bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 674: CRISPR and drug screens identify ERK as the mediator of IFNg-induced melanoma growth inhibition
Authors: Champhekar Ameya S. , Heymans Rachel , Gonzalez Cynthia , Font Guillem Turon , Karin Daniel , Lee June , Damoiseaux Robert , Ribas Antoni 
Published: April 2023

Abstract
Interferon-gamma (IFNg) is critical for the success of immune checkpoint blockade therapy. Disruption of IFNg signaling makes tumors resistant to anti-PD-1/L1 treatment primarily by evasion of the growth inhibition (GI) induced by this cytokine. However, the pathways mediating IFNg-induced GI are largely unknown. We used two independent approaches to delineate the IFNg GI pathway, a chemical genomics screen and a whole genome targeting CRISPR/Cas9 screen in an IFNg GI-sensitive patient-derived melanoma (PDM) cell line. Drug screening revealed that treatment with RAF and ERK inhibitors disrupted IFNg GI in PDM cells. For the CRISPR screen, gene-level analysis showed that the magnitude of enrichment for guide RNAs targeting ERK2 in IFNg-treated cells was comparable to proximal IFNg signaling proteins like JAK1, STAT1, IFNGR2, and JAK2 (&gt;26-fold enrichment for ERK2, p = 2.28e-07). Thus, results from both these experiments converged upon ERK as the primary downstream target of IFNg essential for GI induction. We validated the involvement of ERK by detecting a sustained increase in phospho-ERK1/2 levels following IFNg treatment. In live imaging experiments, we found that blocking ERK activity with the ERK inhibitor Ulixertinib blocks the induction of cell death after IFNg treatment in 17 of 23 (~74%) IFNg-sensitive PDM lines covering all the MAPK mutant and triple wildtype molecular subtypes of melanoma. Decreasing and increasing ERK activity levels using shRNA and overexpression approaches also led to a decrease and increase in IFNg-mediated GI, respectively. We have identified NOXA and DR5 as likely mediators of cell death through the IFNg-ERK GI pathway by comparing gene expression profiles of control and IFNg-treated PDM cells. Finally, phorbol 12-myristate 13-acetate (PMA), a known ERK activator, synergizes with IFNg treatment to induce increased GI in PDM cells (Bliss synergy score 16.87, p = 1.83e-123). In summary, the IFNg-ERK signaling axis mediates cell death downstream of IFNg treatment in melanoma cells. This pathway is active in all melanoma subtypes, making it an attractive target to enhance IFNg GI in tumor cells. Our results provide a new understanding of the IFNg GI pathway that will also be crucial to define mechanisms of GI resistance in tumor cells.
Citation Format: Ameya S. Champhekar, Rachel Heymans, Cynthia Gonzalez, Guillem Turon Font, Daniel Karin, June Lee, Robert Damoiseaux, Antoni Ribas. CRISPR and drug screens identify ERK as the mediator of IFNg-induced melanoma growth inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 674.
Abstract 6764: Multi-parametric comparison of scRNA-seq with CITE-seq and ultrahigh-plex spatial phenotyping of proteins in FFPE head and neck tumor biopsies: An opportunity to generate uniquely comprehensive multi-omic single cell datasets to investigate the tumor microenvironment
Authors: Pratapa Aditya , Jensen Shawn M. , Jhaveri Niyati , Koguchi Yoshinobu , Rajamanickam Venkatesh , Bernard Brady , Christie Tanisha , Piening Brian , Leidner Rom S. , Braubach Oliver , Fox Bernard A. 
Published: April 2023

Abstract
Single cell RNA-seq (scRNA-seq) performed on cell suspensions isolated from tumor biopsies provides substantial insights into the transcriptional state of the cells in the tumor microenvironment (TME). Complementing this work with multi-omic Cellular Indexing of Transcriptomes and Epitopes (CITE-seq), which adds barcoded antibodies to label the surface of isolated cells, allows us to additionally characterize surface proteins. While information gleaned from these studies is dramatically expanding our understanding of the evolving immune response and tumor-immune interactions, it lacks an appreciation of the many spatial relationships that are present within the TME. Spatial phenotyping with the power of single cell resolution and whole slide imaging provides a valuable tool for identifying the cellular architecture and organization of spatial neighborhoods that perform critical roles in tumor progression, resistance, and clinical responses. Here, we explore bioinformatic strategies aimed at combining scRNA-seq and CITE-seq data with single-cell spatial protein data obtained with the PhenoCycler-Fusion (PCF) imaging platform. To this end, we performed whole-slide spatial phenotyping with an ultrahigh-plex PCF panel on FFPE human head and neck tumors. The same biopsies were also enzymatically digested and subjected to CITE-seq and scRNA-seq analysis. The combined multi-omic, single cell dataset provides a uniquely comprehensive account of the cellular states, functional significance and spatial neighborhoods that govern the TME. This study represents a novel approach to integrate high dimensional data from bulk tissue and single-cell spatial technologies to provide deeper insights into tumor biology and, in turn, to develop more informed strategies for combination immunotherapy trials and improved patient outcomes.
Citation Format: Aditya Pratapa, Shawn M. Jensen, Niyati Jhaveri, Yoshinobu Koguchi, Venkatesh Rajamanickam, Brady Bernard, Tanisha Christie, Brian Piening, Rom S. Leidner, Oliver Braubach, Bernard A. Fox. Multi-parametric comparison of scRNA-seq with CITE-seq and ultrahigh-plex spatial phenotyping of proteins in FFPE head and neck tumor biopsies: An opportunity to generate uniquely comprehensive multi-omic single cell datasets to investigate the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6764.
Abstract PL03-01: New insights into carcinogenesis from normal esophagus
Authors: Jones Phil H. 
Published: April 2023

Abstract
All normal tissues studied to date carry somatic mutant clones, the burden of which increases with age. This talk considers how insights into the biology of mutants in normal tissues can inform our understanding of the earliest stages of carcinogenesis. The esophagus becomes a patchwork of mutant clones. As they expand, these clones compete for the limited space available, resulting in selection of the fittest mutant genes. The ability to out compete other mutants in normal tissue does not correlate with carcinogenic potential. For example, NOTCH1 mutant clones colonize most of the esophagus by middle age but NOTCH1 mutations are comparatively rare in squamous cancers. In mouse models Notch pathway mutant clones eliminate microscopic intraepithelial neoplasms and loss of Notch1 markedly slows esophageal tumor growth. In contrast, mutant TP53 is less effective than NOTCH1 at driving clonal expansion but is found in almost all human squamous esophageal cancers and contributes to carcinogenesis in mice.
The normal tissue mutational landscape of the esophagus is shaped by environmental factors. For example, body metabolism alters the behavior of mutant PIK3CA which drives clonal expansions in the esophagus of overweight humans and mice. The mutation causes cells to switch their metabolism to aerobic glycolysis, giving the mutants a proliferative advantage. One way to reduce the competitive advantage of mutants is to increase the fitness of the neighboring cells. Treating cells or mice with metformin, a drug used to treat type 2 diabetes, induces aerobic glycolysis throughout the tissue. This eliminates the growth advantage of Pik3ca mutant clones, showing it may be possible to halt the expansion of oncogenic mutant populations.
Beyond the esophagus, these findings suggest the need to consider the relative prevalence of mutations in normal tissue and the corresponding cancer(s) before deciding if a mutant gene is a cancer driver or not. Variation in cancer risk between different human populations may depend on the proportion of pro- and anti-oncogenic mutants in normal tissue. Understanding how certain mutations can impede cancer development and how environmental factors alter selection of oncogenic mutants in normal tissue may guide new approaches to cancer prevention.
Citation Format: Phil H. Jones. New insights into carcinogenesis from normal esophagus. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-01.
Abstract SY26-01: Mapping cellular plasticity in tumor progression and drug resistance
Authors: Yanai Itai 
Published: April 2023

Abstract
Cellular plasticity is emerging as an important driving force underlying cancer progression and drug resistance. In this talk, I will discuss the concept of cancer cell states present in the tumor prior to treatment, as well as those that accompany resistance to increasing drug doses. In particular, I will discuss work published in our recent manuscript 'Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment' and recent developments in this project. Second, I will discuss our new work of 'Drug-induced adaptation along a resistance continuum in cancer cells'.
Citation Format: Itai Yanai. Mapping cellular plasticity in tumor progression and drug resistance. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY26-01.
Supplementary Figures 1- 7 from ILT3 (LILRB4) Promotes the Immunosuppressive Function of Tumor-Educated Human Monocytic Myeloid-Derived Suppressor Cells
Authors: Singh Latika , Muise Eric S. , Bhattacharya Anannya , Grein Jeff , Javaid Sarah , Stivers Peter , Zhang Jun , Qu Yujie , Joyce-Shaikh Barbara , Loboda Andrey , Zhang Chunsheng , Meehl Michael , Chiang Derek Y. , Ranganath Sheila H. , Rosenzweig Michael , Brandish Philip E. 
Published: April 2023

<p>Figure S1A-C - Dot plots and histograms from flow cytometry analysis of SK-MEL-5-educated M-MDSCs and PBMCs cultured in medium alone.</p><p>Figure S1D - FACS result of cell surface staining of cytokine-induced M-MDSCs and PBMCs cultured in medium alone.</p><p>Figure S1E - Cell surface staining of monocytes cultured in the presence of M-CSF and IL4 and SK-MEL-5-educated M-MDSCs by staining with HLA-DR.</p><p>Figure S2 A-B - ILT3 is highly expressed on CD45+CD33+CD14+ myeloid cells in SK-MEL-5 tumor-infiltrating lymphocytes.</p><p>Figure S3 - Single-cell RNAseq (scRNAseq) of human immune cells in non-small cell lung cancer (NSCLC) public dataset.</p><p>Figure S4 - Association of LILRB4 expression with deconvoluted cell fractions for human tumor types in the TCGA database.</p><p>Figure S5 - Suppression of autologous CD8+ T cell proliferation by cytokine-induced M-MDSCs.</p><p>Figure S6 - CD33+ cells from PBMCs cultured in medium alone are not suppressive.</p><p>Figure S7 - Differentially expressed genes (DEG) between SK-MEL-5 educated M-MDSCs and monocytes.</p><p></p><p></p>
Racial Differences in Student Access to High-Quality Teachers
Authors: Clotfelter Charles T. , Ladd Helen F. , Clifton Calen R. 
Published: April 2023

Abstract
Access to high-quality teachers in K–12 schools differs systematically by racial group. This policy brief reviews the academic research documenting these differences and the labor market forces and segregation patterns that solidify them. It also presents new analysis of differential exposure in North Carolina of white, black, and Hispanic students to teachers with different quality-related credentials across five grade–subject combinations. White students are most often in classrooms taught by teachers with strong credentials and least often by those with weak credentials, not only across the state as a whole, but also within most of the state's counties, especially those whose schools are most segregated by race. To address such disparities, decision makers at all three levels—state, district, and school—have various policy options to consider, with each level having an important role to play.
Introduced Mediterranean painted frogs (Discoglossus pictus) are possible supershedders of the fungus Batrachochytrium dendrobatidis in Catalonia (NE Spain)
Authors: Martínez-Silvestre Albert , Loras-Ortí Fernando , Garcia-Salmeron Alejandro , Pujol-Buxó Eudald , Pérez-Novo Iago , Maluquer-Margalef Joan , Poch Santiago , Thumsová Barbora , Bosch Jaime 
Published: April 2023

Abstract
In 2020 and 2021 we detected in Catalonia (NE Spain) six new episodes of mortality or presence of dying specimens in introduced Mediterranean painted frogs (Discoglossus pictus). All affected individuals were positive to the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). Histological examinations showed intense involvement of the superficial layers of the epidermis and qPCR analyses yielded infection loads greater than 100 000 genomic equivalents of zoospores. These results suggest that this introduced species could behave as a Bd ‘supershedder’, and recommend to control its expansion due to its important role in the dynamic of chytridiomycosis.
Effects of P70 S6 kinase on the ageing process and reproduction of Daphnia pulex (Branchiopoda, Anomopoda)
Authors: Zhao Chun-Pu , Lin Chong-Yuan , Zhang Shun , Wang Ya-Jun , Xu Shan-Liang , Wang Dan-Li , Guo Chun-Yang 
Published: April 2023

Abstract
Daphnia pulex is a natural food widely used in aquaculture, and S6K plays an important role in protein translation and ageing. To explore the function of S6K in the ageing process of D. pulex, we cloned and analysed the full-length cDNA of S6K. With the growth of D. pulex, the expression of S6K mRNA first increased, then peaked at 10 days, and then decreased. Western blot analysis showed that the S6K protein expression increased from 1 to 5 days of age, but did not change significantly from 5 to 25 days of age. RNAi knockdown of S6K, reduced the expression of S6K mRNA and S6K protein, and it causes changes in other genes associated with ageing in both sexes. S6K may be involved in reproductive transformation, affecting reproductive capacity, thus significantly affecting the ageing of D. pulex. miRNA with potential regulation of the S6K gene were screened by the bioinformatics method and validated using a dual luciferase reporter gene system. This study deepens our understanding of the mechanisms of ageing in D. pulex and expands our understanding of the role of S6K in the ageing process.
Richard Kearney’s Sacramental Play between Immanence and Transcendence
Authors: Damen Enrieke 
Published: April 2023

Abstract
This article will discuss anatheist imagination in Kearney’s work. With the help of a poem by Sharon Olds, it will make a case for the sacramental – or anatheist – play between immanence and transcendence as a crucial motif to interpreting Kearney’s philosophy. Firstly, illustrating that the sacramental opens the door to a more embodied and carnal understanding of Kearney’s hermeneutics. Secondly, drawing on insights from my research, I’ll argue in a short history of anatheist imagination that there’s a continuity between the sacramental and Kearney’s early work on the hermeneutics of the possible. Finally, the article concludes with some considerations on the philosophical and/or theological character of Kearney’s emphasis on the sacramental imagination as a hermeneutic stance.
The Onset of a Blocking Event as a “Traffic Jam”: Characterization with Ensemble Sensitivity Analysis
Authors: Polster Christopher , Wirth Volkmar 
Published: April 2023

Abstract
Recently, Nakamura and Huang proposed a theory of blocking onset based on the budget of finite-amplitude local wave activity on the midlatitude waveguide. Blocks form in their idealized model due to a mechanism that also describes the emergence of traffic jams in traffic theory. The current work investigates the development of a winter European block in terms of finite-amplitude local wave activity to evaluate the possible relevance of the “traffic jam” mechanism for the flow transition. Two hundred members of a medium-range ensemble forecast of the blocking onset period are analyzed with correlation- and cluster-based sensitivity techniques. Diagnostic evidence points to a traffic jam onset on 17 December 2016. Block development is sensitive to upstream Rossby wave activity up to 1.5 days prior to its initiation and consistent with expectations from the idealized theory. Eastward transport of finite-amplitude local wave activity in the southern part of the block is suppressed by nonlinear flux modification from the large-amplitude blocking pattern, consistent with the expected obstruction in the traffic jam model. The relationship of finite-amplitude local wave activity and its zonal flux as mapped by the ensemble exhibits established characteristics of a traffic jam. This study suggests that the traffic jam mechanism may play an important role in some cases of blocking onset and more generally that applying finite-amplitude local wave activity diagnostics to ensemble data is a promising approach for the further examination of individual onset events in light of the Nakamura and Huang theory.

Significance Statement
Blocking is an occasional phenomenon in the mid- and high-latitude atmosphere characterized by the stalling of weather systems. Episodes of blocking are linked to extreme weather but their occurrence is not completely understood. A recent theory suggests that blocks may form in the jet stream like traffic jams on a highway. The onset mechanism contained in the theory could explain why forecasts of blocking are sometimes poor. In this work, we investigate the formation of a 2016 European winter block in the context of the traffic jam theory. Though questions remain regarding the implications for forecast uncertainty, our findings strongly support the notion of a traffic jam onset.
Atmospheric Drivers of Tasman Sea Marine Heatwaves
Authors: Gregory Catherine H. , Holbrook Neil J. , Marshall Andrew G. , Spillman Claire M. 
Published: April 2023

Abstract
Marine heatwaves (MHWs) can severely impact marine biodiversity, fisheries, and aquaculture. Consequently, there is an increasing desire to understand the drivers of these events to inform their predictability so that proactive decisions may be made to reduce potential impacts. In the Tasman Sea (TS), several relatively intense and broad-scale MHWs have caused significant damage to marine fisheries and aquaculture industries. To assess the potential predictability of these events, we first determined the main driver of each MHW event in the TS from 1993 to 2021. We found that those MHWs driven by ocean advection—approximately 45% of all events—are generally longer in duration and less intense and affected a smaller area compared with the remaining 55%, which are driven by air–sea heat fluxes, are shorter in duration, and are more surface intense. As ocean advection–driven events in the TS have been closely studied and reported previously, we focus here on atmospherically driven MHWs. The predictability of these events is assessed by identifying the patterns of atmospheric pressure, winds, and air–sea heat fluxes in the Southern Hemisphere that coincide with MHWs in the Tasman Sea. We found that atmospherically driven MHWs in this region are more likely to occur during the positive phase of the asymmetric Southern Annular Mode (A-SAM)—which presents as an atmospheric zonal wave-3 pattern and is more likely to occur during La Niña years. These A-SAM events are linked to low wind speeds and increased downward solar radiation in the TS, which lead to increased surface ocean temperatures through the reduction of mixing.

Significance Statement
The purpose of this study is to understand factors of the atmosphere that contribute to an accumulation of heat in the upper ocean in the Tasman Sea to better inform predictability. Higher incidences of ocean extreme thermal events (known as marine heatwaves) in this region are becoming increasingly more common and threatening the important marine industries that support the people of both Australia and New Zealand. We need to know the sources of this extra heat to understand whether such events can be predicted. Previous studies have found the East Australian Current to be responsible for around half of these events, and our results show a connection between a known atmospheric pattern and the other half. As we continue to improve our ability to anticipate this pattern, this suggests that we may also be able to predict these extreme heating events.
Trends in Northern Hemispheric Snow Presence
Authors: Jia Yisu , Lund Robert , Kong Jiajie , Dyer Jamie , Woody Jonathan , Marron J. S. 
Published: April 2023

Abstract
This paper develops a mathematical model and statistical methods to quantify trends in presence/absence observations of snow cover (not depths) and applies these in an analysis of Northern Hemispheric observations extracted from satellite flyovers during 1967–2021. A two-state Markov chain model with periodic dynamics is introduced to analyze changes in the data in a cell by cell fashion. Trends, converted to the number of weeks of snow cover lost/gained per century, are estimated for each study cell. Uncertainty margins for these trends are developed from the model and used to assess the significance of the trend estimates. Cells with questionable data quality are explicitly identified. Among trustworthy cells, snow presence is seen to be declining in almost twice as many cells as it is advancing. While Arctic and southern latitude snow presence is found to be rapidly receding, other locations, such as eastern Canada, are experiencing advancing snow cover.

Significance Statement
This project quantifies how the Northern Hemisphere’s snow cover has recently changed. Snow cover plays a critical role in the global energy balance due to its high albedo and insulating characteristics and is therefore a prominent indicator of climate change. On a regional scale, the spatial consistency of snow cover influences surface temperatures via variations in absorbed solar radiation, while continental-scale snow cover acts to maintain thermal stability in the Arctic and subarctic regions, leading to spatial and temporal impacts on global circulation patterns. Changing snow presence in Arctic regions could influence large-scale releases of carbon and methane gas. Given the importance of snow cover, understanding its trends enhances our understanding of climate change.