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Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1-YAP Mechanotransduction.
Get PDFMetabolic dysfunction-associated steatotic liver disease (MASLD) is shaped by metabolic injury and tissue mechanics. This study investigated whether liver stiffening occurs early in MASLD and how extracellular matrix (ECM) mechanics interact with lipid droplet (LD) overload to promote inflammation, fibrogenesis, and lipid dysmetabolism. Clinical data, mouse models, and in vitro experiments are integrated. Liver stiffness shifted modestly with steatosis but increased substantially in the presence of inflammation. In a diet-induced mouse model, liver stiffness increased before overt fibrosis. In cultured hepatocytes, stiff matrices combined with free fatty acid (FFA) induced steatosis synergistically amplified pro-inflammatory and pro-fibrotic signals, accompanied by cytoskeletal remodeling and nuclear deformation. YAP acted as a central mechanosensitive amplifier: stiffness drove YAP nuclear localization, and YAP knockdown blunted cytokine induction and fibrogenic gene expression under stiff + FFA conditions. Stiffness and LD overload jointly promoted lipogenesis and impaired lipophagy via YAP. Piezo1 is upregulated by stiff + FFA; its inhibition reduced Ca2⁺ influx and prevented YAP activation. Collectively, early liver stiffening, together with LD-derived intracellular stress, engages a Piezo1-YAP axis that amplifies inflammation, fibrogenesis, and disordered lipid metabolism, consistent with a proposed feed-forward loop mechanism accelerating MASLD progression
Check-worthy Arabic Claim Detection across topics for Automated Fact-checking Systems
Get PDFFact-checkers eagerly seek facts from massive amounts of information. With the rapid growth of information in the last decade, especially through social media, the need for Automated Fact-Checking (AFC) systems in journalism has become increasingly urgent, as they support and expedite fact-checking efforts to prevent the early spread of misinformation. Researchers from various organizations have proposed AFC systems that construct the fact-checking pipeline into multiple tasks: claim monitoring, claim detection, claim verification, and revealing claim justification. As part of tasks in the AFC system, detecting check-worthy claims is a critical step, as it aims to identify which sentences require fact-checking from collections of claims. Sentences that are most likely to be claims are then ranked by checkworthiness. Early in my PhD research, I observed that state-of-the-art check-worthy claim detection models struggle to generalize to new topics that were not encountered during the training phase. The present study advances research in this direction by proposing novel methods for check-worthy claim detection in Arabic texts. It begins by introducing the task, along with existing datasets, models, and related work, followed by a series of experiments focused on cross-topic claim detection. These experiments explore various techniques, such as zero-shot and few-shot learning settings, data augmentation methods, and domain adaptation strategies grounded in gradual learning. The experimental results demonstrate that the proposed approaches lead to notable improvements in MAP across multiple settings, including fewshot learning with data augmentation, contextual word-level augmentation, and similarity-driven gradual learning scenarios. These improvements are further supported by statistical significance analysis, indicating that the observed performance gains are unlikely to be attributable to random variation. The work is further extended through an investigation into normalizing dialectal Arabic claims into Modern Standard Arabic (MSA), addressing a key linguistic challenge in the Arabic language. Collectively, these studies highlight the complexity of the task and demonstrate how claim detection models can benefit from these strategies. The thesis is composed of three core experimental chapters, each contributing to a distinct dimension of the problem: (i) The first chapter presents strategies for detecting check-worthy claims across diverse topics, leveraging zero-shot and few-shot learning combined with data augmentation techniques to enhance generalizability to new topics; (ii) The second chapter introduces a domain adaptation approach through a similarity-driven gradual topic learning framework, enabling the model to adapt effectively to unfamiliar topics; and (iii) The third chapter investigates the impact of dialectal variation and demonstrates the effectiveness of normalizing Arabic dialects into MSA to improve check-worthy claim detection models. The thesis advances research in fact-checking in the Arabic language, highlighting important issues that need to be addressed in the future to better deal with different topics and dialects
Wasafiri: The History of a Little Magazine and the Material Conditions Affecting the Publication and Reception of BAME Writing in Britain 1980 – 2020
No full textThe central aim of this thesis is to explore the background and history of Wasafiri, giving unique access to this “little magazine” known since the early 1980s for its pioneering role in providing a critical forum and platform for Caribbean, African, South Asian and Black British writers. Drawing on its unique archive now housed in the British Library Contemporary Collections, the history of this magazine will act as a paradigm to offer broader insights into the material conditions affecting the production, publication and reception of BAME writing in Britain from the 1980s to 2020. The socio-political, educational and publishing landscape of Wasafiri’s formative years are the context and rationale for the questions raised within the thesis to investigate what factors shaped the magazine’s inception and any influence the magazine has since brought to bear on the literary sector through its curation and publication of Black and Asian British writing. Drawing on primary data from the archive and methodologies from postcolonial and global literary studies combined with book and magazine history, the thesis will focus on four key areas. 1) Britain’s relationship with immigration, the rise of Black British identity and activism and its subsequent influence on the education curriculum; 2) The impact of government policy on funding of the Arts and Culture industries. Considering how this has changed over time and how Wasafiri navigated these policies; 3) The British publishing industry’s perception and publication of Black and Asian British authors and writing in contrast to Wasafiri’s approach; and finally, 4) Focusing on Wasafiri’s archive, interrogating its importance and place in British history and how this illuminates and contributes to debates about decolonising the curriculum across the educational and publishing sectors, the cultural and theoretical shifts in the literary landscape and magazine culture
Genetic analysis of patients with undiagnosed short stature identified novel dominant negative GH receptor variants which provide important insights into GHR physiology
No full textBeyond ‘Expressed Emotion’: Development and validation of a contextual measure of family communication and involvement in the context of psychosis in Ethiopia
No full textUnderstanding Critical Thinking Skills with Generative AI in a Transnational Education Setting
No full textEnhancing financial advisory quality in emerging markets: the role of strategic planning, FinTech adoption, and policy in service delivery
Get PDFAbstract This study investigates the significant losses experienced by Iranian traders from 2020 to 2023, attributed to poor trading technology, a lack of servant leadership, and ineffective financial marketing strategies, which have raised concerns about the future of financial services and the brokerage industry. The aim is to develop a model that examines the impact of strategic planning and financial marketing strategies on the quality of financial advice, considering the mediating role of Fintech acceptance and the moderating role of servant leadership. The findings reveal that strategic planning significantly influences FinTech acceptance and the quality of financial advice, while the effect of financial marketing on advisory quality is inconclusive. Additionally, FinTech acceptance positively mediates the relationship between strategic planning and advisory quality but not for financial marketing strategies. The moderating role of servant leadership was also confirmed, showing a positive influence by strengthening the relationship between strategic planning and the quality of financial advice. This study fills both theoretical and practical gaps by integrating FinTech adoption, strategic planning, and financial marketing strategies in exploring financial advice quality. It contributes to the literature by providing a comprehensive view of these interconnected factors. Practically, the research addresses the "Black Wednesday Issue" in the Tehran stock market, where many investors suffered losses, offering insights to enhance financial advice and mitigate future risks, benefiting researchers, financial institutions, policymakers, and the general public.</jats:p
What has happened to river macroinvertebrate biodiversity in England and Wales over the past 30 years?
Get PDFRisk of hypertension in people with HIV in the USA initiating modern antiretroviral regimens: pooled analysis of blood pressure data from five clinical trials
No full textAbstract Background People with HIV have a greater risk of cardiovascular disease than the general population. Current literature suggests that some ARTs may exacerbate this risk. Objectives To estimate the risk of hypertension in treatment-naïve people with HIV receiving integrase strand transfer inhibitor (INSTI)/tenofovir alafenamide (TAF) or INSTI/non-TAF versus NNRTI/non-TAF regimens. Methods Post hoc pooled analysis evaluating data from US participants in five Phase 3 randomized studies. Adjusted prevalence of Stage 1 and 2 hypertension (American College of Cardiology/American Heart Association criteria) and conditional odds of higher blood pressure ratios were estimated using proportional odds mixed-effect regression through 108 weeks after ART initiation. Time to incident hypertension through 96 weeks was modelled using Cox proportional-hazards regression. Results In total, 2411 participants were included (528, 749 and 1134 received NNRTI/non-TAF, INSTI/non-TAF and INSTI/TAF regimens, respectively). Nearly half of participants had hypertension (Stage ≥1) at baseline. The Week 96 adjusted estimates of risk of hypertension (95% CI) were 1.06 (0.99, 1.13) and 1.12 (0.98, 1.27) for Stages ≥1 and ≥2 hypertension, respectively, for NNRTI/non-TAF versus INSTI/non-TAF, and 1.01 (0.95, 1.08) and 1.02 (0.91, 1.17) for Stages ≥1 and ≥2 hypertension, respectively, for NNRTI/non-TAF versus INSTI/TAF. There were no significant differences in conditional odds of high blood pressure between treatment groups. No significant differences were identified in time to incident composite hypertension for INSTI/non-TAF and INSTI/TAF versus NNRTI/non-TAF regimens; estimated hazard ratios (approximate 95% CI) were 0.88 (0.66, 1.17) and 0.98 (0.75, 1.28), respectively. Conclusions Results suggest the risk of hypertension is not significantly different across INSTI/TAF, INSTI/non-TAF and NNRTI/non-TAF regimens. </jats:sec
Female Travel in the Islamicate Mediterranean, 1100-1500: Theory and Practice
No full textThis dissertation contributes to the field of women’s history and the history of the Islamicate Mediterranean in the late Medieval period, providing an examination of the contexts and conditions under which women travelled. Whilst women’s social history in the Islamicate world has much advanced in recent decades, there has not been to date a detailed study of female travellers. This dissertation offers an analysis and consolidation of secondary literature as well as examining primary sources, covering juridic texts, European and Muslim travelogues, Arabic chronicles and Islamic biographical dictionaries, documents from the Cairo Geniza and Muslim legal documents from the Ayyubid and Mamluk periods. I argue that despite scholarly concerns about the desirability of female travel, opinion varied greatly both among the legal schools and across time, thereby providing women with a wide latitude of interpretation as to their religious obligations to travel both accompanied and unaccompanied. A wealth of cross-cultural narrative sources as well as Jewish and Muslim administrative documentation indicate that women were visible on both the roads and seas of the Islamicate Mediterranean, and were found travelling for a wide range of purposes, including Ḥajj, other pilgrimages, knowledge-seeking and teaching, family visitation, marriage and economic necessity. I argue that there were many contexts where female travel experiences across the whole region intersected and aligned, regardless of religious affiliation. Whilst there were greater social and practical restrictions on women, who travelled in far fewer numbers than men, I argue that women did travel over land and sea more frequently than has been supposed. Indeed for a few women, for example, some upper- and middle-class Muslim scholars, travelling for religious and scholarly activity was a way of life. The first chapter covers the legal opinions of scholars from the differing Sunni schools throughout the period on the subject women’s travel, including whether or not a woman is permitted to travel without a close relative (maḥram), thus framing the elite scholarly view on the permissibility of female travel. The second chapter analyses narratives texts, covering travelogues from both the Muslim and Christian worlds and Islamic biographical dictionaries, including a detailed examination of al-Sakhāwī ’s al-Ḍawʾ ʾal-lamiʻ li-ʾahl ʾal-qarn ʾal-tasiʻ, one of the largest extant compilations of the activities of female scholars. The third chapter examines the documents from the Cairo Geniza and the Ḥaram al-Sharīf collections, analysing disparate types of documentation, including personal letters, estate documents, and marriage contracts to highlight the social and economic circumstances for which women travelled