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Life History Enlightened Therapies: Cell Cycle Mapping to Identify Molecular Targets to Prevent Hepatocellular Carcinoma
Full text linkBackground and objectives
Life history enlightened therapies (LHETs) were originally developed in cancer to combat therapeutic resistance by targeting pathological cell state transitions that enable evolutionary rescue and adaptation to therapy. In this paper we expand the scope of LHETs to cancer prevention, namely metabolic dysfunction-associated steatohepatitis (MASH)-induced hepatocellular carcinoma (HCC) initiation. We focus on endocycling, a process wherein cells undergo whole-genome duplication via mitotic skipping, as a keystone life history transition that promotes HCC initiation.
Methodology
A key obstacle to LHET translation is the lack of systematic methods that capture cellular life histories and their molecular drivers. To address this gap, we introduce cell cycle mapping, a technique that integrates in situ multiplexed immunofluorescence imaging with manifold learning to visualize the life history of proliferating cells and proteins involved in transitions to pathological cell states.
Results
Mathematical modeling demonstrated how endocycling can create an environment that promotes HCC initiation and revealed the potential for endocycle-targeting therapies to prevent HCC. Using cell cycle mapping on human MASH liver tissues, we identified the molecular factors that drive pathological endocycling (Wee1, CDK2, and RAIDD), providing new therapeutic targets for pre-clinical investigation.
Conclusions and implications
This application illustrates how cell cycle mapping can uncover key proteins that drive disease-associated cell state transitions and broaden the scope of LHETs from therapy resistance to cancer prevention. More broadly, our study establishes a generalizable pipeline for inferring the life history of cells in diseased tissues and potential interventions for disease management
Video Games and Competition Law
No full textThis chapter offers a broad analysis of the past, present, and potential future application of EU and UK competition law to video games companies. It covers enforcement of the law on anticompetitive agreements, merger control, and abuse of dominance, plus complementary regimes regulating the digital economy. Beyond providing an accessible overview for those without prior knowledge of competition law, the chapter also highlights peculiarities of investigations into the gaming sector vis-à-vis other areas of enforcement. Furthermore, the chapter identifies several practices by video games companies which have not yet been subject to scrutiny, but could be. It also explores the implications for gaming of the EU Digital Markets Act and UK Digital Markets, Competition and Consumers Act. While cloud streaming services and mobile gaming are significant beneficiaries of these new regulatory regimes, comparable obligations on digital games stores would require significant changes by the console giants
Tensor extriangulated categories
Full text linkA tensor extriangulated category is an extriangulated category with a symmetric monoidal structure that is compatible with the extriangulated structure. To this end we define a notion of a biextriangulated functor (formula), with compatibility conditions between the components. We have two versions of compatibility conditions, the stronger depending on the higher extensions of the extriangulated categories. We give many examples of tensor extriangulated categories. Finally, we generalise Balmer's classification of thick tensor ideals to tensor extriangulated categories
Using the Rate of Global and Pointwise Microperimetry Change to Predict Structural Conversion in Intermediate Age-Related Macular Degeneration
Full text linkPurpose
Studies evaluating functional change in age-related macular degeneration (AMD) using microperimetry often measure the difference in global mean sensitivity at interval time points versus baseline. We evaluate the rate of global and pointwise microperimetry change in intermediate AMD (iAMD) in the multicenter MACUSTAR (Registration NCT03349801) study and assess their prognostic value in structural conversion to late-stage AMD.
Design
Prospective study.
Subjects
Four hundred forty-seven subjects with iAMD (Beckman classification) from 20 European sites.
Methods
Subjects that underwent mesopic microperimetry on ≥3 follow-up visits were included. Two methods of assessing functional progression were evaluated: (1) global mean sensitivity regression and (2) pointwise sensitivity regression at fastest progressing N number of locations (N from 1 to 10). Rates of microperimetry progression were then evaluated in an initial series of visits prior to structural conversion to late-stage AMD.
Main Outcome Measures
Area under the receiving operating characteristic (AUC) curves and Cox proportional hazard models were used to assess risk of structural conversion based on rate of functional progression.
Results
The mean age of subjects was 72 (standard deviation 7) years. The median number of visits and duration of follow-up was 6 visits and 3 years, respectively. Structural conversion to late-stage AMD was observed in 80 (17.9%) eyes. In the visits prior to conversion, there was a greater rate of global mean sensitivity loss in eyes that eventually developed late-stage AMD compared with those that did not (–1.05 vs. –0.30 decibels/year, P < 0.001). The AUC for classifying structural conversion versus no conversion was 0.72 for global sensitivity progression and 0.75–0.76 for between 1 and 10 fastest progressing N pointwise locations. The rate of global (hazard ratio 1.7, confidence interval [CI] 1.4–2.0) and pointwise (hazard ratio 1.2, CI 1.2–1.3) microperimetry progression in the initial series of visits was significantly associated with structural conversion (P < 0.0001).
Conclusions
In the analysis of longitudinal microperimetry data from the MACUSTAR study, the rate of global and pointwise sensitivity change was significantly greater and strongly prognostic of eyes that developed structural conversion. Our findings support use of these trend-based pointwise analysis methods in assessing functional progression in iAMD.
Financial Disclosure(s)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article
A meta-analysis of false memory in healthy and pathological cognitive aging
Full text linkAlthough there is a consensus about age-related impairments in true memory, the relationship between aging and false memory remains less clear. Both the FuzzyTrace Theory and the Activation-Monitoring Theory postulate possible effects of cognitive aging on the processes of encoding, consolidation, and retrieval. Yet, quantitative analyses of cognitive aging, both healthy (younger vs. older adults) and pathological (older adults vs. mild cognitive impairment, MCI/Alzheimer's disease, AD), on false memory have not been conducted. We meta-analyzed 150 articles with 414 independent effect sizes and found a robust aging effect of false memory, with older adults showing higher levels of false memory than younger adults in both spontaneous (Hedges’ g = 0.538, 95% CI [0.432, 0.644]) and suggestion-induced false memory (Hedges’ g = 0.460, 95%CI [0.255, 0.665]). MCI/AD patients showed significantly higher levels of spontaneous (Hedges’ g = 0.486, 95%CI [0.053, 0.919]) but not suggestion-induced false memory (Hedges’ g = 0.608, 95% CI [-0.286, 1.502]) than healthy older adults. For study and test phase, moderator analyses indicated that experimental material, modality, true memory, paradigm, type of test, and the retention interval significantly influenced aging effect on false memory. For general moderators, participants’ age and education level were also significant. Our results underscore the importance of integrating the FTT and AMT to account for age differences in false memory across types. Both healthy and pathological cognitive aging increase susceptibility to false memory, and the decline in verbatim memory and monitoring functions, combined with hyperactivation during encoding, may account for aging effect in false memor
No foreign language effect in Schizotypy: Evidence from German-English bilinguals
Full text linkPrevious research has suggested that fewer schizophrenic and schizotypal traits are reported in a second language than a mother tongue. Such results make sense in the light of the so-called Foreign Language Effect (FLE), whereby bilinguals make more rational decisions and are less influenced by emotions and biases in a learned second language (L2) than a mother tongue (L1). However, this previous research is to date very limited, and apart from one large-scale quantitative study is based primarily on anecdotal evidence. In the study reported here, we gave German-English bilinguals the Schizotypal Personality Questionnaire in either English or German. If doing the questionnaire in an L2 (here English) makes participants think more rationally and less emotionally, then fewer schizotypal traits should be reported in these participants than those who answer the same questions in their L1 (German). Results failed to support this hypothesis; there was no evidence that bilinguals reported fewer traits in their second language. We interpret these data as suggesting that the link between schizotypy (specifically) and language context may be weaker or less reliable than hitherto supposed
Delaunay Triangulations with Predictions
Full text linkWe investigate algorithms with predictions in computational geometry, specifically focusing on the basic problem of computing 2D Delaunay triangulations. Given a set P of n points in the plane and a triangulation G that serves as a “prediction” of the Delaunay triangulation, we would like to use G to compute the correct Delaunay triangulation DT(P ) more quickly when G is “close” to DT(P ). We obtain a variety of results of this type, under different deterministic and probabilistic settings, including the following:
1. Define D to be the number of edges in G that are not in DT(P ). We present a deterministic algorithm to compute DT(P ) from G in O(n + D log3 n) time, and a randomized algorithm in O(n + D log n) expected time, the latter of which is optimal in terms of D.
2. Let R be a random subset of the edges of DT(P ), where each edge is chosen independently with probability ρ. Suppose G is any triangulation of P that contains R. We present an algorithm to compute DT(P ) from G in O(n log log n + n log(1/ρ)) time with high probability.
3. Define dvio to be the maximum number of points of P strictly inside the circumcircle of a triangle in G (the number is 0 if G is equal to DT(P )). We present a deterministic algorithm to compute DT(P ) from G in O(n log∗ n + n log dvio) time.
We also obtain results in similar settings for related problems such as 2D Euclidean minimum spanning trees, and hope that our work will open up a fruitful line of future research
Apps for people with vision impairment: an international review of practitioner suggestions and app availability
No full textClinical relevance
Assistive smartphone apps play an integral role in supporting people with vision impairment (VI). Low vision rehabilitation (LVR) professionals need an understanding of these tools to provide effective, up-to-date guidance to help patients identify options that can improve daily functioning.
Background
Smartphones and assistive apps are widely used by people with VI, offering versatile and portable tools which support daily activities and promote independence. However, the volume and variability of apps create challenges for practitioners particularly as apps are updated frequently and artificial intelligence is gaining prominence. The purpose of this study is to describe how practitioners identify and make app recommendations.
Methods
An international cross sectional survey of LVR professionals was conducted to identify commonly recommended visual assistive apps. Responses were categorised by country income level and professional group of respondents. A concurrent search of English-language app stores, using predefined terms was performed to identify and compare assistive app availability with practitioner recommendations.
Results
App recommendation patterns varied by practitioner role and region. Optometrists frequently recommended magnifier apps, while therapists tended to suggest computer vision and sighted guide apps. Most commonly recommended apps were Seeing AI and Be My Eyes in high-income countries, and weZoom Magnifying glass and Be My Eyes in lower-income countries. Only two of ten most frequently recommended apps, Seeing AI and Be My Eyes, appeared consistently in app store searches across all four countries and both Android and iOS operating systems.
Conclusion
Comparing practitioner recommendations reflects potential differences in access, awareness, training, device availability, and patient needs. Understanding these insights helps to inform clinical decision-making and encourage more consistent and tailored support to diverse patient populations. Given the rapid pace of app development, regular review of the most suitable apps and clear dissemination of reliable information to practitioners are essential for informed evidence-based decision making
Female Corporate Narcissism and Its Association with Female Corporate Psychopathy
No full textTerms such as ‘corporate leader’, ‘entrepreneur’, and ‘CEO’ conjures up images of a self-centred, assertive, insensitive, and power-driven businessman. These traits comprise of narcissism which has been increasingly applied to describe the destructive behaviours of CEO’s. This increase in public attention has coincided with an increase in research on narcissism within organisational settings, due to the harm it poses to staff well-being and the integrity of the organisation. Hampering this research, however, is the gendered narrative to conceptualise and assess narcissism – an inherently masculine persona – in leadership and managerial roles. The literature on female narcissism in the workplace has been comparatively silent, despite marked gender differences in the presentation of this personality construct. This chapter sets these issues in a gendered context by outlining the descriptive features of female narcissism and how it manifests in interpersonal contexts, followed by a discussion of how female narcissism overlap conceptually and empirically with female psychopathy. The chapter ends with highlighting the theoretical and practical implications of female corporate narcissism, its association with female corporate psychopathy, and its impact on organisational outcomes
Operations & Supply Chain Management: Principles and Practice
Full text linkOperations and Supply Chain Management (OSCM) has continually evolved, incorporating a broad array of strategies, frameworks, and technologies to address complex challenges across industries. This encyclopedic article provides a comprehensive overview of contemporary strategies, tools, methods, principles, and best practices that define the field’s cutting-edge advancements. It also explores the diverse environments where OSCM principles have been effectively implemented. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners
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