tbuckley/cabot-search huggingface dataset:
Abstract MP09: Effect of Estradiol Therapy on Arterial Wall Echomorphology in the Early versus Late Intervention Trial With Estradiol(elite)
Authors: Roksana Karim, Wenrui Xu, Howard N Hodis, Naoko Kono, Intira Sriprasert, Yanji Li, Mingzhu Yan, Frank Stanczyk, Wendy MacK
Journal: Circulation (2020)

Objective: The effect of estradiol therapy (ET) has been evaluated on atherosclerosis progression measured by carotid artery wall thickness. Echogenicity of the arterial wall, a measure of lipid deposition, has not been investigated in relation to ET. Methods: This is a secondary analysis from ELITE. A total of 643 healthy postmenopausal women were randomized within time-since-menopause strata (early (&lt;6 years) and late (&gt;10 years) postmenopause) to daily 1 mg estradiol or placebo. The atherosclerosis outcome for the current analysis is grey scale median (GSM, unitless), a qualitative measure of atherosclerosis based on echogenicity obtained by high resolution ultrasonography of the common carotid arterial wall. Lower GSM values indicate more lipid deposition. GSM and serum concentrations of estradiol (E2) were assessed every 6 months over a median 5-year trial period. Linear mixed effects regression models were used to compare the rate of GSM progression between the randomized groups within time-since-menopause strata. The association of mean on-trial serum E2 levels with GSM progression was also tested using similar mixed effects model. Results: The effect of ET on the annual rate of GSM progression significantly differed between early and late postmenopause strata (p-value for interaction = 0.006). Annual GSM progression rate (95% confidence interval) among women in early postmenopause decreased by -0.30 (-0.63, 0.04) per year among women taking ET compared to -1.41 (-1.77, -1.06) per year among the placebo group (p&lt;0.0001). In contrast, the annual GSM progression rate was not significantly different between ET and placebo among the late postmenopausal women (p=0.37). The positive association between mean on-trial E2 level (pg/ml) and GSM progression rate was stronger and significant among early postmenopausal women (0.008 (0.0007, 0.016)) compared to women in the late postmenopause group (0.003 (-0.006, 0.01)). However, this differential association between E2 level and GSM progression rate was not statistically significant (p-value for interaction = 0.33). Conclusion: Compared to placebo, oral ET significantly reduced progression of lipid deposition in the carotid arterial wall among women in early postmenopause. ET had no such beneficial effect in late postmenopause. Associations between serum estradiol levels and lipid deposition validated those findings. Qualitative assessment of subclinical atherosclerosis (GSM) complements the anatomic assessment by carotid artery intima-media thickness.
The utility of assessing physical activity in ovarian cancer patients following chemotherapy
Authors: K. Zakashansky, S. Higgins, G. Montgomery, P. Dottino, D. Bovbjerg
Journal: Journal of Clinical Oncology (2007)

19666 Objective: The purpose of this preliminary study was to explore the utility of objective assessments of physical activity for investigating the patterns and predictors of reduced physical activity levels in patients receiving standard chemotherapy for ovarian cancer. Methods: Ovarian cancer patients receiving standard regimens of Taxol/Carboplatin chemotherapy (n=9) were recruited prior to their treatment infusion. After signing informed consent, they completed the 20-item Center for Epidemiologic Studies Depression Scale (CESD); post treatment daily activity levels were assessed with a wrist watch-sized, water proof, omnidirectional, actigraphy monitor (Actiwatch-64, Mini Mitter, Bend, OR) worn on the nondominant wrist for the three weeks between treatment cycles. Identical actigraphy data were collected on a sample of healthy female staff (n=9) over a 1 week interval to provide a benchmark for comparison. Results: As expected, waking activity levels in the control sample showed no significant changes across days (p=0.41), so mean levels (343.45 counts) and 95% confidence intervals were calculated for comparison purposes. Chemotherapy patients had significantly lower levels of activity, as well as evidence of recovering physical activity over the 21 days following treatment (p=0.01). Interestingly, the subset (n=4) of patients with higher levels of pretreatment depression (Hi-CESD) did not show significant recovery in physical activity while the Lo-CESD subgroup showed substantial recovery (p=0.001). Conclusions: Objective assessment of physical activity in ovarian cancer patients following chemotherapy treatment reveals significant reduction in activity levels, and a failure to recover in patients with higher levels of pretreatment depression. Actigraphy of daily activity levels may provide a sensitive means of quantifying reductions in physical activity and recovery patterns following chemotherapy treatment for gynecologic cancer. No significant financial relationships to disclose.
サイトカイン依存性ヒト白血病細胞株F-36の樹立および赤血球分化:顆粒球マクロファージコロニー刺激因子またはインターロイキン3を必要とする親系統およびエリスロポエチンを必要とする亜系統 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Chiba S, Takaku F, Tange T, Shibuya K, Misawa C, Sasaki K, Miyagawa K, Yazaki Y, Hirai H
Journal: Blood (1991)
Evaluation of Point-of-Care Decision Support for Adult Acne Treatment by Primary Care Clinicians
Authors: David G. Li, Ashley B. Pournamdari, Kristina J. Liu, Karl Laskowski, Cara Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Acne is a common reason for referral to dermatologists from primary care clinicians. We previously modeled the impact of algorithm-based acne care in reducing dermatology referrals, missed appointments, and treatment delays. <h3>Objective</h3> To prospectively evaluate the downstream outcomes following a real-time, algorithm-based electronic decision-support tool on the treatment of patients referred for acne. <h3>Design, Setting, and Participants</h3> This prospective cohort study included 260 treatment-naive patients referred to a dermatologist for the chief concern of acne, as well as the referring primary care clinicians, at 33 primary care sites affiliated with Brigham and Women’s Hospital from March 2017 to March 2018. <h3>Interventions</h3> We developed and implemented a decision-support tool into the electronic medical record system at an academic medical center. The algorithm identified patients referred to a dermatologist who had not previously been treated for acne and offered guideline-based recommendations for treatment via a real-time notification. <h3>Main Outcomes and Measures</h3> Treatment modification by referring clinicians. <h3>Results</h3> Of 260 patients referred for acne, 209 (80.4%) were women, 146 (56.1%) were non-Hispanic white, and 236 (90.8%) listed English as the preferred language. Patients had a median (quartile 1-quartile 3) age of 28.8 years (24.4-35.1 years) and 185 of 260 had private insurance (71.1%). In total, the algorithm was associated with cancellation of the initial referral in 35 of 260 (13.5%) instances and treatment initiation by the referring clinician in 51 of 260 (19.6%) instances. <h3>Conclusions and Relevance</h3> This decision-support algorithm was associated with a modest reduction in rates of acne-related referrals to dermatologists, and an increased likelihood of treatment initiation by the referring clinician.
Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data
Authors: Caroline A. Bulstra, Jan A. C. Hontelez, Federica Giardina, Richard Steen, Nico J. D. Nagelkerke, Till Bärnighausen, Sake J. de Vlas
Journal: PLoS Medicine (2020)

In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe.We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys.We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.
Role of -2518 MCP-1 polymorphism in cervical cancer development
Authors: A. P. Coelho, A. Nogal, D. Pereira, A. Matos, B. Sousa, A. Araújo, R. Catarino, R. Medeiros
Journal: Journal of Clinical Oncology (2007)

5594 Background: Cervical cancer (ICC) and squamous intraepitelial lesions of the cervix uteri (SIL) constitute serious health problems to women worldwide. ICC occupies the second place in the list of tumours afflicting women. Around 470,000 new cases are diagnosed annually, 80% of which in less developed countries and near half of them resulting in death of the women. MCP-1 chemokine is the main determinant of tumour associated macrophages (TAM) content in the squamous cell carcinoma of the uterine cervix. The aim of our study was the evaluation of the association between the -2518 MCP-1 polymorphism (a biallelic G/A functional polymorphism) and susceptibility to cervical intraepithelial lesions and cervical cancer development. Methods: We analyzed 898 samples of DNA, of which 420 corresponded to healthy women (control group), 130 to women with low and high-grade cervical intraepithelial lesions and 348 to women with cervical cancer. The analysis of the polymorphism and the evaluation of the corresponding genotypes were performed with the PCR-RFLP methodology. Analysis of data was performed using the computer software SPSS for windows. Results: The analysis of the genotipic frequencies of the -2518 MCP-1 genotypes indicates that women carrying genotypes with the G allele present a 29.2% protection for the development of intraepithelial lesions of the cervix uteri (OR=0.708; 95% CI: 0.503–0.998; P=0.048) and a 33.5% protection for the development of squamous cell carcinoma of the cervix uteri. It was also possible to observe an association between the waiting time to onset of cervical cancer and the polymorphism: 59 years for women carrying genotypes with the G allele (95% CI: 56–61years) and 53 years for women with the AA genotype (95% CI: 52–57 years; P=0.005). Also, women with genotypes carrying the G allele present a 2.5 fold higher risk for the progression from early stages of invasive cervical carcinoma (I/II) to clinically more advanced stages (III/IV) (OR=2.26; 95% CI: 1.09–4.67; P=0.026). Conclusions: These findings suggest a role of the -2518 MCP-1 polymorphism in the molecular mechanisms that lead to cervical cancer development and progression. No significant financial relationships to disclose.
Abstract 14407: A Deep Neural Network for Predicting Incident Atrial Fibrillation Directly From 12-Lead Electrocardiogram Traces
Authors: Sushravya M Raghunath, Alvaro Ulloa Cerna, Linyuan Jing, David vanMaanen, Joshua V Stough, Dustin Hartzel, Joseph Leader, Christopher Good, Brandon K Fornwalt, Christopher M Haggerty
Journal: Circulation (2019)

Background: Atrial fibrillation (AF) increases the risk of stroke and hence predictive strategies for detecting incident AF, before stroke occurs, are desired. We hypothesized that a deep learning ...
Profibrotic Activation of Human Macrophages in Systemic Sclerosis
Authors: Rajan Bhandari, Michael S. Ball, Viktor Martyanov, Dillon Popovich, Evelien Schaafsma, Saemi Han, Mohamed ElTanbouly, Nicole M. Orzechowski, Mary Carns, Esperanza Arroyo, Kathleen Aren, Monique Hinchcliff, Michael L. Whitfield, Patricia A. Pioli
Journal: Arthritis & Rheumatology (2020)

Genome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation in SSc. We undertook this study to characterize the activation profile of SSc monocyte-derived macrophages and assessed their interaction with SSc fibroblasts.Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from whole blood from SSc patients (n = 24) and age- and sex-matched healthy controls (n = 12). Monocytes were cultured with autologous or allogeneic plasma to differentiate cells into macrophages. For reciprocal activation studies, macrophages were cocultured with fibroblasts using Transwell plates.The gene expression signature associated with blood-derived human SSc macrophages was enriched in SSc skin in an independent cohort and correlated with skin fibrosis. SSc macrophages expressed surface markers associated with activation and released CCL2, interleukin-6, and transforming growth factor β under basal conditions (n = 8) (P < 0.05). Differentiation of healthy donor monocytes in plasma from SSc patients conferred the immunophenotype of SSc macrophages (n = 13) (P < 0.05). Transwell experiments demonstrated that coculture of SSc macrophages with SSc fibroblasts induced fibroblast activation (n = 3) (P < 0.05).These data demonstrate that the activation profile of SSc macrophages is profibrotic. SSc macrophages are activated under basal conditions and release mediators and express surface markers associated with both alternative and inflammatory macrophage activation. These findings also suggest that activation of SSc macrophages arises from soluble factors in local microenvironments. These studies implicate macrophages as likely drivers of fibrosis in SSc and suggest that therapeutic targeting of these cells may be beneficial in ameliorating disease in SSc patients.
Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials
Authors: Alyson Haslam, Diana Herrera-Perez, Jennifer Gill, Vinay Prasad
Journal: JAMA Network Open (2020)

Quality of life (QoL) is an important consideration in cancer medicine, especially because drugs are becoming more costly and may only result in modest gains in overall survival. However, there has been no descriptive analysis for the points at which QoL is measured in cancer trials.To estimate the prevalence of studies that measure QoL at different points and see how many studies measure QoL for the entirety of a patient's life.This cross-sectional analysis includes all articles on oncology clinical trials in the 3 highest-impact oncology journals, published between July 2015 and June 2018, that reported QoL outcomes.Data were abstracted on when QoL was assessed and the characteristics of these studies.For all 149 studies that met inclusion criteria, QoL assessment was high during treatment (104 articles [69.8%]), during follow-up (81 articles [54.4%]), and after the end of the intervention (68 articles [45.6%]). In 5 of the 149 studies (3.4%), QoL was assessed until death, including in only 1 of the 74 studies on metastatic or incurable cancers. Among these 5 studies, only 1 (20%) used a drug intervention, 1 (20%) used a behavioral intervention, and 2 (40%) used a radiation intervention; only 1 of 5 was in the metastatic setting. The number of studies that reported a positive QoL outcome (ie, QoL outcome was more favorable in the intervention group than in the control group) was between 42 of 81 articles (51.9%) and 16 of 28 articles (57.1%) for most QoL assessment points but only 1 of 5 articles (20%) for studies measuring QoL until death.This study found that most clinical trials assessed QoL during the treatment or intervention and often during a given amount of follow-up but infrequently assessed QoL on disease progression and rarely followed QoL until the end of the patient's life. Most studies reporting QoL until the end of life reported worse QoL outcomes for the intervention group than the control group. Future research and policy recommendations should consider not just short-term QoL outcomes but QoL outcomes throughout the patient's cancer care.
Abstract P213: Chocolate Intake is Associated With Decreased Epigenetic Aging Among African Americans
Authors: Li Chen, Haidong Zhu, Jigar Bhagatwala, Anas Raed, Ying Huang, Howard D Sesso, Yanbin Dong
Journal: Circulation (2020)

Introduction: Chocolate intake has shown potential cardiometabolic health benefits in recent studies. We recently reported an association between chocolate intake and longer telomere length. Epigenetic age acceleration, an emerging marker of biological aging, predicts cardiovascular morbidity and mortality. But the relationship between chocolate intake and epigenetic aging has not been investigated. Hypothesis: We examined the association between chocolate intake and epigenetic aging among African Americans. Methods: A genome-wide methylation scan was performed among 50 overweight and obese African Americans using the Illumina Human Methylation 850K Bead Chip on peripheral blood mononuclear cell DNA. DNA methylation ages were calculated according to the Horvath and the Hannum clocks. Methylation-based age acceleration (ΔAge) was extracted from a linear regression of DNA methylation age on chronological age. Chocolate intake frequency over the past year was obtained by questionnaire, along with other major cardiovascular risk factors. Results: Fifty participants (aged 26.1 ± 9.3 years, 16% male) were included in the study. Fifteen (30%), 20 (40%), and 15 (30%) participants consumed less than 1 serving/month, 1-3 servings/month, and ≥1 serving/week of chocolate, respectively. Chocolate intake of ≥1 serving/week was associated with decreased Δage in both Horvath clock (β= -3.31, p-value = 0.046) and Hannum clock (β= -3.59, p-value = 0.096) after adjustment of age, sex, body mass index, 25(OH)D and CD4%. Conclusions: Chocolate intake may be associated with decreased epigenetic aging, with randomized controlled trials needed to establish any beneficial effects of chocolate intake on epigenetic aging processes.
The association of global gene expression in human colon tumors with germline variation at rs6983267 on 8q24 suggests that this SNP is an eQTL hotspot
Authors: Gordon Okimoto, Maarit Tiirikainen, Naveen Babbar, Jenny Poynter, Lenora Loo, Michael Loomis, John Hopper, Mark Jenkins, Steven Gallinger, Stephen Thibodeau, Robert Haile, Graham Casey, David Duggan, Loic Le Marchand
Journal: Cancer Research (2009)
Abstract P326: Multilevel Analysis Of Concentrated Neighborhood Disadvantage And Cardiometabolic Factors In People Living With Hiv
Authors: Tekeda F Ferguson, Katherine Theal, David Welsh, Patricia E Molina
Journal: Circulation (2020)

Aging persons living with HIV (PLWH) are a vulnerable population at higher risk for chronic illnesses such as metabolic alterations, diabetes, cardiovascular disease, and cancer. Community and specifically, neighborhood, factors may play a key role in the development of comorbidities. Availability of healthy food stores, physical activity resources, walking/physical activity environment, and neighborhood socioeconomic status have all been individually associated with a higher odds of having ideal cardiovascular health scores. We hypothesized that exposure concentrated disadvantage at the community level impact cardio metabolic outcomes in PLWH. We examined this hypothesis in a cross-sectional analysis of the N ew O rleans A lcohol use in H IV [NOAH] Study of adult PLWH under care (n=365). Hypertension (HTN) was defined as a mean systolic ≥130-139 or diastolic blood pressure ≥80-89 mmHg. Metabolic syndrome (MS) was defined as having 3 of 5 conditions: HTN, low high-density lipoproteins (≤40 (men)/50 (women)), high triglycerides (≥ 150mg/dl), high glucose (≥100 mg/dl), waist circumference &gt;88(women)/102(men). Multivariable logistic regression and multilevel binomial regression analyses were performed adjusting for age, race, smoking, and viral load. The majority of participants were African American (83.6%) with a mean age 48.2 ±10.4, 68.8% male and 31.2% female. MS was prevalent in 36.1%, HTN 66.0%, diabetes 14%, dyslipidemia 28.2%, and 27.4% were obese. There was substantial clustering of cardiometabolic outcomes by neighborhood, with intra-class correlations (ICC) near or greater than 20% for BMI, diabetes, hypertension, and metabolic syndrome. Neighborhood concentrated disadvantage explained a significant proportion of the variance in diabetes (ICC drop from 18% to 8%) and the likelihood of having diabetes increases by 33% for each unit increase in neighborhood concentrated disadvantage (odds ratio = 1.33, 95% CI=1.02, 1.74). Our results suggest a significant role of environmental factors on cardio metabolic comorbidities among PLWH. There is a critical need for a deeper understanding of the roles that social determinants at the community and interpersonal levels play in chronic comorbidities in PLWH. Neighborhoods and social spaces are important contexts through which social determinants act to shape health and health behavior. (Supported by: NIH P60AA009803)