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PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m 2 pemetrexed and ≤4 cycles cisplatin (75 mg/m 2 ) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC. Several PD-(L)1 inhibitors have been approved or are in development for the treatment of NSCLC, showing promising efficacy and tolerable safety profiles. Here, the authors present a randomized phase II clinical trial comparing two different anti-PD-1 antibodies, dostarlimab and pembrolizumab, both combined with chemotherapy as first-line treatment in patients with metastatic NSCLC.

Universities face continuous challenges in ensuring rapid and efficient communication during emergencies due to outdated, fragmented, and manual notification systems. This research presents the design, development, and implementation of a multiplatform mobile application to optimize emergency notifications at the Escuela Superior Politécnica de Chimborazo (ESPOCH). The application, developed using the Flutter framework, offers real-time alert dispatch, geolocation services, and seamless integration with ESPOCH’s Security Unit through Application Programming Interfaces (APIs). A descriptive and applied research methodology was adopted, analyzing existing notification workflows and evaluating agile development methodologies. MOBILE-D was selected for its rapid iteration capabilities and alignment with small development teams. The application’s architecture incorporates a Node.js backend, Firebase Realtime Database, Google Maps API, and the ESPOCH Digital ID API for robust and scalable performance. Efficiency metrics were evaluated using ISO/IEC 25010 standards, focusing on temporal behavior. The results demonstrated a 53.92% reduction in response times compared to traditional notification processes, enhancing operational readiness and safety across the campus. This study underscores the importance of leveraging mobile technologies to streamline emergency communication and provides a scalable model for educational institutions seeking to modernize their security protocols.

Interacting receptors at the neuronal plasma membrane represent an additional regulatory mode for intracellular transduction pathways. P2X4 receptor triggers fast neurotransmission responses via a transient increase in intracellular Ca2+ levels. It has been proposed that P2X4 receptor interacts with 5-HT3A receptor in hippocampal neurons, but their binding stoichiometry and the role of P2X4 receptor activation by ATP on this crosstalking system remains unknown. Via pull-down assays, total internal reflection fluorescence microscopy measurements of the receptors colocalization and expression at the plasma membrane, and atomic force microscopy imaging, we have demonstrated that P2X4/5-HT3A receptor complexes can interact each other in a 1:1 stoichiometric manner that is preserved after ATP binding. In addition, macromolecular docking followed by 100 ns molecular dynamic simulations suggested that the interaction energy of P2X4 receptor with 5-HT3A receptor is similar at holo and apo state of P2X4 receptor, and the interacting 5-HT3A receptor decreased the ATP binding energy of P2X4 receptor. Finally, the P2X4 receptor-dependent Ca2+ mobilization is inhibited by the 5-HT3A interacting receptor. Altogether, these findings provide novel molecular insights into the allosteric regulation of P2X4/5-HT3A receptor complex in lipid bilayers of living cells via stoichiometric association, rather than accumulation or unspecific clustering of complexes.

Purpose – The purpose of this paper is to examine and explain what organizes the marketing of retail sustainability. Design/methodology/approach – Theoretically, this paper takes a marketing-as-practice approach and makes use of practice theory to conceptualize the marketing of sustainability. Methodologically, an ethnographic study of three Swedish retail chains and their marketing work has been conducted. Interviews with management, observations made at the stores of these three retailers and various marketing texts and images produced by these retailers form the material analysed. Findings – This paper illustrates three different ways of marketing and enacting sustainability. It shows that sustainability is framed differently and, indeed, enacted differently in order to fit various ideas about who are the responsible consumers. The argument is that rather than consumer demand, supply pressure or media scandals, the marketing of sustainability is in each of the cases studied configured around a specific notion of the responsible consumer. What sustainability work is marketed, through which devices it is marketed, and how it is framed is guided by an idea of whom the retailers’ responsible consumers are, what their lifestyles are, and what they will be interested in. Images of responsible consumers work as configuring agents around which retailing activities and devices are organized. Originality/value – The paper provides an in-depth analysis of the marketing of sustainability and offers a new explanation about what it is that influences the various approach to sustainable marketing taken by retailers.

Purpose - The purpose of this paper is to explore, illustrate, and conceptualize how sustainability service is performed and the role it plays in the promotion of sustainable consumption. Design/methodology/approach - Theoretically, this paper takes a practice theory approach, conceptualizing the provision of sustainability service as a set of complex, socio-material, and performative practices. Methodologically, this paper draws on an ethnographic study of a retail chain - W-Store - and its sustainability service. Interviews with management and focus group interviews with shop assistants and consumers, as well as observations made in-store, make up the material analysed. Findings - The provision of sustainability service is accomplished in this case via three service practices; arranging green shopping trails, answering sustainability questions, and promoting sustainability to green consumers in-store. The analysis shows that the retailing of sustainable products is not simply a matter of including sustainability products in the range and instructing shop assistants to promote them. Sustainability service - as enacted at W-Store - was dependent on the successful combination and configuration of human competence (service staff) and IT and organizational artefacts. There also needed to be congruence between consumers and their images and between retailers and the version of sustainability they were enacting. Finally, the provision of sustainability service required an investigative and adaptive organization capable of keeping up as well as developing vis-a-vis changing sustainability discourses and issues. However, once the necessary conditions had been met, sustainability service worked towards promoting sustainable consumption by making green shopping possible, educating consumers on sustainability issues, and motivating them via positive feedback and dialogue. Originality/value - Underscores the importance of investigating sustainability service and offers both a conceptual approach to and an analysis of this particular type of retail service work.

Purpose The purpose of this paper is to further develop the conceptualization of music consumption in the digital age by examining how contemporary music listening is interweaved with other practices, how it shapes those practices and how it is in turn shaped by them. Design/methodology/approach The paper draws on extensive, qualitative interviews with 15 Swedish music consumers. During the course of these interviews, specific situations of everyday music listening were discussed in detail. Findings Drawing on practice theory and more specifically the concepts of dispersed and integrative practices, the authors identify and explore a mode of music listening that they term soundtracking, which involves choosing and listening to music mainly to accompany other everyday practices. Research limitations/implications As soundtracking grows in importance, music is increasingly consumed as an affective-practical resource. Its significance is then not derived from its ability to demarcate difference and construct consumer identities but from its capacity to evoke emotions and moods than enable and enrich a set of everyday practices. Practical implications When music is consumed as part of soundtracking, issues such as the audio quality of music or ownership of material music media become less important, while aspects such as mobility, accessibility and the adaptability of music increase in importance. This has important implications for how and what music should be produced and marketed. Originality/value This paper offers an alternative view of contemporary music consumption compared to previous research, which has considered music listening primarily as an integrative practice on which the practitioner is fully focussed. The paper also contributes to practice theory by offering an empirically based understanding of a dispersed practice, showing that such practices are neither without shape nor necessarily very simple in their structure.

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin-proteasome system. In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had received one previous line of cyclin-dependent kinase 4 and 6 inhibitor therapy plus one line of endocrine therapy (and up to one additional line of endocrine therapy). Patients were randomly assigned in a 1:1 ratio to receive vepdegestrant at a dose of 200 mg orally once every day of each 28-day cycle or fulvestrant at a dose of 500 mg, administered intramuscularly, on day 1 and day 15 of cycle 1 and on day 1 of subsequent cycles, with randomization stratified according to -mutation status and presence or absence of visceral disease. The primary end point was progression-free survival as assessed by blinded independent central review among the patients with mutations and among all the patients who underwent randomization. Progression-free survival was estimated with Kaplan-Meier methods and hazard ratios with a stratified Cox proportional-hazards model. A total of 624 patients underwent randomization; 313 were assigned to receive vepdegestrant, and 311 to receive fulvestrant. Among the 270 patients with mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P<0.001). Among all the patients, the median progression-free survival was 3.8 months (95% CI, 3.7 to 5.3) with vepdegestrant and 3.6 months (95% CI, 2.6 to 4.0) with fulvestrant (hazard ratio, 0.83 [95% CI, 0.69 to 1.01]; P = 0.07). Adverse events of grade 3 or higher occurred in 23.4% of the patients in the vepdegestrant group and in 17.6% of the patients in the fulvestrant group. Adverse events led to treatment discontinuation in 2.9% and 0.7% of the patients, respectively. Among patients with ER-positive, HER2-negative advanced breast cancer, vepdegestrant was associated with significantly longer progression-free survival than fulvestrant in the subgroup with mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.).

This paper aims to contrast the spillover effects in business failure derived from the geographic proximity among firms of the same sector. To get this purpose, we develop an empirical application based on the analysis of the join-count statistics on a sample of firms of service sector located in the municipality of Murcia (Spain). Our results show significant spatial autocorrelation pattern, therefore, the probability of failure in a firm not only depends on its internal characteristics, but also on the situation of failure of its vicinity peer companies. These results can be an interesting starting point in the development of papers which consider the interdependence effects among closer peer companies in business failure literature.

Purpose – The purpose of this paper is to explore, illustrate, and conceptualize how sustainability service is performed and the role it plays in the promotion of sustainable consumption. Design/methodology/approach – Theoretically, this paper takes a practice theory approach, conceptualizing the provision of sustainability service as a set of complex, socio-material, and performative practices. Methodologically, this paper draws on an ethnographic study of a retail chain – W-Store – and its sustainability service. Interviews with management and focus group interviews with shop assistants and consumers, as well as observations made in-store, make up the material analysed. Findings – The provision of sustainability service is accomplished in this case via three service practices; arranging green shopping trails, answering sustainability questions, and promoting sustainability to green consumers in-store. The analysis shows that the retailing of sustainable products is not simply a matter of including sustainability products in the range and instructing shop assistants to promote them. Sustainability service – as enacted at W-Store – was dependent on the successful combination and configuration of human competence (service staff) and IT and organizational artefacts. There also needed to be congruence between consumers and their images and between retailers and the version of sustainability they were enacting. Finally, the provision of sustainability service required an investigative and adaptive organization capable of keeping up as well as developing vis-á-vis changing sustainability discourses and issues. However, once the necessary conditions had been met, sustainability service worked towards promoting sustainable consumption by making green shopping possible, educating consumers on sustainability issues, and motivating them via positive feedback and dialogue. Originality/value – Underscores the importance of investigating sustainability service and offers both a conceptual approach to and an analysis of this particular type of retail service work.

Purpose - The purpose of this paper is to contribute to the on-going cultural turn in retail marketing by offering an overview of the interdisciplinary field of socio-cultural retailing and discussing how this body of work can contribute conceptually, methodologically and substantively to the field of retail marketing.Design methodology approach - This paper is based on a literature review of socio-cultural retail studies in marketing, cultural geography, sociology, and anthropology. The literature is analysed in relation to the substantive, conceptual and methodological domains of retail marketing.Findings - Drawing on the literature review, the authors argue that socio-cultural retail studies can contribute to the field of retail marketing substantively, conceptually and methodologically, thus broadening its current scope and domains.Originality value - This paper provides an overview of an interdisciplinary field and identifies how it can contribute to the field of retail marketing. It is valuable for retailing researchers interested in socio-cultural approaches to the study of contemporary retailing.