ABSTRACT On freelance platforms, where value is co‐created through the joint effort of freelancers and customers, contract design plays a central managerial role. A key strategic choice concerns price timing: whether prices are set before collaboration begins (early pricing) or after the co‐creation process is completed (late pricing). We develop a game‐theoretic model comparing these contractual regimes. Under rational expectations, early pricing functions as a commitment device that coordinates mutual high effort, leading to superior product quality and welfare relative to late pricing. We test these predictions in a controlled laboratory experiment. Consistent with theory, early pricing leads freelancers to charge higher prices and earn greater profits than under late pricing. However, contrary to theoretical predictions, early pricing does not increase effort by either party and does not improve product quality or overall welfare. Instead, surplus shifts from customers to freelancers. We interpret this divergence as evidence of a behavioral failure of the commitment mechanism: Freelancers use early prices to signal quality but do not follow through with costly effort. Our findings carry important managerial implications for gig economy platforms. Without complementary reputation or monitoring systems, fixed‐price contracts may enable opportunistic behavior rather than support cooperative value creation.

BackgroundUrothelial carcinoma (UC) is a biologically heterogeneous disease, and current molecular classifications have limited integration into clinical decision‐making. To further pursue precision oncology efforts in UC, we developed a molecular classification framework applicable to transcriptomic and proteomic data from non–muscle‐invasive bladder cancer (NMIBC), muscle‐invasive bladder cancer (MIBC) and urothelial cancer cell lines.MethodsUsing a whole‐transcriptome self‐organised map and regularised semi‐supervised clustering of 4439 bulk NMIBC and MIBC transcriptomes and proteomes, and 33 UC cell lines, we identified three molecular UC clusters. Making use of both in silico and in vitro approaches, we selected promising treatment approaches for each cluster.ResultsThe three developed clusters displayed distinct signatures of mRNA, proteins, biological processes, metabolism and essential driver genes. They also differed in prognosis and machine learning‐predicted treatment vulnerabilities and resistance. High‐risk, stroma‐rich Cluster #1 cancers were predicted to respond to selected cytotoxic drugs, ferroptosis inducers and PARP inhibitors. For the aggressive, fast‐proliferating, immune‐infiltrated Cluster #2 tumours with basal/squamous differentiation, cytotoxic agents and EGFR/ERBB‐ and MEK/ERK‐targeting therapies were proposed. Cluster #3 cancers of predominantly luminal papillary phenotype with scarce stroma and immune infiltration were enriched with NMIBC and low‐risk malignancies. For patients with Cluster #3 tumours, selected epigenetic drugs or EGFR/FGFR inhibitors may represent attractive treatment options.ConclusionsOur novel molecular taxonomy holds promise as a practical framework for patient risk stratification and clinical trials in UC. Our molecular classification scheme may facilitate personalised transcriptome‐ and proteome‐based risk assessment and clinical trial design for the development of various therapeutics.key pointsWe developed three UC clusters, applicable for MIBC and NMIBC, which were validated using transcriptomic- and proteomic datasets.Publically available UC cell lines were assigned to the clusters, to have in vitro models representing each cluster.The clusters differ in molecular and biological signatures, with distinct prognostic and therapeutic characteristics.

Mental health challenges are a significant concern among students and trainees in medical fields worldwide, including Japan, where high psychological distress is prevalent. This pilot study examined the feasibility and impact of a 6-day creative arts program designed for Japanese medical and international graduate students. A total of 14 students provided informed consent to participate in the study. Employing a convergent mixed-methods design, quantitative and qualitative data were collected and analyzed independently. Students completed the Comprehensive Inventory of Thriving (CIT) before and after the program to assess changes in psychological well-being. Pre-post differences were examined using paired t-tests. Qualitative data collection included post-program surveys, semi-structured interviews, and six-month follow-up interviews. We conducted thematic analysis to identify key patterns in student experiences. We then examined whether changes in CIT scores correlated with the frequency of qualitative codes to identify potential points of convergence between the two datasets. Thirteen students completed all major components of the study, with an average attendance of 5.2 out of 6 sessions. CIT scores significantly increased from before (M = 198.0, SD = 29.9) to after completing the program (M = 217.3, SD = 20.2), t(12) = -4.89, p = .0004, indicating a significant increase in thriving. Thematic analysis yielded three core themes: (1) Discovery through the underexplored parts of self and surroundings, (2) Rapid community bonding through inspiration, and (3) Creativity as a disruption to stress. Six-month follow-up interviews revealed additional themes related to enduring impact from the intervention: Applying creative insights into everyday life and mindsets. Through the convergent mixed-methods analysis, one pairing reached statistical significance: the change over time in the CIT subscore ‘Meaning’ was strongly correlated with the qualitative code “Out of the ordinary” (r = + 0.868), suggesting that increases in participants’ sense of meaning were strongly associated with the frequency of experiences that felt “Out of the ordinary” during the creativity program. The findings suggest that a creative arts program for medical students is both feasible and effective in promoting well-being, enhancing stress management skills, and deepening self-awareness. The program shows promise for integration into medical education to support students’ holistic development and mental health.

The increasing size of electrophysiological datasets has heightened the need for quality metrics that automatically reject neurons whose activity was recorded with low sensitivity or specificity. One key approach estimates artifactual contamination by assuming that each neuron has a refractory period (RP), a brief time interval following each action potential when further activity cannot occur. However, existing methods cannot be applied without prior knowledge of the neurons’ RP durations, limiting their usefulness in datasets that include neurons from brain regions or species in which RP durations have not been systematically characterized. Here, we find that neurons in some brain regions (thalamus) and species (macaque) have shorter RP durations than commonly assumed, and we introduce a new metric, the Sliding Refractory Period metric, which is robust to variation in a neuron’s RP duration without tuning. We validate the method using simulations, demonstrating that it improves acceptance of uncontaminated spike trains with short or long RP durations while still rejecting contaminated ones. Moreover, by incorporating Poisson statistics into the calculation, the method also improves on prior work by allowing the user to approximately control the false acceptance rate. Our new metric improves quantification of contamination in electrophysiological recordings and enables application of a single tuning-free quality metric to data recorded from diverse brain regions and species.

ABSTRACT Marine fishery management systems are experiencing unprecedented pressure from climate change. Prior research has identified adaptive traits that, when present in a management system, can promote effective responses to these changes and minimise negative outcomes for fish and fishery systems. Understanding the extent to which managers identify these traits as important and actively influencing management can identify gaps and opportunities for putting this theory into practice. To address this, we surveyed 321 fishery management professionals and scientists across all eight U.S. fisheries management regions. Questions focused on 16 adaptive traits related to topics such as systemic flexibility, opportunities for knowledge exchange and agency to act. For each trait, at least 68% of respondents identified the trait as important for supporting adaptation in their region. The two traits relating to fishermen and management's ability to learn and innovate were the most widely identified as important for adaptation. However, when asked about the role of management in influencing these traits, positive perceptions dropped by about 20% (at most 44% agreement per trait). Perceived importance and influence of adaptive traits significantly varied by the education level of survey respondents, with higher education levels correlating with higher perceived trait importance. Mapping this mismatch between perceived importance of adaptive traits and the ability of management to address them provides a blueprint for areas where a shared understanding of climate‐ready fishery goals would benefit both fishermen and regulators under future change.

Visual processing undergoes rapid refinement in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-III). VEP components were characterized by P1 amplitude, latency, and trial-to-trial variability in latency. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both timepoints, showing age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both timepoints was significantly associated with higher cognitive and language scores at 24 months. Variability in visual cortical response timing was the strongest neural correlate of developmental skills in infancy. These findings suggest that temporal variability in early neural responses may reflect adaptive sensory circuit flexibility rather than inefficiency, potentially facilitating experience-dependent tuning of visual pathways. VEPs offer a mechanistic window into how developing sensory systems scaffold individual differences in early developmental trajectories.

BackgroundTreponema pallidum subspecies pallidum causes systemic syphilis, exclusively infects humans in nature and can persist for decades in the absence of treatment despite generating robust adaptive immune responses. The T. pallidum repeat (Tpr) family of outer membrane proteins are immunogenic and are implicated in immune evasion, indicating them to be virulence factors displayed on the spirochete surface. Long-term survival of T. pallidum is largely attributed to sparse surface-exposed outer membrane proteins and antigenic variation in the major surface protein TprK through phase variation. This mechanism has been studied for decades; however, the functions of Tprs of this extracellular pathogen are not yet experimentally determined.MethodsIn this study, the localization and functional roles of TprD and TprK were investigated using a heterologous spirochete expression system and a gain-of-function approach by employing a non-infectious, non-adherent Borrelia burgdorferi B314 strain. Opsonophagocytosis of engineered B. burgdorferi as well as of T. pallidum Nichols and SS14 strains was evaluated using J774A.1 macrophages and mouse antibodies raised against predicted surface-exposed loops of TprD and TprK using IncuCyte system.ResultsBoth TprD and TprK were found to be surface exposed in engineered B. burgdorferi and infectious T. pallidum strains. Expression of these proteins conferred adherence to several mammalian cell lines in vitro. In addition, antibodies we generated recognized TprD and TprK on the surface of spirochetes and significantly enhanced macrophage-mediated opsonophagocytosis.ConclusionOur findings here demonstrate that TprD and TprK function as T. pallidum adhesins that are also targets of opsonic antibodies. These Tprs likely facilitate tissue colonization during infection, while also rendering the pathogen susceptible to immune clearance. Our findings support inclusion of TprD and TprK as components of a multivalent vaccine against syphilis.

Augmented reality (AR) provides real-time three-dimensional visualization for spinal instrumentation, though its role in spinopelvic stabilization remains limited. While AR-assisted pedicle and S2 alar-iliac screw placement has been reported, AR guidance for a dual-iliac quad-rod construct in spinopelvic dissociation has not. We describe AR-assisted minimally invasive placement of L4-L5 pedicle screws and bilateral iliac screws using intraoperative three-dimensional planning. Fixation was completed without complications and remained stable at last follow-up. This case suggests AR navigation may support accurate and efficient execution of complex minimally invasive spinopelvic fixation.

Abstract We develop a probabilistic analogue of the Adaptive Eigenspace Inversion (AEI) method, an algorithm for the adapting regularisation terms towards the recovery of sharp interfaces, from the perspective of Bayesian inverse problems to enable the quantification of uncertainties in the reconstructions. We show that the adaptations of the regularisation terms in AEI is analogous to adapting the prior distributions in a sequence of Bayesian inverse problems. We present a theoretical result, showing that appropriate convergence of the AEI loop will lead to convergence of the resulting Bayesian posteriors in a Wasserstein distance. Furthermore, we present some numerical experiments to demonstrate the performance and wide applicability of the Bayesian extension of AEI in both linear and nonlinear inverse problems. In particular, we observe in our experiments that the posterior means recover sharp edges in the unknown fields, and the posterior variances are largely concentrated around sharp interfaces, a feature that is also observed in other models for recovery of piecewise constant fields.

Learning new tasks requires the brain to reshape the flow of neural activity, but how these changes arise from dynamic neural connectivity remains unclear. Here, we used two-photon photostimulation and calcium imaging to map learning-related changes in connectivity in layer 2/3 of mouse motor cortex, induced by learning of an optical brain-computer interface (BCI) task. Mice rapidly (within minutes) learned to change activity in a conditioned neuron to earn rewards. Activity changes were sparse; the conditioned neuron increased activity more than surrounding neurons. Mapping connectivity before and after learning revealed changes in motor cortex connectivity, enriched in neurons that were active before trial initiation, analogous to motor cortex populations that are active preceding movement. Motor cortex plasticity reroutes preparatory activity to neurons that are active later and control the conditioned neuron. Our findings show how rapid learning can be achieved through structured changes in motor cortex connectivity.