTL immune responses
Authors: Zishan Yang, Miaomiao Xu, Zhenghu Jia, Yuting Zhang, Li Wang, Hongru Zhang, Jingya Wang, Mei Song, Yapu Zhao, Zhenzhou Wu, Liqing Zhao, Zhinan Yin, Zhangyong Hong
Journal: Biomaterials (2017)
TCTAP A-133 Hemostatic Complication Caused by Transpopliteal Retrograde Approach with Angiography-guided Puncture in the Supine Position
Authors: Kenji Yanishi, Kan Zen, Osami Kawarada, Naohiko Nakanishi, Takeshi Nakamura, Satoaki Matoba
Journal: Journal of the American College of Cardiology (2017)