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The fundamental operational range of cyborg insects, which are hybrid robots that combine a living insect with an electronic controller, is inherently restricted to the host's natural environment. To extend their operational range, we developed a wearable diving suit for terrestrial insects. The suit integrates a miniaturised oxygen generation module with a flexible waterproof shell, enabling continuous oxygen supply and isolation from surrounding water. By fitting a cockroach, which is a terrestrial species, into this diving suit, we allowed it to survive and operate in oxygen-deprived environments such as underwater, transforming it into an amphibious cyborg robot capable of operation across land and water. The suit sustained respiration and locomotion for up to 3 h underwater, establishing amphibious cyborg insects that combine biological adaptability with engineered protection for prolonged exploration in extreme, confined environments.
Age-related declines in muscle strength and neuromuscular control make sit-to-stand transitions and walking progressively more difficult, compromising mobility and independence. Although wearable assistive technologies have been proposed to alleviate these challenges, few have demonstrated clear benefits in facilitating sit-to-stand movements for older adults who retain a degree of independent mobility. Here, we introduce a soft hip exosuit designed to assist both sit-to-stand transitions and walking activities. In a feasibility study involving ten older adults, the exosuit increased 1-minute sit-to-stand repetitions by an average of 1.8 and reduced the metabolic cost of walking by 13.6% compared with the unassisted condition. These improvements were achieved while preserving natural kinematics, lower-limb stability, and maintaining a strong sense of agency. Our findings demonstrate that soft exosuits can enhance sit-to-stand and walking performance in older adults while preserving biomechanical naturalness and user autonomy, highlighting their potential for practical home-integrated mobility assistance.
Intraoperative radiation therapy (IORT) with electrons is associated with higher rates of ipsilateral breast tumor recurrence in early-stage breast cancer than whole-breast external beam radiation therapy (EBRT). Although limited randomized and retrospective data suggest that this approach may suit a subset of patients, its role remains uncertain. This study aimed to compare oncological outcomes between technically optimal IORT with electrons and whole-breast EBRT in suitable patients with breast cancer. In this single-center retrospective cohort study, patients were grouped by radiation treatment: IORT with electrons or whole-breast EBRT. Endpoints included disease-free survival (DFS), local control, and breast cancer-specific survival (BCSS). From January 2011 to December 2021, 204 eligible patients were reviewed (IORT, 74; EBRT, 130). The median follow-up was 5.1 years. The 5-year DFS rates were 95.61% for IORT and 98.08% for EBRT (log-rank P = .02). The 5-year local control rates were 98.46% for IORT and 100% (no event) for EBRT (log-rank P = .07). The 5-year BCSS rates were comparable: 98.61% for IORT and 100% (no event) for EBRT (log-rank P = .23). On univariable analysis for DFS, receipt of systemic treatment was a statistically significant protective factor (hazard ratio, 0.09; 95% CI, 0.01-0.74). Receipt of whole-breast EBRT was associated with a reduced risk of events, although this did not reach statistical significance (hazard ratio, 0.12; 95% CI, 0.02-1.01). IORT with electrons was associated with a modest but statistically significant reduction in 5-year DFS in appropriately selected patients compared with whole-breast EBRT, whereas BCSS remained comparable between groups. Therefore, electron-based IORT should be approached with caution and reserved for patients who prioritize treatment convenience.
Various forms of electrical stimulation have been integrated into the multimodal management of spasticity. However, high-frequency electrical stimulation can potentially induce muscle fatigue. The Exopulse Mollii Suit (EMS) is a multichannel full-body garment that delivers low-frequency (20 Hz), low-amplitude (20 V), subthreshold sensory stimulation aimed at reducing spasticity. Primarily, we examined the effects of a single session of the EMS on spasticity in 7 participants with chronic stroke or cervical spinal cord injury (SCI), specifically those with upper or lower limb spasticity impacting function and gait who were able to walk with minimal or no assistance (Functional Ambulatory Category scores of 2-5). We assessed the impact on gait and ambulatory function, as well as user perceptions of usability and acceptability. Participants wore the EMS for 60 minutes, consisting of 30 minutes of standardized goal-directed activities performed in two 15-minute blocks, interspersed with 15-minute rest breaks. Measurements included the Modified Tardieu Scale with surface electromyography for spasticity and functional mobility tests (Functional Ambulatory Category, 10-meter walk test, 5 times sit-to-stand test, and step test). Spatiotemporal gait parameters were quantified using a markerless vision-based motion capture system using the OpenPose BODY25 pose estimation model. On the basis of the Modified Tardieu Scale and surface electromyography signals, improvements in spasticity were only observed in 2 participants. However, 4 participants demonstrated faster walking speeds. Improvements in the 5 times sit-to-stand test and step test were noted in 3 and 4 participants, respectively. Spatiotemporal gait parameters revealed improvements in gait symmetry in 6 participants. Qualitative feedback based on the Assistive Technology Usability Questionnaire for People With Neurological Diseases (NATU Quest) returned positive results in 3 participants. Overall outcomes, defined as meeting the individualized goals of each participant, were positive in 4 participants. This case series provides preliminary evidence that a single session with the EMS may offer benefits for functional mobility and gait quality for individuals with spasticity resulting from stroke or SCI. To our knowledge, this is the first report examining the effects of the EMS in participants with SCI and the first to include spatiotemporal gait parameters associated with its use. However, the small sample size, variable outcomes, and lack of a control group necessitate caution in interpreting these findings and preclude definitive conclusions regarding the efficacy of the EMS. Larger, controlled trials with repeated sessions of EMS use are required to establish the effectiveness and optimal application of the EMS for spasticity management.
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Developing rapid, integrated sensing platforms for on-site pesticide monitoring is critical for food safety evaluation. However, current field-deployable sensors often suffer from poor stability and matrix interference. Herein, a catalytic/fluorescent multifunctional nanostructure (Ru-CN/UCNPs@ZIF-8) was engineered by co-encapsulating oxidase-like Ru-CN and upconversion nanoprobes within a ZIF-8 framework. This integrated architecture enables the highly sensitive detection of chlorpyrifos via the specific inhibition of an acetylcholinesterase-mediated fluorescence recovery cascade. To realize on-site visualization, the sensing system was incorporated into a GelMA hydrogel. Coupled with smartphone imaging, this hydrogel platform achieved a quantitative limit of detection of 1 ng mL-1, exceptional 28-day storage stability, and reliable recoveries (88.78%-112.38%) in fruit and vegetable matrix extraction. Finally, to ensure stable signal acquisition under complex field conditions, a custom portable device featuring an independent excitation module and power supply was fabricated. By effectively isolating environmental light, this hardware-assisted strategy provides a highly stable and precise tool for rapid food safety screening.
[This corrects the article DOI: 10.1371/journal.pone.0324558.].
Aging is accompanied by declines in cognitive, sensory, and motor functions that can adversely affect everyday activities, such as walking while performing a concurrent cognitive task. In this study, we investigate the effects of age and age simulation on dual-task performance, specifically focusing on gait and memory. We compare three groups: young adults (n = 28, Mage = 21.82, SDage = 1.96), young adults wearing an age simulation suit (n = 28, Mage = 22.07, SDage = 1.51), and older adults (n = 28, Mage = 72.82, SDage = 6.74). Participants performed a 2-minute walking test (walking as fast as possible) and a word memory test (learning words presented on a piece of cardboard) under single- and dual- task conditions (repeated measures). Gait parameters, including walking speed, cadence, stride length, and double-support time were recorded using a wearable motion capture system. Mixed-design ANOVAs were conducted with Group as a between-subjects factor and Task Condition as a within-subjects factor. The analyses revealed significant main effects of Task Condition, indicating impairments in both cognitive and gait performance under dual-task conditions (both p < .001), as well as significant main effects of Group, with older adults exhibiting the poorest performance overall (both p < .001). Notably, while memory performance did not differ significantly between young adults with and without the age simulation suit (p = .729), the suit resulted in significantly slower gait speed (p < .001) and alterations in other gait parameters approximating older adults' gait profiles. These results underscore that declines in central attentional capacity combined with peripheral deficits contribute to dual-task interference, potentially increasing instability and fall risk in older populations. Importantly, the group differences reveal how these mechanisms contribute in different ways to age-related performance declines.
Consumer involvement in clinical trials has developed to be a critical driver of feasibility and real-world translation. In gynaecological oncology, patient and clinician priorities can differ, particularly regarding acceptable risks and treatment burden. Vulvar cancer treatment typically involves a groin lymph node dissection, which carries significant morbidity, effecting the long-term health of patients. To address these harms, the Australian National Vulvar Cancer (ANVU) Phase 3 international randomised clinical trial (NCT06476639) will compare standard upfront groin lymph node dissection with serial groin ultrasound monitoring, a less invasive option, to reduce treatment burden without compromising survival. In this paper, research methodologists collaborated to bring consumer perspectives into the trial design to ensure the outcomes reflect what matters most to patients. We conducted a structured co-design workshop involving patients with lived experience of vulvar cancer as well as a multidisciplinary research team. The workshop explored priorities across three stages of care to determine the outcome measures for a clinical trial: before treatment, during treatment, and after treatment. Priority in the short-term was complete cancer removal, with acceptance of some short-term adverse effects. Medium-term priorities focused more on quality of life and functional recovery, as well as fear of recurrence. While long-term priorities identified avoiding chronic harms such as lymphoedema and maintaining a normal daily life, as important. These insights informed the trial's primary endpoint (survival following nodal metastasis at 30 months) and patient-centred secondary outcomes such as health-related quality of life, return to usual activities, and reduced chronic harms. Patient priorities shift as they progress through the various stages of cancer treatment, highlighting the need for dynamic, patient-centred clinical trial designs. The ANVU trial aims to incorporate true co-design in complex surgical oncology research. With consumers as research partners, the team has produced a trial protocol that is scientifically robust as well as grounded in lived experience, increasing its potential for real-world impact. The current paper focuses on co-design of the outcome measures of the trial, however consumer involvement will remain ongoing throughout the ANVU trial to ensure that the research outcomes are accessible and enable women to be provided with treatment options which suit their needs. Clinical trials have traditionally focused of patient survival and been driven by researchers to identify areas of need. Medical research is shifting toward a patient-centred approach, prioritising what matters most to those directly affected. This paper outlines how researchers and women with lived experience of vulvar cancer, a rare cancer affecting the skin and tissue of the vulvar, collaborated to design the outcome measures for an international clinical trial. The trial aims to reduce treatment burden without increasing cancer risk, to ensure women can maintain quality of life after cancer. The collaborative workshop explored what mattered most at three stages of care: before treatment, during treatment, and after treatment. Revealing patient priorities shift over time, with complete cancer removal being a priority in early treatment, functional recovery and fear of recurrence as medium-term priorities, and wellbeing considered in the longer-term. By embedding these insights into the clinical trial, the research team aim to influence everyday clinical decisions and support women to make treatment choices that best suit their individual needs and improve wellbeing.
Evidence on the effectiveness of electromyostimulation (EMS) has been reported in pulmonary rehabilitation, but the benefits have been limited in chronic obstructive pulmonary disease, and clinical trials in advanced idiopathic pulmonary fibrosis were not considered feasible. Recently, whole-body EMS (WB-EMS) has been developed and applied in the area of non-medical commercial application. To date, there are no reports on the application of medical WB-EMS for respiratory diseases. The aim of this study is to investigate the feasibility and acceptability of WB-EMS as an adjunct to pulmonary rehabilitation in patients with chronic respiratory disease. This is a protocol for a pilot, single group, feasibility trial. The e-skin is an EMS suit that can simultaneously load the muscles of the entire body (Xenoma Inc., Tokyo, Japan). Participants will conduct one session per day, once a week for 4 weeks. They perform resistance exercise trainings during EMS under the supervision and guidance of a trained physiotherapist or respiratory physician as a trainer. A physiotherapist controls the HUB attached to the suit with a dedicated mobile application. Each setting of EMS is determined by each segment of electrical stimulation and meets the recommended regimen and guideline criteria for WB-EMS operation. Outcome measures will include Modified Medical Research Council Dyspnoea Scale, pulmonary function test, health-related quality of life, exercise tests including six-minute walk test and one-minute sit-to-stand-test, Barthel Index, muscle strength, body composition analysis, and blood tests such as muscle markers and renal function markers. To assess the feasibility and acceptability of the intervention, participant adherence, retention, and perceived burden will be evaluated. WB-EMS can stimulate both type I and type II muscle fibers and may help counteract preferential type II fiber atrophy frequently observed in CRD. This pilot study focuses on verifying the feasibility and acceptability of WB-EMS as an adjunct to pulmonary rehabilitation. By providing a physiologically distinct, time-efficient training modality that minimizes cardiopulmonary load, WB-EMS could become a promising rehabilitation option for patients with limited exercise tolerance. UMIN-CTR, UMIN000057270. Retrospectively registered 12 March 2025.
Sertraline, a serotonin reuptake inhibitor (SSRI), has been implicated as a drug with repurposing capacities in cancer. This study aimed to evaluate the anticancer efficacy of sertraline alone and in combination with chemotherapeutic agents against pancreatic ductal adenocarcinoma (PDAC) cells. Antiproliferative effects of sertraline and chemotherapeutic agents against SUIT-2, AsPC-1, and MIA-PaCa-2 PDAC cells, either alone or in combination, were determined by MTT assay. Synergistic combinations were further evaluated by clonogenic assays, cell cycle analysis, and Hoechst 33258 apoptosis staining. Reactive oxygen species (ROS) levels were quantified using the DCFH-DA assay. Sertraline exhibited antiproliferative activity against PDAC cells (IC50 = 8.3-16.4 µM). When combined with gemcitabine or mitoxantrone, synergistic cytotoxicity was observed in most cell lines; however, the sertraline-gemcitabine combination demonstrated an additive effect in MIA-PaCa-2 cells. Mean CI values of 0.54 ± 0.06 and 0.80 ± 0.03 in SUIT-2 cells, 0.81 ± 0.04 and 0.79 ± 0.06 in AsPC-1 cells, and 1.06 ± 0.05 and 0.79 ± 0.05 in MIA-PaCa-2 cells, respectively. These combinations suppressed colony formation, altered the cell cycle, and enhanced apoptosis. Additionally, increased ROS generation was observed, particularly in the sertraline-gemcitabine combination, suggesting that oxidative stress may contribute to this interaction. Combinations with doxorubicin or cisplatin did not lead to synergism. These findings provide a rationale for further investigation of sertraline-based combination strategies in pancreatic cancer.
Three-dimensional (3D) printing is increasingly used to build electrochemical sensing platforms because it allows researchers to create complex geometries, combine multiple functional components in a single device, and adjust sensor designs to suit specific analytical applications. In this context, fused filament fabrication (FFF) has gained increasing attention for its ability to use conductive thermoplastic filaments and its suitability for rapid design iterations. This review summarizes recent research on electrochemical sensors produced by FFF printing, emphasizing how factors such as printing parameters, filament composition, post-printing processes, and device design affect electrochemical performance. The discussion also addresses ongoing issues with reproducibility, surface accessibility, and inconsistencies in reported performance. In addition, the review considers a range of routinely employed approaches to enhance electrode performance, including mechanical, chemical, and electrochemical activation, and stresses the importance of achieving an appropriate trade-off between sensitivity, stability, and other practical constraints.
Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.
The cerebellum contributes to sensory, cognitive, emotional, and pain-modulatory processes beyond motor coordination. In temporomandibular disorders (TMD), alterations in spontaneous cerebellar neural activity and strengthened functional connectivity with limbic structures have been reported, suggesting involvement of central neuroplastic mechanisms. Mandibular displacement and occlusal imbalance may further modulate brain networks related to motor regulation, sensory integration, and pain-related emotional processing.In this study, magnetic resonance imaging(MRI) and diffusion tensor imaging(DTI) was used to examine cerebellar connectivity across different mandibular positions in a patient with painful TMD. Functional MRI and diffusion tensor imaging were acquired in three conditions: centric occlusion, centric relation, and stabilization splint. Cerebellar regions of interest were defined using SUIT parcellation, and position-dependent structural-functional connectivity was assessed using diffusion-based tractography and Δ-metrics computed as the difference between the two tractography-derived matrices (Δ = MNI_NORM - COUNT_NORM); scale-invariant similarity metrics were used for between-condition comparisons.Under centric occlusion (CO), the Δ-derived connectivity pattern was sparse and included ROIs with zero-variance profiles, yielding mathematically undefined correlation entries; these were treated as missing values. In contrast, centric relation and stabilization splint conditions demonstrated heterogeneous Δ patterns and structured ROI-wise correlation profiles.In contrast, both centric relation and stabilization splint conditions showed moderate effect sizes in summary metrics. Pairwise comparison of vectorized Δ matrices (upper triangle; N = 378 ROI pairs) demonstrated a moderate association between CR and splint (Pearson r = 0.452, 95% CI 0.368-0.527; p = 2.0 × 10⁻²⁰; cosine similarity = 0.428). The Euclidean distance between Δ vectors was 1554.5, corresponding to a normalized per-element RMS difference of 81.1, and the mean absolute difference was 42.2.These single-subject findings suggest that mandibular position may be associated with measurable differences in Cerebellum-SUIT connectivity profiles in painful TMD. The results should be interpreted as exploratory and hypothesis-generating, and they require confirmation in larger prospective studies before clinical or therapeutic implications can be inferred.
This study investigated retinal interspecific differences between two sympatric lizards from the Turpan Basin of Xinjiang that occupy distinct microhabitats. Eremias roborowskii inhabits shrublands, while Phrynocephalus axillaris lives in open sandy areas. We adopted retinal whole-mounting, paraffin sectioning, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to compare retinal structure, oil droplet traits, photoreceptor arrangement, and ultrastructural characteristics between the two species. Both species exhibited five types of colored oil droplets, a temporal fovea, and a highly vascularized conus papillaris, confirming cone-dominant retinas. P. axillaris had larger oil droplets with an average diameter of 3.719 ± 1.100 μm. In contrast, E. roborowskii showed a higher oil droplet density of 1473 ± 1203 ind/mm2. The inner plexiform layer (IPL) was significantly thicker in E. roborowskii (56.01 ± 14.76 μm) relative to P. axillaris (50.76 ± 15.25 μm). The two species also differed markedly in photoreceptor ultrastructure. E. roborowskii contained mitochondria-rich ellipsoids, while P. axillaris possessed glycogen-enriched paraboloids. These structural variations reflect compatibility with local ambient light conditions. E. roborowskii is predisposed to suit diffuse shrubland light through high droplet density and mitochondrial-dominant ellipsoids, whereas P. axillaris tends to accommodate intense open-field sunlight via larger oil droplets and well-developed paraboloids. This study provides key morphological evidence to reveal how microhabitat divergence drives retinal specialization among desert reptiles.
Flexible behavior requires using past experiences to configure cortical computations to suit current task demands. A central question in neuroscience is how memory representations control such reconfigurations. Although hippocampal (HPC) engrams can drive learned behaviors, prior studies have been largely limited to a fixed stimulus-response computation. Thus, whether engrams can drive retrieval of a set of stimulus-response mappings, rather than a specific response itself, remains unresolved. Moreover, how engrams affect cortical task representations and dynamics so as to produce engram-consistent behavior remains unstudied. Here, we address both questions by combining tagging and reactivation of HPC engrams with simultaneous large-scale recordings in medial prefrontal cortex (mPFC) during a context-dependent task-switching paradigm in mice. We report that HPC engram reactivation caused mice to apply engram-consistent decision-rules rather than a specific motor output. Simultaneous mPFC recordings revealed that reactivating the HPC engram for a given context reinstated the representation of that context in mPFC within hundreds of milliseconds, indicating that it was mediated by rapid network effects, leading to choice behavior consistent with the reactivated HPC engram. Other aspects of endogenous dynamics in mPFC were left remarkably intact. Together, our findings provide direct causal evidence that HPC engrams can configure task-relevant population states of downstream cortical circuits in real time, establishing a neural mechanism by which memory traces control flexible behavior.
Cultural competence is important for health professions educators working in diverse educational and healthcare contexts. However, faculty development programs often focus more on instructional techniques than on educators' reflective, communicative, and adaptive capacities for culturally diverse learning environments. This study examined participants' self-perceived development of cultural competence and learning experiences within a two-year international faculty development program. A convergent mixed-methods study was conducted with 52 health professions educators from 30 universities across three countries. The quantitative component used a single-time-point retrospective pre-post self-assessment survey to examine participants' perceived changes in cultural competence. Paired-sample t-tests and Cohen's dz were used to assess statistical significance and effect sizes. The qualitative component included semi-structured interviews with 13 participants, analyzed using thematic analysis. Quantitative and qualitative findings were integrated to examine convergence, complementarity, and discrepancy. Participants reported statistically significant self-perceived gains in 8 of the 13 measured items. The largest effect was observed for adjustment of cultural understanding, t(51) = - 5.578, p < .001, Cohen's dz = 0.77. A moderate effect was also observed for adjustment of communication strategies, t(51) = - 4.071, p < .001, dz = 0.56. Small-to-moderate effects were observed for cultural self-awareness, knowledge adjustment, social confidence, persistence, and understanding of cultural value frameworks. No statistically significant perceived changes were observed in stress coping, p = .142; immediate cultural sensing, p = .302; or changing behavior to suit different cultural situations, p = .192. Qualitative findings suggested that participants' learning was supported by three interrelated processes: Contextualized Construction, Collaborative Learning, and Dynamic Co-Creation. These processes informed the CoLearn Framework and a developmental pathway from Awareness to Understanding and, for some participants, toward aspects of Adaptation. The program was associated with participants' self-perceived gains in selected dimensions of cultural competence, particularly cultural understanding and communication strategy adjustment. The CoLearn Framework offers an explanatory model for designing reflective, relational, and situated faculty development. More complex dimensions, including stress coping and stable behavioral adaptation, may require immersive practice, institutional support, and longer-term follow-up.
Our aim was to test the hypothesis that independently lowering muscle tissue temperature would attenuate post exercise increases in leg vascular conductance and decreases in arterial blood pressure. Eleven participants (4 females; age, 27 ± 6 years; height, 176 ± 10 cm; weight, 72.8 ± 11.3 kg; and VO2max 39.34 ± 7.69 mlO2.kg.min) completed three trials wherein they donned a water-perfused suit and exercised for 60-minutes at 60% VO2max followed by 60-minutes supine recovery. Different water-circulation protocols were employed to either maintain normal skin and muscle temperatures throughout recovery (Normothermic), lower skin and muscle temperatures during recovery (Cold) or lower muscle temperatures but rewarm the skin temperature back to normal during recovery (Rewarming). Internal (Tcore), skin (Tskin), and muscle temperatures (Tmuscle), mean arterial pressure , leg and cutaneous vascular conductance's were measured. Tcore was not different between trials (P > 0.05). Throughout the final 15 minutes of recovery, Tmuscle was lower (60 minutes: 35.94 ± 0.83°C vs. 36.74 ± 0.27°C, P < 0.05), but Tskin was not different (60 minutes: 33.8 ± 0.5°C vs. 33.9 ± 0.5°C, P > 0.05) in the Rewarming relative to the Normothermic trial. However, mean arterial pressure, leg vascular conductance and cutaneous vascular conductance were not different between Normothermic and Rewarming trials (all P > 0.05). The findings suggest that independently lowering muscle tissue temperature after exercise does not alter whole leg vascular conductance or decreases in arterial blood pressure.
Bioorthogonal chemistry is commonly used in chemical biology for the ligation of biomolecules and exogenous probes. The traditional copper(I)-catalyzed azide-alkyne cycloaddition and strain-promoted azide-alkyne cycloaddition remain key methods of ligating molecules, driven by transition metal catalysis in the former case and by built-in ring strain in the latter. While these 1,3-dipolar cycloadditions famously employ azides to react with alkynes, an alternative reaction partner is found in nitrones, which provide corresponding copper(I)-catalyzed and strain-promoted alkyne-nitrone cycloadditions. The latter are known to achieve faster kinetics than the corresponding azide reactions. Nitrones are also opportune for synthetically accessible electronic tuning of reaction rates, making them ideal for the design of mutually orthogonal labeling approaches. Our lab has demonstrated the versatility of alkyne-nitrone cycloadditions and developed straightforward workflows for the use of copper(I)-catalyzed and strain-promoted ligation reactions for bacterial labeling, including mutually orthogonal dual-labeling schemes. This chapter provides a sample of these methods, which may be easily adapted to suit the specific needs of a given system, for investigators seeking to take advantage of these simple and high-speed bioconjugation reactions.
Cognitive late effects are a common and serious complication of childhood cancer. This risk is particularly high in preschool-aged children, who are in a critical period of cognitive development and thus more susceptible to cognitive late effects. However, interventions targeting cognitive late effects in preschool children with cancer remain scarce and lack a strong evidence base. This study aimed to explore the acceptability and feasibility of Cognifit, an innovative digital gamified cognitive training method, in improving cognitive late effects among preschool children aged 3-6 years with cancer, and to describe the determinants of its implementation. A single-group, pre-post embedded mixed-methods design was employed to evaluate the feasibility, acceptability, adherence, and preliminary effectiveness of CogniFit among preschool children with cancer. Feasibility, acceptability, and adherence were assessed using quantitative indicators and qualitative caregiver interviews. Preliminary effectiveness was evaluated using the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P), Sustained Attention Test, Working Memory Test, and Pediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0). Quantitative and qualitative findings were integrated for analysis. Eighteen children and their caregivers were enrolled in the study; two participants withdrew, and 16 dyads were included in the final analysis. Quantitative findings demonstrated good feasibility and acceptability, with an intervention completion rate of 88.9%, session attendance rate of 81.7%, and duration adherence rate of 72.9%. Qualitative interviews showed that caregivers generally perceived the CogniFit program positively despite challenges related to regular participation and cultural adaptation. Preliminary effectiveness outcomes warrant further evaluation in larger controlled trials. Our study confirmed the feasibility and acceptability of the Cognifit digital gamified intervention for preschool-aged children with cancer and their caregivers. The study underscores the importance of adapting digital gamified interventions to better suit vulnerable populations such as preschool-aged children with cancer and proposes corresponding improvement recommendations. Future research should explore modifications to the intervention protocol while conducting large-scale, multicenter randomized controlled trials to evaluate the effectiveness of the intervention. Chinese Clinical Trial Registry ChiCTR2400092143 https://www.chictr.org.cn/showproj.html?proj=229415.