bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B048: Next Generation Binding: Measuring Cell Avidity to Fully Characterize Cell-Cell Interactions and Understand Mechanism of Action for Cellular Therapies
Authors: Hoang Song-My 
Published: October 2024

Abstract
While conventional assays such as affinity, cytokine secretion, and cytotoxicity provide valuable data at a molecular level, this information is insufficient to fully characterize and select the best cellular therapies. There is still a lack of understanding about cell-cell interactions that drive functional processes. Cell Avidity, the collective strength of interactions between an effector and its target, can help elucidate the mechanism of action for therapeutic candidates. Our highly flexible Cell Avidity platform, the z-Movi Cell Avidity Analyzer, combines fluorescence microscopy with acoustic force to distinguish cell binding in a physiological context. This provides a comprehensive view of cell binding characteristics to interrogate potency, safety, sensitivity, and binding kinetics. Cell avidity has been used to: 1) Engineer CAR-T cells secreting a T-cell engaging molecule to overcome a challenging tumor microenvironment in pancreatic adenocarcinoma. 2) Reveal critical neutrophil-tumor cell interactions in the tumor microenvironment. 3) Identify essential proteins involved in B-cell lymphoma binding to stromal cells in the tumor microenvironment. 4) Fine-tune the affinity/cell avidity of CAR-T cells to mitigate on-target off-tumor toxicity in renal cell carcinoma. 5) Format-tune in vivo-launched bispecific T cell engagers to enhance efficacy against renal cell carcinoma. 6) Characterize the mechanism of action to assess the function and efficacy of NK-cell cytotoxicity. Cell Avidity is an emerging biomarker that directly quantifies the strength of the physical interactions between target and effector cells. We developed a Cell Avidity platform that enables characterization and screening of molecular binders and cellular products, including antibodies, small molecules, and cell therapies.
Citation Format: Song-My Hoang. Next Generation Binding: Measuring Cell Avidity to Fully Characterize Cell-Cell Interactions and Understand Mechanism of Action for Cellular Therapies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B048.
Abstract PR-04: A TROP2/Claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer
Authors: Wu Bogang , Thant Win , Bitman Elena , Liu Ting , Liu Jie , Paschalis Eleftherios I. , Xu Katherine H. , Nieman Linda T. , Ting David T. , Thimmiah Nayana , Sun Sheng , Abelman Rachel O. , Isakoff Steven J. , Spring Laura M. , Bardia Aditya , Ellisen Leif W. 
Published: October 2024

Abstract
Background: Antibody Drug Conjugates (ADCs) targeting Trophoblast Cell-Surface Antigen 2 (TROP2) are emerging as paradigm-changing drugs, but the therapeutically relevant mechanisms of TROP2 itself remain unknown. The goal of this project is to investigate the role of TROP2 in promoting breast cancer aggressiveness and provide insights into the mechanisms of action of TROP2-targeted ADCs. Methods: TROP2 loss-of-function studies were performed in multiple syngeneic mouse mammary tumor models. Truncated TROP2 mutants were reconstituted into CRISPR knockout cells to map essential domains that enable TROP2 tumor-promoting activity. Flow cytometry for tumor infiltrating lymphocytes, tissue histology and immunofluorescence were used to assess tumor microenvironment. Data from immune checkpoint-treated patients were used to test hypotheses from the preclinical findings. Results: We find that TROP2 mediates a mechanism of immune exclusion in Triple-Negative Breast Cancer (TNBC) through association with the essential tight junction protein Claudin 7. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC. Loss-of-function and reconstitution experiments demonstrate TROP2 is sufficient to drive tumor progression in vivo in a CD8 T cell-dependent manner, while its loss deregulates expression and localization of multiple claudins, enabling T cell infiltration. Employing a humanized TROP2 syngeneic TNBC model, we show that TROP2 targeting via Sacituzumab govitecan (SG) induces an anti-PD1 response associated with broad immune cell activation, and TROP2 is highly associated with lack of response to anti-PD1 therapy in human breast cancer. Conclusions: TROP2 mediates immune exclusion and may be targeted to enhance immunotherapy response.
Citation Format: Bogang Wu, Win Thant, Elena Bitman, Ting Liu, Jie Liu, Eleftherios I. Paschalis, Katherine H. Xu, Linda T. Nieman, David T. Ting, Nayana Thimmiah, Sheng Sun, Rachel O. Abelman, Steven J. Isakoff, Laura M. Spring, Aditya Bardia, Leif W. Ellisen. A TROP2/Claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr PR-04.
Abstract PR-05: Nous-209 off-the-shelf vaccine targets neoantigens mutations well represented both in primary and metachronous incident CRCs from Lynch syndrome patients
Authors: De Marco Lorenzo , Micarelli Elisa , Panula Joni , D'Alise Anna Morena , Leoni Guido , Hokkanen Kalle E. , Hämäläinen Eija , Mecklin Jukka-Pekka , Scarselli Elisa , Seppälä Toni 
Published: October 2024

Abstract
Lynch Syndrome (LS) is the most common hereditary cancer syndrome, caused by germline mutations in one of the four DNA mismatch repair (MMR) genes. LS patients have a high risk to develop microsatellite instable (MSI) colorectal cancers. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are very common and shared among different tumors. When indels occur in coding genes they give rise to frameshift peptides (FSPs) with a very high potential to act as safe and potent neoantigens for a vaccine. NOUS-209 is a genetic vaccine encoding 209 neoantigens, shared across sporadic and hereditary MSI tumors, developed for interception and treatment of MSI tumors. Phase 1b trial evaluating NOUS-209 monotherapy in healthy LS carriers showed the induction of a potent and broad immune response. Here, we characterize indels encoding FSPs in a cohort of 50 incident MSI CRC from LS patients detected during routine screening (38 primary tumors; 22 metachronous tumors) by whole Exomeseq NGS. Overall, primary and metachronous tumors have a similar number of indels in coding genes. The repertoire of detected indels is only partially shared (27%) between the two categories of tumors. The 209 indels selected for the NOUS-209 vaccine are instead highly shared (95%) between primary and metachronous tumors. Moreover, the analysis of 8 patients for which both the primary and the metachronous tumor were available confirmed the presence of the 209 mutations both in the first and the second tumor. Therefore, the NOUS 209 vaccine has the potential to prevent tumor occurrence both in previvors and survivors by inducing a broad T cell immune response against recurrent FSP.
Citation Format: Lorenzo De Marco, Elisa Micarelli, Joni Panula, Anna Morena D'Alise, Guido Leoni, Kalle E. Hokkanen, Eija Hämäläinen, Jukka-Pekka Mecklin, Elisa Scarselli, Toni Seppälä. Nous-209 off-the-shelf vaccine targets neoantigens mutations well represented both in primary and metachronous incident CRCs from Lynch syndrome patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr PR-05.
Cost-Effectiveness of a Shock Team Approach in Refractory Cardiogenic Shock
Authors: Taleb Iosif , Giannouchos Theodoros V. , Kyriakopoulos Christos P. , Clawson Antoine , Davis Erin S. , Sideris Konstantinos , Tseliou Eleni , Shah Kevin S. , Tonna Joseph E. , Dranow Elizabeth , Jones Tara L. , Carter Spencer J. , Fang James C. , Stehlik Josef , Ohsfeldt Robert L. , Selzman Craig H. , Hanff Thomas C. , Drakos Stavros G. 
Published: October 2024

BACKGROUND:
Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study’s objective was to compare costs between patients treated with and without a Shock Team and determine if the team’s implementation is cost-effective compared with standard of care.

METHODS:
We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations.

RESULTS:

The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18–92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%;
P
=0.04 and 55.0% versus 40.5%;
P
=0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations.

CONCLUSIONS:
The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.
Three-Year Outcomes Following TAVR in Younger (<75 Years) Low-Surgical-Risk Severe Aortic Stenosis Patients
Authors: Modine Thomas , Tchétché Didier , Van Mieghem Nicolas M. , Deeb G. Michael , Chetcuti Stanley J. , Yakubov Steven J. , Sorajja Paul , Gada Hemal , Mumtaz Mubashir , Ramlawi Basel , Bajwa Tanvir , Crouch John , Teirstein Paul S. , Kleiman Neal S. , Iskander Ayman , Bagur Rodrigo , Chu Michael W.A. , Berthoumieu Pierre , Sudre Arnaud , Adrichem Rik , Ito Saki , Huang Jian , Popma Jeffrey J. , Forrest John K. , Reardon Michael J. 
Published: October 2024

BACKGROUND:
Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients aged <75 years receiving TAVR versus surgery.

METHODS:
The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged <75 years.

RESULTS:

In patients <75 years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum 74); Society of Thoracic Surgeons Predicted Risk of Mortality was 1.7±0.6%. At 3 years, all-cause mortality or disabling stroke for TAVR was 5.7% and 8.0% for surgery (
P
=0.241). Although there was no difference between TAVR and surgery in all-cause mortality, the incidence of disabling stroke was lower with TAVR (0.6%) than surgery (2.9%;
P
=0.019), while surgery was associated with a lower incidence of pacemaker implantation (7.1%) compared with TAVR (21.0%;
P
<0.001). Valve reintervention rates (TAVR 1.5%, surgery 1.5%,
P
=0.962) were low in both groups. Valve performance was significantly better with TAVR than surgery with lower mean aortic gradients (
P
<0.001) and lower rates of severe prosthesis-patient mismatch (
P
<0.001). Rates of valve thrombosis and endocarditis were similar between groups. There were no significant differences in rates of residual ≥moderate paravalvular regurgitation.

CONCLUSIONS:
Low-risk patients <75 years treated with supra-annular, self-expanding TAVR had comparable 3-year all-cause mortality and lower disabling stroke compared with patients treated with surgery. There was significantly better valve performance in patients treated with TAVR.

REGISTRATION:

URL:
https://clinicaltrials.gov
; Unique identifier: NCT02701283.
Is “Application” Everything about Studying for a University Degree? The Multiple Influences Shaping Undergraduates in Chinese Higher Education in Contemporary Times
Authors: ZHUANG Tengteng , XU Xiaoxuan 
Published: October 2024

Abstract
Based on the self-reflection of 22 undergraduate students at a renowned Chinese university regarding their journey towards obtaining a bachelor’s degree, this study reveals the discrepancy between the idealistic functions and missions of higher education as perceived by students and their actual implementations in the real world. It further explores the multifaceted logics exerted by the higher education environment on students during their educational journey. Data analysis shows that contemporary global neoliberalism, alongside traditional Chinese cultural ideologies such as Confucianism and Daoism, significantly impacts the educational philosophies of university students to varying extents. These diverse ideologies drive students to demonstrate varied learning states and behaviors, showcasing the complex interplay of global and local forces in shaping student experiences in higher education.
Caretaker of a collection
Authors: Koops Bert-Jaap 
Published: October 2024

Abstract
When re-assessing women’s roles in the art world, we should not neglect traditional, perhaps stereotypical, functions. Jo van Bilderbeek-Lamaison (1849–1951) exemplifies the importance of caretaking: after her husband’s death in 1918, she played a crucial role in caring for their art collection and bequeathing it to the state. She lived in a Dordrecht house museum (the Rijksmuseum Van Bilderbeek-Lamaison, not publicly accessible), carefully exercising her responsibility ‘in her husband’s spirit’ in house maintenance, loans of artworks, and art preservation – a challenge given the fuel crisis in the 1930s and 1940s.
This case study sheds light on women’s role in the art world around 1900 from the perspective of separate public/private spheres and the associated distinction between productive labour and reproductive/caring labour. The case suggests that caring labour is not be limited to care for people, but can include care for objects, such as an art collection in a house museum.
Quantitative Identification of Moisture Sources over the Tibetan Plateau: Spatial Distributions and Temporal Variabilities
Authors: Guo Xiaoyu , Wang Lei , Tian Lide , Zhang Lin , Zhao Wanglin 
Published: October 2024

Abstract
The imbalanced hydrological cycles and water resource instability over the Tibetan Plateau (TP) are a topic of wide concern. Moisture sources affected by large-scale circulations are the main controls of precipitation and water resource distributions; as such, the quantitative identification of moisture sources is the key to the changes in precipitation or water-related environments, further aids efficient water management over the TP and in downstream regions of Asia. In this study, we primarily identified the spatial distributions and temporal variabilities of TP’s varied moisture sources, using HYSPLIT modeling and spatially dense precipitation isotopes (δ18O). Results showed that 1) moistures from the westerlies (West), the western arm of Indian summer monsoon (ISM) (ISM1), the eastern arm of ISM (ISM2), and the inner TP are the TP’s main moisture sources, with highest proportional contributions being >70%, ∼40%, >80%, and ∼10%–20% at northwest, southwest, and southeast sectors of the study area and the central TP region; 2) each moisture has its own region where it predominates and shows specific trends during 1951–2020 (West-northwest sector-increase, ISM1-southwest sector-increase, ISM2-southeast sector-decrease, and TP-central TP region-increase); 3) each of the moisture proportions and their temporal trends varied with different days of back trajectories (days 02–04–06–08–10), while their spatial patterns are similar; and 4) when verifying the modeled moisture proportions, precipitation δ18O is positively correlated or covaries with dry sources such as the West or TP moisture and inversely for humid ISM (ISM1 or ISM2) moisture. This work will improve our understanding of moisture-related hydrological, meteorological, and ecological studies in the “Asian Water Tower” region.

Significance Statement
The Tibetan Plateau (TP) is undergoing imbalanced hydrological cycles and water resource instability in response to global climate change. As the TP supplies vast quantities of water to Asia’s huge population, the socioeconomic impact caused by these changes is considerable. This study aims to quantitatively identify the spatial distributions and temporal variabilities of varied moisture sources over the TP in recent decades, using high-resolution modeling and ground-based precipitation isotopes. Results show that each moisture has its own region where it predominates and shows specific trends during 1951–2020. These findings can help to explain precipitation patterns or water resource distributions and provide insights into efficient water management over the TP and in downstream regions of Asia.
Domestic violence and depression among Chinese adolescents: The role of self-evaluation
Authors: Fu Wangqian , Zhang Shiqi , Zhu Yuehua , Liu Ruidong 
Published: October 2024

Background: Depression of adolescents seriously affects their mental health as well as the formation and development of sound personality. According to Family Systems Theory, individuals’ mental health is closely related with external (e.g. domestic violence) and internal factor (e.g. self-evaluation). The formation mechanism of depression needs deep investigation in order to provide better educational intervention for students and promote their healthy development. Aim: The study examined the relationship among domestic violence, depression, and self-evaluation. Methods: The data were collected from 1,011 Chinese adolescents ( Mage = 12.04 ± 1.71) by the questionnaire of Family Violence Scale, Depression Questionnaire, and Rosenberg Self Esteem Scale. Results: We found domestic violence and depression were significantly positively correlated ( r = .25, p < .001); self-evaluation was significantly negatively correlated with domestic violence ( r = −.26, p < .001) and depression ( r = −.50, p < .001). Moreover, domestic violence could directly and positively predict depressed psychology, and could also indirectly predict depressed psychology through the mediating effect of self-evaluation. Conclusion: The level of depression of adolescents was closely related with domestic violence and self-evaluation. And self-evaluation played a mediating role between domestic violence and self-evaluation.
Network analysis of correlations between suicide exposure, depression, and anxiety symptoms in adolescents
Authors: He Tianyu , Zou Huijing , Hou Hao , Yu Yijing , Wang Fan , Tian Chunfeng , Luo Dan , Zhou Yang , Zhao Jun , Yang Bing Xiang 
Published: October 2024

Background: Adolescents with a history of suicide exposure, defined as experiencing the suicide death of a family member, friend, or other acquaintances, are more likely to experience mental health issues such as depression or anxiety. Aims: This study aimed to explore prevalence rates and the network of adolescents’ suicide exposure, depression, and anxiety symptoms, and to clarify the correlations between suicide exposure and symptoms of depression and anxiety. Method: A total of 8,957 adolescents were included in this cross-sectional study. Data regarding general information, symptoms of depression and anxiety, and suicide exposure were collected from mid-September to early October 2021. Network analysis was employed to assess relationships between suicide exposure and individual symptoms of both depression and anxiety. Central symptoms were identified by strength; the flow network was visualized to identify symptoms directly related to suicide exposure. Results: The prevalence rates of suicide exposure, depression, and anxiety were 5.28%, 12.87%, and 10.48%. Results indicated that suicide exposure was associated with both depression and anxiety, and had the strongest positive association with suicidal ideation. Central symptoms of the network were sad mood, nervousness, fatigue, irritability, and uncontrollable worry. Bridge symptoms were suicidal ideation and irritability. Appetite changes, suicidal ideation, uncontrollable worry, sleep difficulties, and irritability were symptoms directly related to suicide exposure. Conclusions: There were significant inter-symptom associations between suicide exposure, depression, and anxiety in adolescents. It is recommended that future studies explore whether targeted interventions and long-term monitoring concerning these inter-symptom associations can protect adolescents with suicide exposure.
Asylum-seeker women: Coping strategies and mental wellbeing
Authors: Shishehgar Sara , Gholizadeh Leila , DiGiacomo Michelle , Davidson Patricia Mary 
Published: October 2024

Background: Asylum seekers in Australia are subjected to various punitive measures that can affect their psychological wellbeing. The capacity of asylum seekers to adapt and cultivate effective coping strategies can enhance their resilience, facilitate their settlement processes and promote their overall mental health. Aim: This study aims to explore the coping strategies employed by women who are asylum-seekersthat have the potential to enhance their resilience post migration. Method: A semi-structured qualitative study was conducted with asylum-seeker women from Iran. Data were analysed using an inductive thematic analysis. Results: Seventeen participants described their experiences of applying various strategies to enhance their coping ability, resilience and maintain their mental wellbeing when facing ongoing challenges. Problem-solving strategies included social engagement, adjusting life plans and seeking support from formal and informal resources. Emotion-focussed strategies were positive thinking and maintaining hope, avoidance and spirituality. While emotion-focussed strategies enabled the women to manage their stresses temporarily, problem-solving strategies allowed them to effectively address the challenges they faced after migration. Conclusion: Providing supportive resources for asylum seekers, removing stigma and developing community ties may assist individuals in improving their coping skills, resilience and mental wellbeing.