Critical Functions Research Articles

Enhancing Personalized Mental Health Support Through Artificial Intelligence: Advances in Speech and Text Analysis Within Online Therapy Platforms

Automatic speech recognition (ASR) and natural language processing (NLP) play key roles in advancing human–technology interactions, particularly in healthcare communications. This study aims to enhance French-language online mental health platforms through the adaptation of the QuartzNet 15 × 5 ASR model, selected for its robust performance across a variety of French accents as demonstrated on the Mozilla Common Voice dataset. The adaptation process involved tailoring the ASR model to accommodate various French dialects and idiomatic expressions, and integrating it with an NLP system to refine user interactions. The adapted QuartzNet 15 × 5 model achieved a baseline word error rate (WER) of 14%, and the accompanying NLP system displayed weighted averages of 64.24% in precision, 63.64% in recall, and an F1-score of 62.75%. Notably, critical functionalities such as ‘Prendre Rdv’ (schedule appointment) achieved precision, recall, and F1-scores above 90%. These improvements substantially enhance the functionality and management of user interactions on French-language digital therapy platforms, indicating that continuous adaptation and enhancement of these technologies are beneficial for improving digital mental health interventions, with a focus on linguistic accuracy and user satisfaction.

The trust deficit. EU bargaining for access and control over cloud infrastructures

ABSTRACT European Union (EU) governments rely on a handful of American cloud providers (hyperscalers) for critical state functions, which creates strategic dependencies. The EU data sovereignty agenda aims to manage such dependence, yet hyperscalers criticise it for excluding leading industry players from the EU market and slowing economic growth. In this paper, we argue that sovereignty policies in the cloud are the result of a trust deficit between European governments and American hyperscalers. The trust deficit consists of a continuous bargain by European governments for greater access and control over hyperscalers’ infrastructures. Hyperscalers, in turn, respond to such demands mainly through technology. But is their response sufficient to address the trust deficit? Drawing from technical documents and expert interviews, we find that states and hyperscalers have a fundamentally different understanding of sovereignty; that technology alone cannot address the trust deficit; and that data sovereignty policies in the cloud can be compatible with the digital economy and cybersecurity. Our study is a starting point for further research on the political economy of trust in the governance of digital technologies.

Synaptic Gα12/13 signaling establishes hippocampal PV inhibitory circuits

Combinatorial networks of cell adhesion molecules and cell surface receptors drive fundamental aspects of neural circuit establishment and function. However, the intracellular signals orchestrated by these cell surface complexes remain less understood. Here, we report that the Gα12/13 pathway lies downstream of several GPCRs with critical synaptic functions. Impairment of the Gα12/13 pathway in postnatal hippocampal neurons diminishes inhibitory inputs without altering neuronal morphology or excitatory transmission. Gα12/13 signaling in hippocampal CA1 neurons in vivo selectively regulates PV interneuron synaptic connectivity, supporting an inhibitory synapse subtype-specific function of this pathway. Our studies establish Gα12/13 as a signaling node that shapes inhibitory hippocampal circuitry.

Metaphorical discourse in Beijing Winter Olympic news: a Trinocular Perspective analysis of language, cognition, and social functions

This study utilizes the “Trinocular Perspective” metaphor analysis framework to delve into the language, cognition, and social functions of metaphors in news coverage of the Beijing Winter Olympics and their interactions, thereby revealing the role of metaphors in shaping and articulating the narratives within Olympic news communication. The research indicated that, at the linguistic level, metaphors enhanced the expressiveness and appeal of news discourse through diverse forms and dense distribution. At the cognitive level, metaphors fostered a deeper public understanding of abstract concepts such as the Olympic spirit, the values of a community with a shared future for mankind, China’s national image, and the concept of sustainable development. On the social function level, metaphors will play a pivotal role in building social identity, disseminating values, highlighting social issues, and promoting social change. The language, cognition, and social functions of metaphors were closely interwoven, with linguistic expressions enriching cognitive frameworks, cognitive frameworks guiding the internalization and dissemination of social values, and social functions guiding public cognition through the strategic use of metaphorical language. This study reveals the critical function of metaphors in elevating the narrative richness and dissemination efficacy within the journalism of large-scale international sports competitions.

Soluble TREM2 drives triple-negative breast cancer progression via activation of the AKT pathway.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a key role in immune regulation, particularly within tumor-associated macrophages (TAMs). In triple-negative breast cancer (TNBC), TREM2+ TAMs have been shown to modulate the tumor microenvironment, but the role of its soluble form: soluble triggering receptor expressed on myeloid cells 2 (sTREM2), produced through proteolytic cleavage, remains unclear. In this study, we investigated the effects of sTREM2 on TNBC progression. In vitro, treatment of TNBC cells with recombinant sTREM2 or sTREM2-containing culture supernatant significantly enhanced cell proliferation, invasion, and migration. These effects were further confirmed by the use of TREM2-neutralizing antibodies, which abrogated sTREM2's tumor-promoting activities. In vivo, peri-tumoral injections of recombinant sTREM2 led to a notable acceleration of tumor growth in mouse models. Mechanistically, we found that the effects of sTREM2 were mediated through its binding to the TG2 protein in 4T1 cells, thereby activating the AKT signaling pathway. Collectively, our findings suggest that sTREM2 drives TNBC progression by enhancing critical tumor cell functions, positioning it as a potential therapeutic target for TNBC treatment.

The relative importance of plant‐pollinator network parameters in maintaining seed productivity varies between years

AbstractHuman activities have caused biodiversity loss and climate change, altering critical ecosystem functions. Numerous empirical studies have focused on the relationship between plant diversity and primary productivity or its stability. However, ecosystem functions such as pollination and nutrient cycling would be regulated by biological interactions among multiple trophic levels. Here, we examined the relationship between plant diversity, pollination attributes, and seed productivity in a biodiversity experiment conducted in Inner Mongolia in 2018 and 2019, differing in intra‐annual precipitation patterns. We found that pollinator visitation frequency did not affect seed productivity in both years. In 2018, we observed that flowering plant richness and flower vulnerability had positive effects on seed productivity. In 2019, however, only network evenness had a negative effect on seed productivity. The consistent effect of pollination network structure but not visitation frequency on seed productivity across two growing seasons suggests that complementary plant‐pollinator interactions rather than mass effects of pollinator visitation regulate plant reproduction in the studied system. Since the relative contributions of flowering plant richness and plant‐pollinator interactions on seed productivity would vary due to intra‐annual precipitation patterns, as presented here, observations across multiple years should be required to fully reveal the ecosystem consequences of plant‐pollinator interactions.

Classification of speech arrests and speech impairments during awake craniotomy: a multi-databases analysis.

Awake craniotomy presents a unique opportunity to map and preserve critical brain functions, particularly speech, during tumor resection. The ability to accurately assess linguistic functions in real-time not only enhances surgical precision, but also contributes significantly to improving postoperative outcomes. However, today, its evaluation is subjective as it relies on a clinician's observations only. This paper explores the use of a deep learning based model for the objective assessment of speech arrest and speech impairments during awake craniotomy. We extracted 1883 3-second audio clips containing the patient's response following direct electrical stimulation from 23 awake craniotomies recorded from two operating rooms of the Tokyo Women's Medical University Hospital (Japan) and two awake craniotomies recorded from the University Hospital of Brest (France). A Wav2Vec2-based model has been trained and used to detect speech arrests and speech impairments. Experiments were performed with different datasets settings and preprocessing techniques and the performances of the model were evaluated using the F1-score. The F1-score was 84.12% when the model was trained and tested on Japanese data only. In a cross-language situation, the F1-score was 74.68% when the model was trained on Japanese data and tested on French data. The results are encouraging even in a cross-language situation but further evaluation is required. The integration of preprocessing techniques, in particular noise reduction, improved the results significantly.

The Significance and Usage Strategies of Macromolecules in 3D Printed Ceramic Composites.

3D printing technology enables the creation of complex ceramic structures and enhances the efficiency of customized ceramic production. Polymers play a crucial role in 3D-printed ceramic composites due to their unique processability, yet their significance and application strategies remain underexplored. These polymers not only enable rapid and precise 3D shaping but also offer additional advantages due to their unique and adjustable physicochemical properties. Therefore, the appropriate selection and utilization of polymers are expected to drive new breakthroughs in the field of 3D-printed ceramic composites. This review provides an overview of relevant additive manufacturing technologies and processes, with a specific focus on the strategies for using polymers in 3D-printed ceramic composites, including their roles as binders, templates, preceramics, and matrices. Highlighting the critical functionalities and potential value of these ceramic composites from a practical application perspective.

Envisioning the incorporation of Generative Artificial Intelligence into future product design education: Insights from practitioners, educators, and students

The advancement of Generative Artificial Intelligence (GenAI) has introduced diverse opportunities and challenges in product design, demanding a corresponding evolution in design education. This study investigated GenAI’s roles in product design and its implications for design education through semi-structured interviews with 24 participants, comprising practitioners, educators, and students, who had hands-on experience leveraging GenAI in design. Through thematic analysis, we identified critical functions of GenAI in product design, including generating inspiration, exploring potential solutions, conducting prototyping, performing evaluations, finalizing detailed outputs, and serving as design materials, presenting both opportunities and challenges. Moreover, fully incorporating GenAI in product design requires adaptation in educational initiatives, including capability development, curriculum content, and assessment methods. This study provides insights from a multi-stakeholder perspective, revealing the roles of GenAI in product design and advancing educational curricula to prepare the next-generation designers to be proficient in effectively leveraging GenAI for innovation.

Reduced OTUD7B expression correlates with poor prognosis in PTCL via non-canonical NF-κB.

Peripheral T cell lymphoma (PTCL) is an aggressive and highly heterogeneous lymphoma with a bleak prognosis, highlighting the urgent need for an effective biomarker to guide therapeutic strategies. Ovarian tumor domain-containing 7B (OTUD7B) has been shown to have a critical function in the progression of cancers. However, the prognostic significance of OTUD7B in PTCL remains unexplored. In this study, we demonstrated for the first time that PTCL patients with low expression of OTUD7B had shorter progression-free survival (PFS) and overall survival (OS). In addition, OTUD7B knockdown promoted chemoresistance to doxorubicin in PTCL cell lines, and led to increased translocation of p52 from the cytoplasm to the nucleus. Inhibition of non-canonical NF-κB partially restored the sensitivity of PTCL cells to doxorubicin. Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

Understanding the UI-design features paradox of the skip option in splash advertising: the roles of perceived control and skipping habit

ABSTRACT Splash advertising appears on mobile apps at launch. Since the skip option of splash ads is a critical function for user experience and ad effectiveness, a more in-depth perspective is required to shift attention from the mere presence of the skip option to its UI-design features, and to further explore its influence. This study aims to explore the impact of the UI-design features of the skip option within the context of splash ads on users’ attitudes towards splash ads and the app by examining dual pathways of perceived control and skipping habit. A survey was conducted in China which found that both responsiveness and visual salience of the skip option positively affect perceived control, further enhancing users’ attitudes toward splash ads and the app. However, the visual salience of the skip option would increase users’ skipping habit, further decreasing their attitudes toward splash ads. Additionally, app dependency positively moderates the relationship between perceived control and users’ attitudes toward splash ads and the app. The findings deepen our understanding of the UI-design features of the skip option in splash ads and offer practical insights for app developers and advertisers in striking a balance between user experience and ad effectiveness.

Polycomb in female reproductive health: patterning the present and programming the future.

Epigenetic modifications regulate chromatin accessibility, gene expression, cell differentiation and tissue development. As epigenetic modifications can be inherited via mitotic and meiotic cell divisions, they enable a heritable memory of cell identity and function and can alter inherited characteristics in the next generation. Tight regulation of epigenetic information is critical for normal cell function and is often disrupted in diseases including cancer, metabolic, neurological and inherited congenital conditions. The ovary performs critical functions in female reproductive health and fertility, including oocyte and sex-hormone production. Oocytes undergo extensive epigenetic programming including the establishment of maternal genomic imprints, which are critical for offspring health and development. Epigenetic modifiers also regulate ovarian somatic cells, such as granulosa and theca cells which support oocytes and produce hormones. While ovarian dysfunction contributes to serious ovarian conditions such as primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS) and ovarian cancers, the roles of epigenetic modifications in the ovary and their contribution to ovarian dysfunction are not properly understood. Here we review recent advancements in understanding Polycomb proteins, important epigenetic modifiers that have emerging roles in ovarian development and maternal epigenetic inheritance. Polycomb group proteins (PcGs) contribute to the faithful establishment of epigenetic information in oocytes, a process essential for normal offspring development in mice. Emerging evidence also indicates that PcGs regulate ovarian function and female fertility. Understanding these and similar mechanisms will provide greater insight into the epigenetic regulation of ovarian and oocyte function, and how its disruption can impact reproductive health and maternal inheritance.

The Role of Long Non-coding RNA ZFAS1 in Gliomagenesis: A Scoping Review

Background: Non-coding RNA species play important roles in biological mechanisms that regulate glioma initiation and progression. Recently, evidence suggested that ZNFX1 antisense RNA 1 (ZFAS1) has the ability to act as an oncogene or tumour suppressor, and so plays critical regulatory functions in the development and progression of many types of cancers such as lung, renal and hepatocarcinoma. The roles of ZFAS1 in glioma cancer are still unclear, and there are numerous potential pathways to explore. Objective: The aim of this scoping review is to provide an overview of the role of ZFAS1 in gliomagenesis, outline existing research on its mechanisms in glioma, and identify any knowledge gaps. Method: A literature search was carried out using Scopus, PubMed, and Web of Science (WoS) using a specified search string, and the data gathered was discussed and reported. Results: This scoping review comprised five original research papers that study ZFAS1 and its roles in gliomagenesis. ZFAS1 was found to be highly upregulated in glioma. and overall survival was revealed to be significantly associated with ZFAS1 status and regulated via several pathways and interactions, such as miRNA signalling, Epithelial to Mesenchymal transition (EMT) and Notch signalling pathway. Furthermore, ZFAS1 knockdown decreased cell proliferation, migration, and invasion while promoting cell death, implying that ZFAS1 is involved in glioma cancer progression. Conclusion: The evaluation of their diagnostic importance and therapeutic potential may aid in the development of novel therapies for glioma cancer.

Identification and expression analysis of phosphate transporter (PHT) genesin Brachypodium distachyon in response to phosphorus deficiency.

Phosphorus (P) is a macronutrient that plays a crucial role in critical plant functions. Phosphate transporters (PHTs) ensure the acquisition and translocation of Pi in the plant, thereby playing a key role in maintaining normal plant growth under Pi deficiency conditions. In Brachypodium distachyon, the grass model system, the function of individual PHT genes, remains largely unknown. Here, we identified the complete PHT gene family in B. distachyon, for the first time, and analyzed their expression profiles under Pi deficiency. Overall, 25 PHT genes in B. distachyon (BdPHTs) were identified, which were divided into four clades (PHT1-4). BdPHT genes were found to be unevenly distributed across the five chromosomes. Both segmental and tandem duplication events contributed to PHT gene expansion in B. distachyon which underwent a strong purifying selection. Moreover, exon-intron organization and motif composition were conserved within each PHT group consolidating the classification of the phylogenetic tree. Motif composition differs among the four PHT groups, indicating their functional divergence. Gene expression analysis using real-time quantitative PCR revealed that two BdPHT1 genes (BdPHT1.9 and BdPHT1.10) were upregulated in leaves, and seven (BdPHT1.9, BdPHT1.8, BdPHT1.7, BdPHT1.11, BdPHT1.12, BdPHT1.5, and BdPHT1.13) in roots under P deficiency suggesting their involvement in P uptake and translocation. Therefore, these results lay the foundation for future functional analyses in B. distachyon to improve P deficiency tolerance in B. distachyon and other cereals.

Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera

Exposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response. Here, we report the development and characterization of an IL-8 cleavage inhibition assay to measure the function of anti-SpyCEP antibodies in human sera. The assay was demonstrated to be sensitive, highly specific, linear and reproducible, and suitable for evaluating the function of anti-SpyCEP antibodies induced in humans in vaccine clinical trials and in observational studies of natural immunity.

REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers

Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.

Isolation, Purification, and Comprehensive Flow Cytometry Assessment of Lung Stromal Cells.

Stromal cells are non-hematopoietic cells that consist of endothelial cells and various mesenchymal cell populations. The composition of the stromal cell compartment is diverse in different organs. Numerous recent studies demonstrated that the lung environment contains heterogeneous mesenchymal stromal cell populations with distinctive genomic signatures and location preferences. Besides their role in supporting organ structure and remodeling tissue, mesenchymal stromal cells fulfill critical immune functions. These stromal cells show alterations during lung fibrosis and infectious disorders like COVID-19 or flu infection. To date, their identification and isolation were challenging, and most information about their heterogeneity was derived from scRNAseq data. In this protocol, we describe an isolation, comprehensive flow cytometry assessment, and purification strategy for murine lung stromal cells. The described method is optimized for minimizing cell death while keeping a high level of cell purity. This protocol can be also used for ex-vivo analysis of these cells in downstream functional assays. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of stromal cells from murine lung tissue Basic Protocol 2: Flow cytometry assessment of lung stromal populations Basic Protocol 3: Purification of lung fibroblastic stromal cells Alternate Protocol: Positive selection of fibroblastic stromal cells.

Feed the green for a sustainable and protein-efficient dairy production

CONTEXTIn modern intensive dairy farming, cows are increasingly held indoors and fed arable crops instead of grass to maximize individual animal performance. This leads to environmental issues such as high farm-level nutrient surpluses and loss of grassland plant species diversity as well as a growing competition between food and feed. OBJECTIVEWe conducted this study to define a threshold of concentrate supplementation that ensures a net contribution to the protein supply and evaluate the environmental performance of dairy farms when this level of supplementation is shifted. METHODSIn a first step, we calculated the hePCR (human-edible protein conversion ratio) of 52 dairy farms across a pedo-climatic gradient with varying feeding strategies. Based on farm management data and vegetation surveys, we analyzed the relationship between hePCR and different components of environmental and productive performance, with special interest on farm nutrient balances, grassland biodiversity and grass-based milk production. RESULTS AND CONCLUSIONSOur results show that higher concentrate supplementation levels significantly reduce the efficiency of converting plant protein into food. A critical threshold was identified at a concentrate milk proportion of 30 % or 177 g of concentrate feed per kilogram of milk produced, beyond which net protein contribution shifts to net consumption. Furthermore, we show critical interlinkages between a high protein efficiency and an enhanced environmental performance of the farms, such as higher grassland Shannon diversity and reduced nutrient surpluses. Our study suggests grass-based dairy farming as an integrated solution for enhancing net protein output while simultaneously safeguarding critical ecosystem functions. SIGNIFICANCEWe are in urgent need of sustainable agricultural practices that align an efficient food production with the reduction of negative environmental impacts. Our study is the first that shows direct positive interlinkages between the protein conversion efficiency of dairy farms and their environmental outcome as based on multi-annual management data and comprehensive vegetation surveys.

Pericytes require physiological oxygen tension to maintain phenotypic fidelity

Pericytes function to maintain tissue homeostasis by regulating capillary blood flow and maintaining endothelial barrier function. Pericyte dysfunction is associated with various pathologies and has recently been found to aid cancer progression. Despite having critical functions in health and disease, pericytes remain an understudied population due to a lack of model systems which accurately reflect in vivo biology. In this study we developed a protocol to isolate and culture murine lung, brain, bone, and liver pericytes, that maintains their known phenotypes and functions. We demonstrate that pericytes, being inherently plastic, benefit from controlled oxygen tension culture conditions, aiding their expansion ex vivo. Primary pericytes grown in physiologically relevant oxygen tensions (10% O2 for lung; 5% O2 for brain, bone, and liver) also better retain pericyte phenotypes indicated by stable expression of characteristic transcriptional and protein markers. In functional tube formation assays, pericytes were observed to significantly associate with endothelial junctions. Importantly, we identified growth conditions that limit expression of the plasticity factor Klf4 to prevent spontaneous phenotypic switching in vitro. Additionally, we were able to induce pathological pericyte phenotypic switching in response to metastatic stimuli to accurately recapitulate in vivo biology. Here, we present a robust method for studying pericyte biology in both physiology and disease.

Protein-Protein Interaction and Conformational Change in the Alpha-Helical Membrane Transporter BtuCD-F in the Native Cellular Envelope.

Alpha-helical membrane proteins perform numerous critical functions essential for the survival of living organisms. Traditionally, these proteins are extracted from membranes using detergent solubilization and reconstitution into liposomes or nanodiscs. However, these processes often obscure the effects of nanoconfinement and the native environment on the structure and conformational heterogeneity of the target protein. We demonstrate that pulsed dipolar electron spin resonance spectroscopy, combined with the Gd3+-nitroxide spin pair, enables the selective observation of the vitamin B12 importer BtuCD-F in its native cellular envelope. Despite the high levels of non-specific labeling in the envelope, this orthogonal approach combined with the long phase-memory time for the Gd3+ spin enables the observation of the target protein complex at a few micromolar concentrations with high resolution. In the native envelope, vitamin B12 induces a distinct conformational shift at the BtuCD-BtuF interface, which is not observed in the micelles. This approach offers a general strategy for investigating protein-protein and protein-ligand/drug interactions and conformational changes of the alpha-helical membrane proteins in their native envelope context.