Citations

Abstract Purpose : Inclusive design seeks to ensure that digital health interventions (DHIs) are accessible, acceptable, and useful for older adults by addressing functional, health-related, and socio-cultural needs. This study aimed to identify factors influencing the inclusivity of DHIs for older adults and to compare perspectives derived from the literature, expert interviews, and a focus group with older adults. By triangulating these perspectives, we sought to establish a common set of factors to inform inclusive design guidelines for DHIs targeting older adults. Methods : Inclusive design criteria were identified and triangulated using three complementary sources: a scoping literature review, semi-structured expert interviews, and a focus group with older adults. Convergences and divergences across these sources were analyzed to determine shared and context-specific priorities for inclusive DHI design. Results : Older adults emphasized the importance of emotional reassurance, analog alternatives, and personal contact with healthcare professionals to reduce anxiety and strengthen feelings of safety and trust. Experts highlighted healthcare system integration, co-design processes, regulatory compliance, sustainable financing models, and ethical considerations such as privacy protection and the avoidance of stigmatization. The literature most frequently emphasized equity-related factors, including affordability and insurance coverage, interoperability across devices and platforms, and tailoring content to individual needs. Across all three sources, there was strong convergence regarding the importance of usability, accessibility, personalization, and user support. Conclusions : The findings demonstrate that inclusive DHI design for older adults requires attention not only to usability and accessibility, but also to emotional, ethical, and systemic dimensions. The convergence across literature, expert, and user perspectives suggests that usability, accessibility, personalization, and ongoing user support constitute foundational requirements for inclusive design guidelines for DHIs aimed at older adults.

ABSTRACT Context effects are ubiquitous across sensory systems and reflect a general encoding principle for both simple and complex stimuli. One simple context effect, contraction bias, manifests in two-interval perception tasks as a bias of the perceived magnitude of the first stimulus toward the center of the overall magnitude range. The underlying cause of contraction bias is unclear. One explanation is that a listener’s magnitude estimate of the first stimulus is combined with a perceptual anchor, usually the mean stimulus magnitude, biasing it toward the anchor (sensory model). An alternative explanation is that a listener’s response criterion shifts, based on the magnitude of the stimulus pair, relative to the mean magnitude of the stimuli range (decision model). Two pitch-discrimination experiments were performed to test these hypotheses in the auditory domain. The first was a forced-choice discrimination task, where listeners were asked to identify the higher or lower tone in a pair. The second was a same-different task where listeners indicated whether or not the two tones in a pair differed in frequency. Contraction bias was observed in the higher-lower discrimination task, even after extensive perceptual training with feedback. In contrast, no contraction bias was observed in the same-different task. Computational models of the sensory and decision hypotheses were fit to data from both experiments. The sensory model captured the pattern of results the higher-lower experiment but erroneously predicted a contraction bias in the same-different task. The decision model produced similar predictions to the sensory model in the higher-lower task but correctly predicted no contraction bias in the same-different task, and produced lower prediction errors and more stable parameter estimates in both paradigms. Overall, the results suggest that the underlying nature of the contraction bias may reflect decision, rather than sensory, biases based on the context. AUTHOR SUMMARY Every day, people combine experiential knowledge of the world and incoming sensory information to assess their environment. Interestingly, the environment itself can substantially alter how incoming sensory information is processed and perceived. These so-called context effects occur in all sensory modalities. Here, we examine one such context effect, known as “contraction bias”, in a simple pitch-discrimination task. Prior work argued that the contraction bias occurs because observers make biased estimates of stimulus magnitudes due to the influence of recent stimulus history. By combining behavioral data and computational modeling, we offer a different explanation, more consistent with the available data, which posits that the bias can be accounted for by systematic shifts in observers’ response strategies with changes in relative stimulus magnitudes. The results shed light onto how humans compare and process sensory features within their environment.

Background Evidence to guide the optimal timing of antiplatelet and oral anticoagulants (OACs) therapy after hemorrhagic infarction (HI) versus parenchymal hematoma (PH) is limited and inconsistent, leading to substantial variation in practice. This study's goal was to study the practice pattern and compare clinical outcomes associated with early‐versus‐delayed initiation of antiplatelet/OACs after hemorrhagic transformation (HT). Methods This multicenter, retrospective, cross‐sectional study included patients with acute ischemic stroke and HT. Patients with an HI or PH were categorized by HT to antithrombotic initiation time, and their outcomes—30‐day HT exacerbation, composite outcomes of recurrent stroke/systemic emboli, 90‐day vascular death, and functional outcomes—were compared. Results Of 748 patients, 496 received antiplatelets, and 252 received OACs after HT. The median HT‐to‐antiplatelet time was significantly shorter after HI than PH (1 [interquartile range, 0–2] versus 3 [interquartile range, 1–5] days; P <0.001). There were no statistically significant differences in HT exacerbation and composite outcomes (30‐day), as well as vascular death and unfavorable functional outcomes (90‐day), between patients who received same‐day, early (HI, <1 day; PH, <3 days), or late (HI, >1 day; PH, >3 days) antiplatelets after either HI or PH. Among patients on OACs, those with HI had shorter median HT‐to‐OAC time than PH (7 [interquartile range, 2–15] versus 15 [interquartile range, 7–32] days; P <0.001). Although HT exacerbation rates (30‐day) were comparable between early (HI, <7 days; PH, <15 days) and late (HI, >7 days; PH, >15 days) OAC initiation after either HI or PH, late initiation after PH was accompanied by higher rates of composite outcomes (30‐day) than early initiation (20.7% versus 3%; P =0.044). Regression models adjusted for demographics, National Institutes of Health Stroke Scale, and stroke severity showed no statistically significant association between early initiation of antiplatelets or OACs with HT exacerbation risk. Conclusions Our study found no statistically significant difference in HT exacerbation between early and late initiation of antiplatelets or OACs among patients with HI/PH, while prolonged delay among patients with PH were accompanied by increased systemic thromboembolic events. Although these findings offer preliminary clinical insight, prospective studies are needed.

SUMMARY This protocol describes a standardized and reproducible minimally invasive approach for establishing mouse models of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and osteoradionecrosis of the jaw (ORNJ). The method combines a unified low-trauma oral surgical procedure with disease-specific injury induction strategies to generate robust and clinically relevant models of jaw osteonecrosis. For BRONJ, systemic zoledronic acid administration is coupled with mandibular first molar extraction using tape-assisted mouth opening and customized bent micro-forceps, minimizing soft tissue damage and reducing procedural variability. For ORNJ, a customized lead-shielding platform enables precise, noninvasive mandible-targeted irradiation, producing reproducible bone injury while limiting off-target radiation exposure. Together, these complementary models provide a consistent and minimally invasive framework for investigating jaw osteonecrosis arising from distinct etiologies. The protocol supports comprehensive downstream analyses, including micro-computed tomography, histology, and immunofluorescence, and facilitates mechanistic studies of disease pathogenesis, bone regeneration, and therapeutic intervention.

Abstract Provided herein are novel 6,5-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse, and headaches, and processes for preparing such compounds.

Peritoneal coccidioidomycosis is a rare, disseminated manifestation of Coccidioides infection with limited representation in the literature. We report 37 proven or probable cases from a single institution, including 12 patients (32%) with immunosuppression. Thirty-six patients received antifungal therapy, all of whom demonstrated clinical response. Among 11 (29.7%) patients who completed and stopped therapy after a median duration of 26 months, 2 (5%) experienced a relapse and were successfully retreated. Nine patients (24%) had no known relapse. Thirteen patients (35%) required modification of antifungal regimens, primarily due to azole adverse effects. Treatment approaches and median duration of therapy (57 months) were similar between immunosuppressed and non-immunosuppressed groups. No deaths were attributable to infection. Overall, outcomes were favorable, with strong clinical responses to azole therapy. Patients without identifiable immunologic deficits or additional sites of dissemination, when managed with antifungal therapy and close clinical, radiologic, and serologic monitoring, may achieve good prognosis, particularly when indefinite azole therapy is not feasible.

ABSTRACT Background Inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPNs) share chronic inflammation and immune dysregulation. Aim We evaluated the incidence of MPNs among patients with IBD and clinical outcomes of IBD–MPN coexistence. Methods Two retrospective cohort analyses were conducted using the TriNetX database. First, adults with ulcerative colitis (UC) or Crohn's disease (CD) were compared with matched non‐IBD controls to estimate incident MPN risk. A coexistence second analysis included patients with UC or CD who developed MPNs and then were matched to IBD without MPN controls to assess 5‐year outcomes, including IBD‐related complications, surgical interventions, colorectal cancer (CRC) and primary sclerosing cholangitis (PSC). Medication subgroup analyses were performed to evaluate associations with MPN risk. Results After matching, 3873 patients with UC–MPN and 3474 patients with CD–MPN were included. Compared with matched non‐IBD controls, incident MPN risk was higher in UC (HR 1.60, p = 0.01) and CD (HR 1.56, p < 0.001). In CD, MPN coexistence was associated with higher risks of CRC (HR 1.52, p = 0.012), intestinal fistula (HR 2.84, p < 0.001), obstruction (HR 2.05, p < 0.001), perforation (HR 2.37, p < 0.001), small bowel resection (HR 3.69, p < 0.001) and colectomy (HR 2.10, p < 0.001). In UC, MPN coexistence was associated with higher risks of CRC (HR 1.50, p = 0.001), PSC (HR 1.75, p = 0.03) and pouchitis (HR 1.68, p = 0.003). Exposure to thiopurines (HR 1.28, p < 0.001) was associated with increased MPN risk, whereas TNF, IL‐23 and JAK inhibitors were not. Conclusions IBD is associated with increased MPN risk, and IBD–MPNs coexistence is associated with worse IBD‐related complications and malignancy risk.

Abstract INTRODUCTION Neurodegenerative diseases often involve overlapping alpha‐synuclein (asyn), amyloid beta, and tau proteinopathies, yet the mechanisms, impact, and directionality of their interactions remain unclear. METHODS We induced brain‐wide neuronal asyn/tau pathologies via viral expression of wild‐type asyn, mutant asyn E46K , mutant tau A152T , or both asyn E46K /tau A152T in adult amyloidosis knock‐in mice and controls, either post‐plaque deposition (6 months old) or pre‐plaque (3 months old). Open‐field behavior was assessed baseline and 3 and 6 months post‐transduction, followed by neuropathology and neuroinflammation analyses. RESULTS Post‐plaque induction in amyloid mice increased asyn/tau total and phosphorylated levels and exacerbated amyloid‐related hyperlocomotion/anxiety. Pre‐plaque induction produced robust phosphorylated pathologies irrespective of amyloid, while causing similar amyloid‐dependent behavioral synergy. Tau pathology drove LGALS3 + inflammatory glial responses in white‐matter fibers. DISCUSSION Amyloid context gates vulnerability, with certain synergies manifesting across stages. White‐matter gliosis is a novel mechanism of tau A152T risk. Together, our data argue for the development of stage‐aware, multitarget interventions and biomarkers.

Abstract Background Minimally invasive surgery (MIS) improved outcomes in hepatopancreatobiliary (HPB) cases, yet adoption is slowed by technical complexity and steep learning curves. This retrospective review sought to characterize MIS training variations across three fellowship pathways: HPB, complex general surgical oncology (CGSO), and transplant (TXP). Methods We analyzed anonymized Fellowship Council case logs (2014-2023) for 146 HPB, 55 CGSO, and 51 TXP fellows seeking AHPBA certification. Procedures were categorized by platform and type. Results HPB fellows logged significantly more total robotic cases (HPB: 12.5, CGSO: 8.5, TXP: 1.0, p <0.01), including robotic pancreaticoduodenectomies (HPB 4.4, CGSO 3.0, TXP 0.2, p <0.01) and robotic distal pancreatectomies (HPB 3.8, CGSO 3.2, TXP 0.6, p <0.01). Although TXP fellows performed more open major liver resections (HPB 24.0, CGSO 24.7, TXP 35.2, p <0.01), robotic anatomic (HPB 2.1, CGSO 1.5, TXP 0.03, p 0.01) and non-anatomic liver resections (HPB 1.8, CGSO 1.4, TXP 0.2, p <0.01) were highest among HPB fellows. Discussion Meaningful differences in MIS operative exposure exist across training pathways, with TXP fellows trailing significantly in robotic experience. These findings highlight a critical need for standardized MIS curricula to ensure technical proficiency across all HPB surgery pipelines.