bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B37: Clinical relevance of tumor-infiltrating immune cells in neuroblastoma
Authors: Melaiu Ombretta , Boldrini Renata , Chierici Marco , Furlanello Cesare , Fruci Doriana 
Published: February 2019

Abstract
The presence of tumor-infiltrating T cells is crucial for the development of immunotherapies and the prediction of clinical response for many human cancers. Recently, we have shown that tumor-infiltrating T cells have a prognostic value greater than, and independent of, the criteria currently used to stage neuroblastoma, the most common pediatric extra-cranial solid tumor accounting for 15% of childhood cancer-related death. We demonstrated that expression of PD-L1 in tumor cells is inversely correlated with that of HLA class I, and that when combined they represent a promising prognostic biomarker in neuroblastoma.
To further dissect the immune heterogeneity of neuroblastoma microenviroment, we evaluated the density of infiltrating dendritic cells (iDC), which are crucial for drug-induced anticancer immune response, in the same cohort of NB samples characterized for type, density, and composition of tumor T lymphocytes and expression of tumor PD-L1 and HLA class I. As for T cells, high density of iDCs was correlated with the presence of infiltrating T cells, expression of tumor HLA class I and favorable clinical outcome, suggesting that iDCs may be critical for robust tumor control by improving prediction of patient survival.
Citation Format: Ombretta Melaiu, Renata Boldrini, Marco Chierici, Cesare Furlanello, Doriana Fruci. Clinical relevance of tumor-infiltrating immune cells in neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B37.
Abstract B46: Roles for LKB1 at the immune synapse during B-cell activation and antitumor responses
Authors: Jimenez Laura , Waters Lynnea , Kim Diane N.H. , Walsh Nicole , Teitell Michael A. 
Published: February 2019

Abstract
Defense from infection or cancer is provided by coordinated actions of the innate and adaptive immune system, including B lymphocytes that generate antibodies (Abs) against pathogens or tumor antigens. B cells establish immune synapses with antigen-presenting cells during activation to initiate Ab-production, which may include entrance into a germinal center (GC) reaction to generate very high-affinity Abs. Establishment of an immune synapse requires polarity proteins to coordinate uptake and processing of external antigens. For this, there is a highly conserved family of partitioning defective (Par) proteins that mediates cell polarity in multiple cell types. In particular, Par-3, a member of the Par polarity complex (Par-3, aPKC, Par-6), is a key protein that localizes to the immune synapse and is required for B cell polarization and immune synapse formation. Recently, we showed that LKB1, the mammalian homolog of Par-4 and a regulator of energy metabolism, controls B cell activation, GC formation and differentiation into Ab-producing plasma cells. However, roles for LKB1 in B cell polarity, immune synapse formation and anti-tumor immunity are unknown. Based on previous studies showing that LKB1 induces cell polarity and co-localizes with Par-3, we hypothesize that LKB1 is required for Par complex assembly and controls immune synapse formation during B cell activation. Subcellular analysis of LKB1 by immunofluorescence microscopy in mouse primary B cells reveals LKB1 co-localization with aPKC in membrane protrusions required for immune synapse formation. Interestingly, B cell specific LKB1 knock out (BKO) mice exhibit mislocalization of aPKC/Par complex, loss of lymphoid tissue polarity and spontaneous B cell activation that results in the formation of giant GCs and secretion of proinflammatory cytokines and chemokines. Similar inflammatory profiles with T cell chemoattractants are known to recruit CD8+ cytotoxic T lymphocytes (CTLs) into solid tumors, such as melanoma. These similarities suggest that LKB1 inactivated B cells in the tumor microenvironment could stimulate T cell infiltrates into solid tumors. Our studies suggest that physiologic inactivation of LKB1 in B cells controls B cell activation, GC formation and potentially infiltration of T cells in the tumor microenvironment during anti-tumor responses. We are currently utilizing an exciting genetic mouse melanoma model to examine the role of LKB1 in promoting anti-tumor immunity. Together, our studies assess LKB1 as a target for augmenting adaptive immunity against cancer.
Citation Format: Laura Jimenez, Lynnea Waters, Diane N.H. Kim, Nicole Walsh, Michael A. Teitell. Roles for LKB1 at the immune synapse during B-cell activation and antitumor responses [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B46.
Abstract B53: Intra-tracheal delivery of low-dose bacterial lipopolysaccharides protects against tumor formation in the KP lung adenocarcinoma model
Authors: Sriram Ganapathy , Milling Lauren , Irvine Darrell J. , Yaffe Michael B. 
Published: February 2019

Abstract
While genetically engineered mouse models (GEMM) of lung adenocarcinoma (LUAD) recapitulate some aspects of the histopathology of human LUAD, they poorly reflect the inflammatory components of human LUAD. In this study, we performed repeated weekly intra-tracheal dosing with bacterial lipopolysaccharides (LPS) after adenoviral-Cre (AdCre) delivery into K-RasLSL-G12D/+; p53fl/fl mice to examine the effect of inflammation on lung adenocarcinoma progression. LPS has been historically used to study the acute inflammatory response both locally and systemically in animal models. The typical response involves recruitment and activation of innate immune cells, mainly neutrophils and macrophages, to the site of delivery and/or production of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-1. Repeated long-term conditioning with low-dose LPS results in alveolar wall thickening as observed by uCT and the accumulation of lymphoid aggregates in the lung. However, surprisingly, LPS conditioning drastically reduced tumor incidence from 75% in the control group to 25%. Furthermore, starting LPS delivery four weeks after AdCre instillation, to eliminate any possible LPS effects on adenoviral delivery and K-Ras induction/p53 loss, still resulted in drastically reduced lung tumor formation suggesting that the effect results from an LPS-induced immune response. Two LPS instillations were sufficient to elicit this effect. Short-term antibody-mediated depletion of neutrophils or CD8+ T cells also did not abrogate the effect of LPS on tumor formation. In vitro re-stimulation of CD8+T cells (from blood or spleen) from tumor-free animals with KP tumor cells did not elicit interferon-gamma production, as assayed by intra-cellular cytokine staining and ELISPOT, suggesting that a cell type other than CD8+ T-cells or neutrophils mediates the effect. Interestingly and consistent with the inhibitory effect of LPS on tumor formation, multiple pneumonia diagnoses in COPD patients/smokers has been associated with a lower odds ratio of developing lung cancer in humans. Identifying the cell-type (s) and mechanisms mediating the anti-tumor effect of LPS will help in defining the aspects of immune response that inhibit LUAD progression.
Citation Format: Ganapathy Sriram, Lauren Milling, Darrell J. Irvine, Michael B. Yaffe. Intra-tracheal delivery of low-dose bacterial lipopolysaccharides protects against tumor formation in the KP lung adenocarcinoma model [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B53.
Abstract B64: Characterizing the tumor immune microenvironment of metastatic and nonmetastatic renal clear cell carcinomas and colorectal carcinomas using computational methods
Authors: Kamal Yasmin , Varn Frederick S. , Chen Chao , Frost Hildreth Robert , Amos Christopher I. 
Published: February 2019

Abstract
Cancer is a leading cause of mortality worldwide with most cancer-related deaths attributed to metastatic disease progression. Engaging the immune system to fight cancer has several advantageous features, particularly given the unique role the immune system plays in initiating, maintaining, and fighting tumor metastasis. Here, we examine the tumor immune microenvironment in metastatic (primary stage IV -M1) and non-metastatic (primary stage I/II- M0) tumors in renal clear cell carcinoma (RCCC) and colorectal carcinoma (CRC) through the application of deconvolution algorithms and pathway analyses. Preliminary data suggests the tumor microenvironment varies based on cancer type as well as metastatic disease status, and these differences in immune infiltration significantly affect survival outcomes. The prevailing belief of the association of CD8+ T cells with a positive survival outcome did not hold true for renal clear cell carcinoma in our analysis. We further characterized the heterogeneity of the microenvironments in CRC and RCCC. Specific immune cell types consistently and differentially infiltrate tumors (NK and CD4+ T cells in particular), albeit their cellular status and influences on survival vastly differ based on the tumor type, suggesting each tumor type uniquely evades the immune system to promote metastasis.
Citation Format: Yasmin Kamal, Frederick S. Varn, Jr., Chao Chen, Hildreth Robert Frost, Christopher I. Amos. Characterizing the tumor immune microenvironment of metastatic and nonmetastatic renal clear cell carcinomas and colorectal carcinomas using computational methods [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B64.
Abstract B79: Identification and analysis of tumor-reactive CTLs in ovarian and cervical cancer tissues for developing a personalized immunotherapy
Authors: Nosaka Kazuto , Yoshikawa Yoshiaki , Suzuki Toshihiro , Saito Keigo , Shimomura Manami , Mizuno Shoichi , Suzuki Shiro , Kikkawa Fumitaka , Nakatsura Tetsuya 
Published: February 2019

Abstract
Cancer immunotherapy that target individual mutated neoantigens can mediate tumor regression. Ovarian cancer and cervical cancer are known to have relatively many somatic mutations and are considered to be good indications for immunotherapy. In order to develop personalized immunotherapy, we aimed to clarify the mutated neoantigens of individual patients with these cancers and to characterize the tumor antigen specific CTLs infiltrating into the tumor tissues.
We obtained resected tumor tissues and normal tissues from about 30 patients with ovarian cancer or cervical cancer. In ex vivo assay, we investigated the cell surface markers of CD8+ T cell in tumor and normal tissues and identified that the expression of CD107a or co-inhibitory molecules on CD8+ T cells in tumor tissues was higher than that in normal tissues. These tumor-infiltrating lymphocytes were cultured for 14 days and we could expand the numbers of TILs from all patients’ tumors. At the same time, we tried to establish patient derived xenografts (PDX) mouse model or generate tumor cell lines from these patients. In cases where we could obtain tumor cells by these ways, TILs and autologous tumor cells were co-cultured and we evaluated the tumor reactive CTLs by CD107a assay. Tumor reactive CTLs were enriched by sorting for CD107a+ PD-1+ CD8+ T cells and expanded in vitro. The expanded CD 107a+ PD-1+ CD8+ T cells were co-cultured with autologous tumor cells and expression of CD 107a was analyzed. As a result, the proportion of CD 107a+ cells increased after expansion. Therefore, we could prove that many tumor-reactive CTLs are contained in population of CD107a+ PD-1+ CD8+ T cells.
These results may provide the marker to isolate tumor reactive TILs ex vivo. We will identify candidates of mutated neoantigens by the next generation sequencing combined with bioinformatics prediction and will find the tumor reactive CTLs and these TCRs that recognize these mutated neoantigens.
Citation Format: Kazuto Nosaka, Yoshiaki Yoshikawa, Toshihiro Suzuki, Keigo Saito, Manami Shimomura, Shoichi Mizuno, Shiro Suzuki, Fumitaka Kikkawa, Tetsuya Nakatsura. Identification and analysis of tumor-reactive CTLs in ovarian and cervical cancer tissues for developing a personalized immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B79.
Abstract IA19: New directions in T cell therapies for cancer
Authors: Maus Marcela 
Published: February 2019

Abstract
Engineering T cells with chimeric antigen receptors (CARs) has shown great promise in the clinical setting for B-cell malignancies such as adult and pediatric acute lymphoblastic leukemia (ALL). This therapy is so effective in ALL that based on relatively small numbers of patients, multiple academic centers and their industry partners have received Breakthrough Designation from the FDA to commercialize CAR T cell products. However, successful application of this form of therapy to other cancers is likely to require refinements in the molecular and clinical technologies. Our laboratory is focused on generating next-generation CAR T cells that overcome some of the main barriers for their widespread use: (1) cytokine release syndrome, (2) antigen escape, and (3) susceptibility to immunosuppression. We will discuss our ongoing work in these areas, including some of the successes and obstacles to modeling these systems in the preclinical setting.
Citation Format: Marcela Maus. New directions in T cell therapies for cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA19.
Predictive Model for High-Risk Coronary Artery Disease
Authors: Jang James J. , Bhapkar Manjushri , Coles Adrian , Vemulapalli Sreekanth , Fordyce Christopher B. , Lee Kerry L. , Udelson James E. , Hoffmann Udo , Tardif Jean-Claude , Jones W. Schuyler , Mark Daniel B. , Sorrell Vincent L. , Espinoza Andrey , Douglas Pamela S. , Patel Manesh R. ,   on behalf of the PROMISE Investigators
Published: February 2019

Background:
Patients with high-risk coronary artery disease (CAD) may be difficult to identify.

Methods:
Using the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) cohort randomized to coronary computed tomographic angiography (n=4589), 2 predictive models were developed for high-risk CAD, defined as left main stenosis (≥50% stenosis) or either (1) ≥50% stenosis [50] or (2) ≥70% stenosis [70] of 3 vessels or 2-vessel CAD involving the proximal left anterior descending artery. Pretest predictors were examined using stepwise logistic regression and assessed for discrimination and calibration.

Results:

High-risk CAD was identified in 6.6% [50] and 2.4% [70] of patients. Models developed to predict high-risk CAD discriminated well: [50], bias-corrected C statistic=0.73 (95% CI, 0.71−0.76); [70], bias-corrected C statistic=0.73 (95% CI, 0.68−0.77). Variables predictive of CAD in both models included family history of premature CAD, age, male sex, lower glomerular filtration rate, diabetes mellitus, elevated systolic blood pressure, and angina. Additionally, smoking history was predictive of [50] CAD and sedentary lifestyle of [70] CAD. Both models characterized high-risk CAD better than the Pooled Cohort Equation (area under the curve=0.70 and 0.71 for [50] and [70], respectively) and Diamond-Forrester risk scores (area under the curve=0.68 and 0.71, respectively). Both [50] and [70] CAD was associated with more frequent invasive interventions and adverse events than non-high-risk CAD (all
P
<0.0001).

Conclusions:
In contemporary practice, 2.4% to 6.6% of stable, symptomatic patients requiring noninvasive testing have high-risk CAD. A simple combination of pretest clinical variables improves prediction of high-risk CAD over traditional risk assessments.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01174550.
Extra-Judicial Khulʿ Divorce in India’s Muslim Personal Law
Authors: Vatuk Sylvia 
Published: February 2019

AbstractThis essay examines khulʿ divorce as it is interpreted, understood, and practiced in India by Sunni Hanafi Muslims. My research was part of a broadly focused investigation of the impact of India’s Muslim Personal Law upon women’s well-being, begun in 1998 and on-going. I draw upon ethnographic and archival data collected between 1998 and 2001, as well as a recent review of the relevant case law. Widespread stereotypes represent Indian Muslim women as powerless to free themselves from unhappy marriages. However, they do have several legal options. One is to offer the husband a consideration for granting an extra-judicial divorce by khulʿ. This has distinct advantages over filing for divorce in a court of law. But its downside is that the husband must agree to release his wife from the marriage. Many refuse, others drive hard bargains or create other difficulties for the wife that are discussed in the essay.
Educated with Distinction
Authors: Sassmannshausen Christian 
Published: February 2019

AbstractBeginning in the 1850s, the Ottoman Empire’s educational landscape expanded and diversified. During this era of imperial reforms, discourses around education increasingly focused on the importance of female education. This article uses census material from Tripoli in today’s Lebanon to explore the experiences of students in the wake of these shifts. It examines literacy rates across different social and religious groups and the extent to which educational decisions parents made were biased by gender and class. The analysis reveals that the rate of Muslim boys’ literacy was high even before new schools opened starting in the 1850s. As for the post-reform developments, it shows that although around a quarter of propertied families decided to send their sons and daughters to school, a considerable proportion of Muslim and Christian families privileged sons alone. Still, reforms allowed a number of groups in the generations between 1860 and 1910 to achieve higher rates of literacy, including Muslim and Christian girls as well as the children of artisans.
Empress Dowager Cixi’s Imperial Pedagogy: The School for Female Nobles and New Visions of Authority in Early Twentieth Century China
Authors: Barish Daniel 
Published: February 2019

AbstractAfter the 1861 coup that brought her to power, Empress Dowager Cixi mobilized a variety of traditions of imperial education to cultivate the persona of a classical ruler and cement her place at the center of Qing governance. At the turn of the twentieth century, however, her enemies launched a propaganda campaign that portrayed Cixi not as a legitimate ruler but as the enemy of progress. In response, Cixi herself began a project to refashion the Qing throne, placing new institutions of imperial education for women at the center of efforts to reestablish her domestic authority and reclaim the Qing’s international standing. After reviewing Cixi’s strategies of legitimation from 1861 to 1898, this paper focuses on the Empress’s twentieth-century attempt to construct an educational apparatus to invent and train a group of female nobles who were intended to play a leading role in reforms around the country. In advocating for the role of these women and institutions, Cixi placed herself and a cosmopolitan cohort of women at the center of plans for China’s future. This future was predicated on a refashioned Qing imperial ideology that grounded the legitimacy of the state in part in its participation in global norms and practices of governance. Although the future Cixi imagined for herself and the Qing never materialized, an examination of the project helps shed new light on the politics and culture of the late Qing and beyond.
Intrinsic Valuing and the Limits of Justice: Why the Ring of Gyges Matters
Authors: Paytas Tyler , Baima Nicholas R. 
Published: February 2019

AbstractCommentators such as Terence Irwin and Christopher Shields claim that the Ring of Gyges argument in Republic 2 cannot demonstrate that justice is chosen only for its consequences. This is because valuing justice for its own sake is compatible with judging its value to be overridable. Through examination of the rational commitments involved in valuing normative ideals such as justice, we aim to show that this analysis is mistaken. If Glaucon is right that everyone would endorse Gyges’ behavior, it follows that nobody values justice intrinsically. Hence, the Gyges story constitutes a more serious challenge than critics maintain.
Adaptation of the Pet Attitude Scale to German
Authors: Römpke Anne-Kristin 
Published: February 2019

AbstractThe growing body of research on human-animal bonds highlights the need of common methods and research designs to facilitate comparisons. A well-evaluated and widely used instrument for measuring subjective attitude towards house pets (companion animals) is the Pet Attitude Scale (PAS). The objective of the present study was to develop and validate a cross-cultural version of the PAS for use in German-speaking countries. The scale was translated and back-translated, pre-tested, and tested for reliability and factor structure. Results indicated the German adaptation showed reliability measures comparable to the original version. The factor structure resembled the results of a reevaluation of the PAS. Prediction of companion animal ownership showed good results. The German adaptation of the PAS appears to be reliable and valid for the assessment of the attitude towards companion animals in German-speaking countries.
What the Holy Seed Defiled: The Textual Problem of Genesis 49:4
Authors: Albanese Matthew James 
Published: February 2019

AbstractThe preservation of Gen 49:4c in the Masoretic Text presents readers with a notoriously difficult textual problem. Both ancient and contemporary interpreters disagree widely about its meaning. In this article, I summarize the lexical-syntactical difficulties of Gen 49:4c and survey its diverse interpretations throughout history. I then propose that the grammatical and hermeneutical difficulties of the phrase may be resolved in two steps. We should first modify the vocalization of the suffixed noun yeṣū‛î in order to create the construct form yeṣū‛ê. This suggestion only requires the addition of a single vocalic dot. Second, we must understand the construct form yeṣū‛ê as the head noun of an unmarked relative clause which embeds the following verb ‛ālāh. This proposal creates a precise parallel with the previous line and is corroborated by the genealogical summary in 1 Chron 5:1.
Aesop and Jotham’s Parable of the Trees (Judges 9:8-15)
Authors: Margulies Zachary 
Published: February 2019

AbstractRecent scholarship has entertained the possibility that Jotham’s Parable of the Trees (Judg 9:8-15) is derived from the Greek text of one of Aesop’s Fables (Perry 262). This article refutes this notion, tracing the dependence of Aesop’s fable on one Septuagint tradition, which itself is a translation of the Hebrew. The article goes on to propose a pre-exilic setting for the biblical fable, based not on its foregrounded opinion of monarchy, but on its background assumptions of deity.