tbuckley/cabot-search huggingface dataset:
Abstract 14309: A Novel Fibroblast Activation Inhibitor, NM922, Attenuates Maladaptive Fibrotic Remodeling to Preserve Cardiac Function Following the Onset of Heart Failure
Authors: Jessica M Bradley, Craig M Ziblich, Kazi N Islam, Amanda M Rushing, David J Polhemus, Laura G Corral, Robert W Sullivan, Leah Fung, Kyle W Chan, Cathy A Swindlehurst, David J Lefer
Journal: Circulation (2015)

Background: Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart. These maladaptive structural changes can worsen cardiac function accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor of the conversion of normal fibroblast to the myofibroblast phenotype in the setting of pressure overload induced HF. Methods: Male C57BL/6J mice (10 wks) were subjected to transverse aortic constriction (TAC; 27 g needle) and NM922 (NovoMedix, LLC50 mg/kg/d i.p.) or VEH (DMSO + HS-15) was administered daily starting at 6 wks post TAC. Echocardiography was assessed at baseline and for 16 wks post TAC. At the 16 wk endpoint, mice were sacrificed and hearts were collected for biochemical and molecular assessment. Results: NM922 significantly attenuated TAC-induced left ventricular (LV) dilation at 16 wks post TAC (LVEDD: 3.5 ± 0.1 vs. 4.5 ± 0.2 mm, p &lt; 0.01; LVESD: 2.5 ± 0.2 vs. 3.8 ± 0.3 mm, p &lt; 0.01) compared to VEH. NM922 treated mice displayed reduced wall thickening (LVPWd: 1.0 ± 0.03 vs. 1.2 ± 0.05 mm; p &lt; 0.05) at 10 wks post TAC compared to VEH. LV ejection fraction (LVEF) was preserved in NM922 treated mice at 8-16 wks post TAC compared to VEH (*p &lt; 0.05; **p &lt; 0.001) compared to VEH. Treatment with NM922 resulted in reductions in heart (8.5 ± 0.5 vs. 12.0 ± 0.9 mg/mm; p &lt; 0.01) and lung (8.2 ± 0.3 vs. 11.5 ± 0.6 mg/mm; p &lt; 0.0001) weights compared to VEH. Picrosirius Red staining revealed that NM922 reduced cardiac interstitial collagen volume fraction by 50% (p &lt; 0.05 vs. VEH). Circulating BNP levels trended toward lower (p = 0.08) in the NM922 mice when compared to VEH. Conclusion: Chronic treatment with NM922 following the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of LVEF. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel agent protects the failing heart.
Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children
Authors: Anja Jochmann, Luca Artusio, Angela Jamalzadeh, Prasad Nagakumar, Edgar Delgado-Eckert, Sejal Saglani, Andrew Bush, Urs Frey, Louise J. Fleming
Journal: European Respiratory Journal (2017)

International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma. Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period. 93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21–99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups. Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic.
Epidemia de poliomielitis en Albania, 1996
Authors: M L Ciofi Degli Atti, R Prevots, A Sallabanda, P Malfait, E Diamantil, B Aylward, D Greco, S Wassilak
Journal: Eurosurveillance (1997)

Entre abril y noviembre de 1.996, una importante epidemia de poliomielitis ha ocurrido en Albania, pais declarado libre de esta enfermedad desde 1.985. Aunque Albania no habia declarado poliomielitis en ese intervalo, si habia aumentado el riesgo de introduccion y circulacion de poliovirus 'salvaje'. Este riesgo fue una consecuencia de los problemas ocurridos en el pasado con el mantenimiento de la cadena fria en el suministro de vacunas, de una menor cobertura de vacunacion oral antipoliomielitica (VPO) a principios de los '90 durante la transicion politica y de la apertura de fronteras y la migracion masiva a partir de 1.992, que propicio el establecimiento de contactos con poblaciones procedentes de paises con poliomielitis endemica. Para controlar este riesgo, entre abril y mayo de 1.996 se organizaron los Dias de Inmunizacion Nacional contra la Polio (DIN), dirigidos a todos los ninos menores de 5 anos de edad en Albania, consiguiendose una cobertura del 98%.
Stable gadolinium based nanoscale lyophilized injection for enhanced MR angiography with efficient renal clearance
Authors: Kun Liu, Liang Dong, Yunjun Xu, Xu Yan, Fei Li, Yang Lu, Wei Tao, Huangyong Peng, Yadong Wu, Yang Su, Daishun Ling, Tao He, Haisheng Qian, Shu-Hong Yu
Journal: Biomaterials (2017)
Abstract 18157: Can 3-Dimensional Left Atrial Endocardial Surface Area Tracking Method Be Applied to the Evaluation of Left Atrial Reservoir Function?
Authors: Nobukatsu Akita, Kazuaki Wakami, Kenta Hachiya, Hiroo Sonoda, Shohei Kikuchi, Hiroshi Fujita, Toshihiko Goto, Hidekatsu Fukuta, Tomomitsu Tani, Nobuyuki Ohte
Journal: Circulation (2012)

Background:  Three-dimensional wall motion tracking (3D-WMT, Toshiba) is a newly developed technique that enables us to evaluate left atrial (LA) endocardial surface area deformation, which is named area change ratio (ACR). The peak LA-ACR was obtained at LV end-systole; our hypothesis, therefore, was that peak LA-ACR had relations to not only LV systolic function but also LV early diastolic function. We investigated this issue in comparison with invasively obtained parameters of LV systolic and diastolic function.   Methods:  Study subjects were consecutive 37 patients with sinus rhythm who underwent diagnostic cardiac catheterization and 3D-WMT on the same day. Seven of them had prior myocardial infarction, while the remaining 30 had no localized LV wall motion abnormality. The temporal change of LA-ACR was drawn offline using an echo image analyzer (Ultra-Extend, Toshiba). Initial frame was set at LV end diastole, and then the peak LA-ACR at LV end-systole was calculated. LV pressure was obtained using a catheter-tipped micromanometer, and then left ventriculography was perfumed. From the recorded pressure waves, both peak positive and negative dP/dt values were determined, and then the time constant τ of LV isovolumic relaxation was also computed. LV volumes were calculated from left ventriculography. LV end-systolic volume was indexed to body surface area (LVESVI).   Results:  The peak LA-ACR had significant positive correlations with both peak positive dP/dt (r=0.56, p   Conclusion:  This study indicates that peak LA-ACR reflects LV behavior from LV end systole to early diastole, suggesting the LA-ACR can be used as a parameter of the LA reservoir function.
Abstract 15889: Nanoparticle-Mediated Selective Delivery into Lesions of Myocardial Ischemia-Reperfusion Injury Enhances Cardioprotection by Cyclosporine A in Mice
Authors: Gentaro Ikeda, Tetsuya Matoba, Yasuhiro Nakano, Kazuhiro Nagaoka, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation (2012)

Background:  Therapeutic effect of early reperfusion in acute myocardial infarction (AMI) is limited by ischemia-reperfusion (IR) injury that is known to cause cardiomyocyte necrosis through opening of mitochondrial permeability transition pore (mPTP). Cyclosporine A (CsA) is a potent inhibitor of mPTP opening, and its use at the time of reperfusion can reduce MI size in animals and small clinical study. Because the clinical use of CsA may be limited by adverse effects including renal injury and non-ischemic cardiomyocyte dysfunction, selective delivery of CsA to IR lesions would be preferable. Hence we tested the hypothesis that nanoparticle (NP)-mediated selective delivery of CsA to IR lesions enhances cardioprotective effects of CsA.   Methods and Results:  In a murine model of a 30-min myocardial IR (Fig A), cellular distribution of PLGA NP containing FITC (FITC-NP) or FITC solution was examined. Significant fluorescence FITC signals were noted exclusively in cardiomyocytes of IR lesions after intravenous injection of FITC-NP at the time of reperfusion (Fig B). Interestingly, greater FITC signals were detected in subcellular mitochondrial fractions than in cytosolic fractions from the IR heart (Fig C). Intravenous treatment with CsA at a dose of 10 mg/kg, but not at 1 and 2.5 mg/kg, reduced MI size. Importantly, treatment with CsA-NP containing 1, 2.5, and 10 mg/kg CsA reduced MI size to the similar extent as seen with CsA at 10 mg/kg (Fig D). Treatment with CsA-NP at 1 mg/kg and CsA at 10 mg/kg equally inhibited leakage of cytochrome C from mitochondria, a marker of mPTP opening.   Conclusions: NP-mediated selective delivery to IR lesions, especially to mitochondria fraction of cardiomyocyte, enhanced cardioprotection by CsA. CsA-NP can be developed as a more effective and safer inhibitor of mPTP opening, compared to CsA. Targeting the opening of mPTP with CsA-NP may offer organ protection from IR injury in AMI and other clinical settings (intraoperative cardioprotection).
Health Behavioral Models to Find Reasons for Low Rates of Lung Cancer Screening by Low-Dose Computed Tomography
Authors: Martin C. S. Wong
Journal: JAMA Oncology (2017)

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High antitumor efficacy of a combination between sunitinib, cetuximab and irradiation on an orthotopic head and neck cancer model.
Authors: Alexandre Bozec, Anne Sudaka, Nicolas Toussan, jean-louis fischel, Marie-Christine Etienne Grimaldi, Gerard Milano
Journal: Cancer Research (2008)

4040  Combination of anti-epidermal growth factor receptor (EGFR) therapy with radiotherapy (RT) has demonstrated clinical benefit in head and neck cancer. Recent pre-clinical and clinical studies have suggested promising efficacy of RT combined with anti-angiogenic agents. The aim of the present study was to test the association of a monoclonal antibody directed against EGFR (cetuximab) with a multi-target tyrosine kinase inhibitor directed against VEGFRs (sunitinib) and RT. Investigations were performed on a VEGF-secreting human head and neck cancer cell line (CAL33) with a high EGFR content, injected as orthotopic xenografts into the mouth floor of nude mice. The anti-tumor efficacy of cetuximab (1 mg/kg 5 days a week, i.p. ), sunitinib (20 mg/kg 5 days/week, p.o.) and RT (6 Gy, 3 days/week) administered alone or in combination was assessed at day 10 after starting treatment (animal sacrifice for ethical reasons, 10 animals per treatment group). Tumor volume, proportion of well-differentiated cells, tumor cell proliferation (Ki67), VEGFR2 labeling in tumor cells, number of vessels in the center and at the periphery of the tumor were examined. Bilateral node chain dissection was performed and the number of inflammatory nodes, either invaded or not, was measured. Differences between treatments were tested according to the non-parametric Mann-Whitney test. The interactions between combined treatments were assessed by computing the combination ratio (CR) defined as FTvA x FTvB / FTv (A+B), where FTvx is the fractional tumor volume for the agent x.  As compared to control, concomitant administration of cetuximab and sunitinib produced a marked and significant supra-additive decrease in tumor volume (CR = 1.78, p
Abstract P254: Genetic Risk Score for Height and the Incidence of Venous Thromboembolism: A Prospective Study
Authors: Nicholas S Roetker, James S Pankow, Pamela L Lutsey, Weihong Tang, Michael A Rosenberg, Susan R Heckbert, Mary Cushman, Aaron R Folsom
Journal: Circulation (2016)

Introduction: Several observational studies have shown that taller body height is associated with greater risk of venous thromboembolism (VTE), but it is not known whether the association is causal. We used instrumental variable analysis (Mendelian randomization) to explore the causal relationship between height and VTE using a genetic risk score (GRS) for height as the instrument. Hypothesis: There is a causal relationship between taller standing height and greater risk of VTE, as demonstrated by a Mendelian randomization approach. Methods: We created a weighted GRS for height in white men and women in the Longitudinal Investigation of Thromboembolism Etiology [consisting of two longitudinal cohort studies: Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)] using 668 single nucleotide polymorphisms from a recently published meta-analysis. Incident hospitalized VTE events were identified and verified by physician review of medical records. We estimated the association and causal risk differences (RD) and 95% confidence intervals (CI) for VTE incidence per standard deviation (SD) increment in height (9.4 cm). The association models were adjusted for age, sex, waist circumference, and study site. Results: There were 9,137 ARIC and 3,163 CHS participants at risk for VTE at baseline and with genetic data, and they experienced 367 (ARIC) and 105 (CHS) incident VTE events over a median 22.7 and 11.8 years of follow-up, respectively. Baseline age ranges were 45-64 and 65-98 years and mean heights were 169 and 165 cm in ARIC and CHS, respectively. The GRS was a strong instrument for height (R 2 =0.08 in ARIC and R 2 =0.07 in CHS) and had little to no correlation with other measured VTE risk factors (all R 2 ≤0.01). In ARIC, taller height was associated with greater risk of VTE [association VTE RD: 1.0% per SD in height (95% CI: 0.3 to 1.6%)]. The causal RD had the same magnitude as the association RD, but did not quite reach statistical significance [causal VTE RD per SD in height: 1.1% (95% CI: -0.3 to 2.5%)]. Predicted risks of VTE at the 10th and 90th percentiles of height (157 and 181 cm) were 2.6% and 5.4%, respectively, representing more than a doubling of risk. There was no association between height and VTE risk in CHS [association VTE RD per SD in height: 0.1% (95% CI: -1.0 to 1.2%); causal VTE RD per SD in height: -0.3% (95% CI: -2.5 to 1.9%)]. Conclusion: Taller height was associated with greater VTE risk with some supporting causal evidence in middle-aged adults from ARIC, but there was no relation between height and VTE in older adults from CHS. Future studies should further explore the causal relation between height and VTE among different age groups.
Serum Homocysteine levels are independently associated with mortality in Primary and Secondary Prevention patients derived from a high-risk clinic population.
Authors: Monica Acevedo, Gregory L. Pearce, Dennis L. Sprecher
Journal: Circulation (2001)

0015     Background: Elevated total homocysteine levels (tHCY) have  been implicated as an independent risk factor for mortality in patients  with known and no known CAD. Few data are available that compare tHCY  as a predictor of mortality in both groups. Objectives: In an ongoing,  high-risk cardiovascular Prevention Clinic we sought to determine  whether tHCY showed evidence of short-term mortality independently of  traditional risk factors in primary and secondary prevention patients.  Methods: Short term mortality (mean follow-up 26 ± 15 months) was  assessed in 2441 clinic patients (1103 primary and 1338 secondary  prevention). Cox models were used to assess the unadjusted  relationships between tHCY (quartiles:  14.7 μmol/L) and survival time with hazard ratios (HR) used to  estimate mortality risk. Framingham global risk scores were calculated  for each patient in order to adjust for traditional risk factors (age,  gender, LDL-C, HDL-C, blood pressure, diabetes and smoking). Results:  The mean age of the overall group was 56 ± 12 years, 34% were  women and 62 patients died during the follow-up (18 for primary and 44  for secondary prevention). Serum tHCY quartile showed a relationship to  mortality for primary and secondary prevention patients (HR 3.02 and  1.69 respectively) with and without adjustment for traditional risk  factors and creatinine (Table). Conclusions: Serum homocysteine levels  are independently associated with mortality in primary and secondary  Prevention patients derived from the same high-risk clinic  population.
Lethal (3) malignant brain tumor-like 2 (L3MBTL2) protein protects against kidney injury by inhibiting the DNA damage–p53–apoptosis pathway in renal tubular cells
Authors: Huihui Huang, Chunhua Xu, Yang Wang, Chenling Meng, Wenjing Liu, Yueshui Zhao, Xiao-Ru Huang, Wenxing You, Bo Feng, Zhi-Hua Zheng, Yu Huang, Hui-Yao Lan, Jinzhong Qin, Yin Xia
Journal: Kidney International (2017)
Genetic Architecture and Selection of Chinese Cattle Revealed by Whole Genome Resequencing
Authors: Chugang Mei, Hongcheng Wang, Qijun Liao, Lizhong Wang, Gong Cheng, Hongbao Wang, Chunping Zhao, Shancen Zhao, Jiuzhou Song, Xuanmin Guang, George E Liu, Anning Li, Xueli Wu, Chongzhi Wang, Xiaodong Fang, Xin Zhao, Stephen B Smith, Wucai Yang, Wanqiang Tian, Linsheng Gui, Yingying Zhang, Rodney A Hill, Zhongliang Jiang, Yaping Xin, Cunling Jia, Xiuzhu Sun, Shuhui Wang, Huanming Yang, Jian Wang, Wenjuan Zhu, Linsen Zan
Journal: Molecular Biology and Evolution (2017)

The bovine genetic resources in China are diverse, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Chinese cattle, we analyzed the whole genomes of 46 cattle from six phenotypically and geographically representative Chinese cattle breeds, together with 18 Red Angus cattle genomes, 11 Japanese black cattle genomes and taurine and indicine genomes available from previous studies. Our results showed that Chinese cattle originated from hybridization between Bos taurus and Bos indicus. Moreover, we found that the level of genetic variation in Chinese cattle depends upon the degree of indicine content. We also discovered many potential selective sweep regions associated with domestication related to breed-specific characteristics, with selective sweep regions including genes associated with coat color (ERCC2, MC1R, ZBTB17, and MAP2K1), dairy traits (NCAPG, MAPK7, FST, ITFG1, SETMAR, PAG1, CSN3, and RPL37A), and meat production/quality traits (such as BBS2, R3HDM1, IGFBP2, IGFBP5, MYH9, MYH4, and MC5R). These findings substantially expand the catalogue of genetic variants in cattle and reveal new insights into the evolutionary history and domestication traits of Chinese cattle.
HER1-3 inhibition in patients with colorectal cancer that is wild-type for BRAF, PIK3CA, KRAS, and NRAS mutations (FOCUS-4D): first results from the multi-arm multi-stage phase II/III FOCUS-4 randomised trial
Authors: R Adams, E Brown, L Brown, R Butler, S Falk, D Fisher, R Kaplan, P Quirke, S Richman, L Samuel, J Seligmann, M Seymour, K K Shiu, H Wasan, R Wilson, T Maughan
Journal: The Lancet. Gastroenterology & hepatology (2017)
Abstract 17045: The Association of Depressive Symptoms Prior to Cardiovascular Surgery to Death and the Mitigating Effects of Cardiac Rehabilitation Attendance
Authors: Tami L Bair, Jose Benuzillo, Viet T Le, Heidi T May, Kirk U Knowlton, Donald L Lappé, Joseph B Muhlestein
Journal: Circulation (2016)

Introduction:  Depressive symptoms have been shown to be associated with poor cardiovascular outcomes. Cardiac rehabilitation (CR) has been shown to improve outcomes after cardiovascular surgery, but whether it attenuates the negative effects of depressive symptoms on outcomes needs evaluation.   Methods:  A total of 118 patients undergoing cardiovascular surgery (CABG: 38.1%, Valve: 24.8%, Other: 37.1%) and completed a Patient Health Questionnaire (PHQ)-9 were studied. The PHQ-9 was completed prior to surgery at an outpatient visit (median days completed prior to surgery: 310) and scores were stratified into categories of none-mild (NO-MILD, n=98) and moderate-severe (MOD-SEV, n=20) depressive symptoms. Multivariable Cox hazard regression was utilized to determine the association of pre-surgery PHQ-9 depressive symptoms to death (length of follow-up: NO-MILD=431±343, MOD-SEV=393±324, p=0.65).   Results:  MOD-SEV patients were significantly younger (60.8±12.2 vs. 67.0±10.2 years, p=0.02) and more often smokers (75.0% vs. 36.7%, p=0.002) than NO-MILD. However, being male (61.9%), having hypertension (90.7%), diabetes (61.0%), heart failure (39.0%), and renal failure (29.7%) were similar between the groups. Length of stay was also similar (MOD-SEV: 8.8±5.6 vs. NO-MILD: 7.5±5.2 days, p=0.32). CR was attended by 61.2 % of NO-MILD and 45.5% by MOD-SEV patients. Death occurred in 6.1% and 25.0% of NO-MILD and MOD-SEV patients (p=0.02), respectively. MOD-SEV depressive symptoms were significantly associated with death (hazard ratio [HR]=4.43, p=0.01). This association remained after adjustment by baseline risk factors (HR=4.14, p=0.03), but was attenuated when adjusted by CR attendance (HR=2.12, p=0.28). Among MOD-SEV patients, attendance of CR was significantly associated with a reduced risk of death (HR=0.26, p=0.02).   Conclusion:  The presence of MOD-SEV depressive symptoms prior to cardiovascular surgery was highly predictive of death despite adjustment by baseline risk factors. However, attendance of CR appears to decrease this risk. Further study is required to determine whether other factors contribute to this association.