tbuckley/cabot-search huggingface dataset:
Abstract 1405: PAX2 induces tubular structure in ovarian cancer cells
Authors: Kholoud Alwosaibai
Journal: Cancer Research (2018)

Abstract In adult tissues, PAX2 protein is expressed in normal oviductal epithelial cells (OVE) but not in normal ovarian surface epithelial cells (OSE). Recent studies reported that PAX2 is expressed in serous ovarian carcinoma cases but the role of PAX2 in enhancing ovarian cancer is unrevealed yet. The aim of this study is to understand the biological consequences after Pax2 overexpression in mouse ovarian surface epithelial (MOSE) cells. We found that Pax2 overexpression in MOSE cells induced the formation of vascular channels both in vitro and in vivo, which indicate a possible contribution of PAX2 to ovarian cancer progression by increasing the vascular channels to supply nutrients to the tumor cells. Citation Format: Kholoud Alwosaibai. PAX2 induces tubular structure in ovarian 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 1405.
Abstract 15040: Long Term Outcomes After Transcatheter and Surgerical Closure of Atrial Setpal Defect: Implications From National Populational Based Cohort Study in Propensity Score Matching
Authors: Tien HsingChen, Yung ChuanHsiao, Chia ChiCheng
Journal: Circulation (2014)

Introduction: Transcatheter and surgical closure of atrial septal defect were both standard treatment. However, no randomized controlled trial performed compared them directly. Hypothesis: Surgical closure of atrial septal defect could have worse outcome because surgical wound and anesthesia. Methods: We enrolled 26,605 patients with atrial septal defect from 2004 to 2011. Inclusion criteria is patient received transcatheter or surgical closure for significant hemodynamic changed atrial septal defect and age is more than 18 years-old. Exclusion criteria were patients with heart failure, pulmonary hypertension, any valve disease and any other congenital heart disease. Results: There were 510 patients more than 18 year-old have transcatheter and surgical correction, respectively. Compared with two groups, there were higher risk of ischemic stroke (HR=4.72, P=0.006), systemic thromboembolism (HR=5.31, P=0.003), atrial fibrillation (HR=1.69, P=0.048), heart failure (HR=2.30, P<0.001), and all-cause mortality ...
Insulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Nondiabetic Men
Authors: PäiviLempiäinen, LeenaMykkänen, KaleviPyörälä, MarkkuLaakso, JohannaKuusisto
Journal: Circulation (1999)

Background—The role of a cluster of risk factors characteristic for the insulin resistance syndrome as a predictor for coronary heart disease (CHD) has not been studied previously. Methods and Results—Clustering of cardiovascular risk factors was analyzed by factor analysis to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) in a nondiabetic population of 1069 subjects 65 to 74 years old from eastern Finland followed up for 7 years. There were 151 CHD events (92 for men, 59 for women) during the follow-up period. In men, factor 1 (the insulin resistance factor, which reflected primarily body mass index, waist-to-hip ratio, triglycerides, fasting plasma glucose, and insulin) (hazards ratio [HR] with 95% CI, 1.33, CI 1.08, 1.65, P=0.008), factor 2 (alcohol consumption, high HDL cholesterol, low triglycerides) (HR 0.78, CI 0.63, 0.96, P=0.020), factor 3 (age, systolic blood pressure, urinary albumin/creatinine ratio, left ventricular hypertrophy) (...
Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis
Authors: J.E.J. Buckman, A. Underwood, K. Clarke, R. Saunders, S.D. Hollon, P. Fearon, S. Pilling
Journal: Clinical Psychology Review (2018)

To review and synthesise prognostic indices that predict subsequent risk, prescriptive indices that moderate treatment response, and mechanisms that underlie each with respect to relapse and recurrence of depression in adults. Childhood maltreatment, post-treatment residual symptoms, and a history of recurrence emerged as strong prognostic indicators of risk and each could be used prescriptively to indicate who benefits most from continued or prophylactic treatment. Targeting prognostic indices or their "down-stream" consequences will be particularly beneficial because each is either a cause or a consequence of the causal mechanisms underlying risk of recurrence. The cognitive and neural mechanisms that underlie the prognostic indices are likely addressed by the effects of treatments that are moderated by the prescriptive factors. For example, psychosocial interventions that target the consequences of childhood maltreatment, extending pharmacotherapy or adapting psychological therapies to deal with residual symptoms, or using cognitive or mindfulness-based therapies for those with prior histories of recurrence. Future research that focuses on understanding causal pathways that link childhood maltreatment, or cognitive diatheses, to dysfunction in the neocortical and limbic pathways that process affective information and facilitate cognitive control, might result in more enduring effects of treatments for depression.
More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial
Authors: Julio Rosenstock, Alice Cheng, Robert Ritzel, Zsolt Bosnyak, Christine Devisme, Anna M.G. Cali, Jochen Sieber, Peter Stella, Xiangling Wang, Juan P. Frías, Ronan Roussel, Geremia B. Bolli
Journal: Diabetes Care (2018)

OBJECTIVE To compare insulin glargine 300 units/mL (Gla-300) versus insulin degludec 100 units/mL (IDeg-100) in this first head-to-head randomized controlled trial. RESEARCH DESIGN AND METHODS BRIGHT (NCT02738151) was a multicenter, open-label, active-controlled, two-arm, parallel-group, 24-week, noninferiority study in insulin-naive patients with uncontrolled type 2 diabetes. Participants were randomized 1:1 to evening dosing with Gla-300 (N = 466) or IDeg-100 (N = 463), titrated to fasting self-monitored plasma glucose of 80–100 mg/dL. The primary end point was HbA1c change from baseline to week 24. Safety end points included incidence and event rates of hypoglycemia. RESULTS At week 24, HbA1c improved similarly from baseline values of 8.7% (72 mmol/mol) in the Gla-300 group and 8.6% (70 mmol/mol) in the IDeg-100 group to 7.0% (53 mmol/mol)—least squares mean difference −0.05% (95% CI −0.15 to 0.05) (−0.6 mmol/mol [−1.7 to 0.6])—demonstrating noninferiority of Gla-300 versus IDeg-100 (P &amp;lt; 0.0001). Hypoglycemia incidence and event rates over 24 weeks were comparable with both insulins, whereas during the active titration period (0–12 weeks) the incidence and rate of anytime (24-h) confirmed hypoglycemia (≤70 and &amp;lt;54 mg/dL) were lower with Gla-300. Both insulins were properly titrated and exhibited no specific safety concerns. CONCLUSIONS Gla-300 and IDeg-100 provided similar glycemic control improvements with relatively low hypoglycemia risk. Hypoglycemia incidence and rates were comparable with both insulins during the full study period but lower in favor of Gla-300 during the titration period. The choice between these longer-acting basal insulins may be determined by factors such as access and cost, alongside clinical considerations.
Participation in Get With The Guidelines–Stroke and Its Association With Quality of Care for Stroke
Authors: George Howard, Lee H. Schwamm, John P. Donnelly, Virginia J. Howard, Adam Jasne, Eric E. Smith, J. David Rhodes, Brett M. Kissela, Gregg C. Fonarow, Dawn O. Kleindorfer, Karen C. Albright
Journal: JAMA Neurology (2018)

Get With The Guidelines-Stroke (GWTG-Stroke) is an American Heart Association/American Stroke Association stroke-care quality-improvement program; however, to our knowledge, there has not been a direct comparison of the quality of care between patients hospitalized at participating hospitals and those at nonparticipating hospitals.To contrast quality of stroke care measures for patients admitted to hospitals participating and not participating in GWTG-Stroke.Subpopulation of 546 participants with ischemic stroke occurring during a 9-year follow-up of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a population-based cohort study of 30 239 randomly selected black and white participants 45 years and older recruited between 2003 and 2007. Of those with stroke, 207 (36%) were treated in a hospital participating in GWTG-Stroke and 339 in a nonparticipating hospital. Data were analyzed between July 29, 2017, and April 17, 2018.Quality of care measures including use of tissue plasminogen activator, performance of swallowing evaluation, antithrombotic use in first 48 hours, lipid profile assessment, discharge receiving antithrombotic therapy, discharge receiving a statin, neurologist evaluation, providing weight loss and exercise counseling, education on stroke risk factors and warning signs, and assessment for rehabilitation.Participants treated at participating hospitals had a mean (SD) age of 74 (8) years and 100 of 207 were men (48%), while those seen at nonparticipating hospitals had a mean (SD) age of 73 (9) years, and 161 of 339 were men (48%). Those seen in participating hospitals were more likely to receive 5 of 10 evidence-based interventions recommended for patients hospitalized with ischemic stroke, including receiving tissue plasminogen activator (RR, 3.74; 95% CI, 1.65-8.50), education on risk factors (RR, 1.54; 95% CI, 1.16-2.05), having an evaluation for swallowing (RR, 1.25; 95% CI, 1.04-1.50), a lipid evaluation (RR, 1.18; 95% CI, 1.05-1.32), and an evaluation by a neurologist (RR, 1.12; 95% CI, 1.05-1.20). Those seen in participating hospitals received a mean of 5.4 (95% CI, 5.2-5.6) interventions compared with 4.8 (95% CI, 4.6-5.0) in nonparticipating hospitals (P < .001).These data collected independently of the GWTG-Stroke program document improved stroke care for patients with ischemic stroke hospitalized at participating hospitals.
Abstract 5635: The development to peptide vaccine targeting heat shock protein 90 to overcome resistance to HER-2 target drugs in breast cancer
Authors: Jinho Kang
Journal: Cancer Research (2018)

Abstract HER-2 overexpression is observed in approximately 25% of all breast cancers and is associated with poorer overall survival and decreased time to relapse. Target therapies directed against HER-2 have been developed and used clinically, but many patients continue to develop resistance. Breast cancer is immunogenic and well suited to treatment via immunomodulation. HSP90 is a chaperon for most of the important signal transduction system in HER-2 type breast cancer; HER-2, ER / PR and Akt, the downstream protein of PI3K. Therefore, HSP90 is considered as a potential therapeutic target in order to improved treatment of HER-2 positive resistant breast cancer. Immunotherapy targeting HSP90 has been tried before, however, no clinically available vaccine due to limitation of autologous cell-based approach. We questioned whether HSP90 was an immune target in HER-2 positive breast cancer. First, HSP90-specific IgG antibody immunity was detected in the sera from HER-2 positive breast cancer patients. Next, potential MHC class II epitopes derived from HSP90 with high binding affinity across multiple human HLA genotypes were identified using in silico algorithms. Top 11 peptides were synthesized and Th1 vs Th2 immunity were assessed in human PBMCs. After IFN-γ and IL-10 ELISPOT assays, epitopes inducing Th1-directed immunity were selected for in vivo experiments. Immunogenecity of HSP90 peptides vaccine was evaluated in FVB mice model and showed strong antigen-specific T cell responses in IFN-γ ELISPOT assay. Then, we assessed the anti-tumor effect of immunization with HSP90 peptides vaccine in MMTV-neu-transgenic mouse model after autologous cancer cell implantation. Peptides vaccines derived from HSP90 significantly inhibited tumor growth compared with control group (mean ± SD; 1896 ± 1211 mm3 vs. mean ± SD; 774 ± 136 mm3, respectively; p &amp;lt; 0.05). The tumor-inhibitory effect was associated with HSP90 peptide-specific IFN-γ-secreting T cell responses in immunization group. Also, immunohistochemical staining of tumors derived from immunized mice was performed to examine immune microenvironment and the protein expression of HER-2 pathways. Taken together, multi-epitope peptides vaccine derived from HSP90 is immunogenic in breast cancer patients and is a promising tumor antigen. Based on efficacies in tumor-rejection in vivo, further research in combination with immune modulating antibodies will be performed in the lapatinib-resistant tumor model. Citation Format: Jinho Kang. The development to peptide vaccine targeting heat shock protein 90 to overcome resistance to HER-2 target drugs in breast 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 5635.
Emricasan (IDN‐6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension
Authors: Guadalupe Garcia‐Tsao, Michael Fuchs, Mitchell Shiffman, Brian B. Borg, Nikolaos Pyrsopoulos, Kirti Shetty, Juan F. Gallegos‐Orozco, K. Rajender Reddy, Eyob Feyssa, Jean L. Chan, Mason Yamashita, James M. Robinson, Alfred P. Spada, David T. Hagerty, Jaime Bosch
Journal: Hepatology (2018)

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan‐caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open‐label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] &gt;5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49‐80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End‐Stage Liver Disease score of 8 (range 6‐15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] –1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] –3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase‐3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti‐inflammatory effect.
Abstract 16996: Controlled Pauses (“Stutter”) CPR Did Not Improve ROSC or 4-hour Survival in a Porcine Model of VF-induced Cardiac Arrest
Authors: Alexander Esibov, Tyson G Taylor, Sharon B Melnick, Fred W Chapman, Gregory P Walcott
Journal: Circulation (2015)

Introduction: Ischemic post-conditioning (IPC) has shown promise in mitigating ischemia-reperfusion injury. Controlled pauses during CPR (CP-CPR) following cardiac arrest (CA) and prolonged downtime may help invoke IPC mechanisms and have been shown to improve neurological outcome in swine. We tested whether CP-CPR would improve return of spontaneous circulation (ROSC) and/or 4-hr survival rates, compared with standard CPR from a mechanical chest compression device (M-CPR), following prolonged downtime in a porcine model of ventricular fibrillation (VF)-induced CA. Methods: Twenty anesthetized and instrumented pigs were block randomized to two protocols. Following 10 min of VF, mechanical CPR was initiated (100 comp/min, 50% duty cycle, 2 inch depth). Over the first 5 minutes of CPR, the M-CPR protocol group received continuous chest compressions, while the CP-CPR protocol included four 20-sec pauses in compressions starting at 40, 100, 160, and 220 sec. All other interventions were the same in the two groups. After 5 minutes, a first shock was delivered during a pause. If the shock failed to convert to a perfusing rhythm for ≥ 30 s with a systolic aortic pressure (sAoP) ≥ 50 mmHg for at least the first three contiguous sAoP values, CPR was continued in 2 min cycles, followed by a shock (if indicated) at the end of each cycle, for up to 10 cycles. As soon as these criteria were met between two CPR cycles, ROSC was documented and a post-resuscitation protocol was initiated. During the post-resuscitation protocol, inotropic agents were provided as needed to maintain sAoP ≥ 50 mmHg. Survival was declared if the sAoP was maintained above threshold for 4 hrs following ROSC. Results: Nineteen animals were successfully instrumented for data gathering (9 CP-CPR, 10 M-CPR). In the CP-CPR and M-CPR groups respectively, 3/9 (33%) vs. 5/10 (50%) achieved ROSC (p = 0.46); when ROSC was achieved, time to ROSC was 7.7±1.2 min vs. 5.8±1.1 min (p = 0.08). All animals that achieved ROSC survived to 4 hours. Conclusions: In a porcine model of CA following prolonged VF, CP-CPR did not improve ROSC or 4-hr survival. The trend towards delayed time to ROSC suggests controlled pauses may impair initial resuscitation, even if they ultimately improve neurological outcome. Further studies are warranted.
Abstract 19873: Prognostic Value of Thermodilution-derived Coronary Blood Flow Patterns After Percutaneous Coronary Intervention on Mid-term Left Ventricular Dilation in Patients with ST Elevation Myocardial Infarction
Authors: AkinoriSumiyoshi, KenichiFujii, MasashiFukunaga, MachikoNishimura, TenSaita, TetsuoHorimatsu, HirotoTamaru, KojiroMiki, TakahiroImanaka, TohruMasuyama
Journal: Circulation (2014)

Background: We had reported the thermodilution-derived coronary blood flow pattern (CBFP) after percutaneous coronary intervention (PCI) associated with cardiac events in ST-segment elevation myocardial infarction (STEMI) patients. It was not well known whether the CBFP associated with the left ventricular (LV) dilation after successful PCI in STEMI patients. Methods: Seventy-five patients with STEMI after PCI were enrolled prospectively in this study. Using a pressure sensor/thermistor-tipped guidewire, CBFP was assessed from the thermodilution-curves after PCI. CBFP was classified into 3 groups according to the shape of thermodilution-curve: a normal CBFP (n=39), a distal-embolization CBFP (n=26), or severe microvascular damage CBFP (n=10). Wall-motion score index (WMSI) and left ventricular diameter assessed by cardiac echo were analyzed within 2 weeks and 6 months after PCI serially. Percent change LV diastolic diameter (LVDd) was defined as (LVDd at 6monthes - LVDd at acute phase) / LVDd at acute pha...
Early Detection of Silent Myocardial Impairment in Drug‐Naive Patients With New‐Onset Systemic Lupus Erythematosus
Authors: Qiang Guo, Lian‐Ming Wu, Zi Wang, Jia‐Yan Shen, Xuan Su, Chang‐Qian Wang, Xing‐Rong Gong, Qing‐Ran Yan, Qing He, Wei Zhang, Jian‐Rong Xu, Meng Jiang, Jun Pu
Journal: Arthritis & Rheumatology (2018)

Cardiac magnetic resonance imaging (MRI) has enabled the assessment of myocardial features, from tissue characteristics to functional changes, in patients with systemic lupus erythematosus (SLE). Echocardiography, however, detects cardiac decompensation. This study was undertaken to investigate the use of cardiac MRI to explore early warning signs of silent cardiac involvement and determine treatment timing in SLE.Clinical assessment and cardiac MRI studies were performed in 50 drug-naive patients with new-onset SLE, 60 patients with longstanding SLE, and 50 healthy subjects in a 3-center prospective study.Analysis of cardiac enzymes, the presence and size of regional myocardial fibrosis as indicated by late gadolinium enhancement, strain changes, and biventricular ejection fraction did not indicate cardiac impairment in the patients with new-onset SLE. Native myocardial T1 and extracellular volume (ECV), which are extracellular matrix indices, were elevated in the patients with new-onset SLE (mean ± SD 1,369 ± 79 msec versus 1,092 ± 57 msec in the control group for native T1; 32 ± 5% versus 24 ± 3% in the control group for ECV; P < 0.001 for both). The elevation was independent of SLE disease activity.This is the first study to indicate that drug-naive patients with new-onset SLE, even those with inactive disease, are likely to have silent cardiac impairment. Structural and functional changes in the myocardium are related to SLE disease stage; this finding indicates the value of early detection of myocardial involvement. Native myocardial T1 values and ECV, rather than currently used clinical rheumatic and cardiac indices, could serve as early detection markers of myocardial injury before the presence of visual fibrosis and functional decompensation.
Opioids vs Nonopioids for Chronic Back, Hip, or Knee Pain
Authors: Edward Covington, Charles Argoff, Steven P. Stanos
Journal: JAMA (2018)

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