Journals
2025 EN
Schubert Antonia · Mongkolsittisilp Ajaree · Kobitski Andrei
+14 more
WNT signaling governs development, homeostasis, and aging of cells and tissues, and is frequently dysregulated in pathophysiological processes such as cancer. WNT proteins are hydrophobic and traverse the intercellular space between the secreting and receiving cells on various carriers, including extracellular vesicles (EVs). Here, we address the relevance of different EV fractions and other vehicles for WNT5a protein, a non‐canonical WNT ligand that signals independently of beta‐catenin. Its highly context‐dependent roles in cancer (either tumor‐suppressive or tumor‐promoting) have been attributed to two distinct isoforms, WNT5a Short (WNT5aS) and WNT5a Long (WNT5aL), resulting from different signal peptide cleavage sites. To explore possible differences in secretion and extracellular transport, we developed fusion constructs with the fluorescent proteins (FPs) mScarlet and mOxNeonGreen. Functional reporter assays revealed that both WNT5a isoforms inhibit canonical WNT signaling, and EVs produced by WNT5a‐bearing tumor cells, carrying either of the WNT5a isoforms, induced invasiveness of the luminal A breast cancer cell line MCF7. We used fluorescence intensity distribution analysis (FIDA) and fluorescence correlation spectroscopy (FCS) to characterize at single‐molecule sensitivity WNT5aL‐bearing entities secreted by HEK293T cells. Importantly, we found that most WNT5aL proteins remained monomeric in the supernatant after ultracentrifugation; only a minor fraction was EV‐bound. We further determined the average sizes of the EV fractions and the average number of WNT5aL proteins per EV. Our detailed biophysical analysis of the physical nature of the EV populations is an important step toward understanding context‐dependent WNT cargo loading and signaling in future studies.
Journals
2025 EN
Dornelas Maria · Antão Laura H. · Bates Amanda E.
+482 more
ABSTRACT Motivation Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample‐level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format csv and. SQL.
Journals
2025 EN
Moisan Louis · Gravel Dominique · Gauthier Gilles
+2 more
ABSTRACT Aim Seasonally migratory species generate large movements of organisms and biomass between distant breeding and non‐breeding grounds. However, our understanding of how migratory species shape global networks of interconnected communities (meta‐communities) remains limited. Migratory links between communities can be measured in different ways (e.g., species occurrence, abundance or biomass), each providing complementary information by modulating the relative importance of species in meta‐communities. We aim at investigating to what extent measuring migratory links using species occurrence, abundance or biomass can reveal alternative structures (i.e., topology) in a meta‐community linking an Arctic breeding ground to remote non‐breeding grounds. Location We use as a study case the High‐Arctic vertebrate community of Bylot Island (Nunavut, Canada), along with ecoregions of North and South America, Europe and Africa. Time Period Present. Major Taxa Studied Terrestrial Arctic birds (30 species) and mammals (5 species). Methods We first consider species occurrence at the non‐breeding grounds to define migratory links within the meta‐community. Secondly, we measure the number of individuals and the amount of biomass travelling along those links. Finally, we compare the meta‐community structure under each scenario using a migration network representation. Results Patterns of species occurrence, abundance and biomass reveal that temperate ecoregions of South and especially North America maintain strong ecological connections with the vertebrate community of Bylot Island. However, the structural role of species within the network can vary substantially depending on how migratory links are measured (i.e., contrasting topological anomalies). Using abundance or biomass to measure migratory links results in a finer partitioning of the network into modules compared to using species occurrence alone. Main Conclusions We highlight that using different metrics of migratory links reveals unique, yet complementary structural features of meta‐communities. These findings contribute to assessing the vulnerability of communities to perturbations occurring in distant but connected environments through migration.
Journals
2025 EN
Bideault Azenor · Barbier Matthieu · Sentis Arnaud
+2 more
ABSTRACT Aim Understanding the direct (e.g., on biological rates) and indirect (e.g., through changes in species richness) effects of temperature on food web properties, in the context of latitudinal gradients and climate warming. We focus on species interactions and predict variations in two metrics of food web properties: trophic control and temporal variability. Location Global oceans. Time Period 2001–2018. Major Taxa Studied Marine fish species. Methods We use a modelling approach coupled with a global dataset of fish food webs. Species occurrences are obtained from data sources, while trophic interactions are predicted by a size‐based niche model calibrated with a global interaction dataset. Interaction strengths are constrained by allometric scaling laws for predation and biomass. We investigate how predictors varying with latitude (temperature, species richness, productivity, food web structure) drive latitudinal variations in trophic regulation and variability. Results Our results suggest a latitudinal gradient in two metrics of community dynamics, with both trophic feedback strength (underlying phenomena such as cycles and cascades) and temporal stability increasing with latitude. In our model, this variation is tied directly and indirectly to temperature, and we find that direct effects of temperature are weaker than (or at most equal to) indirect effects. The direct effect on interaction rates decreases trophic feedbacks yet increases variability. The organism‐level temperature–size rule is found to increase both feedback and variability. Finally, community‐level indirect effects (species richness and connectance) impact trophic control but not variability. Climate warming moderately affects trophic control, variability and total biomass, but more strongly alters individual species biomass. Main Conclusions Our study improves understanding of the drivers of latitudinal variation in food web properties and helps disentangle the direct and indirect effects of temperature. Indirect effects are predicted to drive biogeographic variation in food web properties, while direct effects such as short‐term warming could have stronger consequences at the species level.
Journals
2025 EN
Saultier Paul · Grino Michel · Falaise Céline
+9 more
Abstract Background Platelet transfusion is considered the standard treatment for preventing or controlling severe haemorrhage in Glanzmann thrombasthenia (GT). However, platelet transfusion can have detrimental effects, including the production of anti‐GPIIb/IIIa isoantibodies or anti‐HLA antibodies (Ab) and platelet transfusion refractoriness. Recombinant activated factor VII (rFVIIa) has been proposed as an alternative treatment to platelet transfusion. Methods We analyzed data from 77 case reports including 100 subjects to investigate the effectiveness and safety of rFVIIa in combination with platelets or antifibrinolytics for preventing or treating non‐surgical bleeds, as well as surgical and obstetrical procedures in GT. Results The dosage of rFVIIa was consistent with previous recommendations (90 µg/kg per infusion). In subjects without Ab/refractoriness ( n = 56), rFVIIa was effective in managing 93% of non‐surgical bleeds ( n = 42), 91% of minor ( n = 11) and 92% of major ( n = 26) surgical procedures and 89% of obstetrical procedures ( n = 9). In subjects with Ab/refractoriness ( n = 44), rFVIIa was effective in managing 90% of non‐surgical bleeds ( n = 39), and 75% of minor ( n = 12) and 100% of major ( n = 17) surgical procedures. The use of rFVIIa was safe, with 4 (2.7%) serious adverse events associated with rFVIIa. Conclusion Although the use of rFVIIa is currently restricted to subjects with Ab/refractoriness or when platelets are not available, our findings suggest expanding the indications for rFVIIa to encompass GT without Ab/refractoriness. Frontline use of rFVIIa may be proposed when clinically possible to mitigate the risks associated with platelet transfusion.
Journals
2025 EN
Grand François · BlancJouvan Florence · Mourey Guillaume
+17 more
ABSTRACT Introduction Discrepancies in factor IX activity (FIX:C) measurements between one‐stage clotting assays (OSAs) have been observed following infusion with recombinant factor IX extended half‐life concentrates (EHL‐rFIX) in the treatment of haemophilia B. These variations, primarily due to differences in activated partial thromboplastin time (APTT) reagents, complicate clinical decision‐making. Objectives The aim of this study was to evaluate whether drug‐specific calibrations for albumin‐fused recombinant FIX (rFIX‐FP) and Fc‐fused recombinant FIX (rFIX‐Fc) could reduce inter‐reagent discrepancies. Methods In a multicentre field study involving 20 laboratories, plasma samples spiked with rFIX‐FP, rFIX‐Fc or standard rFIX were tested using different APTT reagents. FIX:C was measured with usual and drug‐specific calibration. Data were analysed for compliance (target range: 80%–120% of expected values), interlaboratory variability and intralaboratory reproducibility. Results Usual calibration resulted in significant discrepancies among reagents, with compliance rates varying widely. Drug‐specific calibration significantly improved compliance for all reagents tested, except for one concentration with rFIX‐Fc. Interlaboratory variability decreased markedly, with coefficients of variation dropping from 19.4%–36.0% (usual calibration) to 6.0%–12.4% (specific calibration). Intralaboratory reproducibility was consistent whatever the type of calibration. Conclusion Drug‐specific calibration for EHL‐rFIX reduces reagent‐related variability in OSA FIX assays, ensuring reliable and standardised results. This approach facilitates monitoring with a single reagent system, improving laboratory efficiency. Wider availability of validated calibrators remains crucial for broader adoption and standardisation.
Journals
2025 EN
Burns Catherine · Kilkenny Monique F. · Purvis Tara
+16 more
ABSTRACT Background Co‐design helps to align research with end‐user needs, but there is no consistent method for reporting co‐design methodology and evaluation. We share our experiences co‐designing the Love Your Brain digital platform for stroke prevention. We evaluated the core attributes that guided our co‐design approach, including recruitment, focus group coordination, participant engagement and satisfaction. Methods Online co‐design focus groups were conducted fortnightly (May 2023 to March 2024) with two cohorts (health knowledge experts and community members; n = 8 sessions per cohort) to design the content and structure of Love Your Brain. Snowballing methods and purposive sampling were used to recruit participants in Australia. Coordination involved tracking the time spent by the research team for one round of focus groups. Participant engagement was measured through focus group attendance and survey feedback and analysed using descriptive statistics and thematic analysis. Count and length of verbal and/or written contributions during focus groups were summarised with descriptive statistics as a measure of engagement, with differences between cohorts assessed using χ 2 /Wilcoxon rank‐sum tests. Participant satisfaction was evaluated using survey responses and input at a final evaluative focus group. Results Sixteen health knowledge experts (clinicians/researchers) and 28 community members expressed interest, of which 10 health knowledge experts and 12 community members (including 9 people with lived experience of stroke) participated. Conducting two identical focus groups required 29 h of project manager/coordinator time, 8–11 h for facilitators and 6.5–8.5 h for chief investigators. Most participants (86%) attended ≥ 5/8 focus groups. Engagement was enhanced through pre‐reading material, structured/well‐organised focus groups and experienced facilitators. All participants contributed at each focus group, with varying levels of input. Health knowledge experts preferred written contributions over verbal contributions and wrote longer messages compared to community members. Community members spoke for a longer duration than health knowledge experts. Participant satisfaction was high, with participants reporting that the research team ‘always valued our opinions’. Importance was placed on a final evaluative focus group, and participants stated that their contributions were incorporated into the final product. Conclusion Our research emphasises relationships between coordination, participant engagement and satisfaction and the importance of considering resourcing requirements for successful co‐design of digital health projects. Patient or Public Contribution People with lived experience, including caregivers of people with stroke, and members of the public, participated in the co‐design focus groups. The Love Your Brain Management Committee includes people with lived experience of stroke who contributed to the oversight of this study and the preparation of this manuscript.
Journals
2025 EN
Purvis Tara · Burns Catherine · Barker Seamus
+17 more
ABSTRACT Background The majority of strokes are preventable through effective risk factor management. Existing primary prevention strategies have insufficient reach and effectiveness. Digital health technologies offer the potential to overcome some of these barriers. The aim of this study was to co‐design the ‘Love Your Brain’ digital platform, including an online education program (Massive Open Online Course, MOOC) and text messaging system, for community stroke prevention education and management. Methods Using snowballing methods, expressions of interest were sought from community members and health knowledge experts (e.g., health professionals and researchers) from across Australia. Participants were purposively selected for diversity in age, sex, location, education (community) and profession (health knowledge experts). A series of eight focus groups were planned. From May 2023 to August 2023, seven online focus groups were undertaken separately with each cohort, to explore perceptions related to the core functions, content and design features. Their insights were used to develop the digital platform. Following a testing period, a final focus group was held with each cohort (March 2024) to evaluate the digital platform further. Focus groups were recorded with participant consent. Recordings and transcripts, live chats and interactive polls from the focus groups were analysed using inductive and deductive thematic approaches, with themes mapped to the Framework for the Design and Evaluation of MOOCs. Results Twelve community members and ten health knowledge experts participated in at least one of the eight focus groups, with overall 86% attending five or more. Although some diversity existed in group opinions about the delivery and content, all participants emphasised the importance of using simple, easy‐to‐understand language and layout throughout, with the inclusion of a variety of statistics, personal stories and expert information. Focusing on emotional motivation was perceived as essential for engagement with the digital platform. Furthermore, being able to personalise the content and provide options for people to explore more advanced information (via external resources and a project‐specific website with trusted links) was considered advantageous. Conclusion Co‐design with community and knowledge expert cohorts informed and enriched the development of the Love Your Brain digital platform. The co‐designed platform is currently being piloted in a feasibility trial. Patient or Public Contribution People with lived experience of stroke, along with family/caregivers and members of the public, actively participated in the co‐design focus groups. The Love Your Brain Management Committee comprises lived experience stroke survivors and carers who worked in partnership with researchers and clinicians to provide oversight and guidance to the development and implementation of all stages of the study, including the preparation of this manuscript.
Journals
2025 EN
Kilkenny Monique F. · FreakPoli Rosanne · Burns Catherine
+14 more
ABSTRACT Objectives Globally, stroke is a common cause of death and disability. More than 80% of strokes are reported to be preventable through effective management of modifiable risk factors. Text messages can encourage changes in health behaviour. The Love Your Brain project involves the development and evaluation of a digital health platform for stroke prevention in Australia. In this study, we aimed to develop a text message system and content for this digital platform. Method The first phase involved reviewing a repository of existing health promotion messages from prior research on stroke. The second phase included co‐designing the content and delivery of the messaging system with community members ( n = 12) and health knowledge experts ( n = 10) through 16 focus groups. New messages were then developed and formatted. These messages were reviewed by subject matter experts, then adjusted for reading age ≤ Grade 10. The final phase included the development of the messaging platform. Results Among 1500+ pre‐existing messages reviewed for suitability, ≈10% were adapted for primary prevention. Focus group participants reported that receiving messages on weekdays was preferred and ‘ having a choice’ was beneficial. No consensus was reached regarding message frequency. Weblinks and shorteners were felt to be untrustworthy by participants; therefore, a Love Your Brain website using one hyperlink was developed. New messages were co‐designed and personalised with greetings and sign‐offs to increase engagement. All messages were revised by at least three of eight experts. After editing, 98% were readable at ≤ Grade 10 reading age and 79% at ≤ Grade 8. A REDCap message platform was built to enable personalisation at any time regarding the selection of ‘healthy choices’ relevant to participants' risk factors and preferences for the number of messages per week. Conclusion Integrating prior research and co‐design enriched the text message platform, including content and delivery. This system can be adapted for other conditions and cultural needs to deliver relevant health information. Patient or Public Contribution People with lived experience of stroke including family/caregivers. and members of the public, actively participated in the co‐design focus groups. The Love Your Brain Management Committee includes people with lived experience of stroke who work in partnership with researchers and clinicians to provide oversight of all stages of the study and the preparation of this manuscript.
Journals
2025 EN
Purvis Tara · Ross Andrew G. · Blennerhassett Jannette M.
+21 more
ABSTRACT Background Often people experience ongoing health challenges after stroke. The Australian Stroke Clinical Registry collects patient‐reported outcomes after stroke. Many patients report challenges that are potentially addressable through additional support. Aims To co‐design a registry‐based, hospital‐initiated, follow‐up service for people who report major health‐related challenges between 90 and 180 days after their stroke. Methods Iterative, consensus‐based methods were used to co‐design a follow‐up service intervention including eligibility criteria, clinical protocol (consultation/communication forms and pathways) and implementation requirements (e.g., training manual) (May 2022–March 2023). Stakeholders, including Australian‐based clinicians providing stroke care, researchers and people with lived experience of stroke, were involved in each stage. Data collection: Stage 1 (development), (i) scoping survey; (ii) two consensus meetings; (iii) interviews with key informants ( n = 3); (iv) online modified Delphi survey; Stage 2 (testing and finalisation), (v) piloting of the follow‐up service intervention at one hospital, with service coordinator/study team interview and participant satisfaction surveys and; (vi) final review (modified Delphi survey). Consensus was defined in the modified Delphi surveys as ≥ 80% ‘agreement’ or verbal consensus via open voting during meetings. Additional recommendations from each step were iteratively incorporated to refine the intervention. Results Scoping survey results ( n = 41/108 respondents, 38% response rate) highlighted the need for broad inclusion criteria and the involvement of carers/support person and general practitioners. During the consensus meetings (16/18, 89% stakeholders attended at least one), verbal consensus was achieved for the eligibility criteria, and additional recommendations were made for the referral report and components within the clinical protocol and training manual. After the final Stage 1 modified Delphi survey ( n = 10, two cohorts), 70%–100% consensus was achieved for the referral report, clinical protocol components and training manual, which were then piloted with six eligible participants. Feedback from the pilot testing ( n = 3 coordinator/staff interviews; n = 5 satisfaction surveys) led to further clinical protocol modifications. Agreement was reached for all additional recommendations during the final modified Delphi survey round (16/29 respondents, 55%). Conclusion We describe an iterative, consensus‐based co‐design process which resulted in a novel, registry‐based follow‐up service intervention for people living with stroke reporting major health challenges. A feasibility randomised controlled trial is the next stage. Patient or Public Contribution People with lived experience of stroke, including their family/caregivers, actively participated throughout the co‐design process to develop and test the follow‐up service intervention. There was lived experience representation with scoping survey responses, as well as within the working group and independent review group who were involved with the consensus meetings and modified Delphi process. Survey feedback from people with stroke who piloted the developed service intervention was also integral to informing the final service intervention.