tbuckley/cabot-search huggingface dataset:
Association between population mean and distribution of deviance in demographic surveys from 65 countries: cross sectional study
Authors: Fahad Razak, SV Subramanian, Shohinee Sarma, Ichiro Kawachi, Lisa Berkman, George Davey Smith, Daniel J Corsi
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objectives</h3> To examine whether conditions related to scarcity at the left side of the distribution (anaemia, severe chronic energy deficiency, and underweight) are as strongly related to population means as conditions of excess at the right side of the distribution (overweight and obesity). <h3>Design</h3> Observational study. <h3>Setting</h3> 65 countries, with nationally representative cross sectional data from 1994 to 2014 obtained from the Demographic Health Surveys. <h3>Participants</h3> Non-pregnant women aged 20-49. Sample of 65 countries and n=524 380 for analysis of BMI; sample of 44 countries and n=316 465 for analysis of haemoglobin. <h3>Main outcome measures</h3> The association between mean and prevalence of each category. For BMI, prevalence of severe chronic energy deficiency (SCED, BMI &lt;16.0), underweight (BMI &lt;18.5), overweight (BMI &gt;25) and obese (BMI &gt;30.) were measured; for haemoglobin, prevalence of anaemia (haemoglobin &lt;12.0 g/dL) and severe anaemia (haemoglobin &lt;8.0 g/dL) were examined. <h3>Results</h3> There was a strong association between mean BMI and prevalence of overweight (r<sup>2</sup>=0.98; r=0.99; β=8.3 (8.0 to 8.6)) and obesity (r<sup>2</sup>=0.93; r=0.97; β=4.2 (3.9 to 4.5)). For left sided conditions, a moderate to strong association was found between mean BMI and prevalence of underweight (r<sup>2</sup>=0.67; r=−0.82; β=−2.7 (−3.1 to −2.2)), and a weaker association for SCED (r<sup>2</sup>=0.38; r=−0.61; β=−0.32 (−0.43 to −0.22)). There was a moderate association between mean haemoglobin and prevalence of anaemia (r<sup>2</sup>=0.46; r=−0.68; β=−10.8 (−14.5 to −7.1)) and a weaker association with severe anaemia (r<sup>2</sup>=0.30; r=-0.55; β=−0.55 (−0.81 to −0.29)). <h3>Conclusions</h3> The associations between population means and prevalence of conditions of scarcity such as low BMI and anaemia were substantially weaker than the associations of mean BMI with conditions of excesses such as overweight and obesity.
Abstract 14137: Phospholipase A2 Receptor 1 is Involved in Cardiac Fibrosis of Pressure-loaded Heart Through Modulation of Migratory Responses to Collagen in Myofibroblasts
Authors: Kazunori Watanabe, Yuki Fujihara, Hiroki Kishi, Kazuyuki Yamaguchi, Yosuke Watanabe, Kazuhiro Watanabe, Daisuke Fujioka, Kazuto Nakamura, Kenichi Kawabata, Kiyotaka Kugiyama
Journal: Circulation (2017)

Introduction: Phospholipase A2 receptor 1 (PLA2R) has multiple biological functions beyond a receptor for secretory PLA2s. PLA2R requires interaction with other transmembrane receptor to transmit intracellular signaling. This study was aimed to elucidate possible role of PLA2R in cardiac fibrosis in pressure-loaded heart using PLA2R-deficient (KO) mice and its molecular mechanisms. Methods and Results: Compared with PLA2R wild-type (WT) hearts, PLA2R KO hearts exhibited a 20% increase in LV end-diastolic diameter on echocardiography, a 31% decrease in myocardial fibrosis on Masson’s trichrome staining, and a 45% decrease in the number of α-SMA-positive fibroblasts in fibrous area 4 weeks after transverse aortic constriction (TAC). PLA2R was primarily found in myofibroblasts in the fibrous area of PLA2R WT hearts after TAC. The PLA2R KO myofibroblasts showed a 30% decrease in the integrin β1-mediated migratory response to collagen I, compared with PLA2R WT myofibroblasts. In surface plasmon resonance analy...
Abstract 4087: Investigating the novel role of Hippo signaling in mouse pancreas
Authors: Ming Gao, Jun Liu, Francis E. Sharkey, Howard C. Crawford, Randy L. Johnson, Yidong Chen, Pei Wang
Journal: Cancer Research (2018)

Abstract Background: Large tumor suppressor kinase 1 and 2 are the core kinases of the Hippo signaling pathway, and play critical roles in regulating cell growth and organ size during animal development. Inactivation of the Hippo signaling pathway has been demonstrated to initiate tumor development in certain organs. However, the function of Lats1&amp;2 in the pancreas is still elusive. Methods and results: To investigate the function of Lats1&amp;2 in the pancreas, we generated mice with adult pancreatic acinar cell-specific deletion of Lats1&amp;2 genes. Interestingly, instead of enlarging of the pancreas or pancreatic tumorigenesis, the deletion of Lats1&amp;2 genes in pancreatic acinar cells resulted in severe inflammation of the pancreas. To further examine the mechanisms, we took advantage of a Rosa26 reporter to trace individual Lats1&amp;2 null cells in vivo. We found that the loss of Lats1&amp;2 did not affect cell growth directly but activated pancreatic stellate cells. This was followed by immune cell infiltration and acinar-to-ductal metaplasia in Lats1&amp;2 null pancreas. Our RNA seq data revealed several cytokines and chemokine genes, such as ctgf, spp1, cxcl12, cxcl16, were gradually unregulated with time in Lats1&amp;2 null pancreas before immune cell infiltration. Finally, we revealed the phenotype of Lats1&amp;2 DKO mouse was in a YAP1/TAZ-dependent manner. Conclusion and significance: In our present study, our data suggested that deletion of the Lats1&amp;2 genes in acinar cells caused pancreatitis through activation of pancreatic stellate cells directly. Our study discovered a new mechanism of the inflammatory response initiated by pancreatic epithelial cells and regulated by the Hippo signaling pathway, which is likely to be useful for the identification of new strategies for controlling pancreatic inflammation and prevention of pancreatic cancer. Citation Format: Ming Gao, Jun Liu, Francis E. Sharkey, Howard C. Crawford, Randy L. Johnson, Yidong Chen, Pei Wang. Investigating the novel role of Hippo signaling in mouse pancreas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4087.
Abstract 2364: The phosphatase PRL-3 is a pro-survival oncogene in acute lymphoblastic leukemia
Authors: Min Wei, Kristin O'Leary, Jinpeng Liu, Chi Wang, Jessica Blackburn
Journal: Cancer Research (2018)

Abstract PRL-3, phosphatase of regenerating liver 3, is one member of a subfamily of protein tyrosine phosphatases that belongs to the dual-specificity phosphatases (DSPs). Accumulating evidence shows that PRL-3 is a biomarker of tumor progression and metastasis and high PRL-3 expression is associated with reduced overall and disease-free survival in a variety of solid tumors, suggesting it's importance in tumor recurrence. However, the role for PRL-3 in leukemia relapse has not yet been described. We have found that PRL-3 contributes to Acute Lymphoblastic Leukemia (ALL) malignancy by acting as a pro-survival gene, both in vitro and in vivo. Expression of PRL-3 in a MYC-induced zebrafish T-cell ALL model showed that PRL-3 expressing ALL had shorter latency and higher penetrance, compared with the fish injected with rag2:Myc; rag2:GFP alone. Growth after transplantation at low cell number was also significantly faster in the PRL3 expressing T-ALL, suggesting that PRL-3 plays an important role in ALL development and progression. We found PRL-3 to be highly expressed in a majority of human ALL compared to normal peripheral blood mononuclear cells (PBMNC), which suggests clinical relevance. Analysis of gene expression microarray data of 119 patient samples reveals that PRL-3 was highly expressed in 58% of the patients. In addition, PRL-3 had the highest expression in the most aggressive and treatment resistant subgroups of T-ALL, the TAL/LMO and Immature subtypes. PRL-3 is also expressed by human T-ALL cell lines using quantitative RT- PCR and immunoblotting. PRL-3 knockdown leads to significant apoptosis in T-ALL cells. The treatment of T-ALL cells using small molecule drugs including 2-cyano-2-ene-ester compound (Analog 3) and thieno [3,2-b] pyridine 1-oxide (thienopyridone) , also resulted in significant growth inhibition of T-ALL cells in part through &amp;gt;4-fold increase in apoptosis, measured by annexin V staining. In summary, our study provides evidence for a role of PRL-3 in T- ALL malignancy, and suggests that PRL3 may be a useful drug target in the treatment of this disease. Our future studies are focused on identifying the mechanisms by which PRL3 promotes T-ALL progression and survival. Citation Format: Min Wei, Kristin O'Leary, Jinpeng Liu, Chi Wang, Jessica Blackburn. The phosphatase PRL-3 is a pro-survival oncogene in acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2364.
Abstract 2728: Circulating levels of Resokine, a soluble modulator of the immune system, are upregulated in both experimental cancer models and in patients across multiple tumor types
Authors: Ryan Adams, Elisabeth Mertsching, Leslie Nangle, Kathy Ogilvie, Steven Crampton, John Bruner, Samantha Tyler, Sanna Rosengren, Andrea Cubitt, David King, John Mendlein
Journal: Cancer Research (2018)

Abstract Resokine is a newly identified regulator of immune cell activity, and circulating levels of Resokine in normal individuals may represent a soluble set-point control to modulate T cell activity. Resokine activity is a non-canonical function arising from the tRNA synthetase gene family, and the activity is effected by a 60 amino acid N-terminal domain arising from the gene for histidyl-tRNA synthetase which is present in the full-length protein as well as multiple splice variants that have lost their original tRNA synthetase functionality. Resokine is secreted from cells, including tumor cell lines, and in vitro studies have demonstrated that Resokine can inhibit the activation of immune cells. In vitro, for example, Resokine addition during T cell activation induced by antibodies to CD3 and CD28, can result in reduced levels of inflammatory cytokines such as IL-2, interferon gamma, and TNF alpha; inhibition of the up-regulation of cell-surface activation markers, such as CD69, CD40L and 4-1BB; and inhibition of release of the cytotoxic mediator granzyme B. We have tested levels of circulating Resokine in both mice with syngeneic tumors as well as &amp;gt;300 cancer patients across multiple tumor types. In normal C57Bl6 mice serum levels of Resokine ranged from 70-250pM (n=10) whereas in mice bearing B16F10 tumors, levels were significantly higher (450-3000pM, p&amp;lt;0.001) and correlated with tumor size. Resokine levels in normal human volunteers exhibit a more variable range, from 8pM to &amp;gt;2333pM (n=148), with 18% of individuals having levels &amp;lt;30pM, which was set as the active threshold level based on the concentration required to inhibit T cell activation in vitro. In contrast, samples across &amp;gt;300 cancer patients with different tumor types, exhibited higher circulating levels with only 4% of individuals having levels below the activity threshold of 30pM. This data is consistent with the hypothesis that tumors secrete Resokine as an additional mechanism to down-regulate immune activity, and suggests further investigation of the utility of Resokine levels as a new biomarker of immune activity in patients. Citation Format: Ryan Adams, Elisabeth Mertsching, Leslie Nangle, Kathy Ogilvie, Steven Crampton, John Bruner, Samantha Tyler, Sanna Rosengren, Andrea Cubitt, David King, John Mendlein. Circulating levels of Resokine, a soluble modulator of the immune system, are upregulated in both experimental cancer models and in patients across multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2728.
Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion
Authors: YutakaMatsui, HiromitsuTakagi, XuepingQu, MahaAbdellatif, HideyukiSakoda, TomoichiroAsano, BethLevine, JunichiSadoshima
Journal: Circulation Research (2007)

Autophagy is an intracellular bulk degradation process for proteins and organelles. In the heart, autophagy is stimulated by myocardial ischemia. However, the causative role of autophagy in the survival of cardiac myocytes and the underlying signaling mechanisms are poorly understood. Glucose deprivation (GD), which mimics myocardial ischemia, induces autophagy in cultured cardiac myocytes. Survival of cardiac myocytes was decreased by 3-methyladenine, an inhibitor of autophagy, suggesting that autophagy is protective against GD in cardiac myocytes. GD-induced autophagy coincided with activation of AMP-activated protein kinase (AMPK) and inactivation of mTOR (mammalian target of rapamycin). Inhibition of AMPK by adenine 9-β-d-arabinofuranoside or dominant negative AMPK significantly reduced GD-induced autophagy, whereas stimulation of autophagy by rapamycin failed to cause an additive effect on GD-induced autophagy, suggesting that activation of AMPK and inhibition of mTOR mediate GD-induced autophagy. Au...
Thromboplastic and Fibrinolytic Activities in Vessels of Animals
Authors: Tageastrup, Karolbuluk
Journal: Circulation Research (1963)

Thromboplastic activity and concentration of plasminogen activator were assayed in the coats of arteries and veins from a number of species. The widely differing patterns found in these species suggest great variation in the tendency to deposit fibrin on the interior surface of the vessels. Several modes of regulating fibrin deposition after intimal injury exist in the animal organism. These observations may assist the evaluation of data obtained in experiments on animals, and they demonstrate certain limitations with respect to conclusions on pathology in man.
Regional Sympathetic Nervous Activity and Oxygen Consumption in Obese Normotensive Human Subjects
Authors: MarioVaz, GarryJennings, AndreaTurner, HelenCox, GavinLambert, MurrayEsler
Journal: Circulation (1997)

Background Disturbed sympathetic nervous function may be of importance in obesity; sympathetic underactivity could contribute to deficient thermogenesis, positive energy balance, and weight gain, while in contrast, sympathetic nervous overactivity would predispose to the development of obesity-related hypertension. Global indices of sympathetic nervous system (SNS) function such as plasma or urinary norepinephrine (NE) have been unable to define SNS status in obesity. Since regional SNS activity can be altered in the absence of global changes, we investigated SNS activity in the heart, kidneys, and hepatomesenteric bed in healthy human subjects across a wide body mass index (BMI) range of between 19.6 and 35.5. Methods and Results Whole-body and regional plasma NE kinetics using [3H]-labeled NE were assessed. Regional oxygen consumption was measured by combining arteriovenous differences in oxygen content and regional blood flow. Arterial plasma NE and whole-body plasma NE spillover were unrelated to BMI....
Pioglitazone, a Peroxisome Proliferator–Activated Receptor-γ Agonist, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction
Authors: TetsuyaShiomi, HiroyukiTsutsui, ShunjiHayashidani, NobuhiroSuematsu, MasakiIkeuchi, JingWen, MinakoIshibashi, ToruKubota, KensukeEgashira, AkiraTakeshita
Journal: Circulation (2002)

Background— Peroxisome proliferator–activated receptor-γ activators have recently been implicated as regulators of cellular proliferation and inflammatory response such as cytokine expression. Because proinflammatory cytokines play a critical role in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of pioglitazone treatment in an experimental model of chronic heart failure. Methods and Results— Mice with extensive anterior MI were treated with placebo or pioglitazone (3 mg · kg−1 · d−1) as a dietary supplement for 4 weeks starting 6 hours after surgery. Infarct size and glucose levels were similar among all groups. LV cavity dilatation and dysfunction by echocardiography were significantly attenuated in MI mice given pioglitazone. LV end-diastolic pressure was increased in MI mice and was significantly reduced by pioglitazone treatment. Pioglitazone partially normalized LV dP/dtmax and dP/dtmin, indices of LV contractile function, which were significantly reduced ...
Abstract 14158: Impact of Statin Following Endovascular Aneurysm Repair in Patients With Abdominal Aortic Aneurysm
Authors: Kiyonori Nanto, Osamu Iida, Masashi Fujita, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Tatsuya Shiraki, Takashi Kanda, Akihiro Sunaga, Takuya Tsujimura, Shota Okuno, Koji Yanaka, Yasuhiro Matsuda, Takuya Ohashi, Junichi Tazaki, Masaaki Uematsu
Journal: Circulation (2015)

Introduction: Endovascular aneurysm repair (EVAR) has been an established treatment for abdominal aortic aneurysm (AAA). Although statin use has been shown associated with better long-term survival following open AAA surgery, its impact on EVAR has not been systematically explored. Methods: We retrospectively analyzed a multicenter database of 368 consecutive patients (age, 76 ± 8 years; 84% male) undergoing EVAR for AAA between November 2006 and December 2013. The outcome measure was overall survival following EVAR. Independent predictor associated with the outcome was assessed by Cox proportional hazard regression model. Furthermore, the association between the statin use and the outcome was assessed. Results: During the follow-up of 30 ± 20 months, 38 patients died from cardiovascular disease (33%), cancer (23%) or infection (23%). Survival rate was 96% and 81% at 1 and 5 years, respectively. In Cox regression analysis, statin use (in 213 AAA patients, 58%) was negatively associated with the mortality [HR, 0.34; P = 0.002]. There was a significant interaction effect between statin and preoperative aneurysm size. The adjusted hazard ratio of statin for mortality was 0.19 (95% confidence interval (CI): 0.08 to 0.48, p &lt; 0.001) in patients with preoperative aneurysm size &lt; 55 mm, whereas it was 1.00 (95% CI: 0.31 to 3.19, p = 1.000) in those with preoperative aneurysm size ≥ 55 mm. (Figure) Conclusions: In this retrospective study, statin use was associated with a better long-term survival following EVAR for AAA, particularly in those with preoperative diameter &lt;55mm.
T Cells With Similar T-Cell Receptor β-Chain Complementarity-Determining Region 3 Motifs Infiltrate Inflammatory Lesions of Synthetic Peptides Inducing Rat Autoimmune Myocarditis
Authors: HaruoHanawa, TakayukiInomata, YujiOkura, SatoruHirono, YusukeOgawa, TohruIzumi, MakotoKodama, YoshifusaAizawa
Journal: Circulation Research (1998)

Abstract—Experimental autoimmune myocarditis (EAM) resembles the giant cell myocarditis seen in humans, and recurrent forms lead to dilated cardiomyopathy. EAM has been shown to be a T cell–mediated autoimmune myocarditis. We have previously shown that cDNA encoding Vβ complementarity-determining region (CDR) 3 from heart– and pericardial space–infiltrating T cells in EAM induced by rod cardiac myosin contains more restricted sequences than that from normal spleen T cells. Recently, it has become apparent that several epitopes of EAM exist in rod cardiac myosin; therefore, T cells infiltrating into lesions may recognize certain epitopes in EAM induced by rod cardiac myosin. In this study, we examined heart– and pericardial space–infiltrating T-cell clonotypes in EAM induced by synthetic peptides of cardiac myosin. EAM was produced by immunization with synthetic peptides corresponding to N-terminally acetylated amino acids 1539 to 1555 of rat cardiac myosin α heavy chain. Five of 12 rats receiving syntheti...
NON-INVASIVE DIAGNOSIS OF ESOPHAGEAL VARICES IN CHILDREN: A PROSPECTIVE, MULTICENTRE, VALIDATION STUDY
Authors: Juan Cristobal Gana, Dan Turner, Giorgina Mieli-Vergani, Mark Davenport, Tamir A. Miloh, Yaron Avitzur, Jason Yap, Veronique Morinville, Herbert Brill, Simon C. Ling
Journal: Hepatology (2010)
Abstract 2578: Expression of epiregulin/amphiregulin associates with prognosis in recurrent/metastatic head and neck cancer treated with cetuximab
Authors: Yasunao Kogashiwa, Hitoshi Inoue, Kiyomi Kuba, Masanori Yasuda, Mitsuhiko Nakahira, Masashi Sugasawa
Journal: Cancer Research (2018)

Abstract Objectives: The anti-EGFR antibody cetuximab, combined with chemotherapy, is the standard therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, the response rate and survival benefit are limited. The purpose of this study was to investigate the expression of the epidermal growth factor receptor ligands epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC. Materials and methods: We conducted a retrospective analysis of 37 patients diagnosed with R/M HNSCC. Tumor samples from biopsy specimens or surgical specimens were analyzed for EREG and AREG mRNA gene expression, and clinical outcomes evaluated. Survival rates were estimated by Kaplan-Meier analysis. Cox proportional hazard regression was used to test the potential association between ligand expression, overall survival (OS), and progression free survival (PFS). Results: Values of EREG ≤ 15.87 and AREG ≤ 11.80, determined by receiver operating characteristic (ROC) curve analysis, were associated with significantly longer OS (p=0.03 and p=0.01, respectively), as well as PFS (p=0.04 and p=0.04, respectively). EREG and AREG expression levels were significantly correlated (r=0.73, p&amp;lt;0.01). Multivariate analysis revealed that AREG expression was significantly associated with OS and PFS. Conclusion: R/M HNSCC patients with higher EREG and AREG gene expression appear to benefit more from cetuximab combined with chemotherapy than those with lower expression. The potential for these ligands as prognostic biomarkers for cetuximab-containing regimens requires further evaluation. Citation Format: Yasunao Kogashiwa, Hitoshi Inoue, Kiyomi Kuba, Masanori Yasuda, Mitsuhiko Nakahira, Masashi Sugasawa. Expression of epiregulin/amphiregulin associates with prognosis in recurrent/metastatic head and neck cancer treated with cetuximab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2578.
Abstract IA31: Targeting immune receptor mutations in lymphoma
Authors: Hans-Guido Wendel
Journal: Clinical Cancer Research (2017)

Abstract The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors. Accordingly, administration of the HVEM ectodomain protein (solHVEM(P37-V202)) binds BTLA and restores tumor suppression. To deliver solHVEM to lymphomas in vivo, we engineered CD19-targeted chimeric antigen receptor (CAR) T cells that produce solHVEM locally and continuously. These modified CAR-T cells show enhanced therapeutic activity against xenografted lymphomas. Hence, the HVEM-BTLA axis opposes lymphoma development, and our study illustrates the use of CAR-T cells as “micropharmacies” able to deliver an anticancer protein. Citation Format: Hans-Guido Wendel. Targeting immune receptor mutations in lymphoma [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr IA31.