bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B38: Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity
Authors: Guarnerio Jlenia 
Published: December 2022

Abstract
Soft-tissue sarcomas (STS) are mesenchymal tumors that affect almost 200,000 individuals worldwide each year. Surgery is the standard treatment, followed by anthracycline-based chemotherapy, either alone or in combination with ifosfamide. Still, the 5-year survival rate is below 20% for advanced and metastatic STS. A main clinical challenge is creating and implementing therapies that can successfully treat the primary tumors so that the disease burden is eradicated, and relapsing lesions are prevented. Immunotherapy approaches such as anti-PD1/PDL1 have produced only marginal results for sarcoma patients. Novel investigations in this respect are hindered by the lack of knowledge of the sarcoma immune microenvironment and the scarcity of STS immune-competent mouse models. We therefore developed a mouse model of undifferentiated pleiomorphic sarcoma (UPS), one of the most aggressive STS subtypes, and employed single-cell RNA-sequencing to characterize the immune composition of the UPS mass. scRNA-seq showed that macrophages, the main immune cells in sarcoma, exhibit distinct activation states, ranging from anti-tumorigenic to pro-tumorigenic. Notably, sarcoma cells used the pleiotropic cytokine Macrophage Migration Inhibitory Factor (MIF) to interact with macrophages expressing the CD74 receptor, to switch macrophages’ activation state and pro-tumorigenic potential. Blocking the expression of MIF in sarcoma cells favored the accumulation of macrophages with inflammatory and antigen-presenting profiles, hence reducing tumor growth. These data pave the way for testing new therapies aimed at re-shaping the sarcoma microenvironment, in combination with the standard of care.
Citation Format: Jlenia Guarnerio. Single-cell RNA-seq analysis of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B38.
Abstract B41: Reprogramming immunosuppressive tumor-associated macrophages potentiates standard-of-care therapy in melanoma
Authors: Tichet Melanie , Chryplewicz Agnieszka , Hanahan Douglas 
Published: December 2022

Abstract
Cutaneous melanoma is a highly aggressive cancer capable of distant and lethal metastatic spread. Recent breakthroughs have come from understanding oncogenic signaling and cancer immunobiology. Targeted therapies successfully block MAPK signaling in BRAFV600e mutant melanoma with remarkably high clinical responses followed by rapid relapse, whereas checkpoint inhibitors activating the immune response induce long-lasting responses, albeit only in a subset of patients. These limitations have driven interest in understanding innate and acquired resistance. Using an immunocompetent genetically-engineered mouse model of BRAF-driven melanoma, which phenocopies the human disease in its development, histopathology, and response to therapy, we focused on the tumor microenvironment (TME), seeking to elucidate resistance mechanisms. Our investigations have revealed that tumor-associated macrophages (TAMs) are a critical component of the TME, predominantly polarized toward a pro-tumoral “M2-like” phenotype, producing immunosuppressive factors and exhibiting extensive immuno-suppressive capabilities suggesting that they might significantly hinder immune responses in the melanoma TME. Seeking to assess their functional importance, we have found that combining conventional strategies with TAMs-reprogramming agents stimulates anti-tumor immune responses, leading to improved survival and responsiveness to standard-of-care therapies. These data highlight the central role played by macrophages in melanoma progression and demonstrate that pharmacologic reprogramming of macrophages represents a new therapeutic modality with the potential to elicit more effective anti-tumor immune responses against this devastating disease.
Citation Format: Melanie Tichet, Agnieszka Chryplewicz, Douglas Hanahan. Reprogramming immunosuppressive tumor-associated macrophages potentiates standard-of-care therapy in melanoma [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B41.
Abstract B50: Discovery of multiple mechanisms of immune evasion that accelerate primary melanomagenesis in a genetic model with low tumor mutation burden
Authors: Wilson Emily C , Wee Yinshen , Wang Junhua , Rich Coulson P , Rogers Aaron , Wolff Roger K , Holmen Sheri L , Grossmann Allie H 
Published: December 2022

Abstract
Although immune checkpoint blockade (ICB) therapy can improve outcomes in advanced melanoma, early detection and treatment focused on preventing metastasis remain the optimal approaches for superior survival. Immune evasion occurs early in melanoma development and as such, some patients with high-risk Stage II (nonmetastatic) disease benefit from ICB. These human data highlight a critical need to understand the complex process of immune evasion during melanoma formation and early progression. To this end, we interrogated the tumor immune microenvironment of the RCAS-CRE inducible, Dct::TVA; BrafV600E; Cdkn2aNull murine model of melanoma. Tumor development occurs rapidly and at high frequency in these mice, without exposure to ultraviolet light or mutagenic carcinogens, modeling an important molecular class of melanoma with low mutation burden, which generally occurs in young patients. Using single-cell RNA sequencing and immunostaining, we discovered that primary tumors show evidence of an adaptive immune response that is restricted by myeloid-derived suppressor cells, regulatory T cells and PD-L1 expression. Systemic anti-PD-1 treatment reduced tumor incidence and significantly delayed tumor onset. Despite the low mutation burden, our data demonstrate the presence of a smoldering adaptive immune response that can be unleashed with ICB to limit tumor formation. Importantly, unlike syngeneic allograft models, our genetic model provides a unique opportunity to interrogate tumor-intrinsic mechanisms of immune evasion during an auspicious time window that spans from - tumor initiation to high-risk, pre-metastatic disease. Thus, we have identified a useful in vivo tool for the discovery of novel mechanisms of immune evasion and for testing therapeutic interventions in early-stage disease.
Citation Format: Emily C Wilson, Yinshen Wee, Junhua Wang, Coulson P Rich, Aaron Rogers, Roger K Wolff, Sheri L Holmen, Allie H Grossmann. Discovery of multiple mechanisms of immune evasion that accelerate primary melanomagenesis in a genetic model with low tumor mutation burden [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B50.
Abstract B56: Quiescent cancer cells resist T cell attack by forming an immune-suppressive niche
Authors: Baldominos Pilar , Barbera-Mourelle Alex , Barreiro Olga , Huang Yu , Wight Andrew , Agudo Judith 
Published: December 2022

Abstract
Immunotherapy is a promising treatment for Triple-Negative Breast Cancer (TNBC), but patients relapse, highlighting the need to understand mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent. Quiescent Cancer Cells (QCCs) form clusters with reduced immune infiltration. They also display superior tumorigenic capacity and higher expression of chemotherapy resistance and stemness genes. We adapted single-cell-RNA-sequencing with precise spatial resolution to profile infiltrating cells inside and outside the QCC niche. This transcriptomic analysis revealed hypoxia-induced programs and identified more exhausted T-cells, tumor-protective fibroblasts, and dysfunctional dendritic cells inside clusters of QCCs. This uncovered differential phenotypes in infiltrating cells based on their intra-tumor location. Thus, QCCs constitute immunotherapy-resistant reservoirs by orchestrating a local hypoxic immune-suppressive milieu that blocks T-cell function. Eliminating QCCs holds the promise to counteract immunotherapy resistance and prevent disease recurrence in TNBC.
Citation Format: Pilar Baldominos, Alex Barbera-Mourelle, Olga Barreiro, Yu Huang, Andrew Wight, Judith Agudo. Quiescent cancer cells resist T cell attack by forming an immune-suppressive niche [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B56.
Abstract B64: Evaluation of doxorubicin and PD-1/CTLA-4 immune blockade combination therapy in the MCA-205 murine model
Authors: Therrien Nicholas R , Powers Kyle , Kemp Lindsey , Tellez Cristiam Moreno , Wilky Breelyn A 
Published: December 2022

Abstract
Background: Soft tissue sarcoma is a rare form of cancer primarily affecting connective tissue in adults. Standard chemotherapy includes the anthracycline doxorubicin which has previously been shown in a variety of cancer models to induce immunogenic cell death (ICD). ICD is driven, in part, by the upregulation and/or translocation of molecules such as calreticulin and annexin I, known as damage associated molecular patterns (DAMPs). We aimed to investigate the ICD capacity of anthracyclines doxorubicin and mitoxantrone and explore activity in combination with anti-PD1 and CTLA-4 checkpoint inhibitors.Methods: We treated a variety of human osteosarcoma cell lines and MCA-205 mouse fibrosarcoma cells with doxorubicin and mitoxantrone and measured expression of DAMPs and immunosuppressive markers via multiplex flow cytometry. We also measured anti-tumor activity of doxorubicin with and without PD1/CTLA4 blockade in the murine sarcoma model MCA-205. After tumors were harvested, we analyzed tumor-infiltrating lymphocytes to determine the effects of treatment on phenotype, quantity, activation status, function, clonality, and expression of immune checkpoint proteins.Results: We found expression of Annexin I and TRAIL-R2 on the cell surface of osteosarcoma cell lines treated with anthracyclines and significant inhibition of tumor growth with the combination of doxorubicin plus PD1/CTLA4 blockade compared to either doxorubicin or checkpoint blockade alone. Profiling of TILs revealed a marked increase in CD8:CD4 ratio and increased expression of checkpoint proteins including PD1, 41BB and TIM3 in the combination of doxorubicin plus checkpoint blockade. Finally, increased preponderance of the TCRVb 5.1-5.2 clonotype was observed with the combination in TIL, which was not observed in spleen or peripheral blood samples.Conclusion: We have observed early evidence of improved anti-tumor effects with combination doxorubicin plus PD1/CTLA4 along with reshaping of the TIL repertoire, suggesting that doxorubicin may improve immunogenic cell death and supporting clinical investigation in human sarcoma patients.
Citation Format: Nicholas R Therrien, Kyle Powers, Lindsey Kemp, Cristiam Moreno Tellez, Breelyn A Wilky. Evaluation of doxorubicin and PD-1/CTLA-4 immune blockade combination therapy in the MCA-205 murine model [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B64.
Abstract IA07: The Power of ONE: Immunology in the age of single cell genomics
Authors: Amit Ido 
Published: December 2022

Abstract
The immune system is a complex, dynamic and plastic network composed of various interacting cell types that are constantly sensing and responding to environmental cues. From very early on, the immunology field has invested great efforts to characterize the various immune cell types and elucidate their functions. However, accumulating evidence indicates that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of immune processes. Single cell genomics hold the potential to revolutionize the way we characterize complex immune cell assemblies and study their spatial organization, dynamics, clonal distribution, pathways, and crosstalk. This emerging field can greatly affect basic and translational research of the immune system. I will discuss how recent single cell genomic studies are changing our perspective of various immune related pathologies from cancer to autoimmune disease and neurodegeneration. Finally, I will consider recent and forthcoming technological and analytical advances in single cell genomics and their huge potential impact on the future of immunology research and immunotherapy.
Citation Format: Ido Amit. The Power of ONE: Immunology in the age of single cell genomics [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr IA07.
Autocratic Union Organization and Foreign Direct Investment in the Mexican Automotive Parts Sector, 2004–2018
Authors: Tuman John P. , Erlingsson Hafthor 
Published: December 2022

Abstract
Due to its size and importance, the Mexican automobile industry was an important topic in negotiations for the usmca agreement. A particularly contentious issue was the allegation that foreign direct investment (fdi) in Mexican parts plants has been facilitated by autocratic unions affiliated with the Confederation of Mexican Workers (ctm). Although this issue has been widely noted, there has been little systematic research on the topic. In this paper, we seek to fill this gap in the literature. Using panel data, we examine the determinants of fdi in the automotive parts sector in Mexico’s 31 states and Mexico City (formerly df) from 2004 to 2018. The study makes four contributions to the literature. First, we demonstrate empirically that fdi in the sector concentrated in Mexican states with a higher lagged unionization rate. Second, controlling for the type of union organization, the study shows that fdi was positively associated with states where the ctm was already well-established in the automobile industry. Alternatively, fdi was negatively associated with states where independent and democratic unions had previously organized. Third, we clarify the conditions under which firms prefer pre-emptive unionization with the ctm to the alternative of union avoidance. Finally, the study points to the importance of education and transportation infrastructure in fdi decisions.
Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma
Authors: Giordano Federica , Lenna Stefania , Baudo Gherardo , Rampado Riccardo , Massaro Matteo , De Rosa Enrica , Ewing April , Kurenbekova Lyazat , Agostini Marco , Yustein Jason T. , Taraballi Francesca 
Published: December 2022

AbstractSmall-molecule tyrosine kinase inhibitors (TKIs) represent a potentially powerful approach to the treatment of osteosarcoma (OS). However, dose-limiting toxicity, therapeutic efficacy, and targeting specificity are significant barriers to the use of TKIs in the clinic. Notably among TKIs, ponatinib demonstrated potent anti-tumor activity; however, it received an FDA black box warning for potential side effects. We propose ponatinib-loaded biomimetic nanoparticles (NPs) to repurpose ponatinib as an efficient therapeutic option for OS. In this study, we demonstrate enhanced targeting ability and maintain potent ponatinib nano-therapeutic activity, while also reducing toxicity. In in vitro two- and three-dimensional models, we demonstrate that ponatinib-loaded biomimetic NPs maintain the efficacy of the free drug, while in vivo we show that they can improve tumor targeting, slow tumor growth, and reduce evidence of systemic toxicities. Though there is limited Pon encapsulation within NPs, this platform may improve current therapeutic approaches and reduce dosage-related side effects to achieve better clinical outcomes in OS patients.Graphical Abstract
Potential of green synthesized titanium dioxide nanoparticles for enhancing seedling emergence, vigor and tolerance indices and DPPH free radical scavenging in two varieties of soybean under salinity stress
Authors: Abdalla Hanan , Adarosy Marwa H. , Hegazy Hegazy S. , Abdelhameed Reda E. 
Published: December 2022

Abstract
Background
Considering titanium dioxide nanoparticles (TiO2 NPs) role in plant growth and especially in plant tolerance against abiotic stress, in the present work, TiO2 NPs were green synthesized using an aqueous solution of Aloe vera leaf extract as a capping agent and titanium tetrachloride as a precursor. These green synthesized TiO2 NPs were characterized using different techniques: UV spectrophotometer, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). Results revealed that synthesized TiO2 NPs possess a tetragonal morphology with a size ranging from 10 to 25 nm. Additionally, the present work evaluated the effects of three concentrations of TiO2 NPs (0, 30 and 50 ppm) and six NaCl concentrations (0, 25, 50, 100, 150 and 200 mM) and their interactions with respect to germination parameters, vigor indices, oxidative stress and DPPH free radical scavenging of two varieties of soybean (Glycine max L. var. 22 and 35).

Results
Results demonstrated that all germination traits and vigor indices were negatively affected under all salinity levels. Also, the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were significantly increased by increasing the NaCl concentrations in two soybean varieties. Most interestingly, TiO2 NPs (30 ppm) mediated positive effects on germination parameters, reducing H2O2 and MDA contents by enhancing antioxidant (decreasing IC50) whereas 50 ppm showed an intermediate response under both control and saline soil conditions.

Conclusion
Our findings demonstrate the growth enhancement effects of TiO2 NPs application as well as its ameliorative potential in dealing with salinity.
Breastfeeding-oriented education for parturients separated from their hospitalized infants: a qualitative study of nurses’ perspectives in Shanghai, China
Authors: Feng Haoxue , Liu Ying , Li Junying , Jiang Hui 
Published: December 2022

Abstract
Background
The benefits of breastfeeding for both mother and baby are well recognized. However, the separation of the mother-newborn dyad leads to a lower breastfeeding rate. These parturients who are separated from their hospitalized infants are sometimes unaware of the importance of breastfeeding, while nurses do know how important health education on breastfeeding is and how it can be improved. This descriptive qualitative study aimed to explore the experiences of nurses regarding health education on breastfeeding and summarize the potential ways to improve it.

Methods
A descriptive phenomenological qualitative approach was utilized in this study, and in-depth, semi-structured interviews were conducted with nurses at a tertiary A-grade obstetrics-and gynecology-specialized hospital in Shanghai, China. The purposive and snowball sampling method was used and Colaizzi’s seven-step phenomenological analysis was employed. The Consolidated criteria for Reporting Qualitative research (COREQ) was followed to report findings.

Results
Fifteen nurses participated in the study and shared their suggestions based on their experiences. Four overarching themes emerged from the data: (1) extending the education duration, (2) enriching the educational content, (3) expanding the education subjects, and (4) perfecting the educational process. Each theme included several subthemes.

Conclusion
Health education on breastfeeding should focus on the time, content, subjects, and process as a whole. The nurses’ statements provided a reference for nursing or hospital supervisors to take measures to improve education and increase the breastfeeding rate of hospitalized neonates. Further research from the perspectives of parturients and their family members is needed, to find out what the key points are that all of them attach importance to.
Risk stratification of lateral neck recurrence for patients with pN1a papillary thyroid cancer
Authors: Xu Siyuan , Huang Hui , Huang Ying , Wang Xiaolei , Xu Zhengang , Liu Shaoyan , Liu Jie 
Published: December 2022

Abstract
Background
Lateral neck is not recommended for dissection in patients with pN1a papillary thyroid cancer (PTC), but its recurrence risk has not been well stratified. We aimed to develop a risk stratification system for lateral neck recurrence in patients with pN1a PTC.

Methods
Patients with pN1a PTC who underwent thyroidectomy and unilateral central compartment dissection from 2000–2016 were enrolled. The association between number of central lymph node metastases (CLNMs) and lateral neck recurrence was comprehensively assessed using a Cox proportional hazards model with restricted cubic spline. Stratification was then performed based on CLNMs and other significant risk factors selected by multivariate analysis. Lateral neck recurrent-free survival (LRFS) rate of each stratification was estimated with Kaplan–Meier curve and comparison was performed using log-rank test.

Results
Ninety-six (3.8%) lateral neck recurrences were identified during a median follow-up of 62 months among a total of 2500 admitted cases. An increasing number of CLNMs was associated with compromised LRFS for up to 6 CLNMs (P < 0.001), and CLNMs > 3 indicated significantly worse 5-year LRFS than that of CLNM ≤ 3 (90.6% vs. 98.1%, P < 0.001). When stratification with CLNMs and primary tumor size (selected by multivariate analysis, HR (95%CI) = 4.225(2.460–7.256), P < 0.001), 5-year LRFS rates of high- (CLNMs > 3 and primary tumor size > 2 cm), intermediate- (CLNMs > 3 and primary tumor size 1–2 cm) and low-risk (primary tumor size ≤ 1 cm or CLNMs ≤ 3) groups were 78.5%, 90.0% and 97.9%, respectively (P < 0.05).

Conclusions
The number of CLNMs combined with primary tumor size seems to effectively stratify lateral neck recurrence risk for patients with pN1a PTC.