Proportional-integral-derivative (PID) controllers remain the cornerstone of industrial automation owing to their robustness and operational simplicity. However, tuning PID parameters for nonlinear processes presents persistent challenges, often requiring system linearization and repeated recalibration under varying operating conditions. Although both traditional and reinforcement learning (RL)-based auto-tuning methods have shown considerable promise, their dependence on direct trial-and-error interactions with live processes raises substantial safety and feasibility concerns in industrial environments. This study presents a novel PID generator framework that leverages virtual environments to enable safe and efficient offline training. Simplified first-order plus dead-time systems are constructed to emulate the slow nonlinear dynamics of target processes, serving as interactive surrogate environments for RL agent training. To address performance discrepancies under varying operating conditions, a reward normalization mechanism-a critical yet previously underexplored component for reliable RL-based PID tuning-is proposed. Furthermore, an enhanced actor-critic architecture is adopted to further improve learning efficiency and policy convergence. Once training is complete, the agent autonomously generates optimal PID parameters for target processes without requiring online retraining or direct process interaction. The effectiveness and robustness of the proposed framework are validated through comprehensive numerical simulations and real-world industrial experiments. The results demonstrate its capacity to adaptively and reliably determine optimal PID parameters for nonlinear systems, thereby bridging the gap between advanced RL methodologies and practical industrial control applications.
Complex endovascular aortic repair (EVAR) frequently requires simultaneous femoral and upper-extremity access, particularly during multibranched endograft implantation, branched thoracic EVAR, and other procedures requiring target-vessel catheterization from the arm. In hybrid operating rooms, the arm-side operator often has a limited or obstructed view of the primary fluoroscopy monitor because of the image intensifier, patient position, equipment, radiation shielding, or distance from the main display. Although secondary monitors can be used, they may be small, poorly positioned, or difficult to align with the operator's working angle. We describe a simple wearable headset-assisted fluoroscopic visualization technique using commercially available components, including XREAL One Pro glasses (XREAL, Inc), a wireless high-definition multimedia interface transmission module, and a digital visual interface-to-high-definition multimedia interface connector. The system allows the live fluoroscopic image to be displayed as an individualized virtual monitor within the operator's field of view while preserving awareness of the operative field through a see-through display and adjustable shading. The headset can provide a stable three-degree-of-freedom or six-degree-of-freedom image as needed. This technique may be particularly useful for the arm-side operator during multibranch endograft procedures or branched thoracic EVAR, where precise wire, catheter, sheath, and bridging stent manipulation is required. Wearable headset-assisted fluoroscopic visualization may simplify hybrid operating room setup, reduce dependence on monitor positioning, and improve operator ergonomics. Further evaluation is needed to assess its effect on procedure efficiency, fluoroscopy time, radiation exposure, operator workload, and safety.
Time-series prediction based on historical data is essential in numerous scientific fields, such as weather prediction and financial markets analysis. However, obtaining strong predictive accuracy together with high computational efficiency remains challenging. To address this challenge, we propose a brain-inspired neural network-based echo state network (BINN-ESN). It uses a modified continuous coupled neural network (MCCNN) as the neural model, which is inspired by the mammalian visual cortex. Our results indicate a system-dependent trade-off: While deep learning baselines generally achieve stronger single-step accuracy, BINN-ESN shows stronger long-term predictive stability on most evaluated systems and requires substantially less total computation than the GPU-accelerated long short-term memory (LSTM) baseline in long-term experiments. Our code is available at https://github.com/Jizhao-Liu/code-for-BINN-ESN.
Antineutrophilic cytoplasmic antibodies glomerulonephritis (ANCA-GN) is the most common type of crescentic glomerulonephritis in the elderly. It is life-threatening, and early detection is key to facilitating complete remission with treatment. Albeit rare, more reports are implicating hydralazine use in the development of ANCA-associated vasculitis (AAV) and ANCA-GN. Classic treatment involves the use of corticosteroids with cyclophosphamide (+/- plasmapheresis) in ANCA-GN. However, a definite therapeutic approach and duration for drug-induced AAV has yet to be studied in clinical trials. In our case, we aim to provide another approach that would one day improve and structure therapy guidelines for drug-induced AAV. We present a 75-year-old female patient, with medical history of hypertension, atrial fibrillation status post ablation on anticoagulation, pulmonary hypertension, who came to the nephrology clinic with symptoms of fatigue, anorexia, nausea, weight loss, hemoptysis, and rise in serum creatinine to 2.39 mg/dL from baseline of 0.65 mg/dL, and by admission to the hospital in August 2024 was 4.6 mg/dL. Anti-MPO and anti-histone antibodies were positive; complement was normal. Renal biopsy confirmed pauci-immune necrotizing GN with crescents. Therapy included steroids, rituximab, cyclophosphamide, and plasmapheresis with clinical improvement and complete remission of extra-renal disease.
Porcine reproductive and respiratory syndrome is one of the most devastating diseases affecting global swine production. Viral nonstructural protein 12 (nsp12) is a key factor in viral replication during viral subgenomic RNA synthesis. We identified the host E3 ubiquitin ligase RING finger protein 187 (RNF187) as a novel anti-porcine reproductive and respiratory syndrome virus (PRRSV) host-restriction factor. RNF187 directly interacts with nsp12, and the overexpression of RNF187 significantly inhibits the expression of the viral nucleocapsid (N) protein and the titer of viruses, whereas the knockdown of RNF187 promotes viral replication. Mechanistic studies showed that RNF187 mediates the degradation of nsp12 in a dose-dependent manner. This degradation process can be blocked by the autophagy inhibitor, 3-methyladenine (3-MA). These results indicate that RNF187 degrades nsp12 via the autophagy pathway rather than the proteasome pathway. Mechanistically, RNF187 acts as a scaffold protein to recruit the autophagic cargo receptor NDP52 and promotes the K63-linked polyubiquitination at lysine 130 (K130) of nsp12, thereby targeting nsp12 for autophagy-lysosomal degradation. This study revealed a novel host defense mechanism mediated by the RNF187-NDP52 axis, which restricts PRRSV infection by targeting nsp12, thereby providing a potential target for the development of antiviral strategies.
Chaperones are essential for Clp protease that governs protein quality control in chloroplast. However, it remains poorly understood whether and how individual ClpC proteins play distinct roles in plant growth and development. In this study, we isolated a new allele of clpc2, designated sot11, from genetic suppressor screening of the thf1 leaf variegation phenotype. DNA sequencing combined with protein structural modeling revealed that the sot11 mutation causes a substitution of Thr to Ile at position 868 located within a loop region of ClpC2, leading to partial loss-of-function of ClpC2. Genetic and phenotypic assays demonstrated that sot11 suppresses not only thf1-mediated but also var2/ftsh2-mediated leaf variegation. Notably, sot11 fails to restore high-light hypersensitivity and the reduced FtsH protease levels observed in thf1. In addition, CRISPR-Cas9-generated complete knockout mutants of clpc2 exhibit severe growth retardation, markedly shortened roots, and pronounced anthocyanin accumulation, compared to the wild type (WT) plants, revealing a dosage-dependent relationship between ClpC2 activity and plant fitness. Taken together, these findings suggest that ClpC2 plays an important role in both shoot and root growth, opening a new avenue for investigating the organ-specific molecular mechanisms underlying ClpC2 function.
Tertiary lymphoid structures (TLS) are associated with prognosis in solid tumours. Their value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer remains uncertain. Three published TLS signatures were scored by single-sample gene set enrichment analysis in oestrogen receptor-positive luminal tumours. The Cancer Genome Atlas Breast Invasive Carcinoma cohort (TCGA-BRCA) included 632 cases, of which 379 met strict consensus. METABRIC included 1086 cases, of which 663 met strict consensus. Logistic models adjusted for age and pathological tumour stage. Strict consensus, majority vote, and continuous scores were compared. Performance assessment included bootstrapped changes in area under the receiver-operating-characteristic curve, Brier scores, calibration, and decision-curve analysis. Survival was evaluated in METABRIC and explored in TCGA-BRCA. Strict-consensus TLS status was not associated with nodal positivity in TCGA-BRCA (adjusted odds ratio: 0.95, 95% confidence interval: 0.62-1.45, P = 0.822). METABRIC was similar (odds ratio: 0.76, 95% confidence interval: 0.55-1.06, P = 0.105). Full-cohort METABRIC analyses detected small majority-vote and continuous-score associations, absent in TCGA-BRCA. Across specifications, bootstrapped changes in area under the receiver-operating-characteristic curve ranged from 0.0002 to 0.0089, with minimal Brier-score improvement and no stable decision-curve benefit. In METABRIC, the univariable overall survival association attenuated after age adjustment (hazard ratio: 1.33-1.10). TCGA-BRCA survival analyses were nonsignificant. TLS transcriptomic signals showed small, cohort-dependent associations with nodal status but no reproducible or clinically meaningful incremental predictive value. These data do not support replacing sentinel lymph node biopsy with a TLS signature in oestrogen receptor-positive luminal breast cancer.
Single-inhaler triple therapy (SITT) combining an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist (ICS/LABA/LAMA) represents the current ceiling of inhaled pharmacotherapy for moderate-to-very-severe chronic obstructive pulmonary disease and severe uncontrolled asthma. Five device platforms are currently approved: two extrafine formulations delivering beclomethasone dipropionate/formoterol/glycopyrronium (the Modulite solution pressurised metered-dose inhaler [pMDI] and the NEXThaler breath-actuated dry powder inhaler [DPI]); the co-suspension pMDI Aerosphere platform (budesonide/glycopyrrolate/formoterol); the standard-particle Ellipta DPI (fluticasone furoate/umeclidinium/vilanterol); and the low-resistance, single-dose capsule-based DPI Breezhaler (mometasone furoate/indacaterol/glycopyrronium). Despite a shared pharmacological class, these systems differ in aerosol physics, particle engineering, intrapulmonary deposition patterns, and device-patient interaction. Furthermore, some of them are authorized only for COPD or asthma. This narrative review examines the technology and in vivo deposition evidence for each SITT platform, discusses real-world performance determinants (particle size, flow dependency, technique robustness), and proposes an expert-informed framework for patient-level device selection. Methodological limitations include reliance on in silico Functional Respiratory Imaging data when in vivo scintigraphy is unavailable, and inconsistent dose denominators across studies (emitted vs. metered dose). Cross-platform comparisons are limited by heterogeneous methodologies, and no SITT platform has demonstrated universal superiority. In platform-specific studies, NEXThaler shows relatively high lung deposition (∼55% of emitted dose) though flow-dependent; Aerosphere is robust to inhalation technique variations; Modulite provides extrafine, peripheral delivery; Ellipta and Breezhaler offer once-daily convenience with moderate deposition. Rational device selection requires structured assessment of patient inspiratory capacity, disease phenotype, coordination, and adherence. Head-to-head scintigraphy and prospective imaging-outcome studies represent major evidence gaps.
Children and young people (CYP) with life-limiting conditions (LLCs) comprise a clinically heterogeneous population with diverse disease trajectories and survival patterns. However, studies evaluating long-term survival according to disease group and sociodemographic characteristics remain limited. We assessed long-term survival patterns among CYP with LLCs and evaluated differences in mortality outcomes according to disease group and selected sociodemographic characteristics. Cohort study. Using the Korean National Health Insurance database, we identified individuals aged 0-24 years who were newly diagnosed with LLCs between 2011 and 2013. Patients were followed from the date of diagnosis until death or December 31, 2020. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate long-term mortality outcomes according to disease groups and sociodemographic indicators, including insurance premium-based income categories and residential area. In total, 175,813 CYP with LLCs were included. Survival patterns differed significantly across disease groups, age groups, and income levels. Disease group distribution varied by age, with premature and neonatal conditions predominating in infancy. Survival probabilities were lowest among children aged < 1 year and among medical aid beneficiaries. Premature and neonatal disorders and cardiovascular diseases were associated with the shortest observed survival durations. Male patients demonstrated a higher hazard of death from cancer (hazard ratio [HR] 1.83), metabolic diseases (HR 1.61), and neurologic and neuromuscular diseases (HR 1.33) compared to female patients. Higher hazard ratios among medical aid beneficiaries were observed primarily in patients with metabolic, neurologic and neuromuscular diseases, whereas residence-related differences in survival were observed among patients with cardiovascular diseases. Distinct survival trajectories exist across disease groups among CYP with LLCs. Early mortality predominates in premature and neonatal disorders and cardiovascular diseases, whereas more prolonged survival patterns are observed in cancer and neurologic disorders. These findings may inform the development of disease-specific integrated treatment strategies, long-term care planning, and supportive care policies for CYP with LLCs and their families. Children and young people with life-limiting conditions often live with severe illnesses that require ongoing medical care and support. These conditions include cancer, neurologic disorders, heart disease, respiratory disease, metabolic disorders, and severe neonatal conditions. Some children die soon after diagnosis, while others survive for many years with complex healthcare needs. Understanding these survival patterns is important for planning treatment, supportive care, and pediatric palliative care services. In this study, we used national health insurance data from Korea to examine long-term survival among 175,813 children and young people aged 0–24 years who were diagnosed with life-limiting conditions between 2011 and 2013. We followed patients for up to 10 years after diagnosis. Survival differed greatly depending on the type of disease. Children with premature and neonatal conditions or cardiovascular diseases had the shortest survival times, with many deaths occurring within the first year after diagnosis. In contrast, children with neurologic disorders and cancer often survived for longer periods after diagnosis. Survival was also lower among infants younger than 1 year and among children from lower-income families receiving medical aid support. In some disease groups, boys had a higher risk of death than girls. Regional differences were generally small, although children with cardiovascular diseases living outside metropolitan areas had poorer survival outcomes. These findings show that children and young people with life-limiting conditions have different healthcare and support needs depending on their disease and social circumstances. The results may help improve long-term care planning, supportive services, and healthcare policies for affected children and their families.
Accurate short-horizon water-quality forecasting is important for environmental monitoring systems that aim to move from passive observation toward timely, data-driven intervention. Next-day pH prediction is particularly relevant because pH reflects aquatic chemical balance, pollutant behavior, and ecosystem health. This study addresses next-day pH prediction in a spatio-temporal monitoring context using the public Water Quality Prediction dataset from Georgia, USA, where distributed monitoring records reflect temporal continuity and spatial dependency. Here, spatio-temporal refers to the multi-site and time-indexed dataset structure rather than to an explicit graph-based spatial neural architecture. A two-stage learning framework is used: baseline models are first benchmarked under a unified protocol, and the strongest baseline is then refined through metaheuristic hyperparameter optimization. The framework combines preprocessing, comparative benchmarking, and optimizer-guided refinement, with RegNet as the focal predictive model and the Ocotillo Optimization Algorithm (OCOA) as the hyperparameter search mechanism. OCOA-RegNet is compared with optimizer-assisted RegNet variants based on PSO, GA, WOA DE, MVO, BA, SFS, BBO, and APO. In the baseline stage, RegNet achieved the strongest untuned performance, with an RMSE of 0.0285. In the optimization stage, OCOA + RegNet achieved the lowest RMSE, [Formula: see text] across independent runs, under the adopted protocol. These findings indicate that next-day pH forecasting benefits from both model selection and disciplined hyperparameter optimization, supporting the proposed workflow as a decision-support component for distributed water-quality monitoring.
Bioimpedance analysis (BIA) is a non-invasive method for estimating fat-free mass (FFM) and fat mass (FM) via resistance (Rz) and reactance (Xc). Despite its potential, its usefulness and accuracy in children remain controversial. We obtained body composition measurements from 2954 visits involving 1547 participants (aged 5-21 years) using segmental BIA measurements and skinfold-based equations (Slaughter et al.). Four independent analyses were conducted: (1) agreement of Rz and Xc measurements between body segments was assessed; (2) sex- and age-specific reference curves for height-normalized resistance (Rz/H) and reactance (Xc/H) were developed; (3) associations between changes in BMI-SDS, Rz/H, and Xc/H (SDS) were examined; and (4) FM estimates derived from the proprietary algorithm, an alternative formula-based BIA algorithm, and skinfold-based equations were compared with age adjustment. Segmental Rz/H and Xc/H measurements showed "excellent" (>0.9) intraclass correlations for all segments. Concordance correlation coefficients indicated variable agreement between methods. Age- and sex-specific Rz/H and Xc/H percentile curves showed similar progressions across body segments. Rz/H (SDS) and Xc/H (SDS) showed a clear association with BMI-SDS, with lower values in participants with obesity. Estimated FFM and FM showed discrepancies between estimation methods depending on weight status rather than age. Rz/H and Xc/H showed consistent age-related patterns but were strongly influenced by BMI-SDS. While agreement between FM estimates was good in normal-weight children, substantial discrepancies were observed in those with obesity. These findings suggest that current BIA-based estimation approaches may be unreliable in children and adolescents with obesity.
Armed conflict disrupts health systems and daily self-care practices, yet quantitative evidence on its impact on oral health is scarce. This study compared self-reported oral health status, hygiene behaviours, and access to dental care among residents of the Gaza Strip before and during the 2023-2024 war. A comparative cross-sectional survey was conducted among 599 Gaza residents using a structured, self-developed 34-items online questionnaire. Participants reported oral health conditions and behaviours for two periods: before October 2023 and during the war. Paired categorical data were analysed using Bowker's test of symmetry for multi-category variables, and McNemar's test for binary variables, and subgroup associations were examined using chi-square tests. Significant deterioration was observed across all 12 assessed domains (p < 0.001 for 11 variables; p = 0.013 for the remaining variable). The proportion reporting severe oral pain increased from 6.5% pre-war to 73.8% during the war, while those reporting no pain decreased from 25.5% to 2.0%. Favourable self-rated dental status (excellent/good) declined from 85.3% to 9.7%, and the proportion reporting healthy gums decreased from 88.1% to 12.4%. Twice-daily tooth brushing fell from 77.5% to 9.5%, and complete cessation of brushing increased from 0.8% to 38.4%. Unmet dental care needs rose from 11.7% to 92.7%, with insecurity and lack of dental services as the main barriers. Stress-related oral habits increased markedly, and 86.0% of participants reported dependence on canned foods. Overall, 95.5% perceived their oral health to have worsened since the onset of the war. The Gaza war was associated with profound deterioration in self-reported oral health status, hygiene practices, and access to dental care. These findings highlight oral health as a neglected dimension of humanitarian crises and underscore the need to integrate essential dental services into emergency health responses and post-conflict reconstruction.
This paper critically examines the evolution of nursing leadership over the past century, exploring how changing historical, social and professional contexts have influenced styles and their ongoing relevance to contemporary nursing practice. Using a historical analysis guided by Lewenson and Hermann's framework, primary sources, including archival materials and foundational texts, were examined alongside secondary scholarly literature and historical commentaries. Leadership approaches were reviewed by decade and mapped against key nursing theories, healthcare developments and broader social movements to construct a timeline of leadership discourse. Findings demonstrate a progression from predominantly hierarchical, autocratic and bureaucratic leadership models characteristic of the early and mid-20th century, particularly during wartime and post-war periods, toward more relational, collaborative and adaptive approaches. Transformational leadership emerged alongside nursing professionalisation during the 1980s, while servant and authentic leadership gained prominence in response to growing emphasis on equity, inclusion and person-centred care in the 2010s. More recently, adaptive, emotionally intelligent and ambidextrous leadership styles have become increasingly important for addressing healthcare complexity, workforce resilience, innovation and change. The analysis highlights nursing leadership as a dynamic, context-dependent and deeply relational construct. Understanding its evolution can support nurse leaders, educators and other healthcare providers to critically reflect on practice, foster inclusive and resilient teams and apply evidence-informed leadership strategies that promote sustainable, patient-centred care in rapidly changing healthcare environments.
Due to increased life expectancy, patients with chronic respiratory failure treated with home ventilation have an increasing likelihood of requiring surgery in their lifetime. Evidence on the safety and feasibility of surgery in this population is scarce. Retrospective analysis of all surgical procedures under general anaesthesia in patients included in the chronic home ventilation registry at Ghent University Hospital. Between 1 October 2006 and 1 March 2022, 128 surgical procedures were performed on 53 (female: 25) patients with a median age of 52 yr, BMI of 25 kg/m2, Charlson Comorbidity Index of 2 and FVC of 1.12 L (34%). 21 patients were ventilated via tracheostomy. The most common cause of respiratory failure was neuromuscular disease and tetraplegia (28 patients). Most procedures were minor (e.g. tracheostomy revisions), but 30 non-elective or emergency procedures (including 7 laparotomies) were registered. Respiratory complications occurred in 25 procedures (19%) and were associated with length of stay (p < 0.001) and hospital mortality (p = 0.029). Four patients (8%) died, all after emergency surgery, with one death deemed not attributable to the underlying respiratory failure (intracerebral haemorrhage). The ARISCAT score (median: 19; range: 0-86) was significantly associated with respiratory complications, length of stay, and hospital mortality (all p < 0.05). Surgery is feasible in chronically ventilated patients, though the risk of respiratory complications and death after surgery, particularly if non-elective, is not negligible. The ARISCAT score was associated with outcomes and appears to be a valuable tool for risk assessment in this population.
To evaluate the real-world performance of a transformer-based natural language processing (NLP) system for extracting Social Determinants of Health (SDoH) from clinical notes, using survey-based SDoH measures a reference comparators. This study was conducted at the University of Florida Health in adults with at least 2 clinical encounters in the prior year. A research survey was completed by 1001 participants; sampling targeted 50% Black patients to support subgroup analyses. Comparative analyses were restricted to the 414 participants who also had Epic SDoH survey data and clinical notes available for NLP extraction. We compared concepts extracted by the SOcial DeterminAnts (SODA) NLP pipeline against the independently administered research survey, which served as the primary reference standard, and against the structured Epic-embedded SDoH questionnaire. Nine domains were evaluated: abuse, alcohol use, drug use, education, financial constraints, housing, physical activity, social cohesion, and transportation. Sensitivity, specificity, positive predictive value, negative predictive value, and F1 scores were calculated by domain. The NLP pipeline more consistently aligned with negative survey responses than with patient-reported social needs, although performance was lower in some domains, especially alcohol use and financial constraints. Sensitivity was higher only for alcohol use (55%); the lowest values were for abuse (5%), drug use (0%), and financial constraints (16%). These results cannot be attributed to SODA extraction alone. They reflect some combination of social information not being recorded in clinical notes, content that was recorded but not extracted, and mismatches between extracted concepts and survey definitions, and the present analysis cannot separate these contributions. The 2 surveys agreed only modestly with each other, so no single instrument provides a definitive ground truth. The pipeline more consistently aligned with negative survey responses than with patient-reported social needs. Because the 2 surveys agreed only modestly, the reference itself is imperfect, and apparent NLP performance depends in part on which survey is used as the comparator. Apparent gaps in NLP performance reflect both how social risks are recorded in clinical notes and how patients disclose them across different survey settings, in addition to limits of the extraction pipeline. Improving documentation practices, integrating locally tuned large language models, and monitoring subgroup performance may all be needed to make SDoH identification tools reliably detect social needs across patient populations.
Persistent and semi-volatile organic contaminants remain important atmospheric tracers because of their environmental persistence, multiple emission pathways and capacity for regional transport. This study investigated the spatial and seasonal variability of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in northeastern France. Nitrogen-doped carbon-coated silicon carbide foam (NMC@SiC) passive air samplers were deployed at six urban, suburban and rural sites in the Strasbourg metropolitan area between 2018 and 2020. Twenty-one OCPs, sixteen PAHs, and twenty-two PCBs were quantified by gas chromatography-tandem mass spectrometry. PAHs exhibited the clearest spatial and seasonal variability, with higher concentrations at urban sites and cold-season or autumn enhancements depending on the location. Naphthalene dominated the PAH profile, while diagnostic ratios suggested dominant combustion inputs, including traffic, residential heating and biomass or solid-fuel burning. PCBs showed weaker spatial contrasts and more homogeneous distributions, with profiles dominated by penta-, hexa- and hepta-chlorinated congeners, indicating diffuse legacy contamination, possible PCB-containing materials, industrially influenced areas and regional redistribution. OCPs were dominated by dichlorodiphenyltrichloroethane-related compounds and hexachlorocyclohexane isomers, reflecting historical residues and secondary volatilization from contaminated environmental reservoirs. These findings highlight the combined influence of current urban emissions, persistent legacy reservoirs, secondary re-emissions and regional atmospheric transport on organic contaminant distributions in northeastern France.
Interpersonal touch is a fundamentally multidimensional and multisensory experience and as such is highly subjective. By whom, where and how we are touched determines how we react to and feel about it. Previous research using topographical body tasks has mainly examined where people feel comfortable being touched by others. Using the BodyMap Tool, we mapped distinct somatoperceptions associated with positive and negative social touch videos, comparing physical sensations and emotional responses. We quantified these patterns with a BodyMap Score (BMS) reflecting valence and spatial coverage. Positive videos elicited higher physical than emotional BMS, whereas negative videos showed the opposite pattern, with broader emotional than physical somatoperceptions. Individual differences further modulated these effects: touch-avoidant participants showed reduced BMS for positive touch, and participants reporting pain exhibited overall lower BMS, though this reduction was attenuated for positive stimuli. These findings highlight the complex and context-dependent bodily representation of social touch.
Inflammatory activation is involved in the pathogenesis of heart failure (HF). ATPase H+-Transporting Accessory Protein 2 (ATP6AP2) is an auxiliary subunit of the V-ATPase, and its role in HF is not fully understood. To assess the role and regulatory mechanisms and therapeutic potential of ATP6AP2 in HF, we used a cardiac-specific ATP6AP2 conditional knockout (CKO) mouse model and observed spontaneous cardiac dysfunction, myocardial fibrosis and cardiomyocyte apoptosis in mice. Further studies showed that ATP6AP2 promoted stimulator of interferon genes (STING) degradation through the lysosome-dependent pathway. ATP6AP2 knockdown significantly upregulated STING protein levels, activated the STING-TBK1-IRF3 signaling axis, and promoted pro-inflammatory factor expression and cardiomyocyte apoptosis. In mice with myocardial infarction (MI), myocardial overexpression of ATP6AP2 or treatment with H-151 inhibited the activation of the STING signaling pathway, ameliorated cardiomyocyte apoptosis and inflammatory responses, thereby improving cardiac function. In addition, in macrophages treated with conditioned medium from hypoxia-exposed cardiomyocytes, the levels of pyroptosis-related proteins were markedly increased, whereas ATP6AP2 overexpression or STING inhibition reduced pyroptosis. ATP6AP2 likewise attenuates inflammation and pyroptosis caused by hypoxia in cardiac organoids. In conclusion, activating ATP6AP2 could serve as a promising therapeutic option in HF.
Ecological niches are shaped by both abiotic conditions and biotic interactions and shifts in species composition, such as the loss of competitors or habitat availability, can trigger cascading changes in community dynamics. Emerging infectious diseases offer natural experiments to observe such shifts in real time. Since its detection in 2006, white-nose syndrome (WNS), caused by the fungal pathogen Pseudogymnoascus destructans, has decimated several North American bat species, with mortality closely tied to species-specific susceptibility. Yet, disease alone does not account for ongoing changes in bat populations. Habitat availability, landscape composition, and landscape configuration may also strongly influence bat capture rates and community dynamics following WNS invasion. We evaluated long-term changes in bat capture rates on Fort Campbell Military Installation, Tennessee and Kentucky, USA, to determine whether variation in capture rates of non-susceptible species was associated with declines in WNS-susceptible species or with landscape composition and configuration. Using 30 years of mist-net capture data (1998-2023), we modeled capture rates of four non-susceptible species (Eptesicus fuscus, Lasiurus borealis, Myotis grisescens, and Nycticeius humeralis) at both installation and site spatial scales. Candidate models included capture rates of WNS-susceptible species, forest composition and configuration metrics, temperature, and precipitation. Installation-level analyses were conducted using generalized linear models, whereas site-level analyses used zero-inflated negative binomial models to account for excess zeros and overdispersion. Results reveal that some non-susceptible species exhibited post-WNS increases, but these trends were species- and scale-dependent and not universally consistent with ecological release. Furthermore, landscape features, particularly forest cover and patchiness, significantly explained variation in capture rates across space and time for certain species. These findings indicate that bat community dynamics at Fort Campbell reflect the combined influence of disease and habitat availability rather than a singular driver. This study underscores the complexity of post-disease community restructuring and highlights the need to consider interacting ecological stressors when assessing wildlife responses to disturbance and emphasizes the need for integrated approaches to wildlife conservation.
Computer-integrated surgical navigation systems are often run in the OR with the assistance of a technician for controlling the user interface and advising on technical details of the system. In lower-resource healthcare settings, limited access to additional OR staff and technical training for operating navigation systems can represent a barrier to sustainably deploying a low-cost surgical navigation solution. Recent advancements in locally deployable large language models (LLMs) have improved their ability to answer technical questions based on source materials and safely perform limited tasks on behalf of a user. The objective of this paper is to explore the feasibility of using a network of local LLM-based agents to act as a natural language interface for a low-cost surgical navigation system, facilitating hands-free manipulation of the user interface and providing documentation-grounded technical guidance. We propose the navigation offline virtual agent (NOVA), an end-to-end architecture that integrates distinct local LLM-based agents for knowledge tasks, action tasks, and delegation between the agents. Two semisynthetic benchmark datasets were generated for ablation studies of individual agents, and a prototype was built which integrates these agents into NousNav, an open-source neuronavigation system. The agents based on local LLMs were found to perform comparably to closed-source, commercially hosted LLMs. In a user study with nine participants, NOVA facilitated hands-free patient registration with a mean end-to-end latency of 10.4 ± 2.4  s and an 81% command success rate. This work demonstrates that local LLM-based agents can be deployed to support users of low-cost navigation systems by providing a context-aware natural language interface, representing an important step toward reducing technician dependence in low-cost surgical navigation.