bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells of colorectal cancer patients’ stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells
Authors: Schwarz Sandra , Schmitz Johanna , Löffler Markus W , Ghosh Michael , Rammensee Hans-Georg , Olshvang Evgenia , Markel Marvin , Mockel-Tenbrinck Nadine , Dzionek Andrzej , Krake Susann , Arslan Basak , Kampe Kapil Dev , Wendt Anne , Bauer Peter , Mullins Christina S , Schlosser Andreas , Linnebacher Michael 
Published: December 2022

BackgroundPatients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc).MethodsColorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients’ Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay.Results100 tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. The neoantigens originated from single nucleotide substitutions in the genesIQGAP1, CTNNB1,andTRIT1. Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment.ConclusionThese results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
Patient-oriented risk score for predicting death 1 year after myocardial infarction: the SweDen risk score
Authors: Rylance Rebecca Tremain , Wagner Philippe , Olesen Kevin K W , Carlson Jonas , Alfredsson Joakim , Jernberg Tomas , Leosdottir Margret , Johansson Pelle , Vasko Peter , Maeng Michael , Mohammed Moman Aladdin , Erlinge David 
Published: December 2022

ObjectivesOur aim was to derive, based on the SWEDEHEART registry, and validate, using the Western Denmark Heart registry, a patient-oriented risk score, the SweDen score, which could calculate the risk of 1-year mortality following a myocardial infarction (MI).MethodsThe factors included in the SweDen score were age, sex, smoking, diabetes, heart failure and statin use. These were chosen a priori by the SWEDEHEART steering group based on the premise that the factors were information known by the patients themselves. The score was evaluated using various statistical methods such as time-dependent receiver operating characteristics curves of the linear predictor, area under the curve metrics, Kaplan-Meier survivor curves and the calibration slope.ResultsThe area under the curve values were 0.81 in the derivation data and 0.76 in the validation data. The Kaplan-Meier curves showed similar patient profiles across datasets. The calibration slope was 1.03 (95% CI 0.99 to 1.08) in the validation data using the linear predictor from the derivation data.ConclusionsThe SweDen risk score is a novel tool created for patient use. The risk score calculator will be available online and presents mortality risk on a colour scale to simplify interpretation and to avoid exact life span expectancies. It provides a validated patient-oriented risk score predicting the risk of death within 1 year after suffering an MI, which visualises the benefit of statin use and smoking cessation in a simple way.
Clusters of lifestyle behaviors associated with atherosclerosis risk factors in children and adolescents with congenital heart disease: Floripa CHild Study
Authors: Honicky Michele , Cardoso Silvia M. , de Lima Luiz R.A. , Silva Diego A.S. , de Lima Tiago R. , Back Isabela de C. , Moreno Yara M.F. 
Published: December 2022

Secondary cardiovascular disease is the main cause of mortality in congenital heart disease (CHD) patients. The cardiovascular risk could be widely prevented with adherence to a healthy lifestyle; however, clusters of lifestyle behaviors related to atherosclerosis risk factors in children and adolescents with CHD remain unclear. We aimed to describe the clusters of lifestyle behaviors of children and adolescents with CHD and to evaluate their association with atherosclerosis risk factors. We conducted a cross-sectional study on 227 children and adolescents with CHD (median age:10.02 [IQR:7.08–13.02] years). Dietary intake, physical activity (PA), and sedentary behavior (SB) were evaluated. Clusters of lifestyle behaviors were determined using a two-step cluster analysis. Atherosclerosis risk factors evaluated include body fat mass, central obesity, blood pressure, lipid parameters, glucose, C-reactive protein, and carotid intima-media thickness (cIMT). Multiple logistic regressions were used. The “unhealthy: high SB + low PA” cluster was associated with elevated body fat mass, central obesity, and elevated cIMT. Furthermore, the “unhealthy: low PA + unhealthy eating habits” cluster was associated with elevated body fat mass, central obesity, and elevated glucose. The unhealthier lifestyle behavior clusters were associated with atherosclerosis risk factors in children and adolescents with CHD. Multidisciplinary strategies to promote healthy behaviors are needed to prevent cardiovascular disease in later life.
Wormholes, killing horizons and naked singularities: light surfaces in axially symmetric spacetimes
Authors: Pugliese D. , Quevedo H. 
Published: December 2022

AbstractWe study several classes of exterior and interior axially symmetric spacetimes, such as wormholes, accelerating black holes, and binary black hole systems, from the point of view of light surfaces related to the generators of Killing horizons. We show that light surfaces constitute a useful framework for the study of the more diverse axially symmetric geometries. In particular, we point out the existence of common properties of the light surfaces in different spacetimes. We introduce a deformation of the Kerr–Newman metric and apply the light surfaces framework to analyze several generalizations in a compact form. As particular examples, we analyze static and spinning wormhole solutions, black holes immersed in external (perfect fluid) dark matter, spacetimes with (Taub) NUT charge, acceleration, magnetic charge, and cosmological constant, binary Reissner–Nordström black holes, a solution of a (low-energy effective) heterotic string theory, and the $$(1+2)$$

(
1
+
2
)

dimensional BTZ geometry.
Geodesic motion in Euclidean Schwarzschild geometry
Authors: Battista Emmanuele , Esposito Giampiero 
Published: December 2022

AbstractThis paper performs a systematic investigation of geodesic motion in Euclidean Schwarzschild geometry, which is studied in the equatorial plane. The explicit form of geodesic motion is obtained in terms of incomplete elliptic integrals of first, second and third kind. No elliptic-like orbits exist in Euclidean Schwarzschild geometry, unlike the corresponding Lorentzian pattern. Among unbounded orbits, only unbounded first-kind orbits are allowed, unlike general relativity where unbounded second-kind orbits are always allowed.
A comparative numerical study of a semi-infinite heat conductor subject to double strip heating under non-Fourier models
Authors: Awad Emad , Fayik Mohsen , El-Dhaba Amr R. 
Published: December 2022

AbstractThe present work considers a two-dimensional (2D) heat conduction problem in the semi-infinite domain based on the classical Fourier model and other non-Fourier models, e.g., the Maxwell–Cattaneo–Vernotte (MCV) equation, parabolic, hyperbolic, and modified hyperbolic dual-phase-lag (DPL) equations. Using the integral transform technique, Laplace, and Fourier transforms, we provide a solution of the problem (Green’s function) in Laplace domain. The thermal double-strip problem, allowing the wave interference within the heat conductor, is considered. A numerical technique, based on the Durbin series for inverting Laplace transform and the trapezoidal rule for calculating an integral form of the solution in the double-strip case, is adopted to recover the solution in the physical domain. Finally, discussions for different non-Fourier heat transfer situations are presented. We compare among the speeds of hyperbolic heat transfer models and shed light on the concepts of flux-precedence and temperature-gradient-precedence, hallmarks of the lagging response idea. Otherwise, we emphasize the existence of a relationship between the waves speed and the time instant of interference onset, underlying the five employed heat transfer models.
Underground research laboratories, an important support to the Belgian Regulatory Body's Research and Development programme and the management of uncertainties
Authors: Bernier Frédéric J. , Detilleux Valéry , Lemy Frank , Pochet Guillaume M. , Surkova Maryna , Volckaert Geert , Mommaert Chantal 
Published: December 2022

Abstract

In order to fulfil its mission, the Belgian Regulatory Body (constituted in Belgium by FANC and Bel V) has set up its own Research & Development programme, independent from the Waste Management Organisation's one. The Regulatory Body's Research & Development programme is mostly intended to investigate safety issues with the objective to be able to assess if the safety concept developed by the Waste Management Organisation fulfils the defined safety requirements. It includes the development and the follow-up of
in situ
experiments in underground research laboratories (e.g. in the Mont Terri project in Switzerland and at Tournemire in France). Such activities are essential to maintain and improve the scientific and technical skills, to strengthen the independence from the Waste Management Organisation and to build public confidence in the regulatory function.

More generally, Research & Development in underground research laboratories is important to the Regulatory Body as it allows investigating processes, technologies and activities important to safety under
in situ
conditions. In particular, it is essential to accurately identify and characterize the processes upon which the safety functions of a disposal system rely, as well as processes that may affect the system performance. It is also necessary to demonstrate that construction and operational methods and technologies are technically feasible and can be implemented as assumed in the safety case. Such research and development activities are of great importance to properly manage some of the key uncertainties associated with a disposal programme and in particular to identify, characterize and reduce them where needed.
Effects of Glycyrrhizin (GL) Supplementation on Survival, Growth Performance, Expression of Feeding-Related Genes, Activities of Digestive Enzymes, Antioxidant Capacity, and Expression of Inflammatory Factors in Large Yellow Croaker (Larimichthys crocea) Larvae
Authors: Wang Yuntao , Xu Wenxuan , Zhang Jianmin , Liu Jiahui , Wang Zhen , Liu Yongtao , Mai Kangsen , Ai Qinghui 
Published: December 2022

A 30-day feeding trial was conducted to determine the effects of dietary glycyrrhizin (GL) on survival, growth performance, expression of feeding-related genes, activities of digestive enzymes, antioxidant capacity, and expression of inflammatory factors of large yellow croaker larvae with an initial weight of

3.78
±
0.27

mg. Four 53.80% crude protein and 16.40% crude lipid diets were formulated with supplementation of 0%, 0.005%, 0.01%, and 0.02% GL, respectively. Results indicated that larvae fed diets with GL had higher survival rate and specific growth rate than the control (

P
<
0.05

). Compared with the control, the mRNA expression of orexigenic factor genes including neuropeptide Y (npy) and agouti-related protein (agrp) were significantly increased in larvae fed the diet with 0.005% GL, while the mRNA expression of anorexigenic factor genes including thyrotropin-releasing hormone (trh), cocaine and amphetamine regulated transcript (cart), and leptin receptor (lepr) were significantly decreased in larvae fed the diet with 0.005% GL (

P
<
0.05

). The trypsin activity in larvae fed the diet with 0.005% GL was significantly higher than the control (

P
<
0.05

). The alkaline phosphatase (AKP) activity in larvae fed the diet with 0.01% GL was significantly higher than the control (

P
<
0.05

). A clear increase of total glutathione (T-GSH) content, activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) was observed in larvae fed the diet with 0.01% GL compared with the control (

P
<
0.05

). Moreover, the mRNA expression of interleukin-1β (il-1β) and interleukin-6 (il-6) (proinflammatory genes) in larvae fed the diet with 0.02% GL were significantly lower than the control (

P
<
0.05

). In conclusion, the supplementation of 0.005% -0.01% GL could enhance the expression of orexigenic factor genes, activities of digestive enzymes and antioxidant capacity, ultimately improving the survival, and growth performance of large yellow croaker larvae.
Meta-Analysis of Human Cancer Single-Cell RNA-Seq Datasets Using the IMMUcan Database
Authors: Camps Jordi , Noël Floriane , Liechti Robin , Massenet-Regad Lucile , Rigade Sidwell , Götz Lou , Hoffmann Caroline , Amblard Elise , Saichi Melissa , Ibrahim Mahmoud M. , Pollard Jack , Medvedovic Jasna , Roider Helge G. , Soumelis Vassili 
Published: December 2022

Abstract

The development of single-cell RNA sequencing (scRNA-seq) technologies has greatly contributed to deciphering the tumor microenvironment (TME). An enormous amount of independent scRNA-seq studies have been published representing a valuable resource that provides opportunities for meta-analysis studies. However, the massive amount of biological information, the marked heterogeneity and variability between studies, and the technical challenges in processing heterogeneous datasets create major bottlenecks for the full exploitation of scRNA-seq data. We have developed IMMUcan scDB (https://immucanscdb.vital-it.ch), a fully integrated scRNA-seq database exclusively dedicated to human cancer and accessible to nonspecialists. IMMUcan scDB encompasses 144 datasets on 56 different cancer types, annotated in 50 fields containing precise clinical, technological, and biological information. A data processing pipeline was developed and organized in four steps: (i) data collection; (ii) data processing (quality control and sample integration); (iii) supervised cell annotation with a cell ontology classifier of the TME; and (iv) interface to analyze TME in a cancer type–specific or global manner. This framework was used to explore datasets across tumor locations in a gene-centric (CXCL13) and cell-centric (B cells) manner as well as to conduct meta-analysis studies such as ranking immune cell types and genes correlated to malignant transformation. This integrated, freely accessible, and user-friendly resource represents an unprecedented level of detailed annotation, offering vast possibilities for downstream exploitation of human cancer scRNA-seq data for discovery and validation studies.

Significance:
The IMMUcan scDB database is an accessible supportive tool to analyze and decipher tumor-associated single-cell RNA sequencing data, allowing researchers to maximally use this data to provide new insights into cancer biology.
Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity
Authors: Williams Hannah L. , Dias Costa Andressa , Zhang Jinming , Raghavan Srivatsan , Winter Peter S. , Kapner Kevin S. , Ginebaugh Scott P. , Väyrynen Sara A. , Väyrynen Juha P. , Yuan Chen , Navia Andrew W. , Wang Junning , Yang Annan , Bosse Timothy L. , Kalekar Radha L. , Lowder Kristen E. , Lau Mai Chan , Elganainy Dalia , Morales-Oyarvide Vicente , Rubinson Douglas A. , Singh Harshabad , Perez Kimberly , Cleary James M. , Clancy Thomas E. , Wang Jiping , Mancias Joseph D. , Brais Lauren K. , Hill Emma R. , Kozak Margaret M. , Linehan David C. , Dunne Richard F. , Chang Daniel T. , Koong Albert C. , Hezel Aram F. , Hahn William C. , Shalek Alex K. , Aguirre Andrew J. , Nowak Jonathan A. , Wolpin Brian M. 
Published: December 2022

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in &gt; 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell–cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC.

Significance:
A high-throughput pipeline using multiplex immunofluorescence in pancreatic cancer reveals striking expression subtype intratumoral heterogeneity with implications for therapy selection and identifies co-expressor cells that may serve as intermediates during subtype switching.
Abstract PR006: Single-molecule and single-cell epigenetics: Decoding the epigenome for cancer research and diagnostics
Authors: Shema Efrat 
Published: December 2022

Abstract
Genes and genomic elements are packaged by chromatin structures that regulate their activity. We developed a novel high-throughput single-molecule imaging technology to decode combinatorial modifications on millions of individual nucleosomes. We apply this technology to image nucleosomes and delineate their combinatorial epigenetic patterns, and how these patterns are deregulated in cancer. In addition, we adapt single-cell technologies based on CyTOF to profile the global levels of multiple histone modifications in single cells, thus revealing epigenetic heterogeneity in cancer. Our research focuses on pediatric gliomas harboring lysine to methionine substitution of residue 27 on histone H3 (K27M). We provide evidence for widespread effects of the H3-K27M oncohistone on multiple core epigenetic pathways, and highlight the capability of single-molecule and single-cell tools to reveal mechanisms of chromatin deregulation and heterogeneity in cancer. We also harness the single-molecule technology as a novel liquid biopsy approach, by comprehensively profiling combinatorial epigenetic marks of plasma-isolated nucleosomes. Applying this analysis to a cohort of plasma samples detect colorectal cancer at high accuracy and sensitivity, even at early stages. Finally, combining this proteomic analysis with single-molecule DNA sequencing reveals the tissue-of-origin of the tumor.
Citation Format: Efrat Shema. Single-molecule and single-cell epigenetics: Decoding the epigenome for cancer research and diagnostics. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr PR006.
Abstract IA013: Early-onset colorectal cancer: Emerging risk factors and early detection
Authors: Cao Yin 
Published: December 2022

Abstract
Early-onset colorectal cancer (CRC) is increasing in the United States and globally. Compared to CRC diagnosed at older ages, patients with early-onset CRC experienced significant diagnostic delays, with tumors of advanced clinicopathological features and unknown etiology. While screening recommendations have been recently lowered to age 45 in the United States, about half of early-onset CRC cases are diagnosed before age 45, thus will not be detected via screening. This presentation will review emerging risk factors of early-onset CRC throughout the life course, as well as clinical signs and symptoms associated with early-onset CRC.
Citation Format: Yin Cao. Early-onset colorectal cancer: Emerging risk factors and early detection [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA013.
Abstract IA015: Combined single cell atlasing and organoid modeling reveal progressive plasticity during human colorectal cancer metastasis
Authors: Ganesh Karuna 
Published: December 2022

Abstract
Metastatic cancers invariably relapse due to the emergence of therapy resistant subclones that are capable of self-renewal, slow cell-cycling, tumor re-initiation and therapy resistance. However, the molecular mechanisms that underpin the phenotypic plasticity of metastasis stem cells, their relationship to tumor initiating cancer stem cells and macrometastasis, and the co-evolution of the immune response to dynamically emerging tumor regenerative states are not understood. We are adopting a patient-derived functional biospecimen approach combining (1) hypothesis-generation using transcriptomics, epigenomics and spatial/histological analysis of patient samples of primary and metastatic gastrointestinal (GI) cancer with (2) mechanistic dissection in cutting-edge patient-derived organoid models, including co-cultures with immune/stromal cells, and (3) genetically engineered and orthotopic transplantation models of metastatic GI cancer. By profiling, lineage tracing and genetically interrogating the evolving transcriptomic and chromatin landscapes of regenerative metastatic states, we are defining the molecular mechanisms that underpin the phenotypic plasticity of metastatic cancer, and the co-evolution of the tumor microenvironmental response to dynamically emerging tumor regenerative states. Our approach is unveiling crucial signaling nodes required for metastatic plasticity that can be therapeutically targeted to improve outcomes for patients with advanced cancer.
Citation Format: Karuna Ganesh. Combined single cell atlasing and organoid modeling reveal progressive plasticity during human colorectal cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA015.