In this paper, the distributed Nash equilibrium seeking problem is addressed for the second-order systems without velocity measurement. The Nash equilibrium seeking methods with finite/fixed-time convergence are designed to obtain fast convergence speed and excellent steady-state performance, respectively. Firstly, a finite-time velocity observer is proposed to observe the players' own velocity in a finite time for second-order systems in the absence of velocity measurement. A distributed finite-time estimator is designed to obtain the position of other players using topology information. Based on the designed observer and estimator, a Nash equilibrium seeking strategy is proposed with finite time convergence. What's more, a strategy to find a Nash equilibrium with a fixed time convergence is suggested. This is based on a fixed time velocity observer and a distributed position estimator. The idea is to avoid being dependent on the settling time of the initial states of the system. Then, based on Lyapunov function as well as finite- and fixed-time stability, the convergence conditions of the studied closed-loop system are deduced. Finally, numerical examples are given to verify the effectiveness of the proposed algorithm.
First permanent molars (FPMs) erupt early and remain exposed to the oral environment for prolonged periods, making them particularly susceptible to dental caries, molar-incisor hypomineralization (MIH), restorative failure, and repeated restorative intervention. When long-term prognosis becomes unfavorable, extraction may represent a biologically appropriate treatment option. Favorable spontaneous eruptive adaptation of the second permanent molar (SPM) has been associated with several radiographic and developmental variables. This retrospective radiographic study evaluated demographic and panoramic radiographic parameters associated with favorable eruption potential of SPMs in children with indicated FPM extraction and investigated whether established radiographic conditions were present at the time extraction decisions were made. Following ethical approval, panoramic radiographs of 500 pediatric patients presenting with extraction-indicated FPMs (n = 712) were retrospectively evaluated. Demographic characteristics, dentition stage, number and location of affected FPMs, and extraction indications were recorded. Radiographic assessment included evaluation of SPM developmental stage according to Demirjian classification, SPM angulation, and presence of a third permanent molar (TPM) germ. Statistical analyses were performed using SPSS version 29.0. Descriptive statistics, chi-square tests, and multivariable logistic regression analyses were applied, with statistical significance established at p < 0.05. The mean age of the study population was 128.39 ± 22.11 months; 54.6% were girls and 45.4% boys. Extensive carious destruction (91.4%), repeated treatment interventions, severe structural breakdown, and MIH-related defects represented the principal indications for extraction. Radiographically, 17.6% of SPMs were classified as Demirjian stage E and 27.4% as stage F. Mesial angulation was observed in 55.2% of cases, while a TPM germ was present in 74.2%. However, only 12.8% of cases (62 patients, 91 teeth) fulfilled all predefined radiographic conditions associated with favorable eruption potential following FPM extraction. Radiographic conditions associated with favorable eruption potential of SPMs were present in only a limited proportion of cases at the time FPM extraction decisions were established. These findings highlight the discrepancy between theoretically favorable developmental timing conditions and the clinical realities of pediatric dental practice, where extraction is frequently necessitated by advanced structural disease. Systematic radiographic evaluation of SPM developmental stage, angulation, and TPM germ presence should therefore be incorporated into individualized treatment planning.
The continuous use of antibiotics and the emergence of multidrug-resistant bacteria, particularly Methicillin-resistant Staphylococcus aureus (MRSA), have become significant global health concerns. Therefore, it is imperative to explore non-antibiotic therapeutic options. Existing antimicrobial modalities, such as single-modality photothermal therapy (PTT), exhibit limited penetration depth and bacterial suppression and do not offer any advantageous biocatalytic activity. To address these challenges, we present a metal-regulated MXene nanozyme, Ag@V2C, designed to facilitate synergistic PTT and chemodynamic therapy (CDT) under second near-infrared (NIR-II) irradiation. The localized surface plasmon resonance of the nanoplatform, along with the silver-decorated V2C MXene, achieves a photothermal conversion efficiency (PCE) of 52 ± 2% for deep-tissue photothermal ablation. Furthermore, Ag@V2C functions as a nanozyme with inherent oxidase and peroxidase activities, generating reactive oxygen species (ROS) for CDT. Under NIR-II irradiation, the catalytic and photothermal effects are significantly enhanced. Insights from density functional theory calculations elucidate the interactions between Ag@V2C and its substrate, as well as the improved catalytic performance. Transcriptomic analysis indicates that treatment with Ag@V2C disrupts key bacterial biosynthetic and metabolic pathways, including aminoacyl-tRNA biosynthesis, pyrimidine metabolism, and central carbon metabolism. Consequently, it interferes with bacterial viability and resistance. In murine models of subcutaneous abscess and acute pneumonia, we demonstrate that Ag@V2C under NIR-II radiation effectively cures deep MRSA infections, promotes wound closure, and alleviates pulmonary inflammation, all while exhibiting good biosafety. This research proposes an effective strategy to combat MRSA infections through metal-regulated nanozyme design, NIR-II-amplified synergistic therapy, and transcriptomic mechanistic insights, showcasing strong translational potential.
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We present an experimentally feasible implementation of a secure multiparty computation application enabled by quantum oblivious transfer (QOT) on an entanglement-based physical layer. The QOT protocol uses polarization-encoded entangled states to share oblivious keys between two parties with quantum key distribution (QKD) providing authentication. Our system integrates the post-processing for QOT and QKD, both sharing a single physical layer, ensuring efficient key generation and authentication, respectively. Authentication involves hashing messages into a cryptographic context, verifying tags, and replenishing keys. This process uses a parallel QKD pipeline specifically for authentication, not for secure key generation. Oblivious keys are generated over a distance up to 25.8 km with a channel loss of 8.47 dB. In a back-to-back setup, a QOT rate of [Formula: see text] OTs/second is achieved, corresponding to 1 minute and 53 seconds per OT, primarily limited by the entanglement source. Using pre-distributed oblivious keys improved the rate to 0.11 OTs/second, or 9.1 seconds per OT. The considered QOT protocol is statistically correct, computationally secure for an honest receiver, and statistically secure for an honest sender, assuming a computationally hiding, statistically binding commitment. An experimentally feasible use case is demonstrated for privacy-preserving fingerprint matching against no-fly lists for border control. The fingerprint is secret-shared across two sites, ensuring security, while the matching is performed using the MASCOT protocol, supported by QOT. The application required 128 1-out-of-2 OTs, each with message length of 128 bits, with the highest security achieved in 20 minutes and 39 seconds. This work demonstrates the feasibility of QOT in secure quantum communication applications.
Central venous catheters (CVCs) are essential in modern healthcare. Insertion of a CVC promotes a hypercoagulable environment, in part through activation of the intrinsic coagulation pathway. We have previously shown that blood obtained from newly inserted CVCs demonstrates immediate coagulation activation, with differences between samples collected directly after insertion and after flushing of the catheter. The aim of this randomised trial is to compare early coagulation activation between four commonly used CVCs and to assess whether the different CVCs demonstrate different degrees of coagulation activation. This is a single-centre, randomised, parallel-group trial where adult patients (≥18 years) with a clinical indication for a two-lumen CVC will be eligible for inclusion. Participants will be randomised in a 1:1:1:1 ratio to receive one of four commercially available CVCs. The calculated sample size is 88 participants. Two blood samples will be obtained from each newly inserted CVC, the first obtained from the initial backflow of blood within seconds after insertion and the second after flush and discard. Samples will be analysed using rotational thromboelastometry with the non-activated thromboelastometry (ROTEM NATEM) and plasma-based coagulation assays. The primary outcome is the between-group comparison of the change in ROTEM NATEM clotting time between the two samples. Secondary outcomes include within-group and overall cohort comparisons of changes in clotting time. Additional secondary outcomes are between-group, within-group and overall cohort comparisons of changes in other ROTEM NATEM parameters, including clot formation time, alpha angle and maximum clot firmness, and changes in plasma-based coagulation markers, including prothrombin time-international normalised ratio, activated partial thromboplastin time, Factor VII, Factor XII and thrombin-antithrombin complex concentration. The results may help identify catheter materials that are less prone to activate coagulation and support in the selection and development of CVCs. This study has been approved by the Swedish Ethical Review Authority (#2022-00265-0). Written informed consent will be obtained from all participants before inclusion. The results will be published in a peer-reviewed journal and presented at scientific meetings. NCT07014722.
While recent studies have estimated the carbon footprint of surgical pathology, they did not consider the many other impacts this activity has on the environment. We aimed to estimate the environmental impacts of the preparation of hematoxylin-phloxine-saffron (HPS) staining, Congo red (CR) staining, and immunofluorescence (IF) staining for a biopsy analysis. We used a comprehensive life cycle assessment methodology of 18 environmental indicators. Life cycle assessment is a standardized and robust method for comprehensively assessing the various environmental impacts of a process throughout its entire life cycle. All contributing items (eg, materials, reagents, electricity) within the different technical steps in the surgical pathology department were considered. For the entire procedure (HPS + CR + IF), the electricity consumption of the cryostat for IF staining was the main contributing item for all indicators (from 19.4%-75.8%), except land use. The other most impactful contributing items were (1) single-use materials used during specimen grossing (second or third largest contributing item for 8 indicators), (2) electricity consumption during slide/block storage (second largest contributor for 6 indicators), (3) materials and consumables used during sample receipt (third largest contributor for 6 indicators), (4) materials used during cryostat section (third largest contributor for 6 indicators), and (5) reagents used during IF staining (second or third largest contributor for 5 indicators). Interestingly, for formalin fixation, the main environmental impacts were represented by global warming, fine particle matter formation, and human toxicity. These data allow us to better understand the environmental impacts of our activities and to propose more pertinent eco-design solutions.
Paroxysmal Sympathetic Hyperactivity (PSH) is a well-recognized complication following severe traumatic brain injury (TBI), with an incidence of 5-33% in the acute phase, characterized by episodic autonomic and motor hyperactivity. Management is often challenging, and a subset of patients develop refractory PSH despite optimized first- and second-line therapies. Cannabidiol (CBD) possesses neuroregulatory and autonomic-modulating properties demonstrated in preclinical TBI studies and epilepsy trials including Epidiolex studies, but its role in PSH has not been previously described. We report the case of a 44-year-old South Indian gentleman with severe TBI following a road traffic accident (GCS 5: E1V1M3) with CT brain showing bilateral frontotemporo-parietal acute subdural hematoma with mass effect. He underwent emergency bilateral decompressive craniectomy and required mechanical ventilation with tracheostomy. Three weeks post-injury, he developed recurrent PSH episodes (4-6 episodes per day) characterized by severe tachycardia (heart rate 140-180 bpm), hypertension (systolic blood pressure > 180 mmHg), hyperthermia (up to 40 °C), diaphoresis, and dystonic posturing. The diagnosis of PSH was established using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM), with a total score of 28 (Clinical Feature Scale: 18, Diagnosis Likelihood Tool: 10), indicating probable PSH. Infective, metabolic, epileptic, and structural causes were excluded. Despite treatment with multiple conventional agents at maximum tolerated doses-including bromocriptine (titrated from 1.25 mg twice daily to 40 mg/day), baclofen (10 mg/day), gabapentin (titrated from 150 mg/day to 300 mg/day), propranolol (15 mg three times daily), clonidine (0.2 mg/day), dexmedetomidine infusion (72-h infusion), and fentanyl (infusion followed by patches)-the autonomic storms persisted, fulfilling criteria for refractory PSH. Cannabidiol oil (100 mg/mL) was therefore initiated as adjunctive therapy at 100 mg twice daily (approximately 3 mg/kg/day) and titrated to a 100-150-100 mg/day regimen over one week via nasogastric tube. Within the first week, there was a marked reduction in episode frequency (from 4 to 6 per day to less than 1 per 48 h) and severity, with PSH-AM scores decreasing from 28 (CFS: 18, DLT: 10) to 16 (CFS: 6, DLT: 10), and opioid and sedative infusions were successfully withdrawn. By the second week, complete resolution of PSH episodes was achieved with a PSH-AM score of 4. No adverse effects were observed, including no hepatic dysfunction, excessive sedation, or hemodynamic instability. This case highlights a potential adjunctive role for cannabidiol in refractory PSH following severe TBI. While causality cannot be inferred from a single observation, the sustained clinical improvement after failure of conventional therapies warrants further prospective investigation.
Cisplatin-induced neurotoxicity is driven in part by neuroinflammation and oxidative injury in vulnerable brain regions. Glycine has anti-inflammatory and antioxidant properties that may offer neuroprotection against chemotherapy-related brain damage. Twenty-five adult male BALB/c mice were randomized into five groups (n = 5/group) Group 1 received cisplatin for 14 days; Group 2 received cisplatin plus glycine for 14 days; Group 3 received cisplatin for 28 days; Group 4 received cisplatin for 14 days followed by glycine for 14 days; and Group 5 received cisplatin for 28 days with glycine introduced from day 14 to day 28. Cisplatin was administered intraperitoneally at 3 mg/kg every fourth day, and glycine was given subcutaneously at 1 g/kg daily. The primary outcome was serum TNF-α measured by ELISA. Secondary outcomes were neuronal integrity and optical density in the hippocampus and frontal cortex assessed by Nissl staining. Data were analyzed using one-way ANOVA with Tukey post-hoc testing. Serum TNF-α levels differed significantly among groups (F = 230.422, p < 0.001). Mean TNF-α concentrations were 150.0 pg/mL in Group 1, 130.2 pg/mL in Group 2, 201.4 pg/mL in Group 3, 159.4 pg/mL in Group 4, and 171.0 pg/mL in Group 5. Prolonged cisplatin exposure (Group 3) produced the highest TNF-α levels, whereas concurrent glycine administration during the 14-day regimen (Group 2) resulted in the lowest levels. Compared with the 28-day cisplatin group, both delayed glycine treatment (Group 4) and glycine introduced during the second half of cisplatin exposure (Group 5) were associated with lower TNF-α concentrations. Histological analysis demonstrated reduced Nissl staining intensity and neuronal preservation in cisplatin-only groups, particularly Group 3, whereas glycine-treated groups showed better preservation of neuronal architecture and optical density in the hippocampus and frontal cortex. Glycine attenuated cisplatin-induced neuroinflammation and preserved neuronal integrity in the hippocampus and frontal cortex of mice. These findings support further preclinical evaluation of glycine as a low-cost adjuvant strategy to reduce chemotherapy-associated neurotoxicity.
Transcription factor-based cell-free biosensors are attractive for rapid and portable antibiotic detection, yet their performance is often constrained by limited sensitivity and high background signals. Here, we developed enhanced cell-free biosensors using RNA fluorescent aptamers and evaluated the Pepper-HBC620 system as a low-background, high-signal-to-noise reporter compared with the widely used Broccoli aptamer. To overcome intrinsic sensitivity limitations, two complementary strategies were employed. First, the concentrations of DNA templates and transcription factors were simultaneously reduced while maintaining constant molar ratios, which effectively lowered the activation thresholds for erythromycin and tetracycline. Second, tandem fluorescent aptamer modules (4×Broccoli and 8×Pepper) were designed as enzyme-free signal amplifiers. RNA secondary structure prediction and in vitro transcription confirmed that the tandem constructs preserved proper folding and displayed fluorescence intensities proportional to aptamer copy number without altering excitation or emission wavelengths. By integrating these strategies, strong fluorescence outputs were obtained with substantially reduced amounts of DNA templates and regulatory proteins. The optimized mphO-4×Broccoli biosensor achieved a detection limit of 0.1 μM for erythromycin, while the tetO-8×Pepper system enabled tetracycline detection down to 0.05 μM with a shortened response time. Overall, this study establishes tandem RNA aptamer-based cell-free biosensors for sensitive antibiotic detection.
Very high-power short-duration (vHPSD) radiofrequency ablation (RFA) is an alternative strategy for pulmonary vein isolation. However, rapid temperature rises may cause complications. The QDOT Micro is designed to detect temperature rises for automatic power and irrigation flow adjustments. We compared how differences in ablation electrode design between three RFA catheters impact vHPSD lesions. vHPSD RFA was performed within a validated gel tank model. Four-second ablations were delivered with stable contact force using the QDOT, SmartTouch, and TactiFlex SE at 60, 70, 80, and 90 watts, positioned perpendicular (90°), oblique (45°), and parallel (0°) to the ablation target, utilizing 0.9% and 0.45% "half-normal" saline (HNS) irrigation. The SmartTouch and TactiFlex were operated in power-controlled mode, and each configuration was repeated three times, with images captured every second to characterize lesions. In total, 216 vHPSD lesions were delivered. At 90 W, 90°, and 0.9% saline, the QDOT produced lesions with a mean depth of 1.93 mm. The TactiFlex produced shallower lesions, with a mean depth of 1.88 mm (p = 0.02), and the SmartTouch produced the deepest, with a mean depth of 2.37 mm (p < 0.001). The mean diameter of QDOT lesions, at 4.63 mm, was comparable to TactiFlex lesions (4.58 mm, p = 0.8), whilst the SmartTouch lesions were significantly wider than both the QDOT and TactiFlex (6.04 mm, p < 0.001). Steam-pop risk, based on lesion temperature, was lowest for the TactiFlex. vHPSD lesions produced with the QDOT achieved greater dimensions and temperatures than those with the TactiFlex under controlled conditions, suggesting a difference in the cooling profile of the ablation electrodes. vHPSD with the SmartTouch or 0.45% HNS are likely to increase the risk of steam pops.
Detecting atrial fibrillation (AF) is crucial for preventing stroke recurrence in embolic stroke of undetermined source (ESUS). However, prospective data directly comparing a single-lead patch electrocardiogram (ECG) with standard Holter monitoring remain limited. The AVANT-GARDE trial was a prospective, multicenter study comparing a 72-h patch ECG with 24-h Holter monitoring. Among 113 acute ischemic stroke patients, 90 with ESUS formed the primary cohort, and 23 non-ESUS patients with left atrial enlargement were included as an ancillary cohort. Patients underwent simultaneous monitoring at baseline, with an additional 72-h patch monitoring at 6 months for the ESUS cohort. At baseline, AF was identified in 13.3% of the cohort, associated with larger LA size (41.8±5.1 mm vs. 38.3±5.9 mm; p=0.037). The 72-h patch ECG monitor demonstrated a higher AF detection rate at baseline than 24-h Holter in both the ESUS cohort (16.7% vs. 5.6%, p=0.002) and the overall cohort (14.2% vs. 4.4%, p=0.001). At 6 months, two additional AF episodes (any duration) were identified, increasing cumulative detection rates to 18.9% in the ESUS cohort and 15.9% in the overall cohort (p<0.001 vs. baseline Holter). However, the number of prolonged AF episodes lasting ≥30 seconds did not differ significantly between the two modalities. Extended patch ECG monitoring enhances the AF detection rate over conventional Holter in patients with ESUS. For short-duration AF (<30 seconds), it should be interpreted as an exploratory marker of subclinical atrial cardiopathy requiring long-term clinical surveillance. Large-scale studies are warranted to confirm these clinical findings.
Neuropathological and biomarker evidence implicates tau dysregulation as a downstream component of Huntington's disease (HD) pathobiology, yet its in vivo distribution has not been characterised using second-generation tau-PET tracers. We aimed to define the regional organisation, stage dependence and clinical relevance of tau-sensitive PET signal across the HD disease spectrum. Fifty-four participants (13 healthy controls, 9 premanifest mutation carriers and 32 manifest carriers) underwent 60-minute dynamic [¹⁸F]PI-2620 PET imaging. Tau-PET signal was quantified using distribution volume ratios (DVR) derived from reference-tissue kinetic modelling. Analyses combined region-of-interest and whole-brain mapping with threshold-based positivity profiling, modelling of cumulative genetic disease burden (CAP), and clinico-anatomical association analyses. Tau-PET abnormalities showed a spatially ordered pattern dominated by subcortical involvement. The globus pallidus exhibited the strongest effect, with marked DVR increases and high positivity rates emerging in premanifest carriers and approaching saturation in manifest HD. Additional subcortical changes involved the putamen, whereas caudate DVR decreased in manifest disease. Cortical effects were more modest and selectively involved posterior associative regions. CAP modelling supported predominantly monotonic subcortical stage-related profiles, while limbic and cortical regions showed heterogeneous cross-sectional patterns. Clinico-anatomical analyses linked subcortical tau-PET signal with genetic burden and motor severity and limbic signal with psychiatric symptoms. Tau-sensitive PET signal represents a spatially ordered and stage-dependent feature of HD and identifies a reproducible pallidal signature linked to disease burden, supporting its potential as a biomarker for patient stratification and mechanistic monitoring in therapeutic studies targeting downstream pathological processes. NCT07503743.
Acute orthopedic fractures pose significant treatment challenges, requiring efficient and effective management to improve patient outcomes. This study compares the efficiency and prognosis of fast-track surgical management versus conventional early definitive treatment in managing acute orthopedic fractures. This retrospective cohort study included 116 patients with acute orthopedic fractures treated between June 2024 and June 2025. Patients were assigned to either a fast-track surgical management group (fast-track group, n = 60) or a conventional early definitive treatment group (control group, n = 56). The primary outcome was in-hospital mortality. Secondary outcomes included operation time, intraoperative blood loss, transfusion volume, body temperature recovery time, time to first ambulation, length of hospital stay, hospitalization cost, postoperative pain assessed using the Visual Analog Scale (VAS) at 24, 48, and 72 h, fracture healing quality, postoperative complications, and 6-month health-related quality of life evaluated using the 36-Item Short Form Health Survey (SF-36). Logistic regression analyses were performed to identify factors associated with in-hospital mortality. In-hospital mortality was significantly lower in the fast-track group compared with the control group (5.00% vs. 16.07%, P = 0.044). The fast-track group demonstrated significantly shorter operation time, reduced intraoperative blood loss and transfusion requirements, earlier postoperative ambulation, shorter hospitalization duration, and lower total medical costs (all P < 0.05). VAS scores at 24, 48, and 72 h were consistently lower in the fast-track group (all P < 0.05). The overall complication rate was significantly reduced (5.26% vs. 19.15%, P = 0.027). The good healing rate was higher in the fast-track group (P = 0.013). At 6 months, several SF-36 domains, including physical functioning, role physical, vitality, social functioning, and general health, were significantly higher in the fast-track group (all P < 0.05). Multivariable logistic regression analysis demonstrated that fast-track group remained significantly associated with lower in-hospital mortality (OR = 0.352, 95% CI: 0.118-0.947, P = 0.041), whereas higher Injury Severity Score was an independent risk factor (OR = 1.196, 95% CI: 1.031-1.387, P = 0.018). Fast-track surgical management was associated with lower in-hospital mortality, enhanced perioperative efficiency, reduced complications, and improved functional recovery compared with conventional early definitive treatment in patients with acute orthopedic fractures.
Curiosity is a fundamental driver of human cognition and behaviour throughout the lifespan. Distinct from the instrumental value of information in helping to achieve a pre-defined goal, curiosity can be defined as an intrinsic taste for information itself. Although existing research has suggested a role for curiosity in enhancing learning outcomes, questions remain regarding the mechanisms underlying the curiosity-learning relationship. In the current work, we explored the interplay between curiosity, confidence, and learning in relation to the perceived "knowability" of information. Drawing on Loewenstein's information gap theory and the classical observation that curiosity is maximum at intermediate states of knowledge, we propose that curiosity is influenced by the availability of potential answers, reflecting the subjective perception of information's knowability. We conducted two online experiments using trivia questions, wherein participants estimated the number of candidate answers they had in mind for each question, reported their curiosity and confidence regarding the correct answer, and their surprise when told it. Five days later they completed a memory test for those answers. Results indicate that greater availability of candidate answers predicted heightened curiosity, moderate confidence, and enhanced memory retention. These results were replicated in a second experiment despite controlling for prior knowledge. This finding suggests that curiosity is not solely triggered by an information gap but also by the perception that information is retrievable. Our study highlights the significance of subjective perceptions of information accessibility in understanding curiosity and its impact on learning. These findings contribute to the growing body of research investigating the cognitive processes underpinning curiosity and its implications for effective learning strategies.
Cervical cancer remains a major cause of morbidity and mortality among women in Uganda. Although the Human Papillomavirus (HPV) vaccine is highly effective in preventing cervical cancer, completion of the recommended two-dose schedule remains low, particularly in rural settings. Rukiga District was selected for this study due to persistently low HPV second-dose (HPV2) completion rates compared with national targets. This study assessed health facility-level barriers influencing HPV vaccine completion among adolescent girls aged 9-14 years in rural Uganda. A mixed-methods cross-sectional study was conducted between June and September 2022 in selected Health Centre II (HC II), Health Centre III (HC III), and Health Centre IV (HC IV) facilities in Rukiga District. A household survey involving 292 caregivers of eligible adolescent girls was conducted using systematic random sampling. The primary outcome was completion of the two-dose HPV vaccination schedule (HPV2). Quantitative data were analysed using logistic regression to identify factors associated with vaccine completion. In addition, 21 key informant interviews involving 11 healthcare workers and 10 Village Health Team (VHT) members were conducted and analysed thematically to explore contextual barriers affecting HPV vaccine uptake and completion. The HPV vaccine completion rate was 23.49%, indicating low coverage. In multivariable analysis, vaccine stock-outs and cold-chain challenges (adjusted odds ratio [AOR] = 1.75, 95% confidence interval [CI]: 1.04-2.93; p = 0.004) and understaffing of healthcare workers (AOR = 1.97, 95% CI: 1.05-3.68; p = 0.006) were the only statistically significant predictors of HPV vaccine completion. Although limited healthcare worker knowledge (AOR = 0.94, 95% CI: 0.70-1.24) and absence of government programmes targeting out-of-school girls (AOR = 0.97, 95% CI: 0.73-1.29) were not statistically significant in the adjusted model, qualitative findings highlighted them as important contextual barriers. Additional challenges identified included weak outreach systems, transportation constraints, misconceptions about HPV vaccination, and limited community awareness. HPV vaccine completion in rural Uganda remains low and is strongly influenced by health system constraints, particularly vaccine supply-chain disruptions and human resource shortages. Strengthening vaccine logistics, improving staffing levels, enhancing healthcare worker capacity, and expanding outreach strategies targeting underserved populations are essential for improving vaccine completion and achieving national immunisation targets.
To investigate the knowledge, attitudes and practices (KAP) of parents of children born moderate to late preterm (32 to <37 weeks' gestation) regarding their children's neurodevelopment. A cross-sectional study. This study was conducted from March to June 2025 at the Second People's Hospital of Changzhou. Parents of children born moderate to late preterm were surveyed in the outpatient clinic when their children were at preschool age. No. KAP scores were assessed using a questionnaire, and differences among parents were compared across different demographic characteristics. KAP scores were converted to percentages and interpreted using a 70% descriptive cut-off. Structural equation modelling was employed to investigate the inter-relationships among the KAP dimensions. This study included 499 participants, with a mean maternal age of 34.03±5.42 years; the majority were women (92.79%). The mean knowledge score was 7.22±3.53 (out of a possible maximum of 18), the mean attitude score was 23.91±5.16 (out of a possible maximum of 35) and the mean practice score was 25.84±5.08 (out of a possible maximum of 40). The knowledge scores correlated with the attitude (r=0.193, p<0.001) and practice (r=0.558, p<0.001) scores, while the attitude scores correlated with the practice scores (r=0.312, p<0.001). The path analysis revealed that knowledge had a direct influence on attitude (β=0.290, p=0.011) and practice (β=0.582, p=0.006). Attitude had a direct influence on practice (β=0.228, p=0.012). Knowledge also had an indirect influence on practice through its impact on attitude (β=0.066, p=0.005). Parents' KAP scores were below the descriptive 70% sufficiency threshold, particularly for knowledge, suggesting unmet needs for clearer follow-up communication and family-centred neurodevelopmental education. Interventions should focus on strengthening family-centred education, clearer follow-up communication and parental engagement in neurodevelopmental monitoring and early intervention.
Noise-induced hearing loss (NIHL) is the second leading cause of deafness globally. However, effective pharmacological treatments remain unavailable. Excitotoxicity, an early NIHL event, is a central mechanism in degeneration of cochlear synapses established between inner hair cells (IHCs) and spiral ganglion neurons (SGNs). This excitotoxic damage can trigger the degradation of the neurotrophic TrkB receptor, thereby inhibiting brain-derived neurotrophic factor (BDNF) signaling and challenging neurotrophin-based therapies for hearing loss. We employed an ex vivo model of excitotoxicity, where excitotoxicity was induced in cochlear explants by overstimulation of excitatory glutamate receptors, and an in vivo model of noise overexposure. The effects of excitotoxicity on the neurotrophic system and cell architecture were established by immunohistochemistry. Hearing function was evaluated in vivo by the auditory brainstem responses (ABR) test, performed before and after noise overexposure. In this study, we evaluated the therapeutic potential in the inner ear of MTFL457, a cell-penetrating peptide designed to prevent TrkB-FL degradation in brain excitotoxicity. MTFL457 showed efficient distribution across cochlear cell types in both ex vivo and in vivo models, supporting its ability to reach the inner ear and suggesting that it can cross the blood-labyrinth barrier after systemic administration. In explants undergoing excitotoxicity, MTFL457 prevented TrkB-FL dysregulation, partially restored downstream prosurvival signaling, and significantly reduced neuronal damage and features associated with cochlear synaptopathy. In vivo, despite known sex-dependent differences in susceptibility to noise-induced damage, treatment with MTFL457 preserved auditory function and synaptic integrity in both males and females, although the magnitude of protection varied between sexes. Together, these findings support a protective effect of MTFL457 in models of excitotoxic cochlear injury. These results support the therapeutic potential of peptide MTFL457 for treatment of NIHL and possibly other types of sensorineural hearing loss likewise associated with excitotoxicity.
Targeted therapies have improved outcomes in ROS1-rearranged NSCLC "ROS1", but real-world evidence on evolving treatment sequencing and survival to understanding this rare cancer remains sparse. ROS1 cases identified from the Australian multicentre AURORA cohort between 2012 and 2025 were analysed. Demographic, diagnostic, and treatment data were extracted, with systemic therapies mapped to report sequencing and discontinuation. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Multivariable Cox models assessed clinical correlates of outcome. Among 5,189 NSCLC cases within AURORA, 115 (2.2 %) were ROS1 positive. Median age was 58 years; 64 % female; 85 % had de novo advanced disease, 14 % baseline brain metastases. Amongst n = 16 with early-stage, 59 % recurred. In total n = 104/115 (90 %) were treated for advanced disease, median 2 lines; range 1-8, 32 % did not receive a second line. First-line ROS1-inhibitor therapy (ROS1i) was given to 74 % (n = 77), including early-generation (n = 63; crizotinib/entrectinib) and later-generation ROS1i's (n = 14; repotrectinib/zidesamtinib/lorlatinib). Across all lines, 96 % received a ROS1i including 63 % with later-generation, and 53 % participated in a clinical trial. Median PFS with first line early-generation ROS1i was 17 months(mo), 48mo for first line later-generation ROS1i (p = 0.071). Median OS was 56mo overall, 80mo with first line later-generation ROS1i. Median OS was 26mo in those with brain metastases at diagnosis versus 58mo without (p = 0.010) and 41mo in those with PD-L1 ≥ 50 % versus 62mo 0-49 % (p = 0.017). This multicentre real-world cohort describes longitudinal ROS1 management with evolving treatments. Favourable survival likely reflects reflex molecular testing, access to ROS1i, and high clinical trial enrolment.
The design of smartwatch antennas confronts two challenges. The forward problem is related to how to reduce the performance degradation caused by the arm effect, while the inverse problem involves how to diminish the electromagnetic exposure of the antenna to the human body, especially for children who are sensitive to radiation. This paper presents a smartwatch antenna featuring a metamaterial protection layer, which satisfies the requirements of 4 G communication and Wi-Fi. The smartwatch antenna loaded with the metamaterial layer is fabricated. The electromagnetic exposure dose is simulated, and the reflection coefficient of the antenna is measured when it is worn on the arms of adults and children, respectively. Simulation and measurement results demonstrate that the addition of the metamaterial layer can alleviate the frequency shift; the bandwidth is improved by 8.8%, and the gain is enhanced by 7.8% at most. Furthermore, the peak specific absorption rate (SAR) values in the arms of children and adults decrease by up to 6% and 14%, respectively, conforming to the safety limits stipulated by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The findings indicate that the proposed metamaterial layer with reflective performance can mitigate the reduction in radiation performance caused by the arm and concurrently minimize the radiation dose absorbed by the arm. This presents a viable strategy for electromagnetic radiation protection. Smartwatch antennas face two main challenges: first, The wearer’s arm can interfere with antenna performance, and second, the antenna’s electromagnetic radiation may affect the human body – especially children, who are more sensitive to such exposure. This study introduces an innovative solution using a specially engineered material layer placed between the antenna and the arm. Tests and simulations show that this material layer helps maintain stable signal quality by reducing frequency shifts and improving antenna strength. It also significantly cuts radiation absorption in the arm – by up to 6% for children and 14% for adults – keeping it within international safety guidelines. In simple terms, this research makes smartwatches work better and safer, offering added protection, particularly for young users.