tbuckley/cabot-search huggingface dataset:
Abstract P366: Examining the Impact of Captivity in Men and Women on the Slaves Returning to South Sudan
Authors: Joseph Feldman, Cholene Espinoza, Brian J Beckord, Niketa Kumar, William Chaplin, Rupa L Iyengar, Ernani Sadural, Barry Soloway, Sarah Timmapuri, Chinwe Ogedegbe
Journal: Circulation (2014)

Background: South Sudan became an independent state on July 9 2011, after having endured two civil wars with Republic of the Sudan lasting 51 years. Over the 51 years approximately 300,000 South Sudanese were abducted and in held in captivity in the Republic of the Sudan. The South Sudanese abductees suffered abuse and deprivation. Presently it is estimated that 35,000 are still in captivity. Assessing the health status of returning South Sudanese citizens immediately after their return is imperative. The aim of this report is to examine the effect of captivity on heart rate, (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and basic chemistry panel between men and women. Methods: In March of 2013, an American medical team performed health assessments for 48 hours in the state of Bahr el Gazal located in the northwest region of South Sudan. All returnees received health assessments within four days of their return. Health assessments defined as returnees’ demographics, along with their full history and physical examination. During physical exam height, weight, SBP, DBP, and HR, electrolytes and blood urea nitrogen (BUN) were recorded and analyzed. Results: Analysis was run on 186 participants, 50.5% (94) male, and 49.5% (92) female. Females were significantly younger at age of abduction, whereas men spent a significantly longer time in captivity (Table). SBP and DBP were significantly higher in males compared to females, even after adjusting for Age (p = 0.002, p = 0.036). HR was significantly less in males compared with females, even when adjusting for age (p &lt; 0.001). BUN was significantly lower in females compared to males adjusting for age (p &lt; 0.001) Conclusion: Although a majority of measurements in both men and women slaves returning to South Sudan fell within normal ranges, it is crucial to continue to monitor this group’s cardiovascular health because their deprivation while in captivity may have significantly impacted their health and risk for long term cardiovascular disease.
Modified-CVAD Or Modified-Cbad Compared To High Dose Cyclophosphamide For Peripheral Blood Stem Cell Mobilization In Patients With Multiple Myeloma
Authors: Suzanne C Gettys, Alison M Gulbis, Kaci Wilhelm, Yvonne T Dinh, Gabriela Rondon, Muzaffar H. Qazilbash
Journal: Blood (2013)
Psychotic symptoms and suicidal behavior in hospitalized children
Authors: R Livingston, H S Bracha
Journal: American Journal of Psychiatry (1992)

Association of psychotic symptoms with suicidal behavior was studied in 90 hospitalized prepubertal children. Children with psychotic symptoms were more likely to have threatened or attempted suicide. The association of visual hallucinations with suicidal behavior was stronger than that of auditory hallucinations or psychotic ideation. The authors speculate that psychosis in general and visual hallucinations especially may be indicators of suicide risk among children.
Blood pressure and risk of stroke in patients with cerebrovascular disease
Authors: A. Rodgers, S. MacMahon, G. Gamble, J. Slattery, P. Sandercock, C. Warlow
Journal: BMJ (1996)

There is widespread clinical uncertainty about lowering blood pressure in patients with ischaemic cerebrovascular disease. This often manifests as comparatively high thresholds for starting treatment and modest targets in reducing blood pressure. Concern has arisen partly from reports of a J shaped association between blood pressure and recurrent stroke in these patients.1 This relation may, however, be because severe strokes are associated both with a fall in blood pressure2 and independently with a relatively high risk of stroke recurrence, rather than from any adverse effects of low blood pressure itself. If this were true, then people with a history of minor cerebrovascular disease would have direct and continuous relations between usual blood pressure and risk of stroke, as observed in people without cerebrovascular disease.3

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Abstract 11852: Role of Lox-1 in Mitochondrial Dna Damage and NLRP3 Inflammasome Activation
Authors: Zufeng Ding, Sadip Pant, Abhishek Deshmukh, Jawahar L Mehta
Journal: Circulation (2014)

Objective: This study tested the hypothesis that mitochondrial DNA damage could trigger NLRP3 inflammasome activation during inflammation, and LOX-1 may play a critical role in this process. Methods and Results: We performed studies in cultured human THP1 macrophages exposed to ox-LDL or LPS,which are often used as inflammation stimuli in vitro . We examined and confirmed the increase in LOX-1 expression when cells were treated with ox-LDL or LPS. Parallel groups of cells were treated with LOX-1 Ab to bind LOX-1. In accordance with our previous studies in endothelial cells and smooth muscle cells, LOX-1 Ab markedly reduced ox-LDL- as well as LPS-stimulated LOX-1 expression. To assess mitochondrial ROS generation, MitoSOX™ Red mitochondrial superoxide indicator was used. Both fluorescence staining and flow cytometry analysis showed that LPS induced (more than ox-LDL) mitochondrial ROS generation. Pretreatment with LOX-1 Ab significantly attenuated mitochondrial ROS generation in response to ox-LDL or LPS. Then we observed mtDNA damage in THP1 cells exposed to ox-LDL or LPS. Importantly, pretreatment with LOX-1 Ab protected mtDNA from damage in response to both stimuli. This was also confirmed by q-PCR (mtDNA/nDNA ratio) analysis. Further, ox-LDL or LPS induced the expression of phos-NF-kB p65, caspase-1 p10 and p20, and cleaved proteins IL-1β and IL-18. Of note, NLRP3 inflammasome was activated in response to ox-LDL or LPS in a similar manner. Pretreatment of cells with LOX-1 Ab treatment blocked or significantly attenuated these inflammatory responses. Conclusions: These observations based on in vitro observations indicate that LOX-1 via ROS generation plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation.
Abstract 11710: Plasma Mid-Regional Pro-Atrial Natriuretic Peptide and N-terminal Pro-Brain Natriuretic Peptide Can Discriminate Between Paroxysmal and Persistent Lone Atrial Fibrillation
Authors: Ian C Chang, Jenny P Chong, Erin Austin, Chwee N Quay, Lingli Gong, Arthur M Richards, Lieng H Ling, Lin Y Chen
Journal: Circulation (2014)

Purpose: The progression from paroxysmal to persistent atrial fibrillation (AF) is associated with an increased prevalence of cardiovascular comorbidities. Plasma atrial and B-type natriuretic peptides are increased in atrial fibrillation. We sought to determine whether mid-regional pro-ANP (MRproANP) and N-terminal pro-brain natriuretic peptide (NTproBNP) can discriminate between paroxysmal vs. persistent lone AF. Methods: We enrolled patients with lone AF (patients aged &lt;60 years without hypertension, diabetes, or structural heart disease). Biomarkers were measured in normal sinus rhythm. We compared the ability of MRproANP versus NTproBNP in discriminating between paroxysmal and persistent lone AF by estimating the area under the ROC curve (AUC). Results: We enrolled 68 paroxysmal and 13 persistent lone AF patients (median age, 48 and 50 years; 88% and 92% male, respectively). Median MRproANP (121.5 v. 56.6 pmol/L, P&lt;0.001) and NTproBNP (292.0 v. 48.0 pmol/L, P=0.004) were higher in persistent than paroxysmal lone AF. MRproANP (AUC [95% CI] 0.82 [0.72-0.92]) was marginally better than NTproBNP (0.76 [0.65-0.88]) in discriminating between paroxysmal and persistent lone AF, P=0.06 (Figure). The AUC of using both markers (0.85 [0.75-0.94]) was not significantly different from MRproANP alone (P=0.08), but was slightly better than NTproBNP alone (P=0.03). Conclusions: MRproANP and NTproBNP may be helpful in discriminating between paroxysmal and persistent lone AF. Further prospective studies are needed to assess whether these biomarkers can predict progression of paroxysmal to persistent lone AF.
Interferon-γ Increases Expression of Chemokine Receptors CCR1, CCR3, and CCR5, But Not CXCR4 in Monocytoid U937 Cells
Authors: Davide Zella, Oxana Barabitskaja, Jennifer M. Burns, Fabio Romerio, Daniel E. Dunn, Maria Grazia Revello, Giuseppe Gerna, Marvin S. Reitz Jr, Robert C. Gallo, Frank F. Weichold
Journal: Blood (1998)
Sellar Tumors: Pituitary Adenomas and Craniopharyngiomas
Authors: Robert G. Louis, Robert Dallapiazza, John A. Jane
Journal: Neuro-Oncology (2012)

Overall, pituitary tumors account for 10–15% of all intracranial neoplasms. Functionally active pituitary adenomas may secrete prolactin, growth hormone, adrenocorticotrophic hormone, or thyroid-stimulating hormone and most often present with syndromes related to the specific hormone being overproduced. Conversely, nonfunctioning adenomas usually do not come to clinical attention until they cause symptoms related to mass effect including visual disturbances and hypopituitarism. While prolactinomas may be treated medically with dopamine agonists, surgery remains the primary treatment for all other types of pituitary tumors. The trans-sphenoidal route offers the safest and most effective approach for resection of most pituitary adenomas. Craniopharyngiomas are clinically and radiographically heterogeneous tumors which, although benign, are often locally recurrent and invasive. Although select craniopharyngiomas can be approached trans-sphenoidally, a significant number of these tumors require craniotomy. Suprasellar extension of both craniopharyngiomas and pituitary macroadenomas can complicate surgical access and lead to incomplete resection. Suppressive medical therapy and radiotherapy or radiosurgery may control residual pituitary adenomas. Residual craniopharyngiomas may be adequately treated with radiation therapy.
Abstract 13357: MDCO-216 (ApoA-I Milano/POPC) Induces Reverse Cholesterol Transport in Stable Coronary Artery Disease Patients with a Dose Proportional Pharmacokinetics after Single Ascending Doses
Authors: S. Eralp Bellibas, David Kallend, Alain Bobillier, Herman Kempen, Peter L Wijngaard
Journal: Circulation (2014)

Introduction: MDCO-216, a complex of dimeric recombinant apolipoprotein A-I Milano (apoA-I M) and a phospholipid (POPC), is currently under development to improve cardiovascular outcomes by reducing plaque burden in patients with atherosclerotic disease. An earlier version of MDCO-216 has been shown effective in animal models and in patients with ACS. The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD) and safety of MDCO-216, manufactured by an improved process, first time in stable coronary artery disease (CAD) patients. Methods: 24 patients with known stable CAD received a single dose of MDCO-216 (10, 20, 30 or 40 mg/kg) or placebo (in 2:1 ratio) as a 2 hour IV infusion in a double-blind, randomised design. Blood samples were collected for PK and anti-drug Antibody (ADA) analysis. Ex-vivo cholesterol efflux assays were used as exploratory PD biomarkers for MDCO-216 activity. Results: Plasma mean T 1/2 of MDCO-216 ranged from 45 to 59 hours (53 hr. in average) and median T max ranged between 2 to 3 hours. No obvious difference in CL was observed with increases in dose and this ranged from 0.7 to 0.8 mL/hr/kg. Exposure parameters (C max and AUC) increased with dose in a dose-proportional manner. No ADA was detected with any dose at any time point. Dose-dependent increases in ABCA1-mediated efflux (up to 4-fold above baseline) and smaller increases of SRB1-mediated efflux occurred rapidly after infusion. The dose-response analysis for ABCA1-mediated efflux best fitted into a sigmoid E max (maximum effect) PD model and predicts an E max of 12.7% which saturates around a 16 mg/kg dose (see figure). Conclusions: This data is consistent with the findings of the previous IVUS study in ACS patients with MDCO-216 where maximum regression of atherosclerotic plaque burden was seen at a dose of 15 mg/kg; and support further development of this agent as a potential treatment for atherosclerotic disease.
Abstract 88: Simple Stepstool Adjuncts Improve Depth and Duration of AHA Guideline-Compliant Chest Compressions
Authors: Shirley D Viteri, Michael G McBride, Robert M Sutton, Frances M Nadel, Dana Niles, Akira Nishisaki, Xuemei Zhang, Stephen M Paridon, Robert A Berg, Vinay M Nadkarni
Journal: Circulation (2011)

Introduction AHA guideline-compliant chest compressions (CCs) during cardiac arrest improve survival. Few studies assess optimal use of stepstools (adjuncts) to improve compliance of these guidelines. Hypothesis Stepstool use will increase the depth and duration of AHA guideline-compliant CC delivery in a pediatric cardiac arrest manikin model. Methods IRB-approved prospective, randomized trial conducted on healthcare providers who routinely deliver CCs at work. Volunteers performed 2 sessions of continuous CCs on a pediatric manikin, in random order on separate days. CCs were performed with vs. without use of a 13cm stepstool on a standard-height hospital stretcher (70cm) until maximal fatigue or 10 min. Quality parameters (CC depth, rate, % CCs with residual leaning force &gt;2.5kg) were recorded using a CPR-sensing automated feedback-enabled defibrillator. Data were analyzed in 30-second epochs. “AHA guideline-compliant” CCs were defined by achieving all 3 criteria: average depth ≥38mm, rate 90-120 CC/min, and residual leaning force in &lt;20% of CCs. “Time to failure” was defined as the first epoch where AHA guideline-compliant CC criteria were not met. Analysis included descriptive summaries, Student's t-test, Poisson regression, and Cox regression to produce a failure-time analysis. Results All 21 providers completed both sessions: 62.5% male; median age 34 years, range 28-60; median height 173cm, range 163-190cm. With stepstool adjunct, subjects attained goal mean CC depth ≥38mm in over twice as many epochs (RR 2.26; CI: 1.24, 4.12; p=0.008), without significant difference in mean rate or % CCs with leaning force &gt;2.5kg. Median time to failure (duration) to perform AHA guideline-compliant CCs was significantly longer with stepstools (3.5min) than without stepstools (6.0min) (HR 1.53; CI: 1.06, 2.21; p=0.023). Conclusions Stepstool adjunct increased the frequency of attaining goal depth, and time to failure (duration) of AHA guideline-compliant CCs, without increasing residual leaning force in this pediatric cardiac arrest manikin model. With stepstools, AHA guideline-compliant CCs were delivered for close to twice as long. Assessment in the clinical setting is warranted to evaluate the utility of these findings.
Abstract 19040: Exome Sequencing of Extreme Phenotypes Identifies B4GALT2 as a Determinant of Clopidogrel Response Variability
Authors: Stuart Scott, Jean-Philippe Collet, Inga Peter, Yao Yang, Roger Hajjar, Gilles Montalescot, Jean-Sebastien Hulot
Journal: Circulation (2014)

There is wide interindividual variability in platelet aggregation in response to clopidogrel and high/low on-treatment platelet reactivity (HPR/LPR) is associated with more frequent adverse cardiovascular events. The CYP2C19*2 allele is the major genetic determinant of clopidogrel responsiveness but only accounts for ~12% of the variation thus urging for identification of additional variants. In a cohort of 636 coronary artery disease (CAD) patients, those with the most extreme pharmacodynamic response to clopidogrel were identified as LPR (P2Y12 reaction units (PRU)&lt;50 and ADP-induced residual platelet aggregation (RPA)&lt;5%) vs HPR (PRU&gt;235 and RPA&gt;60%). Four patients from each group with wild-type CYP2C19 ( *1/*1) were subjected to exome sequencing (average 70X). Identified variants that clustered in the LPR or HPR groups (3 or 4 carriers vs. 0) were identified and the probabilities of observing the clustering of each variant according to reported European minor allele frequencies (MAF) were calculated. Forty-nine of the identified variants with the lowest probablilities (18 LPR, 31 HPR, p&lt;0.001) were genotyped across the remaining 628 coronary patients, which identified a significant association between two B4GALT2 variants (c.909C&gt;T; p.Ile303= and c.366G&gt;C; p.Gln122His, D’=0.68, r 2 =0.30) and treatment response. Carriers of c.909C&gt;T (MAF=0.102) had lower PRU (p=0.0077) and RPA (p=0.0008) compared to non-carriers, as did carriers of c.366G&gt;C (MAF=0.070) with lower PRU (p=0.0211) and RPA (p=0.0046). Notably, these effects were independent of CYP2C19*2 , suggesting an alternative biological pathway from clopidogrel metabolism. B4GALT2 is a platelet galactosyltransferase that catalyzes the biosynthesis of glycoconjugates and is involved in intercellular recognition and/or adhesion. Taken together, these data implicate B4GALT2 c.909C&gt;T and c.366G&gt;C as genetic determinants of clopidogrel sensitivity by directly influencing platelet aggregation. Their impact on clinical outcomes of CAD patients deserves further investigation.
Abstract 20451: Hedgehog Signaling and Cardiomyocyte Proliferation
Authors: Bhairab N Singh, Stefan M Kren, Wuming Gong, Cyprian Weaver, Kathy Bowlin, Elizabeth Braunlin, Mary G Garry, Naoko Koyano-Nakagawa, Daniel J Garry
Journal: Circulation (2014)

Background: In contrast to adult mammalian heart, lower vertebrates such as newt exhibit a dramatic capacity for regeneration in response to injury. Understanding the underlying mechanisms and signaling pathways in newt could form the basis for regenerative therapies in mammals. In the present study, we explored the role of hedgehog (HH) signaling during cardiac regeneration. Methods and Results: To investigate cardiac regeneration (CR) in vivo, we performed ventricular resection studies in adult newt heart. Whole mount and histochemical studies revealed CR within 30 d of resection injury. Functional assessment by echocardiographic analysis showed improved ejection fraction from 22 ± 5% at 4 d to 42 ± 3% at 30 d of regeneration relative to control (60 ± 3%). Gene clustering and qRT-PCR analysis at 7d post injury indicated enrichment of hedgehog (HH) signaling factors including Shh and ptch1 by 3- and 2-fold respectively, suggesting a critical requirement of HH signaling at early stages of CR. We determined HH signaling is essential as pharmacological inhibition of the HH pathway resulted in complete ablation of CR. Using EdU-labeling and immunohistochemical analyses, we showed that HH signaling regulates proliferation of both epicardial and myocardial cells, as inhibition of the HH pathway reduced EdU-positive nuclei from 15 ± 2% to 5 ± 3%. In contrast, qRT-PCR analysis from murine hearts postnatal day (P) 2 to P14, showed reduced levels of HH signaling factors and cell-cycle associated mRNAs by 3.5-fold with concomitant increase of p21 by 2-fold. This implies HH signals are required for the proliferative process. Consistent with the newt studies, activation of HH in murine neonatal ventricular cardiomyocytes (NVCM) promoted cardiomyocyte proliferation, increasing positive nuclei from 10 ± 2% to 25 ± 3%, while inhibition of HH signaling reduced positivity to 6 ± 3%. qRT-PCR analysis established that activation of HH signaling in NVCM resulted in up regulation of transcripts associated with cardiomyocyte proliferation. Conclusion: These data indicated that HH signaling pathways modulate cardiomyocyte proliferation providing potential therapeutic targets for achieving mammalian cardiac regeneration.
Experimental Therapies Hold Promise for Treating Amyotrophic Lateral Sclerosis
Authors: M J Friedrich
Journal: JAMA (2005)

ALTHOUGH NUMEROUS AGENTS have been tested for their efficacy against amyotrophic lateral sclerosis (ALS), only one to date— riluzole—has been shown to slow this progressive neurodegenerative disorder. But while modestly effective, riluzole cannot ultimately stem the relentless loss of motor neurons that occurs in patients with ALS. Nevertheless, clinical trials are yielding lessons that are helping researchers design more effective strategies against ALS. Such data, as well as novel insights into the processes that give rise to the disease, are pointing to new treatments involving methods such as gene therapy and RNA silencing, as discussed at the 2004 Annual Meeting of the Society for Neuroscience.
Abstract 3842: Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer
Authors: Nawale Hajjaji, Dorothee Chocteau, Sylvie Gerard, Marie Brigitte Orgerie
Journal: Cancer Research (2014)

Abstract Purpose Weight change (gain or loss) in early breast cancer patients is associated with worse survival. However, limited research investigates the impact of weight change in the neoadjuvant setting in women with HER2 overexpressing breast cancer. The goals of this study were to examine i) the relationship between weight change during trastuzumab-based neoadjuvant chemotherapy and pathologic response, and ii) determine whether weight change during post-operative trastuzumab was associated with outcome. Patients and methods From March 2004 to March 2013, 52 patients diagnosed with invasive non-metastatic HER2 overexpressing breast cancer were recruited from H.S. Kaplan Cancer center, France. They received trastuzumab-based neoadjuvant chemotherapy (NAC) before surgery, followed by adjuvant trastuzumab. Patients were distributed in the “weight loss” or “weight gain/stable” categories according to their relative weight change after NAC, and after adjuvant trastuzumab. Logistic regression was used to examine associations between weight change and pathologic response. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to evaluate the relationship between weight change and progression free survival (PFS). Results Median age was 50 years (range 21 to 71 years); 25% of women experienced body weight loss during NAC, 40% had stable body weight, and 35% gained weight. In multivariate analysis, weight loss was significantly associated with worse pathologic complete response (pCR) in tumor compared with the weight gain/stable group (OR = 0.18; 95% CI, 0.04 to 0.84). There was no difference in pCR in nodes according to weight change (OR = 0.34; 95% CI, 0.06 to 1.76). Body mass index was not associated with pCR. At a median follow up time of 3 years, PFS was not associated with weight change during NAC but with weight change during adjuvant trastuzumab. PFS was worse in patients loosing weight during adjuvant trastuzumab (OR = 0.05; 95% CI, 0.01 to 0.34). Conclusion Weight loss was associated with worse pCR to trastuzumab-based neoadjuvant chemotherapy. In addition, weight loss during adjuvant trastuzumab was associated with worse PFS. These results suggest that weight control and promotion of weight maintenance in women with HER2 overexpressing breast cancer should be integrated within cancer treatment to optimize patient outcomes. Citation Format: Nawale Hajjaji, Dorothee Chocteau, Sylvie Gerard, Marie Brigitte Orgerie. Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3842. doi:10.1158/1538-7445.AM2014-3842