bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB179: Automated viable circulating tumor cell (CTC) isolation enables efficient single-cell multi-omics analysis in a clinical setting
Authors: Dickerson Janet , Dufek Dylan , Huff Robbie , Jones Stephenie , Barber-Singh Jennifer , Brandt Christopher , Muller-Cohn Judy , Muller Rolf , Wang Yipeng 
Published: April 2023

Abstract
Circulating tumor cells (CTCs) are rare cells found in peripheral blood or other body fluids of cancer patients. Single-cell multi-omics analysis of CTCs can provide critical information and insights for tumor heterogeneity, early detection, residual disease, recurrence, and response and resistance to therapies. However, the adoption of single cell analysis in a clinical setting has been challenging due to complicated and lengthy workflows, lack of automation, low throughput, cell loss, inefficient cell picking, and nucleic acid degradation. To overcome these challenges, we have developed the fully automated LiquidScan liquid biopsy platform as a solution for CTC enrichment and single cell isolation. Whole blood samples were collected from breast, prostate, and lung cancer patients using BioFluidica blood collection tubes. CTCs were enriched with LiquidScan platform coupled with microfluidic affinity selection of rare cells with antibodies against cancer specific surface markers. Cell eluates released from microfluidic chips were further sorted and individual cells were placed into individual wells of PCR plates. The isolated single cells were processed with either whole genome amplification for DNA analysis or pre-amplification of RNA for transcriptome profiling. Cell viability and RNA integrity were assessed for enriched cells post LiquidScan processing. Whole blood samples were directly loaded to microfluidic chips and processed (capture, wash, release and elute) using Hamilton robot for automated processing with no require to red blood cell lysis. The sample processing time was approximately 3 hours with up to 8 samples processed simultaneously. Enriched cells were 70% viable on average post LiquidScan sample processing. The RNA RIN score for the enriched cells was 6 on average. Success rate of DNA amplifications and RNA pre-Amplifications were both over 90% across all samples processed.
The LiquidScan platform provides a solution for fast, automated single viable cell isolation making downstream molecular analysis possible in a clinical setting. Protocols for RNA pre-amplification and DNA sequencing including copy number analysis and targeted resequencing have been developed. Single cell DNA methylation and proteomics assay development is in progress.
Citation Format: Janet Dickerson, Dylan Dufek, Robbie Huff, Stephenie Jones, Jennifer Barber-Singh, Christopher Brandt, Judy Muller-Cohn, Rolf Muller, Yipeng Wang. Automated viable circulating tumor cell (CTC) isolation enables efficient single-cell multi-omics analysis in a clinical setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB179.
Abstract LB279: Targeting microglial metabolic rewiring synergizes with immune checkpoint blockade therapy for glioblastoma
Authors: Ye Zengpanpan , Ai Xiaolin , Zhao Linjie , Rich Jeremy N. , Zhou Shengtao 
Published: April 2023

Abstract
Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2 +/−) or microglia-specific Nr4a2 (Nr4a2 fl/fl Cx3cr1 cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacological NR4A2 inhibition attenuated the pro-tumorigenic TIME, and targeting the NR4A2 or SQLE enhanced therapeutic efficacy of immune checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer.
Citation Format: Zengpanpan Ye, Xiaolin Ai, Linjie Zhao, Jeremy N. Rich, Shengtao Zhou. Targeting microglial metabolic rewiring synergizes with immune checkpoint blockade therapy for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB279.
Abstract LB301: Molecular pharmacology and broad synergy of the novel ATR inhibitor M1774 with DNA damaging anticancer agents
Authors: Jo Ukhyun , Arakawa Yasuhiro , Zimmermann Astrid , Taniyama Daiki , Mizunuma Makito , Jenkins Lisa M , Kumar Suresh , Zenke Frank T , Pommier Yves 
Published: April 2023

Abstract
Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase orchestrates DNA damage response and repair pathways stimulated by replicative stresses. Recent studies have established that pharmacological inhibition of ATR is clinically promising. As M1774 is an oral ATR inhibitor in clinical development, we explored the molecular basis by which M1774 induces cancer cell death. As a single agent, we found that M1774 suppresses cancer cell viability at nanomolar concentrations with a potency higher than ceralasertib and berzosertib, but lower than gartisertib (M4344) and elimusertib in the small cell lung cancer (SCLC) cell lines H146, H82, and DMS114. We found that M1774 efficiently suppresses the ATR/CHK1 checkpoints. While M1774 alone induced apoptosis and G2/M cell cycle arrest at micromolar concentrations, at a non-toxic low dose, M1774 enhanced TOP1 inhibitor-mediated cancer cell death by preventing replication arrest and inducing DNA damage detected by EdU and γH2AX staining. Tandem mass tagging (TMT) coupled with mass spectrometry revealed that M1774 combined with SN-38 increases the expression of replication-related proteins (TIPIN, CDC45, TIMELESS, and RPA1) and G2/M-related proteins (PLK1 and CCNB1). To establish the synergistic combinations of M1774 with clinical anticancer DNA damaging agents in preclinical models, we performed experiments in cancer cell lines, patient-derived organoids, and xenograft models. Low doses of M1774 significantly synergized with the clinical TOP1 inhibitor SN-38, the TOP2 inhibitor etoposide, cisplatin, and the PARP inhibitor talazoparib in SCLC cell lines. We also found that M1774 significantly reversed chemoresistance to DNA-damaging agents in cancer cells lacking SLFN11 expression, suggesting that SLFN11 expression can be utilized for combination therapy with M1774 as a biomarker. The synergistic efficacy between M1774 and DNA-damaging agents was confirmed in SCLC patient-derived organoids, colon cancer patient-derived organoids, and H82 SCLC xenografts. Together, these results provide insights into the molecular mechanism and potential combination strategies for M1774 in cancer therapy.
Citation Format: Ukhyun Jo, Yasuhiro Arakawa, Astrid Zimmermann, Daiki Taniyama, Makito Mizunuma, Lisa M Jenkins, Suresh Kumar, Frank T Zenke, Yves Pommier. Molecular pharmacology and broad synergy of the novel ATR inhibitor M1774 with DNA damaging anticancer agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB301.
Abstract LB347: A lung-mimicking synthetic metastatic niche reveals N1 neutrophils drive breast cancer metastatic dormancy in the lungs
Authors: Wang Jing , Ocadiz-Ruiz Ramon , Hall Matthew , Bushnell Grace , Orbach Sophia , Decker Joseph , Raghani Ravi , Zhang Yining , Morris Aaron , Jeruss Jacqueline , Shea Lonnie 
Published: April 2023

Abstract
3D scaffolds mimicking the environment in the primary tumor or metastatic organs can deconstruct complex niche signals and facilitate the study of cancer progression and metastasis. Here, we reported that a subcutaneous 3D scaffold implant acted as a lung-mimicking dormant metastatic niche in mouse models of metastatic breast cancer, recruiting lung-tropic circulating tumor cells yet suppressing their growth through potent in situ antitumor immunity. We compared it with the immunosuppressive lungs developing lethal metastases and the dormant lungs suppressing tumor growth derived from breast cancer models with varying tumor aggressiveness and host immunity. Our data suggested that breast cancer-induced Gr1+CD11b+Ly6G+ granulocytic myeloid cells (neutrophils) infiltrated the scaffold implants and lungs, secreting the same signal to facilitate the metastatic seeding of lung-tropic cancer cells in these two types of niches. However, circulating neutrophils with opposing phenotypes and functions (N1 and N2) were selectively recruited and enriched in the dormant scaffolds/lungs and immunosuppressive lungs, respectively, responding to two distinct groups of chemoattractants. N1 or N2 neutrophils established activated or suppressive immune environments in the metastatic niches, directing different fates of cancer cells. The clinical relevance of these scientific findings was validated by the strong positive correlation of a high N1-to-N2 neutrophil chemoattractant ratio with a low-grade primary tumor, a low metastases incidence, and a better prognosis in breast cancer patients. Overall, our study revealed the multifaceted roles of neutrophils in regulating lung metastasis and underscored the importance of N1 neutrophils in driving breast cancer metastatic dormancy in the lungs, inspiring next-generation immunotherapy.
Citation Format: Jing Wang, Ramon Ocadiz-Ruiz, Matthew Hall, Grace Bushnell, Sophia Orbach, Joseph Decker, Ravi Raghani, Yining Zhang, Aaron Morris, Jacqueline Jeruss, Lonnie Shea. A lung-mimicking synthetic metastatic niche reveals N1 neutrophils drive breast cancer metastatic dormancy in the lungs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB347.
Abstract LB348: A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors
Authors: Jiang Yan 
Published: April 2023

Abstract
Background: Multiple studies support the gut microbiome as playing a key role in response to immune checkpoint blockade (ICB). Habitual dietary fiber intake has been associated with improved response to ICB. We conducted a pilot feasibility study of a high-fiber dietary intervention (HFDI) in melanoma survivors.
Methods: Melanoma survivors (BMI &lt;40 kg/m2, currently not on active therapy) were enrolled to a 6-week controlled feeding study in which all meals were provided by MD Anderson Cancer Center Bionutrition Research Core. Target daily fiber intake was up to 50 g/day derived from whole foods. The primary outcome was compliance. Blood and stool were collected q 2 weeks. Whole genome shotgun sequencing (WGS) was performed on fecal specimens, and metabolomics was conducted using mass spectroscopy on blood and stool.
Results: Ten participants were enrolled, of which 60% were female. Average BMI was 31.4 kg/m2, and average baseline fiber intake was 17.8 g/day (range 7.4-28.3 g/day). Overall compliance was 88% (95% CI 83%-93%) with 45.8 g/day fiber reached (range 40.0-50.0 g/day). HFDI was well-tolerated with 1 participant experiencing grade 2 diarrhea and all other AEs were grade 1: diarrhea (40%), bloating (50%), flatulence (60%) and abdominal pain (10%). Exploratory analyses of global and targeted metabolomics showed increases in the short chain fatty acid acetate, shifts in omega-3/6 PUFAs, and indole/tryptophan metabolism. Stool WGS analyses showed that the largest shifts in gut microbiome structure in those who started with the lowest baseline fiber intake.
Conclusion: A HFDI is well-tolerated and feasible in a melanoma population. The expected shifts in metabolome and gut microbiome observed with HFDI support that participants were compliant. Thus, this intervention is currently being tested in a Phase II study in metastatic melanoma patients receiving ICB.
Citation Format: Yan Jiang. A controlled high fiber dietary intervention alters metabolome and gut microbiome in melanoma survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB348.
Scaling Approaches to Quasigeostrophic Theory for Moist, Precipitating Air
Authors: Bäumer Daniel , Hittmeir Sabine , Klein Rupert 
Published: April 2023

Abstract
Quasigeostrophic (QG) theory is of fundamental importance in the study of large-scale atmospheric flows. In recent years, there has been growing interest in extending the classical QG plus Ekman friction layer model (QG–Ekman) to systematically include additional physical processes known to significantly contribute to real-life weather phenomena. This paper lays the foundation for combining two of these developments, namely, Smith and Stechmann’s family of precipitating quasigeostrophic (PQG) models on the one hand, and the extension of QG–Ekman for dry air by a strongly diabatic layer (DL) of intermediate height (QG–DL–Ekman) on the other hand. To this end, Smith and Stechmann’s PQG equations for soundproof motions are first corroborated within a general asymptotic modeling framework starting from a full compressible flow model. The derivations show that the PQG model family is naturally embedded in the asymptotic hierarchy of scale-dependent atmospheric flow models introduced by one of the present authors. Particular emphasis is then placed on an asymptotic scaling regime for PQG that accounts for a generic Kessler-type bulk microphysics closure and is compatible with QG–DL–Ekman theory. The detailed derivation of a moist QG–DL–Ekman model is deferred to a future publication.
Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post–CD19-directed CAR T-cell therapy: an EPICOVIDEHA survey
Authors: van Doesum Jaap A. , Salmanton-García Jon , Marchesi Francesco , Di Blasi Roberta , Falces-Romero Iker , Cabirta Alba , Farina Francesca , Besson Caroline , Weinbergerová Barbora , Van Praet Jens , Schönlein Martin , López-García Alberto , Lamure Sylvain , Guidetti Anna , De Ramón-Sánchez Cristina , Batinić Josip , Gavriilaki Eleni , Tragiannidis Athanasios , Tisi Maria Chiara , Plantefeve Gaëtan , Petzer Verena , Ormazabal-Vélez Irati , Marques de Almeida Joyce , Marchetti Monia , Maertens Johan , Machado Marina , Kulasekararaj Austin , Hernández-Rivas José-Ángel , Gomes da Silva Maria , Fernández Noemí , Espigado Ildefonso , Drgoňa Ľuboš , Dragonetti Giulia , Metafuni Elisabetta , Calbacho Maria , Blennow Ola , Wolf Dominik , van Anrooij Bjorn , Nunes Rodrigues Raquel , Nordlander Anna , Martín-González Juan-Alberto , Liévin Raphaël , Jiménez Moraima , Gräfe Stefanie K. , García-Sanz Ramón , Córdoba Raúl , Rahimli Laman , van Meerten Tom , Cornely Oliver A. , Pagano Livio 
Published: April 2023

Abstract
Patients with previous CD19-directed chimeric antigen receptor (CAR) T-cell therapy have a prolonged vulnerability to viral infections. Coronavirus disease 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real-world data on the impact of vaccination and treatment on patients with COVID-19 after CD19-directed CAR T-cell therapy are lacking. Therefore, this multicenter, retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared with patients infected with previous variants (7% vs 58% [P = .012]). Twenty-six patients were vaccinated at the time of the COVID-19 diagnosis. Two vaccinations showed a marked but unsignificant reduction in the risk of COVID-19–caused mortality (33.3% vs 14.2% [P = .379]). In addition, the course of the disease appears milder with less frequent intensive care unit admissions (39% vs 14% [P = .054]) and a shorter duration of hospitalization (7 vs 27.5 days [P = .022]). Of the available treatment options, only monoclonal antibodies seemed to be effective at reducing mortality from 32% to 0% (P = .036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death. This trial was registered at www.clinicaltrials.gov as #NCT04733729.
T-RHEX-RNAseq – a tagmentation-based, rRNA blocked, random hexamer primed RNAseq method for generating stranded RNAseq libraries directly from very low numbers of lysed cells
Authors: Gustafsson Charlotte , Hauenstein Julia , Frengen Nicolai , Krstic Aleksandra , Luc Sidinh , Månsson Robert 
Published: April 2023

Abstract
Background
RNA sequencing has become the mainstay for studies of gene expression. Still, analysis of rare cells with random hexamer priming – to allow analysis of a broader range of transcripts – remains challenging.

Results
We here describe a tagmentation-based, rRNA blocked, random hexamer primed RNAseq approach (T-RHEX-RNAseq) for generating stranded RNAseq libraries from very low numbers of FACS sorted cells without RNA purification steps.

Conclusion
T-RHEX-RNAseq provides an easy-to-use, time efficient and automation compatible method for generating stranded RNAseq libraries from rare cells.
BSA modification of bacterial surface: a promising anti-cancer therapeutic strategy
Authors: He Zhongming , Chen Kun , An Yu , He Jie , Zhang Xiaoli , Tang Lannan , Sun Fa , Jiang Kehua 
Published: April 2023

Abstract
Background
Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics.

Methods and objective
Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated.

Results
BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines.

Conclusion
BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.
Graphical analysis of multi-environmental trials for wheat grain yield based on GGE-biplot analysis under diverse sowing dates
Authors: Saeidnia Fatemeh , Taherian Majid , Nazeri Seyed Mahmoud 
Published: April 2023

Abstract
Background
Information on the nature and extent of genetic and genotype × environment (GE) interaction is extremely rare in wheat varieties under different sowing dates. In the present study, the GGE biplot method was conducted to investigate genotype × environment interaction effects and evaluate the adaptability and yield stability of 13 wheat varieties across eight sowing dates, in order to facilitate comparison among varieties and sowing dates and identify suitable varieties for the future breeding studies.

Results
Considerable genotypic variation was observed among genotypes for all of the evaluated traits, demonstrating that selection for these traits would be successful. Low broad sense heritability obtained for grain yield showed that, both genetic and non-genetic gene actions played a role in the control of this trait, and suggested that indirect selection based on its components which had high heritability and high correlation with yield, would be more effective to improve grain yield in this germplasm. Hence, selection based on an index may be more useful for improvement of this trait in recurrent selection programs. The results of the stability analysis showed that the environmental effect was a major source of variation, which captured 72.21% of total variation, whereas G and GE explained 6.94% and 18.33%, respectively. The partitioning of GGE through GGE biplot analysis showed that, the first two PCs accounted for 54.64% and 35.15% of the GGE sum of squares respectively, capturing a total of 89.79% variation. According to the GGE biplot, among the studied varieties, the performance of Gascogen was the least stable, whereas Sirvan, Roshan, and Pishtaz had superior performance under all sowing dates, suggesting that they have a broad adaptation to the diverse sowing dates. These varieties may be recommended for genetic improvement of wheat with a high degree of adaptation.

Conclusion
The results obtained in this study demonstrated the efficiency of the GGE biplot technique for selecting high yielding and stable varieties across sowing dates.