tbuckley/cabot-search huggingface dataset:
Abstract 20075: Post-transplant Outcomes for Congenital Heart Disease Patients Bridged to Transplant With Ventricular Assist Deivces
Authors: Raheel Rizwan, Chet Villa, Farhan Zafar, Dennis Wells, Roosevelt Bryant, Clifford Chin, Angela Lorts, David L Morales
Journal: Circulation (2016)

Introduction:  Ventricular assist devices (VAD) use as a bridge-to-transplant (BTT) for children of congenital heart disease (CHD) with end-stage heart failure is challenging, yet has been increasingly described. However, its impact on post-transplant outcomes is unknown. This study describes the post-transplant outcomes of CHD patients BTT with a VAD.   Methods:  United Network of Organ Sharing database from January 1, 2006 to June 30, 2015 was analyzed for all CHD patients undergoing heart transplantation. Patients were divided into two groups based on VAD use and presence of CHD; +CHD/+VAD and +CHD/-VAD. Pre transplant characteristics and post-transplant outcomes were compared between the groups. +CHD/+VAD post-transplant survival was also compared with -CHD/+VAD and -CHD/-VAD cohorts.   Results:  There were 1871 heart transplant recipients who had CHD, 72% (1348) were  0.05). Also, 1y and 5y Kaplan-meier survival was not different when comparing +CHD/+VAD with -CHD/+VAD and -CHD/-VAD. [Table]   Conclusion:  Although more ill pre-transplant, CHD patients BTT with a VAD have similar post-transplant outcomes compared to CHD patients without a VAD and to other heart transplant patients. Therefore, VAD support in CHD patients may negate certain risk factors for poor post-transplant outcomes in this challenging cohort.
Constitutive multiple drug resistance in tumor stem cells
Authors: Vera S. Donnenberg, James D. Luketich, Julie A. Deloia, Adam M. Brufsky, Neil A. Christie, Jeffrey A. Romoff, Albert D. Donnenberg
Journal: Cancer Research (2005)

2047   Failure to eradicate cancer may be as fundamental as a misidentification of the target. Current therapies succeed at eliminating bulky disease and proliferating cells, but miss a tumor reservoir that leads to disease recurrence and metastasis. Advances in the understanding of normal tissue development and repair provide a basis for revisiting oncogenesis, tumor heterogeneity, and drug resistance. In order to test the hypothesis that tumor stem cells, small resting cells with the stem cell-like properties of self-renewal, protection, and apoptosis resistance, exist as rare populations in heterogeneous tumors, we used flow cytometry to simultaneously measure tumor and stem cell markers, and constitutive multiple drug resistance transporter expression and activity ( side population ) in cancer specimens (breast, ovarian, lung, colon, renal, prostate). We concentrated on pleural effusions and ascites, where analysis is not confounded by the presence of normal tissue stem cells. In all cases (n=28) we have succeeded in detecting cytokeratin+, ESA+, CD45-, MDR+ tumor cells of small resting morphology. Building on the findings of the Clarke laboratory, we have shown that these cells are contained within the tumorigenic CD44+/CD24 negative or dim population. Small resting tumor cells are cytokeratin dim, exclusively display P-gp (ABCC1) activity (rhodamine 123 transport) and also express the classical stem cell markers c-kit (CD117), Thy-1 (CD90) and the MDR transporter ABCG2 (BCRP1). This population represents the best candidate for the resting tumor stem cell and is present in pleural effusions at a frequency of ∼1/100,000 cells. In ovarian and breast cancer we have isolated this subset and demonstrated long-term in vitro clonogenicity at frequencies
Abstract 07: Perceptions of Neighborhood Environment are Associated with Shorter Telomere Length in African American Women
Authors: Samson Y Gebreab, Pia Riestra, Rumana J Khan, Ruihua Xu, Amadou Gaye, Sharon K Davis
Journal: Circulation (2016)

Objectives: Telomere length (TL) is increasingly being used as a biomarker of cellular aging and age-related cardiovascular diseases (CVD), but the associations between perceptions of neighborhood environment and TL among African Americans is understudied. This study examined whether perceptions of neighborhood environment were associated with TL in African Americans after adjustment for potential confounders. Methods: Data was obtained from the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) study recruited from April 2012 and September 2013. 252 (170 women and 82 men) African Americans aged 30 to 55 years were included. TL was measured from peripheral blood mononuclear cells using quantitative real-time polymerase chain reaction. Perceptions of neighborhood environment were assessed using a 12- item scale administered to study participants. The items were summed and averaged to create a score index representing social cohesion, problems and overall unfavorable perception of neighborhood environment. Multivariable linear regression models were used to examine the associations of perceptions of neighborhood environment with TL. Results: On average, women had significantly longer TL than men (4868.6 vs. 4574.8 base pairs, p=0.01). After controlling for socio-demographic variables, and CVD and psychosocial risk factors, a one standard deviation (SD) increase in perception of neighborhood problems was associated with shorter TL (mean difference[[Unable to Display Character: &amp;#8201;]]=[[Unable to Display Character: &amp;#8201;]]-106 base pairs; standard error (SE)=42, p[[Unable to Display Character: &amp;#8201;]]=[[Unable to Display Character: &amp;#8201;]]0.014) among women. Overall unfavorable perception of neighborhood environment was also associated with shorter TL among women (mean difference[[Unable to Display Character: &amp;#8201;]]=[[Unable to Display Character: &amp;#8201;]]-80; SE=38, p=[[Unable to Display Character: &amp;#8201;]]0.034). Better perception of social cohesion was associated with longer TL, but did not reach statistical significance (mean difference = 32, SE=29, p=0.282). No consistent association was observed between perceptions of neighborhood environment and TL among men. Conclusions: Our findings suggest that perceptions of neighborhood environment may be predictive of cellular aging in African American women. Future longitudinal studies are needed to better determine the causal mechanisms underlying these associations.
TAXANE ASSOCIATED WITH TRASTUZUMAB INDUCED EARLY VENTRICULAR IMPAIRMENT: CORRELATION WITH BIOLOGICAL MARKERS OF CHRONIC INFLAMMATION AND OXIDATIVE STRESS
Authors: Christian Cadeddu, Alessandra Piras, Dessi Mariele, Clelia Madeddu, Martino Deidda, Giovanni Mantovani, Giuseppe Mercuro
Journal: Journal of the American College of Cardiology (2013)
Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis
Authors: Lieve Van Hoovels, Julie Jacobs, Bert Vander Cruyssen, Stefanie Van den Bremt, Patrick Verschueren, Xavier Bossuyt
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Rheumatoid factor (RF) and anti-cyclic citrullinated protein/peptide antibodies (ACPA) are integrated in the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA). The objectives of this study were to evaluate the technical and diagnostic performance of different RF and ACPA assays and to evaluate whether differences in performance impact RA classification. Methods Samples from 594 consecutive patients who for the first time consulted a rheumatologist (44 of whom were diagnosed with RA) and 26 extra newly diagnosed patients with RA were analysed with six different RF assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euroimmun) and seven different ACPA assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euro Diagnostica, Euroimmun). Results We found differences in analytical performance between assays. There was poor numerical agreement between the different RF and ACPA assays. For all assays, the likelihood ratio for RA increased with increasing antibody levels. The areas under the curve of receiver operating characteristic analysis of the RF (range 0.676–0.709) and ACPA assays (range 0.672–0.769) only differed between some ACPA assays. Nevertheless, using the cut-off proposed by the manufacturer, there was a large variation in sensitivity and specificity between assays (mainly for RF). Consequently, depending on the assay used, a subgroup of patients (13% for RF, 1% for ACPA and 9% for RF/ACPA) might or might not be classified as RA according to the 2010 ACR/EULAR criteria. Conclusion Due to poor harmonisation of RF and ACPA assays and of test result interpretation, RA classification according to 2010 ACR/EULAR criteria may vary when different assays are used.
Updated efficacy and safety results from the phase I study of intermittent dosing of the dual MEK/RAF inhibitor, RO5126766 in patients (pts) with <i>RAS/RAF</i> mutated advanced solid tumours.
Authors: Samuel John Harris, Maria Jose de Miguel Luken, Desamparados Roda Perez, Raquel Perez Lopez, Mona Parmar, Vasanthi Prathapan, Hasina Hassam, Alison Joanne Turner, Sonia Serrano Fandos, Emma Hall, Holly Tovey, Nina Tunariu, Juanita Suzanne Lopez, Timothy Anthony Yap, Johann S. De Bono, Udai Banerji
Journal: Journal of Clinical Oncology (2016)

2582 Background: RO5126766 is a novel MEK inhibitor with functional RAF inhibition. A dose escalation Phase 1 study, comparing 2 intermittent schedules, has previously been reported, with a recommended phase 2 dose (RP2D) of 4 mg twice weekly (Monday/Thursday (M/Th)). We now present results from the expansion cohort of this study, which aims to assess tolerability and preliminary activity in pts with KRAS, NRAS or BRAFmutated tumours. Methods: Pts with KRAS, NRAS or BRAF mutated tumours were treated with RO5126766 at the RP2D dose of 4 mg M/Th in 4 week cycles. Tumour assessment was performed with CT imaging every 2 cycles. Tumour pharmacodynamics was assessed in pre and post treatment biopsies where available. Results: To date, 18 evaluable pts (8 Non Small Cell Lung Carcinoma (NSCLC), 4 colorectal, 3 ovarian, 1 endometrial, 1 uterine carcinosarcoma, 1 melanoma) have been treated. Pts had received 1-7 (median 3) lines of treatment previously. Skin rashes were common G1-2 12pts, G3-4 4pts. Other adverse events were CK elevation, visual disturbances, peripheral oedema, mucositis, dry skin, diarrhoea and fatigue. Toxicities were manageable, however, dose reduction to 3.2 mg or 2.4 mg was required in 10 pts. Tumour size reduction was seen in 4/8 (50%) of pts with KRAS mutant NSCLC, of which 3/8 (37.5%) were RECIST partial responses (PR). The 8 NSCLC pts, had previously received 1-4 (median 2) lines of treatment, all having received platinum doublet chemotherapy. G12V, G12R and unknown codon 12/13 mutations were detected in responding NSCLC pts. RECIST PR was seen in 1 pt with KRAS mutated endometrial carcinoma and 1 pt with KRAS mutated ovarian cancer, whilst additionally, 1 pt with BRAF mutated ovarian cancer showed tumour size reduction. These two ovarian carcinoma pts had both received two separate MEK/BRAF inhibitors previously. Currently 5 pts overall remain on study and responses range from 4 -16.8 months. Recruitment is ongoing with plans to expand further in KRASmutated malignancies. Conclusions: These preliminary results, especially in KRAS mutant NSCLC pts who have been previously treated with standard of care chemotherapy, are encouraging. Clinical trial information: NCT02407509.
Determinants of health related quality of life (HRQoL) in adult patients with hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE)
Authors: Marina Lluncor, Donatella Lamacchia, Adriana Hernanz, Maria Pedrosa, Ana Alvez, Rosario Cabañas, Nieves Prior, Teresa Caballero
Journal: Journal of Allergy and Clinical Immunology (2018)
Evaluation of Residual Minimum Response with Free Serum Light Chains in Patients with Multiple Myeloma Diagnosis
Authors: Espinoza Ramiro, Labardini Juan, Cervera Eduardo, Karen Perez, Cristina Barrera, Myrna Candelaria, Alejandro Sosa, Laura Garcia, Celia Lopez, Magnolia Vieyra, Nidia Zapata
Journal: Blood (2017)
Predictors of early discontinuation of chemotherapy (EDC) in patients (pts) age 65 or older with stage IV non-small cell lung cancer (NSCLC).
Authors: Ajeet Gajra, William P. Tew, Molly Hardt, Supriya Gupta Mohile, Cynthia Owusu, Heidi D. Klepin, Cary P. Gross, Stuart M. Lichtman, Vani Katheria, Arti Hurria
Journal: Journal of Clinical Oncology (2012)

e18133 Background: NSCLC accounts for the highest cancer related mortality. Older pts suffer higher chemotherapy (chemo) toxicity (tox). Inability to complete a planned chemo course is associated with poor outcome. We studied factors associated with EDC (defined as chemo duration of ≤ 6 weeks) in pts ≥ age 65 with stage IV NSCLC. Methods: We conducted a subset analysis of pts with stage IV NSCLC (n=100) enrolled in a multi-site prospective study (n=500) which identified predictors of chemo tox in pts age &gt; 65 (Hurria et al, JCO 2011). Bivariate analysis and multivariate logistic regression were utilized to identify factors associated with EDC among pts with stage IV NSCLC including: sociodemographics, chemo factors (1 st vs. 2 nd + line; single vs doublet), labs (hemoglobin [Hb], liver function, creatinine clearance, albumin) and geriatric assessment (GA) variables (functional status, comorbidity, social support, psychological, cognitive and nutritional status). Results: Of the 100 pts (median age 73, range 65-89) with stage IV NSCLC, 33 had EDC. Of these 67% was for disease progression, 15% tox and 15% for both progression and tox. Majority received 1 st line (58%) and doublet chemo (67%). In bivariate analysis (p values &lt;0.01 for all), pts with EDC were more likely to receive single agent (52% vs. 24%) and 2 nd + line chemo (70% vs 28%)and have lower mean Hb (11.3 vs 12.7 g/dl) and albumin levels (3.4 vs 4.0 g/dl). GA variables associated with EDC include poorer physical function [lower score on Medical Outcomes Study physical health (MOS physical), MD rated Karnofsky performance status (KPS), self rated KPS, and MOS social activity, and need assistance with instrumental activities of daily living; p&lt;0.01 for each variable]. On multivariate analysis, factors independently associated with EDC include 2 nd + line chemo (OR=5.93; 95%CI = 2.25-15.61) and lower MOS physical score of &lt;70 (OR= 4.19; 95% CI= 1.56-11.29). Conclusions: In older pts with NSCLC, factors associated with chemo duration of &lt; 6 weeks include 2 nd + line chemo and poor physical function best assessed by MOS physical in this cohort. These simple factors may help the practicing oncologist identify older pts with NSCLC at greatest risk for EDC.
Direct visualisation of hepatitis B virus (HBV)-specific cytotoxic T cells with an human leucocyte antigen (HLA) class I peptide tetrameric complex allows a new insight into their actual frequency.
Authors: M K Maini, G S Ogg, C Boni, M Pilli, C Ferrari, A J McMichael, R Williams, D Vergani, A Bertoletti
Journal: Hepatology (1998)
Realizing the Mass Public Benefit of Evidence-Based Psychological Therapies: The IAPT Program
Authors: David M. Clark
Journal: Annual Review of Clinical Psychology (2018)

Empirically supported psychological therapies have been developed for many mental health conditions. However, in most countries only a small proportion of the public benefit from these advances. The English Improving Access to Psychological Therapies (IAPT) program aims to bridge the gap between research and practice by training over 10,500 new psychological therapists in empirically supported treatments and deploying them in new services for the treatment of depression and anxiety disorders. Currently IAPT treats over 560,000 patients per year, obtains clinical outcome data on 98.5% of these individuals, and places this information in the public domain. Around 50% of patients treated in IAPT services recover, and two-thirds show worthwhile benefits. The clinical and economic arguments on which IAPT is based are presented, along with details of the service model, how the program was implemented, and recent findings about service organization. Limitations and future directions are outlined.
Abstract 10: Widening Rural Disadvantage in United States Premature Heart Disease Mortality: Trends by Region and Race/Ethnicity, 2000 - 2013
Authors: Elizabeth B Pathak, Colin J Forsyth
Journal: Circulation (2016)

Objectives: The purpose of this study was to quantify rural and metropolitan trends in premature heart disease (HD) mortality using the most up-to-date data available (through 2013). To our knowledge this is the first study to analyze these geographic disparities for Hispanics (HSP), Asians/Pacific Islanders (API), and American Indians/Alaska Natives (AI/AN). Methods: Annual age-adjusted HD death rates for adults aged 25-64 years were analyzed for 2000-2013. Rates were calculated for 5 racial/ethnic groups (Non-Hispanic Whites (WNH), Non-Hispanic Blacks (BNH), HSP of any race, Non-Hispanic API, and Non-Hispanic AI/AN). County-level data were aggregated by urbanicity: large central metro (LCM), large fringe metro (LFM), medium/small metro (MSM), and micropolitan/rural (RURAL). Region was defined as South (16 states) and Non-South. All data were obtained from the National Vital Statistics System on CDC WONDER. Average annual percent change (AAPC) was calculated by linear regression of the log-transformed death rates using SAS 9.4. Results: In 2013, the national population-at-risk predominantly resided in metro areas. However, there were more than 10 million RURAL adults aged 25-64 years in the South (16.2% of the region) and more than 13.4 million in the non-South (12.9% of the region). Nationwide, HD death rates were lowest in the LFM counties. In the South, the rate ratio (RR) for RURAL vs. LFM areas in 2011-2013 was 1.76 (95% CI 1.73 to 1.79) for WNH, 2.00 (95% CI 1.85 to 2.16) for HSP, 1.78 (95%CI 1.71 to 1.82) for BNH, 1.57 (95% CI 1.22 to 2.03) for API, and 3.13 (95% CI 2.47 to 3.96) for NNH. In the non-South, RURAL vs. LFM RRs were smaller, with the exception of API (RR 2.37, 95% CI 2.07 to 2.71). Temporal trend analyses revealed significantly smaller AAPC in RURAL areas (see Table). Conclusions: Higher death rates coupled with slower declines have resulted in a widening rural disadvantage in premature HD mortality in the United States from 2000 to 2013, particularly for WNH, HSP, BNH, and AI/AN in the South, and WNH in the non-South.
Abstract 18555: Sleep Duration and Risk of Coronary Heart Disease, Sudden Cardiac Death and All-Cause Mortality
Authors: Hassan Khan, Setor Kunutsor, Kai Savonen, Jari A Laukkanen
Journal: Circulation (2016)

Introduction:  Sleep duration has been shown to be associated with mortality, however do similar observations extend to cause specific events including coronary heart disease (CHD) or sudden cardiac death (SCD) and whether they remain independent of traditional cardiovascular risk factors is unclear.   Hypothesis:  To examine the relationship between sleep duration and risk of CHD, sudden cardiac death and all-cause mortality.   Methods:  Sleep duration was reported at baseline in 2,354 men aged 42-61 years from the Kuopio Ischemic Heart Disease study. Clinical characteristics and follow up data were collected and multivariate Cox proportional hazards modelling was used to test associations.   Results:  A total of 314 fatal CHD events, 201 sudden cardiac events and 997 all-cause mortality events were reported during a median follow-up of 23.2 years. Age-adjusted hazard ratio (HR) comparing the top quartile (> 10 hours) of sleep duration versus the bottom quartile (   Conclusions:  Longer duration of sleep was associated with significant all-cause mortality independent of cardiovascular risk factors. However mechanistic links between these findings remains to be explored further.
Episodic memory solves both social and nonsocial problems, and evolved to fulfill many different functions
Authors: Raymond A. Mar, R. Nathan Spreng
Journal: Behavioral and Brain Sciences (2018)

Abstract The episodic memory system is flexible and complex, and likely evolved in response to a wide range of survival-relevant problems in our evolutionary past, both social and nonsocial. Episodic memory allows us to recollect and infer details that may have seemed trivial on encoding, but are now known to be relevant. This memory aids humans in navigating their uncertain environment.
Endothelial Tie1–mediated angiogenesis and vascular abnormalization promote tumor progression and metastasis
Authors: Silvia La Porta, Lise Roth, Mahak Singhal, Carolin Mogler, Carleen Spegg, Benjamin Schieb, Xianghu Qu, Ralf H. Adams, H. Scott Baldwin, Soniya Savant, Hellmut G. Augustin
Journal: Journal of Clinical Investigation (2018)

The endothelial tyrosine kinase receptor Tie1 remains poorly characterized, largely owing to its orphan receptor status. Global Tie1 inactivation causes late embryonic lethality, thereby reflecting its importance during development. Tie1 also plays pivotal roles during pathologies such as atherosclerosis and tumorigenesis. In order to study the contribution of Tie1 to tumor progression and metastasis, we conditionally deleted Tie1 in endothelial cells at different stages of tumor growth and metastatic dissemination. Tie1 deletion during primary tumor growth in mice led to a decrease in microvessel density and an increase in mural cell coverage with improved vessel perfusion. Reduced angiogenesis and enhanced vascular normalization resulted in a progressive increase of intratumoral necrosis that caused a growth delay only at later stages of tumor progression. Concomitantly, surgical removal of the primary tumor decreased the number of circulating tumor cells, reduced metastasis, and prolonged overall survival. Additionally, Tie1 deletion in experimental murine metastasis models prevented extravasation of tumor cells into the lungs and reduced metastatic foci. Taken together, the data support Tie1 as a therapeutic target by defining its regulatory functions during angiogenesis and vascular abnormalization and identifying its role during metastasis.
Association between bisphosphonate use and risk of undergoing knee replacement in patients with osteoarthritis
Authors: Yan Chen, Jinmin Zhao, Shan Lao, Weijia William Lu
Journal: Annals of the Rheumatic Diseases (2018)

Osteoarthritis (OA) is the most common joint disorder and the major cause of chronic musculoskeletal pain and mobility disability in elderly populations worldwide.1 Currently there is no effective pharmacological treatment for OA, necessitating joint replacement to reduce joint pain and improve physical functions at advanced stages of the disease.2 It has been reported that abnormal subchondral bone resorption and bone loss play an important role in both OA initiation and progression.3–5 Therefore, antiresorptive drugs are suggested to be potential OA therapies.6 We read with deep interest a recent article published in this journal by Neogi et al , who found that in elderly women with newly diagnosed knee OA, those who use bisphosphonates had lower risk of knee replacement than non-users, and suggested that treatment with bisphosphonates has a potential beneficial effect on knee OA.7 We really appreciate the great work performed by the authors; nevertheless, some worthwhile issues need to be further explored.

First, the definition of knee OA at baseline is not clearly described in the study. Nowadays there is no consensus on the classification criteria of knee OA despite extensive epidemiological and clinical studies. The two criteria most frequently used are the American College of Rheumatology (ACR) classification criteria8 and the Kellgren and Lawrence (K-L) system.9 The ACR classification criteria depend on clinical (such as pain, aching or …