tbuckley/cabot-search huggingface dataset:
Abstract P463: Objectively Measured Moderate-to-Vigorous Physical Activity is Associated With Decreased Myosteatosis in African Caribbean Adults
Authors: Iva Miljkovic, Allison Kuipers, Ryan Cvejkus, Victor Wheeler, Joseph Zmuda
Journal: Circulation (2020)

Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases. Therefore, a lifestyle modification that reduces myosteatosis would be of great public health importance. However, studies examining the association of relevant lifestyle factors with this ectopic fat depot are lacking, particularly in African ancestry populations who have a very high burden of cardio-metabolic diseases. The aim of this study was to examine the relation between objectively measured physical activity and sedentary behavior with computed tomography measured calf muscle attenuation among middle-aged and elderly African-Caribbeans from the population-based Tobago Health Study. Preliminary analyses were conducted among 134 women (mean age 59 yrs, mean BMI 31.6 kg/m 2 ) and 355 men (mean age 62 yrs, mean BMI 28 kg/m 2 ). Physical activity was measured using the SenseWear Pro armband worn for 4-7 days. We calculated the mean duration of waking time engaged in light physical activity (LPA), moderate to vigorous activity (MVPA), and sedentary behavior (SB) per day. Skeletal muscle attenuation (mg/cm 3 ) reflects the fat content of the muscle such that greater skeletal muscle fat infiltration is reflected by lower attenuation. Women spent less time in LPA (146 vs. 270 min/day) and MVPA (15 vs. 41 min/day), but more time in SB (789 vs. 647 min/day) than men (all p&lt;0.0001) after adjustments for gender differences in age. Muscle attenuation was lower among women compared with men (70.5 vs. 72.7 mg/cm3; age and BMI adjusted p&lt;0.0001). In both women and men, muscle attenuation was positively correlated with the LPA and MVPA, and inversely with time spent in SB (spearman correlation coefficients (r) ranged from 0.21 to 0.39, all p&lt;0.006 adjusted for age). Upon additional adjustment for BMI, in both women and men, the association of muscle attenuation with MVPA remained significant (r=0.21 and r=0.18, respectively, both p&lt;0.03), but there was no association with LPA. Percent time spent in SB was associated with muscle attenuation only among women after additional adjustment for BMI (women: -0.16, p=0.052), and we also found a significant sex interaction effect of SB on muscle attenuation (p=0.035). Our preliminary findings suggest that there is significant association between MVPA and myosteatosis among middle-aged and elderly African Caribbeans. However, SB may only be relevant for myosteatosis among women. Future analyses will be conducted in a larger sample from this cohort to confirm our findings and to test for independence from other potential confounding factors, such as diet, sleep patterns, adiposity distribution, and diabetes.
Amino acid transporters: Emerging roles in drug delivery for tumor-targeting therapy
Authors: Ling Zhang, Chengguang Sui, Wenhan Yang, Qiuhua Luo
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Amino acid transporters, which play a vital role in transporting amino acids for the biosynthesis of mammalian cells, are highly expressed in types of tumors. Increasing studies have shown the feasibility of amino acid transporters as a component of tumor-targeting therapy. In this review, we focus on tumor-related amino acid transporters and their potential use in tumor-targeting therapy. Firstly, the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are reviewed. Secondly, the recognition requirements are discussed, focusing on the "acid-base" properties, conformational isomerism and structural analogues. Finally, recent developments in amino acid transporter-targeting drug delivery strategies are highlighted, including prodrugs and nanocarriers, with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated endocytosis. We aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.
超高温性古細菌Pyrococcus horishii OT3の蛋白質-蛋白質相互作用
Authors: Usui K, Katayama S, Kanamori-Katayama M, Ogawa C, Kai C, Okada M, Kawai J, Arakawa T, Carninci P, Itoh M, Takio K, Miyano M, Kidoaki S, Matsuda T, Hayashizaki Y, Suzuki H
Journal: Genome biology (2005)
Abstract P234: Associations of Clinical Characteristics and Health-related Behaviors With Physical Activity Levels in Stage B Heart Failure Patients
Authors: Maira Tristao Parra, Meredith A Pung, Kathleen Wilson, Christopher Pruitt, Barry H Greenberg, Paul Mills
Journal: Circulation (2020)

Hypothesis: insufficiently active heart failure patients will report poorer QoL, more fatigue and depressive mood compared to active patients. Aims: To characterize clinical characteristics and health-related behaviors according to physical activity (PA). Also, to explore predicting factors of quality of life (QoL). Methods: Cross-sectional analysis of a cohort of Stage B HF patients. PA classification was set as active, moderately active or insufficiently active, according to the LTEQ questionnaire. For QoL, the SF-36 questionnaire was used. ANOVAS, Chi-Square tests or likelihood ratios and unadjusted multiple regression models were calculated. Significance was set at p ≤ 0.05. Results: In this cohort, 277 HF patients completed the PA questionnaire. The prevalence of active patients was higher than moderately active and insufficiently active (53.3% vs 15.2% and 29.6%), respectively. Younger age (p = 0.044), lower waist circumference (WC) (p = 0.002), and lower waist-to-hip ratio (p = 0.046) were associated with being active. The prevalence of Type II diabetes mellitus (T2DM) in the active groups was significantly lower (p = 0.001). Physically active groups had cases of mild LV enlargement (1.4% and 7.5%, respectively), while no cases were observed among insufficiently active patients (p = 0.017). PA was positively associated with less fatigue (p= 0.002), more vigor (p = 0.001), more self-efficacy (p &lt; 0.001), and better quality of life (p = 0.002). Patients who were less physically active had more inflammation (CRP, p = 0.015; IL-6, p &lt;0.001; TNF-α: p = 0.033, and IL-1ra, p = 0.001). WC (β =-0.16, p = 0.008), glucose (β =-0.12, p &lt; 0.001) and fatigue (β = - 0.39, p &lt; 0.001) predicted general health perception (R 2 = 0.449). For physical functioning (high scores reflects performing PA without limitations due to health), WC (β = - 0.28, p = 0.001), sleep (β = - 1.50, p = 0.003) and fatigue (β = - 0.32, p = 0.018) were significant predictors (R 2 = 0.422); while age (β = 0.36, p &lt;0.001) physical activity (β = 0.051, p = 0.055), sleep (β = 0.50, p =0.046), fatigue (β = -0.37, p &lt;0.001) and depression (β = -1.12, p &lt;0.001) predicted emotional well-being (R 2 = 0.696). Conclusion: Physically active heart failure patients had a better anthropometric profile and lower prevalence of T2DM. In this cohort, PA was not a significant predictor for general and physical functioning, but it remained relevant for predicting emotional well-being.
Origins, Admixture Dynamics, and Homogenization of the African Gene Pool in the Americas
Authors: Mateus H Gouveia, Victor Borda, Thiago P Leal, Rennan G Moreira, Andrew W Bergen, Fernanda S G Kehdy, Isabela Alvim, Marla M Aquino, Gilderlanio S Araujo, Nathalia M Araujo, Vinicius Furlan, Raquel Liboredo, Moara Machado, Wagner C S Magalhaes, Lucas A Michelin, Maíra R Rodrigues, Fernanda Rodrigues-Soares, Hanaisa P Sant Anna, Meddly L Santolalla, Marília O Scliar, Giordano Soares-Souza, Roxana Zamudio, Camila Zolini, Maria Catira Bortolini, Michael Dean, Robert H Gilman, Heinner Guio, Jorge Rocha, Alexandre C Pereira, Mauricio L Barreto, Bernardo L Horta, Maria F Lima-Costa, Sam M Mbulaiteye, Stephen J Chanock, Sarah A Tishkoff, Meredith Yeager, Eduardo Tarazona-Santos
Journal: Molecular Biology and Evolution (2020)

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.
CALGB 150002: Correlation of HER2 and chromosome 17 (ch17) copy number with trastuzumab (T) efficacy in CALGB 9840, paclitaxel (P) with or without T in HER2+ and HER2- metastatic breast cancer (MBC)
Authors: P. A. Kaufman, G. Broadwater, K. Lezon-Geyda, L. G. Dressler, D. Berry, P. Friedman, E. P. Winer, C. Hudis, M. J. Ellis, A. D. Seidman, L. N. Harris
Journal: Journal of Clinical Oncology (2007)

1009 Background: Accurate assessment of HER-2 is critical in MBC and predicts benefit from T. We have previously shown low level amplification of HER-2 associated with ch17 polysomy is common in IHC 2+ cases that are FISH(-). However, the clinical relevance of this is unknown. Methods: CALGB 150002, a correlative companion to 9840, was designed to assess the predictive role of HER-2 in MBC pts treated with weekly vs q 3W P ± T. Pts HER-2(-) locally were randomized to ±T. 585 pts were enrolled in 9840; 304 blocks were available for central analysis with DAKO HercepTest (IHC) and Pathvysion (FISH). Logistic regression was used to test HER-2:ch17 ratio and HER-2 copy # as predictor of response rate (RR) to T in HER-2(+) pts. 1-sided Fisher’s Exact Test was used to compare RR of P vs P+T in pts with ch17 polysomy on central testing (&gt;2.2 copies ch17/cell), but defined as HER-2(-) locally and randomized to T. Results: In pts HER-2(+) locally, FISH is a significant predictor of RR to P+T. A higher HER-2:ch17 ratio is associated with a higher RR by logistic regression (p=0.033, n=95). No interaction is seen between HER-2 and P schedule, p=0.71. On central testing of cases IHC(-) locally, 16/140 (11%) were IHC 3+ and 5/133 (4%) HER-2 amplified. In 21 HER-2(-) cases reclassified as HER-2 3+ or FISH (+) centrally, we do not find a difference in RR to P vs P+T. However among 133 cases HER-2(-) locally and central FISH(-) we find 32 with ch17 polysomy (copy # ch17 = 2.2); 12 treated with P alone, and 19 with P+T (see table for RR). Conclusions: These data suggest a higher RR to P+T in HER-2(+) pts with a higher HER-2:ch17 ratio, consistent with a relationship between RR to T and HER-2 copy #. In FISH(-) cases we note an increased RR to P+T vs P in cases with ch17 polysomy, typically reported clinically as HER-2(-). This analysis suggests that T might be effective in a subpopulation of breast cancer conventionally defined as HER-2(-), but in fact displaying low level HER-2 amplification. [Table: see text] [Table: see text]
Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma
Authors: Dongrui Wang, Renate Starr, Wen-Chung Chang, Brenda Aguilar, Darya Alizadeh, Sarah L. Wright, Xin Yang, Alfonso Brito, Aniee Sarkissian, Julie R. Ostberg, Li Li, Yanhong Shi, Margarita Gutova, Karen Aboody, Behnam Badie, Stephen J. Forman, Michael E. Barish, Christine E. Brown
Journal: Science Translational Medicine (2020)

CAR T cells using chlorotoxin as the tumor-targeting domain recognize and kill glioblastoma with high specificity and potency.
Trastuzumab with taxanes in HER2-ECD(+), IHC/CISH(-) advanced and heavily pretreated, chemotherapy-refractory breast cancer patients: Findings from a case series
Authors: A. Ardavanis, P. Kountourakis, S. Malliou, F. Kyriakou, S. Koumna, E. Kardara, A. Garoufalli, I. Yioti, G. Rigatos
Journal: Journal of Clinical Oncology (2007)

1089 Background: The “invisible” potential of a tumor is responsible for the discrepancy sometimes observed between favourable initial pathological profile and aggressive clinical course. We describe a series of Breast Cancer patients with refractory to standard chemotherapy advanced tumors without HER2-amplification/overexpression treated with trastuzumab (TZB). Methods: Twenty five patients progressing under anthracyclines and taxanes were selected on the basis of increased HER2-ECD levels at entry (&gt;16 ng/ml) and lack of HER2-amplification/overexpression in the primary tumor documentation. In 22/25, TZB 6 mg/m 2 with either docetaxel 75 mg/m 2 q3w or paclitaxel 90 mg/m 2 weekly were administered for six courses or less if toxicicity or progression was documented; TZB alone had to be continued thereafter until progression. Serial HER2-ECD were performed during therapy. Results: No objective response was noted; however, in 5 and 11 pts minor response and stabilization respectively was noted. All minor responders and stabilized patients experienced subjective improvement. Toxicity was acceptable. Median time to progression has not yet been reached, actually 5+mos; in 9 patients the progression-free period is 12 months from start of therapy. Median HER2-ECD declined from 54ng/ml at baseline to 14.3ng/ml at 28 weeks from treatment start. Conclusion: Although the sample size of this case-series is small, our findings suggest that, in HER2 negative patients with clinical aggressive behaviour and refractoriness to standard chemotherapy, HER2 positivity should be assessed by serum ECD levels and the addition of trastuzumab may be a valuable therapeutic option. However, these findings should be confirmed in larger number of patients. No significant financial relationships to disclose.
Abstract 15187: Better Treatment Response for Patients Receiving an Initial ICD for Secondary Prevention in the Patient and Partner Randomized Trial
Authors: Jonathan P Auld, Elaine A Thompson, Cynthia M Dougherty
Journal: Circulation (2019)

Background: The P+P is a patient and partner-focused behavioral intervention with demonstrated efficacy to improve outcomes following an initial implantable cardioverter defibrillator (ICD). Little...
Inhibition of PU.1 ameliorates metabolic dysfunction and non-alcoholic steatohepatitis
Authors: Qiongming Liu, Junjie Yu, Liheng Wang, Yuliang Tang, Quan Zhou, Shuhui Ji, Yi Wang, Luis Santos, Rebecca A. Haeusler, Jianwen Que, Prashant Rajbhandari, Xiaoguang Lei, Luca Valenti, Utpal B. Pajvani, Jun Qin, Li Qiang
Journal: Journal of Hepatology (2020)
Abstract MP20: Evening Chronotype is Associated With Poor Cardiovascular Health and Adverse Health Behaviors in a Diverse Population of Women
Authors: Nour Makarem, Jacob Paul, Elsa-Grace Giardina, MING LIAO, Brooke Aggarwal
Journal: Circulation (2020)

Background: Chronotype is the behavioral manifestation of an individual’s innate circadian rhythm. Evening chronotype (i.e. being a “night owl”) is linked to elevated chronic disease and mortality risk in European and Asian populations. Evidence from US cohorts is limited, particularly among women, in whom evening chronotype prevalence becomes higher from midlife onward, coinciding with life stages and hormonal changes associated with higher cardiovascular disease (CVD) risk. Hypothesis: Being a definite evening chronotype would be associated with poor cardiovascular health (CVH) and elevated cardiometabolic risk factors. Methods: Participants were 506 diverse women (mean age=37±16y, 62% racial/ethnic minority) in the AHA Go Red for Women Strategically Focused Research Network at Columbia University. Chronotype was measured using the Morningness-Eveningness Questionnaire (MEQ), the most widely used validated tool by circadian biologists to ascertain chronotype. Higher scores reflected greater morningness. Participants were also categorized as “evening” vs. “intermediate/morning” chronotypes based on their MEQ scores. Health behaviors (diet, physical activity, sleep, and sedentary time) were assessed using validated questionnaires. Health factors (BMI, blood pressure, fasting glucose, and cholesterol) were assessed at the clinic visit. Overall CVH was evaluated using the AHA Life’s Simple 7 (LS7) score (0-8: poor, 9-14: moderate to high). Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopause were used to examine associations of chronotype with CVH, clinical risk factors, and health behaviors. Results: Overall, 13% of women identified as being evening chronotypes. Higher MEQ scores (i.e. greater morningness) were associated with higher AHA LS7 scores (β=0.02, p=0.01), indicative of more favorable CVH. Higher MEQ scores were also associated with having a lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β=-0.07, p&lt;0.0001), a lower Insomnia Severity Index (β=-0.14, p&lt;0.0001), shorter time to fall asleep (β=-0.28, p=0.04), and less sedentary time (β=-0.11, p=0.001). In contrast, being an evening chronotype was associated with higher odds of poor CVH (OR (95%CI): 2.41 (1.20-4.85)), not meeting AHA diet (OR (95%CI): 2.89 (1.59-5.23)) and physical activity guidelines, (OR (95%CI): 1.78 (1.03-3.07)), and having short sleep (&lt;7h) (OR (95%CI): 2.15 (1.24-3.73)) or insomnia symptoms (OR (95%CI): 2.69 (1.53-4.75)). Conclusions: Women with evening chronotypes have greater odds of having poor CVH and adverse health behaviors after adjustment for sociodemographic factors and menopausal status. Chronotype may be important to consider and target in lifestyle interventions aimed at CVD prevention, particularly among middle-aged and older women who are prone to sleep changes.
The construction of in vitro nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration
Authors: Xiaotong Yang, Xianchun Chen, Ting Lei, Lin Qin, Yang Zhou, Chuan Hu, Qingfeng Liu, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2020)

In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an in vitro nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by up-regulated expression of Sialyl Lewis A antigen (SLAA) and integrin β1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. In vivo, the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect in vivo, the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-γ, IL-2 and secretory IgA (sIgA) compared with [email protected] group. Collectively, the study constructed in vitro M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.
Screening Tool Identifies Older Adults With Cancer at Risk for Poor Outcomes
Authors: Ryan D. Nipp, Leah L. Thompson, Brandon Temel, Charn-Xin Fuh, Christine Server, Paul S. Kay, Sophia Landay, Daniel E. Lage, Lara Traeger, Erin Scott, Vicki A. Jackson, Nora K. Horick, Joseph A. Greer, Areej El-Jawahri, Jennifer S. Temel
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Oncologists often struggle with managing the complex issues unique to older adults with cancer, and research is needed to identify patients at risk for poor outcomes. Methods: This study enrolled patients aged ≥70 years within 8 weeks of a diagnosis of incurable gastrointestinal cancer. Patient-reported surveys were used to assess vulnerability (Vulnerable Elders Survey [scores ≥3 indicate a positive screen for vulnerability]), quality of life (QoL; EORTC Quality of Life of Cancer Patients questionnaire [higher scores indicate better QoL]), and symptoms (Edmonton Symptom Assessment System [ESAS; higher scores indicate greater symptom burden] and Geriatric Depression Scale [higher scores indicate greater depression symptoms]). Unplanned hospital visits within 90 days of enrollment and overall survival were evaluated. We used regression models to examine associations among vulnerability, QoL, symptom burden, hospitalizations, and overall survival. Results: Of 132 patients approached, 102 (77.3%) were enrolled (mean [M] ± SD age, 77.25 ± 5.75 years). Nearly half (45.1%) screened positive for vulnerability, and these patients were older (M, 79.45 vs 75.44 years; P =.001) and had more comorbid conditions (M, 2.13 vs 1.34; P =.017) compared with nonvulnerable patients. Vulnerable patients reported worse QoL across all domains (global QoL: M, 53.26 vs 66.82; P =.041; physical QoL: M, 58.95 vs 88.24; P &lt;.001; role QoL: M, 53.99 vs 82.12; P =.001; emotional QoL: M, 73.19 vs 85.76; P =.007; cognitive QoL: M, 79.35 vs 92.73; P =.011; social QoL: M, 59.42 vs 82.42; P &lt;.001), higher symptom burden (ESAS total: M, 31.05 vs 15.00; P &lt;.001), and worse depression score (M, 4.74 vs 2.25; P &lt;.001). Vulnerable patients had a higher risk of unplanned hospitalizations (hazard ratio, 2.38; 95% CI, 1.08–5.27; P =.032) and worse overall survival (hazard ratio, 2.26; 95% CI, 1.14–4.48; P =.020). Conclusions: Older adults with cancer who screen positive as vulnerable experience a higher symptom burden, greater healthcare use, and worse survival. Screening tools to identify vulnerable patients should be integrated into practice to guide clinical care.