bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B002: ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma
Authors: Mandal Jayaprakash , Yu Zheng-Cheng , Shih Ie-Ming , Wang Tian-Li 
Published: March 2024

Abstract
The intricate interplay between chromatin remodelers, transcriptional regulation, and downstream cellular processes is gradually unraveling. AT-rich interactive domain-containing protein 1A (ARID1A), a tumor suppressor and chromatin remodeler, is frequently mutated in endometrium-related malignancies including ovarian or uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). How ARID1A mutation alters downstream signaling is yet to be established. Based on the TCGA proteomics datasets, MAPK and ARID1A are negatively correlated in endometrial cancer. Yet, the underlying molecular mechanism of this association remains unclear. Using ARID1A-proficient and ARID1A-deficient isogenic human endometrial epithelial cells, we explored transcriptomic changes and discovered notable downregulation of a MAPK phosphatase, dual-specificity phosphatase 4 (DUSP4), in ARID1A-deficient cells. This expression pattern was further validated in additional pairs of isogenic cell lines, ES-2, MCF10a, and HCT116. Chromatin immunoprecipitation sequencing (ChIP-seq) was utilized to assess active and repressive transcription histone marks on global and 5’ transcriptional regulatory regions of DUSP4. ChIP-seq demonstrated decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 enhancer and promoter regions of ARID1A-deficient cells, suggesting ARID1A's role in modulating chromatin accessibility and gene expression. Furthermore, a positive correlation between ARID1A and DUSP4 expression was established using a Pax8-driven conditional knockout mouse cohort and in human endometroid carcinoma tissues. Moreover, an inverse expression correlation between ARID1A and the phosphatase substrates of DUSP4, including p-p38, p-JNK, and p-ERK in the MAPK signaling pathway, was observed in this genetically engineered murine model and in the TCGA datasets of human uterine carcinomas. Interestingly, ectopic DUSP4 expression decreased cell proliferation, and MAPK pathway targeting, specifically via ERK inhibitor Ulixertinib, significantly mitigated tumor growth in vivo. In conclusion, our findings suggest ARID1A modulates DUSP4 expression by remodeling the chromatin landscape which leads to an inhibitory effect on the MAPK pathway and suppresses tumor progression. ARID1A-DUSP4-MAPK axis offers a promising avenue for developing targeted therapies against ovarian or uterine CCC and EMCA.
Citation Format: Jayaprakash Mandal, Zheng-Cheng Yu, Ie-Ming Shih, Tian-Li Wang. ARID1A loss activates MAPK signaling via DUSP4 downregulation: a mechanistic insight in endometrial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B002.
Abstract B033: Functional characterization of ALK5 (TGFBR1) mutations in endometrial cancer
Authors: Yu Eun-Jeong , Bell Daphne W. 
Published: March 2024

Abstract
ALK5 (TGFBR1) is a transmembrane receptor serine/threonine kinase that transduces TGF-b (Transforming Growth Factor b) signaling to activate SMAD2/3-dependent and -independent pathways. The purpose of this study is to determine the functional effects of ALK5 mutations in endometrial cancer (EC). Using nine in silico algorithms, we found that 79% (23 of 39) of ALK5 kinase domain mutations in EC are predicted to impact protein function. To test these predictions experimentally, constructs expressing wildtype-, constitutively active-, kinase-dead, or mutant-ALK5, including ALK5-A230V, were transfected into NIH3T3 cells, which have low endogenous ALK5 levels. Following TGF-β stimulation, we observed that transient exogenous expression of ALK5-A230V, located in the ATP-binding pocket, delayed SMAD2/3 signal transduction and altered SMAD-independent signaling. We further showed that the ALK5-A230V mutant has reduced protein stability via a ubiquitin-dependent protein degradation mechanism. Our structural modeling predicts that SB431542, a small molecule ATP-competitive inhibitor of ALK5 will bind to the ALK5-A230V mutant with less affinity than to wildtype ALK5. We, therefore, examined the inhibitory effect of SB431542 on wildtype- and mutant-ALK5 activity using a Smad-binding element (SBE) luciferase reporter assay in combination with TGF-β stimulation. SBE luciferase activity in ALK5-A230V-transfected cells was inhibited less by SB431542 than in wildtype-ALK5 transfected cells indicating that ALK5-A230V is less sensitive to SB431542 than wildtype ALK5, potentially due to the changes in affinity. Our findings are novel and show that the ALK5-A230V mutant is a partial loss-of-function mutant that attenuates TGF-b signal transduction and has reduced sensitivity to an ALK5 small molecule inhibitor.
Citation Format: Eun-Jeong Yu, Daphne W. Bell. Functional characterization of ALK5 (TGFBR1) mutations in endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B033.
Abstract PR006: ARID1A/B mutations retarget mSWI/SNF chromatin remodeler activity and define a spectrum of dedifferentiation in endometrial carcinoma
Authors: St. Laurent Jessica D. , Xu Grace , Cervantas Kasey , Patil Ajinkya , Sankar Akshay , Chen Shary , Kolin David , Wang Yemin , Huntsman David G. , Kadoch Cigall 
Published: March 2024

Abstract
Dedifferentiated/undifferentiated endometrial carcinoma (DEC/UEC) is a highly aggressive histologic subtype of uterine cancer with a higher incidence among non-Hispanic Black women. Recent exome-wide sequencing studies have revealed frequent and often concomitant mutations in the ARID1A and ARID1B genes in over 50% of DEC/UEC cases and 30% of all endometrial carcinomas. The mSWI/SNF family of chromatin remodelers are critical regulators of cell type-specific chromatin accessibility and gene expression, existing in three distinct forms: canonical BAF (cBAF), Poly bromodomain-associated BAF (PBAF), and non-canonical BAF (ncBAF). The paralog subunits, ARID1A and ARID1B, specifically nucleate the assembly of cBAF complexes. However, the precise role ARID1A/ARID1B mutations (cBAF loss) play in the development of dedifferentiated endometrial carcinoma remains unclear. In this study, we define an expression signature associated with endometrial “dedifferentiation” by profiling the well-differentiated and dedifferentiated components of cBAF loss DEC cases through laser capture microdissection followed by RNA sequencing. Introduction of ARID1A or ARID1B in cBAF loss DEC cell lines demonstrated the restoration of cBAF assembly, confirmed by glycerol gradient and IP mass spectrometry. Upon the expression of ARID1A or ARID1B, we observed widespread chromatin occupancy and DNA accessibility at distinct paralog-specific sites, along with common sites associated with epithelial lineage differentiation, estrogen receptor, and PI3K/AKT pathway signaling. These findings align with the differentiation signature, defined in DEC cases demonstrating downregulation of genes associated with Myc targets, cell cycle checkpoint pathways, and DNA repair, suggesting these pathways represent potential therapeutic avenues for targeting DEC/UEC. Collectively, these data establish that well-differentiated endometrial carcinoma and DEC/UEC with mSWI/SNF mutations represent a spectrum of cBAF loss, defining the unique roles of ARID1A and ARID1B in endometrial carcinoma development. Furthermore, these findings imply that cBAF loss drives the widespread changes in DEC morphology, gene expression, and clinical behavior, enhancing our understanding of the etiology and therapeutic options for these cancers.
Citation Format: Jessica D. St. Laurent, Grace Xu, Kasey Cervantas, Ajinkya Patil, Akshay Sankar, Shary Chen, David Kolin, Yemin Wang, David G. Huntsman, Cigall Kadoch. ARID1A/B mutations retarget mSWI/SNF chromatin remodeler activity and define a spectrum of dedifferentiation in endometrial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR006.
Combining TIGIT Blockade with MDSC Inhibition Hinders Breast Cancer Bone Metastasis by Activating Antitumor Immunity
Authors: Monteran Lea , Ershaid Nour , Scharff Ye’ela , Zoabi Yazeed , Sanalla Tamer , Ding Yunfeng , Pavlovsky Anna , Zait Yael , Langer Marva , Caller Tal , Eldar-Boock Anat , Avivi Camila , Sonnenblick Amir , Satchi-Fainaro Ronit , Barshack Iris , Shomron Noam , Zhang Xiang H.-F. , Erez Neta 
Published: March 2024

Abstract
Bone is the most common site of breast cancer metastasis. Bone metastasis is incurable and is associated with severe morbidity. Utilizing an immunocompetent mouse model of spontaneous breast cancer bone metastasis, we profiled the immune transcriptome of bone metastatic lesions and peripheral bone marrow at distinct metastatic stages, revealing dynamic changes during the metastatic process. We show that cross-talk between granulocytes and T cells is central to shaping an immunosuppressive microenvironment. Specifically, we identified the PD-1 and TIGIT signaling axes and the proinflammatory cytokine IL1β as central players in the interactions between granulocytes and T cells. Targeting these pathways in vivo resulted in attenuated bone metastasis and improved survival, by reactivating antitumor immunity. Analysis of patient samples revealed that TIGIT and IL1β are prominent in human bone metastasis. Our findings suggest that cotargeting immunosuppressive granulocytes and dysfunctional T cells may be a promising novel therapeutic strategy to inhibit bone metastasis.
Significance: Temporal transcriptome profiling of the immune microenvironment in breast cancer bone metastasis revealed key communication pathways between dysfunctional T cells and myeloid derived suppressor cells. Cotargeting of TIGIT and IL1β inhibited bone metastasis and improved survival. Validation in patient data implicated these targets as a novel promising approach to treat human bone metastasis.
Targeting the DHX9 RNA Helicase to Induce Antitumor Immunity in Small-Cell Lung Cancer
Authors: Chiappinelli Katherine B. 
Published: March 2024

Summary:Murayama and colleagues establish DHX9 as an exciting new target to induce viral mimicry and downstream antitumor immunity. The potential for use in combination with existing immune therapies is especially exciting in SCLC, an immunologically cold and deadly disease.See related article by Murayama et al., p. 468 (10) .
Free, Prior, and Informed Consent
Authors: Klein Laurence , Muñoz-Torres María Jesús , Fernández-Izquierdo María Ángeles 
Published: March 2024

Abstract
Free, Prior, and Informed Consent (fpic) is crucial for the exercise of indigenous peoples’ right to self-determination, a binding human rights norm, as it provides them with the opportunity to determine how their lands and resources are developed. While numerous companies have committed to respecting fpic in their corporate policies, there continues to be a huge disconnect between public rhetoric and actions on the ground, and indigenous peoples generally struggle to have a meaningful voice in decision-making processes that concern them. Even if the United Nations Guiding Principles on Business and Human Rights (ungp, 2011) have compelled companies to gain ground with regards to their responsibility to respect human rights, the ‘do-no-harm’ principle does not require them to take positive actions towards fulfilling human rights. This approach is inconsistent with the moral foundation of human rights, which implies duties, and does not account for the substantial economic and political power that increases companies’ potential as guarantors of human rights. Based on the normative and moral legitimacy sustaining the narrative on corporate human rights obligations and the political, moral and legal imperative behind fpic, this article asserts that companies have a normative obligation to observe fpic, which they ought to operationalise in the context of heightened requirements regarding their human rights due diligence.
Legal Issues in the Demands for Self-Determination in Nigeria
Authors: Adigun Muyiwa , Oniemola Peter K. , Adeyemo Deborah D. 
Published: March 2024

Abstract
There have been different ethnic political struggles calling for self-determination through secession in Nigeria since independence. There have also been calls for ‘restructuring’ the Nigerian federation to achieve what is called ‘true federalism’ believing that it is the only panacea for each ethnic group to achieve relative independence and self-determination within Nigeria. In addition, the question of control over natural resources has been a major issue in claims for self-determination. This article examines the legal issues involved in these self-determination demands in Nigeria. It finds that self-determination started as a moral or political concept before it developed into a legal concept under international law. Under international law, self-determination has emerged as external self-determination, internal self-determination, self-determination as indigenous autonomy, self-determination as a right against intervention and economic self-determination. It has also manifested in the same form in constitutional law. Against the backdrop of these findings, it is argued that self-determination demands assume three different legal forms in Nigeria manifesting as the right to external self-determination, the right to internal self-determination and the right to economic self-determination. It is further argued that there is no right to external self-determination or secession in Nigeria. In addition, it is argued that internal self-determination manifests as the right against discrimination on ethnic grounds in Nigeria and that it constitutes a fundamental right. Lastly, it is argued that the right to economic self-determination does not exist in Nigeria as natural resources are vested in the government while the interests of the people are undermined.
Being/Having a Muslim Voice
Authors: Stjernholm Simon 
Published: March 2024

Abstract
This article investigates attempts at, and the implications of, speaking publicly for Islam in Denmark, with special attention to the notion of “voice.” First, I present a theoretical framework for an analytical focus on voice, and develop a distinction between “being” and “having” a voice. In the analysis that follows, I focus on three recent Danish podcast series produced by and featuring Muslims that to various extents all address issues related to Islam. Thereafter I discuss the effectiveness of the studied podcasts’ efforts to be and have a Muslim voice in light of the analytical concepts “recognition” and “resonance.”
Molecular phylogeny of Gryllidea (Orthoptera: Ensifera) by mitochondrial genomes reveals the patterns of subapical spurs and dorsal spines on hind tibiae
Authors: Yu Zhe-Yuan , Hu Tian-Hao , Li Kai , He Zhu-Qing 
Published: March 2024

Abstract
The phylogeny of Gryllidea remains a controversy due to inconsistent findings from morphological and molecular studies. In order to investigate the phylogenetic relationships among subfamilies in Gryllidea, we sequenced and analyzed the mitochondrial genomes of five species from different subfamilies. Our analysis included a total of 41 mitochondrial genomes from Gryllidea, and the resulting phylogenetic trees revealed following relationship (((((Gryllidae + Oecanthidae) + Phalangopsidae) +Trigonidiidae) + Mogoplistidae) + Myrmecophilidae) + Gryllotalpidae. The phylogenetic analysis indicated that Itarinae and Landrevinae were grouped in Gryllidae, and Euscyrtinae grouped together with Podoscirtinae in Oecanthidae. We focused on the presence of subapical spurs and dorsal spines on hind tibiae for ancestral character state reconstruction. The results indicated that hind tibiae of Gryllidea exhibited multiple transitions between only subapical spurs and only dorsal spines states.
Reactivating Decoloniality in Black British Research-Activism
Authors: Van Arkadie Raphael 
Published: March 2024

Abstract
This article presents a reflection on the reactivation of decolonial theories and concepts through a research-activist project and perspective. The work is based on qualitative research carried out during my master’s degree at the University of Bristol. It places itself between Bristol’s Black communities and their relationship with an ontology of Whiteness enforced by White institutions. By using the concept of ‘acting white’ (Fordham 2008), and reflecting on my own movement between Black and White spaces, I address this ontological struggle both as a member of the Bristol Black community as well as through my role as a researcher. I use my position as a way of reflecting more deeply on the movement between White and Black spaces, how this engages our longer history of decolonial activism, and what this means for mitigating the imposition of the ontology of Whiteness on my own research and role in my community. This research, which followed the Black Lives Matter (blm) protests of 2020, took place in a context of renewed engagement with decolonisation, and heightened awareness of the conditions of Black spaces for those within the Bristol community, which are brought into the discussion surrounding Black identity and community in the UK and Bristol.
Preserving the Sacred Text: An Appraisal of Recent Meâl Bans in Türkiye
Authors: Ozsahin M. Cuneyt , Akin H. Bahadir 
Published: March 2024

Abstract
Recently, there have been heated debates in Türkiye as a result of the legal action taken by the Presidency of Religious Affairs (pra) to ban the translations of the Qur'an on the grounds that it contains “objectionable” interpretations of passages contrary to “the fundamentals” of Islam. This study argues that, throughout history, the sacred text has been of symbolic importance and thus the authorities have sought to exert control over it. After a review of the recent cases, a conclusion is drawn that the political views as well as the unconventional religious interpretations may have been the driving factors in the decision to ban meâls. Moreover, there is the distinct possibility that the spread of modernist Islamic interpretations via the Internet, particularly Qur’anism, which has been directly targeted by the pra in official sermons, may be another contributing factor in translation bans.
Nonequilibrium Fluctuations of Global Warming
Authors: Yin Jun , Porporato Amilcare , Rondoni Lamberto 
Published: March 2024

Abstract
While the warming trends of Earth’s mean temperature are evident at climatological scales, the local temperature at shorter time scales are highly fluctuating. Here we show that the probabilities of such fluctuations are characterized by a special symmetry typical of small systems out of equilibrium. Their nearly universal properties are linked to the fluctuation theorem and reveal that the progressive warming is accompanied by growing asymmetry of temperature distributions. These statistics allow us to project the global temperature variability in the near future, in line with predictions from climate models, providing original insight about future extremes.
Differentiating ‘pure’ and comorbid self-identified burnout: Diagnostic and management implications
Authors: Tavella Gabriela , Parker Gordon 
Published: March 2024

Objective A previous study identified categorically differing scores on the Sydney Burnout Measure (SBM) between individuals with self-identified burnout with ( n = 354) or without ( n = 188) a history of mental illness. The current study examined whether the SBM’s validity held in both scenarios. Method The factorial structure and scores on the SBM measure were compared between the two groups. Results Similar underlying symptom constructs were identified. The group with a mental illness history had higher general factor scores, suggesting more severe burnout. The group without such a history (and thus a ‘purer’ burnout state) had higher scores on the empathy loss factor, suggesting its greater specificity to burnout than to other psychological states. Conclusions Burnout appears to be experienced similarly by those with and without a mental illness history as measured by the SBM.
Off-label prescribing of psychotropics in a psychiatric patient population in Australia
Authors: Kyrios Mietta , Levido Jesse , Talbot Daniel , Harris Anthony 
Published: March 2024

Background This study aimed to investigate the practice of off-label prescribing in both in- and outpatient psychiatry practice. Methods One-hundred inpatient and 100 outpatient medical records from adult patients of an Australian psychiatry service from 2020 to 2021 were examined to determine the prevalence of off-label prescribing as defined by Therapeutic Goods Administration (TGA) indications, adherence to Royal Australian and New Zealand College of Psychiatrists (RANZCP) treatment guidelines, frequency of off-label prescription, and the quality of documentation and informed consent process. Results Most prescribing events in both in- and outpatient settings were either on-label or off-label but consistent with RANZCP guidelines. Patients with a schizoaffective disorder diagnosis or displaying aggression were most likely to receive off-label prescriptions. There was no significant difference between in- and outpatient groups in the quality of documentation or consent process. Conclusions In general, off-label prescribing across groups was common, but many decisions were then in line with RANZCP recommendations. That there is a discrepancy between clinical and regulatory bodies has implications for how off-label status is decided.