tbuckley/cabot-search huggingface dataset:
Abstract MP78: Progression of Valvular Calcification and Risk of Incident Stroke: The Multi-ethnic Study of Atherosclerosis (MESA)
Authors: Oluwaseun Fashanu, Anas Bizanti, Ahmad Al-Abdouh, Di Zhao, Matthew J Budoff, Isac C Thomas, W T Longstreth, Erin D Michos
Journal: Circulation (2020)

Introduction: Stroke is a leading cause of morbidity and mortality in the United States. Identification of individuals at risk for stroke is important for implementation of preventive therapies. Prevalent valvular calcification (VC) has been shown to be associated with stroke but less is known about associations of VC progression with stroke. Methods: Progression (interval increase &gt;0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. Results: We studied 5,606 multiethnic participants (39.6% White, 26.9% Black, 21.4% Hispanic, 12.2% Chinese) free of baseline CVD enrolled in MESA. Baseline mean ± SD age was 62 ± 10 years; 53% were women; 12% had prevalent AVC and 9% prevalent MAC at the baseline visit; 83% had no progression of VC, 14%, progression at one site (AVC or MAC), and 3% progression at both sites (AVC and MAC) at follow-up. Over a median of 12 years, 214 total and 170 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p&gt;0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratios (95% CI) 1.59 (1.11 - 2.27)] and ischemic stroke [1.64 (1.10 - 2.43)] in the whole cohort (model 3) and after further adjustment for baseline coronary artery calcification (model 4) ( Table ). Results remained significant for total stroke risk after excluding participants with interim atrial fibrillation or coronary heart disease [1.60 (1.01 - 2.54)]. In women, AVC progression was associated with ischemic stroke [1.87 (1.04 - 3.36)] (p-for-interaction=0.03). Conclusion: Progression of MAC over 2.4 years is associated with increased risk of total and ischemic stroke, and in women, AVC progression with higher ischemic stroke risk.
Abstract P299: Changes in Race-Sex Specific Population Attributable Fraction for Obesity-Related Diabetes, 2001-2016
Authors: Natalie Cameron, Megan McCabe, Lucia Petito, Norrina B Allen, Mercedes R Carnethon, Sadiya S Khan
Journal: Circulation (2020)

Introduction: Estimating effects of population-level increases in obesity on diabetes has important implications for public health policy. Therefore, we used the population attributable fraction (PAF) to quantify trends in the burden of obesity on incident diabetes in key sex and race/ethnicity subgroups over time. Hypothesis: PAFs for obesity attributable incident diabetes will be greatest for women, differ by race/ethnicity and increase over time. Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated unadjusted and adjusted hazard ratios (HRs) of obesity on incident diabetes mellitus (DM). We included non-Hispanic White (NHW), non-Hispanic Black (NHB) and Hispanic-Mexican (MA) MESA participants with available data on body mass index and key covariates and without DM at baseline. Next, we estimated the prevalence of obesity in four pooled groups of NHANES survey cycles from 2001-2016 with similar characteristics to MESA participants (age 45-80 years, NHW, NHB, and MA without cardiovascular disease). Lastly, we combined estimates from MESA and NHANES to quantify unadjusted and adjusted PAFs (adjusted for age, income, education, physical activity and diet). Leveraging the objective longitudinal assessment of incident DM in MESA and a nationally representative sample of NHANES, we estimated broadly generalizable PAF estimates over time. Results: Of 3869 MESA participants, mean age was 61 (± 10) years with 47% men, 56% NHW, 31% NHB, and 13% MA. Incidence of DM was 11% with overall adjusted HR of 2.75 (95% CI 2.26, 3.34) for obesity. Prevalence of obesity increased from 34% (32, 37) in 2001-2004 to 41% (39, 44) in 2013-2016. Overall adjusted PAFs ranged from 0.23 to 0.52 over the study period (TABLE), with greatest estimates in NHW women. Conclusions: In conclusion, over time, the proportion of diabetes due to obesity has increased across multiple subgroups of the population, further highlighting the health burden of obesity in the population.
IMPACT OF HEART RATE ON DIAGNOSTIC ACCURACY OF SECOND GENERATION 320-DETECTOR COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY
Authors: Nitesh Nerlekar, Arthur Nasis, Brian Ko, Michael Leung, James Cameron, Dennis Wong, Peter Psaltis, Ian Meredith, John Troupis, sujith seneviratne
Journal: Journal of the American College of Cardiology (2014)
The use of in-vitro drug resistance levels as a predictor of outcome in soft tissue sarcoma
Authors: L. Schleicher, M. Hesdorffer, R. Taub
Journal: Journal of Clinical Oncology (2007)

20510 Background: We have assayed in-vitro drug resistance and immunohistochemical staining for drug resistance markers (MDR-1, MRP) in patients with metastatic soft tissue sarcoma patients. We looked at resistance to Cisplatin, Doxorubicin, and Ifosphamide, prior to beginning chemotherapy. The aim of this study was to investigate the validity of in-vitro drug resistance testing as a predictor of outcome. Methods: Viable tumor samples obtained at time of recurrence or metastasis from 13 patients with metastatic soft tissue sarcoma were tested by a semiquantitative 12 hour tritiated-thymidine uptake cell-proliferation assay (EDR test, Oncotech Inc., Tusin, California) for resistance to the chemotherapy drugs cisplatin, doxorubicin, and ifosphamide. The mean drug resistance level for these three drugs was plotted against survival in months, both from time of metastasis and time of initiation of chemotherapy. Mean resistance was also correlated with positive staining for either MDR-1 or MRP. Results: There was no relationship found between the mean drug resistance and survival, either from time of metastasis (correlation coefficient -0.0596) or time of initiation of chemotherapy (correlation coefficient - 0.1864). There was no correlation between mean drug resistance and; 1) presence of MDR-1 staining (correlation coefficient -0.1269), 2) presence of MRP staining (correlation coefficient -0.2175), 3) presence of either staining for MDR-1 or MRP (correlation coefficient -0.2636). Conclusions: 1) In-vitro drug resistance is not predictive of outcome in patients with soft tissue sarcoma. 2) There is no correlation between the mean drug resistance and positive staining for either MDR-1 or MRP. No significant financial relationships to disclose.
The Effect of Mepolizumab on the Lungs in a Boy with Hypereosinophilic Syndrome
Authors: Keren Armoni Domany, Shelly I. Shiran, Dikla Adir, Moran Lavie, Dror Levin, Nir Diamant, Guy Gut, Shira Benor
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Paramagnetic Rim Sign in Radiologically Isolated Syndrome
Authors: Suradech Suthiphosuwan, Pascal Sati, Martina Absinta, Melanie Guenette, Daniel S. Reich, Aditya Bharatha, Jiwon Oh
Journal: JAMA Neurology (2020)

Paramagnetic Rim Sign in Radiologically Isolated SyndromeIndividuals with radiologically isolated syndrome (RIS) have incidental magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis (MS). 1 Recent studies using susceptibility-based imaging have shown that a subgroup of chronic MS white matter lesions (WMLs) have a rim of paramagnetic susceptibility-associated signal loss at the lesion edge, the paramagnetic rim sign (PRS), that is associated with the presence of iron inside phagocytes, which indicates chronic, active demyelination. 2,3The objective of this study was to determine whether patients with RIS have WMLs that are positive for PRS (PRS+).
Bevacizumab 5mg/kg can be safely infused over 10 minutes
Authors: D. L. Reidy, K. Y. Chung, J. P. Timoney, V. Park, E. Hollywood, N. Sklarin, R. Muller, L. Saltz
Journal: Journal of Clinical Oncology (2007)

4135 Background: Bevacizumab is a humanized monoclonal antibody that targets VEGF. Due to concerns for potential infusion- related hypersensitivity reactions (HSRs), initial phase I trials used an initial 90, 60, 30 minute infusion sequence. We sought to determine if the initial prolonged infusion was still necessary and in addition, if, on the basis of available clinical experience, an infusion time of less than 30 minutes could be safely used. Methods: We used computerized pharmacy records to identify all patients who received bevacizumab at our institution in the first two years of commercial availability (2/1/04- 6/30/06). Our institutional adverse drug reaction reporting program was utilized to identify any infusion reactions possibly related to bevacizumab and patient medical records were reviewed for confirmation Results: A total of 1,077 patients were treated with 10,606 doses of bevacizumab, and 765 of these patients received a 5 mg/kg dose (total of 8,494 doses). No HSRs occurred with the 90, 60, 30 minute infusion sequence in the first 202 patients. The standard infusion rate was then modified to 30 minutes for all bevacizumab doses. No HSRs were encountered. The infusion was again modified to a rate of 0.5 mg/kg/min. Of the 370 patients who received a total of 2,311 doses of bevacizumab at 5 mg/kg over 10 minutes, six (1.6 %) experienced events of minor clinical consequence that were felt to be possibly consistent with non-serious HSRs Conclusions: 90 and 60 minute initial infusion times are unnecessary. Use of a standard infusion rate of 0.5 mg/kg/min is safe, logical, justifiable, and is the current policy at our institution. No significant financial relationships to disclose.
Current and Future Outlook on Disease Modification and Defining Low Disease Activity in Systemic Sclerosis
Authors: Vivek Nagaraja, Marco Matucci‐Cerinic, Daniel E. Furst, Masataka Kuwana, Yannick Allanore, Christopher P. Denton, Ganesh Raghu, Vallerie Mclaughlin, Panduranga S. Rao, James R. Seibold, John D. Pauling, Michael L. Whitfield, Dinesh Khanna
Journal: Arthritis & Rheumatology (2020)

Systemic sclerosis (SSc) is an autoimmune rheumatic disease with heterogeneous clinical manifestations and a variable course in which the severity of the pathology dictates the disease prognosis and course. Among autoimmune rheumatic diseases, SSc has the highest mortality rate among all rheumatic diseases, though there are exciting new therapeutic targets that appear to halt the progression of SSc manifestations such as skin or lung fibrosis. In selected patients, high-intensity regimens with autologous stem cell transplantation can favorably modify the course. In what was once thought to be an untreatable disease, targeted therapies have now changed the outlook of SSc to a treatable disorder. Herein, we discuss the targeted therapies modifying the outlook on selected organ involvement and creating opportunities for future treatment. We also present a framework for defining low disease activity in SSc.
Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance
Authors: Miguel Angel Merlos Rodrigo, Ana Maria Jimenez Jimemez, Yazan Haddad, Khaldon Bodoor, Pavlina Adam, Sona Krizkova, Zbynek Heger, Vojtech Adam
Journal: Drug Resistance Updates (2020)
Interleukin‐36 (IL‐36) system in the 1‐fluoro‐2,4‐dinitrobenzene (DNFB) mouse model of allergic contact dermatitis
Authors: Angela Zaladonis, Xinyan Zhang, Katherine K. Manupipatpong, Sowmiya Kalaiselvan, Pilar Alvarez, Liselotte E. Jensen
Journal: Allergy (2020)
Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection
Authors: Chloe Orkin, Keikawus Arasteh, Miguel Górgolas Hernández-Mora, Vadim Pokrovsky, Edgar T. Overton, Pierre-Marie Girard, Shinichi Oka, Sharon Walmsley, Chris Bettacchi, Cynthia Brinson, Patrick Philibert, Johan Lombaard, Marty St. Clair, Herta Crauwels, Susan L. Ford, Parul Patel, Vasiliki Chounta, Ronald D’Amico, Simon Vanveggel, David Dorey, Amy Cutrell, Sandy Griffith, David A. Margolis, Peter E. Williams, Wim Parys, Kimberly Y. Smith, William R. Spreen
Journal: New England Journal of Medicine (2020)

Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection.We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm).At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48.Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.).
Social Safety Theory: A Biologically Based Evolutionary Perspective on Life Stress, Health, and Behavior
Authors: George M. Slavich
Journal: Annual Review of Clinical Psychology (2020)

Social Safety Theory hypothesizes that developing and maintaining friendly social bonds is a fundamental organizing principle of human behavior and that threats to social safety are a critical feature of psychological stressors that increase risk for disease. Central to this formulation is the fact that the human brain and immune system are principally designed to keep the body biologically safe, which they do by continually monitoring and responding to social, physical, and microbial threats in the environment. Because situations involving social conflict, isolation, devaluation, rejection, and exclusion historically increased risk for physical injury and infection, anticipatory neural–immune reactivity to social threat was likely highly conserved. This neurocognitive and immunologic ability for humans to symbolically represent and respond to potentially dangerous social situations is ultimately critical for survival. When sustained, however, this multilevel biological threat response can increase individuals’ risk for viral infections and several inflammation-related disease conditions that dominate present-day morbidity and mortality.
Characterization of Endovascular Abdominal Aortic Aneurysm Repair Surveillance in the Vascular Quality Initiative
Authors: Zachary J. Wanken, Spencer W. Trooboff, Barbara Gladders, Jesse A. Columbo, Niveditta Ramkumar, Andrea M. Austin, David H. Stone, Matthew W. Mell, Art Sedrakyan, Philip P. Goodney
Journal: Circulation (2020)
Abstract P6-04-25: Epidermal growth factor receptor as therapeutic target in hormone receptor-positive breast cancer
Authors: Yisun Jeong, Soo Youn Bae, Daeun You, Seung Pil Jung, Hee Jun Choi, Isaac Kim, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Jeong Eon Lee, Sangmin Kim, Seok Jin Nam
Journal: Cancer Research (2020)

Abstract Background/Aims: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. Methods: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. Results: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells was significantly decreased by combined tamoxifen and gefitinib. Conclusion: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression. Citation Format: Yisun Jeong, Soo Youn Bae, Daeun You, Seung Pil Jung, Hee Jun Choi, Isaac Kim, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Jeong Eon Lee, Sangmin Kim, Seok Jin Nam. Epidermal growth factor receptor as therapeutic target in hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-04-25.
Abstract P496: The Development of Anthropometric Measures Over Time and Predictors for Overweight and Obesity
Authors: Hawazen Atalla, Bledar Daka, Ulf Lindblad, Margareta I Hellgren
Journal: Circulation (2020)

Background: Today, more people die because of obesity and it′s comorbidities than due to malnutrition and actions to prevent the development of overweight and obesity is urgently needed. Different measurements, such as body mass index and waist circumference (WC) may develop differently with age and play different roles in the development of cardiovascular and metabolic disease. Objective: The purpose of this study was to examine the development of anthropometric measures in men and women and to identify possible biochemical predictors for at least five percent weight increase over ten years, considering the modifying effect of physical activity. Methods: In the Vara Skövde Cohort, a longitudinal, prospective study, 1327 randomly selected individuals (35-75 years) participated in two examinations, 2002-2005 and 2012-2014. All participants (657 men, 670 women) were carefully examined with body weight and height, WC and fasting venous blood samples. Validated questionnaires about socioeconomic factors and lifestyle were completed. Physical activity was reported on a 4-graded scale and dichotomized into a high and low level of physical activity. Data are analyzed with T-Test and logistic regression and adjusted for age, sex, weight at baseline, smoking, education, physical activity, plasma glucose and triglycerides. Results: Mean age at baseline was 48.8 years. Mean body weight increased till the age of 55 years, 2.4 kg (SD 6.0, P &amp;#8804 0.0001), and decreased significantly thereafter, -1.1 kg (SD 6.3, P= 0.001) without any difference between men and women. Contrary, WC increased continuously over the years in all age-groups, 4 cm (SD 7.4, P &amp;#8804 0.001). Further, no normal weight person became obese at follow- up. Individuals who maintained or increased their level of physical activity to high had a significantly lower risk for weight increase as compared to those who remained or decreased their level of physical activity to a low level (OR 0.7, CI 0.7 - 0.9, P= 0.008). Serum concentration of LDL (low density lipoprotein) was inversely associated with 5% weight increase after ten years (OR 0.7, CI 0.6-0.7, P &amp;#8804 0.001). We did not find that education level, psychological stress or sleep quality at baseline predicted body weight change. Conclusion: While body weight peaked at the age of 55 years, abdominal obesity increased continuously during the follow-up time. Maintained physical activity seems to limit this increase and emphasizes the importance of a high level of physical activity over the years. The risk of a low concentration of LDL for weight gain needs to be further examined.