Wilson's disease (WD) features aberrant hepatic copper accumulation with oxidative and inflammatory injury. Single-target probes responsive to Cu2+ or reactive oxygen species alone have limited specificity for WD imaging in complex biological environments. Here, we report a near-infrared AND logic fluorescent probe, namely DHU-LP, for the simultaneous detection of Cu2+ and hypochlorous acid (HOCl) to enable specific WD imaging. DHU-LP, constructed by integrating an Oxazine 1 fluorophore with a bis(pyridin-2-ylmethyl)amine Cu2+-binding unit, exhibited a pronounced turn-on response at 669 nm only when both Cu2+ and HOCl were present, but showed negligible fluorescence in the presence of either analyte alone. Mechanistic studies confirmed that Cu2+ coordination promoted HOCl-triggered probe activation. DHU-LP displayed good sensitivity and selectivity for the Cu2+/HOCl combination, low cytotoxicity, and favorable liver-targeting capability. In cellular imaging, the probe differentiated WD patient-derived fibroblasts from normal ones under conditions via combined Cu2+/HOCl stimulation signal. In vivo imaging further showed a marked fluorescence response in the liver of WD mice, whereas negligible signal was observed in wild-type mice. This work provides a dual-analyte fluorescent probe for WD-related imaging and highlights the utility of AND logic design for improving imaging specificity in metal-overload-associated disease models.
Atlantic cod possess a unique immune system due to the loss of the MHC II antigen-presenting system and an extreme expansion of the MHC class I repertoire. Additional modifications are demonstrated within the innate immune system with losses and expansions of Toll-like receptor (TLR) genes. While Atlantic cod has lost its mammalian orthologs for plasma membrane localized TLRs, such as TLR1/6 and TLR2, it has expanded its intracellular TLRs including TLR7, -8, and -9. It has been hypothesized that teleost-specific TLR1-family related members TLR14 and TLR25 localize at the plasma membrane with the potential function to recognize bacterial surface components, compensating for the loss of cell surface TLRs. In this study, we have investigated the intracellular localization and function of Atlantic cod TLR14 and TLR25 using super-resolution microscopy in an Atlantic cod cell line and primary cells. Our results show that these TLRs localize to endolysosomes, and colocalize with LysoTracker, Rab5, and Rab7. Interestingly, TLR14 is also present at the plasma membrane, suggesting a function at the cell surface. In cells infected with Francisella noatunensis subsp. noatunensis (Fnn), these TLRs colocalize with the internalized bacteria. While the localization of both TLR14 and TLR25 to late endosomal compartments increases upon infection with Fnn, only TLR25 relocates to the perinuclear region and triggers up-regulation of the pro-inflammatory cytokines IL-6 and IL-18. Overall, our findings provide novel insight into the function of teleost-specific TLRs in Atlantic cod which indicates that these TLRs employ different strategies for microbial detection and activation.
Inflammation is a core driver of the initiation and progression of multiple diseases. Inflamed microenvironments are typically characterized by hypoxia and abnormally elevated viscosity. Precise monitoring of nitroreductase (NTR) activity and microenvironmental viscosity is essential for mechanistic studies, early diagnosis and condition assessment of inflammatory diseases. Herein, a dual-responsive fluorescent probe (HBT-QN-2) that simultaneously responds to NTR and microenvironmental viscosity was successfully designed and synthesized. The probe is inherently fluorescence-quenched but can be specifically reduced by NTR to generate a distinct orange-red fluorescence signal at 582 nm. Moreover, the fluorescence intensity is further enhanced with the increase of environmental viscosity, enabling monitoring of both NTR activity and viscosity changes. HBT-QN-2 exhibits excellent specificity and high sensitivity toward NTR, with a low detection limit of 5.7 × 10-4 U mL-1. Cell imaging experiments confirm that HBT-QN-2 enables real-time monitoring of endogenous NTR levels under varying hypoxic conditions and responds to increased viscosity in LPS-induced inflamed cells, demonstrating the potential for identifying inflammation related diseases.
Artificial intelligence (AI) is rapidly integrating into health professions education and clinical practice, creating significant opportunities alongside new ethical challenges. Although current international and professional guidance establishes essential values, it offers limited direction for how clinicians, educators, learners, and institutions should act in routine educational, research, and clinical contexts. The CARE-AI (Contextual, Accountable, Responsible, and Equitable Artificial Intelligence) project responds to this practice-level gap by articulating guidance that moves beyond values toward professional accountability and equity, with explicit attention to educational, research, and clinical practice contexts. The study objective was to develop and validate a consensus-based, actionable framework of principles to guide responsible AI use across health professions education, research, and clinical care. We conducted a 3-phase modified Delphi consensus study, reported in accordance with the Accurate Consensus Reporting Document. Phase 1 involved 2 international professional meetings and 3 purposively sampled focus groups (AI or technology, health professions education, and ethics or professionalism) to adapt and refine draft principles using an exploratory qualitative approach. Phase 2 used an online survey with a 5-point importance scale and prespecified consensus criteria (inclusion ≥70%: high ratings; exclusion ≥70%: low ratings). Phase 3 used include, exclude, or undecided voting on revised principles. Quantitative thresholds determined consensus. Qualitative free-text comments informed iterative refinement. Participants represented diverse communities of practice across health professions education, clinical care, patient partners, ethics, and digital health, spanning multiple professional roles and training levels. Across all phases, 303 unique participants contributed to the study. Phase 1 focus groups (n=61) provided early insight and direction. In phase 2, the first Delphi survey round, 242 participants initiated the survey, with 120 (49.6%) participants completing it. In phase 3, the second Delphi survey round, 103 participants were invited based on expressed interest at the end of the first round; 78 participants initiated the survey and 75 completed it (75/78, 96.2% of starters). In phase 2, of the 61 statements, 58 (95%) met the inclusion criteria, and participants submitted 1887 comments (697 were content rich), prompting clearer accountability language, stronger equity commitments, and more usable wording. In phase 3, all 10 principles and their statements met the inclusion criteria. Participants contributed 224 comments (179 were content rich) that informed final refinements. Endorsement was near unanimous: 96% (72/75) agreed or strongly agreed that the framework clearly defined professionalism expectations for AI to meet educational, technological, and ethical needs in the health professions. The Health CARE-AI Framework, with its preamble and 10 principles, articulates actionable, consensus-validated guidance that moves from values to competence, into professional accountability, and toward structural commitments to equity. Paired with a companion implementation guide and toolkit, the framework is intended to support use across education, research, and clinical settings.
Objective: The dispatch of a locum doctor (DLD) system is an important aspect of the clinical settings in remote islands, where securing doctors is a major challenge. This study investigated the conditions associated with DLD requests and observed an association between DLD requests and several regional factors in rural clinics on remote islands in Japan. Materials and Methods: Questionnaires regarding DLD requests were mailed to all rural clinics on remote islands managed under the rural plans of the prefectural governments of Japan in December 2022. The regional factors assessed included population size (large remote islands: population ≥1,000 people), doctor staffing on islands (single or multiple doctors within an island), and distance between rural clinics and the nearest core hospitals, which are designated at the prefectural level of Japan to support and collaborate with rural clinics (long distance, ≥25 km). The association between DLD requests and regional characteristics was analyzed with and without DLD requests. Results: Of the 72 rural clinics (32%) that responded completely to the questionnaire, 27 (38%) had made DLD requests. In the logistic regression analysis, DLD requests were positively associated with long distances from core hospitals (odds ratio [OR]=3.82, 95% confidence interval [CI]: 1.26-11.6) and the presence of a single doctor on the island (OR=5.24, 95% CI: 1.73-15.9). Conclusion: These results indicate that DLD requests may be more frequent from remote islands, which were far from core hospitals, and those staffed by a single doctor. Measures based on these results may contribute to the development of efficient medical support systems for remote islands in Japan.
This study aimed to investigate the effects of WeChat-based multidisciplinary team care (WMDT) in patients with ischemic stroke. Patients with ischemic stroke who received WMDT care (N = 89) or routine care (N = 102) were consecutively included in this prospective cohort study. The modified Rankin scale (mRS), Barthel index, EuroQol Five-Dimensions 3-Level Questionnaire (EQ-5D-3L), and patient satisfaction were evaluated at weeks 0 (at discharge), 4, and 8. The mRS score (1.6 ± 1.0 vs. 1.9 ± 1.1, p = 0.060) and percentage of patients with an mRS score > 2 (19.8% vs. 29.5%, p = 0.131) both tended to be lower in the WMDT care group than in the routine care group at week 8. The Barthel index was significantly greater (62.6 ± 13.9 vs. 57.2 ± 13.5, p = 0.009), but the EQ-5D-3L score was significantly lower (7.9 ± 1.6 vs. 8.5 ± 1.8, p = 0.022) in the WMDT care group than in the routine care group at week 8. In addition, the overall satisfaction rate was significantly greater in the WMDT care group than in the routine care group (83.7% vs. 70.5%, p = 0.036). WMDT care demonstrates potential benefits in functional recovery and significantly improves quality of life and patient satisfaction in patients with ischemic stroke.
Tissue repair and regeneration represent multifaceted processes involving a coordinated interplay of diverse cell types, growth factors, and cytokines. Following tissue injury, innate immune cells serve as the primary cellular responders that infiltrate the damaged microenvironment, clear cellular debris, and undergo phenotype transitions essential for establishing a proregenerative environment. To facilitate functional recovery, three-dimensional scaffolds are conventionally used to give physical signals and structural support. However, these constructs frequently encounter barriers in host-scaffold integration, potential material cytotoxicity, and the induction of adverse chronic foreign body responses (e.g., chronic inflammation), which continue to hinder their successful clinical translation. In this regard, natural polysaccharides, including hyaluronic acid, alginate, and mannans, represent promising biomaterials for multifunctional scaffold engineering due to their extracellular matrix (ECM)-mimetic properties, high biocompatibility, rapid degradation, and tunable physicochemical characteristics. Moreover, the unique sugar moieties inherent to these polysaccharides can function as pathogen-associated molecular patterns and directly interact with pattern recognition receptors expressed on host immune cells. These receptor-ligand interactions trigger intracellular signaling cascades, driving the secretion of downstream cytokines and chemokines, guiding immune cells toward proregenerative phenotypes, and remodeling the ECM to achieve functional tissue repair. In this review, the dual functionality of natural polysaccharides in tissue engineering is described, emphasizing their role as physical supports and active immunomodulatory platforms in regenerative medicine. We critically evaluate the immuno-active motifs within natural polysaccharides, reveal their receptor-mediated interactions with immune cell subsets, and highlight recently reported polysaccharide constructs across distinct tissue targets. We also outline engineering design principles to modulate the chemical, structural, and biophysical properties of immune-active scaffolds. Furthermore, we explore the clinical progress of these scaffolds, addressing current milestones alongside ongoing regulatory and manufacturing challenges. This review provides key design criteria to guide the rational development of next-generation, immuno-instructive polysaccharide constructs for immune-mediated tissue regeneration.
The concept of congenital anal stenosis remains poorly defined, encompassing anatomically distinct conditions that may differ in pathogenesis and management. This study aimed to re-evaluate the current concept of congenital anal stenosis through a systematic review and histological examination of representative cases. We conducted a systematic review of English-language publications to assess clinical characteristics, treatment methods, and outcomes in patients diagnosed with congenital anal stenosis. In addition, we performed histological analysis of surgical specimens obtained from two representative surgical cases. Among 28 identified studies involving 70 cases, 50 cases without Currarino syndrome responded well to bougie dilatation or minor anoplasty. In contrast, 20 cases (28.6%) associated with Currarino syndrome showed poor response to conservative treatment and frequently required treatment of associated presacral lesions or more invasive procedures. Histopathological analysis of two representative surgical cases revealed dense fibrosis located between the dentate line and the anal verge, supporting the possibility that anal membranous stenosis can occur as a distinct skin-level lesion. Our findings support reconsidering the terminology of congenital anal stenosis and suggest that congenital skin-level anal stenosis should be distinguished from anorectal stenosis. Further anatomical and histopathological studies are needed to validate this framework.
In early 2024, Lao People's Democratic Republic experienced a surge in dengue cases approaching levels of its 2013 epidemic, underscoring the persistent threat of dengue during the monsoon season. Although awareness of preventive behaviours is high, inconsistent adoption has limited their effectiveness. In response, the Ministry of Health, in collaboration with the World Health Organization, implemented an innovative, humour-driven risk communication and community engagement (RCCE) campaign targeting individuals who perceived dengue as a routine health concern. To capture attention and increase message retention, the April to September campaign employed an actor dressed as a giant mosquito who deliberately and humorously interrupted daily activities. The strategy used pre-tested materials, a strong social media presence, and television and radio to promote mosquito control, symptom recognition and timely medical care for severe dengue. The impact was assessed through nationwide phone and online surveys and social media analytics. The campaign reached almost 2.9 million unique users (68.2% of whom were using the country's most popular social media platform), generating more than 27 million content views and 86 342 interactions. Post-campaign surveys indicated a sharp rise in public concern about dengue (from 21% [42/200] to 56% [224/400], indicating they were "very concerned") and high awareness of key messages, with 81% (324/400) stating they would seek immediate care for severe symptoms. The humour-based approach was rated as appealing or very appealing by 76% (304/400) of respondents, with 90% (360/400) reporting increased likelihood of preventive action. These findings demonstrate that culturally relevant, humour-based RCCE, integrated across digital and traditional media, may be effective in enhancing awareness and shifting perceptions.
Western studies have reported associations between facial wrinkling and chronic obstructive pulmonary disease (COPD), suggesting a shared susceptibility to tissue aging. However, data on Asian populations are limited, and population-specific differences in skin biology may modify these relationships. To investigate the association between facial wrinkle severity and COPD characteristics in Thai patients and to identify independent predictors of wrinkle severity. This cross-sectional study enrolled 93 Thai patients with COPD. Facial wrinkles were assessed using the Daniell grading scale (a validated six-point subjective clinical grading system) and the Antera 3D imaging system (an objective three-dimensional topographic imaging device). Multivariable linear and logistic regression analyses were performed to identify independent predictors of wrinkle severity after adjustment for age, sex, body mass index (BMI), cumulative smoking exposure, occupational sun exposure, and post-bronchodilator FEV1 % predicted. Mean age was 72.6±8.8 years (90.3% male). Severe facial wrinkling, defined as a Daniell score ≥4, was present in 41.9% of the patients. The Daniell grading scale and Antera 3D measurements showed a moderate-to-strong correlation (Spearman's ρ=0.68, p<0.001). In multivariable analyses, age was consistently associated with both objective wrinkle depth (β=0.08; 95% CI: 0.01-0.24; p=0.042) and severe wrinkling (OR=1.15; 95% CI: 1.06-1.23; p<0.001). Higher body mass index was inversely associated with objective wrinkle severity (β=-0.34; 95% CI: -0.65 to -0.03; p=0.031) but not with severe Daniell-grade wrinkling. COPD-related characteristics, including FEV1 % predicted, cumulative smoking exposure, and smoking-related COPD status, showed no significant associations with wrinkle severity after adjustment. Among Thai patients with spirometry-confirmed COPD, no significant association was detected between facial wrinkle severity and the COPD-related characteristics assessed. Age was the most consistent independent predictor of wrinkle severity, while higher BMI showed an inverse association with objective wrinkle measurements only. These findings differ from those reported in Western populations and support population-specific validation before applying facial wrinkling as a cutaneous marker of COPD-related disease burden.
Individual variability shapes how diseases manifest, how patients respond to therapy and how rare phenotypes arise. Conventional experimental approaches obscure variation by averaging which limits mechanistic insight and predictive accuracy. We present a computational framework that builds digital twins of human-induced pluripotent stem cell-derived cardiomyocytes from a single optimized voltage clamp experiment. The framework depends on massive synthetic datasets comprising simulated cells that span broad ionic and electrophysiological ranges. These synthetic data make it possible to control parameters precisely, explore biological variability comprehensively, and train models beyond the limits of experimental data. A neural network trained on synthetic data then inferred biophysical parameters from experimental recordings from live cells, reproducing distinct electrophysiological features. Our study unites computational modeling, data simulation, and learning to enable scalable, precise, individualized cardiac electrophysiology modeling and can be readily extended to any electrically active cell type.
In patients with medically refractory essential tremor, unilateral Gamma Knife radiosurgery (GKS) of the Ventral Intermedius Thalamic nucleus (VIM) is known to improve contralateral tremor with a good safety. Safety of staged bilateral GKS of the VIM has never been strictly evaluated. Our aim was to determine whether staged bilateral VIM-GKS is safe and effective and would avoid side effects, due to bilaterality of the surgery, while providing improvement of tremor impairment. We conducted a prospective, single-arm, phase 2 trial of second-side GKS of the VIM in 33 patients with severe essential tremor and no relevant speech or balance problems. A comprehensive assessment before surgery, as well as 6 and 12 months post-surgery, included a complete neuropsychological testing, the evaluation of voice, speech, gait, posture, tremor severity, activities of daily living, disease related Quality of Life and MRI. The primary endpoint was safety. All patients completed the study after the one year follow up period (19 male, 14 female, 32 right VIM-GKS and 1 left). A single adverse event was observed (hemi-proprioceptive ataxia and dysarthria due to hyper-response 11 months after VIM-GKS). The mean delay between the first and the second GK was 28.7 months. The postoperative cognitive assessment as well as the evaluation of speech, gait and balance showed no significant worsening. The tremor severity score significantly improved by 58.5%, the disability score by 84.8% and the functional impact score by 68.6%. Four patients failed to respond while for the 29 remaining, the mean improvement of the treated upper limb tremor was 74.4%. Quality of life at 12 months was significantly improved. In selected patients with bilaterally disabling essential tremor and without speech, gait or balance concerns, staged bilateral VIM-GKS can be performed with a good safety profile and leads to a major reduction of the tremor and improvement of the quality of life. If confirmed by larger series and longer follow-up, bilateral staged VIM-GKS could be considered as a good option for selected patients presenting with a severe drug-resistant bilaterally disabling essential tremor.
Generative artificial intelligence (GenAI), particularly large language models (LLMs), is rapidly integrating into clinical settings. However, its net effect on dermatological practice remains poorly defined. This study investigates the dual impact of GenAI on clinician-patient communication using a multi-component data approach. We conducted an exploratory multi-component cross-sectional study from February 2025 to January 2026 in the dermatology departments of two tertiary hospitals in China. This study included physician surveys (n = 25), outpatient questionnaires (n = 60), and standardized case assessments. For the standardized component, 20 physicians completed two cases under randomized no-AI and AI-assisted pre-consultation preparation sequences, yielding 80 assessment records. The AI-assisted condition used DeepSeek-R1 for 5 min of pre-consultation preparation before a 10-min standardized patient encounter. Physician GenAI use frequency was associated with lower emotional exhaustion (r_s = -0.692, p = 0.002) and higher communication self-efficacy (r_s = 0.848, p < 0.001). In the adjusted physician model, GenAI use frequency was associated with higher PCSES scores (B = 3.204, 95% CI 2.263 to 4.145), and this association was maintained in leave-one-out analyses (B range 3.010-3.374), a parsimonious model (B = 3.151), and a model excluding influential observations (B = 3.055). Patient GenAI users reported higher communication satisfaction than non-users (18.46 ± 2.48 vs. 15.17 ± 2.43, p < 0.001). In standardized cases, the AI-assisted condition was associated with higher estimated marginal scores for information gathering (difference 3.175, 95% CI 0.605 to 5.745), information giving (5.675, 95% CI 3.432 to 7.918), structural efficiency (5.575, 95% CI 3.751 to 7.399), and total score (2.490, 95% CI 1.374 to 3.606). Humanistic care showed a reduction in the AI-assisted condition in the primary mixed-effects model; however, this difference did not reach statistical significance. Sensitivity analyses using fully adjusted mixed-effects models accounting for period, condition order, and case order indicated a consistent negative effect of AI assistance on humanistic care (B = -3.414, 95% CI -5.723 to -1.105), indicating the sensitivity of this outcome to model specification, with a consistent negative effect observed in fully adjusted models. These exploratory findings suggest that GenAI-assisted preparation was associated with stronger information organization and communicative efficiency in dermatology, while not automatically improving empathic or humanistic communication. GenAI should therefore be positioned as a supervised supportive tool rather than as a replacement for clinical judgment or relational care.
Sleep disturbances are frequent in childhood and have been associated with emotional vulnerability and modifiable lifestyle behaviours. The relative and combined contributions of child anxiety, parental anxiety, and unstructured daily routines to paediatric sleep disturbances remain incompletely characterized. We conducted a cross-sectional study of 306 otherwise healthy children aged 3-14 years. Parents completed validated questionnaires assessing sleep disturbances, child anxiety, parental anxiety, and daily lifestyle habits, including evening screen exposure. Multivariable linear regression, mediation, and cluster analyses were performed to identify correlates of sleep disturbances and distinct profiles. Clinically significant sleep disturbances were identified in 39.2% of participants. Higher child trait anxiety was consistently associated with greater sleep disturbance severity (all P < .001). Evening screen exposure was independently associated with higher sleep disturbance scores (P < .05). Parental trait anxiety not directly associated with sleep disturbances both directly and indirectly through child trait anxiety, which mediated approximately 30% of the association (P < .001). Cluster analysis identified three distinct profiles, including two groups with comparable sleep disturbance severity but contrasting characteristics: one marked by high emotional vulnerability and one by predominant lifestyle dysregulation. Conclusion: Sleep disturbances are strongly associated with trait anxiety and independently related to evening screen exposure, while parental anxiety appears to exert its effect both directly and, in part, indirectly through child anxiety. Similar sleep complaints may reflect different underlying emotional and lifestyle mechanisms. A multidimensional assessment integrating anxiety screening and evaluation of evening habits may improve early identification of at-risk children and support targeted preventive strategies within routine paediatric care.
To determine the association between self-reported falls and level of social support or changes in social support among older adults. Data from two repeated surveys were collected from the Mayo Clinic Biobank. Participants completed a baseline survey at the time of enrollment in the Mayo Clinic Biobank and a 10-year follow-up survey. We used logistic regression models to assess the association of seven social support variables reported in the baseline survey with fall-related outcomes reported in the follow-up survey. Similar analyses were conducted to assess the association of changes in the level of social support with falls and fall-related outcomes, adjusting for baseline social support, age, and gender. A total of 37,210 participants responded to the surveys. The median participant age was 67 years for those who did not report a fall in the past year in the follow-up survey and 72 years for those who reported a fall. The proportion of self-reported gender was similar for those with falls (60.3% female, 39.7% male) and without falls (62.0% female, 38.0% male). Higher levels of baseline social support were associated with a lower likelihood of falls. Participants without social isolation had lower odds of falls than those with social isolation (odds ratio, 0.64; 95% CI, 0.60-0.68). Increased levels of social support were also associated with a lower likelihood of fall-related outcomes. Our findings highlight the importance of social support that increases concomitant with age to reduce risk of falls among older adults.
Rooks, MDL, Winters, JD, Royer, SD, Hoch, MC, Bergin, R, Morelli, N, Conley, C, Djafar, TE, Sheppard, LR, Flaherty, CW, and Heebner, NR. Psychological self-report questionnaires are not associated with decrements in physical performance in special operations forces unit training. J Strength Cond Res 40(8): e777-e783, 2026-Special Operations Forces (SOF) unit training may elicit nonfunctional overreaching (nFOR). Although psychological self-report (PSR) tools are commonly used to screen for nFOR, their utility in SOF settings remains unclear. This study aimed to assess performance decrements after deployment training and correlations with PSR questionnaires. Fifty-four male, active-duty SOF operators underwent performance and PSR assessments before and after an 8-month training phase. Performance measures included body fat, agility, vertical jump (VJ), anaerobic capacity, 30 yd sprint and a 10 yd split time, ball toss, isometric midthigh pull (IMTP), and aerobic capacity. Psychological self-report measures included depression, sleep quality, alertness, post-traumatic stress, and the Defense and Veterans Pain Rating Scale. Spearman's rank correlations were calculated between changes in performance and PSR as well as changes in performance with post-training PSR. Alpha was p < 0.05 a priori. After unit training phase, subjects demonstrated poorer scores in body fat, agility, VJ, anaerobic capacity, 10 and 30 yd sprints; and improved IMTP and pain subscales for sleep, mood, and stress. Agility changes were correlated with changes in alertness and pain affecting mood and stress. Aerobic capacity changes were correlated with changes in alertness. When observing PSR at post-training, changes in agility were correlated with depression, changes in anaerobic capacity were correlated with overall pain, and changes in 30 and 10 yd sprints were correlated with sleep quality. No other significant correlations were observed. Coaches should be aware that SOF operator training could result in nFOR, but exercise caution using PSR as a screen. Future research should identify other screens sensitive to nFOR in SOF.
Pulmonary hypertension (PH) is characterized by progressive pulmonary vascular remodeling, rising right-ventricular afterload, and eventual maladaptation, which is a major determinant of prognosis. While established therapies mainly target vasoconstrictive pathways, recent development has shifted toward disease-modifying strategies that address remodeling, inflammation, and metabolic dysfunction in PH patients. This Special Report summarizes selected breakthrough therapeutic targets in PH, focusing on mechanisms supported by strong causal rationale and evaluated in at least Phase II clinical testing. Covered pathways include bone morphogenetic proteins/activin signaling rebalancing, growth factor and kinase inhibition, zinc transport targeting, inflammatory and immune-directed approaches, and metabolic modulation. We emphasize translational relevance, current clinical status, and key challenges limiting broader implementation of these approaches. The next advance in PH treatment will depend not only on identifying effective targets but also on improving precision in their deployment. Three barriers are especially important: responder heterogeneity, incomplete benefit-risk stratification, and uncertainty about target engagement in vivo. Therefore, biomarker-guided enrichment, integrated safety profiling, and practical pharmacodynamic readouts should become central elements of trial design. In parallel, expansion of the therapeutic toolbox, including stress-sensing, adrenergic, senescence, and hypoxia-related pathways, may increase the likelihood of matching individual patients to effective disease-modifying therapy.
The complex process and high costs of respiratory diseases diagnostic brought a heavy burden on patients. Traditional lung auscultation enables rapid respiratory assessment but is experience-dependent, leading to diagnostic inaccuracy. Wearable sensors acquire accurate pulmonary signals for diagnosis but lack sufficient stretchability to maintain skin contact during breathing, leading to interfacial detachment and data corruption. In this study, a stretchable and self-healable acoustic sensor is fabricated based on bio-based piezoelectric elastomer (BBPE) to realize fast respiratory diseases identification. The BBPE is synthesized with mass of C═O dipoles to achieve high piezoelectricity, and its long backbone and crosslinking network ensure low elastic modulus and high stretchability. Thus, the piezoelectric acoustic sensor can sensitively respond to sound sources with a detection error of less than 0.1%. By converting the pulmonary sounds into voltage signal, the acoustic sensor can effectively identify several types of respiratory diseases. Besides, the acoustic sensor shows a high elongation over 1200% and enables rapid self-healing efficiency over 79% with cut damage at 37°C, ensuring high accuracy and long lifetime. Thus, the stretchable and self-healable acoustic sensor shows great potential in fast respiratory diseases identification fields.
Objective: This study aimed to identify the degree of influence of clinical educators for improving clinical nursing competencies of new graduate nurses assigned in intensive care unit (ICU) and also to suggest ways to educate new graduate nurses in the ICU. Materials and Methods: A self-administered, unmarked web-based questionnaire survey method was employed. The quality of clinical educators was measured using the Clinical Educator Quality Scale, and the clinical nursing competency of new graduate nurses was measured using the Clinical Nursing Competence Self-Assessment Scale (CNCSS). Multiple regression analysis was performed with the four CNCSS factors as dependent variables and clinical educator quality and personal and organizational background as independent variables. Results: A total of 125 participants responded to the survey; 57 (45.6%) were admitted to the ICU, while 68 (54.4%) to the surgical ward. In the ICUs, the "competence in basic nursing practice", "competence in coordinating the care environment and team system", and "competence in studying in nursing practice" influenced the attitude toward new graduate nurses. In the surgical wards, 'sex and leadership' influenced "competence in basic nursing practice", and "competence in developing nursing care". A supervisor who monitors their daily work and supports their job affected "competence in coordinating the care environment and team system" and "competence in studying nursing practice". Conclusion: We identified distinct factors that affected clinical nursing competence in ICUs and surgical wards. Therefore, new graduate nurses must be educated with different emphases, particularly in the ICUs.
Artificial intelligence (AI) is reshaping future work and increasing university students' concerns about career uncertainty and employability. Existing research offers limited insight into why students respond differently to the same AI-related career uncertainty. Drawing on cognitive appraisal theory, this study examines how the AI job replacement threat influences students' career goal adjustment intentions through challenge and hindrance appraisals, as well as whether proactive personality shapes these appraisal processes. Two studies were conducted. Study 1 used a scenario-based experiment with 205 university students to manipulate high versus low AI job replacement threat. Independent-samples t-tests and partial least squares structural equation modeling (PLS-SEM) were used for data analysis. Study 2 used survey data from 458 career-entry students to test the proposed moderated mediation model using PLS-SEM. Artificial intelligence job replacement threat increased both challenge and hindrance appraisals. Challenge appraisal mediated the relationship between AI job replacement threat and career goal reengagement intention, whereas hindrance appraisal mediated the relationship between AI job replacement threat and career goal disengagement intention. Proactive personality strengthened the relationship between the AI job replacement threat and challenge appraisal, as well as the indirect effect on career goal reengagement intention. However, proactive personality did not significantly weaken the hindrance appraisal pathway. The findings suggest that AI job replacement threat functions as a dual-meaning source of career uncertainty in the context of AI-driven labor market transformation. While proactive personality facilitates opportunity-oriented career adaptation, it does not eliminate perceptions of structural career threat, highlighting the limits of individual agency in navigating future work uncertainty.