tbuckley/cabot-search huggingface dataset:
Prevalence, Characteristics, and Outcomes of Patients Presenting With Cardiogenic Unilateral Pulmonary Edema
Authors: DavidAttias, NicolasMansencal, BertranAuvert, AntoineVieillard-Baron, AurélieDelos, PascalLacombe, RolandN'Guetta, FrançoisJardin, OlivierDubourg
Journal: Circulation (2010)

Background—Cardiogenic unilateral pulmonary edema (UPE) is a rare entity, frequently leading to initial misdiagnosis. We sought to assess the prevalence of UPE and to determine its impact on prognosis compared with bilateral pulmonary edema. Methods and Results—We studied the characteristics and outcomes of patients admitted to our institution for cardiogenic pulmonary edema during an 8-year period. The study population included 869 consecutive patients. The prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%). In patients with UPE, blood pressure was significantly lower (P≤0.01), whereas noninvasive or invasive ventilation and catecholamines were used more frequently (P=0.0004 and P<0.0001, respectively). The prevalence of severe mitral regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%, respectively (P<0.0001). In patients with UPE, use of antibiotic therapy and delay in treatment were significantly higher (P<0.0001 and P=0.003, respectively). In-...
Prognostic factors in survival of patients with cerebral metastases.
Authors: Lijerka Markulin-Grgic, Vlastimir Kukura
Journal: Journal of Clinical Oncology (2012)

e12505 Background: The problem of cerebral metastases is a great one and seems to become more and more important thanks to earlier diagnosis and the possibilities of effective treatment. In this analysis 330 patients with cerebral metastases, treated at the Clinic of Oncology, School of Medicine, Zagreb, Croatia, over 13 years, from 1995 - 2007 are dealt with. The most common primary tumor was bronchus carcinoma in 201/330 patients (60.91%), then breast carcinoma in 48/330 patients (14.54%), melanoma in 16/330 patients (4.85%), gastrointestinal tumors in 17/330 patients (5.15%), hypernephroma in 9/330 patients (2.73%), ovarian carcinoma in 10/330 patients (3.03%), cervical small cell carcinoma in 4/330 patients (1.21%), testicular tumors in 5/330 patients (1.52%) and in 20/330 patients (6.06%) the primary was not found. Methods: The patients were treated by surgery, radiotherapy and chemotherapy in various combinations. Results: There is a significantly better survival in female patients with cerebral metastases from breast carcinoma in comparison to other primary tumors (p&lt;0.001). The patients with longer symptom-free period up to the diagnosis of the secondaries in the brain had significantly better survival (p&lt;0.001). Better survival was achieved in younger patients (p&lt;0.05). Conclusions: Considering the applied therapy methods, the best survival results were obtained in patients treated by a combination of surgery, radiotherapy and chemotherapy.
Abstract 894: Overexpression and extended degradation rate of Axl in acquired gefitinib-resistant non-small cell lung cancer cells
Authors: Donghwa Kim, Duc-Hiep Bach, Ji-Young Hong, Hyen Joo Park, Sang Kook Lee
Journal: Cancer Research (2018)

Abstract Non-small cell lung cancer (NSCLC) is a major type of lung cancer which accounts for approximately 80-85% of all lung cancers. Epidermal growth factor receptor (EGFR)- targeted tyrosine kinase inhibitors (TKIs), such as gefitinib have improved the survival of NSCLC patients with activating mutations in EGFR. However, the drug responses are only transient because tumors acquire resistance via secondary mutations in EGFR (T790M) or amplification of other receptor tyrosine kinases (RTKs) including MET or AXL. Therefore, the precise mechanisms of chemoresistance and finding the novel ways of targeting cancer cells are needed to be identified. AXL, a TAM (Tyro3, AXL, Mer) family member, has been studied as a tumorigenesis, chemoresistance, and EMT marker. Also, we found that AXL is overexpressed in EGFR mutated gefitinib-resistant non-small lung cancer cells (PC9-gef) compared to its parent cells (PC9). Moreover, the AXL degradation rate was found to be suppressed. These findings suggest that the modulation of AXL turnover can be a therapeutic target to overcome gefitinib-resistance. In this study, we confirmed the possibilities of overcoming gefitinib-resistance through the down-regulation and turnover acceleration of AXL by employing yuanhadine, an anti-tumor agent derived from Daphne Genkwa. Yuanhuadine was also effectively suppressed the tumor growth in nude mouse xenograft models implanted with PC9 or PC9-gef cells. Therefore, regulation of AXL expression by modulating its degradation rate can be a therapeutic strategy to overcome acquired gefitinib-resistance in NSCLC. Citation Format: Donghwa Kim, Duc-Hiep Bach, Ji-Young Hong, Hyen Joo Park, Sang Kook Lee. Overexpression and extended degradation rate of Axl in acquired gefitinib-resistant non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 894.
Abstract 2231: Insulin and multi-system alterations in non-diabetic American adults: NHANES 1999-2016
Authors: Neil E. Caporaso, Rena R. Jones, Lisa L. Kahle, Barry I. Graubard
Journal: Cancer Research (2018)

Abstract Epidemiological evidence for a relationship between insulin resistance and cancer is emerging, and insulins' complex actions suggest that its dysregulation results in multisystem alterations. Using cross-sectional demographic and laboratory data from the continuous NHANES conducted from 1999-2016. we surveyed the range of multisystem alterations observed in normal (not diabetic or prediabetic) adult subjects in relation to variation in insulin and glucose levels. The homeostatic model of insulin resistance (HOMA-IR) was used as the key outcome measure of insulin resistance. We examined cardiovascular (BP), respiratory (FEV1, FVC), renal (BUN, creatinine), inflammatory (C-reactive protein, fibrinogen), lipid (triglycerides, LDL, HLD), hematologic (WBC, hemoglobin, cell counts), and nutritional (vitamin levels) factors in relation to HOMA-IR, C-peptide, Hgb1Ac and fasting glucose levels after adjustment for demographic (age, gender, smoking, alcohol, race, SES) and anthropometric (BMI) factors. Every system exhibited highly significant associations with insulin/glucose measures. Strong correlations (p &amp;lt; 0.0001, Pearson, accounting for sample weights) of HOMA-IR were observed with waist size, systolic and diastolic blood pressure, triglycerides, HDL (inverse), LDL and inflammatory markers: fibrinogen, C-reactive protein, ferritin. Measured serum levels of vitamin C, vitamin D, and folate (RBC), were inversely associated with HOMA-IR. The relationship for selected variables, to HOMA-IR quartiles is shown below. In a broad, representative sample of up to 9000 non-diabetic US subjects, we relate insulin resistance to adverse changes in anthropometric, cardiovascular, renal, metabolic, inflammatory and nutritional markers. Analyses accounting for NHANES sample design, confounding and potential interactions will be reported. Our preliminary results suggest that insulin resistance is linked to perturbations in normal function across numerous systems. HOMA-IR Quartiles, adjusted (95% CI)1st2nd3rd4thFerritin79.1(71-87)75.9 (70-82)82.3 (76-89)96.2 (82-110)BP (d)69.7 (69-71)71.8 (70-73)71.4 (70-73)73.2 (72-75)HDL60.8 (60-62)56.3 (56-57)54.1 (53-55)51.3 (50-52)WBC6.37 (6.3-6.5)6.44 (6.3-6.6)6.68 (6.5-6.8)6.96 (6.8-7.1) Citation Format: Neil E. Caporaso, Rena R. Jones, Lisa L. Kahle, Barry I. Graubard. Insulin and multi-system alterations in non-diabetic American adults: NHANES 1999-2016 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2231.
Abstract 240: SNP-mediated repression of DCBLD1 by YY1 may explain a GWAS finding on lung cancer
Authors: Yu Wang, Rongna Ma, Hongyan Lin, Xiao Yu, Herbert Yu, Biyun Qian
Journal: Cancer Research (2018)

Abstract Genome-wide association studies (GWAS) have identified many cancer-associated single nucleotide polymorphisms (SNP) with limited understanding of their real implication in cancer. To study the biological relevance of a GWAS-discovered SNP, we performed linkage disequilibrium (LD) analysis on rs9387478 and identified four potentially functional SNPs. We found that SNP rs17079281 C&amp;gt;T was associated with lung cancer in 766 Chinese cases and 773 matched controls, and the association was validated by another independent study (558 cases and 534 controls). Luciferase assay and CRISP/Cas9-generated genotype experiments showed that transcription factor YY1 suppressed DCBLD1 expression in an allele-specific manner, higher inhibition to T than to C alleles. In vitro and in vivo experiments on gain and loss of function further demonstrated that DCBLD1 behaved like an oncogene for lung cancer. These findings suggest that rs17079281 genotype may differentially affect YY1's suppression on DCBLD1 which influences the risk of lung cancer as an oncogene. Citation Format: Yu Wang, Rongna Ma, Hongyan Lin, Xiao Yu, Herbert Yu, Biyun Qian. SNP-mediated repression of DCBLD1 by YY1 may explain a GWAS finding on lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 240.
Tissue Factor Cytoplasmic Domain Stimulates Migration by Activation of the GTPase Rac1 and the Mitogen-Activated Protein Kinase p38
Authors: IlkaOtt, BertholdWeigand, RuthMichl, IsabellSeitz, NooshinSabbari-Erfani, Franz-JosefNeumann, AlbertSchömig
Journal: Circulation (2005)

Background— Tissue factor (TF), the surface receptor for the serine protease factor VIIa (FVIIa) and the initiator of the extrinsic coagulation cascade, supports vessel development and tumor metastasis by activation of extracellular, protease-dependent signaling pathways. The molecular mechanisms that do not require proteolytic activity of FVIIa are not yet known. The aim of the study, therefore, was to investigate the effects of active-site–inhibited FVIIa (FFR-FVIIa) on TF-mediated signaling. Methods and Results— After stimulation with FVIIa and FFR-FVIIa, migration and activation of the GTPase Rac (Rac1) or the mitogen-activated protein kinase p38 (p38) were analyzed in J82 cells. FVIIa and FFR-FVIIa stimulated migration and activation of Rac1 and p38 in a TF-specific, dose- and time-dependent manner. Enhancement of migration required activation of Rac1 and p38, because it was abolished after inhibition with SB203580 or overexpression of dominant negative p38 and Rac1. The cytoplasmic domain of TF was ...
A signature of miRNAs in the blood to help prognosticate prostate cancer at the time of diagnosis.
Authors: Ailsa Roberg Sita-Lumsden, Damien Leach, Andrea Zivi, Mathias Winkler, Jonathan Waxman, Charlotte Bevan
Journal: Journal of Clinical Oncology (2017)

e16558 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Around 80% of PCas are diagnosed as early, localised stage yet a subset of these will metastasise and eventually prove fatal. Management decisions are based on risk stratification systems. However, these systems are not able to clearly distinguish indolent from aggressive PCa’s and as a result many patients with indolent cancers may be over treated. Circulating microRNAs (miRNA) may be an easily accessible, suitable biomarker to distinguish true indolent from clinically significant early PCas thus reducing overtreatments. Methods: Blood samples from 24 men with benign prostatic hypertrophy (BPH, n = 8), localised PCa (n = 8) or metastatic PCa (n = 8) were collected at time of diagnosis. All men had intact prostates and were naïve to any endocrine or other cancer therapy. A platform of circulating miRNAs were analysed in serum using Abcam FireflyTM technology. Data collected were independently verified using real-time qPCR (Exiqon TM ). The miRNAs identified as being significantly different between groups were then analysed in a published dataset. Results: Serum levels of seven of the miRs examined were significantly different in patients with prostate cancer compared to control across both platforms (miR-10b, miR-125b, miR-210, miR-21, miR-378a, miR-483 and miR93 all with P values &lt; 0.005). A further four miRNAs could differentiate between the benign and metastatic cohorts (miR-126 P = 0.008, miR-150 P = 0.05, miR375 P = 0.007). Kaplein-Meier analysis further identified that the serum levels of four miRNAs showed significant association with survival rates (miR-21 P = 0.032, miR-126 P = 0.032, miR-150 P = 0.032, miR-93 P = 0.019). On examination in a cohort of 280 men from The Cancer Genome Atlas (TCGA), four miRs from the cohort had significantly different expression in patients who eventually relapsed (miR-21 P = 0.048, miR-375 P = 0.021, miR-210 P = 0.0003, miR-93 P = 0.008) Conclusions: Our circulating miRNA based signature could be used to stratify men at prostate cancer diagnosis and help identify those who are likely to harbour micro metastases and would benefit more from an early radical treatment. The data is being validated in larger cohorts.
Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization
Authors: Matteo Bianchi, Hannah L. Turner, Bartek Nogal, Christopher A. Cottrell, David Oyen, Matthias Pauthner, Raiza Bastidas, Rebecca Nedellec, Laura E. McCoy, Ian A. Wilson, Dennis R. Burton, Andrew B. Ward, Lars Hangartner
Journal: Immunity (2018)

Characterizing polyclonal antibody responses via currently available methods is inherently complex and difficult. Mapping epitopes in an immune response is typically incomplete, which creates a barrier to fully understanding the humoral response to antigens and hinders rational vaccine design efforts. Here, we describe a method of characterizing polyclonal responses by using electron microscopy, and we applied this method to the immunization of rabbits with an HIV-1 envelope glycoprotein vaccine candidate, BG505 SOSIP.664. We detected known epitopes within the polyclonal sera and revealed how antibody responses evolved during the prime-boosting strategy to ultimately result in a neutralizing antibody response. We uncovered previously unidentified epitopes, including an epitope proximal to one recognized by human broadly neutralizing antibodies as well as potentially distracting non-neutralizing epitopes. Our method provides an efficient and semiquantitative map of epitopes that are targeted in a polyclonal antibody response and should be of widespread utility in vaccine and infection studies.
Vaccination Trends in Patients With Heart Failure
Authors: Ankeet S Bhatt, Li Liang, Adam D DeVore, Gregg C Fonarow, Scott D Solomon, Orly Vardeny, Clyde W Yancy, Robert J Mentz, Yevgeniy Khariton, Paul S Chan, Roland Matsouaka, Barbara L Lytle, Ileana L Piña, Adrian F Hernandez
Journal: JACC Heart Failure (2018)
Abstract 12875: Serum Neutrophil Gelatinase-associated Lipocalin Has a Predictive Value for the Neurological Outcome of Post Cardiac Arrest Victims
Authors: Tadashi Kaneko, Motoki Fujita, Yasuaki Ogino, Hiroki Irie, Shinsuke Iwashita, Ryuichi Karashima, Masashi Kamikawa, Hiromichi Tanaka, Ryosuke Tsuruta, Shunji Kasaoka
Journal: Circulation (2015)

Introduction: Neutrophil gelatinase-associated lopocalin (NGAL) is well known as the biomarker of acute kidney injury. Currently, serum NGAL is reported as the biomarker which is associated with mortality and multiple organ dysfunction syndrome in septic patients. In this study, we measured serum NGAL in post cardiac arrest syndrome (PCAS) patients to investigate the predictive value of neurological outcome. Hypothesis: Serum NGAL is associated with favorable neurological outcome of PCAS patients. Methods: 43 cases of PCAS patients were measured serum NGAL on day 1 and 2, and serum neuron specific enolase (NSE) was also measured on day 2. Patients were divided into two group (group G: CPC 1-2 and group P: CPC 3-5, CPC: cerebral performance categories). Serum NGAL and NSE were compared between group G and P. Receiver operation characteristic (ROC) curve analysis were performed of both NGAL and NSE. Results: Group G (n = 20) and P (n = 23) were analyzed. Serum NGAL showed significant difference in day 2 (G: 282±116 ng/mL v.s. P: 299±87 ng/mL in day1: P = 0.609, G: 185±124 ng/mL v.s. P: 353±110 ng/mL in day 2: P&lt;0.001). The ROC curve analysis showed area under the curve of NGAL in day 2 was 0.871, and the area of NSE in day2 showed 0.918. Conclusions: Serum NGAL in PCAS patients had the predictive value for neurological outcome which is comparable to serum NSE. (This study was supported by grants from Japanese Ministry of Health, Labour and Welfare: No. 25462824)
Abstract 15285: Notch3 is Required for the Cardiac Adaptation to Hypertension
Authors: HélèneRagot, RégineMerval, MathildeBaudet, EvelynePolidano, LoubinaFazal, ClaudeDelcayre, ChristosChatziantoniou, Jane-LiseSamuel
Journal: Circulation (2014)

Background: The Notch3 receptor has a role in the integrity of resistance arteries by controlling the maturation of vascular smooth muscle cells (VSMC). Hypertension in Notch3 null mice (N3-/-) rapidly induced a heart failure. The mechanistic pathways being not defined, we hypothesize that alterations of the coronary tree secondary to Notch3 invalidation might trigger the development of heart failure in response to hypertension. Methods: N3-/- and WT C57/Bl6J mice were used. At 11 week of age, WT and N3-/- mice were implanted with Alzet mini-pumps filled with Angiotensin 2 (Ang2, 1μg/kg/min) or NaCl for 28 days (n=15-23/ group). Results: Normotensive N3-/- mice showed ventricular hypertrophy (+20%, p<0.001 vs WT) combined with defects of coronary artery tree including decrease in F-actin content in the media (-20%, p<0.05) and in arteriolar density (p<0.05). In response to Ang2, N3-/- mice were less hypertensive than the WT +Ang2 mice (157±9mmHg vs 184±7mmHg, P<0.05) but developed a more severe failing he...
Abstract 158: No-Flow-Fraction, ROSC, and Discharge Rate in In-Hospital Resuscitations Before and After the 2010 Guidelines
Authors: Norbert Papkalla, Torsten Richter, Cynthia Poenicke, Carsten Herkner, Anne Osmers, Sigrid Brenner, Axel Heller, Uta Schwanebeck, Thea Koch, Michael P Müller
Journal: Circulation (2013)

Introduction: The 2010 resuscitation guidelines strongly emphasize the reduction of time without chest compressions. The no-flow-fraction (NFF) is defined as time without chest compressions divided...
Quality of life and patient satisfaction after one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage breast reconstruction (BRIOS): primary outcome of a randomised, controlled trial
Authors: Vera Lidwina Negenborn, Danny Aschwin Young-Afat, Rieky Elise Gustina Dikmans, Jan Maerten Smit, Henri Adolf Hubert Winters, Johan Peter William Don Griot, Johannes Wilhelmus Rembertus Twisk, Pieter Quinten Ruhé, Marcus Antonius Maria Mureau, Oren Lapid, Esther Moerman, Adriaan Anne William Martinus van Turnhout, Mathias Joseph Petrus Franciscus Ritt, Mark-Bram Bouman, Margriet Gezina Mullender
Journal: The Lancet Oncology (2018)
SIRT1 Acts as a Modulator of Neointima Formation Following Vascular Injury in Mice
Authors: LiLi, Hui-NaZhang, Hou-ZaoChen, PengGao, Li-HuaZhu, Hong-LiangLi, XiangLv, Qing-JunZhang, RanZhang, ZhaoWang, Zhi-GangShe, Yu-ShengWei, Guan-HuaDu, De-PeiLiu, Chih-ChuanLiang
Journal: Circulation Research (2011)

Rationale:Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events involved in the pathophysiology of vascular diseases. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), has been reported to have the function of antiatherosclerosis, but its role in neointima formation remains unknown. Objective:The present study was designed to investigate the role of SIRT1 in the regulation of neointima formation and to elucidate the underlying mechanisms. Methods and Results:A decrease in SIRT1 expression was observed following carotid artery ligation. smooth muscle cell (SMC)–specific human SIRT1 transgenic (Tg) mice were generated. SIRT1 overexpression substantially inhibited neointima formation after carotid artery ligation or carotid artery wire injury. In the intima of injured carotid arteries, VSMC proliferation (proliferating cell nuclear antigen (PCNA)–positive cells) was significantly reduced. SIRT1 overexpression markedly inhibited VSMC proliferation and migration and induced...
Abstract 16750: Access to Alcohol and Heart Disease Among Hospitalized Patients: A Natural Experiment
Authors: Jonathan W Dukes, Thomas A Dewland, Eric Vittinghoff, Jeffrey E Olgin, Mark J Pletcher, Judith A Hahn, Gregory M Marcus
Journal: Circulation (2015)

Background: Alcohol may have important effects on heart disease, but studies have generally relied on self-reported alcohol consumption and have yielded conflicting results. We utilized differences in county-level alcohol sales laws as a natural experiment to investigate the relationship between alcohol consumption and heart disease. Hypothesis: Wet counties residents have higher rates of atrial fibrillation (AF) and lower rates of myocardial infarction (MI) and congestive heart failure (CHF) related admissions. Methods: All counties in Texas with no restriction (“wet”) or complete prohibition (“dry”) of alcohol sales or a change in such laws between 2005 and 2010 were identified. Data from the Texas Inpatient Research Data File was used to characterize the hospitalizations of adult residents of those counties. Differences in alcohol use rates were validated using alcohol abuse and alcoholic liver disease outcomes. Adjustment covariates included age, race, ethnicity, sex, diabetes, hypertension, obesity, CHF, CAD, lung disease, and valvular disease. Results: Among 1,106,968 patients; wet county residents had a greater incidence of alcohol abuse (HR 1.36, 95% CI 1.23-1.50, p &lt;0.001) and alcoholic liver disease (HR of 1.81, 95% CI 1.51-2.16, p &lt;0.001). After adjustment, wet county residents exhibited a greater incidence of AF (HR 1.07, 95% CI 1.01-1.13, p 0.013) and a lower incidence of MI (HR 0.89, 95% CI 0.84-0.96, p 0.001). There was no statistically significance difference in CHF rates (HR 0.96, 95% CI 0.92-1.01, p 0.072). Among the seven counties that converted from dry to wet during the study period, statistically significantly higher rates of alcohol abuse, alcoholic liver disease, AF and CHF were observed after the conversion (Figure). Conclusions: Greater access to alcohol is associated with more alcohol abuse, alcoholic liver disease and AF, and less MI and CHF, though there is an increased risk of CHF shortly after alcohol sales are liberalized.