tbuckley/cabot-search huggingface dataset:
Abstract P097: Association Of Non-appetitive Eating With Hypertension In Women: Mediation By Body Mass Index
Authors: Anna K Poon, Alison Field, Karen Mitchell, Ashley Gearhardt, Benita Jackson, Eric Rimm, Janet W Rich-Edwards
Journal: Circulation (2021)

Introduction: Although non-appetitive eating phenotypes are associated with body mass index, the extent to which they are associated with hypertension is unknown. Hypothesis: We hypothesize that non-appetitive eating phenotypes are associated with hypertension. Methods: We examined participants in a substudy on disordered eating conducted in 2013-2015, nested within the prospective cohort, Nurses’ Health Study 2. Non-appetitive eating was defined by: 1) binge eating with loss of control; 2) disinhibited eating; 3) coping-motivated eating; and 4) food addiction. Prevalent hypertension was defined by self-reported clinician diagnosis. Odds ratios and 95% confidence intervals (OR, 95% CI) were used to estimate the association of non-appetitive eating with prevalent hypertension, adjusted for age and race. The difference method was used to estimate the proportion of the associations mediated by body mass index. Results: After excluding missing exposure (n=421), the analytic sample included n=4,687 women (of n=5,108 women). Average age was 60 years (range: 49 to 68); 18% (n=824) reported binge eating with loss of control; average disinhibited eating score was 3 (range: 0 to 7); average coping-motivated eating score was 2 (range: 1 to 5); and 7% (n=349) reported food addiction. Non-appetitive eating was associated with higher odds of hypertension. Binge eating with loss of control was associated with 60% higher odds (95% CI: 1.37, 1.87) of hypertension. Per unit, disinhibited eating was associated with 18% (95% CI: 1.14, 1.21) and coping-motivated eating was associated with 38% (95% CI: 1.29, 1.47) higher odds of hypertension. Food addiction (yes versus no) was associated with a 108% higher odds (95% CI: 1.67, 2.60) of hypertension. Body mass index mediated more than 85% of the associations of each non-appetitive eating phenotype with hypertension. Conclusions: Non-appetitive eating is associated with hypertension. Body mass index explained almost all of the associations between non-appetitive eating and hypertension. Prospective studies are needed to confirm the direction of the associations.
Long covid: coding is caring
Authors: Nikhil Mayor, Ruby Tsang, Mark Joy, FD Richard Hobbs, Simon de Lusignan
Journal: BMJ (2021)

Research, 24 April

Sivan and colleagues1 and Ayoubkhani and colleagues2 describe the scale of adverse health outcomes for people admitted to hospital with covid-19. We agree that key questions of this complex, heterogeneous patient group are yet to be answered—such as whether particular symptom clusters exist, the impact on disparities, and whether young, fit people are disproportionately affected.3

For our health system to rise to the challenge of long covid we need …
SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity
Authors: Muthukumar Ramanathan, Ian D Ferguson, Weili Miao, Paul A Khavari
Journal: The Lancet Infectious Diseases (2021)

virions required for cell entry and is a convergent feature in more transmissible SARS-CoV-2 variants arising in multiple geographical regions.Finally, characterisation of binding between variant spike proteins and cognate human receptor ACE2 on the basis of microscale thermophoresis represents a potential surveillance strategy for predicting enhanced transmissibility of emerging SARS-CoV-2 variants harbouring novel spike mutations.
Tip60 activates Hoxa9 and Meis1 expression through acetylation of H2A.Z, promoting MLL-AF10 and MLL-ENL acute myeloid leukemia
Authors: Kazutsune Yamagata, Mika Shino, Yukiko Aikawa, Shuhei Fujita, Issay Kitabayashi
Journal: Leukemia (2021)
Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis
Authors: Cheng-Chi Chang, Min-Liang Kuo, Jen-Liang Su, Szu-Ta Chen
Journal: Cancer Research (2004)

4908  Background: Advanced cancer cells show higher invasive and metastatic abilities. Several members of CCN [CTGF (connective tissue growth factor), Cyr61 (cysteine-rich 61), Nov (nephroblastoma overexpressed)] family can modulate the invasive phenotype of human carcinoma. CTGF is highly expressed in normal lung cells. We investigated the possibility that CTGF may regulate lung adenocarcinoma invasion and metastasis. Methods: We compared vector control and CTGF gene transfected cells for invasive activity in vitro as well as metastatic ability in an animal model. We also used CTGF deletion mutants and antisense oligonucleotides to confirm the downstream effecter. Further, CTGF expression in 78 lung adenocarcinoma specimens was determined by immunohistochemistry. All statistical tests were two-sided. Results: Overexpression of CTGF in CL1-5 and A549 cells decreased invasiveness (all P
Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways
Authors: Won Jin Ho, Rossin Erbe, Ludmila Danilova, Zaw Phyo, Emma Bigelow, Genevieve Stein-O’Brien, Dwayne L. Thomas, Soren Charmsaz, Nicole Gross, Skylar Woolman, Kayla Cruz, Rebecca M. Munday, Neeha Zaidi, Todd D. Armstrong, Marcelo B. Sztein, Mark Yarchoan, Elizabeth D. Thompson, Elizabeth M. Jaffee, Elana J. Fertig
Journal: Genome biology (2021)

Abstract Background The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung are the most common sites of PDAC metastasis, and each have been differentially associated with prognoses and responses to systemic therapies. A deeper understanding of the molecular and cellular landscape within the tumor microenvironment (TME) metastasis at these different sites is critical to informing future therapeutic strategies against metastatic PDAC. Results By leveraging combined mass cytometry, immunohistochemistry, and RNA sequencing, we identify key regulatory pathways that distinguish the liver and lung TMEs in a preclinical mouse model of metastatic PDAC. We demonstrate that the lung TME generally exhibits higher levels of immune infiltration, immune activation, and pro-immune signaling pathways, whereas multiple immune-suppressive pathways are emphasized in the liver TME. We then perform further validation of these preclinical findings in paired human lung and liver metastatic samples using immunohistochemistry from PDAC rapid autopsy specimens. Finally, in silico validation with transfer learning between our mouse model and TCGA datasets further demonstrates that many of the site-associated features are detectable even in the context of different primary tumors. Conclusions Determining the distinctive immune-suppressive features in multiple liver and lung TME datasets provides further insight into the tissue specificity of molecular and cellular pathways, suggesting a potential mechanism underlying the discordant clinical responses that are often observed in metastatic diseases.
Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis
Authors: Hanan A. Al-Nazal, Emily Cooper, Mei Fong Ho, Sharareh Eskandari, Victoria Majam, Ashwini Kumar Giddam, Waleed M. Hussein, Md. Tanjir Islam, Mariusz Skwarczynski, Istvan Toth, Sanjai Kumar, Ali Zaid, Michael Batzloff, Danielle I. Stanisic, Michael F. Good
Journal: Cell Host & Microbe (2021)
Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia with t(6;9)(p23;q34);dek-NUP214 Is Followed By a Low Relapse Risk and Favorable Outcome in Early Phase- a Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Marina Diaz Beya, Myriam Labopin, Johan Maertens, Alijurf Mahmoud, Alois Gratwohl, Dietrich W Beelen, Harry C. Schouten, Gérard Socié, Antonius Vmb Schattenberg, Rainer Schwerdtfeger, Liisa Volin, Mauricette Michallet, Emmanuelle Polge, Mohamad Mohty, Jordi Esteve, Arnon Nagler
Journal: Blood (2017)
Abstract 16948: A Comprehensive and High Accurate Pipeline for Mouse Retinal Vasculature Characterization
Authors: Xuelin Wang, Shumin Wang, Guofu Zhu, Jordan Rhen, Jinjiang Pang, Zhengwu Zhang
Journal: Circulation (2020)

Rationale: Vascular morphological features reflect the vessel biological functions and analysis of these features is critical for understanding physiological and pathological process of vascular development and vascular diseases. Mouse retinal vasculature is a well-recognized and commonly used animal model for angiogenesis and microvascular remodeling. Thus, a powerful tool to analyze morphological changes of retinal vasculature is in urgent need. Objective: Develop a comprehensive and high accurate pipeline to analyze morphological changes of mouse retinal vasculature. Methods and Results: Retinas from postnatal mice at P2-P7 are harvested and retinal vasculatures are visualized by isolectin B4 whole mount staining. A comprehensive software, Vessel Tech, is developed to perform vessel segmentation, network reconstruction and analysis. Vessel Tech relies on recent advancements in the convolutional neural network and techniques from network data analysis to provide high accuracy vascular identification and comprehensive vascular morphological feature extraction. Compared with existing blood vessel analysis softwares, Vessel Tech shows great improvement in accuracy. Based on the reconstructed vessel network, various metrics of angiogenesis and micro-remodeling are extracted and statistically analyzed. Conclusions: We generated and verified a novel pipeline, named “Vessel Tech”, which could automatically process retinal vascular images, reconstruct vessel network with high accuracy and assay global and local vascular characteristics. The development of Vessel Tech provides a powerful tool to precisely study the physiological and pathological variations during vascular development and vascular diseases.
Abstract P165: Hypertension, Dietary And Exercise Habits In Pregnancy - A Case Control Study
Authors: Lara C Kovell, Angela Essa, Claire V Meyerovitz, Sarah Ferreira, Leslie Panella, Sheikh Moinul, Benjamin Maxner, Stephen P Juraschek
Journal: Circulation (2021)

Background: Hypertension (HTN) in pregnancy is increasing in the United States and is implicated in nearly 40% of maternal deaths. While national guidelines recommend the Dietary Approaches to Stop Hypertension (DASH) diet for all women with HTN, adherence to DASH dietary habits in pregnant women with HTN is unknown. Objective: We determined the differences in diet and exercise habits in pregnant women with HTN compared to pregnant women with normal blood pressure (BP). Methods: Pregnant women with HTN and normal BP were recruited at 24-32 weeks gestation. HTN was defined by a provider diagnosis prior to 20 weeks gestation or BP ≥140/90 mm Hg at the time of recruitment. The normal BP group had systolic BP &lt;120 mm Hg. Dietary intake was characterized using the Block Sodium and Fruit-Vegetable-Fiber surveys. The Pregnancy Physical Activity Questionnaire was used to determine the type, duration, and intensity of physical activity. Differences across hypertension status were compared using Chi-square Student's t-tests. Results: The mean age of the HTN group was 33.8 years and 31.3% were Black, while the mean age of the normal BP group was 30.4 years and 6.5% were Black. The HTN group reported lower sodium intake (HTN = 2,366 mg/day, normal BP = 3,221 mg/day; p &lt; 0.01). However, the HTN and normal BP groups reported similar fruit, vegetable, fiber, magnesium, and potassium intake (Table). There were no significant differences in light, moderate, or vigorous activity between groups. Conclusions: While pregnant women with HTN reported lower sodium intake, they consumed similar amounts of fruit, vegetable, fiber, magnesium, and potassium compared to women with normal BP. Future work should identify barriers to healthy lifestyle habits to improve the implementation of evidence-based dietary strategies for BP control in pregnant women.
Abstract 15778: The Impact of Health Insurance Status on Heart Transplant Recipients
Authors: Mehreen Iqbal, Yulin Zhang, Selena Gonzales, John Dykes, Christopher S Almond
Journal: Circulation (2020)

Introduction: Gaps in insurance coverage have been associated with diminished access to health care for children with chronic illness. Continuity of coverage is associated with improved long-term clinical outcomes among adolescent heart transplant (HT) recipients, but the relationship between insurance status and post-transplant outcomes has not been described across all pediatric HT recipients. Hypothesis: HT recipients with changes in insurance status will have worse outcomes as opposed to those with continuous coverage. Methods: We queried the United Network for Organ Sharing (UNOS) registry for patients age 0-18 receiving isolated HT or heart re-transplant between 2006 and 2019 and included them in the analysis if they survived at least one year post-transplant. Patients were categorized by insurance coverage at wait listing, HT, and one year follow-up. Cox proportional hazards models were used to characterize the association between coverage pattern and long-term patient survival. Results: Among the 3,247 patients in the analysis, insurance coverage patterns included continuous private (37%), continuous public (46%), gain of private (6%), and loss of private (11%). Patients who had continuous public insurance were more likely to be Black or Hispanic, adolescent, and require ICU care. In a multivariate Cox model, continuous public insurance was associated with increased mortality risk (HR = 1.46, P = 0.014), while loss of private insurance trended towards increased risk (HR = 1.14, P = 0.014). Figure 1 illustrates Kaplan-Meier conditional survival curves according to insurance trajectory. Multivariate sub-group analysis by Black race demonstrated no differences in outcomes by coverage pattern. Conclusions: In comparison to those with continuous private insurance, having continuous public insurance is associated with higher risk of adverse outcomes in pediatric HT recipients, but it does not account for disparate outcomes in Black patients.
Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells
Authors: Bo Wang, Shoichi Iriguchi, Masazumi Waseda, Norihiro Ueda, Tatsuki Ueda, Huaigeng Xu, Atsutaka Minagawa, Akihiro Ishikawa, Hisashi Yano, Tomoko Ishi, Ryoji Ito, Motohito Goto, Riichi Takahashi, Yasushi Uemura, Akitsu Hotta, Shin Kaneko
Journal: Nature Biomedical Engineering (2021)
Joint association between accelerometry-measured daily combination of time spent in physical activity, sedentary behaviour and sleep and all-cause mortality: a pooled analysis of six prospective cohorts using compositional analysis
Authors: Sebastien Chastin, Duncan McGregor, Javier Palarea-Albaladejo, Keith M Diaz, Maria Hagströmer, Pedro Curi Hallal, Vincent T van Hees, Steven Hooker, Virginia J Howard, I-Min Lee, Philip von Rosen, Séverine Sabia, Eric J Shiroma, Manasa S Yerramalla, Philippa Dall
Journal: British Journal of Sports Medicine (2021)

Objective To examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality. Methods Federated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis. Participants 130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden. Main outcome All-cause mortality (follow-up 4.3–14.5 years). Results Studies using wrist and hip accelerometer provided statistically different results (I 2 =92.2%, Q-test p&lt;0.001). There was no association between duration of sleep and all-cause mortality, HR=0.96 (95% CI 0.67 to 1.12). The proportion of time spent in moderate to vigorous physical activity was significantly associated with lower risk of all-cause mortality (HR=0.63 (95% CI 0.55 to 0.71) wrist; HR=0.93 (95% CI 0.87 to 0.98) hip). A significant association for the ratio of time spent in light physical activity and sedentary time was only found in hip accelerometer-based studies (HR=0.5, 95% CI 0.42 to 0.62). In studies based on hip accelerometer, the association between moderate to vigorous physical activity and mortality was modified by the balance of time spent in light physical activity and sedentary time. Conclusion This federated analysis shows a joint dose–response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour.
Abstract 14858: Conditional Deletion of Lysyl Oxidase Improves Vascular Function in Apoe <sup>-/-</sup> Mice
Authors: Filipe F Stoyell Conti, Diana Hernandez, Miguel Rojas, Laisel Martinez, Roberto I Vazquez-Padron
Journal: Circulation (2020)

Introduction: Lysyl oxidase (LOX) is a copper-dependent amino-oxidase that initiates covalent cross-linking of collagen and elastin, modifies growth factor action and controls gene expression. LOX upregulation is associated with cardiovascular diseases. Because embryonic LOX knockout (KO) mice die perinatally of aortic aneurysms and cardiovascular dysfunction, the studies about LOX function in cardiovascular disease has relied mostly on the use of beta-aminopropionitrile. However, this irreversible inhibitor also inhibits other members of LOX family. Hypothesis: To overcome this limitation, we hypothesized that conditional inactivation of lysyl oxidase would improve vascular function in apoE -/- mice. Methods: We developed, for the first time, a global (LOX f/f CAG-CreERT2 ApoE -/- ) and a smooth muscle cell (SMC) specific (LOX f/f Myh11-CreERT2 ApoE -/- ) LOX conditional knockout mice. Results: LOX inactivation in SMC decreased immature collagen crosslinking in the aorta, carotid pulse wave velocity and blood pressure. It led to a significant reduction in atherosclerotic plaque deposition in the aorta after 16 weeks of high-fat diet (HFD). Global inactivation of LOX, on the other hand, also reduced the systolic blood pressure and prevented vascular stiffness after 4 weeks of HFD. In in-vitro studies, we found that LOX is present in the extracellular space and the nucleus of SMC. Bulk RNA-seq revealed that LOX deletion elevated the expression of SMC alpha-actin, transgelin, and filamin A genes, which are typically present in the contractile phenotype. Conclusion: Our data show that conditional deletion of LOX is atheroprotective and improved vascular and hemodynamic function in ApoE KO mice.
Abstract 15260: Higher Levels of Osteoblast-lineage Cells Are Associated With Cardiac Allograft Vasculopathy Progression
Authors: Ilke Ozcan, Takumi Toya, Michel Corban, Ali Ahmad, Darrell Loeffler, Hunter Ostlie, Sudhir Kushwaha, Lilach O Lerman, Amir LERMAN
Journal: Circulation (2020)

Introduction: Cardiac allograft vasculopathy (CAV) is a major determinant of long term graft survival. Endothelial progenitor cells (EPC) expressing osteocalcin (OC) have been linked to atherosclerosis. However, little is known regarding bone-forming osteoblast-lineage (OL) cells, and their role in atherosclerosis and CAV. Methods: Heart transplant patients undergoing serial Intravascular Ultrasound (IVUS) and progenitor cell studies were included in the study. OL cells, defined as cells positive for alkaline phosphatase (AP) and OC, were counted using flow cytometry on the day of baseline IVUS. A follow up IVUS was done 3 years later. Gray-scale and virtual-histology IVUS were used to evaluate vessel size, plaque burden, and plaque composition (fibrous, fibrofatty, necrotic core, calcified). Patients were divided into two groups by the median change (Δ) in necrotic core volume and plaque volume over 3 years. Results: A total of 55 patients (mean age 52±15 years, 65% males) were included. At baseline, median time after transplant was 4.2 years. Average vessel area at baseline and three years were 15.8 ±4.6 and 15.3 ±5.4 mm2, respectively (p=0.32). However, 24/55 patients (44%) had positive remodeling. The number of OL cells was positively correlated with Δvessel (r=0.36, p=0.01) and Δlumen areas. (r=0.30, p=0.02). Patients with greater Δplaque volume and Δnecrotic core volume had higher OL cell levels compared to those with below medians (Δplaque volume: 95 [30,348] vs. 30 [10, 90] OL per 100,000 counts, p=0.01; Δnecrotic core volume: 95 [22.5, 320] vs. 30 [10, 90] OL per 100,000 counts, p=0.03) (Fig. 1A and 1B). Conclusions: The number of OL cells in heart transplant patients correlates with positive vascular remodeling, accompanied by increased lumen area over 3 months. Furthermore, patients with unstable plaque features had higher OL cells, suggesting a possible role in pathologic plaque progression.
Dual Targeting of Chromatin Stability By The Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Shows Significant Preclinical Efficacy in Neuroblastoma
Authors: Lin Xiao, Klaartje Somers, Jayne Murray, Ruby Pandher, Mawar Karsa, Emma Ronca, Angelika Bongers, Rachael Terry, Anahid Ehteda, Laura D. Gamble, Natalia Issaeva, Katerina I. Leonova, Aisling O'Connor, Chelsea Mayoh, Pooja Venkat, Hazel Quek, Jennifer Brand, Frances K. Kusuma, Jessica A. Pettitt, Erin Mosmann, Adam Kearns, Georgina Eden, Stephanie Alfred, Sophie Allan, Lei Zhai, Alvin Kamili, Andrew J. Gifford, Daniel R. Carter, Michelle J. Henderson, Jamie I. Fletcher, Glenn Marshall, Ricky W. Johnstone, Anthony J. Cesare, David S. Ziegler, Andrei V. Gudkov, Katerina V. Gurova, Murray D. Norris, Michelle Haber
Journal: Clinical Cancer Research (2021)

We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma.The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN-amplified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to examine histone eviction, heterochromatin transcription, and chromatin compaction.The combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137/panobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination.The combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. On the basis of its potential to boost IFN and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.