tbuckley/cabot-search huggingface dataset:
Correlation of Snail expression and survival in patients with early-stage triple-negative breast cancer (TNBC).
Authors: S. Jiralerspong, S. Liu, S. L. Palla, G. B. Mills, M. Hung, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2010)

10525 Background: In breast and other cancers, tumors reactivate a developmental program, the epithelial-mesenchymal transition (EMT), to increase cell motility and facilitate invasion and metastasis. Snail is a transcription factor that has been implicated in triggering EMT. We hypothesized that Snail expression is an important mediator of invasion, metastasis, and decreased survival in breast cancer. Methods: We analyzed protein levels of Snail and EMT markers using reverse-phase protein arrays (RPPA) of 334 primary breast cancers from the frozen tumor bank at M. D. Anderson, obtained from patients with early-stage disease. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product and compared among groups via the log-rank test. Multivariate analysis was conducted via Cox proportional hazards models. Results: 267 patients had complete clinical data. Median age was 61 (range 27-88). 84% had stage I-II disease, 16% stage III. 66% of tumors were hormone- receptor (HR) positive, 3% HER2-positive, 31% TN. Prognostic factors were similar in the low- and high-Snail groups. At a median follow-up of 30.3 months, there were 65 recurrences and 65 deaths. Among TNBC patients, in a univariate model, estimated RFS was marginally significantly worse in the high-Snail vs. the low-Snail group (hazard ratio [hr], 2.11; 95% CI = 0.91, 4.88; p = 0.082). This became significant after adjustment for age and stage in a multivariate model (hr, 2.44; 1.01,5.88; p = 0.047). Strikingly, Snail was a marker of early relapse in TNBC patients, with a 2-year relapse rate of 41% in high-Snail vs. 19% in low-Snail patients. RFS was not different between high- and low-Snail groups in the HR-positive subset (p = 0.737). For all patients, high Snail expression correlated with an increase in the mesenchymal marker fibronectin (p < 0.001, Fisher's exact), consistent with the occurrence of EMT in high- Snail tumors. Conclusions: Snail expression is correlated with decreased RFS, in particular early relapse at < 2 years, in early-stage TNBC patients. TNBC patients with high Snail expression may be candidates for therapy to prevent metastases, in the form of inhibitors of the Snail pathway or EMT. No significant financial relationships to disclose.
Abstract P377: Insulin, Muscle Mass and Exercise Performance in Overweight Women
Authors: Benjamin Leon, Andrea Carnie, Shannon Jenkins, Kevin Smith, Gloria Zalos, Kong Y Chen, Richard O Cannon
Journal: Circulation (2012)

Introduction Obesity is associated with many negative health impacts, including hyperinsulinemia and reduced exercise performance, despite being associated with greater lean skeletal mass which works as the insulin-targeting and exercising organ. Purpose of Study We delineated the associations amongst cardiorespiratory capacity, fat mass, skeletal mass distributions, and fasting plasma insulin in overweight, non-diabetic women. Methods One hundred and seventy-two sedentary women, age 22 to 68 years (range), body mass index (BMI) (34.2 ± 6.3 [mean ± SD]; range 25.3 to 57.6 kg/m 2 ), underwent dual energy x-ray absorptiometry for body composition, fasting insulin, and graded treadmill exercise test using the Bruce protocol with measurement of oxygen consumption (peak VO 2 ). Results After adjustment for age, fasting insulin (9.8 ± 8.1; range 1.9 to 47.6 mcU/ml) was positively associated with BMI (r = 0.43, p&lt;0.001), fat mass (r = 0.41, p&lt; 0.001), load-bearing skeletal muscle mass (lower extremity lean mass; r = 0.29, p&lt; 0.001), and non-load-bearing skeletal muscle mass (upper extremity lean mass; Figure, Panel A). By multiple regression analysis with age, fat mass and lower and upper extremity lean masses as covariates, fat mass, age and upper extremity lean mass (Figure, Panel B) were independent negative predictors of peak VO 2 (all p&lt; 0.01). Lower extremity, however, trended to be positively predictive of peak VO 2 (p = 0.067). Conclusions In non-load-bearing muscle, increased lean mass associated with elevated plasma insulin is predictive of reduced oxygen consumption during exercise, suggesting additional load that may diminish cardiorespiratory exercise performance or intrinsic impairment in skeletal muscle function. In load-bearing muscle, compensatory hypertrophy due to increased fat and lean mass loads may preserve exercise performance.
Chromosomal Aberrations Induced by Hyponitrite and Hydroxylamine Derivatives&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ellen Borenfreund, Mathilde Krim, Aaron Bendich
Journal: JNCI Journal of the National Cancer Institute (1964)

Hydroxylamine and certain of its derivatives induced fragmentations, translocations, and rearrangements of the metaphase chromosomes of mouse embryo and Chinese hamster cells. The compounds included: N-methylhy-droxylamine; N-hydroxyurethan, a carcinogen; hydroxyurea, which exerts a leukopenic action in patients with chronic granulocytic leukemia; N-hydroxyaminoacetic acid, derived from the tumor-inhibitor hadacidin; and hyponitrous acid, which can be formed in situ from hydroxylamines. Since these agents induced main-chain cleavage of isolated deoxyribonucleic acid (DNA) in solution, it is believed that the observed morphological aberrations are due to a direct attack on the DNA of the chromosome.
Abstract 9637: Associations of Routine Repeat Stress Echocardiography With Outcomes in Stable Patients With Prior Abnormal Testing
Authors: Serge C Harb, Sinziana Seicean, Thomas H Marwick
Journal: Circulation (2013)

Background: The optimal follow-up (f-up) strategy of stable medically managed pts with previous abnormal stress imaging test results is unknown. While repeat testing is considered inappropriate early (&lt;2 y) after the initial test, the appropriateness of later testing is indeterminate. We sought to compare the effects of a repeat testing f-up strategy to that of no repeat testing. Methods: We identified 606 stable pts [mean (SD) age 62.7(10.7); 52% male] with abnormal stress echocardiography (SE) results. Among these, 105 had a repeat SE &gt;2 y after the initial test (cases) while 501 did not have repeated testing (controls). Pts were followed for 6.7 y for the occurrence of revascularization (RVS), overall and cardiac death (CD), myocardial infarction (MI) and a composite outcome of CD+MI. Association of the f-up strategy with outcomes was assessed using Cox models. Results: The baseline characteristics of both groups were similar. The rate of outcomes was similar in both groups except more frequent referral for RVS in cases (7.6% vs. 3.4%, p=0.04). Cox regression analyses failed to identify any significant association between the f-up strategy and any of the specified outcomes (Fig.1). The site, extent (single vs. multi-vessel) and type of the SE abnormality (ischemia or scar) were also not predictive of outcome. Conclusion: Routine, repeat testing during f-up is associated with higher referral rate for RVS in medically-managed pts with abnormal prior stress imaging, but no identifiable survival benefit.
Evaluation of the correlation of baseline blood pressure (BP) and plasma renin activity (PRA) with bevacizumab (B)-mediated hypertension in patients with early-stage breast cancer
Authors: M. N. Dickler, H. L. McArthur, B. Nulsen, S. Patil, J. Sealey, J. Laragh, C. Merali, R. Steingart, C. Hudis, H. Rugo
Journal: Journal of Clinical Oncology (2009)

602 Background: Although hypertension (HTN) develops in 20–30% of bevacizumab (B)-treated cancer patients, no accurate clinical predictors of B-mediated HTN have been identified. We evaluated baseline blood pressure (BP) and plasma renin activity (PRA) as potential predictors of B-mediated HTN among breast cancer patients enrolled in an adjuvant chemotherapy-B study. Methods: In this phase II study, B was administered concurrently (10 mg/kg IV q2wk x 8) with pegfilgrastim-supported chemotherapy (AC at 60/600 mg/m 2 q2wk x4 then nab-paclitaxel at 260 mg/m 2 q2wk x4) and continued at 15 mg/kg q3wk thereafter for a total one year of B therapy. The primary endpoint was cardiac safety. A secondary endpoint was the prospective exploration of PRA as a predictor of HTN. Patients with baseline BP &gt;150/100 mmHg were excluded from the study. Peripheral blood for PRA was collected at baseline, week 8, week 16 and every 3 months during B administration. In this preliminary analysis, baseline data was available for 65 of the 80 enrolled patients. Baseline BP and PRA values for those who did and did not develop grade 2–4 HTN were evaluated by Wilcoxon rank sum test. Results: The baseline characteristic medians are: age 45y (27–75), baseline diastolic BP 70 mmHg (52–95), baseline systolic BP 120 mmHg (90–146), and number of B cycles administered 20 (1–21). Twenty-one patients (32%) developed grade 2–4 HTN. Median diastolic and systolic BP among patients with grade 2–4 HTN was 78 and 124 mmHg, respectively, versus 70 and 115.5 mm Hg, respectively, among patients without grade 2–4 HTN (p = 0.0256 and p = 0.0228). There was no significant association between baseline PRA values and the development of grade 2–4 HTN versus not (p = 0.2917). Conclusions: At the time of this preliminary analysis, both baseline diastolic and systolic BP appear to positively predict the development of B-mediated grade 2–4 HTN while baseline PRA does not. Studies exploring the relationship between serial PRAs and the development of HTN for all study participants are ongoing. [Table: see text]
Abstract 2: Automated Dissociation Of Neonatal Hearts And Immunomagnetic Purification Of Cardiomyocytes, Cardiac Fibroblasts And Endothelial Cells
Authors: Manuel Kernbach, Josephine Riesen, Anne Maria Wiencierz, Andreas Bosio, Peter Christalla, Dominik Eckardt
Journal: Circulation Research (2014)

Pure cardiovascular cell lineages are a requisite for an unbiased and cell-type specific investigation of (patho-) physiological mechanisms involved in heart failure. Moreover, pure heart cells are needed as building blocks for cardiac tissue engineering. Therefore, we developed a rapid and automated heart dissociation protocol followed by an immunomagnetic enrichment of the three major heart cell types, namely cardiomyocytes (CMs), cardiac fibroblasts (Fibs) and endothelial cells (Endos) from both, mouse and rat neonatal hearts. First, we developed an enzyme mix optimal for the dissociation of neonatal mouse and rat hearts by screening our enzyme library. Next, we optimized the dissociation by utilizing our gentleMACS technology resulting in a fast (1 h), robust, and fully automated heart dissociation protocol. Analysis of the dissociated heart cells prior to cell purification showed: (i) high cell vitalities (&gt;90%), (ii) high frequencies of α-actinin-positive CMs (ca. 60%) and (iii) vimentin-positive non-CMs with a frequency of ca. 40%. In order to selectively enrich various cell-types from these heterogenous cell populations, we performed a cell-surface marker screen. We identified several candidates for the composition of antibody cocktails enabling selective enrichment of mouse and rat CMs, Fibs or Endos with purities of up to 97%. CMs grown in 2D cultures showed spontaneous beating activity and the expression of sarcomeric proteins. Additionally, heart cells were cultured on decellularized mouse heart slices. Analysis of the slice cultures after recellularization showed (i) partial restoration of synchronous contractions and (ii) orientated and elongated heart cells. Purified Fibs were highly proliferative and could be expanded 34-fold over an analyzed culture period of 15 days. Finally, functionality of the purified endothelial cells was proven by Dil-LDL endocytosis. In summary, we established an automated protocol for the dissociation of neonatal hearts, enabling the subsequent immunomagnetic enrichment of CMs, Fibs and Endos which can readily be utilized for 2D cell culture assays or to generate in vitro heart muscle models and surrogate tissue for myocardial repair.
The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema
Authors: Stanley S. Schwartz, Solomon Epstein, Barbara E. Corkey, Struan F.A. Grant, James R. Gavin, Richard B. Aguilar
Journal: Diabetes Care (2016)

The current classification system presents challenges to the diagnosis and treatment of patients with diabetes mellitus (DM), in part due to its conflicting and confounding definitions of type 1 DM, type 2 DM, and latent autoimmune diabetes of adults (LADA). The current schema also lacks a foundation that readily incorporates advances in our understanding of the disease and its treatment. For appropriate and coherent therapy, we propose an alternate classification system. The β-cell-centric classification of DM is a new approach that obviates the inherent and unintended confusions of the current system. The β-cell-centric model presupposes that all DM originates from a final common denominator-the abnormal pancreatic β-cell. It recognizes that interactions between genetically predisposed β-cells with a number of factors, including insulin resistance (IR), susceptibility to environmental influences, and immune dysregulation/inflammation, lead to the range of hyperglycemic phenotypes within the spectrum of DM. Individually or in concert, and often self-perpetuating, these factors contribute to β-cell stress, dysfunction, or loss through at least 11 distinct pathways. Available, yet underutilized, treatments provide rational choices for personalized therapies that target the individual mediating pathways of hyperglycemia at work in any given patient, without the risk of drug-related hypoglycemia or weight gain or imposing further burden on the β-cells. This article issues an urgent call for the review of the current DM classification system toward the consensus on a new, more useful system.
Is axillary lymph node dissection necessary after sentinel lymph node biopsy in patients with mastectomy and pathological N1 breast cancer?
Authors: Yun Fu, Debra Chung, Minh-An D. Cao, Sophia Apple, Helena R. Chang
Journal: Journal of Clinical Oncology (2014)

101 Background: Recently, axillary lymph node dissection (ALND) was shown to be unnecessary in patients with lumpectomy and 1-2 positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether patients with mastectomy and pathological N1 disease found by SLNB could forego ALND. Methods: 214 patients with primary invasive breast cancer who were treated by mastectomy and lymph node staging surgery (SLNB or ALND) at UCLA were identified between Jan. 2002 and Dec. 2010. Patients were grouped by their first nodal surgery into SLNB (subgroups: observation, radiation and additional ALND with or without radiation) and ALND groups (subgroups: ALND with or without radiation). Results: After a median follow up of 43.6 months, in the SLNB group, the 5-year OS rate was worse in the observation group (71%) when compared to 94% in the additional ALND group and 100% in the radiation group (p=0.031). Systemic recurrence rate in patients with positive SLNs was also significantly higher in the observation group (17.4%) when compared with 7.8% in the additional ALND and no recurrence in the radiation group (p=0.046). Her-2 expression (p=0.006, HR 7.493, 95%CI 1.781~31.520) was found to predict OS. Young age (p=0.024, HR 0.921, 95%CI 0.857~0.989), higher histological grades (p=0.021, HR 5.571, 95%CI 1.295~23.954), and positive Her-2 status (p=0.013, HR 8.916, 95%CI 1.590~49.995) were significant in predicting systemic recurrence in the multivariate analysis with type of nodal surgery and radiation controlled. Compared to the SLNB group, pain (p=0.021) and lymphedema (p=0.043) occurred more frequently in the ALND group. Conclusions: Radiation was as effective as complete ALND in patients with mastectomy and N1 disease detected by SLNB for OS and relapse free survival rates, yet radiation after SLNB had fewer side effects than ALND. SLNB followed by radiation could replace ALND in patients with mastectomy and pathological N1 breast cancer identified by SLNB.
Improved Designs for Cluster Randomized Trials
Authors: Catherine M. Crespi
Journal: Annual Review of Public Health (2015)

Studies in which clusters of individuals are randomized to conditions are increasingly common in public health research. However, the designs utilized for such studies are often suboptimal and inefficient. We review strategies to improve the design of cluster randomized trials. We discuss both older but effective design concepts that are underutilized, such as stratification and factorial designs, as well as emergent ideas including fractional factorial designs and cluster randomized crossover studies. We draw examples from the recent literature and provide resources for sample size and power planning. Given the inherent inefficiencies of cluster randomized trials, these design strategies merit wider consideration and can lead to studies that are more cost-effective and potentially more rigorous than traditional approaches.
Profile of patients hospitalized with COPD acute exacerbation in respiratory department in Tunisia
Authors: Hela Kamoun, Ines Zendah, Ibtihel Khouaja, Samar Sakka, Amel Khattab, Leila Bayahi, Habib Ghedira
Journal: European Respiratory Journal (2011)

In developing countries, Respiratory departments are facing new challenges with the huge increase in the number of patients hospitalized with COPD acute exacerbations with limits in ICU beds availability and delay in the management. The aim of this study is to outline the profile of patients with COPD exacerbation hospitalized in a respiratory department in Tunisia.

Methods: One hundred and one files of male patients, randomly selected among whom hospitalized in a Respiratory male department in Tunis (Tunisia) during the last 20 years for acute COPD exacerbation, are analyzed.

Results: The patients, aged 65 years-old [IC95%: 63-67], are heavy smokers with cigarette consumption of 57 PxA [IC95%: 51-64] and 50% have comobidities and 15% have a history of myocardial ischemia. Two periods of increased hospitalization are observed: December-January and March-April.

Acute respiratory failure with a PaO2<60mmHg is observed in 90% of these patients and Hypercarbia in 15%. Pneumonia is diagnosed in 30% of these patients and bacteria is revealed in 12% mainly Haemophilus Influenzae (9%). Oxygenotherapy is required in 75% of patients and Non Invasive Ventilation (NIV) in 25%, used during the last 5 years. Two patients died during hospitalization and the duration of hospital stay is 17 days [IC95%: 14-19].

Conclusion: High prevalence of acute respiratory failure and Hypercarbia is observed in patients hospitalized with COPD acute exacerbations in respiratory departments in Tunisia with a long duration of hospital stay.
Efficacy of basis therapy and level of immunoregulatory T-cells (T-regs) in COPD
Authors: Natalya Kirillova, Elena Kremer, Ivan Deev, Ludmila Ogorodova, Georgiy Chernogoruk, Evgeny Kulikov, Sergey Fedosenko
Journal: European Respiratory Journal (2012)

Background. COPD is heterogeneous disease with variable clinical and radiographic signs, different response to therapy and rate of decline in lung function and survival of patients. The levels of T-regs could influence on the efficiency of the basis therapy of COPD.  Aim and objectives. Compare the data of COPD clinical course dynamics during basic therapy and levels of inducible (CD4+FOXP3+) T-regs.  Methods. Were included 60 patients with COPD stages II-IV, mean age was 57,8±1,09 years, m/f=50/10, mean duration of disease was 10,6±1,05 years. The observation period was 24 weeks after administration of appropriate basis therapy (GOLD reccomendations). At visits were performed spirometry, index BODE, SGRQ. Peripheral blood mononuclear cells were isolated from heparinized blood on Ficoll density gradient (1,077 g/ml). The circulating percentage of CD4+FoxP3+ T-regs in peripheral blood was estimated by the flow cytometry analysis (FACSCalibur Becton Dickinson, USA) using appropriate monoclonal antibodies.  Results. Persons with the levels of CD4+FoxP3+ T-regs cells less than 7% in peripheral blood, were characterized by significant reductions in SGRQ-scores from 53,29±0,36 points at visit 1 to 48,24±4,13 points at visit 2 (p 0,05).  Conclusions. High level of CD4+FoxP3+ T-regs (>7%) is associated with impaired response to basis therapy COPD.
Abstract 18278: Anabolic-Androgenic Steroid Use is Associated With Systolic and Diastolic Left Ventricular Dysfunction
Authors: Rory B Weiner, Stephanie K Isaacs, Adolph M Hutter, Gen Kanayama, James I Hudson, Michael H Picard, Harrison G Pope, Aaron L Baggish
Journal: Circulation (2013)

Background: Illicit anabolic-androgenic steroid (AAS) abuse is a worldwide public health problem. While several small recent human studies suggest that AAS abuse leads to left ventricular (LV) dysfunction, this association remains incompletely explored. We therefore examined LV function in long-term AAS users (≥2 years of lifetime AAS) and age-matched, non-user comparison men. Methods: All participants underwent a structured clinical interview to obtain a detailed medical history, prior use of AAS and other illicit drugs, and exercise exposure followed by standard 2-dimensional transthoracic echocardiography. LV systolic function was assessed by LV ejection fraction (bi-plane method) and LV diastolic function was assessed using early LV relaxation velocity (E’). Groups were compared by linear regression with adjustment for traditional cardiovascular risk factors and lifetime use of other drugs. Results: We evaluated 33 weightlifting current AAS users (mean [SD] age 44.0 [5.7] years), 18 weightlifting prior AAS users with &gt; 3 months of abstinence (42.4 [4.2] years), 19 non-AAS-using weightlifters (43.2 [5.2] years), and 18 non-AAS-using non-weightlifting men (42.4 [5.2] years). Current AAS users had significantly lower LV ejection fractions than non-AAS-using weightlifters and non-weightlifting men (Table). Similarly, current AAS users showed impaired diastolic function compared to non-AAS-using weightlifters and non-weightlifting men (Table). Of note, prior AAS users showed no significant difference from the two non-AAS comparison groups, and were significantly better than current users on both indices of LV function. Conclusions: Current AAS use is associated with statistically and clinically significant impairment of LV function. Although further confirmatory study is required, these findings suggest that AAS-induced LV dysfunction is a serious but potentially reversible pathology that regresses with AAS abstinence.