bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P056: Rapid serial immunoprofiling of the tumor immune microenvironment by fine needle sampling
Authors: Oh Juhyun , Carlson Jonathan C. T. , Landeros Christian , Lee Hakho , Ferguson Scott , Faquin William C. , Clark John R. , Pittet Mikael J. , Pai Sara I. , Weissleder Ralph 
Published: January 2022

Abstract
As the field of cancer immunotherapy brings forth novel and combinatorial agents, there is increasing effort to discover and integrate predictive and/or prognostic biomarkers into treatment algorithms in order to optimize cancer care. While tissue-based methods can elucidate tumor-immune cell compositions at a single time point, serial assessment of the tumor immune microenvironment (TME) can provide unique insight into how various therapies may modulate target tumor and/or immune cell populations over time. We propose that single-cell sampling via fine needle aspirates (FNA) can facilitate such analyses with a favorable risk-benefit profile. Thus, we developed and optimized a multiplexed bioorthogonal approach (FAST-FNA) which has been coupled with a deep learning algorithm that allows for comprehensive cellular analyses of FNA samples. We demonstrate that the FAST-FNA assay reproducibly captures the TME profile as compared to standard labor-intensive flow cytometry and immunohistochemical assays, and, furthermore, allows for time course analysis of the evolving TME in mouse and human cancers in vivo. The translational significance of the FNA-based technology is highlighted in the ability to rapidly assess PD-L1 expression within the TME and is further extended through the serial quantitation of both tumor and immune cell markers in cancer patients treated with immunotherapy. Collectively, these data indicate that FAST-FNA can serve as a robust and versatile clinical tool to monitor the evolving TME and has the potential to provide early insight into treatment response.
Citation Format: Juhyun Oh, Jonathan C. T. Carlson, Christian Landeros, Hakho Lee, Scott Ferguson, William C. Faquin, John R. Clark, Mikael J. Pittet, Sara I. Pai, Ralph Weissleder. Rapid serial immunoprofiling of the tumor immune microenvironment by fine needle sampling [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P056.
Abstract P058: Tumor-targeted IL-2 by engineered mesenchymal stem cells reinvigorates CD8+ T cells
Authors: Bae Joonbeom , Liu Longchao , Timmerman Casey , Hsu Eric , Zhang Anli , Zhu Jiankun , Fu Yang-Xin 
Published: January 2022

Abstract
Tumor microenvironment (TME) generates immunosuppressive niche to induce CD8+ tumor infiltrating lymphocytes (TILs) exhaustion. Therapeutic targeting to functionally reinvigorate CD8+ T cells is a promising strategy to enhance antitumor immunity. While interleukin-2 (IL-2) based therapies cause potent T cell activation and proliferation, the clinical application remains challenging due to short half-life and severe toxicity at therapeutic doses. To address this, we engineered mesenchymal stem cells (MSCs) to successfully proliferate and turn on or off CD8 T cell-preferential IL-2 mutein/Fc fusion protein (SIL2-EMSC) to target cytotoxic T cells in the TME. Peritumoral administration of SIL2-EMSCs permits local production of sufficient SIL2 inside the TME and induces complete tumor regression without adverse toxicity. Mechanistically, SIL2-EMSC remodels the TME that activates and expands preexisting CD8+ TILs. Furthermore, local treatment of SIL2-EMSC elicits systemic antitumor responses for the clearance of distal tumor and metastasis. In advanced tumors, SIL2-EMSCs can overcome resistance to immune check blockade (ICB) and β-lapachone (β-lap) chemotherapy. The therapeutic benefits of SIL2-EMSC were also observed in humanized mouse models. Overall, tumor-targeted delivery of cytokines by next generation of MSCs reverses immunosuppressive environment, improves antitumor effects, and synergize with various therapies without adverse toxicity.
Citation Format: Joonbeom Bae, Longchao Liu, Casey Timmerman, Eric Hsu, Anli Zhang, Jiankun Zhu, Yang-Xin Fu. Tumor-targeted IL-2 by engineered mesenchymal stem cells reinvigorates CD8+ T cells [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P058.
Abstract P076: Humanized anti-αvβ3 antibody engineered to selectively promote macrophage-mediated cancer cell death
Authors: Wettersten Hiromi I. , Shepard Ryan M. , Weis Sara M. , Cheresh David A. 
Published: January 2022

Abstract
Integrin αvβ3, an epithelial-to-mesenchymal transition marker, promotes drug resistance and metastasis in a range of epithelial cancers. Hence, a humanized anti-αvβ3 antibody (Etaracizumab), developed in the 1990s, was designed to eliminate αvβ3+ cells via NK-mediated antibody-dependent cellular-cytotoxicity (ADCC). Etaracizumab has been tested in clinical trials and proven to be safe with some activity in a subset of patients. However, in a recent examination of the immune microenvironment of αvβ3+ human epithelial tumors, we observed a large number of tumor-associated macrophages (TAMs) but minimal accumulation of NK or T cells. This suggests the efficacy of Etaracizumab may have been limited based on the relative lack of NK cells in αvβ3+ tumors. Therefore, we re-engineered Etaracizumab by changing its Fc receptor binding properties to favor TAM engagement over NK cells. This newly designed anti-αvβ3 antibody (ABT-101) while binding to αvβ3 with the same affinity as Etaracizumab, not only eliminates tumor cells via TAM-mediated ADCC but promotes a two-fold increased anti-tumor activity in mice and accumulates to a higher degree in tumors compared to Etaracizumab. Based on these preclinical findings, ABT101 is currently being evaluated in IND enabling studies with the hope to initiate phase I clinical trials in mid-2022.
Citation Format: Hiromi I. Wettersten, Ryan M. Shepard, Sara M. Weis, David A. Cheresh. Humanized anti-αvβ3 antibody engineered to selectively promote macrophage-mediated cancer cell death [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P076.
Abstract P078: Synergistic immunotherapy effects of anti-COVID-19 and anti-cancer vaccines in preventing tumors and infections
Authors: Garimella Narayana 
Published: January 2022

Abstract
To assure efficacy, safety and security of medicines and products including those of cancer and infection prevention ones, the concepts of immunology and immunotherapy, treatments, therapeutics, research, reviews, approvals and according agency, nation and world-wide managements are highly important. Often rationally planned combinations of U.S. Food and Drug Administration (USFDA) approved medicines in preventing or treating the same or similar or multiple diseases are realized to be pharmacologically and biologically effective in mechanisms and toxicologically safe in applications. Because, multiple mechanisms are simultaneously combined in enhancing systemic immunities within the permissible limits of the doses. In this work, the immunology and immunotherapy aspects of both anti-cancer vaccines and anti-COVID-19 vaccines are taken into account to prevent current and future occurrences of cancer and infectious diseases. Though the intended mechanisms of actions are only disease specific and are primarily different between anti-cancer and anti-COVID-19 vaccines, their combinations are worthwhile in providing synergistic effects against carcinogenesis, metastasis and infections. Based on the chemical, biological and pharmacological input and output information for both kinetics and dynamics of vaccines including mRNA-1273, BNT162b2, and JNJ-78436735 to prevent covid-19 are explored in combinations with anti-cancer vaccines including Human Papillomavirus (HPV) Vaccine and Hepatitis B Vaccine (HBV). In addition to safety and efficacy, mRNA, viral-vector, protein and antigen mechanisms, pH, vaccine-vaccine interactions, independent and combined dose regimens, toxicities, solubilities, intrinsic and extrinsic covariates were taken into account for careful planning of combinations. Simultaneous dual combinations from both groups were improved to three to five levels of combinations. It was realized that these combinations qualify for pre-clinical followed by clinical-investigations further. Also, these conclusions promised us to explore additional new and approved vaccines of these indications.
Citation Format: Narayana Garimella. Synergistic immunotherapy effects of anti-COVID-19 and anti-cancer vaccines in preventing tumors and infections [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P078.
Abstract PR09: Macrophage promotion of anti-androgen resistance in prostate cancer bone disease
Authors: Li Xue-Feng , Selli Cigdem , Unciti-Broceta Asier , Carragher Neil O. , Hu Hai-Yan , Sawyers Charles L. , Qian Bin-Zhi 
Published: January 2022

Abstract
Metastatic castration resistant prostate cancer (mCRPC) is the final stage of prostate cancer (PC) that acquires resistance to androgen deprivation therapies (ADT). Despite many recent progresses in the mechanistic understanding of ADT resistance, the specific contribution of the metastatic microenvironment in mCRPC remains largely unknown. A novel in vivo model of androgen dependent bone metastatic PC was developed in address this question. Our identified that macrophages are the major stromal cells in bone metastatic PC. Using multiple genetic models, we demonstrated that macrophages, both monocyte-derived and bone resident populations, were critical for bone metastatic PC to develop resistance to enzalutamide, a clinically used anti-androgen. Mechanistically, macrophages drove resistance through induction of a wound healing like response in prostate cancer cells, which was strongly supported by bioinformatics analysis of multiple patient mCRPC datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth of mCRPC. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.
Citation Format: Xue-Feng Li, Cigdem Selli, Asier Unciti-Broceta, Neil O. Carragher, Hai-Yan Hu, Charles L. Sawyers, Bin-Zhi Qian. Macrophage promotion of anti-androgen resistance in prostate cancer bone disease [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr PR09.
A sociologia católica de Alceu Amoroso Lima contra a sociologia durkheimiana no Brasil
Authors: Carvalho Filho Juarez Lopes 
Published: January 2022

A fundação da sociologia por Durkheim assiste na França ao retorno da filosofia tomista, resultado de uma “estranha aliança” entre a Igreja católica e os intelectuais. Buscando impedir o avanço das ciências sociais, em especial da sociologia durkheimiana, e estabelecer o catolicismo social, a “sociologia católica” encontra seus fundamentos no tomismo e no ensino social de Leão xiii. Após situar a tensão entre sociologia católica e sociologia durkheimiana na França, o artigo objetiva analisar os mecanismos de difusão do neotomismo francês no Brasil, e suas influências na formação de uma sociologia católica brasileira; identificar os agentes sociais e os órgãos que contribuíram com a profissionalização do ensino da sociologia. De cunho histórico e bibliográfico, ele se inscreve numa sociologia dos intelectuais, consagrando um lugar especial a Alceu Amoroso Lima, figura central no corpus da tradição intelectual católica brasileira. A pesquisa conclui que Amoroso Lima se alinha aos católicos sociais franceses por sua origem social, sua trajetória no espaço acadêmico, que combina fracassos universitários e reconversão do capital social e simbólico; e sua inscrição no campo filosófico ligado ao espiritualismo bergsoniano no início e, mais tarde, ao neotomismo de Maritain. Tais prerrogativas lhe dão direito de entrar no campo das ciências sociais rivalizando com a sociologia acadêmica em via de institucionalização.
Legitimidade e obediência: diálogos da Criminologia com a Teoria sociológica
Authors: Natal Ariadne , Castelo Branco Frederico , Alvarez Marcos Cesar 
Published: January 2022

O artigo discute concepções de legitimidade e de obediência sugeridas por algumas abordagens da teoria social. Dispõe-se a problematizar perspectivas que examinam tais noções no âmbito de pesquisas sociológicas e criminológicas, com foco em análises de instituições de segurança e de justiça. Partindo dos escritos de Weber sobre ordens legítimas e os tipos de dominação, exploramos as propostas de operacionalização da legitimidade elaboradas por Beetham e Coicaud. Em seguida, introduzimos o debate de criminólogos contemporâneos como Tyler, Bottoms e Tankebe, que se focam na legitimidade das leis e da polícia. Por fim, discutimos os entraves para a mensuração da legitimidade e apresentamos solução adotada no contexto brasileiro.
Seeing the World From Others’ Perspective: 14-Month-Olds Show
Altercentric Modulation Effects by Others’ Beliefs
Authors: Kampis Dora , Kovács Ágnes Melinda 
Published: January 2022

Abstract
Humans have a propensity to readily adopt others’ perspective, which often influences their behavior even when it seemingly should not. This altercentric influence has been widely studied in adults, yet we lack an understanding of its ontogenetic origins. The current studies investigated whether 14-month-olds’ search in a box for potential objects is modulated by another person’s belief about the box’s content. We varied the person’s potential belief such that in her presence/absence an object was removed, added, or exchanged for another, leading to her true/false belief about the object’s presence (Experiment 1, n = 96); or transformed into another object, leading to her true/false belief about the object’s identity (i.e., the objects represented under a specific aspect, Experiment 2, n = 32). Infants searched longer if the other person believed that an object remained in the box, showing an altercentric influence early in development. These results suggest that infants spontaneously represent others’ beliefs involving multiple objects and raise the possibility that infants can appreciate that others encode the world under a unique aspect.
“Everyone Thought My Library Assistant was My Mum”. Visually Impaired and Blind Students’ Experiences of Interactions with Support and Other Staff in Higher Education
Authors: Croft Emma 
Published: January 2022

Abstract
This article explores visually impaired (vi) and blind students’ experiences of support as an undergraduate student in UK higher education (he) by focusing specifically on relationships and interactions between vi and blind students and support staff within Higher Education. Participants within this research show how their experiences highlight an uneven and often exclusionary Higher Education landscape. Constructions of disability and impairment show a complex relationship between support provision as it is offered and experienced. The findings overall suggest the experience of support is more than the placing together of student and support worker and concerns the management of this relationship, particularly around underlying assumptions about being vi. Support is not unnecessary or unwelcome, instead, the complexity of the relationship, the additional work associated with support experienced by these students, combine to shape academic experience.
A Hybrid Bulk Algorithm to Predict Turbulent Fluxes over Dry and Wet Bare Soils
Authors: Grachev Andrey A. , Fairall Christopher W. , Blomquist Byron W. , Fernando Harindra J. S. , Leo Laura S. , Otárola-Bustos Sebastián F. , Wilczak James M. , McCaffrey Katherine L. 
Published: January 2022

Abstract
Measurements made in the Columbia River basin (Oregon) in an area of irregular terrain during the second Wind Forecast Improvement Project (WFIP2) field campaign are used to develop an optimized hybrid bulk algorithm to predict the surface turbulent fluxes from readily measured or modeled quantities over dry and wet bare or lightly vegetated soil surfaces. The hybrid (synthetic) algorithm combines (i) an aerodynamic method for turbulent flow, which is based on the transfer coefficients (drag coefficient and Stanton number), roughness lengths, and Monin–Obukhov similarity; and (ii) a modified Priestley–Taylor (P-T) algorithm with physically based ecophysiological constraints, which is essentially based on the surface energy budget (SEB) equation. Soil heat flux in the latter case was estimated from measurements of soil temperature and soil moisture. In the framework of the hybrid algorithm, bulk estimates of the momentum flux and the sensible heat flux are derived from a traditional aerodynamic approach, whereas the latent heat flux (or moisture flux) is evaluated from a modified P-T model. Direct measurements of the surface fluxes (turbulent and radiative) and other ancillary atmospheric/soil parameters made during WFIP2 for different soil conditions (dry and wet) are used to optimize and tune the hybrid bulk algorithm. The bulk flux estimates are validated against the measured eddy-covariance fluxes. We also discuss the SEB closure over dry and wet surfaces at various time scales based on the modeled and measured fluxes. Although this bulk flux algorithm is optimized for the data collected during the WFIP2, a hybrid approach can be used for similar flux-tower sites and field campaigns.
A Vertically Resolved MSE Framework Highlights the Role of the Boundary Layer in Convective Self-Aggregation
Authors: Yao Lin , Yang Da , Tan Zhe-Min 
Published: January 2022

Abstract
Convective self-aggregation refers to a phenomenon in which random convection can self-organize into large-scale clusters over an ocean surface with uniform temperature in cloud-resolving models. Previous literature studies convective aggregation primarily by analyzing vertically integrated (VI) moist static energy (MSE) variance. That is the global MSE variance, including both the local MSE variance at a given altitude and the covariance of MSE anomalies between different altitudes. Here we present a vertically resolved (VR) MSE framework that focuses on the local MSE variance to study convective self-aggregation. Using a cloud-resolving simulation, we show that the development of self-aggregation is associated with an increase of local MSE variance, and that the diabatic and adiabatic generation of the MSE variance is mainly dominated by the boundary layer (BL; the lowest 2 km). The results agree with recent numerical simulation results and the available potential energy analyses showing that the BL plays a key role in the development of self-aggregation. Additionally, we find that the lower free troposphere (2–4 km) also generates significant MSE variance in the first 15 days. We further present a detailed comparison between the global and local MSE variance frameworks in their mathematical formulation and diagnostic results, highlighting their differences.
Subseasonal Meteorological Drought Development over the Central United States during Spring
Authors: Jong Bor-Ting , Newman Matthew , Hoell Andrew 
Published: January 2022

AbstractDiagnosis of rapidly developing springtime droughts in the central United States has mostly been made via numerous individual case studies rather than in an aggregate sense. This study investigates common aspects of subseasonal “meteorological drought” evolution, here defined as persistent precipitation minus evapotranspiration (P− ET) deficits, revealed in early (1 April–15 May) and late (16 May–30 June) spring composites of 5-day running mean JRA-55 reanalysis data for three different central U.S. regions during 1958–2018. On average, these droughts are initiated by a quasi-stationary Rossby wave packet (RWP), propagating from the western North Pacific, which arises about a week prior to drought onset. The RWP is related to a persistent ridge west of the incipient drought region and strong subsidence over it. This subsidence is associated with low-level divergent flow that dries the atmosphere and suppresses precipitation for roughly 1–2 weeks, and generally has a greater impact on the local moisture budget than does reduced poleward moisture transport. The resulting “dynamically driven” evaporative demand corresponds to a rapid drying of the root-zone soil moisture, which decreases around 40 percentiles within about 10 days. Anomalous near-surface warmth develops only after theP− ET deficit onset, as does anomalously low soil moisture that then lingers a month or more, especially in late spring. The horizontal scale of the RWPs, and of the related drought anomalies, decreases from early to late spring, consistent with the climatological change in the Pacific Rossby waveguide. Finally, while this composite analysis is based upon strong, persistentP− ET deficits, it still appears to capture much of the springtime development of “flash droughts” as well.
Does Breast Cancer Subtype Impact Margin Status in Patients Undergoing Partial Mastectomy?
Authors: Horattas Ileana , Fenton Andrew , Gabra Joseph , Mendiola Amanda , Li Fangyong , Namm Jukes , Solomon Naveenraj , Gass Jennifer , Lum Sharon , Murray Mary , Howard-McNatt Melissa , Dupont Elisabeth , Levine Edward , Brown Eric , Ollila David , Chiba Akiko , Chagpar Anees B. 
Published: January 2022

Background Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Methods Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Results Molecular subtype was significantly correlated with race ( P = .011), palpability ( P = .007), and grade ( P < .001). Subtype did not correlate with Hispanic ethnicity ( P = .760) or lymphovascular invasion ( P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Discussion Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.