bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C029: PM2.5-induced drug resistance in lung cancer
Authors: Chen Chi-Yuan , Chan Chieh-Wen , Wang Tong-Hong 
Published: November 2024

Abstract
Long-term exposure to PM2.5 air pollution is a significant contributor to lung cancer incidence. Our previous studies have shown that such exposure promotes lung cancer progression by activating the EGFR (epidermal growth factor receptor) and AhR (aryl hydrocarbon Receptor) pathways. We observed that in lung cancer cells with EGFR mutations, prolonged PM2.5 exposure induces EGFR activation, resulting in accelerated tumor cell growth both in vitro and in vivo. This suggests that PM2.5 may play a role in the resistance to EGFR-TKI (tyrosine kinase inhibitor) therapies, raising concerns about treatment efficacy. To explore this, we exposed the EGFR-mutant lung cancer cell line to PM2.5 for 90 days. Our results revealed that long-term exposure not only reduced the therapeutic effect of EGFR-TKIs but also increased the expression of cMyc, a gene linked to poor prognosis and drug resistance. We further confirmed that PM2.5-induced EGFR-TKI resistance is driven by the AhR-cMyc pathway. AhR, activated by environmental toxins in PM2.5, increases cMyc expression, leading to drug resistance. When we administered cMyc inhibitors, the PM2.5-exposed cells regained sensitivity to EGFR-TKI therapy. These findings indicate that targeting the AhR-cMyc pathway could be a promising approach to overcome PM2.5-induced resistance in lung cancer treatment. Further research is needed to explore the broader implications of environmental pollution on cancer therapy and to develop strategies to counteract the effects of pollutants like PM2.5.
Citation Format: Chi-Yuan Chen, Chieh-Wen Chan, Tong-Hong Wang. PM2.5-induced drug resistance in lung cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C029.
Abstract C040: Spatial transcriptomics unveils disparities in tumor microenvironment dynamics between breast cancer responders and non-responders
Authors: Mo Jeremy , Zhang Hanyun , Harvey Kate , Swarbrick Alexander 
Published: November 2024

Abstract
Spatial transcriptomics is revolutionizing our understanding of cellular dynamics and interactions in the tumor microenvironment (TME). By mapping distinct cellular populations and their interactions, we can gain valuable insights into tumor behavior. To investigate these dynamics in breast cancer, we conducted Xenium In-situ spatial transcriptomics on twenty formalin-fixed paraffin-embedded (FFPE) samples taken from eight patients undergoing neoadjuvant chemotherapy. These samples have been taken pre-treatment, mid-treatment and post-treatment from four cases with pathological complete response (pCR), and four cases with residual disease (RD) at time of surgery. Our analyses have found distinct cellular composition changes between pCR and RD cases. Patients with RD demonstrated an increase in endothelial, perivascular-like (PVL) and epithelial cells from pre- to post-treatment. This was accompanied by a decrease in myeloid and malignant epithelial cells at mid-treatment. In contrast, patients with pCR demonstrated increases in cancer-associated fibroblasts (CAFs) and myeloid cells, with reductions in plasmablasts and cancer epithelial cells at mid-treatment. This suggests that an increase in CAF and myeloid cells observed between pre-treatment and mid-treatment samples may be predictive of response. We performed ligand-receptor (LR) analyses, which demonstrated diverse myeloid interactions in RD cases and diverse CAF interactions in pCR cases in pre-treatment samples. Mid-treatment samples exhibited a decrease in interactions for CAFs, myeloid and T cells in pCR and RD cases. The most frequently identified CAF LR interactions, as senders, were between TGFB1/TGFB3 and TGFBR1/TGFBR2, while the most frequently identified myeloid LR interactions were between PDCD1LG2 - PDCD1 (encoding PDL2 & PD1), CCL8 - ACKR1 (encoding Atypical Chemokine Receptor 1) and CCL2 - ACKR1. Our findings indicate that the dynamic changes in cellular composition and interactions within the TME differs between responders and non-responders. To further explore these differences, we plan to perform spatially constrained analyses to identify unique cellular niches that may serve as potential biomarkers for informing novel therapeutic strategies.
Citation Format: Jeremy Mo, Hanyun Zhang, Kate Harvey, Alexander Swarbrick. Spatial transcriptomics unveils disparities in tumor microenvironment dynamics between breast cancer responders and non-responders [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C040.
Abstract IA007: Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs
Authors: Chia Shi B. , Johnson Bryan J. , Hu Junxiao , Vermeulen Roel , Chadeau-Hyam Marc , Guntoro Fernando , Montgomery Hugh , Boorgula Meher , Sreekanth Varsha , Goodspeed Andrew , Davenport Bennett , Valenca-Pereira Felipe , Zaberezhnyy Vadym , Schleicher Wolfgang E , Gao Dexiang , Cadar Andreia N. , Papanicolaou Michael , Beheshti Afshin , Baylin Stephen B. , Costello James , Bartley Jenna M. , Morrison Thomas E. , Aguirre-Ghiso Julio A. , Rincon Mercedes , DeGregori James 
Published: November 2024

Abstract
Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis.
Citation Format: Shi B. Chia, Bryan J. Johnson, Junxiao Hu, Roel Vermeulen, Marc Chadeau-Hyam, Fernando Guntoro, Hugh Montgomery, Meher Boorgula, Varsha Sreekanth, Andrew Goodspeed, Bennett Davenport, Felipe Valenca-Pereira, Vadym Zaberezhnyy, Wolfgang E Schleicher, Dexiang Gao, Andreia N. Cadar, Michael Papanicolaou, Afshin Beheshti, Stephen B. Baylin, James Costello, Jenna M. Bartley, Thomas E. Morrison, Julio A. Aguirre-Ghiso, Mercedes Rincon, James DeGregori. Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA007.
Abstract PR006: Arginine dependent immuno-metabolic reprogramming by metabolic enzyme PFKFB4 underpins breast tumor immune tolerance
Authors: Dai Tao , Dimeck Alphonse N. , Wang Hai , Liu Song , Abrams Scott I. , Dasgupta Subhamoy 
Published: November 2024

Abstract
Competition for nutrients in the tumor microenvironment (TME) can deprive cytotoxic T lymphocytes essential metabolites required for infiltration and activation. However, the underlying mechanisms by which tumor intrinsic oncogenic pathways control extracellular nutrient abundance to impart immunosuppressive TME is not well understood. Here, we show that oncogenic metabolic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) constraints arginine availability in the TME, thereby suppressing CD8+ T cell cytotoxic functions allowing triple negative breast cancer (TNBC) immune evasion. Genetic ablation of PFKFB4 in breast tumor implantation mouse models resulted in tumor regression and effectively cleared residual tumors. Metabolic profiling of tumor interstitial fluid (TIF) demonstrated that increased arginine availability enhanced CD8+ T cell effector function in PFKFB4-depleted tumors. PFKFB4 is a bifunctional metabolic enzyme with a functional kinase and a phosphatase domain. Our mechanistic studies revealed that PFKFB4 functions as a protein kinase that phosphorylates and activates transcriptional coregulator NCOA3, which then induces NF-kB-dependent transcriptional activation of lipocalin-2, a siderophore-binding protein functioning as a cytokine. ELISA confirmed that increased secretion of lipocalin-2 by PFKFB4 reprogrammed the tumor-associated macrophages (TAMs) towards a pro-tumorigenic phenotype. This phenotypic switch triggered arginine catabolism, due to rapid induction of arginase 1 (ARG1)-positive macrophages, that metabolically out competed CD8+ T cells impeding their proliferation. Phenocycler-based immunostaining of human breast tissue microarray revealed that breast tumors with increased levels of PFKFB4 had reduced infiltrating CD8+ T cells associated with poor clinical outcome, underscoring our findings that immuno- metabolic crosstalk regulated by PFKFB4 is a critical mediator of immune evasion in TNBC.
Citation Format: Tao Dai, Alphonse N. Dimeck, Hai Wang, Song Liu, Scott I. Abrams, Subhamoy Dasgupta. Arginine dependent immuno-metabolic reprogramming by metabolic enzyme PFKFB4 underpins breast tumor immune tolerance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR006.
Chapter 4: Politics of the Memory of Deportation and Interethnic Relations in Post-2014 Crimea
Authors: Muratova Elmira 
Published: November 2024

Abstract
This article analyses the Crimean Tatars’ politics of the memory of deportation in post-Soviet Crimea, and focuses on the changes in these politics since Russia’s annexation of Crimea in 2014. This article is organized as follows. First, I outline the main memory-related practices associated with deportation, following the mass repatriation of Crimean Tatars in the early 1990s. Second, I describe the changes that have occurred in the politics of the memory of deportation since the 2014 annexation of Crimea. Third, I use interviews and social media analysis to show how these changes were perceived by the Crimean Tatars. Finally, based on expert interviews, I discuss how these changes affected interethnic relations in Crimea. I argue that Russia’s policy regarding the Crimean Tatars’ memory of the deportation in annexed Crimea is intended to depoliticize and regulate it according to official narratives about the Soviet past, and has the potential to exacerbate interethnic relations.
Chapter 5: Consequences of War-Induced Displacement and the Shifting Cartography of Belonging of Ukraine’s Ahiska (Meskhetian) Turks, Crimean Tatars, and Roma since 2014
Authors: Sereda Viktoriya , Homanyuk Mykola 
Published: November 2024

Abstract
This article focuses on consequences of Russian aggression and war-induced displacement on minority groups that are often overlooked by both Ukrainian minority studies within Ukraine as well as by international migration research: the Ahiska (Meskhetian) Turks, Crimean Tatars, and Roma. Due to their location in the south and east of the country, all three were strongly affected by Russian aggression in 2014, and especially after the full-scale invasion which began on 24 February 2022. Most research on displaced Ukrainian nationals focuses on the West-East (European Union (EU)-Russia) nexus and ignores the South. This article compares the experience of displacement of the three groups, in relation to 1) migration to Türkiye (for Ahiska Turks and Crimean Tatars) and 2) resettlement to other countries and internal displacement (for the Roma). It focuses on the (trans)national experience of displacement for minorities, as well as how this displacement and the response of receiving countries affects their sense of belonging. The study is based on a mixed-method approach combining desk research and qualitative in-depth interviews conducted with representatives of each community between 2014 and 2023, both in Ukraine and in their destination countries.
Chapter 6: The Impact (or Not) of the War in Ukraine on Russian Minorities and Minorities Policy
Authors: Bowring Bill 
Published: November 2024

Abstract
In this article I show how the Russian Federation (Russia) seeks to sustain an impression of business as usual in its minorities policy and administration, while normalising as far as possible the results of its illegal annexation of Crimea in 2014, and its full-scale invasion of Ukraine on 24 February 2022. I start with the controversial All-Russian Census, 2020–2021, conducted from October to December 2021, and the disputes concerning its results. Second, I turn to the Fifth Report submitted by Russia to the Advisory Committee on the Framework Convention for the Protection of National Minorities (FCNM) on 13 April 2021. Third, I pay close attention to the activities of the Federal Agency for Affairs of Nationalities (ethnic minorities), FADN, and its Director Igor Barinov, which have continued their programme of work. Fourth, Putin’s war on Ukraine has impacted directly on Russia’s ethnic minorities, which have supplied the great majority of young soldiers.
Chapter 13: Educational Reform in Estonia and Latvia
Authors: Pettai Vello 
Published: November 2024

Abstract
Russia’s war in Ukraine has put renewed pressure on the Russian-speaking minorities of Estonia and Latvia. A particularly delicate realm in which this stress is playing out is Russian-language education. The authorities in both countries have made a decision in 2022 to phase out Russian-language education at all levels, meaning that these schools will gradually be transferred to the national language within three to six years. This article reviews the history of minority educational reform in Estonia and Latvia, and it outlines the details of the current transition. It assesses these changes both politically and in the light of international legal norms, finding that the reforms represent a clear shift in the paradigm of ‘minority integration’ toward greater nation-state preponderance.
Atmosphere–Ocean–Sea Ice Feedbacks Sustain Recent Barents Sea Ice Loss despite Cooler Atlantic Water Inflow
Authors: Chatterjee Sourav , Semmler Tido , Screen James , Furevik Tore , Selivanova Julia , Raj Roshin P. , Murukesh Nuncio , Ravichandran M. 
Published: November 2024

Abstract
Winter sea ice cover has declined faster in the northern Barents Sea (NBS) than in the rest of the Arctic Ocean. One of the key elements controlling sea ice extent in the NBS is the inflow of warm and saline Atlantic water (AW) through the Barents Sea Opening. We show that despite a pronounced decadal variability in the AW temperature with a cooling trend since the mid-2000s, sea ice in the NBS continues to decline. We find that the sea ice decline is partly caused by reduced oceanic heat loss in the southern Barents Sea (SBS) and subsequent transport of warmer AW downstream to the NBS. Moreover, reduced heat loss contributes to increased sea surface height (SSH) in the SBS and sets up a meridional SSH gradient between SBS and NBS. This reduces the inflow of colder Arctic waters from the eastern Barents Sea, which contributes to further warming in the NBS. Results from idealized coupled climate model experiments with reduced Arctic sea ice suggest that these observed features can be driven by sea ice loss. Thus, despite the AW cooling trend, positive feedback from sea ice loss in the NBS, which involves reduced oceanic heat loss in the SBS and less inflow of cold Arctic waters, favors a continuous decline of sea ice in the NBS.

Significance Statement
Barents Sea region of the Arctic, with the largest changes in terms of atmospheric warming and sea ice loss, is of crucial importance not only for the Arctic region but also has potential implications for weather and climate in midlatitudes and the tropics. Here, in this study, we employ comprehensive approach with observational datasets and climate model experiments to identify recent on-going changes in Barents Sea climate and highlight the importance of sea ice loss in it.
Unclear Trajectory and Uncertain Benefit: Creating a Lexicon for Clinical Uncertainty in Patients with Critical or Advanced Illness Using a Delphi Consensus Process
Authors: McGowan Samuel K. , Corrales-Martinez Maria-Jose , Brender Teva , Smith Alexander K. , Kim Shannen , Harrison Krista L. , Mills Hunter , Lee Albert , Bamman David , Cobert Julien 
Published: November 2024

Background Clinical uncertainty is associated with increased resource utilization, worsened health-related quality of life for patients, and provider burnout, particularly during critical illness. Existing data are limited, because determining uncertainty from notes typically requires manual, qualitative review. We sought to develop a consensus list of descriptors of clinical uncertainty and then, using a thematic analysis approach, describe how respondents consider their use in intensive care unit (ICU) notes, such that future work can extract uncertainty data at scale. Design We conducted a Delphi consensus study with physicians across multiple institutions nationally who care for critically ill patients or patients with advanced illnesses. Participants were given a definition for clinical uncertainty and collaborated through multiple rounds to determine which words represent uncertainty in clinician notes. We also administered surveys that included open-ended questions to participants about clinical uncertainty. Following derivation of a consensus list, we analyzed participant responses using thematic analysis to understand the role of uncertainty in clinical documentation. Results Nineteen physicians participated in at least 2 of the Delphi rounds. Consensus was achieved for 44 words or phrases over 5 rounds of the Delphi process. Clinicians described comfort with using uncertainty terms and used them in a variety of ways: documenting and processing the diagnostic thinking process, enlisting help, identifying incomplete information, and practicing transparency to reflect uncertainty that was present. Conclusions Using a consensus process, we created an uncertainty lexicon that can be used for uncertainty data extraction from the medical record. We demonstrate that physicians, particularly in the ICU, are comfortable with uncertainty and document uncertainty terms frequently to convey the complexity and ambiguity that is pervasive in critical illness. Highlights Question: What words do physicians caring for critically ill patients use to document clinical uncertainty, and why? Findings: A consensus list of 44 words or phrases was identified by a group of experts. Physicians expressed comfort with using these words in the electronic health record. Meaning: Physicians are comfortable with uncertainty words and document them frequently to convey the complexity and ambiguity that is pervasive in critical illness.
Evolving dementia care: An explorative study on the lived experience of older adults living with dementia in nursing homes using observational and biometric sensor data
Authors: Hammink JHW (Coosje) , van Buuren LPG (Leonie) , Moor JA (Nienke) , Derks DAJA (Daantje) , Mohammadi M (Masi) 
Published: November 2024

Introduction This study explores the lived experiences of older adults with dementia in Dutch nursing homes, focusing on daily activities and emotional responses. With a growing number of older adults with dementia, gaining a deeper understanding of their lived experience is imperative. Methods Using a mixed-method narrative approach involving observations, informal interviews, and physiological monitoring through wearable sensors, the study engaged eight participants in psychogeriatric wards across two Dutch nursing homes. Observations and interviews aimed to provide context to daily activities, while wearable sensors tracked emotional responses through heart rate (HR) and heart rate variability (HRV). Results Key activities included eating, drinking, communication, mobility, and inactivity. Positive experiences were consistently observed during eating and drinking and communication, respectively influenced by the nursing home’s social and organizational structures and social and personal contexts. In contrast, mobility and inactivity exhibited diverse physiological responses, reflecting a range of stress, concentration, or relaxation. Conclusion & Discussion This study offers valuable insights into the lived experiences of older adults with dementia in nursing homes. It highlights the generally positive nature of eating and drinking, shaped by social and organizational factors. Communication’s impact varies with individual context. The study also reveals a complex interplay of emotions during activities related to mobility and inactivity, as evidenced by diverse physiological responses. Regarding implications for dementia care, the study emphasizes the need to redefine ‘inactivity’ as ‘under-stimulation,’ assess appropriate (in)activity levels, and acknowledge the significance of the nursing home’s physical and organizational context. This redefinition should distinguish between ‘physical’ and ‘mental’ inactivity, address concerns related to under-stimulation, and cater to individual preferences. Recognizing the residents’ restricted environment and reliance on care professionals and volunteers underscores the urgency of tailored approaches. Addressing these implications can provide fresh perspectives for evolving dementia care, creating a more supportive environment that promotes well-being.