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This exploratory study examines how discursive design—using provocative, speculative artifacts to spark reflection and discussion—might expand public health experts’ problematization of approaches to tailoring and targeting interventions. Cultural tailoring and targeting (CTT) refers to adapting interventions for specific sociocultural populations. Because LGBTQ+ communities experience disproportionately high rates of tobacco use, this study applies discursive intervention concepts within this context to explore how they might help experts critically engage with CTT strategies for reaching LGBTQ+ populations more effectively. To investigate this, two pairs of discursive intervention concepts were designed and presented to three focus groups of public health experts. Each pair juxtaposed a conventional intervention approach with a more provocative, unfamiliar one—for example, deepfake-driven behavior disruption. The goal was to document the type of conversation discursive design could stimulate around CTT considerations and generate insights relevant to the value of design methodologies to foster new ways to problematize public health matters. Findings indicate that the concepts prompted critical conversations about CTT, although the depth and focus of engagement varied. Those with greater expertise in LGBTQ+ issues engaged more with CTT mechanisms and implications, while others focused on implementation and feasibility concerns—essential to intervention development but outside the study’s focus. These patterns highlight who should be included in such efforts and how they should be engaged from a facilitation perspective, raising important considerations for methodological refinements and future research. Overall, this initial exploration aims to uncover the potential of discursive design to deepen understanding of CTT interventions and inform more responsive, innovative approaches to addressing tobacco use among priority populations.

The purpose of the present study was to investigate the long-term stability of water-referenced GABA and Glx neurometabolite concentrations in the sensorimotor cortex using MRS and to assess the long-term stability of GABA- and glutamate-related intracortical excitability using transcranial magnetic stimulation (TMS). Healthy individuals underwent two sessions of MRS and TMS at a 3-month interval. A MEGA-PRESS sequence was used at 3 T to acquire MRS signals in the sensorimotor cortex. Metabolites were quantified by basis spectra fitting and metabolite concentrations were derived using unsuppressed water reference scans accounting for relaxation and partial volume effects. TMS was performed using published standards. After performing stability and reliability analyses for MRS and TMS, reliable change indexes were computed for all measures with a statistically significant test–retest correlation. No significant effect of time was found for GABA, Glx and TMS measures. There was an excellent ICC and a strong correlation across time for GABA and Glx. Analysis of TMS measure stability revealed an excellent ICC for rMT CSP and %MSO and a fair ICC for 2 ms SICI. There was no significant correlation between MRS and TMS measures at any time point. This study shows that MRS-GABA and MRS-Glx of the sensorimotor cortex have good stability over a 3-month period, with variability across time comparable to that reported in other brain areas. While resting motor threshold, %MSO and CSP were found to be stable and reliable, other TMS measures had greater variability and lesser reliability.

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains’ left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. •Method optimized for obtaining accurate estimates of GABA levels with 1H-MRS in MS.•Neurometabolite levels are linked to regional MTR, a marker of microstructural damage.•Elevated sensorimotor GABA levels are linked to motor performance of MS participants.

Through a case study in Southern Quebec (Canada), the assessment of environmental flows in light of the effects of climate change is investigated. Currently, the 7Q2 flow metric (7-day average flow with a 2-year return period) is used for water abstraction management. Several flow metrics were calculated using flow time series simulated by a deterministic hydrological model (HYDROTEL) and climate change scenarios as inputs. Results were compared within homogeneous low flow regions defined using ascendant hierarchical clustering, for the 1990, 2020 and 2050 horizons and annual, summer and winter periods. The impact of each flow metric on the potential availability of physical habitat was analyzed using the wetted perimeter as a proxy. Results indicated that: (1) the increasing non-stationarity of simulated flow data sets over time will complicate the use of frequency analysis to calculate the 7Q2 flow metric; (2) summer low flow values are expected to be lower than winter low flows; and (3) flow-duration curve metrics like the LQ50 (median discharge value of the month with the lowest flow) may become relevant environmental flow metrics by 2050. Results question current water abstraction management tools and permit us to anticipate future local and regional issues during low flow periods.

This paper presents the bibliometric and visualization method applied to a dataset of 729 documents published in the collaborative economy research field. Four steps are described in details: (1) the delimitation of the field of study; (2) the selection of databases, keywords, and search criteria; (3) the extraction, cleaning, and formatting; and finally (4) the co-citation analysis and visualization. The method validation section shows the results obtained by applying our methodological procedure to an author network analysis as well as a source title network analysis. This study is unique which presents a co-citation analysis coupled with a network visualization applied to the rapidly growing research area of the collaborative economy as a whole and not only of the collaborative tourism and hospitality research, as has been previously. The originality of this method lies firstly in the fact that the data were extracted from two databases (Scopus and Web of Science) instead of one as is commonly done in analytic studies. Secondly, VOSviewer was our main analytical tool performing the co-citation analysis and the network visualizations.

Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and characterization of specific biomarkers. In this study, we assessed the hypoxic regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response adaptor/scaffold protein which regulates leukocyte differentiation and motility. Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and generation of MSC stably expressing the transcription factor hypoxia inducible factor 1alpha (HIF-1α) resulted in increased endogenous 3BP2 expression as well as cell migration. Analysis of the 3BP2 promoter sequence revealed only one potential HIF-1α binding site within the human but none in the murine sequence. An alternate early signalling cascade that regulated 3BP2 expression was found to involve membrane type-1 matrix metalloproteinase (MT1-MMP) transcriptional regulation which gene silencing abrogated 3BP2 expression in response to hypoxia. Collectively, we provide evidence for a concerted HIF-1α/MT1-MMP signalling axis that explains the induction of adaptor protein 3BP2 and which may link protein binding partners together and stimulate oncogenic MSC migration. These mechanistic observations support the potential for malignant transformation of MSC within hypoxic tumour stroma and may contribute to evasion of the immune system by a tumour.

In some hydrological systems, mitigation strategies are applied based on short-range water temperature forecasts to reduce stress caused to aquatic organisms. While various uncertainty sources are known to affect thermal modeling, their impact on water temperature forecasts remain poorly understood. The objective of this paper is to characterize uncertainty induced to water temperature forecasts by meteorological inputs in two hydrological contexts. Daily ensemble water temperature forecasts were produced using the CEQUEAU model for the Nechako (regulated) and Southwest Miramichi (natural) Rivers for 1–5-day horizons. The results demonstrate that a larger uncertainty is propagated to the thermal forecast in the unregulated river (0.92–3.14 °C) than on the regulated river (0.73–2.29 °C). Better performances were observed on the Nechako with a mean continuous ranked probability score (MCRPS) <0.85 °C for all horizons compared to the Southwest Miramichi (MCRPS ≈ 1 °C). While informing the end-user on future thermal conditions, the ensemble forecasts provide an assessment of the associated uncertainty and offer an additional tool to river managers for decision-making.

A pivotal role in guiding mesenchymal stem cell (MSC) differentiation has recently been attributed to the primary cilium. This solitary, non-motile microtubule-based organelle emerging from the cell surface acts as a sensorial membrane structure reflecting developmental and adaptive processes associated with pathologies including human cystic kidney disease, skeletal malformations, obesity and cancer. Given that the intrinsic hypoxic adaptation of MSC remains poorly understood within ischemic tissues or hypoxic tumours, we questioned whether the hypoxia inducible factor-1α (HIF-1α) might be a downstream effector regulating cilium maintenance. We show that murine bone marrow-derived MSC cultured under hypoxic conditions (1.2% O2) lose their primary cilia in a time-dependent manner. Gene silencing of HIF-1α prevented cilia loss in hypoxic cultures, and generation of MSC expressing a constitutively active HIF-1α (MSC-HIF) was found to decrease primary cilium formation. A Wnt pathway-related gene expression array was also performed on MSC-HIF and indicated that the secreted Frizzled-related proteins (sFRP)-1, –3 and –4 were down-regulated, while sFRP-2 was up-regulated. Overexpression of recombinant sFRP-2 or gene silencing of sFRP-1, –3 and –4 in MSC led to primary cilium disruption. These results indicate a molecular signalling mechanism for the hypoxic disruption of the primary cilium in MSC involving an HIF-1α/sFRP axis. This mechanism contributes to our understanding of the adaptive processes possibly involved in the oncogenic transformation and tumour-supporting potential of MSC. Our current observations also open up the possibility for the primary cilia to serve as a biomarker in MSC adaptation to low oxygen tension within (patho)physiological microenvironments.

The lectin from Canavalia ensiformis (Concanavalin-A, ConA), one of the most abundant lectins known, enables one to mimic biological lectin/carbohydrate interactions that regulate extracellular matrix protein recognition. As such, ConA is known to induce membrane type-1 matrix metalloproteinase (MT1-MMP) which expression is increased in brain cancer. Given that MT1-MMP correlated to high expression of cyclooxygenase (COX)-2 in gliomas with increasing histological grade, we specifically assessed the early proinflammatory cellular signaling processes triggered by ConA in the regulation of COX-2. We found that treatment with ConA or direct overexpression of a recombinant MT1-MMP resulted in the induction of COX-2 expression. This increase in COX-2 was correlated with a concomitant decrease in phosphorylated AKT suggestive of cell death induction, and was independent of MT1-MMP’s catalytic function. ConA- and MT1-MMP-mediated intracellular signaling of COX-2 was also confirmed in wild-type and in Nuclear Factor-kappaB (NF-κB) p65 −/− mutant mouse embryonic fibroblasts (MEF), but was abrogated in NF-κB1 (p50) −/− and in I kappaB kinase (IKK) γ −/− mutant MEF cells. Collectively, our results highlight an IKK/NF-κB-dependent pathway linking MT1-MMP-mediated intracellular signaling to the induction of COX-2. That signaling pathway could account for the inflammatory balance responsible for the therapy resistance phenotype of glioblastoma cells, and prompts for the design of new therapeutic strategies that target cell surface carbohydrate structures and MT1-MMP-mediated signaling. Concise summary Concanavalin-A (ConA) mimics biological lectin/carbohydrate interactions that regulate the proinflammatory phenotype of cancer cells through yet undefined signaling. Here we highlight an IKK/NF-κB-dependent pathway linking MT1-MMP-mediated intracellular signaling to the induction of cyclooxygenase-2, and that could be responsible for the therapy resistance phenotype of glioblastoma cells.

This article introduces Alasdair MacIntyre’s concept of proxy as a social role providing moral guidelines to address the challenges associated with designing for vulnerable populations from a caring perspective. While user-centered design approaches paved the way to empowering design interventions, a genuine shift from a curing to a caring perspective has yet to be fully embraced. Failing to adopt a caring approach is a point of contention for preventing designers from truly empathizing with their users and recognizing significant factors affecting the quality of user experience. To address that question, we discuss how MacIntyre’s moral framework considers the complex realities of vulnerable and dependent people and how to approach them. Through MacIntyre’s account of the proxy, it will be argued that design can adopt a caring approach by allowing consideration of the facts of dependency on others as social differences but not abnormalities. It will be suggested that adopting the proxies would prepare designers to face the challenges of advocating for users by leading them to consider the situation of dependent people as socially normal. Relying on insight from moral philosophy, this article suggests how design may embrace a genuine empathic stance in regard to the vulnerable.