Nanobodies to GPVI as alternative reagents for platelet spreading

Platelet spreading assays are widely used to assess platelet adhesion, cytoskeletal remodeling and receptor‑specific signaling, but current GPVI ligands such as Collagen Related Peptide (CRP‑XL) suffer from non‑defined structure, batch variability, and high cost. Nanobodies targeting GPVI offer an attractive alternative due to their defined stoichiometry and recombinant production. Here, we evaluated whether GPVI‑binding nanobodies can support GPVI‑dependent platelet spreading. Using automated image analysis, we compared spreading on monovalent Nb2, trivalent Nb2‑3 and CRP‑XL. Monovalent Nb2 supported full spreading in only a subset of platelets, with reduced adhesion compared to CRP‑XL. In contrast, trivalent Nb2‑3 induced platelet adhesion and spreading indistinguishable from CRP‑XL, with comparable morphology, actin organization and spread area at concentrations ≥0.1 µg mL −1 . Spreading on Nb2‑3 was inhibited by soluble Nb2 and by Src kinase blockade, confirming GPVI‑dependent signaling, while the non‑blocking nanobody Nb28 had no inhibitory effect. Notably, Nb28 alone supported spreading, demonstrating that ligand‑induced GPVI clustering, rather than binding site location, drives activation. These findings show that Nb2‑3 is a potent and reproducible alternative to CRP‑XL, offering a well‑defined and standardizable reagent for GPVI‑dependent static platelet spreading assays.

Some cost-conscious care strategies for dermatology

Are potential remittive properties of OX-40 inhibitors something to be excited about?

Management of adult vitiligo: approved topical JAK inhibitor and standard therapies

Vitiligo is a chronic autoimmune depigmenting disorder. Ruxolitinib 1.5% cream is currently the only therapy specifically approved for its treatment. In addition, clinical guidelines recommend off label standard therapies, including topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), phototherapy (narrowband UVB or excimer devices), and selected off-label systemic regimens. This review summarizes the scientific evidence on approved and guideline-recommended treatments for adult vitiligo, using a PRISMA-based approach. Only English-language articles published between 2000 and 2025 were included. Interventions comprised approved therapies and standard treatments recommended by guidelines. Outcomes evaluated were changes in Facial and Total Vitiligo Area Scoring Index (F-VASI/T-VASI), quality of life, and safety. Risk of bias was assessed using the Risk of Bias 2 (RoB 2) tool for randomized controlled trials (RCTs) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for non-randomized studies. Ruxolitinib cream demonstrated superior F-VASI responses compared with vehicles in phase II–III RCTs. Evidence supports the efficacy of potent or very potent TCS, TCI, and NB-UVB or targeted 308-nm devices in localized disease. Systemic regimens show benefits in selected clinical scenarios, although supporting evidence remains heterogeneous. Treatment selection should be individualized based on disease activity, extent, anatomical site, and patient preferences.

IL-39 in the IL-23/IL-12 axis of psoriasis

On-label persistence in psoriasis after switching to guselkumab, tumor necrosis factor inhibitors, interleukin-17 inhibitors, or apremilast from other advanced therapies

To compare on-label persistence among adults with psoriasis who switched from other advanced therapies to guselkumab versus subcutaneous tumor necrosis factor inhibitors (SC TNFi), subcutaneous interleukin-17 inhibitors (SC IL-17i), or apremilast. This retrospective cohort study used U.S. claims data from the IQVIA PharMetrics® Plus database (2016– 2023). Overlap propensity score weights were used to balance cohorts on baseline characteristics. On-label persistence was defined as the absence of drug discontinuation (event) and any dose change relative to the U.S. label (censoring). Survival analyses were used to assess on-label persistence from the start of the maintenance phase. At 12, 18, and 24 months after the start of the maintenance phase, respectively, on-label persistence was 190%, 180%, and 179% more likely on guselkumab versus SC TNFi; 78%, 87%, and 91% more likely on guselkumab versus SC IL-17i; and 187%, 199%, and 193% more likely on guselkumab versus apremilast (all p < 0.001). Patients experiencing suboptimal outcomes with other psoriasis-indicated advanced therapies achieved higher on-label persistence after switching to guselkumab, raising the potential for improved disease control relative to other treatment options.

Ethics of incomplete disclosure in delusional infestation

To hell with toxic masculinity?: a case for retaining a debated concept

This article contributes to the literature on men and masculinities that debates the relative importance and definition of the concept of toxic masculinity. We argue that, despite some well-developed critiques, the concept retains potential analytic usefulness for scholars. We discuss toxic masculinity, including the genesis and evolution in scholarly thinking about this concept as an inherent trait, its overlaps and distinctions to Raewyn Connell’s prominent conceptualization of hegemonic masculinity, its use as an analytical tool in masculinity research and recent discussions of a digital form of toxic masculinity in the post-#MeToo era. We propose that a significant difference between hegemonic masculinity and toxic masculinity concerns that the former is achieved and practised consensually rather than simply through violence, whereas toxic masculinity is perpetuated coercively and violently towards others. Although hegemonic masculinity is harmful as it legitimates gender inequality, toxic masculinity, in its enactment of misogyny and violence, can be seen and used as part of a conceptual toolbox to understand and analyse men’s extremely harmful behaviours. Thus, we contend that the concept of toxic masculinity can be adopted as supplementary to the concept of hegemonic masculinity, and/or be seen as a radicalized product of the practice of hegemonic masculinity.

Examining the frequency, severity and associated factors of burnout in Nebraska physical therapists

Recognizing the adverse effects of burnout on clinician well-being and patient care, there has been a surge in national interest in this subject. However, within the physical therapy profession, the extent of burnout has not been as deeply examined. This study aimed to 1) describe the frequency and severity of burnout of Nebraska physical therapists using the Maslach Burnout Inventory and 2) explore potential associations of burnout with sociodemographic and work environment characteristics. Using a cross-sectional design, 2057 licensed physical therapists in Nebraska were invited to complete a survey that included the Maslach Burnout Inventory, demographic information, work environment factors, and stressors. Burnout profiles were generated based on Maslach Burnout Inventory subscale scores and scores were compared to previously established cutoffs. Associations between burnout and sociodemographic and work environment factors were analyzed, and key stressors for each burnout profile were identified. The overall response rate was 23.5%. Approximately half of respondents exhibited engagement, while the remainder experienced at least one dimension of burnout, with 9.9% displaying a full burnout profile. Work environment factors, such as workload, autonomy, flexibility, time off, ethics, supervisor and coworker support, and professional judgment, contributed more significantly ( p  < .001) to burnout than sociodemographic characteristics ( p  < .05). The top stressors among participants with burnout were workload/productivity standards, hours worked per week, and student loan debt. These findings suggest that burnout, driven by emotional exhaustion, is a concern for Nebraska physical therapists. Addressing modifiable work environment factors could help reduce burnout and enhance workforce well-being.

Use of immersive virtual reality to explore visual search behaviour in individuals with visuospatial neglect after stroke

Visuospatial neglect (VSN) is a common post-stroke disorder characterized by impaired attention toward the contralesional hemispace, affecting interaction with the environment. Traditional assessments (e.g., pen-and-paper tests) may not detect subtle deficits in visual search behaviour, particularly in complex, dynamic settings. This study introduces an immersive virtual reality (VR) visual search task designed to assess visual search behaviour across peri- and extra-personal spaces. By integrating eye-and-head tracking, we aimed to characterize search behaviour and evaluate group differences among individuals with stroke with VSN (VSN+, n  = 11), those without VSN (VSN-, n  = 10), and healthy controls (HC, n  = 11). Additionally, we examined how task parameters (target position, spatial context, and difficulty) influenced search behaviour. Results show that VSN+ exhibited least efficient search strategies, with longer search times than VSN- and HC and more extended search paths than HC. Notably, VSN- also demonstrated visual search inefficiencies, suggesting that conventional assessments may overlook subtle visuospatial impairments. Search deficits were most pronounced in extra-personal space and under increased task demands. Despite a limited sample size, these findings highlight the potential of VR-tasks to characterize visual search behaviour. Further research on larger, more diverse samples is needed to evaluate its potential diagnostic utility.