Search Results (546)

Early parent–child interactions are crucial for children’s social–emotional development. Mental state talk (MST)—language referring to thoughts, feelings, and intentions—is a key contributor. MST may be reduced in hearing parents of deaf or hard-of-hearing (DHH) children, who face unique communication challenges. Yet, existing research on MST in hearing parents of DHH children and on MST use by DHH children themselves is limited and fragmented, often focusing on MST quantity in a single context. Few studies have examined MST quality, variation across contexts, or its relationship with children’s social–emotional functioning. This study addresses these gaps by investigating MST quantity and quality across two activities and its associations with children’s MST and social–emotional development. Forty-eight hearing parent–DHH child dyads (ages 2–5) participated. MST was studied during storybook reading and free play. Children completed tasks on emotion understanding and theory of mind; parents reported on MS vocabulary and family characteristics. The results showed that parents adjusted MST complexity based on children’s age but not audiological characteristics. MST varied by activity, with different contexts eliciting distinct types of MST. Parental and child MST were associated, though not linked to children’s task performance. Findings highlight the importance of diverse interaction contexts and suggest a need for longitudinal research on MST’s developmental impact. Full article

In dealing with emergency events, it is very important when making scientific and correct decisions. As an important premise, the creation of information needs is quite essential. Taking earthquakes as a type of unexpected event, this paper constructs a large and model-driven system for automating the generating process of information requirements for earthquake response. This research explores how the different departments interact during an earthquake emergency response, how the information interacts with each other, and how the information requirement process operates. The system is designed from three points of view, building a knowledge base, designing and developing prompts, and designing the system structure. It talks about how computers automatically make info needs for sudden emergencies. During the experimental process, the backbone architectures used were four Large Language Models (LLMs): chatGLM (GLM-4.6), Spark (SparkX1.5), ERNIE Bot (4.5 Turbo), and DeepSeek (V3.2). According to the desired system process, information needs is generated by real-word cases and then they are compared to the gathered information needs by experts. In the comparison process, the “keyword weighted matching + text structure feature fusion” method was used to calculate the semantic similarity. Like true positives, false positives, and false negatives can be used to find differences and calculate metrics like precision and recal. And the F1-score is also computed. The experimental results show that all four LLMs achieved a precision and recall of over 90% in earthquake information extraction, with their F1-scores all exceeding 85%. This verifies the feasibility of the analytical method a chatGLM dopted in this research. Through comparative analysis, it was found that chatGLM exhibited the best performance, with an F1-score of 93.2%. Eventually, Python is used to script these aforementioned processes, which then create complete comparison charts for visual and test result checking. In the course of researching we also use Protege to create the knowledge requirements ontology, so it is easy for us to show and look at it. This research is particularly useful for emergency management departments, earthquake emergency response teams, and those working on intelligent emergency information systems or those focusing on the automated information requirement generation using technologies such as LLMs. It provides practical support for optimizing rapid decision-making in earthquake emergency response. Full article

Here, we show that the aureolic acid-class antibiotic, olivomycin A, exerts potent anticancer activity in renal cell carcinoma (RCC) by disrupting both cell survival and metastatic programs. In A-498 (wild-type p53) and 786-O (loss-of-function in p53 and PTEN) cells, olivomycin A markedly inhibited migratory capacity and reversed epithelial–mesenchymal transition (EMT), as shown by downregulation of nuclear Snail and the mesenchymal marker N-cadherin and restoration of the epithelial markers, E-cadherin and ZO-1. In parallel, olivomycin A induced apoptosis through distinct p53-dependent mechanisms: In A-498 cells, apoptosis was primarily mediated through the intrinsic pathway, characterized by the upregulation of Puma, Bak, and activation of caspase-9. In 786-O cells, caspase-8 activation and Bid truncation were observed alongside mitochondrial involvement, suggesting possible cross-talk apoptotic cascades. Notably, in p53-mutant 786-O cells, treatment with olivomycin A elicited severe genotoxic stress accompanied by robust DNA damage signaling, excessive reactive oxygen species (ROS) accumulation, and lysosomal activation, culminating in extensive mitochondrial removal. Such changes were weaker in p53-wild-type A-498 cells, suggesting that the altered p53 context sensitizes RCC cells to olivomycin A-mediated mitochondrial quality control mechanisms. Collectively, our findings delineate a multifaceted mechanism whereby olivomycin A coordinates EMT suppression, apoptotic induction, and mitochondrial clearance. Thus, olivomycin A has potential as a therapeutic candidate that can target both survival and metastatic pathways in heterogeneous genetic backgrounds. Full article

Fatigue is a multidimensional phenomenon with profound implications for performance, health, and wellbeing. Its complexity means that no single discipline can adequately explain its causes or management, highlighting the need for integrative approaches. This article introduces the F.L.A.M.E.S. framework, a psychological model that integrates self-report, physiological, emotional, and contextual perspectives on fatigue. The framework combines validated assessment tools with evidence-based management strategies including goal setting, motivational self-talk, attentional control, and emotion regulation and embeds these within proactive, reactive, and preventative approaches. Applications are illustrated through case studies in sport, healthcare, and education, showing how the model can be co-constructed with practitioners to ensure ecological validity and uptake. By linking mechanisms to management and scaling solutions across domains, the F.L.A.M.E.S. framework provides a roadmap for enhancing performance, resilience, and sustainable wellbeing. Full article

This article explores Ludwig Wittgenstein’s conception of the will through close engagement with his primary texts, the Tractatus Logico-Philosophicus, Notebooks 1914–1916, and Philosophical Investigations, demonstrating profound resonances with Catholic mystical theology and social teaching. By integrating insights from Peter Tyler’s analysis of mystical strategies, Richard McDonough’s defense of Wittgenstein’s persistent mysticism, and the grammatical Thomism of Herbert McCabe, David Burrell, and Fergus Kerr, this study shows how Wittgenstein’s distinction between empirical and ethical will enriches Catholic theology in three crucial ways: First, it provides a philosophically rigorous account of the transcendental dimensions of moral agency that avoids both determinism and Pelagianism. Second, through Wittgenstein’s analysis of language-games and forms of life, it offers resources for articulating how Catholic doctrine operates within distinctive practices of prayer, sacrament, and ethical commitment. Third, by revealing the grammatical constraints on God-talk, it strengthens the apophatic tradition’s emphasis on divine transcendence while grounding concrete ethical action in subsidiarity and solidarity. Drawing upon Continental philosophy’s emphasis on responsibility and transcendence, this article demonstrates that Wittgenstein’s mystical philosophy, far from being merely speculative, provides essential conceptual tools for contemporary Catholic theological method and pastoral practice. Full article

Composting can be perceived as an art and science of converting organic waste into a rich and nutritious soil amendment—compost. The existing literature talks about how and what parameters need to be monitored in the process of composting and what actions are to be taken to optimize the process. In this paper, the development, deployment and data analytics of a compost monitoring system are presented, wherein not only the parameters to be measured but also the topology, mechanical design and battery operation details, which are crucial for the deployment of the system, are considered. Having realized that the temperature plays an important role in the process of composting, a contactless method of monitoring the compost temperature, using thermal imaging, has been investigated. Results showing the screenshots of the successfully developed system, plots of the obtained data and the inferences drawn from them are presented. This work not only contributes to the composting data, which is scarce, but also brings out the advantages of using thermal images in addition to temperature sensor probes. Full article

Background/Objectives: The aims of this study are to define the roles of the neurotrophic tyrosine receptor kinase genes NTRK1, NTRK2 and NTRK3 (NTRK1/2/3) in CRC and to determine the clinicopathological, molecular, cancer signalling and potential predictive significances of NTRK1/2/3 expression in CRC, irrespective of NTRK gene fusion. Methods: Standard statistical tests in SPSS were utilised to interrogate the associations and correlations between NTRK1/2/3 expression and clinicopathological, molecular and genomic features in two CRC cohorts. NTRK1/2/3 expression deregulation was also investigated using correlation and regression analyses. Furthermore, gene set enrichment analysis (GSEA) and pathway/drug ontology enrichment analysis (POEA/DOEA) were utilised to interrogate the enrichment of cancer signalling pathways, as well as NTRK and other tyrosine kinase inhibitor response in the CRC cohorts. Results: Whilst NTRK1 expression was higher in the CRC subset with microsatellite instability, NTRK2/3 expression was preferentially overexpressed in the microsatellite stable subsets. Moreover, there was differential NTRK1/2/3 expression with respect to clinicopathological and molecular/genomic indices. In addition, this study demonstrated that NTRK1/2/3 expression was deregulated by a combination of copy number alterations (NTRK2), aberrant methylation (NTRK1/2/3) and potentially and cryptic gene fusion (NTRK3). Furthermore, GSEA and POEA demonstrated that NTRK1/2/3-high CRC subsets exhibited enrichment of and cross-talks among the NTRK signalling pathways, as well as of known cancer signalling pathways. The GSEA and DOEA showed that NTRK signalling was enriched for kinase inhibitors responses, representing evidence that NTRK1/2/3 expression may serve as biomarkers for multiple kinase inhibitors, including entrectinib—the tissue-agnostic kinase inhibitor for cancers with NTRK gene fusions. Conclusions: The results demonstrated that fusion-negative NTRK signalling may be active in CRC and may contribute to the molecular pathogenesis and biology of the disease. The results also demonstrated that the NTRK1/2/3 expression may be predictive multiple kinase inhibitors. Full article

In “Notes on Talks with Wittgenstein”, Waismann reports Wittgenstein saying that in speaking about ethics “I can only appear as a person speaking for myself.” If we combine this with another remark, “What is Good is Divine too. That, strangely enough, sums up my ethics”, it suggests that an understanding of Wittgenstein’s personal involvement with the teachings of Christianity is fundamental for an interpretation of his “Lecture on Ethics” (1929) and “Lectures on Religious Belief” (1938). From the evidence of his personal writings, in particular the coded notebooks of 1914–16 and MS183, which record remarks made in 1930–32, 1936–37, Wittgenstein’s relationship to the teaching of Christianity is complex. During WW1, Wittgenstein found a form of Christian teaching immensely helpful, it seemed to him the only sure way to happiness. This influence is still apparent in “Lecture on Ethics”. Remarks made in 1936–37 show Wittgenstein’s relationship with Christianity becoming more troubled, as his critical self-consciousness arising from thoughts about the teaching of the New Testament become increasingly debilitating. He begins to find that the Christian teaching is becoming a source of madness rather than one of happiness. He accepts that a life of faith would require him to live a completely different life from the one that suits him. He begins to think that an ordinary life and his philosophical work might be the solution to his state of unhappiness. In “Lectures on Religious Belief”, Wittgenstein’s remarks are made from a position which is more personally disengaged. Wittgenstein is now investigating religious belief as a human phenomenon and not as something with which he is any longer personally involved, but his personal experience, particularly his experience of loss of faith, is still fundamental to how he understands the phenomenon. Full article

LoRa is a long-range, low-power wireless communication technology widely used in Internet of Things (IoT) applications. However, its conventional implementation through Long Range Wide Area Network (LoRaWAN) presents operational constraints due to its centralized topology and reliance on gateways. To overcome these limitations, this work designs and validates a gateway-free mesh communication system that operates directly on commercially available commodity microcontrollers, implementing lightweight self-healing mechanisms suitable for resource-constrained devices. The system, based on ESP32 microcontrollers and LoRa modulation, adopts a mesh topology with custom mechanisms including neighbor-based routing, hop-by-hop acknowledgments (ACKs), and controlled retransmissions. Reliability is achieved through hop-by-hop acknowledgments, listen-before-talk (LBT) channel access, and duplicate suppression using alternate link triggering (ALT). A modular prototype was developed and tested under three scenarios such as ideal conditions, intermediate node failure, and extended urban deployment. Results showed robust performance, achieving a Packet Delivery Ratio (PDR), the percentage of successfully delivered DATA packets over those sent, of up to 95% in controlled environments and 75% under urban conditions. In the failure scenario, an average Packet Recovery Ratio (PRR), the proportion of lost packets successfully recovered through retransmissions, of 88.33% was achieved, validating the system’s self-healing capabilities. Each scenario was executed in five independent runs, with values calculated for both traffic directions and averaged. These findings confirm that a compact and fault-tolerant LoRa mesh network, operating without gateways, can be effectively implemented on commodity ESP32-S3 + SX1262 hardware. Full article

Current systems for exchanging medical records struggle with efficiency and privacy issues. While establishing the Electronic Medical Record Exchange Center (EEC) in 2012 was intended to alleviate these issues, its centralized structure has brought about new attack vectors, such as performance bottlenecks, single points of failure, and an absence of patient consent over their data. Methods: This paper describes a novel EMR Gateway system that uses blockchain technology to exchange electronic medical records electronically, overcome the limitations of current centralized systems for sharing EMR, and leverage decentralization to enhance resilience, data privacy, and patient autonomy. Our proposed system is built on two interconnected blockchains: a Decentralized Identity Blockchain (DID-Chain) based on Ethereum for managing user identities via smart contracts, and an Electronic Medical Record Blockchain (EMR-Chain) implemented on Hyperledger Fabric to handle medical record indexes and fine-grained access control. To address the dual requirements of cross-platform data exchange and patient privacy, the system was developed based on the Fast Healthcare Interoperability Resources (FHIR) standard, incorporating stringent de-identification protocols. Our system is built using the FHIR standard. Think of it as a common language that lets different healthcare systems talk to each other without confusion. Plus, we are very serious about patient privacy and remove all personal details from the data to keep it confidential. When we tested its performance, the system handled things well. It can take in about 40 transactions every second and pull out data faster, at around 49 per second. To give you some perspective, this is far more than what the average hospital in Taiwan dealt with back in 2018. This shows our system is very solid and more than ready to handle even bigger workloads in the future. Full article

This exploratory study investigates the usability of performance metrics for generative adversarial network (GAN)-based models for speech-driven facial animation. These models focus on the transfer of speech information from an audio file to a still image to generate talking-head videos in a small-scale “everyday usage” setting. Two models, LipGAN and a custom implementation of a Wasserstein GAN with gradient penalty (L1WGAN-GP), are examined for their visual performance and scoring according to commonly used metrics: Quantitative comparisons using FID, SSIM, and PSNR metrics on the GRIDTest dataset show mixed results, and metrics fail to capture local artifacts crucial for lip synchronization, pointing to limitations in their applicability for video animation tasks. The study points towards the inadequacy of current quantitative measures and emphasizes the continued necessity of human qualitative assessment for evaluating talking-head video quality. Full article

Agape, philia, and eros are the forms of love that receive most attention in the work of the French philosopher Paul Ricœur. The general consensus among commentators is that when Ricœur talks about agape, he means a love that is all about giving, with no expectation of receiving anything in return; and when he talks about eros, he means something close to erotic love or erotic desire. This article builds on the research of two French commentators, Olivier Abel and Jérôme Porée, to offer a more detailed account of what Ricœur says about love of neighbour and concern for others, and where he says it, during one very specific period: 1947–1960. That is the period when Ricœur was very committed to education reform in France. However, the article disputes Abel and Porée’s interpretation of what Ricœur means by eros in Fallible Man, a work of philosophical anthropology published in 1960. The article shows that Ricœur’s interpretation of eros, far from being the standard one, is in fact highly original, and a perfect example of the imaginative use of philosophical resources that marked his early career. The article also discusses The Symbolism of Evil, a second work of philosophical anthropology that Ricœur published the very same year. In the context of that discussion, it draws attention to two references to “love” that link back to the eros of Fallible Man. It then offers a close reading of Marguerite Léna’s insightful commentary on a remarkable passage from The Symbolism of Evil, where Ricœur talks about the essential roles that love and fear play in all forms of education, including moral education. Full article

Routine collection of Patient-Reported Outcomes (PROs) can enhance patient–pharmacist communication and identify medication-related concerns. This study aims to explore the influence of RxTalk™, an electronic PRO tool, on patients’ attributes and the dynamics of communication. Secondary aims include describing patients’ experiences with RxTalk™ and identifying suggestions for improvements. This study is part of a pilot randomized controlled trial in which patients used RxTalk™ in the pharmacy while being observed before they spoke with the pharmacist. Patients’ interactions with pharmacists were tape-recorded and analyzed, and patients were interviewed within one week. We integrated data from RxTalk™, patient observations, taped encounters, and interviews to provide a thicker description of patients’ experiences with RxTalk™ and its impact on their communication. A total of 70% of patients found RxTalk™ easy to use, and 59% perceived RxTalk™ as very useful to extremely useful. Triangulated findings show that RxTalk™ met patients’ social and informational needs, improved their communication skills, and cultivated a sense of privacy to share concerns. Furthermore, RxTalk™ validated the appropriateness of reporting any health concerns, not simply medication concerns. As patients had a positive experience with RxTalk™, pharmacists should consider integrating PRO tools into their daily services to improve patient interactions and quality of care. Full article

We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary KIT mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of CLDN1 or inhibition of its activity by PDS-0330 effectively restored GIST’s sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA CLDN1). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R cells. Importantly, decreased tumor size and weight were observed in IM-resistant GIST xenografts treated with a combination of IM and PDS-0330. Furthermore, the combined treatment of IM-resistant tumors induced an increase in intratumoral apoptosis and other changes, as defined by the histopathologic response rate. Based on the co-immunoprecipitation and immunofluorescence microscopy data, we also demonstrated the strong interaction pattern between CLDN1 and FGFR2. Of note, the inhibition or knockdown of CLDN1 effectively decreased the phosphorylation of FGFR2 and FRS-2, a well-known FGFR adaptor protein, thereby illustrating CLDN1’s ability to regulate FGFR-signaling and thereby promote FGFR-mediated survival in KIT-inhibited GIST. Consequently, CLDN1 inhibition in GIST effectively disrupted the FGFR-mediated pathway and re-sensitized tumor cells to IM. In concordance with these data, molecular profiling of CLDN1-inhibited GIST T-1R cells illustrated a significant decrease in the majority of FGFR transcripts, including FGFR2, 3, and 4. Additionally, several FGFR ligands (e.g., FGF14, -19, and -23) were also down-regulated in PDS-0330-treated GIST. Notably, exogenous FGF-2 increased CLDN1 expression in a time-dependent manner. In contrast, pan-FGFR inhibitors effectively reduced CLDN1 levels in IM-resistant GIST T-1R cells, thereby illustrating a cross-talk between CLDN1- and FGFR-mediated pathways in IM-resistant GIST. Based on subcellular fractionation and immunofluorescence microscopy data, we also observed partial relocalization of CLDN1 into the cytoplasm in IM-resistant GIST. Notably, PDS-0330 effectively abrogated this relocalization, suggesting that changes in CLDN1 subcellular distribution might also impact GIST resistance to IM. Lastly, based on our small cohort clinical study (n = 24), we observed the increased expression of CLDN1 in most “high-risk” primary GIST known to be associated with poor prognosis and aggressive behavior, thereby illustrating the prognostic value of increased CLDN1 expression in GIST and providing a further rationale to evaluate the effectiveness of CLDN1 inhibition for GIST therapy. Full article

RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24–48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4–6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells. Full article