tbuckley/cabot-search huggingface dataset:
Topological Arrangement of Cardiac Fibroblasts Regulates Cellular Plasticity
Authors: Jingyi Yu, Marcus M. Seldin, Kai Fu, Shen Li, Larry Lam, Ping Wang, Yijie Wang, Dian Huang, Thang L. Nguyen, Bowen Wei, Rajan P. Kulkarni, Dino Di Carlo, Michael Teitell, Matteo Pellegrini, Aldons J. Lusis, Arjun Deb
Journal: Circulation Research (2018)

Rationale: Cardiac fibroblasts do not form a syncytium but reside in the interstitium between myocytes. This topological relationship between fibroblasts and myocytes is maintained throughout postnatal life until an acute myocardial injury occurs, when fibroblasts are recruited to, proliferate and aggregate in the region of myocyte necrosis. The accumulation or aggregation of fibroblasts in the area of injury thus represents a unique event in the life cycle of the fibroblast, but little is known about how changes in the topological arrangement of fibroblasts after cardiac injury affect fibroblast function. Objective: The objective of the study was to investigate how changes in topological states of cardiac fibroblasts (such as after cardiac injury) affect cellular phenotype. Methods and Results: Using 2 and 3-dimensional (2D versus 3D) culture conditions, we show that simple aggregation of cardiac fibroblasts is sufficient by itself to induce genome-wide changes in gene expression and chromatin remodeling. Remarkably, gene expression changes are reversible after the transition from a 3D back to 2D state demonstrating a topological regulation of cellular plasticity. Genes induced by fibroblast aggregation are strongly associated and predictive of adverse cardiac outcomes and remodeling in mouse models of cardiac hypertrophy and failure. Using solvent-based tissue clearing techniques to create optically transparent cardiac scar tissue, we show that fibroblasts in the region of dense scar tissue express markers that are induced by fibroblasts in the 3D conformation. Finally, using live cell interferometry, a quantitative phase microscopy technique to detect absolute changes in single cell biomass, we demonstrate that conditioned medium collected from fibroblasts in 3D conformation compared with that from a 2D state significantly increases cardiomyocyte cell hypertrophy. Conclusions: Taken together, these findings demonstrate that simple topological changes in cardiac fibroblast organization are sufficient to induce chromatin remodeling and global changes in gene expression with potential functional consequences for the healing heart.
Integrating Health and Mental Health Services: A Past and Future History
Authors: Benjamin G. Druss, Howard H. Goldman
Journal: American Journal of Psychiatry (2018)

The authors trace the modern history, current landscape, and future prospects for integration between mental health and general medical care in the United States. Research and new treatment models developed in the 1980s and early 1990s helped inform federal legislation, including the 2008 Mental Health Parity and Addiction Equity Act and the 2010 Affordable Care Act, which in turn are creating new opportunities to further integrate services. Future efforts should build on this foundation to develop clinical, service-level, and public health approaches that more fully integrate mental, medical, substance use, and social services. [AJP AT 175: Remembering Our Past As We Envision Our Future July 1928: A President Takes Stock Adolf Meyer: "I sometimes feel that Einstein, concerned with the relativity in astronomy, has to deal with very simple facts as compared to the complex and erratic and multicontingent performances of the human microcosmos, the health, happiness and efficiency of which we psychiatrists are concerned with." (Am J Psychiatry 1928; 85(1):1-31 )].
Non-invasive liver tests in electronic health records of patients with non-alcoholic fatty liver disease: combined analysis from four European countries
Authors: N. Dhalwani, M. Alexander, K. Loomis, N. Sattar, D. Waterworth, M. Mosseveld, P. Rijnbeek, J. van der Lei, T. Duarte-Salles, D. Prieto-Alhambra, D. Ansell, A. Pasqua, F. Lapi, P. Egger, S. Kendrick, W. Alazawi
Journal: Journal of Hepatology (2018)
A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib in combination with bendamustine and rituximab for previously untreated chronic lymphocytic leukemia.
Authors: Gilles A. Salles, Nicole Lamanna, Bipinkumar R. Amin, Ralph V. Boccia, Nashat Y. Gabrail, Muhammad-Ali A. Zaydan, Michelle Wong, Adeboye H. Adewoye, Paolo Ghia
Journal: Journal of Clinical Oncology (2014)

TPS7123 Background: PI3Kδ is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib (GS-1101) is a first-in-class, targeted, highly selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). A recent phase 3 trial demonstrated that idelalisib plus rituximab is highly active in pts with relapsed CLL compared to placebo plus rituximab: patients receiving idelalisib had improved rates of overall response (81% vs. 13%) and overall survival at 12 months (92% vs. 80%), with an acceptable safety profile (Furman et al, 2014). The regimen of bendamustine + rituximab has demonstrated efficacy in the treatment of patients with previously untreated CLL. Methods: 280 patients with previously untreated CLL and measurable lymphadenopathy will be enrolled in this global phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Pts will be randomized in a 1:1 ratio to Arm A or B of the study. On Arm A, subjects will receive idelalisib (150 mg BID continuously for 96 weeks) plus rituximab (6 infusions of 375 – 500 mg/m2 over 6 months) and bendamustine (12 infusions of 90 mg/m2 over 6 months). In Arm B, subjects will receive placebo instead of idelalisib. Stratification factors include IGHV mutational status, del(17p) status, and Rai stage. The primary endpoints of the study are minimal residual disease and PFS. The secondary endpoints are ORR, nodal response rate, CR, and OS. The difference in PFS will be compared between Arm A and Arm B in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Jan 2014. Clinical trial information: NCT01980888.
Former specialist registrar wins appeal against “flawed” decision to strike him off
Authors: Clare Dyer
Journal: BMJ (2018)

A former specialist registrar at Guy’s and St Thomas’s NHS Foundation Trust in London has won a High Court appeal against a “flawed” decision of the Medical Practitioners Tribunal Service to strike him off the UK medical register.1

The tribunal decided in May 2017 that Ganeshmoorthi Arunachalam should be struck off, even though the General Medical Council had argued at the tribunal hearing that he should be suspended.

In May to July 2014 Arunachalam sent inappropriate personal messages to one trainee doctor, named as “A,” although without using sexual language. And in November 2014 he nudged and tickled another junior, “B,” four …
Hypertension Across a Woman’s Life Cycle
Authors: Nanette K. Wenger, Anita Arnold, C. Noel Bairey Merz, Rhonda M. Cooper-DeHoff, Keith C. Ferdinand, Jerome L. Fleg, Martha Gulati, Ijeoma Isiadinso, Dipti Itchhaporia, KellyAnn Light-McGroary, Kathryn J. Lindley, Jennifer H. Mieres, Mary L. Rosser, George R. Saade, Mary Norine Walsh, Carl J. Pepine
Journal: Journal of the American College of Cardiology (2018)
Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective
Authors: Laurent Alric, Isabelle Ollivier-Hourmand, Emilie Bérard, Sophie Hillaire, Maeva Guillaume, Anais Vallet-Pichard, Brigitte Bernard-Chabert, Veronique Loustaud-Ratti, Marc Bourlière, Victor de Ledinghen, Isabelle Fouchard-Hubert, Valerie Canva, Anne Minello, Eric Nguyen-Khac, Vincent Leroy, David Saadoun, Dominique Trias, Stanislas Pol, Nassim Kamar
Journal: Kidney International (2018)
Polymorphism in cancer-associated fibroblasts (CAFs) related genes and clinical outcome in metastatic colorectal cancer (mCRC) patients (pts) enrolled in two independent randomized phase III trials: TRIBE and FIRE-3.
Authors: Alberto Puccini, Martin D. Berger, Ryuma Tokunaga, Madiha Naseem, FRANCESCA BATTAGLIN, Shu Cao, Joshua Millstein, Shivani Soni, Michelle McSkane, Wu Zhang, Fotios Loupakis, Sebastian Stintzing, Volker Heinemann, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2018)

645 Background: Tumor microenvironment plays a critical role for CRC development and progression. CAFs are the most dominant cellular components which orchestrate tumor cell proliferation, survival and invasion and have been shown to be associated with prognosis in pts with CRC. We aimed to evaluate whether single-nucleotide polymorphisms (SNPs) in CAFs related genes predict outcome in mCRC pts treated with first-line FOLFIRI/bevacizumab (bev) in TRIBE and FIRE-3 trials. Methods: The OncoArray, a custom array by Illumina including 530K SNP markers, was used to genotype genomic DNA from blood samples and served as our database, from which 15 functional SNPs within 9 genes (OPN, CD44, TCN, CD63, TIMP1, SLIT2, ROBO1, LOXL2, INHBA) related to CAF pathway were analyzed. Results: A total of 451 pts were included. Those treated with FOLFIRI/bev in TRIBE (N = 215, median PFS/OS: 9.7/26.3 months (mts)) and FIRE-3 (N = 107, median PFS/OS: 11.6/31.5 mts) served as discovery and validation cohorts respectively, while FIRE-3 FOLFIRI/cetuximab arm (N = 129, median PFS/OS: 12.8/49.8 mts) was used as the control. In overall pts in discovery set, OPN (osteopontin) rs11728697 any C variants showed longer PFS (median 10.8 vs 9.0 mts; HR = 0.68, 95%CI = 0.49-0.95; p = 0.025) and OS (median 30.6 vs 23.8 mts; HR = 0.69, 95%CI = 0.50-0.95; p = 0.025) than the homozygous wild type genotype (T/T) in multivariable analysis. These data were validated in the FIRE-3 cohort in OS both in univariate (median 49.3 vs 23.7 mts; HR = 0.40, 95%CI = 0.21-0.77; p &lt; 0.001) and in multivariable analyses (HR = 0.31, 95%CI = 0.16-0.60; p &lt; 0.001). However, the favorable impact on outcome was not shown among C allele carriers treated with FOLFIRI/cetuximab in the control arm. Conclusions: Our findings confirm that CAFs play a crucial role in mCRC and suggest that OPN polymorphisms could serve as predictive biomarkers for mCRC pts treated with first-line FOLFIRI/bev.
Self-monitoring and reminder text messages to increase physical activity after colorectal cancer (CRC): A pilot randomized controlled trial.
Authors: Erin Van Blarigan, Katherine Van Loon, Stacey A. Kenfield, June M. Chan, Emily Mitchell, Hilary Chan, Li Zhang, Alan Paciorek, Galen Joseph, Angela Laffan, Yoshimi Fukuoka, Christine Miaskowski, Jeffrey A. Meyerhardt, Alan P. Venook
Journal: Journal of Clinical Oncology (2018)

615 Background: Over 1.3 million people in the US are living with CRC. Physical activity is associated with lower risk of CRC mortality. Interventions are needed to increase physical activity after CRC diagnosis. Methods: We conducted a pilot RCT to determine the feasibility (adherence, attrition) and acceptability of a 12-wk intervention using a Fitbit Flex™ and daily text messages to increase physical activity after CRC. Eligible patients had to have colon or rectal cancer of any stage, be disease free or have stable disease, able to speak and read English, and access to Internet and a mobile phone. Individuals with contraindications to moderate-to-vigorous physical activity (MVPA) or exercising ≥30 min ≥5 d/wk were excluded. We explored the impact of the intervention (n = 20) vs. usual care (n = 21) on MVPA via ActiGraph GT3X+ accelerometers pre-/post-intervention. Results: The intervention was feasible and acceptable. On average, participants were 54 y, BMI 28 kg/m 2 and enrolled 1.5 y after diagnosis; 59% were women, 73% were White, and 61% were stage III. The intervention arm wore their Fitbits a median of 74 d (89% of study days, IQR: 23-83 d) and responded to 74% (34) of the 46 text messages that asked for a reply (IQR: 28-82%). Older participants were more likely to wear the Fitbit ( r: 0.72; p &lt; 0.001). Married participants were more likely to wear the Fitbit and respond to texts compared to unmarried (96% vs. 32% wear time, p: 0.02 and 85% vs. 46% response rate, p: 0.006). Most patients (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. On average, the intervention arm increased MVPA by 14 min/d, while the control arm increased by only 1 min/d, but there was no statistically significant difference in change in MVPA between groups (mean difference comparing change in MVPA in the intervention vs. control: 13 min/d; 95% CI: -14, 40; p: 0.33). Conclusions: A 12-wk physical activity intervention with a Fitbit and text messages is feasible and acceptable among CRC patients after treatment. Larger studies are needed to determine whether the intervention increases physical activity. Clinical trial information: NCT02966054.
A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma
Authors: Bryan M. Burt, William G. Richards, Hyun-Sung Lee, Sylvia Bartel, Marcelo C. Dasilva, Ritu R. Gill, Michael T. Jaklitsch, Bruce E. Johnson, Scott J. Swanson, Raphael Bueno, David J. Sugarbaker
Journal: Journal of Thoracic Oncology (2018)
Abstract 16872: Increased Production of Oxidized Phosphatidylcholine Molecules in Patients Presenting With ST Elevation Myocardial Infarction (STEMI)
Authors: Rachael Searle, David Allen, Devin Hasanally, Rakesh Chaudhary, Amir Ravandi
Journal: Circulation (2015)

Introduction: Despite restoration of blood flow to myocardium after ischemia, a large percentage of myocardial cells die after reperfusion. This phenomenon is termed ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPC) are generated in the presence of reactive oxygen species, which are abundant during I/R. We aimed to determine the change in OxPC in patients presenting with STEMI who undergo primary Percutaneous Coronary Intervention (PCI). Methods: Blood samples were collected from subjects with STEMI (n=27) and subjects with non-obstructive CAD (n=20) prior to, and at completion of PCI/angiography respectively. The complete oxidative lipidomic profile at the onset of STEMI and after PCI was compared to control prior to and after diagnostic angiography. The oxidative lipidomic profile was established and compared using high-performance electrospray mass spectrometry. Results: Seventy nine distinct OxPCs were identified in human plasma which included fragmented OxPCs, terminal furans, isoprostanes and long-chain products. There were 17 compounds that showed a significant increase in the STEMI population when compared to control. The largest changes seen overall were in the fragmented OxPCs. Fragmented OxPCs in control vs pre PCI STEMI had a significant rise from 8.9 vs 21.8 ng/ml of plasma, (p = 0.0001) and STEMI post PCI increased to 8.9 vs 29.7 ng/ml of plasma, (p = 7.1x10-5). When organizing molecules by functional group, fragmented carboxylic acid OxPCs were the most abundant in plasma with pre vs post PCI levels increasing from 12.8 to 22.2 ng/ml of plasma (p= 0.03). Conclusion: We have shown for the first time that OxPC molecules are present in patients with STEMI and are increased when compared to control patients. There is also a significant increase in OxPC levels after PCI in the STEMI population. These changes represent increases in OxPC during ischemia and a further increase after reperfusion injury. Given the potent biological activity of OxPCs, the attenuation of their activity may be a novel therapeutic approach to reduce the deleterious effects of I/R.
P506Adverse left ventricular remodeling and the serum levels of matrix metalloproteinases, biomarkers of myocardium dysfunction and inflammation in patients with acute primary anterior STEMI
Authors: M Kercheva, A Gusakova, T Ryabova, V Ryabov
Journal: Cardiovascular Research (2018)

Conclusion:In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT3/PGC-1a signaling.
TCTAP C-223 Diffusely Calcified Long Lesion Treated Using Rotablation
Authors: Hanbit Park, Sang Yong Om, Yong-Hoon Yoon, Minsoo Kim, Sang-Cheol Cho, Kyusup Lee, Osung Kwon, Do-Yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
P143Mechanisms involved in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity
Authors: V Cachofeiro Ramos, G Marin-Royo, J Gutierrez-Tenorio, E Martinez-Martinez, M Miana, N Lopez-Andres, R Jurado-Lopez, I Gallardo, J A San Roman, M L Nieto
Journal: Cardiovascular Research (2018)
Austrian doctors secure potential reprieve for scrapped smoking ban
Authors: Ned Stafford
Journal: BMJ (2018)

A campaign led by Austrian doctors to provide smoke free areas in some public places has forced the new right wing government to place petitions in polling stations across the country and could lead to a referendum on the issue.

The newly elected governing coalition of Chancellor Sebastian Kurz in March abolished a law approved in 2015 that banned smoking in pubs and restaurants and that was due to take effect on 1 May. The coalition took the unprecedented action despite a highly …
P548Four-and-a-half LIM-domain 2 secretion is increased in the dilated aorta of bicuspid aortic valve patients
Authors: V Van De Pol, K B Kurakula, L R Bons, J W Roos-Hesselink, M C Deruiter, M J Goumans
Journal: Cardiovascular Research (2018)

Results: Hyperglycemia(1961.4 in DMþCKDþHC vs 8.961.5 mmol/l in CON, P<0.001), CKD (glomerular filtration rate: 132614 vs 19169 ml/min, P<0.01) and hypercholesterolemia (8.261 vs 1.760.1 mmol/l, P<0.001) were successfully induced.Myocardial oxygen delivery was impaired in DMþCKDþHC swine both at rest and during exercise (P<0.05),forcing the myocardium to increase its oxygen extraction, resulting in reduced coronary venous oxygen content compared to CON (both P<0.05) suggestive of impaired NO bioavailability.However, the response to SNP was increased in the DMþCKDþHC swine (*P¼0.043,figure), indicating an increased NO sensitivity.PDE5 inhibition resulted in a mild decrease in myocardial oxygen extraction (CON P¼0.14, DMþCKDþHC †P¼0.01,figure) that was similar in DMþCKDþHC and CON swine (P¼0.92).This was supported by a similar PDE5 activity in myocardial tissue of both groups (P¼0.26).Conclusions: Impaired NO bioavailability in coronary microvasculature of swine with multiple comorbidities seems to be compensated by a higher sensitivity to NO and maintained PDE5 signaling.
TCTAP C-220 Successful Transcatheter Aortic Valve Replacement for the Treatment of Severe Aortic Stenosis with Bicuspid Aortic Valve
Authors: Sung-yun Jung, KangUn Choi, Jung-Hee Lee, Chan-Hee Lee, Jang-Won Son, Ung Kim, Jong-Seon Park, Dong-Gu Shin
Journal: Journal of the American College of Cardiology (2018)
Regulatory T cells modulate the concentration of short chain fatty acids and the Th function in response to induced bacterial traslocation episodes, and improve the integrity of the gut barrier in an experimental cirrhosis model
Authors: O. Juanola, I. Gómez-Hurtado, P. Piñero, R. García-Villalba, A. Marín, E. Caparrós, F.T. Rodrigo, P. Zapater, J.M. González-Navajas, F.T.-B. Barberán, R. Francés
Journal: Journal of Hepatology (2018)
Screening for Prostate Cancer
Authors: Jill Jin
Journal: JAMA (2018)

US Preventive Services Task Force; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Douglas K. Owens, MD, MS; Kirsten Bibbins-Domingo, PhD, MD, MAS; Aaron B. Caughey, MD, PhD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; Mark Ebell, MD, MS; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Martha Kubik, PhD, RN; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Albert L. Siu, MD, MSPH; Chien-Wen Tseng, MD, MPH, MSEE
Cost-effectiveness of exercise therapy in the treatment of non-specific neck pain and low back pain: a systematic review with meta-analysis
Authors: Gisela Cristiane Miyamoto, Chung-Wei Christine Lin, Cristina Maria Nunes Cabral, Johanna M van Dongen, Maurits W van Tulder
Journal: British Journal of Sports Medicine (2018)

Objective To investigate the cost-effectiveness of exercise therapy in the treatment of patients with non-specific neck pain and low back pain. Design Systematic review of economic evaluations. Data sources The search was performed in 5 clinical and 3 economic electronic databases. Eligibility criteria for selecting studies We included economic evaluations performed alongside randomised controlled trials. Differences in costs and effects were pooled in a meta-analysis, if possible, and incremental cost-utility ratios (ICUR) were descriptively analysed. Results Twenty-two studies were included. On average, exercise therapy was associated with lower costs and larger effects for quality-adjusted life-year (QALY) in comparison with usual care for subacute and chronic low back pain from a healthcare perspective (based on ICUR). Exercise therapy had similar costs and effect for QALY in comparison with other interventions for neck pain from a societal perspective, and subacute and chronic low back pain from a healthcare perspective. There was limited or inconsistent evidence on the cost-effectiveness of exercise therapy compared with usual care for neck pain and acute low back pain, other interventions for acute low back pain and different types of exercise therapy for neck pain and low back pain. Conclusions Exercise therapy seems to be cost-effective compared with usual care for subacute and chronic low back pain. Exercise therapy was not (more) cost-effective compared with other interventions for neck pain and low back pain. The cost-utility estimates are rather uncertain, indicating that more economic evaluations are needed. Registration PROSPERO, CRD42017059025.