Patients receiving maintenance hemodialysis (MHD) have a markedly increased incidence of urinary tract infection (UTI) because of impaired immune function, reduced urine output, and complications related to medical procedures. Post-void residual urine volume (PVR) is a key indicator of bladder emptying function. Elevated PVR is associated with urinary retention and bacterial colonization and is considered an indicator related to higher UTI risk. However, previous studies have mainly examined the cross-sectional association between a single PVR measurement and UTI risk. In patients receiving MHD, PVR often changes dynamically because of autonomic neuropathy, diabetic cystopathy, and fluctuations in volume status; therefore, a single assessment may not fully capture longitudinal changes. Group-based trajectory modeling (GBTM) can identify distinct longitudinal patterns, but evidence regarding its use to characterize PVR trajectories in the MHD population and assess their association with UTI risk remains limited. Clinical data were retrospectively collected from 302 patients who received regular MHD treatment at our hospital from January 2021 to December 2024. PVR was measured by ultrasonography every 3-6 months. GBTM was applied to repeated PVR measurements to identify trajectory classes. The optimal model was selected according to the Bayesian information criterion (BIC), average posterior probability (APP), odds of correct classification (OCC), and clinical interpretability. Baseline characteristics and UTI occurrence were compared among trajectory groups, and baseline characteristics of included and excluded patients were compared. Kaplan-Meier analysis and the log-rank test were used to compare cumulative UTI incidence. Posterior-probability-weighted Cox proportional hazards regression and Fine-Gray competing-risk models with death as a competing event were used to assess the association between PVR trajectories and UTI risk. In an exploratory analysis, death and nonfatal study-exit events were also combined as competing events. Restricted cubic spline (RCS) regression was used to explore the dose-response association between baseline PVR and first UTI risk. Robustness was evaluated using a clinically parsimonious Cox model, Firth penalized partial-likelihood Cox regression, and other sensitivity analyses. GBTM identified three PVR trajectories: low-level stable (138 patients, 45.7%), moderate-level increasing (103 patients, 34.1%), and persistently elevated (61 patients, 20.2%). During a median follow-up of 26.8 months, 60 patients (19.9%) developed a first UTI. The proportions of UTI in the low-level stable, moderate-level increasing, and persistently elevated groups were 10.1%, 22.3%, and 37.7%, respectively (χ²=20.78, P < 0.001). In the fully adjusted Cox model, the moderate-level increasing group showed a borderline association with higher first UTI risk (hazard ratio [HR] = 1.96, 95% confidence interval (CI): 1.01-3.82, P = 0.047), but this association did not reach statistical significance in the Fine-Gray competing-risk model (subdistribution hazard ratio [SHR] = 1.85, 95% CI: 0.94-3.64, P = 0.073). The persistently elevated group was independently associated with higher first UTI risk in both the Cox model (HR = 3.35, 95% CI: 1.68-6.68, P = 0.001) and the Fine-Gray model (SHR = 3.12, 95% CI: 1.53-6.36, P = 0.002). RCS exploratory analysis suggested a nonlinear association between baseline PVR and first UTI risk (overall association test P < 0.001; nonlinearity test P = 0.012); the slope of the HR curve tended to increase around approximately 80 mL, and this value was used to describe an exploratory curve feature in this study sample. Among MHD patients with measurable urine output who were able to complete serial PVR assessment, a persistently elevated PVR trajectory was independently associated with higher first UTI risk, and baseline PVR showed a nonlinear dose-response association with first UTI risk. Serial PVR assessment may provide supplementary risk-stratification information for MHD patients with measurable urine output. Not applicable.
Neurodegenerative and neuropsychiatric disorders lack disease-modifying therapies. The microbiota-gut-brain (MGB) axis, particularly short-chain fatty acid (SCFA)-producing microbiota dysbiosis, has emerged as a conserved driver of neuroinjury pathogenesis. Natural food-derived polysaccharides have been explored as prebiotic substrates, but their clinical translation is hindered by poor target specificity, high interindividual heterogeneity, and low bioavailability. Engineered food-derived polysaccharides, as a next-generation precision prebiotic platform, enable rational tailoring of molecular fine structures via targeted physical, chemical, biological, and combinatorial modification technologies, aiming for strain-specific directional modulation of intestinal SCFA-producing microbiota and multi-pathway neuroprotection through the MGB axis. In this review, we systematically delineate the bidirectional regulatory mechanisms between SCFA-producing microbiota and neural homeostasis, dissect disease-specific pathological cascades driven by SCFA-producing microbiota dysbiosis, and discuss conflicting findings on the dual effects of SCFAs. We further propose a full-chain framework of the structure-activity relationship of engineered polysaccharides, dissecting core modification strategies, strain-specific targeting mechanisms, and a multi-dimensional efficacy evaluation system for these precision prebiotics. Additionally, we assess safety evaluation status, major global regulatory differences, and core clinical translation bottlenecks. Finally, we outline key unresolved challenges and propose a conceptual roadmap for AI-assisted rational design of precision prebiotics, personalized microbiota-adapted intervention strategies, and multicenter clinical translation directions. This review provides a mechanism-driven theoretical framework and practical guidance for developing engineered food-derived polysaccharides as precision nutrition interventions for neuroinjury-related disorders.
Arrhythmias after paediatric cardiac surgery occur frequently and contribute to postoperative morbidity and mortality. There is limited literature assessing the safety and efficacy of common antiarrhythmics administered in this population. We systematically searched PubMed and EMBASE for literature on antiarrhythmic use in children <18 years of age after cardiac surgery from 2000 to 2024. Two reviewers independently screened abstracts and then reviewed full-text manuscripts to determine eligibility. We identified 28 studies of 3,752 patients across 11 different antiarrhythmics: flecainide, procainamide, esmolol, landiolol, propranolol, amiodarone, sotalol, dexmedetomidine, digoxin, ivabradine, and magnesium. Most studies were small, with 17 enrolling fewer than 100 children. Only eight studies were randomised, 16 were retrospective, 12 were prospective, and one was multicenter. Safety and efficacy endpoints varied widely, limiting our ability to combine data for meta-analysis. Overall, evidence supporting the use of these drugs in children after cardiac surgery was limited. Although antiarrhythmics are commonly used in children after cardiac surgery, randomised trials with standardised endpoints to guide choice of therapy are lacking. Pragmatic trials to generate real-world data should be considered to further evaluate the safety and efficacy of various antiarrhythmics in this population.
Wound healing is a complex process involving various factors and reconstruction of tissue structures. Platelets and their bioactive substances play an indispensable role in various stages of wound healing. Tissue engineering scaffolds are instrumental in maintaining, repairing, and enhancing tissue structure and function. Combining platelet concentrates with tissue engineering scaffolds heralds a novel direction for wound healing research. In this combination, platelet concentrates serve as tissue repair facilitators, while scaffolds function as tissue support and drug release platforms. This synergistic approach produces superior tissue repair outcomes in comparison to using either method independently. As a result, it is crucial to consolidate the application of platelet concentrates with tissue engineering scaffolds in the context of wound healing. This review begins by exploring the role of platelet concentrates and tissue engineering scaffolds in wound healing, while also outlining the essential criteria that scaffolds must meet. It then summarizes the application advances of platelet concentrates combined with tissue engineering scaffolds in wound healing. Finally, we highlighted current limitations in translation, including interpatient variability, formulation reproducibility, and complex regulatory hurdles. Developing innovative strategies and delving deeper into potential molecular mechanisms will drive further advancements in wound healing therapies through biomaterials engineering.
Adenovirus type 7 (AdV-7) frequently causes outbreaks in crowded settings such as military barracks and schools. This study seeks to deepen understanding of individual-level virus transmission mechanisms and examine how intervention timing and stringency shape epidemic trends. Methodological innovations in model construction allow refined description and reconstruction of transmission processes, offering methodological support for epidemic analysis and prediction. Based on the framework of this model, additional simulation models tailored to other scenarios can also be developed. We constructed a time-varying multilevel social contact network (trainees, class monitors, team leaders, company officers) matching field survey data's statistical characteristics, used an individual-based dynamic model to simulate AdV-7 transmission, calibrated parameters via fitting predicted and real incidence data, and verified reliability through sensitivity analysis. Results identified trainees as key transmitters; effective reproduction number (Re) surged above 3 initially and fell below 1 after isolation and contact restrictions took effect on Day 14 following the first index case. New cases declined after a brief surge, consistent with real epidemic trends. Sensitivity analysis revealed significant positive correlations between infection numbers, trainees' susceptibility, and isolation timing. The study confirms the model's validity, showing timely early warning, isolation, and social distancing effectively control the epidemic.
Biliary organoids, as an emerging three-dimensional (3D) in vitro modeling technology, have demonstrated significant value in studying biliary development, elucidating disease mechanisms, drug screening, and enabling personalized medicine. This review provides a comprehensive overview of the current strategies for constructing biliary organoids, including their cellular sources, differentiation pathways, and functional characteristics. Particular emphasis is placed on their strengths and limitations in recapitulating biliary physiology, modeling biliary tract cancers (BTCs), and performing pharmacological and toxicological assessments. The article further analyzes major technical challenges, such as low modeling efficiency, limited structural and functional fidelity, absence of microenvironmental simulation, and issues of standardization and ethics. Future directions are proposed in the areas of multicellular co-culture systems, dynamic cultivation technologies, high-throughput platforms, and clinical translation pipelines. As a versatile and evolving tool, biliary organoids are poised to serve as a critical bridge between basic research and clinical applications, offering new insights and methodologies for the study and precision treatment of biliary tract cancers.
The metabolism of microbial communities is essential for host and environmental health. The rational design of microbiomes with targeted functional properties is an important objective but remains challenging due to complex interactions and environmental heterogeneity. Community-function landscapes address this challenge by statistically inferring impacts of species presence or absence on function. Similar to fitness landscapes, community-function landscapes estimate both additive effects and interactions (epistasis) between species that influence function. We apply landscapes to design synthetic consortia to degrade the toxic contaminant bisphenol-A (BPA). Using synthetic communities of ten BPA-degrading bacteria, we map community-function landscapes across increasing BPA concentrations, where higher BPA means greater toxicity. Epistasis increases with toxicity, indicating that collective effects become more important for degradation. Designed communities are able to remediate BPA in contaminated soils. Our results demonstrate that toxicity can drive epistatic interactions in community-function landscapes and that these landscapes can guide microbial consortia design for bioremediation.
Healthcare systems face increasing pressure to deliver high-quality care while managing rising patient volumes and operational complexity. Although Electronic Medical Records (EMRs) generate large volumes of clinical data, hospitals often lack integrated operational intelligence capable of transforming fragmented information into actionable insights. This study presents the conceptual architecture of the Dedalus Command Centre, a platform designed to support real-time operational coordination in healthcare environments. The architecture was developed using a design-oriented research approach involving a multidisciplinary working group and a structured concept development process including stakeholder engagement, operational workflow analysis, architecture design, prototype validation, and platform implementation. The resulting platform consists of three logical layers: a real-time data layer integrating heterogeneous hospital data streams, an analytics and intelligence layer providing predictive and simulation capabilities, and a user application layer delivering operational dashboards and role-based tools. The proposed architecture enables real-time operational monitoring and predictive insights to support improved situational awareness, patient flow management, and coordinated hospital operations. Ongoing studies aim to evaluate its impact on hospital operational performance.
Cognitive motor dissociation (CMD) is associated with long-term recovery in acute brain injury, but CMD testing is only available in few centers. Our objective was to identify surface EEG patterns with high sensitivity or positive predictive value (PPV) for CMD in patients with acute disorders of consciousness to refine allocation of this resource-intensive test. In this observational cohort study, we enrolled clinically unresponsive, acutely brain injured patients who underwent continuous surface EEG and CMD assessments. CMD was detected by applying a machine learning algorithm to EEG acquired during a motor command paradigm presentation. Electroencephalographers blinded to CMD test results applied standardized ACNS criteria to the EEGs acquired during CMD assessments. We calculated accuracy measures of surface EEG findings for CMD test results using generalized estimating equations, with an exchangeable matrix and accounting for repeated measures per patient. We included 185 patients (mean age: 62 ± 17; 85 [46%] female) and 282 CMD assessments. CMD testing was positive in 39 (14%) assessments. Sensitivity and PPV of normal background voltage, symmetry, and continuity were, respectively, 77% (95% CI: 60%-88%) and 19% (95% CI: 13%-26%), 74% (95% CI: 58%-86%) and 14% (95% CI: 10%-20%), and 74% (95% CI: 58%-86%) and 14% (95% CI: 9%-19%). All EEGs with burst suppression, suppression, sporadic epileptiform discharges, lateralized periodic discharges, bilateral independent periodic discharges, electrographic seizures, and brief potentially ictal rhythmic discharges had negative CMD tests. Surface EEG findings are not reliable to screen for CMD or to identify patterns conferring higher CMD pretest probability.
To quantitatively evaluate changes in the gastrocnemius muscle of rabbits following acute cold exposure and subsequent peritoneal lavage rewarming therapy using multimodal ultrasound. Thirty healthy adult male New Zealand white rabbits, each weighing approximately (4.0 ± 0.2) kg, were selected and randomly divided into three groups(n = 10 per group): the Peritoneal Lavage + Rewarming Platform group, the Rewarming Platform group, and Blank Control group. Models for cold exposure and rewarming therapy were established across four distinct time points: T1 (normothermia), T2 (hypothermia), T3 (rewarming stage 1), and T4 (rewarming stage 2). B-mode ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) were employed to measure the following parameters in the rabbit gastrocnemius muscle at each time point and in each group: muscle belly thickness, tendon thickness, pennation angle, mean Young’s modulus (Emean), maximum Young’s modulus (Emax), and CEUS parameters. This was performed to evaluate changes in peripheral microcirculation following acute cold exposure and peritoneal lavage rewarming therapy. Parameters were compared within each group across different time points and among the three groups at the same time point. For pathological examination, three rabbits from each group were selected for tissue sampling at the T4 time point. Additionally, a separate cohort of 15 rabbits underwent tissue sampling as follows: 3 rabbits at T1, 3 rabbits at T2, and 3 rabbits from each group at T3. The collected gastrocnemius muscle samples were processed for transmission electron microscopy (TEM) and immunohistochemical (IHC) staining to observe morphological and cellular changes. (1) Body Temperature Comparison: Body temperature in all three groups decreased significantly at T2 compared to T1 (P < 0.05). By T4, body temperature had returned to normal levels in all groups, with no significant difference compared to T1 (P > 0.05). The Peritoneal Lavage + Rewarming Platform Group showed a significantly faster body temperature recovery rate during the T2–T3 period compared to the Rewarming Platform Group and the Blank Control Group (P < 0.05). No significant difference in recovery rate was observed between the Rewarming Platform Group and the Blank Control Group during T2–T3 (P > 0.05). There was no significant difference in rewarming rate among the three groups during the T3–T4 period (P > 0.05). (2) Conventional Ultrasound Parameters: At T2, the muscle belly thickness, tendon thickness, and pennation angle of the gastrocnemius muscle showed statistically significant differences compared to T1 and T4 within each group (P < 0.05). No significant difference was found between T1 and T4 (P > 0.05). There were no significant differences in these parameters among the three groups at any corresponding time point (P > 0.05). (3) SWE Parameters: In all three groups, both Emax and Emean at T2 were significantly different compared to T1 and T4 (P < 0.05). No significant difference was observed between T4 and T1 (P > 0.05). No significant differences were found among the three groups at any corresponding time point (P > 0.05). (4) CEUS Parameters: At T2, parameters including Rising Time (RT), Time to Peak (TTP), Descent Slope (DS), Falling Time (FT), and mean Transition Time (mTT) showed statistically significant differences compared to T1 and T3 (P < 0.05). No significant difference was observed between T3 and T1 (P > 0.05). There were no significant differences among the three groups at any corresponding time point (P > 0.05). (5) Transmission Electron Microscopy and Immunohistochemistry: TEM revealed swelling of some organelles in gastrocnemius muscle cells after acute cold exposure, which returned to normal after rewarming therapy. Immunohistochemical results showed no statistically significant differences in the Average Optical Density (AOD) of BNIP-3 in the gastrocnemius muscle across the different time points (P > 0.05). Under acute cold exposure conditions, the gastrocnemius muscle entered a contracted state, characterized by an increase in Young’s modulus values, a decrease in the pennation angle, and a slowdown in peripheral microcirculation. The rewarming rate achieved with peritoneal lavage therapy was faster than that in the other two groups, and the resulting prognosis showed no significant difference from the control group. Multimodal ultrasound can rapidly and effectively assess morphological changes and alterations in microcirculatory perfusion in the rabbit gastrocnemius muscle following acute cold exposure and rewarming therapy. Specifically, contrast-enhanced ultrasound enables the quantitative evaluation of the improvement in microcirculation and the effectiveness of the rewarming treatment. The online version contains supplementary material available at 10.1038/s41598-026-48013-4.
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. It reduces quality of life and increases the risk of complications such as stroke. Although progress has been made in understanding its pathogenesis, the key cellular subtypes and therapeutic targets remain unclear. We applied single-cell transcriptomics to identify critical cellular subtypes in AF. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning were used to screen AF-related genes. Mendelian randomization (MR) and colocalization analyses were performed to assess causal relationships between these genes and AF. Single-cell analysis showed a significant increase in macrophages in AF, especially SPP1-expressing macrophages, which may drive AF onset and progression. HdWGCNA identified AF-related gene modules. Three genes, LRCH1, RSRC2 and VAMP2, were found to be causally associated with AF. MR analysis confirmed their significant causal effects. The accumulation of SPP1-expressing macrophages may drive the onset and progression of AF. Furthermore, LRCH1, RSRC2, and VAMP2 were identified as key causal genes for AF, providing novel insights into its molecular mechanisms and potential therapeutic targets.
Composite indices integrating inflammation and lipid metabolism have emerged as promising markers for coronary heart disease (CHD), yet their comparative performance and discriminative ability for identifying CHD status remain incompletely understood. In this hospital-based study, 270 patients were enrolled, including 99 with CHD and 171 without CHD. Exposures included C-reactive protein (CRP) and composite indices (TG/HDL, LDL/HDL, AIP, CRP/HDL, and CRP/TG). Logistic regression, restricted cubic spline (RCS), and subgroup analyses were used to evaluate associations with CHD. Machine learning models were developed using significant predictors, and model performance was assessed by AUC, calibration, and decision curve analysis. SHapley Additive exPlanations (SHAP) were applied to interpret model outputs. After multivariable adjustment, TG/HDL (OR = 2.74, 95% CI: 1.10-7.10), LDL/HDL (OR = 3.01, 95% CI: 1.21-7.81), and AIP (OR = 6.59, 95% CI: 1.61-28.51) were associated with increased odds of CHD, whereas CRP and CRP-based indices were not. RCS analyses indicated no significant nonlinearity, suggesting monotonic associations. Subgroup analyses showed generally consistent results across key strata. In classification modeling, ensemble tree-based methods performed best, with random forest and XGBoost achieving the highest discrimination ability (AUC = 0.748). SHAP analysis identified age and lipid-related composite indices as the primary contributors to CHD classification. Lipid-related composite indices, particularly TG/HDL, LDL/HDL, and AIP, are robust markers associated with CHD status and can be effectively integrated into machine learning models for individualized CHD classification.
This paper addresses the distributed predefined-time optimal adaptive formation control problem in heterogeneous systems consisting of unmanned aerial vehicles (UAVs) and unmanned ground vehicles (UGVs). To cope with asymmetric state constraints in the planar subsystem, a nonlinear mapping along with a relaxation function is employed to transform the constrained states into an equivalent unconstrained form. Then, the single critic structure is integrated into the command filtered backstepping design framework to derive the distributed predefined-time optimal formation controller, where the adaptive fuzzy approximation is utilized to approximate unknown nonlinearities and the auxiliary performance function. It is demonstrated that the formation errors converge within a predefined time, while the positions of vehicles remain within the prescribed constraints. Finally, simulation results are provided to validate the effectiveness of the proposed control scheme.
Narcolepsy type 1 (NT1) is a chronic neurological disorder characterised by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep. Current pharmacological treatments often have limited efficacy, significant side effects or potential for abuse. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that has shown promise in regulating sleep-wake cycles and neural network activity. Preliminary evidence from our prior study on Transcutaneous Auricular Vagus Nerve Stimulation in patients with NT1 (TARGET-NT1 study) suggests potential benefits of taVNS for NT1. The TARGET-2 trial aims to evaluate the efficacy and safety of bilateral taVNS compared with unilateral taVNS and sham stimulation in patients with NT1. TARGET-2 is a randomised double-blind trial. A total of 153 participants with NT1 will be recruited from four centres in China. Participants will be randomly allocated (1:1:1) to receive either (1) bilateral taVNS (active stimulation on both ears), (2) unilateral taVNS (active stimulation on the left ear only) or (3) sham taVNS (minimal intensity stimulation on both ears). Participants and outcome assessors are blinded. The intervention will be administered twice daily for 30 min per session over 12 weeks. The primary outcome is the change in the Epworth Sleepiness Scale (ESS) score from baseline to the 12-week endpoint. Secondary outcomes are changes in the narcolepsy severity scale score, Pittsburgh Sleep Quality Index, fatigue severity scale score, 14-item Hamilton Anxiety Rating Scale score and 17-item Hamilton Depression Rating Scale score, as well as responder rates (proportion with ≥25% ESS reduction) from baseline to week 12. Safety will be assessed by monitoring adverse events. Ethical approval has been granted by the Medical Ethical Committee of Xijing Hospital (Approval Number: XJLL-KY-20252403). Written informed consent will be obtained from all participants before initiating any study-specific procedures. The results will be submitted for publication in a peer-reviewed journal. The anticipated completion date for reporting of the study results is 31 March 2027. Chinese Clinical Trial Registry, ChiCTR2500110531 (registered on 15 October 2025).
Postpyloric enteral feeding is recommended for ICU patients at high risk of aspiration. However, blind placement carries a rare yet potentially life-threatening risk of tube misplacement into the pleural cavity. We present a case in which blind insertion of a fine-bore naso-intestinal tube led to intrapleural malposition in an elderly patient with a history of radiotherapy for nasopharyngeal carcinoma (NPC). A 78-year-old Chinese man with severe dysphagia following radiotherapy for NPC underwent tracheotomy due to respiratory failure and was subsequently transferred to the ICU. The naso-intestinal tube was inserted blindly, and its position was considered appropriate based on limited fluid aspiration and auscultation. Nine hours later, chest radiography revealed that the tube had traversed through the trachea, entered the right lower-lobe bronchus, extended into the pleural cavity, and terminated mid-thorax. The tube was promptly removed and accurately repositioned into the stomach under laryngoscopic guidance. Blind postpyloric tube placement in patients with radiation-induced anatomical and neurological changes following NPC may result in silent intrapleural misplacement. Immediate pH testing combined with radiographic confirmation is crucial to prevent this potentially fatal complication.
The trade-off between mechanical robustness and ionic conductivity in gel materials impedes their application in flexible electronics. Herein, a eutectogel is engineered via a synergistic strategy that integrates a ternary deep eutectic solvent (DES) (choline chloride/ethylene glycol/zinc chloride) with dynamic Zn2 + coordination. Through in situ photopolymerization of 1-vinylimidazole in the ternary DES, a dynamically cross-linked organic-inorganic hybrid network is constructed. Crucially, Zn2 + ions play a dual role: they form reversible Zn2 +-imidazole coordination sites, enhancing the mechanical properties with an elongation at break of 1100% and a Young's modulus of 0.23 MPa, while inducing coordination-driven densification of the amorphous network. This compaction effect tightens the polymer network without triggering crystallization, while accessible ion-transport pathways are retained within the amorphous network. Consequently, the eutectogel exhibits a high ionic conductivity of 0.38 mS cm- 1, overcoming the typical conductivity loss in high-strength gels. Using these properties, a flexible strain-sensing system with Bluetooth transmission is developed. It can capture real-time motor signals and convert them into visual commands, highlighting its potential for wireless assistive monitoring, particularly in rehabilitation for hemiplegic patients. This work provides a promising strategy for achieving a balance between mechanical robustness and ionic conductivity in soft materials by regulating the amorphous structure.
Cortical control of movement is a distributed computation spanning multiple densely interconnected regions. Although we have rich anatomical atlases and a coarse understanding of how function maps to areas and subregions, we lack a detailed account of how behaviorally relevant activity is organized across the cortical sheet. Here, we trained head-fixed mice to perform a 15-target reach-to-grasp task while we performed cellular-resolution, two-photon calcium imaging across five regions of sensorimotor cortex (>39,000 layer 2/3 neurons). We characterized each neuron's trial-averaged peri-event activity with interpretable metrics and mapped these response properties across areas, revealing large-scale spatial structure. Neuronal response profiles often shifted abruptly at anatomical borders: motor areas showed sharper tuning and more linear relationships with target location, whereas somatosensory areas displayed more heterogeneous response patterns. Neural response properties also differed according to somatotopic representation. Nonlinear dimensionality reduction of the neural feature matrix revealed that areas varied in their average response profiles, but that areas did not have well-separated feature distributions; instead, each area contained subpopulations. Neurons in each subpopulation had characteristic response profiles and were distributed across multiple cortical areas. The spatial distributions of the subpopulations overlapped, with neurons from different subpopulations salt-and-pepper intermingled in the overlap zones. Together, these results describe novel activity structure across sensorimotor cortex and identify several distinct but spatially overlapping subpopulations with characteristic activity patterns during reach-to-grasp behavior. Reaching out to grab a cup of coffee may feel effortless, but it requires the brain to coordinate a precise sequence of movement commands. This control is supported by the sensorimotor cortex, the part of the brain's wrinkled outer layer involved in integrating incoming sensory feedback with outgoing movement commands. Researchers have traditionally divided the sensorimotor cortex into separate anatomical areas based on the shapes of neurons as well as their connectivity to other brain structures. This area-based view has shaped our understanding of the sensorimotor cortex based on the idea that different areas generally serve different functions. However, it has been less clear whether these functions change sharply at the borders dividing regions or whether groups of neurons within an area might perform different functions. Anatomical areas have long formed the basic unit for studying cortical function, yet recent work shows that movement-related activity is far more widely distributed than this view assumes. Understanding how the cortex controls movement, therefore, requires mapping the responses of large numbers of individual neurons across different areas, and determining how responses relate to known anatomical and somatotopic boundaries. Salimian, Grier and Kaufman sought to characterize how responses of single neurons are distributed across anatomically defined sensorimotor areas in the cortex of mice while they performed reach-to-grasp movements. Salimian et al. characterized the activity of nearly 40,000 individual neurons across different areas of the sensorimotor cortex of mice using interpretable features obtained from their activity during a challenging forelimb control task. Neural response features were then organized into coherent spatial gradients spanning motor and somatosensory cortical areas. The results showed that the spatial patterns possessed sharp transitions that closely aligned with anatomical and somatotopic borders. Clustering cells based on their features identified four unique subpopulations with characteristic response profiles, whose members were widely distributed across all recorded areas, but with different prevalence in each. The spatial distributions of these subpopulations formed overlapping zones, in which neurons from different subpopulations intermingled. The findings of Salimian et al. suggest that a complete understanding of the sensorimotor cortex requires mapping the distributed neuronal networks, instead of just focusing on separate, specialized areas. In the future, this view could inform clinical technologies such as the placement of recording electrodes for brain-computer interfaces that help paralyzed people move, or stimulation-based maps used to guide surgical resection of brain tissue. In addition, they may inform the design of neural networks for controlling robots, where sensory feedback must be integrated into choosing motor commands. However, realizing such benefits would first require confirming that these subpopulations exist in the human brain and elucidating their contributions to movement control.
Brain-computer interfaces (BCIs) promise to extend human movement capabilities by enabling direct neural control of supernumerary effectors, yet integrating augmented commands with multiple degrees of freedom without disrupting natural movement remains a key challenge. Here, we propose a tactile-encoded BCI that leverages sensory afferents through a tactile-evoked P300 paradigm, allowing reliable decoding of supernumerary motor intentions even when superimposed with voluntary actions. The interface was evaluated in a multi-day experiment comprising a single motor recognition task to validate baseline BCI performance and a dual-task paradigm to assess the potential influence between the BCI and natural human movement. The interface achieved real-time and reliable decoding of four supernumerary degrees of freedom, with significant performance improvements after three days of training. After training, performance did not differ significantly between the single-task and dual-task conditions, and natural movement remained unimpaired during concurrent supernumerary control. Lastly, the interface was deployed in a movement augmentation task, demonstrating its ability to command two supernumerary robotic arms for functional assistance during bimanual tasks. These results establish a neural interface paradigm for movement augmentation through stimulation of sensory afferents, expanding motor degrees of freedom without impairing natural movement.
Studies on the effects of γ-radiation on nonhuman primate (NHP) brains are limited, despite the critical need to understand the impact of radiation exposure on the brain from various sources like radiotherapy equipment, space travel, and potential nuclear events. We investigated molecular and neuropathological changes in rhesus macaque brains after a single 5.8 Gy total-body γ-radiation exposure. We analyzed samples dissected from frontal cortex (FCtx), hippocampus (Hippo), and cerebellum (CRB) of irradiated (RAD) vs. unirradiated/control (CTRL) animals. Western blotting and digital PCR (dPCR) analyses were used to measure different phosphorylated-Tau (pTau) forms and neurodegeneration markers (i.e., amyloid protein precursor [APP], neurofilament-light chain [NFL], glial fibrillary acidic protein [GFAP], ionized calcium-binding adapter molecule 1 [IBA1/AIF1], and myelin basic protein [MBP]). We detected lower levels of different forms of soluble pTau species (pTau181, and pTau217, among others) in RAD vs. CTRL animals across all three examined brain regions. While APP and GFAP levels were unchanged in the FCtx, increased IBA1 and NFL levels were detected alongside decreased MBP levels. Moreover, dPCR data identified decreased expression of GFAP and MBP in the FCtx. Importantly, the molecular changes observed were not accompanied by overt signs of neurodegeneration or cellular abnormalities upon neuropathological assessment. These findings in irradiated NHPs' brains are novel and indicate that a single total-body γ-radiation exposure significantly alters soluble pTau levels after a few weeks from irradiation without causing obvious neurohistological damage. These results open intriguing new possibilities of exploring γ-radiation-based strategies to modulate the progression of tauopathies, including Alzheimer's disease.
Non-O1/Non-O139 Vibrio cholerae isolates were recovered from three water samples from Lake Wonderwood near Seminole Beach, Florida. Two draft genomes assembled into five contigs (~4.1 Mb; GC 47.6%) and shared the same MLST type, whereas the third assembled into three contigs (~4.0 Mb; GC 47.4%) with a distinct MLST type.