Periostin Exon 17 Skipping Enhances the Efficacy of Local Adeno-Associated Viral-Microdystrophin Administration in a Fibrotic Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive genetic disorder primarily affecting boys, characterized by muscle degeneration due to mutations in the DMD gene encoding dystrophin, a crucial protein for muscle fiber integrity. The disease leads to significant muscle weakness and eventually to loss of ambulation. Adeno-associated viral (AAV)-microdystrophin (MD) gene therapy shows promise in preclinical and clinical settings. However, muscle fibrosis, a consequence of chronic inflammation and extracellular matrix remodeling, exacerbates disease progression and may hinder therapeutic efficacy. Periostin, a matricellular protein involved in fibrosis, is upregulated in DMD rodent models and correlates with collagen deposition. We previously developed an antisense oligonucleotide strategy to induce exon 17 skipping and so reduce periostin expression and collagen accumulation in the fibrotic D2.mdx mouse model of DMD. Here, we investigated the combined effects of periostin modulation and AAV-MD1 treatment. We found that systemic periostin splicing modulation significantly improved muscle function, assessed by forelimb grip strength and treadmill performance. Importantly, periostin exon skipping increased the MD protein expression. These findings suggest that targeting periostin in conjunction with MD therapy could represent a valid therapeutic strategy for DMD.</p

Spheres of resonance:How consumers contribute to atmosphere’s dynamics and plurality

Consumer experiences often build on resonant atmospheres that touch, seduce, or thrill consumers. Lack of resonance can diminish an atmosphere, alienate consumers, and render experiences meaningless. However, the way in which consumers contribute to atmospheres’ evolving resonance and plural nature has nonetheless been undertheorized. We address this question by operationalizing the concept of spheres of resonance, which we develop based on a multi-sited ethnography at the iconic holiday resort Club Med. Drawing on theory of resonance, we explain atmospheres are consumed through co-evolving spheres of resonance emerging in bodily encounters that momentarily envelop people and groups. Our findings show how these spheres co-exist but can also overlap, merge, and clash, influencing how atmospheres are felt and mobilized. Overall, we expand prior understandings of consumption atmospheres beyond a “mono-spherical” view and contribute to theory on the dynamics of atmospheres and resonance in consumer research

Loneliness, office space arrangement and mental well-being of Gen Z PR professionals.:Falling into the trap of an agile office?

Purpose – The purpose of the study was to assess how the well-being and loneliness of public relations and communication professionals are impacted by the post-pandemic characteristics of the work environment: flexible work schemes, non-territorial office arrangements and video communication technologies. It was hypothesised that the post-pandemic workplace landscape poses several new challenges to the practice of PR – an industry which invariably relies on working with other people and demands a good level of social resilience. Loneliness and well-being both depend on the experience of having good and efficient social relationships, but the pandemic has directly and indirectly led to their deterioration.Design/methodology/approach – The project employed a correlational design and used an online survey system to collect responses from Gen Z professionals employed in the public relations and communications industry in the UK and the US via the Prolific platform. Demographical and workplace- related characteristics were assessed to investigate links with loneliness (measured using a three-item scale adopted from Russell et al., 1980 in Hughes, 2004) and well-being (using a short Warwick- Edinburgh Mental Well-being Scale scale). Causal relationships between data were tested using regression analysis for continuous variables and analysis of covariance for categorical factors. Bootstrapping was used to test mediated relationships that explain loneliness, job satisfaction and the well-being of Gen Z PR professionals.Findings – Several types of flexible working schemes, defined as the ability to work from home on any number of weeks, showed an impact on loneliness and job satisfaction but not on well-being. However, all remaining aspects of the post-pandemic office did manifest as important predictors. In the sample, 30% of Gen Z PR professionals showed signs of mild to clinical levels of depression, and the best protection from this state was the presence of a significant other. Lower levels of loneliness were related to non-territorial office arrangements and job satisfaction. The use of hot desks and open-plan arrangements led to a significantly lower level of job satisfaction than a traditional, cellular office. Both excessive online meetings and face-to-face only interactions led to marginally lower levels of loneliness and job satisfaction.Research limitations/implications – The present research is limited in several aspects. Firstly, while the project evaluated loneliness, job satisfaction and mental well-being (with each of these elements including a component of the requirement for building effective relationships), the quality of relationships built by PR professionals was not measured. Secondly, the project focused only on post-pandemic aspects of the workplace and did not cover other important components of job satisfaction. Lastly, the measure of online meetings was declarative rather than behavioural, and greater control of the number of online meetings held would be required to show more reliable links between variables.Practical implications – This study calls for proposing recommendations for employers to develop organisational-level measures and programmes to counteract loneliness. While traditionally intimate relationships of employees were not a direct focus of HR programmes, employers should develop elements of organisational culture that would support employees in building effective intimate relationships. Separately from this, despite immediate financial benefits, employers should avoid using open-space and hot desk policies, as they contribute negatively to job satisfaction (and indirectly to well-being). The sample of UK and US professionals was chosen for analysis because in these countries employers have more capacity to introduce changes to tangible characteristics of the workplace and work culture, which may positively impact the well-being of their employees.Social implications – It is expected that both employers and employees will revisit their approach to post- pandemic financial and logistic challenges related to the workplace. A lower level of job satisfaction and well- being is linked to the lack of assigned office space, but the ability to work exclusively from home leads to loneliness. Employees – when offered this possibility – should work in offices they are provided. Employers must appreciate the negative link between open and hot-desking policies and job satisfaction and well-being of their employees.Originality/value – This study is the first to examine the post-pandemic workplace and personal characteristics of public relations and communications professionals in the UK and US and show how they impact job satisfaction and well-being. The study shows that 30% of employed in the PR industry are at risk of depression or anxiety. The connecting factor between personal and work-related characteristics that explains this problem is loneliness

DECML:Distributed Edge Consensus Machine Learning Framework

The increasing reliance on interdependent data-driven services in the Internet of Things (IoT), smart homes, and Industry 4.0 is hindered by siloed security and privacy measures. Existing solutions like federated learning and distributed machine learning, with their various approaches such as differential privacy and homomorphic encryption, while promising, face challenges in ensuring robust security and privacy. We introduce Distributed Edge Consensus Machine Learning (DECML), a novel framework that enables secure, privacy-preserving insights sharing among multiple stakeholders without exposing underlying data or models. DECML distributes queries and aggregates responses through independent nodes, achieving accuracy comparable to local deployments with minimal added latency. Our evaluation, using standard datasets and a 20-node network, demonstrates DECML's potential for collaborative decision-making without compromising privacy. This has significant implications for domains such as cybersecurity, healthcar

Leveraging Multimodal Shapley Values to Address Multimodal Collapse and Improve Fine-Grained E-Commerce Product Classification

Multimodal models can experience multimodal collapse, leading to sub-optimal performance on tasks like fine-grained e-commerce product classification. To address this, we introduce an approach that leverages multimodal Shapley values (MM-SHAP) to quantify the individual contributions of each modality to the model's predictions. By employing weighted stacked ensembles of unimodal and multimodal models, with weights derived from these Shapley values (MM-SHAP), we enhance the overall performance and mitigate the effects of multimodal collapse. Using this approach we improve previous results (F1-score) from 0.67 to 0.79