bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion
Authors: Yan Linlin , Wu Mingming , Wang Tianyu , Yuan Hui , Zhang Xiao , Zhang Huafeng , Li Tao , Pandey Vijay , Han Xinghua , Lobie Peter E. , Zhu Tao 
Published: February 2024

Abstract

Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate antitumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSC) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC–mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer.

Significance:
MIF secreted by breast cancer stem cells induces metabolic reprogramming in bulk tumor cells and engenders an immunosuppressive microenvironment, identifying MIF targeting as a strategy to improve immunotherapy efficacy in breast cancer.
ROR2/Wnt5a Signaling Regulates Directional Cell Migration and Early Tumor Cell Invasion in Ovarian Cancer
Authors: Grither Whitney R. , Baker Breanna , Morikis Vasilios A. , Ilagan Ma. Xenia G. , Fuh Katherine C. , Longmore Gregory D. 
Published: February 2024

Abstract

Adhesion to and clearance of the mesothelial monolayer are key early events in metastatic seeding of ovarian cancer. ROR2 is a receptor tyrosine kinase that interacts with Wnt5a ligand to activate noncanonical Wnt signaling and has been previously shown to be upregulated in ovarian cancer tissue. However, no prior study has evaluated the mechanistic role of ROR2 in ovarian cancer. Through a cellular high-throughput genetic screen, we independently identified ROR2 as a driver of ovarian tumor cell adhesion and invasion. ROR2 expression in ovarian tumor cells serves to drive directed cell migration preferentially toward areas of high Wnt5a ligand, such as the mesothelial lined omentum. In addition, ROR2 promotes ovarian tumor cell adhesion and clearance of a mesothelial monolayer. Depletion of ROR2, in tumor cells, reduces metastatic tumor burden in a syngeneic model of ovarian cancer. These findings support the role of ROR2 in ovarian tumor cells as a critical factor contributing to the early steps of metastasis. Therapeutic targeting of the ROR2/Wnt5a signaling axis could provide a means of improving treatment for patients with advanced ovarian cancer.

Implications:
This study demonstrates that ROR2 in ovarian cancer cells is important for directed migration to the metastatic niche and provides a potential signaling axis of interest for therapeutic targeting in ovarian cancer.
Estrogen Receptor Mutations as Novel Targets for Immunotherapy in Metastatic Estrogen Receptor–positive Breast Cancer
Authors: Goldberg Jonathan , Qiao Na , Guerriero Jennifer L. , Gross Brett , Meneksedag Yagiz , Lu Yoshimi F. , Philips Anne V. , Rahman Tasnim , Meric-Bernstam Funda , Roszik Jason , Chen Ken , Jeselsohn Rinath , Tolaney Sara M. , Peoples George E. , Alatrash Gheath , Mittendorf Elizabeth A. 
Published: February 2024

Abstract

Estrogen receptor–positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes with HLA-A*0201. We then validated the binding affinity and stability of the top predicted peptides through in vitro binding and dissociation assays and showed that these peptides bind HLA-A*0201 with high affinity and stability. Using tetramer assays, we confirmed the presence and expansion potential of antigen-specific CTLs from healthy female donors. Finally, using in vitro cytotoxicity assays, we showed the lysis of peptide-pulsed targets and breast cancer cells expressing common ESR1 mutations by expanded antigen-specific CTLs. Ultimately, we identified five peptides derived from the three most common ESR1 mutations (D538G, Y537S, and E380Q) and their associated wild-type peptides, which were the most immunogenic. Overall, these data confirm the immunogenicity of epitopes derived from ESR1 and highlight the potential of these peptides to be targeted by novel immunotherapy strategies.

Significance:
Estrogen receptor (ESR1) mutations have emerged as a key factor in endocrine therapy resistance. We identified and validated five novel, immunogenic ESR1-derived peptides that could be targeted through vaccine-based immunotherapy.
NRF2 Activation in Trp53;p16-deficient Mice Drives Oral Squamous Cell Carcinoma
Authors: Hamad Samera H. , Sellers Rani S. , Wamsley Nathan , Zolkind Paul , Schrank Travis P. , Major Michael B. , Weissman Bernard E. 
Published: February 2024

Abstract

Aberrant activation of the NRF2/NFE2L2 transcription factor commonly occurs in head and neck squamous cell carcinomas (HNSCC). Mouse model studies have shown that NRF2 activation alone does not result in cancer. When combined with classic oncogenes and at the right dose, NRF2 activation promotes tumor initiation and progression. Here we deleted the tumor suppressor genes p16INK4A and p53 (referred to as CP mice), which are commonly lost in human HNSCC, in the presence of a constitutively active NRF2E79Q mutant (CPN mice). NRF2E79Q expression in CPN mice resulted in squamous cell hyperplasia or dysplasia with hyperkeratosis in the esophagus, oropharynx, and forestomach. In addition, CPN mice displayed oral cavity squamous cell carcinoma (OSCC); CP mice bearing wild-type NRF2 expression did not develop oral cavity hyperplasia, dysplasia or OSCC. In both CP and CPN mice, we also observed predominantly abdominal sarcomas and carcinomas. Our data show that in the context of p53 and p16 tumor suppressor loss, NRF2 activation serves oncogenic functions to drive OSCC. CPN mice represent a new model for OSCC that closely reflects the genetics of human HNSCC.

Significance:
Human squamous cancers frequently show constitutive NRF2 activation, associated with poorer outcomes and resistance to multiple therapies. Here, we report the first activated NRF2-driven and human-relevant mouse model of squamous cell carcinoma that develops in the background of p16 and p53 loss. The availability of this model will lead to a clearer understanding of how NRF2 contributes to the initiation, progression, and therapeutic response of OSCC.
Response inhibition in premotor cortex corresponds to a complex reshuffle of the mesoscopic information network
Authors: Bardella Giampiero , Giuffrida Valentina , Giarrocco Franco , Brunamonti Emiliano , Pani Pierpaolo , Ferraina Stefano 
Published: February 2024

Abstract
Recent studies have explored functional and effective neural networks in animal models; however, the dynamics of information propagation among functional modules under cognitive control remain largely unknown. Here, we addressed the issue using transfer entropy and graph theory methods on mesoscopic neural activities recorded in the dorsal premotor cortex of rhesus monkeys. We focused our study on the decision time of a Stop-signal task, looking for patterns in the network configuration that could influence motor plan maturation when the Stop signal is provided. When comparing trials with successful inhibition to those with generated movement, the nodes of the network resulted organized into four clusters, hierarchically arranged, and distinctly involved in information transfer. Interestingly, the hierarchies and the strength of information transmission between clusters varied throughout the task, distinguishing between generated movements and canceled ones and corresponding to measurable levels of network complexity. Our results suggest a putative mechanism for motor inhibition in premotor cortex: a topological reshuffle of the information exchanged among ensembles of neurons.
The Transgression List in Šurpu Tablet IV and Its Sordid Moral Implications
Authors: Feder Yitzhaq 
Published: February 2024

Abstract
Modern scholarship has become more attentive to the interrelation between performative and scholastic factors in the production of ancient Near Eastern ritual texts. This article aims to shed light on the compositional processes responsible for the integration of a list of transgressions into Šurpu Tablet 4. This analysis is facilitated by the identification of a close parallel from the Namerimburruda tradition. The comparison of these texts illuminates the subtle manner by which scribe responsible for Šurpu IV appropriated earlier materials to fit the theological and rhetorical aims of the new composition. This focused case study can serve as a point of departure for further research on the flexible roles of interpolated sin lists in ancient Near Eastern literature.
Predictive Modelling in Underwater Archaeology. A Case Based on Mesolithic Coastal Settlements in Denmark
Authors: Giatsiatsou Paschalina 
Published: February 2024

Abstract
Research on underwater archaeological sites has been adversely affected by various socioeconomic (specialized equipment, lack of know-how, legal framework, etc.) and environmental (weather conditions, site formation processes, etc.) challenges. Interdisciplinary approaches, especially technology integration, can help introduce a methodology to evaluate these factors and mitigate limitations to enhance the information retrieved and assist the interpretation process. One such approach may be predictive modelling while developing methodologies based on predictive models can be assets in research. The work presented in this article is based on this approach and assesses the use of predictive models based on six case studies. It is an effort to evaluate whether targeting sub-areas when excavating on limited time and budget can help clarify the interpretation of the information collected from these areas.
Apollo and Maria: Two 17th-Century Warships Found at Vaxholm, Sweden
Authors: Höglund Patrik , Hansson Jim 
Published: February 2024

Abstract
In October 2019, the wrecks of two warships were found in the inlet to Stockholm. According to historical sources, Vasa’s three so-called sister ships might have been sunk in the area to block off a strait. These large ships were launched in the years 1629–1634 and built by the same master shipbuilder who participated in the construction of Vasa. However, after further archaeological investigations, the two ships were identified as Apollo and Maria, two medium-sized warships launched in 1648. The wrecks shed light on a twenty-year period when ships of this type were prioritized because they were considered more practical and offered more value for money. The ships were heavily constructed and could carry heavy armament for their size. They could be at sea in difficult conditions and be used for a variety of purposes. Despite the fact that the investigations did not match initial hopes of finding Vasa’s sister ships, important results were achieved. In 2021, Äpplet, one of Vasa’s sister ships, was found in the vicinity of Apollo and Maria.
Of Welfare, Sacred Places, and “Rice Christians”: Freedom of Religion and Multiple Religious Belonging
Authors: Erlings Esther 
Published: February 2024

Abstract
When governments are structurally unable to provide social services, or when disaster strikes, relief organisations tend to step in. This is also the case in South and East Asia. Such organisations may be faith-based, leading to the emergence of what Asians colloquially call “rice Christians”: persons who (allegedly) convert to a religion in order to access services, or out of loyalty to the aid-supplying organisation. Such converts may continue to practice their traditional religions and beliefs. This raises the question whether rights to religion or belief are still available to “rice Christians” when governments, e.g., seek to redevelop a sacred site that formed part of their original belief system. The present article addresses that question, drawing upon the concept of multiple religious belonging (‘mrb’) and a 2017 decision of the African Court on Human and Peoples’ Rights in which the court accepted that individuals may adhere to multiple religions, especially where conversion happened within a missionary context and the now-claimed belief is Indigenous or traditional. It argues in favour of recognition of mrb within the context of freedom of religion, which would mean that also “rice Christians” can continue to rely on original belief systems to protect their practices and places.
Observed Energetic Adjustment of the Arctic and Antarctic in a Warming World
Authors: Prince Hamish D. , L’Ecuyer Tristan S. 
Published: February 2024

Abstract
Satellite observations reveal that decreasing surface albedo in both polar regions is increasing the absorption of solar radiation, but the disposition of this absorbed energy is fundamentally different. Fluxes of absorbed solar radiation, emitted thermal radiation, and net energy imbalances are assessed for both polar regions for the last 21 years in the Clouds and Earth’s Radiant Energy System record. Arctic absorbed solar radiation is increasing at 0.98 ± 0.69 W m−2 decade−1, consistent with the anticipated response to sea ice loss. However, Arctic thermal emission is responding at a similar rate of 0.94 ± 0.55 W m−2 decade−1. This is surprising since the radiative impact of ice loss would be expected to favor increasing solar absorption. We find however, that clouds substantially mask trends in Arctic solar absorption relative to clear sky while having only a modest impact on thermal emission trends. As a result, the Arctic net radiation imbalance has not changed over the period. Furthermore, variability of absorbed solar radiation explains two-thirds of the variability in annual thermal emission suggesting that Arctic thermal fluxes rapidly adjust to offset changes in solar absorption and re-establish equilibrium. Conversely, Antarctic thermal emission is not responding to the increasing (although not yet statistically significant) solar absorption of 0.59 ± 0.64 W m−2 decade−1 with less than a third of the annual thermal variability explained by accumulated solar absorption. The Arctic is undergoing rapid adjustment to increasing solar absorption resulting in no change to the net energy deficit, while increasing Antarctic solar absorption represents additional energy input into the Earth system.

Significance Statement
The polar regions of Earth are undergoing ice loss through ongoing global warming, reducing the ice cover and decreasing solar reflectivity, which would be expected to warm these regions. We use satellite observations to measure the trends in solar absorption and emitted thermal radiation over the Arctic and Antarctic for the last two decades. Arctic thermal emission is increasing at a compensating rate to solar absorption with a close relationship between these processes. Conversely, Antarctic thermal emission is not responding to solar absorption demonstrating that Antarctic surface temperatures are not significantly influenced by the region’s reflectivity. The Arctic is undergoing rapid adjustment to increasing solar absorption through warming, while increasing Antarctic solar absorption represents additional energy input into the Earth system.
Comparisons between Short- and Long-Lived Cross-Equatorial Flow Events over the Maritime Continent: Perspective from the Intraseasonal Oscillation
Authors: Zhao Xiaoxuan , Lu Riyu , Sun Jianqi , Xu Ke , Li Chaofan 
Published: February 2024

Abstract
The duration of cross-equatorial flow (CEF) events over the Maritime Continent (MC) varies greatly, from 3 days to more than 1 month. In this study, we classify CEF events into short- and long-lived ones using a threshold of 7 days, and conduct separate investigations on their statistical and evolution characteristics, as well as the associated physical processes from the perspective of two dominant modes of the intraseasonal oscillation. Results indicate that short-lived events, characterized by westward-propagation southerly anomalies, are largely dependent on the 10–25-day oscillation, while the contribution of the 30–60-day component is negligible. The associated enhanced convection is primarily confined to the western North Pacific (WNP) and moves northwestward, accompanied by an anomalous cyclone. In contrast, long-lived events show consistent changes among different CEF branches, characterized by southerly anomalies dominating the MC, which benefit from the favorable background of the 30–60-day oscillation. Associated convection anomalies show a dipole pattern, with enhanced convection over WNP and suppressed convection over the Indian Ocean. The enhanced WNP convection gradually migrates northward, inducing CEF anomalies via a continuous anomalous cyclone, while the suppressed convection can be found to slightly expand to the MC. Meanwhile, the 10–25-day oscillation shows similar magnitude and evolution with that in short-lived events, but is no longer crucial to the establishment of long-lived events.
Maximizing the Volume of Collocated Data from Two Coordinated Suborbital Platforms
Authors: Schlosser Joseph S. , Bennett Ryan , Cairns Brian , Chen Gao , Collister Brian L. , Hair Johnathan W. , Jones Michael , Shook Michael A. , Sorooshian Armin , Thornhill Kenneth L. , Ziemba Luke D. , Stamnes Snorre 
Published: February 2024

Abstract
Suborbital (e.g., airborne) campaigns that carry advanced remote sensing and in situ payloads provide detailed observations of atmospheric processes, but can be challenging to use when it is necessary to geographically collocate data from multiple platforms that make repeated observations of a given geographic location at different altitudes. This study reports on a data collocation algorithm that maximizes the volume of collocated data from two coordinated suborbital platforms and demonstrates its value using data from the NASA Aerosol Cloud Meteorology Interactions Over the western Atlantic Experiment (ACTIVATE) suborbital mission. A robust data collocation algorithm is critical for the success of the ACTIVATE mission goal to develop new and improved remote sensing algorithms, and quantify their performance. We demonstrate the value of these collocated data to quantify the performance of a recently developed vertically resolved lidar + polarimeter–derived aerosol particle number concentration (Na) product, resulting in a range-normalized mean absolute deviation (NMAD) of 9% compared to in situ measurements. We also show that this collocation algorithm increases the volume of collocated ACTIVATE data by 21% compared to using only nearest-neighbor finding algorithms alone. Additional to the benefits demonstrated within this study, the data files and routines produced by this algorithm have solved both the critical collocation and the collocation application steps for researchers who require collocated data for their own studies. This freely available and open-source collocation algorithm can be applied to future suborbital campaigns that, like ACTIVATE, use multiple platforms to conduct coordinated observations, e.g., a remote sensing aircraft together with in situ data collected from suborbital platforms.

Significance Statement
This study describes a data collocation (i.e., selection) process that aims to maximize the volume of data identified to be simultaneously collected in time and space from two coordinated measurement platforms. The functional utility of the resultant dataset is also demonstrated by extending the validation of aerosol particle number concentration derived from standard lidar and polarimeter data products from a suborbital mission that used two aircraft platforms.
ICD-11 post-traumatic stress disorder and complex post-traumatic stress disorder in mental health support-seeking former-serving Australian defence force veterans
Authors: Bressington Daniel , Hyland Philip , Steele Hannah , Byrne Mitchell , Mitchell David , Keane Carol , Shevlin Mark , Ho Grace , Murta Janina Catalao Dionisio , Easpaig Bróna Nic Giolla , Liu Xianliang , Zhai Jianxia , Murphy Dominic , Karatzias Thanos 
Published: February 2024

Background: ICD-11 complex post-traumatic stress disorder is a more severe condition than post-traumatic stress disorder, and recent studies indicate it is more prevalent among military samples. In this study, we tested the psychometric properties of the International Trauma Questionnaire, assessed the relative prevalence rates of post-traumatic stress disorder and complex post-traumatic stress disorder in the sample population and explored relationships between complex post-traumatic stress disorder and post-traumatic stress disorder and a range of risk factors. Methods: Survey participants ( N = 189) were mental health support-seeking former-serving veterans of the Australian Defence Force (ADF) recruited from primary care. Confirmatory factor analysis was used to test the factorial validity of the International Trauma Questionnaire. Results: The latent structure of the International Trauma Questionnaire was best represented by a two-factor second-order model consistent with the ICD-11 model of complex post-traumatic stress disorder. The International Trauma Questionnaire scale scores demonstrated excellent internal reliability. Overall, 9.1% (95% confidence interval = [4.8%, 13.5%]) met diagnostic requirements for post-traumatic stress disorder and an additional 51.4% (95% confidence interval = [44.0%, 58.9%]) met requirements for complex post-traumatic stress disorder. Those meeting diagnostic requirements for complex post-traumatic stress disorder were more likely to have served in the military for 15 years or longer, had a history of more traumatic life events and had the highest levels of depression, anxiety and stress symptoms. Conclusion: The International Trauma Questionnaire can effectively distinguish between post-traumatic stress disorder and complex post-traumatic stress disorder within primary care samples of Australian Defence Force veterans. A significantly greater proportion of Australian Defence Force veterans met criteria for complex post-traumatic stress disorder than post-traumatic stress disorder. Australian military mental health services should adopt the International Trauma Questionnaire to routinely screen for complex post-traumatic stress disorder and develop complex post-traumatic stress disorder specific interventions to promote recovery in Australian Defence Force veterans with complex post-traumatic stress disorder.