bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis
Authors: Bui Nam Q. , Nemat-Gorgani Neda , Subramanian Ajay , Torres Ileana A. , Lohman Marta , Sears Timothy J. , van de Rijn Matt , Charville Gregory W. , Becker Hans-Christoph , Wang David S. , Hwang Gloria L. , Ganjoo Kristen N. , Moding Everett J.
Published: June 2023

AbstractPurpose:
Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS.
Experimental Design:
We enrolled 30 patients with unresectable or metastatic STS to a phase II clinical trial. Patients received ipilimumab and nivolumab for four doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle.
Results:
ctDNA was detected in at least one sample for 96% of patients. Pretreatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pretreatment to postcryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed.
Conclusions:
ctDNA represents a promising biomarker for monitoring response to treatment in patients with advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STS to immunotherapy.
Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: June 2023

Purpose:

About 50% of breast cancers are defined as HER2-low and may benefit from HER2-directed antibody–drug conjugates. While tissue sequencing has evaluated potential differences in genomic profiles for patients with HER2-low breast cancer, genetic alterations in circulating tumor DNA (ctDNA) have not been well described.

Experimental Design:

We retrospectively analyzed 749 patients with metastatic breast cancer (MBC) and ctDNA evaluation by Guardant360 from three academic medical centers. Tumors were classified as HER2-low, HER2-0 (IHC 0) or HER2-positive. Single-nucleotide variants, copy-number variants, and oncogenic pathways were compared across the spectrum of HER2 expression. Overall survival (OS) was evaluated by HER2 status and according to oncogenic pathways.

Results:

Patients with HER2-low had higher rates of PIK3CA mutations [relative risk ratio (RRR), 1.57; P = 0.024] compared with HER2-0 MBC. There were no differences in ERBB2 alterations or oncogenic pathways between HER2-low and HER2-0 MBC. Patients with HER2-positive MBC had more ERBB2 alterations (RRR, 12.43; P = 0.002 for amplification; RRR, 3.22; P = 0.047 for mutations, in the hormone receptor–positive cohort), fewer ERS1 mutations (RRR, 0.458; P = 0.029), and fewer ER pathway alterations (RRR, 0.321; P < 0.001). There was no difference in OS for HER2-low and HER2-0 MBC [HR, 1.01; 95% confidence interval (CI), 0.79–1.29], while OS was improved in HER2-positive MBC (HR, 0.32; 95% CI, 0.21–0.49; P < 0.001).

Conclusions:

We observed a higher rate of PIK3CA mutations, but no significant difference in ERBB2 alterations, oncogenic pathways, or prognosis, between patients with HER2-low and HER2-0 MBC. If validated, our findings support the conclusion that HER2-low MBC does not represent a unique biological subtype.
Abstract A047: Panorama of complex structural variants in primary localized prostate cancer
Authors: Olsen André , Favero Francesco , Li Yilong , Girma Etsehiwot , Feran Breon , Papenfuss Tony , Helin Kristian , Reimand Jüri , Weischenfeldt Joachim
Published: June 2023

Prostate cancer (PCa) is a hormone-driven disease characterized by an abundance of structural variations (SV). Deconvolving the SV patterns can both inform on prior mutational processes leading to cancer, and be leveraged to identify patients with more aggressive disease. Under the auspices of the Pan Prostate Cancer Group (PPCG) consortium, we used whole genome sequencing of 812 treatment naive PCa patients to study both simple and complex SVs. In total, we classified 15,708 simple SVs and 1,448 complex SV events. Complex SVs such as chromothripsis, chromoplexy and templated insertion were found in more than half of the cohort. We also detected tandem duplicator phenotype (TDP) in a subset of the patients associated with CDK12 aberrations. Breakpoint recurrence analysis of driver genes revealed disruption of e.g. PTEN and formation of TMPRSS2-ERG fusion genes frequently coincide with occurrences of specific complex SV types, suggesting specific mutational processes driving these alterations of these cancer genes. Based on the simple and complex SV classifications we extracted six SV signatures, including two TDP-like signatures, distinct deletion-specific SV signatures and a signature characteristic of AR binding sites. We found signatures associated with disease markers, including Gleason score, risk scores, as well as age. Together, these findings provide insights into mechanisms driving SV formation and driver gene alterations in PCa, with potential for identifying markers of aggressive disease.

Citation Format: André Olsen, Francesco Favero, Yilong Li, Etsehiwot Girma, Breon Feran, Tony Papenfuss, Kristian Helin, Jüri Reimand, Joachim Weischenfeldt. Panorama of complex structural variants in primary localized prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A047.
Abstract A058: Lineage plasticity is associated with an altered MAX cistrome through super-enhancer remodeling
Authors: Kobelev Maxim , Ganguli Dwaipayan , Namekawa Takeshi , Talal Amina , Scurll Joshua , Zoubeidi Amina
Published: June 2023

Background: Roughly 20% of late stage prostate cancer patients display a lineage conversion from typical androgen receptor (AR) driven castrate resistant prostate cancer (CRPC) to a particularly lethal neuroendocrine prostate cancer (NEPC) phenotype as a result of AR pathway inhibition (ARPI). Notably, the mutational landscape of CRPC and NEPC is quite similar, suggesting that epigenetic changes may guide this lineage conversion. Our objective was to explore changes in active epigenetic marks with a particular focus on super-enhancers (SEs) and identify factors that regulate these active regions during lineage plasticity. Methods: We performed ChIP-seq for H3K27ac, H3K4me3 and various TFs in our CRPC and ENZ resistant (ENZR) NEPC-like cell models. We leveraged publicly available H3K27ac data in cell lines as well as PDX models to validate our findings. RNA-seq was integrated with our ChIP-seq results to create a signature which we applied to patient data sets. GIGGLE analysis was used to identify candidate factors at SEs. Results: CRPC and NEPC showed similar active marks at promoters however, enhancer elements were significantly remodeled. We observed extensive remodeling of SEs in our ENZR model compared to CRPC and these unique regions showed greater H3K27ac signals in other ENZR models such as NCI-H660. SE linked genes are associated with stemness pathways and are strongly upregulated as a result of ARPI in vitro, and in vivo. Factor enrichment analysis of these regions showed enrichment for MAX and MYC family binding similar to small cell lung cancer cell lines. ChIPseq for MYC and MAX in our cell models revealed an expansion of MAX binding and contraction of MYC binding in our ENZR model compared to CRPC. In particular, we saw increased binding of MAX at plasticity SEs without MYC suggesting an interaction with MYCL or other factors since MYCN is not expressed in our models. Conclusions: This work improves our understanding of the epigenetic changes that occur during lineage plasticity and ARPI resistance. SE analysis in our models suggests that MAX may be activating these regions with MYCL or independently of the MYC family. MYCL expression is upregulated in NEPC and has higher expression than MYCN suggesting a potential role during lineage plasticity.

Citation Format: Maxim Kobelev, Dwaipayan Ganguli, Takeshi Namekawa, Amina Talal, Joshua Scurll, Amina Zoubeidi. Lineage plasticity is associated with an altered MAX cistrome through super-enhancer remodeling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A058.
Abstract B002: Lactate metabolism regulates chromatin accessibility and prostate luminal differentiation
Authors: Goldstein Andrew S. , Giafaglione Jenna M. , Crowell Preston D.
Published: June 2023

Lineage transitions are a central feature of prostate development, tumorigenesis and treatment resistance. While epigenetic changes drive prostate lineage transitions, whether upstream metabolic signaling modulates prostate lineage identity remains unclear. Investigations into prostate metabolism are focused primarily on targeting energy metabolism without considering how altering metabolism may influence epigenetic state or cellular differentiation. To understand the relationship between metabolism and prostate lineage identity, we developed an approach to perform metabolic profiling and nutrient tracing on primary prostate epithelial cells and demonstrated that basal and luminal cells exhibit distinct metabolic features. Furthermore, we show that basal to luminal differentiation in vivo and in three-dimensional ex vivo culture is accompanied by metabolic changes consistent with increased glucose oxidation. Using genetic and pharmacological approaches, we identify the mitochondrial pyruvate carrier (MPC) as a regulator of prostate luminal identity in benign and prostate cancer cells. Low MPC expression is inversely correlated with luminal differentiation and associated with poor response to androgen receptor inhibition in clinical prostate cancer. Mechanistically, our results suggest that MPC inhibition likely impairs luminal differentiation through accumulation of intracellular lactate. Increasing intracellular lactate levels is sufficient to alter chromatin accessibility at lineage-specific genes and impair luminal differentiation in prostate epithelial cells. These findings indicate that upstream metabolism is a regulator of chromatin accessibility and prostate lineage differentiation, suggesting that alterations in tumor metabolism may contribute to lineage plasticity and resistance to androgen receptor blockade in prostate cancer.

Citation Format: Andrew S. Goldstein, Jenna M. Giafaglione, Preston D. Crowell. Lactate metabolism regulates chromatin accessibility and prostate luminal differentiation [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B002.
Abstract B047: Characterizing the landscape of extracellular vesicles from prostate cancer cell lines
Authors: Ludwig Megan , Sychev Zoi , Day Abderrahman , Bergom Hannah , Hwang Justin , Drake Justin M.
Published: June 2023

Multiple subtypes of prostate cancer can emerge in the advanced stages of disease, such as androgen receptor (AR+), AR indifferent with neuroendocrine features (AR-/NE+), and those without AR or NE features (double negative, DN). These latter variants are particularly aggressive and incredibly lethal. Extracellular vesicles (EVs), also known as exosomes, are small particles that are important mediators of cell-cell communication and have been nominated as potential biomarkers of disease state. We hypothesized that the proteome of extracellular vesicles contains enough information about their originating cell that they can distinguish between prostate cancer subtypes. To address this, we isolated EVs from prostate cancer cell lines of differing subtypes – AR+ (LNCaP, LNCaP95, C4-2, 22RV1), AR-/NE+(NCI-H660, EF1, LASCPC-01), and AR-/NE- (PC3, DU145) – and prepared the EV proteome for quantitative mass spectrometry analysis. This identified 2,000+ proteins in the EVs for each cell line. From our analysis, we found that the EVs from cell lines of similar subtypes clustered together with several hundred proteins statistically different between the three groups. Interestingly, we also found that EVs contained enough protein information to utilize already developed gene signature scores for AR or NE activity. EVs isolated from the AR-/NE+ cell line NCI-H660 scored over 90% with a 121 gene NE signature and included proteins such as SYP, CHGA, and UCHL1. EVs from all the AR+ cell lines displayed >80% AR activity that was driven by high expression of PSA and STEAP1. This supports the idea that we can use the proteome of tumor-derived EVs to identify signature molecular markers that are already known to the field to develop liquid-based biomarker assays. Further work in the clinical setting is needed to evaluate the ability for EVs to be specific, informative biomarkers for prostate cancer disease status.

Citation Format: Megan Ludwig, Zoi Sychev, Abderrahman Day, Hannah Bergom, Justin Hwang, Justin M. Drake. Characterizing the landscape of extracellular vesicles from prostate cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B047.
Abstract B075: Anti-human LIV-1 antibody drug conjugate for treatment of metastatic prostate cancer
Authors: Zhao Xiaobei , Chen Gang
Published: June 2023

In the worldwide male population, prostate cancer has the most frequent malignancy; out of all the cancer-related causes of deaths, it is also one of the most common. With the advance of new therapies of androgen receptor pathway inhibitors, patient survival rates have improved significantly. There are still tremendous unmet needs, however, for the patients with treat-refractory metastatic castration-resistant prostate cancer (mCRPC). LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer. Previous studies with immunohistochemical (IHC) analysis showed that LIV-1 is expressed by estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) and ER-/PR-/Her2- (triple-negative) breast cancers. These studies also showed that in healthy human tissues, LIV-1 expression is limited to hormonally-regulated organs (prostate, uterus, and breast). The broad expression of LIV-1 in prostate and breast cancer tumors in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). We generated an ADC, BRY812, consisting of a humanized anti-LIV-1 mAb conjugated to monomethyl auristatin E (MMAE), via a novel conjugation method that prevents MMAE from coming off of the antibody during the circulation. The PK studies in rat and monkey showed that the free MMAE released from ADC is 1 to 2 log lower compared with approved ADCs prepared by the standard conjugation method. Low free MMAE concentration significantly lowers the risk of off target toxicity by the ADC. In vitro and in vivo studies demonstrated the antitumor activity of BRY812 for the treatment of prostate and ER+ and triple-negative breast cancers with a better safety profile and a larger therapeutic window. The humanized LIV-1 ADC, BRY812 is currently in preclinical toxicity studies and will advance to First-in-Human trials in April, 2023.

Citation Format: Xiaobei Zhao, Gang Chen. Anti-human LIV-1 antibody drug conjugate for treatment of metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B075.
Abstract PR001: An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and AR therapy resistance
Authors: Mu Ping , Li Xiaoling , Wang Yunguan
Published: June 2023

Tumor mutational burden and heterogeneity fuel resistance to many targeted therapies, which inevitably limits the clinical outcome of patients. The cytosine deaminase APOBEC proteins are major drivers of mutagenesis in human cancer, with over 70% of tumors exhibiting a mutational signature that is impacted by APOBEC activity. Nevertheless, the mechanisms through which tumor cells hijack the powerful APOBEC mutagenesis machinery to promote heterogeneity and therapy resistance remain largely unknown. Through a multi-disciplinary approach integrating bulk and single cell RNA-Seq (scRNA-Seq), whole-genome exome-sequencing (WES), and CRISPR library screening, we identified a long sought-after cell-intrinsic mechanism that prevents APOBEC-driven mutagenesis in non-malignant cells. The loss of this “molecular brake” unleashes APOBEC3B-driven mutagenesis in malignant cells, which then becomes a key mutator and represents the long sought-after molecular source of driver mutations in some frequently mutated genes in cancers, including FOXA1, EP300, and AR. Functional screening identified eight crucial drivers for Androgen Receptor (AR)-targeted therapy resistance in prostate cancer that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3, and AR. Finally, contrary to conventional understanding, our study reveals that driver mutations in FOXA1 induced by APOBEC3B, not mutations in AR, evolutionarily outcompete other driver mutations and eventually dominate the resistant tumors. Collectively, these results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring targeted therapy resistance and could be the potential therapeutic targets to overcome resistance.

Citation Format: Ping Mu, Xiaoling Li, Yunguan Wang. An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and AR therapy resistance [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR001.
Supplementary Figure S1 from (R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers
Authors: Gunn Kathryn , Myllykoski Matti , Cao John Z. , Ahmed Manna , Huang Bofu , Rouaisnel Betty , Diplas Bill H. , Levitt Michael M. , Looper Ryan , Doench John G. , Ligon Keith L. , Kornblum Harley I. , McBrayer Samuel K. , Yan Hai , Duy Cihangir , Godley Lucy A. , Koivunen Peppi , Losman Julie-Aurore
Published: June 2023

Characterization of isogenic TF-1 cell lines expressing TET2-targeting shRNAs.
Data from Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer
Authors: Bianchi Anna , De Castro Silva Iago , Deshpande Nilesh U. , Singh Samara , Mehra Siddharth , Garrido Vanessa T. , Guo Xinyu , Nivelo Luis A. , Kolonias Despina S. , Saigh Shannon J. , Wieder Eric , Rafie Christine I. , Dosch Austin R. , Zhou Zhiqun , Umland Oliver , Amirian Haleh , Ogobuiro Ifeanyichukwu C. , Zhang Jian , Ban Yuguang , Shiau Carina , Nagathihalli Nagaraj S. , Montgomery Elizabeth A. , Hwang William L. , Brambilla Roberta , Komanduri Krishna , Villarino Alejandro V. , Toska Eneda , Stanger Ben Z. , Gabrilovich Dmitry I. , Merchant Nipun B. , Datta Jashodeep
Published: June 2023

Abstract
We have shown that KRAS–TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS–TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell–dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF–TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell–neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC.
Significance:
By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell–excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer.

This article is highlighted in the In This Issue feature, p. 1275
Unique Issues Facing Sexual and Gender Minorities in Cancer
Authors: Scout NFN
Published: June 2023

There are few resources available that help providers understand unique issues sexual and gender minority (SGM) people face related to cancer screening and care. This article helps fill the gap by providing some of the top-line issues providers and policymakers should know, as assembled by one of the leading experts in this field, the executive director of the National LGBT Cancer Network. The sexual and gender minority (SGM) cancer field has matured significantly in recent years, providing greater insight into the barriers and challenges experienced by this population. Not only are risks of cancer for the population higher, but SGM people also experience low access to tailored resources and ultimately lower satisfaction with care after treatment. This article will lay out key issues related to cancer and this population, including changing demographics, no presumption of care, other access to care barriers, systematic data suppression, and then the lack of population-specific cancer research. It will also review the first step in building a more welcoming clinical practice and give resources for additional steps.
Data from The Immunopeptidome from a Genomic Perspective: Establishing the Noncanonical Landscape of MHC Class I–Associated Peptides
Authors: Bedran Georges , Gasser Hans-Christof , Weke Kenneth , Wang Tongjie , Bedran Dominika , Laird Alexander , Battail Christophe , Zanzotto Fabio Massimo , Pesquita Catia , Axelson Håkan , Rajan Ajitha , Harrison David J. , Palkowski Aleksander , Pawlik Maciej , Parys Maciej , O'Neill J. Robert , Brennan Paul M. , Symeonides Stefan N. , Goodlett David R. , Litchfield Kevin , Fahraeus Robin , Hupp Ted R. , Kote Sachin , Alfaro Javier A.
Published: June 2023

Abstract
Tumor antigens can emerge through multiple mechanisms, including translation of noncoding genomic regions. This noncanonical category of tumor antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry (MS) to enable the discovery of noncanonical MHC class I–associated peptides (ncMAP) from noncoding regions. Considering that the emergence of tumor antigens can also involve posttranslational modifications (PTM), we included an open search component in our pipeline. Leveraging the wealth of MS-based immunopeptidomics, we analyzed data from 26 MHC class I immunopeptidomic studies across 11 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant PTMs, using spectral matching and controlled their FDR to 1%. The noncanonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 55%. The data reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive therapeutic targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targets for T-cell therapies or vaccine development.
Data from Clonal Spreading of Tumor-Infiltrating T Cells Underlies the Robust Antitumor Immune Responses
Authors: Aoki Hiroyasu , Tsunoda Mikiya , Ogiwara Haru , Shimizu Haruka , Abe Haruka , Ogawa Tatsuro , Abe Takaya , Shichino Shigeyuki , Matsushima Kouji , Ueha Satoshi
Published: June 2023

Abstract
The repertoire of tumor-infiltrating T cells is an emerging method for characterizing effective antitumor T-cell responses. Oligoclonal expansion of the tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrate here that the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased in tumor-bearing mice treated with monoclonal anti–programmed death-ligand 1 (PD-L1) or anti-CD4, which correlated with antitumor effects. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) represents characteristics of antitumor T-cell responses induced by anti-CD4 and anti–PD-L1 treatment.
A vida como texto: Lotman numa casca de noz
Authors: Pilshchikov Igor
Published: June 2023

Este artigo fornece uma visão geral da biografia intelectual de Iúri Lotman. Ele aborda suas contribuições como historiador da literatura russa e teórico literário, fundador da Escola de Semiótica Tártu-Moscou, estudioso da vida e da obra de Púchkin, teórico da biografia literária, semiótico, teórico cultural e iluminista.
Iessiênin de frente para trás
Authors: Nogueira André Bacciotti
Published: June 2023

Introdução para um trabalho tradutório extensivo sobre a poesia de Serguei Iessiênin, partindo de seus começos e da aceitação de sua origem camponesa, em contraposição à perspectiva consolidada, na recepção post-mortem do poeta, e que se vale da polêmica e estigma de seu suicídio como ponto de partida. Este artigo serve de apresentação aos poemas de Iessiênin que trago na seção de traduções.
Serguei Iessiênin, primeiros poemas
Authors: Nogueira André Bacciotti
Published: June 2023

Coletânea de 34 poemas juvenis de Serguei Iessiênin, datados entre 1912 e princípios de 1917, traduzidos ao português. Este trabalho de tradução é apresentado pelo artigo precedente: “Iessiênin de frente para trás”.
Vladímir S. Solovióv: poemas
Authors: Bernardini Aurora
Published: June 2023

Este trabalho apresenta as traduções poéticas de cinco poemas do filósofo e poeta russo Vladímir Solovióv.
Entrevista com Viatchesláv Glébovitch Kupriyánov
Authors: Beriózkina Liubóv
Published: June 2023

Trata-se da tradução de uma entrevista (2022) realizada por Liubóv Beriozkina com o poeta Viatchesláv Kupriyánov (1939) sobre o desenvolvimento do verso livre (verlibr) na Rússia, a definição do gênero e a sua recepção no meio literário.
Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline
Authors: Patrizz Anthony , El Hamamy Ahmad , Maniskas Michael , Munshi Yashasvee , Atadja Louise , Ahnstedt Hilda , Howe Matthew , Bu Fan , Mulkey Daniel K. , McCullough Louise D. , Li Jun
Published: June 2023

BACKGROUND:

Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS:

Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2–3 months) and aged (20 months) male and female mice. Animals were exposed to a variety of gas conditions to assess the contribution of peripheral and central chemoreceptors. A battery of cognitive tests was performed to examine behavioral function.

RESULTS:

Middle cerebral artery occlusion led to disordered breathing characterized by hypoventilation and apneas. Cognitive decline correlated with the severity of disordered breathing. Distal permanent middle cerebral artery occlusion, which produces a smaller cortical infarct, also produced breathing disorders and cognitive impairment but only in aged mice.

CONCLUSIONS:

Our data suggest that poststroke apnea is associated with cognitive decline and highlights the influence of aging on breathing disorders after stroke. Therefore, the treatment of respiratory instability may be a viable approach to improving cognitive outcomes after stroke.
“Eastern Literature” as Happenstance?
Authors: Jia Yan
Published: June 2023

This essay examines how “Eastern literature” was perceived and presented in the making of world literature in 1980s China, an era of political and cultural opening-up, through the lens of Indian literature included in the magazine Shijie Wenxue. Although the magazine’s editors discursively championed the idea of geographic all-inclusiveness, the larger conjuncture brought “Western literature” to the forefront of attention. “Eastern” authors and texts, in contrast, were confined to a state of “happenstance,” due to the occasional manner of their presentation. However, by re-reading Shijie Wenxue on three levels, I argue that the magazine managed to produce a relatively eclectic and “thick” knowledge of Indian literature, which would have otherwise been neglected because of its tokenistic appearance and low visibility. Adopting a more creative and critical mode of reading, one can turn the seemingly Western-centric project of Shijie Wenxue into a useful archive for readers with a special interest in “Eastern literature.”
National Dreams, Worldly Visions
Authors: Novillo-Corvalán Patricia
Published: June 2023

This essay explores the intertwined trajectories of a cluster of Argentine magazines, leftist and avant-garde: Proa, Martín Fierro, Insurrexit, and Revista de Oriente which, in their own peculiar ways, rocked and transformed the Buenos Aires cultural scene. It charts the magazines’ fleeting – though momentous – life-spans and existences at a time of revolution, when small collectives of writers and students spread radical and reformist ideas, formal experimentation, and a vernacular revival. While the nagging question of national identity underpinned the magazines’ literary aesthetics, the essay shows that, from the start, those at the editorial helm increasingly steered them towards the wider waters of world literature. Inasmuch as they realised that the conundrum of how to invent a modern Argentine literature could only be resolved dialectically, facing both inwards and outwards, nationally and transnationally, through the relationship between Argentina, Latin America, and the world at large.
Finding Jesus in the Psalter
Authors: Goswell Gregory
Published: June 2023

A Christological reading of the Psalter in which individual psalms are viewed as primarily the prayers of Jesus is evaluated. This recent evangelical tradition of interpretation goes as far as to assert that the Psalms are only secondarily our prayers. However, while the portrait of David the chief psalmist anticipates Jesus Christ as the ideal Davidic king, this does not require that everything in every psalm be applied to Jesus. When David confesses his sins and failings, these words cannot be placed on the lips of Jesus. It remains nonetheless legitimate for believers to make use of the Psalms and apply much of their content to themselves, for, especially in Books IV and V of the Psalter, David sets an example of devotion to God which others are meant to emulate. As well, a Christian rereading of the Psalter sees the God of the psalmist as the Trinity, so that what is said about God can be applied to Jesus Christ.
Social Memory
Authors: Bray D. Luke
Published: June 2023

This article highlights the significance of social memory in Christian missions. Memory is a crucial phenomenon that shapes how individuals perceive reality and make decisions. Social memory, in particular, can aid anthropological researchers and Christian missionaries in engaging with people groups. The article summarizes the history of social memory studies and explores the effects of social trauma on group memory. It emphasizes the importance of understanding the context of a target people’s past for the success of the Christian mission. By examining a social group’s history, missionaries can gain insights into how the group is likely to respond to the Gospel message and how they are likely to interpret and apply it in their lives. Overall, comprehending the context is essential for the success of the Christian mission.
Performance Analysis of Solar Assisted Ground Source Heat Pump to Supply Heating Load and Domestic Hot Water
Authors: Berkane Ahleme , Mounir Aksas , Aouachria Zeroual
Published: June 2023

Algeria’s geographical location offers several advantages related to the extensive use of renewable energy sources such as solar and geothermal. Owing to the vast Algerian territory, the need for isolated areas to be supplied with energy by autonomous systems using sustainable
energy. In this study, we propose a hybrid renewable energy system to provide heating systems for residential buildings and domestic hot water (DHW). Four different solar-assisted ground source heat pump (SAGSHP) combinations are being studied, with the aim of satisfying the energy needs of
a building located in Batna, Algeria. The TRNSYS software allowed us to study the different effects of the parameters on their performance. It turned out that a 7.7 kW ground source heat pump system combined with flat solar collectors is a feasible choice that satisfies our objective. The
extreme annual average values of the heat pump coefficient of performance (COP) obtained are 3.48 and 4.55. In the system, with recharging the borehole, the net energy extracted from the ground is decreased by 30.4% compared to the reference case (GSHP). This can reduce the ground thermal
imbalance problem, which positively affects the stability of the operational system.
Predictors of individual mental health and psychological resilience after Australia’s 2019–2020 bushfires
Authors: Macleod Emily , Heffernan Timothy , Greenwood Lisa-Marie , Walker Iain , Lane Jo , Stanley Samantha K , Evans Olivia , Calear Alison L , Cruwys Tegan , Christensen Bruce K , Kurz Tim , Lancsar Emily , Reynolds Julia , Rodney Harris Rachael , Sutherland Stewart
Published: June 2023

Aims:

We assessed the mental health effects of Australia’s 2019–2020 bushfires 12–18 months later, predicting psychological distress and positive psychological outcomes from bushfire exposure and a range of demographic variables, and seeking insights to enhance disaster preparedness and resilience planning for different profiles of people.

Methods:

We surveyed 3083 bushfire-affected and non-affected Australian residents about their experiences of bushfire, COVID-19, psychological distress (depression, anxiety, stress, post-traumatic stress disorder) and positive psychological outcomes (resilient coping, wellbeing).

Results:

We found high rates of distress across all participants, exacerbated by severity of bushfire exposure. For people who were bushfire-affected, being older, having less financial stress, and having no or fewer pre-existing mental disorders predicted both lower distress and higher positive outcomes. Being male or having less income loss also predicted positive outcomes. Severity of exposure, higher education and higher COVID-19-related stressors predicted both higher distress and higher positive outcomes. Pre-existing physical health diagnosis and previous bushfire experience did not significantly predict distress or positive outcomes.

Recommendations:

To promote disaster resilience, we recommend investment in mental health, particularly for younger adults and for those in rural and remote areas. We also recommend investment in mechanisms to protect against financial distress and the development of a broader definition of bushfire-related impacts than is currently used to capture brushfires’ far-reaching effects.
Election Frequency and Voter Turnout
Authors: Kostelka Filip , Krejcova Eva , Sauger Nicolas , Wuttke Alexander
Published: June 2023

In recent decades, liberal democracies have considerably expanded the scope for citizen participation, calling their citizens to vote in a growing number of popular votes. This research investigates the effects of the rising election frequency on electoral participation. It expands on the voting calculus and theorizes which, when, and how past votes affect current voter turnout. We argue that all election types contribute to a common factor of election frequency, whose high values depress turnout and reduce the effectiveness of party mobilization even in the most important elections. We find support for the new theory using an original database of all significant elections and referendums held in 22 European democracies between 1939 and 2019, two natural experiments, and survey data from the Comparative Study of Electoral Systems. Our findings shed light on contemporary participation trends and have major implications for democratic citizenship and democratic institutional engineering.
Italian ghetto stories: Toward a transnational literary history
Authors: Ziolkowski Saskia Elizabeth
Published: June 2023

This article examines Italian ghetto stories, which are distinguished by confusions of time, continuities, tourism, reflections on collective identities, and movements in and out, in order to outline one potential literary history. In contrast to German-language and Anglophone literary ghettos, Italian ones are generally absent as a critical category from literary debates, though they appear in works by Leon Modena, Israel Zangwill, Rainer Maria Rilke, Umberto Saba, Giorgio Bassani, Elsa Morante, Caryl Phillips, and Igiaba Scego, among others. A transnational approach can bring together works that have not been considered collectively because of disciplinary formations. Italian ghetto fictions expose the disheartening continuities of prejudice and, relatedly, have generally not been considered together because of restrictive ideas about the nation as an organizing principle.
Influence of Electricity Connection on ICT Usage in Six East African Community Countries
Authors: Li Zibiao , Ihirwe Jeanne Paula , Sun Keyuan , Asemota Godwin Norense Osarumwense
Published: June 2023

This article empirically examined the influence of available electricity on information and communication technology (ICT) usage in East African Community (EAC) countries deploying regression analysis. It operationalized ICT usage in terms of the composite index comprising mobile phone, Internet, and electricity access by the percentage of the population who has an electricity connection. The results indicate that (1) a strong beneficial link exists between power access and ICT usage in three EAC countries (Burundi, Kenya, and Rwanda). (2) Employing data flow assumptions for the linear regression analysis in Burundi, Kenya, and Rwanda means that ICT usage can be determined based on electricity access in each of these countries. (3) There is no direct link between electricity access and ICT usage in South Sudan, Tanzania, and Uganda.
Intimate Partner Violence and Its Associated Factors: A Multidimensional Analysis in the Context of India
Authors: Firdaush Shama , Das Pinaki
Published: June 2023

Intimate partner violence (IPV) is a complex phenomenon that involves multiple dimensions of violence and multiple levels of risk factors. This study explores the incidence of IPV experienced by married women in India from a multidimensional perspective and assesses its change during 2005–2006 and 2015–2016 based on the National Family Health Survey (NFHS) unit-level data. A latent class analysis is used to address the degree of multidimensional IPV for identifying the distinct subgroups of women who experience different acts of IPV in India and to explore the multiple risk factors associated with it, which can inform prevention and intervention strategies to reduce its occurrence and impact. Our analysis shows that 39.5 million women were victims of at least one form of violence, of which 4.35 million were severe victims in 2015–2016. There has been a significant reduction in the share of victims of IPV, which was not uniform across different subgroups of women. The results of ordered logit regression reveal that educated couples and those women having decision-making power are less likely to experience higher degree of IPV, whereas the opposite scenario prevails for women who have the attitude of acceptance of violence and experience higher marital control by husband.
A contingent publicness: Entanglements on buses
Authors: Joseph Yogi , Gopakumar Govind
Published: June 2023

A lacuna in our understanding of how publicness of public transit is being constituted is the primary point of departure for this paper. In recent times, publicness has been articulated through two parallel readings – one, a political economic reading that sees publicness through static macrostructural constraints; and two, micro-sociality aboard public transit manifests an in situ and spontaneous public space. Moving beyond the static and the spontaneous, we articulate a dynamic co-constituted notion of publicness. Building upon recent work that examines the entangling of micro- and macropolitics onboard public transit and relying upon a mobile ethnographic approach revolving around situated observation and interviewing surrounding buses located in the Indian metropolis of Bengaluru, this paper offers publicness as a contingent entity that is constituted through the process of transiting.
Post-Reform Placement and Writing Proficiency in Community College Transfer-Level Composition Courses
Authors: Nazzal Jane S. , Olson Carol B. , Chung Huy Q.
Published: June 2023

Objective: Extensive reform has been implemented in community colleges across the nation to help expedite the attainment of students’ academic goals of degree completion and transfer to 4-year institutions. Reform at the institution in this study resulted in replacement of the college writing placement exam and the precollegiate course sequence with an online assessment questionnaire by which students were provided with an automated recommendation based on their high school records to enroll into one of two versions of the transfer-level composition course, either with or without a support course. Examined are: (1) whether students who need the most writing support are effectively positioning themselves to receive it; and (2) whether the new placement policy improves students’ chances for college success while examining its impact on specific student subgroups. Method: An analytic writing assessment and survey were administered to students. Compared are students’ scores on the assessment, their self-reported high-school GPA, and their final course grades. Results: Findings show: (1) no significant differences in academic writing proficiency between students enrolled in the two course types; (2) students mostly followed the college’s recommendation for enrollment based on their high school GPA, which is found to be weakly related to their measured levels of writing proficiency; and (3) generally high course pass rates of students at all levels of proficiency. Contribution: This study generates data that can help inform policy and practice in community colleges and clarify ways to best support students in composition toward achieving their academic goals of degree attainment and transfer.
Artificial neural network modelling for predicting classical air pressure profile curves in building drainage systems
Authors: Mahapatra I , Gormley M
Published: June 2023

Water trap seal loss can lead to the ingress of foul odours from the sewer network carrying harmful pathogens which can affect the health of building occupants. This loss is due to excessive negative or positive pressures within the system as a consequence of rapidly changing flow due to the unsteady nature of air and water flow discharges from appliances. This pressure regime within the system is often represented by a pressure profile along the height of the main vertical stack in the Building Drainage System (BDS). Experimental data from peer-reviewed literature and data from a unique 34-storey drainage test rig have been used as pressure profile data (Test data) for an Artificial Neural Network (ANN) model. Discharge input height (storey number) and discharge flow rate are considered to be the two independent input parameters and the pressure along the vertical stack is considered to be the output. In this work, both a Feed Forward and Back Propagation (FFBP) ANN model and a Radial Basis Function (RBF) ANN model have been used to train the algorithm. The work has confirmed the applicability of the FFBP-ANN model for steady two-phase fluid flow phenomena in BDS and allows for the prediction of pressures in a system for which no pressure data exists, by the prediction of modelled weights, based only on its physical and flow characteristics.

Practical Application: Of great concern to designers of building drainage systems (BDS) is the control of pressure fluctuations within the system to prevent water trap seal loss. Prediction of a pressure profile based on the characteristics of the building – e.g. height, location of water discharge, discharge flow rate and ventilation type, would therefore increase confidence in designs, particularly in tall buildings. The work presented here addresses, for the first time, the applications of two ANN models for predicting the pressure profile in the BDS vertical stack of multi-storey buildings.