bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-317: Use of in vivo microdialysis to evaluate biomarker levels in the tumor and tumor free flank of freely-moving PDX mice
Authors: Heins Mariette , Weichert Loreen , Gorynia Sabine , Flik Gunnar , Rassoulpour Arash 
Published: August 2019

Abstract
The tumor microenvironment (TME) constitutes unique surroundings where cancer cells communicate with one another and with the host immune system by releasing a multitude of factors. Information about the physiological state of the TME can help in gaining a broader understanding of cancer biology and developing novel cancer therapeutics. Previous work has demonstrated the ability to use in vivo microdialysis to monitor the release of adenosine and its metabolites from murine cancer models. To further these findings, we used in vivo microdialysis to measure biomarkers in the patient-derived xenograft (PDX) cancer model. By using human tumor tissue models, we aim to bridge the gap between rodent models and human tumors to help develop better cancer therapeutics.
The current set of studies used microdialysis in different PDX lines representing human tumor models (provided by CRL DRS Freiburg). Xenograft growth was monitored and upon a tumor volume &gt; 400 mm3, the animals underwent surgical implantation of microdialysis probes in the tumor and the tumor-free flank. The implanted probes were perfused with dialysate fluid and samples from the both flanks were continuously collected over several hours. Levels of ATP, inosine and kynurenine metabolites were quantified by EIA or LC-MS/MS analysis.
Analysis of microdialysate samples from tumor and tumor-free flank demonstrated differences in analyte levels between the two sampling sites within one animal indicating that the levels of ATP and metabolites measured in PDX tumors is unique to the tumor microenvironment. In addition, the various PDX models showed differences in biomarker levels between the different tumor types. There is a wide range of biomarkers which are important indicators of energy consumption and provide an insight in the differences in metabolic activity between the different xenografts. Moreover, these data demonstrate that microdialysis can be used to test targeted therapies and follow relevant biomarker levels over time. Thereby, providing better insight in effects of new therapeutic treatments within the patient specific tumor tissue itself.
Citation Format: Mariette Heins, Loreen Weichert, Sabine Gorynia, Gunnar Flik, Arash Rassoulpour. Use of in vivo microdialysis to evaluate biomarker levels in the tumor and tumor free flank of freely-moving PDX mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-317.
Abstract PL04-02: HIV malignancies: From despair to gene therapy
Authors: Noy Ariela 
Published: August 2019

Abstract
HIV antiretroviral therapy has dramatically decreased the relative risk of HIV associated cancer. Nonetheless, the longevity of people living with HIV and the ongoing exposure to a variety of interconnected risk factors results in an increased life time risk of cancer compared with the general population. This includes AIDS defining and non-AIDS defining cancers. Risks increase during breaks in antiviral therapy and reinforce the recommendation that patients should avoid breaks in therapy. The non-HIV factors which interplay in carcinogenesis include immune dysregulation, immunosuppression, viral co-infections, and lifestyle habits that are more prevalent among people living with HIV. In this lecture we will explore these issues as they relate to non-Hodgkin lymphoma, Hodgkin lymphoma, Kaposi sarcoma, anal and cervical cancer, lung cancer and hepatocellular carcinoma. We will outline fundamental principles of therapy with an emphasis on the much-improved prognosis compared to the era before antiviral therapy. We will explore some of the current research questions including the incorporation of lentivirus vectors carrying anti-HIV genes into hematopoietic stem cells. We will also review the impact of anti-HIV bias on cancer clinical trials and the response of the American Society of Clinical Oncology to broaden eligibility in those trials. The approach to cancer in HIV infected patients has evolved dramatically since the recognition of AIDS and patients can now benefit from more definitive approaches to malignancy with far superior outcomes.
Citation Format: Ariela Noy. HIV malignancies: From despair to gene therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL04-02.
Abstract SY19-01: Metabolic consequences and liabilities of TCA cycle truncation in cancer
Authors: Gottlieb Eyal 
Published: August 2019

Abstract
Succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tricarboxylic acid (TCA) cycle enzymes while SDH is also part of the respiratory chain. Despite their key housekeeping activities, the genetic loss of FH or of any of the SDH subunits is associated with susceptibility to cancers. SDH or FH inactivation leads to the accumulation of metabolites which cause the activation of hypoxia-inducible factors and the inhibition of histone and DNA demethylases, establishing pseudohypoxic and hypermethylator phenotype. However, surviving the loss of these essential metabolic enzymes requires a significant metabolic adaptation as backup mechanisms for the dysfunctional TCA cycle and oxidative phosphorylation in these tumors. Identifying these adaptations would reveal effective and specific metabolic vulnerabilities which can serve as potential molecular targets for therapeutic intervention. We have identified in the past a few metabolic essentialities in cells deficient in FH and SDH and now performed a pharmacologic phenotypic synthetic lethal screen to identified effective drugs that specifically kill SDH- and FH-deficient cells. Utilizing metabolomics, we have delineated the molecular target of the effective compounds.
Citation Format: Eyal Gottlieb. Metabolic consequences and liabilities of TCA cycle truncation in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY19-01.
Abstract SY21-01: Analyzing tumor metabolism in patients
Authors: Deberardinis Ralph J. 
Published: August 2019

Abstract
Metabolism is dynamic and responds to a wide range of cell-intrinsic and cell-extrinsic factors. Many human diseases involve perturbations of metabolism at the cellular level, and in many cases normalizing the metabolic state has proven to be therapeutically valuable. Cancer is one such disease, in which factors both intrinsic and extrinsic to the malignant cell impact tumor biology and disease progression. In cancer, cell-intrinsic influences on metabolism include somatically-acquired mutations in oncogenes and tumor suppressor genes, many of which regulate metabolic activity. Cell-extrinsic factors include nutrient access, which may become limiting due to inadequate vasculature and intense fuel utilization, and metabolic interactions with stromal and immune cells. A major challenge in cancer metabolism research is to understand how these various factors culminate in the metabolic phenotype of an intact tumor, and ultimately to identify which altered pathways represent potential therapeutic targets. Among the many metabolic pathways reprogrammed in cancer, nucleotide metabolism and responses to DNA damage are highly integrated with aberrant signaling and gene regulatory networks in cancer. We have taken two parallel approaches to understand metabolic complexity and identify potential therapeutic liabilities in human cancer. The first uses a combination of multi-parametric imaging and intraoperative stable isotope infusions to assess metabolic fluxes in patients with solid tumors, and to compare fluxes between tumors and adjacent tissue. Genomic, histological and metabolic analysis of tumor samples allows us to correlate various intrinsic and extrinsic factors to specific aspects of the metabolic phenotype. The second approach uses standardized culture conditions to assess cell-intrinsic heterogeneity of metabolic preferences and dependencies in large panels of human cancer cell lines. This approach has uncovered liabilities associated with specific molecular subtypes of non-small cell and small cell lung cancerm ncluding several related to nucleotide and nucleic acid metabolism. I will discuss the application of these approaches to metabolic heterogeneity in human cancer, with an emphasis on features relevant to intact tumors and therapeutic liabilities and the role of metabolic imaging in studying cancer metabolism.
Citation Format: Ralph J. Deberardinis. Analyzing tumor metabolism in patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY21-01.
Abstract SY28-03: Extending the paradigm of hormonal dependency of cancer to account for effects of lifestyle on risk and prognosis
Authors: Pollak Michael N. 
Published: August 2019

Abstract
Cancer behavior is determined by cancer metabolism. Abnormalities in cancer cell metabolism are determined in part by intrinsic or autonomous characteristics of each cancer cell, which relate to in part to genetic alterations in oncogenes and cancer suppressor genes, and in part to host effects, which are mediated in large part by hormones and growth factors. Dietary and lifestyle factors that influence cancer risk or cancer prognosis influence levels of hormones such as insulin. We now recognize that these hormones influence the behavior of a subset of common cancers. Attempts to treat cancer by altering the hormonal milieu related to gonadal steroids have led to many widely used treatments for cancer of the breast and prostate, but it remains uncertain if this paradigm can be extended to lifestyle and nutritionally regulated hormones such as insulin, which have been found to be growth-stimulatory in certain preclinical models. We will review these concepts, including recent laboratory and clinical data related to metformin, an anti-diabetic drug under study for possible anti-neoplastic activity.
Citation Format: Michael N. Pollak. Extending the paradigm of hormonal dependency of cancer to account for effects of lifestyle on risk and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY28-03.
Abstract SY30-01: A wrinkle in TiME: How the aging TME drives tumor progression
Authors: Weeraratna Ashani T. 
Published: August 2019

Abstract
Most cancers arise after the age of 50, and the molecular mechanisms that underlie this observation are not well understood. Our overarching goal is to elucidate and target the age-related changes that drive tumor progression. We have made the seminal discovery that aged fibroblasts secrete, or stop secreting, key molecules that affect multiple aspects of tumorigenesis. Our current investigations include: the loss of molecules that maintain ECM integrity, resulting in changes in mechanotransduction and increased metastasis; the secretion of molecules that increase resistance to targeted therapy; the secretion of macromolecules such as lipids that are taken up by melanoma cells in the aged microenvironment, affecting tumor cell metabolism; changes in the aged immune tumor microenvironment; the secretion of non-canonical Wnt molecules that affect cell signaling leading to angiogenesis, metastasis, and therapy resistance. Overall, our studies indicate that the age of the mouse models we study, as well as the patients we treat must be considered in order to understand tumor progression and therapy resistance.
Citation Format: Ashani T. Weeraratna. A wrinkle in TiME: How the aging TME drives tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY30-01.
Abstract SY40-02: YAP/TAZ activity as hallmark of cancer: Biologic properties, upstream regulations, and downstream targets
Authors: Piccolo Stefano 
Published: August 2019

Abstract
Enhanced YAP/TAZ activity is emerging as common trait of multiple solid tumors in humans. Strikingly, in mouse models, adult organs lacking YAP/TAZ are unable to develop tumors without overt side effects for normal tissue homeostasis, making YAP/TAZ prime candidates for cancer therapy. That said, YAP/TAZ have physiological functions during tissue repair, being essential for organ regeneration after injury. YAP/TAZ are typically inactive in normal tissues but potently induced by mechanical and physical cues that the cell receives from its microenvironment, such as extracellular matrix stiffness and topology, and 3D architectural features of the tissue. I will focus on new discoveries on the mechanisms by which YAP/TAZ are controlled by mechanotransduction, and on YAP/TAZ as reprogramming factors in epithelial cells. Indeed, in normal tissues YAP/TAZ activation turns more differentiated normal cells into cells endowed with stem-like properties; in tumors, YAP/TAZ convert non-stem tumor cells into cancer-stem cells, increasing tumor aggressiveness and fueling metastasis. I will also expand on these mechanisms, providing new hints for therapeutic intervention.
Citation Format: Stefano Piccolo. YAP/TAZ activity as hallmark of cancer: Biologic properties, upstream regulations, and downstream targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY40-02.
Impact of Baseline Anemia in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: A Prespecified Analysis From the VALIDATE‐SWEDEHEART Trial
Authors: Wester Axel , Attar Rubina , Mohammad Moman Aladdin , Andell Pontus , Hofmann Robin , Jensen Jens , Szummer Karolina , Erlinge David , Koul Sasha 
Published: August 2019

Background

The impact of baseline anemia in a contemporary acute coronary syndrome (
ACS
) population undergoing percutaneous coronary intervention in the era of predominant radial artery access, potent P2Y12 inhibition, and rare use of glycoprotein
II
b/
III
a inhibitors has not been adequately studied.

Methods and Results

ACS
patients who underwent percutaneous coronary intervention between 2014 and 2016 in the
VALIDATE
‐
SWEDEHEART
(Bivalirudin Versus Heparin in
ST
‐Segment and Non–
ST
‐Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies Registry) trial without missing values for hemoglobin were included (n=5482). Mortality, myocardial reinfarction, and major bleeding at 180 days were assessed using Cox regression models and propensity score matching. All studied comorbidities were more common in
ACS
patients who had anemia (n=792).
ACS
patients with anemia had higher rates of 180‐day mortality (6.9% versus 2.1%; hazard ratio, 1.9; 95%
CI
, 1.3–2.7;
P
<0.001), myocardial reinfarction (4.3% versus 1.9%; hazard ratio, 1.7; 95%
CI
, 1.1–2.7;
P
=0.013), and major bleeding (13.4% versus 8.2%; hazard ratio, 1.3; 95%
CI
, 1.0–1.6;
P
=0.041). The results were most evident in patients with a hemoglobin value <100 g/L, who had a nearly 10 times higher mortality rate.

Conclusions

Baseline anemia in
ACS
patients undergoing percutaneous coronary intervention, treated according to current practice including routine radial artery access, constitutes a high‐risk feature for both ischemic events, bleeding events, and mortality. A multidisciplinary approach is warranted to maximize benefit and minimize patient risk.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier: NCT02311231.
The Influences of Convectively Coupled Kelvin Waves on Multiscale Rainfall Variability over the South China Sea and Maritime Continent in December 2016
Authors: Chen Wei-Ting , Hsu Shih-Pei , Tsai Yuan-Huai , Sui Chung-Hsiung 
Published: August 2019

ABSTRACTWe studied the scale interactions of the convectively coupled Kelvin waves (KWs) over the South China Sea (SCS) and Maritime Continent (MC) during December 2016. Three KWs were observed near the equator in this month while the Madden–Julian oscillation (MJO) was inactive. The impacts of these KWs on the rainfall variability of various time scales are diagnosed, including synoptic disturbances, diurnal cycle (DC), and the onset of the Australian monsoon. Four interaction events between the KWs and the westward-propagating waves over the off-equatorial regions were examined; two events led to KW enhancements and the other two contributed to the formation of a tropical depression/tropical cyclone. Over the KW convectively active region of the MC, the DC of precipitation was enhanced in major islands and neighboring oceans. Over the land, the DC hot spots were modulated depending on the background winds and the terrain effects. Over the ocean, the “coastal regime” of the DC appeared at specific coastal areas. Last, the Australian summer monsoon onset occurred with the passage of a KW, which provided favorable conditions of low-level westerlies and initial convection over southern MC and the Arafura Sea. This effect may be helped by the warm sea surface temperature anomalies associated with the La Niña condition of this month. The current results showcase that KWs and their associated scale interactions can provide useful references for weather monitoring and forecast of this region when the MJO is absent.
On Asymptotic Standard Normality of the Two Sample Pivot
Authors: Majumdar Rajeshwari , Majumdar Suman 
Published: August 2019

The asymptotic solution to the problem of comparing the means of two heteroscedastic populations, based on two random samples from the populations, hinges on the pivot underpinning the construction of the confidence interval and the test statistic being asymptotically standard normal, which is known to happen if the two samples are independent and the ratio of the sample sizes converges to a finite positive number. This restriction on the asymptotic behavior of the ratio of the sample sizes carries the risk of rendering the asymptotic justification of the finite sample approximation invalid. It turns out that neither the restriction on the asymptotic behavior of the ratio of the sample sizes nor the assumption of cross sample independence is necessary for the pivotal convergence in question to take place. If the joint distribution of the standardized sample means converges to a spherically symmetric distribution, then that distribution must be bivariate standard normal (which can happen without the assumption of cross sample independence), and the aforesaid pivotal convergence holds. AMS Classification: 62E20, 62G20
Disease-related stressors of caregiving burden among different types of family caregivers of persons with schizophrenia in rural China
Authors: Peng Man-Man , Chen Hong-Lin , Zhang Tin , Yao Yong-You , Li Zi-Han , Long Lan , Duan Qing-Qing , Lin Fu-Rong , Zen Ya , Chen Jia , Ng Siu-Man , Chan Cecilia Lai-Wan , Ran Mao-Sheng 
Published: August 2019

Background: Little is known about the impacts of schizophrenia on different types of caregiving burden. Aim: This study aims to examine how the severity of schizophrenia, social functioning and aggressive behavior are associated with caregiving burden across different kinship types. Method: The analytic sample included 300 dyads of persons with schizophrenia and their family caregivers in Xinjin, Chengdu, China. The 10th edition of the International Classification of Diseases (ICD-10) was utilized to identify the patients, whose symptom severity, social functioning and aggressive behavior were measured. Caregiving burden was estimated using the Burden Scale for Family Caregivers–short (BSFC-s). Results: A higher level of burden was significantly associated with female caregivers, larger family size, lower income, worse symptoms, poorer functional status and more aggressive behaviors. Parent caregivers showed greater burden if the patients had better functioning of social interest and concern or more aggression toward property. Mother caregivers showed greater burden than fathers. Spouses tended to perceive greater burden if the patients had better marital functioning, poorer occupational functioning or more aggressive behaviors toward property. Patients attacking others or a father with schizophrenia was related to a higher burden of child caregivers. A heavier burden of other relatives was correlated with patients’ more verbal aggression and self-harm. Conclusion: This study shows the distinct impacts of disease-related factors on the caregiving burden across different kinship types. Our findings have implications for health-care professionals and practitioners in terms of developing more targeted family-based or individualized intervention to ameliorate burden according to kinship types and deal with behavioral and functional problems in schizophrenia.
Effect of air quality and dust deposition on power generation performance of photovoltaic module on building roof
Authors: Wang Haidong , Meng Xiangzhe , Chen Jianbo 
Published: August 2019

Due to the dust deposition on the surface of photovoltaic modules and the air pollution, the power generation performance of photovoltaic modules will be significantly affected. In order to quantitatively estimate the effect of air quality and dust deposition on the power generation performance of photovoltaic modules, a distributed photovoltaic system on a building roof in Shanghai is studied in this paper. Both artificial and natural dust deposition conditions are tested in terms of the influence of these factors on the power generation efficiency of photovoltaic modules. The variation of solar radiation intensity with PM2.5 concentration in Shanghai and the variation of photovoltaic module power generation capacity with PM2.5 concentration are tested and analyzed. The experimental results show that the surface dust of photovoltaic module reduces the power and efficiency of photovoltaic module. Experimental comparison between the dusty photovoltaic module and clean photovoltaic module shows that the dust on photovoltaic modules can reduce the power and efficiency significantly, where the highest power generation decrease is 35.226% and the highest power generation efficiency decrease is 5.546% as indicated in the experiments. Result shows that the amount of solar radiation is exponentially correlated to the PM2.5 concentration. Practical application: The influence of air quality and dust deposition on the performance of distributed PV modules is of vital importance under severe particulate pollution in Shanghai. This research helps predict the degradation of the photovoltaic system power generation efficiency, and determine whether to clean up the dust on the photovoltaic system according to accumulated PM concentration. This reduces the cost of cleaning of the dust on photovoltaic system. This study provides theoretical and experimental basis for the design of the building roof mounted solar photovoltaic system according to the local haze condition.