bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of lidocaine after bilateral ESP block
Authors: De Cassai Alessandro , Bonanno Claudio , Padrini Roberto , Geraldini Federico , Boscolo Annalisa , Navalesi Paolo , Munari Marina 
Published: September 2020

IntroductionErector spinae plane (ESP) block is an emerging interfascial block with a wide range of indications for perioperative analgesia and chronic pain treatment. Recent studies have focused their attention on mechanisms of action of ESP block. However, the pharmacokinetics of drugs injected in ESP is, as of now, uninvestigated. The aim of this brief report is to investigate the pharmacokinetics of lidocaine in a series of 10 patients.MethodsWe are reporting a case series of 10 patients undergoing bilateral ESP block for multilevel lumbar spine surgery.ESP was performed with 3.5 mg/kg of lidocaine based on ideal body weight. Lidocaine concentration was dosed at 5, 15, 30 min and at 1, 2 and 3 hours.ResultsTmaxwas 5 min for all the patients. Cmaxranged from 1.2 to 3.8 mg/L (mean: 2.59 mg/L). AUC0-3was high (76%, on average) suggesting an almost complete bioavailability. Age had a negative correlation with T½ of lidocaine.ConclusionsLidocaine pharmacokinetic after ESP block is well-described by a two-compartment model with a rapid and extensive rate of absorption. Nevertheless, its peak concentrations never exceeded the accepted toxicity limit. Elimination half-life was slightly prolonged, probably due to the advanced age of some patients.
Estimating educational outcomes from students’ short texts on social media
Authors: Smirnov Ivan 
Published: September 2020

AbstractDigital traces have become an essential source of data in social sciences because they provide new insights into human behavior and allow studies to be conducted on a larger scale. One particular area of interest is the estimation of various users’ characteristics from their texts on social media. Although it has been established that basic categorical attributes could be effectively predicted from social media posts, the extent to which it applies to more complex continuous characteristics is less understood. In this research, we used data from a nationally representative panel of students to predict their educational outcomes measured by standardized tests from short texts on a popular Russian social networking site VK. We combined unsupervised learning of word embeddings on a large corpus of VK posts with a simple, supervised model trained on individual posts. The resulting model was able to distinguish between posts written by high- and low-performing students with an accuracy of 94%. We then applied the model to reproduce the ranking of 914 high schools from 3 cities and of the 100 largest universities in Russia. We also showed that the same model could predict academic performance from tweets as well as from VK posts. Finally, we explored predictors of high and low academic performance to obtain insights into the factors associated with different educational outcomes.
Abstract A014: Rural-urban differences e-cigarette ever use, the perception of harm, and e-cigarette information-seeking behaviors among U.S. adults in a nationally representative study
Authors: Lewis-Thames Marquita W. ,   Marvin E. LWashington University in St. Louis School of Medicineangston, WashiWashington Lindsay Fuzzella. , Khan Saira , Moore Justin X. , Han Yunan 
Published: September 2020

Abstract
Rural adults are more likely to use some tobacco products and die from tobacco-related diseases than their urban counterparts. The harms and benefits of e-cigarette use are mixed, and similarly, obscure messaging about these harms and benefits have a critical influence on e-cigarette uptake and perceived harms. However, little is known about rural-urban differences in the prevalence of adult e-cigarette daily usage. Using the Health Information National Trends Survey-Food and Drug Administration (HINTS-FDA) cycles 1 and 2, we conducted weighted logistic regressions to assess rural-urban differences in the prevalence of adult e-cigarette daily usage, perceived harm, and e-cigarette information seeking behaviors. This analysis included adults aged 18 and older in the United States. (N=4229). Both rural and urban respondents had a similar history of e-cigarette use. Rural respondents were significantly more likely than urban respondents to trust religious organizations and leaders and tobacco companies for information about e-cigarettes. Rural and urban respondents were equally as likely to believe e-cigarettes are addictive, perceive e-cigarette use as harmful, and believe e-cigarettes are more harmful than smoking cigarettes. They were equally as likely to look for information on e-cigarettes, the health effects of e-cigarettes, and cessation; and, to seek e-cigarette information from healthcare professionals, family and friends, and health organizations and groups. Given our findings, it will be pertinent to continue to research the potential harms of e-cigarette use and develop accurate health communication messages to avoid similar rural-urban disparities observed for cigarette smoking-related outcomes.
Citation Format: Marquita W. Lewis-Thames, Marvin E. LWashington University in St. Louis School of Medicineangston, Lindsay Fuzzella. WashiWashington, Saira Khan, Justin X. Moore, Yunan Han. Rural-urban differences e-cigarette ever use, the perception of harm, and e-cigarette information-seeking behaviors among U.S. adults in a nationally representative study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A014.
G-Protein-Coupled Estrogen Receptor 1 Promotes Gender Disparities in Hepatocellular Carcinoma via Modulation of SIN1 and mTOR Complex 2 Activity
Authors: Feng Guanying , Cai Jingshu , Huang Yunchuanxiang , Zhu Xianjun , Gong Bo , Yang Zhenglin , Yan Chunhong , Hu Zhuowei , Yang Lu , Wang Ziyan 
Published: September 2020

Abstract

Due to its intricate heterogeneity and limited treatment, hepatocellular carcinoma (HCC) has been considered a major cause of cancer-related mortality worldwide. Increasing evidence indicates that G-protein-coupled estrogen receptor 1 (GPER1) can promote estrogen-dependent hepatocellular proliferation by activating AKT signaling. The mTOR complex 2 (mTORC2), whose integrity and activity are modulated by its subunit Sin1, controls the activation of AKT by phosphorylation at position S473. In this study, we investigate the modulation of Sin1 and how estrogen signaling may influence the mTORC2–AKT cascade in HCC cells and a DEN-induced mouse model. We have found that estradiol-dependent Sin1 expression is transcriptionally modulated by GPER1 as well as ERα. GPER1 is able to regulate Sin1 stability via nuclear translocation, therefore increasing Sin1–mTORC2–AKT activation. Moreover, Sin1 interacts with ERα and further enhances its transcriptional activity. Sin1 is highly expressed in acute liver injury and in cases of HCC harboring high expression of GPER1 and constitutive activation of mTORC2–AKT signaling. GPER1 inhibition using the antagonist G-15 reverses DEN-induced acute liver injury by suppressing Sin1 expression and mTORC2–AKT activation. Notably, SIN1 expression varies between male and female mice in the context of both liver injury and liver cancer. In addition, high SIN1 expression is predictive of good prognosis in both male and female patients with HCC who are free from hepatitis virus infection and who report low alcohol consumption. Hence, here we demonstrate that Sin1 can be regulated by GPER1 both through nongenomic and indirect genomic signaling.

Implications:
This study suggests that Sin1 may be a novel HCC biomarker which is gender-dependent and sensitive to particular risk factor.
Neoplastic–Stromal Cell Cross-talk Regulates Matrisome Expression in Pancreatic Cancer
Authors: Honselmann Kim C. , Finetti Pascal , Birnbaum David J. , Monsalve Christian S. , Wellner Ulrich F. , Begg Sebastian K.S. , Nakagawa Akifumi , Hank Thomas , Li Annie , Goldsworthy Mathew A. , Sharma Himanshu , Bertucci François , Birnbaum Daniel , Tai Eric , Ligorio Matteo , Ting David T. , Schilling Oliver , Biniossek Martin L. , Bronsert Peter , Ferrone Cristina R. , Keck Tobias , Mino-Kenudson Mari , Lillemoe Keith D. , Warshaw Andrew L. , Fernández-del Castillo Carlos , Liss Andrew S. 
Published: September 2020

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly desmoplastic reaction, warranting intense cancer–stroma communication. In this study, we interrogated the contribution of the BET family of chromatin adaptors to the cross-talk between PDAC cells and the tumor stroma. Short-term treatment of orthotopic xenograft tumors with CPI203, a small-molecule inhibitor of BET proteins, resulted in broad changes in the expression of genes encoding components of the extracellular matrix (matrisome) in both cancer and stromal cells. Remarkably, more than half of matrisome genes were expressed by cancer cells. In vitro cocultures of PDAC cells and cancer-associated fibroblasts (CAF) demonstrated that matrisome expression was regulated by BET-dependent cancer–CAF cross-talk. Disrupting this cross-talk in vivo resulted in diminished growth of orthotopic patient-derived xenograft tumors, reduced proliferation of cancer cells, and changes in collagen structure consistent with that of patients who experienced better survival. Examination of matrisome gene expression in publicly available data sets of 573 PDAC tumors identified a 65-gene signature that was able to distinguish long- and short-term PDAC survivors. Importantly, the expression of genes predictive of short-term survival was diminished in the cancer cells of orthotopic xenograft tumors of mice treated with CPI203. Taken together, these results demonstrate that inhibiting the activity BET proteins results in transcriptional and structural differences in the matrisome are associated with better patient survival.

Implications:
These studies highlight the biological relevance of the matrisome program in PDAC and suggest targeting of epigenetically driven tumor–stroma cross-talk as a potential therapeutic avenue.
Abstract A13: Yap activity in bile ducts, but not in hepatocytes, is required for normal liver regeneration
Authors: Verboven Elisabeth , Moya Ivan M. , Halder Georg 
Published: September 2020

Abstract
The Hippo-pathway effectors Yap/Taz are assumed to be master regulators of organ regeneration. In the mouse liver, loss of Yap indeed affects the regeneration potential of hepatocytes. However, we found that this is not due to a requirement for Yap in hepatocytes to drive proliferation and regeneration, but is rather due to non-cell autonomous effects of the bile duct defects that develop in the absence of Yap. Developmental deletion of Yap and Taz in liver progenitors, which develop into hepatocytes and bile epithelial cells (BECs), impaired liver regeneration after toxin-induced injury. However, hepatocyte-specific deletion of Yap/Taz in adult mice revealed that Yap/Taz are dispensable in hepatocytes for liver regeneration. In contrast, deletion of Yap/Taz in mature BECs recapitulated the liver regeneration defects that were observed after knockout in liver progenitor cells. Notably, loss of Yap/Taz in BECs impaired bile duct integrity over time, induced a cholestatic liver phenotype, and increased apoptosis in wild-type hepatocytes after toxic liver injury. Our data show that Yap and Taz are required to maintain bile duct integrity, which is essential to maintain the regenerative capacity of adult hepatocytes.
Citation Format: Elisabeth Verboven, Ivan M. Moya, Georg Halder. Yap activity in bile ducts, but not in hepatocytes, is required for normal liver regeneration [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr A13.
Abstract A15: A balance of yki/sd activator and e2f1/sd repressor complexes controls cell survival and affects organ size
Authors: Zhang Peng , Pei Chunli , Yuan Zengqiang , Edgar Bruce A. 
Published: September 2020

Abstract
The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell proliferation and survival, but interactions between these parallel control systems are poorly defined. In this study, we demonstrate that interaction between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby suppresses Yki target gene expression. RBF modifies these effects by reducing E2F1/Sd interaction. This regulation has significant effects on apoptosis, organ size, and progenitor cell proliferation. Using a combination of DamID-seq and RNA-seq, we identified a set of Yki targets that play a diversity of roles during development and are suppressed by E2F1. Further, we found that human E2F1 competes with YAP for TEAD1 binding, affecting YAP activity, indicating that this mode of cross-regulation is conserved. In sum, our study uncovers a previously unknown mechanism in which RBF and E2F1 modify Hippo signaling responses to modulate apoptosis, organ growth, and homeostasis.
Citation Format: Peng Zhang, Chunli Pei, Zengqiang Yuan, Bruce A. Edgar. A balance of yki/sd activator and e2f1/sd repressor complexes controls cell survival and affects organ size [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr A15.
Abstract A26: Classification of glioblastoma tumorsphere depending on the regulatory mechanisms of the Hippo pathway
Authors: Oh Yoojung , Kim Eui Hyun , Lee Dongkyu , Park Junseong , Moon Ju Hyung , Park Hyun Woo , Chang Jong Hee , Kang Seok-Gu 
Published: September 2020

Abstract
Background: Although glioblastoma (GBM) is the most common primary brain tumor, the best available treatment options are still associated with poor prognosis. Recently, the Hippo/YAP signaling pathway has emerged as an important driver of GBM. Nevertheless, extensive studies have not yet been focused on the importance of phosphorylation event in regulating endogenous YAP activity in GBM. Here, we sought to elucidate that the modulation and stabilization of YAP/TAZ in Hippo pathway promote GBM progression.
Methods: A core gene expression signature reflecting Silence of Hippo pathway (SOH) was developed in GBM patient samples to determine whether SOH enhances the tumor progression. In GBM tumorsphere (TS), mRNA levels of YAP1 were determined by microarray, and nuclear YAP1 expression level and its correlation with tumor aggressiveness were assessed through nucleus cytosolic fractionation, quantitative confocal microscopy, Western blot, and TEAD4 reporter assay. Cell proliferation, stemness, and invasive properties were also measured after treatment of YAP siRNA or its inhibitor verteporfin (VP).
Results: GBM patients with SOH signature associated with poor prognosis and shorter survival. GBM TSs exhibited various phosphorylation states of YAP and could be distinguished by its phosphorylation status. GBM TSs with reduced YAP phosphorylation, including TS15-88, and other GBM TSs with higher YAP phosphorylation, which includes TS13-64, showed aggressive or less-aggressive cancer phenotypes, respectively. The siRNA-mediated knockdown of YAP1 significantly suppressed proliferation of TSs, and the results were confirmed using VP. Knockdown of YAP1 not only attenuated the invasiveness and stemness of TSs.
Conclusion: We showed that reduced phosphorylation of endogenous YAP contributes to GBM progression. Moreover, we found that GBM TSs can be classified into two groups based on their YAP phosphorylation. These associations emphasize the YAP signaling network as new therapeutic opportunities in diagnosing and treating GBM.
Citation Format: Yoojung Oh, Eui Hyun Kim, Dongkyu Lee, Junseong Park, Ju Hyung Moon, Hyun Woo Park, Jong Hee Chang, Seok-Gu Kang. Classification of glioblastoma tumorsphere depending on the regulatory mechanisms of the Hippo pathway [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr A26.
Abstract B17: Hyperactivating the Hippo pathway effector TAZ distorts the immune microenvironment in promoting the mesenchymal transformation in glioblastoma
Authors: Yee Patricia , Wei Yiju , Liu Zhijun , Li Wei 
Published: September 2020

Abstract
Glioblastoma (GBM), the deadliest and most common primary brain malignancy in adults, is highly heterogeneous with variable prognoses and treatment responses. The mesenchymal subtype of GBM is associated with the worst prognosis and highest treatment resistance. It is still not clear how GBM mesenchymal differentiation is achieved. Hyperactivity of transcriptional coactivator with PDZ-binding motif (TAZ) was linked to the GBM mesenchymal transformation, although its role in this process remains unclear. Here, by using orthotopic xenograft mouse GBM models, we found that hyperactive TAZ in tumor cells promotes myeloid cells to infiltrate into tumors. Such enhanced myeloid cell infiltration is associated with the mesenchymal transformation and tumor progression. We demonstrated that these TAZ-induced tumorigenic properties rely on its interaction with the transcription factor, TEA domain family member (TEAD). Such interaction induces the transcription of chemokines that are able to recruit the myeloid cells. Specific depletion of the infiltrated myeloid cells is able to slow down the tumor progression. Our studies suggested that recruiting myeloid cells by hyperactive TAZ contributes the mesenchymal transformation and tumor progression in glioblastoma.
Citation Format: Patricia Yee, Yiju Wei, Zhijun Liu, Wei Li. Hyperactivating the Hippo pathway effector TAZ distorts the immune microenvironment in promoting the mesenchymal transformation in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B17.
Abstract B25: An actionable AXL-ABL2-TAZ signaling axis promotes lung adenocarcinoma metastasis to the brain
Authors: Hoj Jacob P. , Mayro Benjamin J. , Pendergast Ann Marie 
Published: September 2020

Abstract
Despite recent work to uncover the biologic mechanisms governing tumor cell metastasis to the brain, new therapeutic approaches for treating patients with brain-metastatic disease have remained elusive. Through the use of in vivo models of brain metastasis and relevant in vitro molecular biology techniques, we identify a novel and targetable autocrine signaling axis required for lung adenocarcinoma metastasis to the brain centered upon the transcriptional coactivator TAZ. Nuclear localization of TAZ drives transcription of target genes AXL and ABL2, which in turn engage in bidirectional tyrosine kinase signaling at the protein level. Activation of ABL2 in turn increases TAZ stability and promotes its nuclear localization, establishing an autocrine feed-forward signaling loop and revealing a previously undescribed mechanism of TAZ nuclear localization dependent on tyrosine kinase activity of ABL2. We further reveal that the Neural Adhesion Molecule L1 (L1CAM), previously identified as a critical mediator of brain metastasis, is a direct target gene of TAZ whose expression is regulated by activation of AXL-ABL2-TAZ signaling. Our findings provide evidence for AXL and ABL2 kinase inhibitors as potential therapeutic strategies for the treatment of brain metastases.
Citation Format: Jacob P. Hoj, Benjamin J. Mayro, Ann Marie Pendergast. An actionable AXL-ABL2-TAZ signaling axis promotes lung adenocarcinoma metastasis to the brain [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B25.
Abstract B31: YAP1-induced cervical carcinogenesis challenges the HPV dogma
Authors: Wang Cheng 
Published: September 2020

Abstract
Aims: HPV infections are common in women but only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and development of cervical cancer. The molecular mechanisms underlying cervical cancer development remain unclear. Although our previous in vitro studies have shown that YAP1 plays a role in the malignant transformation of cervical epithelial cells, whether YAP1 contributes to the cervical carcinogenesis in vivo is unknown. This study aims to determine whether YAP1, alone or interacting with HPV, contributes to cervical carcinogenesis in vivo.
Methods: Cellular and transgenic mouse models were developed to evaluate the role of YAP1 in cervical carcinogenesis.
Results: Keratin-14 promoter-driven expression of constitutively active YAP1 (YAPS127A) in mouse cervical epithelial cells induced invasive cervical cancer, suggesting that hyperactivation of YAP1 is sufficient to induce cervical cancer development. Cervical epithelial cell-specific HPV and YAP1 double knockin mouse models showed that HPV synergizes with YAP1 to promote the initiation and progression of cervical carcinogenesis. Our mechanistic studies demonstrated that hyperactivation of YAP1 in cervical epithelium not only increased the putative HPV receptor molecules and cellular susceptibility to HPV infection, but also disrupted the host cell innate immune system, resulting in failure of HPV viral recognition, suppression of type I IFN production, inhibition of the IFNRs/JAKs/STATs pathway, and blockage of production of antiviral interferon-stimulated genes.
Conclusion: Our results indicated that the YAP1 oncogene plays a central role in cervical cancer development. The synergism between hyperactivated YAP1 and high-risk HPV may be a key driver of cervical cancer initiation and progression. Our finding challenges the dogma that HPV is a necessary agent for the development of cervical cancer, uncovers a novel mechanism for the cervical carcinogenesis, and provides new targets for developing strategies to improve prevention and treatment of cervical cancer.
Note: This abstract was not presented at the conference.
Citation Format: Cheng Wang. YAP1-induced cervical carcinogenesis challenges the HPV dogma [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B31.