bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD2-01: Local and lymphoid immune surveillance mechanisms in “exceptional survivors” of stage 4 cancers following standard of care chemo- and targeted therapies
Authors: Kakkassery Helen , Alaguthurai Thanussuyah , Graham Rosalind , Carpenter Esme , Hossain Farhana , Keane Sean , Irshad Sheeba 
Published: March 2023

Abstract
Breast cancer patients with advanced metastatic disease can exhibit rapid disease progression, disease stabilisation or partial responses of varying duration. However, for reasons that are not fully elucidated, a small fraction of patients will elicit an exceptional durable response to standard anticancer treatments or survive significantly longer than patients with clinically comparable tumours. Here, we investigate the drivers of immune surveillance mechanisms across breast cancer subtypes in stage IV exceptional survivors (n=13) with matched control cohorts of stage IV typical responders (n=6), early breast cancer patients (n=5) and healthy volunteers (n=17). Peripheral blood mononuclear cells (PBMCs) from patients were stained with 8 panels providing 241 non-redundant immune parameters for flow cytometry analysis. Principle Component Analysis (PCA) showed distinct segregation of the exceptional survivors from the other control groups with an immune signature in exceptional survivors constituting of activated NK, CD8 T cells and gamma delta (gd) T cells pointing towards higher innate immunogenicity in these individuals. Specifically, although these metastatic exceptional responder patients possessed comparable NK cell frequencies, the proportion of NKG2D+CD56dimCD16+ NK cells were significantly enriched compared to the typical responders. Additionally, proportions of CD8+ central memory (CD45RA- CD27+) and effector memory (CD45RA- CD27-) gd T cells, were also seen to be significantly increased. Functional in vitro validation of these findings along with scRNA sequencing of lymph node and tumour tissue is currently underway. To our knowledge, this work is the first to explore in depth the immune signatures in the peripheral blood of exceptional survivors with metastatic breast cancer. Elucidating the immunological reasons for favourable atypical responses alongside functional tumour microenvironment analysis offers unique insights for predictive biomarker identification and discovery of axes that could be exploited therapeutically to benefit those with less favourable responses. Written informed consent was obtained from all individuals in accordance with the Declaration of Helsinki under the following research ethics committee; London-Chelsea approved study (REC ID 13/LO/1248).
Citation Format: Helen Kakkassery, Thanussuyah Alaguthurai, Rosalind Graham, Esme Carpenter, Farhana Hossain, Sean Keane, Sheeba Irshad. Local and lymphoid immune surveillance mechanisms in “exceptional survivors” of stage 4 cancers following standard of care chemo- and targeted therapies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD2-01.
Abstract PD4-03: PD4-03 Pelareorep primes the tumor for checkpoint inhibition therapy by activating the interferon-gamma signaling pathway and tumor inflammation signature in early breast cancer patients - results of the AWARE-1 trial
Authors: Loghmani Houra , Gavilá Joaquín , Manso Luis , Coffey Matt , Trauger Richard , Salvador Fernando , Pascual Tomás , Prat Aleix , Heineman Thomas 
Published: March 2023

Abstract
Background The status of the tumor microenvironment (TME) can profoundly affect the response to immune-based therapies for the treatment of cancer. Results previously reported from the AWARE-1 study in early breast cancer patients demonstrated that pelareorep (pela, an oncolytic reovirus), alone or in combination with checkpoint inhibitor (CPI) therapy, modified the inflammatory state of the TME. We also showed that many of pela’s effects on the TME were enhanced by the addition of checkpoint blockade. Here, we report the effect of treatment with pela on selected molecular markers associated with enhanced anti-tumor immunity. Methods Newly diagnosed HR+/HER2- early BC patients were enrolled into two cohorts: Cohort 1 (C1): pela + letrozole (n=10); and Cohort 2 (C2): pela + letrozole + atezolizumab (n=10). Pela was intravenously administered on days 1, 2 and 8, 9, and atezolizumab was given on day 3. For this analysis, tumor biopsies (FFPE samples) collected pre-treatment (D1) and on days 3 (D3, prior to the atezolizumab administration) were examined by GeoMx digital spatial profiling (DSP, using Nanostring’s Cancer Transcriptome Atlas [CTA]). Moreover, the expression of 770 immune-related genes was analyzed using a specific immune panel (n=20). Gene Set Enrichment Analysis (GSEA) (version 4.1.0) was used to assess pela-induced activation pathways. Results GeoMx DSP showed that pela therapy significantly activated IFN-gamma signaling and associated interferon response genes from D1 to D3 (Normalized Enrichment Score [NES] = 3.3, p-values &lt; 0.02) in the cytokeratin-positive subset of the tumor samples. GSEA of the immune dataset (730 immune genes + 30 housekeeping genes) from the whole tissue also showed a significant upregulation of IFN-gamma signaling pathway genes (FDR &lt; 25%, p-value&lt; 0.001). Increases were also observed in genes reported to be associated with an enhanced tumor inflammatory signal (TIS) including PD-L1, IDO1, HLA-E and STAT1 (p-values &lt; 0.005). Conclusions These results demonstrate that treatment with pela alters the TME to induce and enhance anti-tumor immunity. This enhancement of anti-tumor immunity may potentiate the TME for CPI therapy.
Citation Format: Houra Loghmani, Joaquín Gavilá, Luis Manso, Matt Coffey, Richard Trauger, Fernando Salvador, Tomás Pascual, Aleix Prat, Thomas Heineman. PD4-03 Pelareorep primes the tumor for checkpoint inhibition therapy by activating the interferon-gamma signaling pathway and tumor inflammation signature in early breast cancer patients - results of the AWARE-1 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD4-03.
Abstract PD6-10: PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies
Authors: Haddad Philip A. , Zaheer Usman 
Published: March 2023

Abstract
Background/Rationale: Male breast cancer accounts for less than 1 percent of all cancer diagnoses in men. Because it is rare, it does not lend itself to large, randomized trials. In general, the approach to the treatment of early, non-metastatic male breast cancer has largely been extrapolated from female breast cancer trials. Specifically, the data on early-stage post mastectomy radiation therapy (PMRT) is limited, and its benefits remain unclear. Objectives: We conducted this meta-analysis to determine the impact of PMRT on clinical outcomes of men with breast cancer. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of invasive non-metastatic male breast cancer (MBC), comparative studies of PMRT versus none, and studies that reported the incidence of local and distant recurrences as well as survival data in the compared arms. A meta-analysis using the Mantel-Haenszel method for calculating the weighted pooled relative risk (RR) under the fixed effects model. Subsequently, the heterogeneity statistic gets incorporated to calculate the summary RR under the random effects model. Results: Ten retrospective comparative studies with 3912 patients were included and analyzed. Eight studies reported survival data. Six and three studies reported local and distant recurrence incidence, respectively. PMRT did not have an impact on overall survival or distant recurrences. However, PMRT significantly lowered the RR of locoregional recurrences (RR=0.53, 95%CI 0.31-0.92). In addition, when survival was analyzed by TNM stage and N status, PMRT was found to have a significant reduction in RR of death in stage III (RR=0.85, 95%CI 0.75-0.97), N1 (RR=0.77, 95%CI 0.61-0.98), and N2 (RR=0.61, 95%CI 0.49-0.78) disease. Conclusions: This is the first meta-analysis to show that PMRT is associated with a lower relative risk of death in stage III MBC as well as N1 and N2 disease. It also demonstrates a significant reduction in RR of locoregional recurrences. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of PMRT in this MBC patient population.
Citation Format: Philip A. Haddad, Usman Zaheer. PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-10.
Abstract WS2-1: Drug-tolerant persister cells in cancer
Authors: Brugge Joan 
Published: March 2023

Abstract
Despite favorable initial response to therapy, many cancer patients develop recurrent disease and succumb to it within five years of diagnosis. While there has been much progress in characterizing the pathways that contribute to stable genetic drug resistance, non-genetic mechanisms have recently emerged as important drivers of therapy failure in cancer. In my presentation, I will discuss different types of non-genetic, reversible mechanisms that confer therapy resistance, those involving immediate adaptive responses to stresses associated with therapies, and the other states associated with longer term persistence. I will include a discussion of strategies to target the vulnerabilities associated with each of these adaptive responses.
Citation Format: Joan Brugge. Drug-tolerant persister cells in cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr WS2-1.
The Influence of Overminus Lens Therapy on Control of Intermittent Exotropia: A Meta-Analysis of Randomized Clinical Trials
Authors: Song Desheng , Li Jue , Qian Jing , Lou Bin , Chen Zhijun 
Published: March 2023

Background: Intermittent exotropia (IXT) is the most common type of strabismus, overminus lens (OML) therapy is frequently prescribed to treat IXT. Objectives: The purpose of this study was to compare the effectiveness of OML and observation in the treatment of IXT. Method: An exhaustive search of the literature in PubMed, Embase, Web of Science, and Cochrane Library databases was performed until July 2022. No language restrictions were used. The literature was rigorously screened according to eligibility criteria. Weighted mean differences and 95% confidence intervals (CIs) were calculated. Results: A total of 4 articles with 561 participants were included in this meta-analysis. Our pooled results showed that OML demonstrated superior outcomes compared with observation, with greater decreases in distance and near exodeviation control (MD = −1.08, 95% CI: −1.96 to −0.20, p = 0.02; MD, −0.64, 95% CI: −1.15 to −0.13, p &lt; 0.001). Patients who received OML therapy had a greater decrease in the deviation at both distance and near (MD = −4.00, 95% CI: −7.03 to −0.98, p &lt; 0.001; MD = −4.79, 95% CI: −6.29 to −3.30, p &lt; 0.001). There was no statistical difference between the two groups in terms of post-treatment proximal stereopsis (MD, 0.00, 95% CI: −0.08 to 0.08, p = 1.00). Conclusions: The present meta-analysis indicated that OML therapy was effective in improving the control and decreasing exodeviation angle of IXT. However, it seemed not to be effective in improving the level of near stereopsis.
Southern Ocean Surface Temperatures and Cloud Biases in Climate Models Connected to the Representation of Glacial Deep Ocean Circulation
Authors: Sherriff-Tadano Sam , Abe-Ouchi Ayako , Yoshimori Masakazu , Ohgaito Rumi , Vadsaria Tristan , Chan Wing-Le , Hotta Haruka , Kikuchi Maki , Kodama Takanori , Oka Akira , Suzuki Kentaroh 
Published: March 2023

Abstract
Simulating and reproducing the past Atlantic meridional overturning circulation (AMOC) with comprehensive climate models are essential to understanding past climate changes as well as to testing the ability of the models in simulating different climates. At the Last Glacial Maximum (LGM), reconstructions show a shoaling of the AMOC compared to modern climate. However, almost all state-of-the-art climate models simulate a deeper LGM AMOC. Here, it is shown that this paleodata–model discrepancy is partly related to the climate model biases in modern sea surface temperatures (SST) over the Southern Ocean (70°–45°S). Analysis of model outputs from three phases of the Paleoclimate Model Intercomparison Project shows that models with warm Southern Ocean SST biases tend to simulate a deepening of the LGM AMOC, while the opposite is observed in models with cold SST biases. As a result, a positive correlation of 0.41 is found between SST biases and LGM AMOC depth anomalies. Using sensitivity experiments with a climate model, we show, as an example, that changes in parameters associated with the fraction of cloud thermodynamic phase in a climate model reduce the biases in the warm SST over the modern Southern Ocean. The less biased versions of the model then reproduce a colder Southern Ocean at the LGM, which increases formation of Antarctic Bottom Water and causes shoaling of the LGM AMOC, without affecting the LGM climate in other regions. The results highlight the importance of sea surface conditions and clouds over the Southern Ocean in simulating past and future global climates.

Significance Statement
To test the ability of comprehensive climate models, simulations of the Last Glacial Maximum (LGM) have been conducted. However, most models simulated a deeper Atlantic meridional overturning circulation (AMOC) in the LGM, which contradicts paleodata suggesting a shallower AMOC. Here, using multimodel analysis and sensitivity experiments with a climate model, we show that this paleodata–model discrepancy is partly related to model biases in the modern Southern Ocean. Improvements in Southern Ocean surface temperatures and clouds reproduce a colder climate over the Southern Ocean at the LGM, which causes an intense shoaling of the AMOC due to increased formation of Antarctic Bottom Water. These results demonstrate the important effect of model biases over the Southern Ocean on simulating past climates.
Pacific Meridional Mode Does Not Induce Strong Positive SST Anomalies in the Central Equatorial Pacific
Authors: Hu Ruikun , Lian Tao , Feng Jie , Chen Dake 
Published: March 2023

Abstract
The positive phase of the Pacific meridional mode (PMM) is closely related to the onset of El Niño. Previous studies have indicated that positive sea surface temperature anomalies (SSTAs) in the central equatorial Pacific (CEP) during the spring and summer of positive PMM years primarily originate from the northeastern tropical Pacific (NETP) via positive wind–evaporation–SST feedback. We review the evolution of PMM and find weak evidence to support such a linkage. Coupled model experiments show that the positive PMM-regressed SSTAs in the NETP only account for ∼24% of those in the CEP from winter to spring, illustrating the principle that correlation does not necessarily mean causality. The strongest positive PMM SSTAs in the NETP and CEP increase El Niño intensity by 1.07°C, whereas that in the NETP alone increase El Niño intensity by 0.69°C. When the composite SSTAs in the NETP during positive PMM years are used, however, the El Niño intensity is increased merely by 0.17°C. The change in the subsurface temperature in the equatorial Pacific is curtailed for the NETP SSTAs to trigger El Niño, while the wind–evaporation–SST feedback plays a less important role. Our results indicate that the impact of PMM on El Niño might be overestimated by ∼55%. Moreover, a comprehensive understanding about the role of the tropical North Pacific on El Niño can be obtained only when the impact from the western North Pacific is considered.
Analysis of structural variation among inbred mouse strains
Authors: Arslan Ahmed , Fang Zhuoqing , Wang Meiyue , Tan Yalun , Cheng Zhuanfen , Chen Xinyu , Guan Yuan , J. Pisani Laura , Yoo Boyoung , Bejerano Gill , Peltz Gary 
Published: March 2023

Abstract
Background
‘Long read’ sequencing methods have been used to identify previously uncharacterized structural variants that cause human genetic diseases. Therefore, we investigated whether long read sequencing could facilitate genetic analysis of murine models for human diseases.

Results
The genomes of six inbred strains (BTBR T + Itpr3tf/J, 129Sv1/J, C57BL/6/J, Balb/c/J, A/J, SJL/J) were analyzed using long read sequencing. Our results revealed that (i) Structural variants are very abundant within the genome of inbred strains (4.8 per gene) and (ii) that we cannot accurately infer whether structural variants are present using conventional short read genomic sequence data, even when nearby SNP alleles are known. The advantage of having a more complete map was demonstrated by analyzing the genomic sequence of BTBR mice. Based upon this analysis, knockin mice were generated and used to characterize a BTBR-unique 8-bp deletion within Draxin that contributes to the BTBR neuroanatomic abnormalities, which resemble human autism spectrum disorder.

Conclusion
A more complete map of the pattern of genetic variation among inbred strains, which is produced by long read genomic sequencing of the genomes of additional inbred strains, could facilitate genetic discovery when murine models of human diseases are analyzed.
Construct of qualitative diagnostic biomarkers specific for glioma by pairing serum microRNAs
Authors: Li Hongdong , Ma Liyuan , Luo Fengyuan , Liu Wenkai , Li Na , Hu Tao , Zhong Haijian , Guo You , Hong Guini 
Published: March 2023

Abstract
Background
Serum microRNAs (miRNAs) are promising non-invasive biomarkers for diagnosing glioma. However, most reported predictive models are constructed without a large enough sample size, and quantitative expression levels of their constituent serum miRNAs are susceptible to batch effects, decreasing their clinical applicability.

Methods
We propose a general method for detecting qualitative serum predictive biomarkers using a large cohort of miRNA-profiled serum samples (n = 15,460) based on the within-sample relative expression orderings of miRNAs.

Results
Two panels of miRNA pairs (miRPairs) were developed. The first was composed of five serum miRPairs (5-miRPairs), reaching 100% diagnostic accuracy in three validation sets for distinguishing glioma and non-cancer controls (n = 436: glioma = 236, non-cancers = 200). An additional validation set without glioma samples (non-cancers = 2611) showed a predictive accuracy of 95.9%. The second panel included 32 serum miRPairs (32-miRPairs), reaching 100% diagnostic performance in training set on specifically discriminating glioma from other cancer types (sensitivity = 100%, specificity = 100%, accuracy = 100%), which was reproducible in five validation datasets (n = 3387: glioma = 236, non-glioma cancers = 3151, sensitivity> 97.9%, specificity> 99.5%, accuracy> 95.7%). In other brain diseases, the 5-miRPairs classified all non-neoplastic samples as non-cancer, including stroke (n = 165), Alzheimer’s disease (n = 973), and healthy samples (n = 1820), and all neoplastic samples as cancer, including meningioma (n = 16), and primary central nervous system lymphoma samples (n = 39). The 32-miRPairs predicted 82.2 and 92.3% of the two kinds of neoplastic samples as positive, respectively. Based on the Human miRNA tissue atlas database, the glioma-specific 32-miRPairs were significantly enriched in the spinal cord (p = 0.013) and brain (p = 0.015).

Conclusions
The identified 5-miRPairs and 32-miRPairs provide potential population screening and cancer-specific biomarkers for glioma clinical practice.
Composition, structure, and functional shifts of prokaryotic communities in response to co-composting of various nitrogenous green feedstocks
Authors: Matheri Felix , Kambura Anne Kelly , Mwangi Maina , Ongeso Nehemiah , Karanja Edward , Adamtey Noah , Mwangi Elias Kihara , Mwangi Edwin , Tanga Chrysantus , Musyoka Martha Wangu , Runo Steven 
Published: March 2023

Abstract
Background
Thermophilic composting is a promising method of sanitizing pathogens in manure and a source of agriculturally important thermostable enzymes and microorganisms from organic wastes. Despite the extensive studies on compost prokaryotes, shifts in microbial profiles under the influence of various green materials and composting days are still not well understood, considering the complexity of the green material sources. Here, the effect of regimens of green composting material on the diversity, abundance, and metabolic capacity of prokaryotic communities in a thermophilic compost environment was examined.

Methods
Total community 16S rRNA was recovered from triplicate compost samples of Lantana-based, Tithonia-based, Grass-based, and mixed (Lantana + Tithonia + Grass)- based at 21, 42, 63, and 84 days of composting. The 16S rRNA was sequenced using the Illumina Miseq platform. Bioinformatics analysis was done using Divisive Amplicon Denoising Algorithm version 2 (DADA2) R version 4.1 and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States version 2 (PICRUSt2) pipelines for community structure and metabolic profiles, respectively. In DADA2, prokaryotic classification was done using the Refseq-ribosomal database project (RDP) and SILVA version 138 databases.

Results
Our results showed apparent differences in prokaryotic community structure for total diversity and abundance within the four compost regimens and composting days. The study showed that the most prevalent phyla during composting included Acidobacteriota, Actinobacteriota, Bacteroidota, Chloroflexi, and Proteobacteria. Additionally, there were differences in the overall diversity of metabolic pathways but no significant differences among the various compost treatments on major metabolic pathways like carbohydrate biosynthesis, carbohydrate degradation, and nitrogen biosynthesis.

Conclusion
Various sources of green material affect the succession of compost nutrients and prokaryotic communities. The similarity of amounts of nutrients, such as total Nitrogen, at the end of the composting process, despite differences in feedstock material, indicates a significant influence of composting days on the stability of nutrients during composting.