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.
Heart failure (HF) remains a pressing health concern, with rising prevalence globally. Subjectivity and ambiguity in the definition of HF and its antecedent stages have limited research, global surveillance, and prevention programs. To address this, several cardiac societies and foundations convened to standardize the definition of HF in 2021 and designated stage B or pre-HF to identify individuals at risk of developing HF. In subsequent years, substantial progress and changes have been made in aspects of preventing HF, improving HF diagnosis and management, and recognizing the importance of the affected individual's voice. Global differences and disparities in HF are better understood, as are causes and comorbidities leading to differences in care, which are also influenced by access to care. This consensus document presents the Second Universal Definition of Heart Failure, aiming to standardize terminology and facilitate a uniform approach for clinicians, researchers, health systems, and policymakers. In this definition, the classification of HF phenotypes moves away from rigid left ventricular ejection fraction cutoffs, instead grouping HF into reduced, preserved, and improved ejection fraction categories to better reflect clinical realities. A universal classification of HF causes is also proposed. The document also addresses the dynamic trajectories of HF-improvement, remission, and recovery-and highlights the impact of social determinants and geographic variation on HF risk and outcomes. By providing a comprehensive, standardized framework for HF definition and classification, this document seeks to improve prevention, early detection, and management of HF worldwide, ultimately enhancing patient care and advancing global cardiovascular health.
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 role of second surgical opinions (SSOs) in gastrointestinal (GI) cancer care is not well-defined. While SSOs are common, the impact may depend on whether patients ultimately undergo resection with the same surgeon or with a different surgeon after the SSO. We sought to characterize perioperative outcomes relative to SSO among older adults with GI cancers. Using SEER-Medicare data (2000-2019), patients aged 66-90 with primary GI were identified. Cancer-directed resections were categorized into three claims-observed pathways: surgery without SSO, SSO with same-surgeon resection, and SSO with different-surgeon resection. Multivariable regression models assessed the association between operative pathway and perioperative outcomes including complications, extended length of stay (LOS), 90-day readmission and mortality, discharge disposition, and achievement of a composite "textbook outcome." Among 40,603 surgical patients, 56.2% underwent surgery without SSO, 5.3% underwent SSO with same-surgeon resection, and 38.5% underwent SSO with different-surgeon resection. Compared with no SSO, SSO followed by resection with a different surgeon was associated with lower odds of 90-day readmission (aOR 0.92, 95%CI 0.88-0.97), any complications (aOR 0.90, 95%CI 0.84-0.95), extended LOS (aOR 0.93, 95%CI 0.88-0.98), and mortality (aOR 0.67, 95%CI 0.58-0.78), as well as higher discharge-home (aOR 1.05, 95%CI 1.01-1.12) and textbook outcome (aOR 1.12, 95%CI 1.07-1.17). In contrast, SSO with same-surgeon resection was associated with higher complications (aOR 1.14, 95%CI 1.01-1.29), longer LOS (aOR 1.21, 95%CI1.09-1.35), and lower home discharge (aOR 0.77, 95%CI 0.70-0.85) with no survival advantage. Among older adults undergoing GI cancer surgery, SSO followed by resection with a different surgeon was associated with improved perioperative safety and recovery, whereas SSO followed by resection with the same surgeon was not associated with similar benefit. These findings suggest that the value of SSO may lie in its role as a pathway to a different surgical team when clinically appropriate.
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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.
Graft failure remains a major complication in cord blood transplantation (CBT), particularly in patients with nonmalignant diseases, such as inherited metabolic disorders. However, optimal strategies for retransplantation after graft failure remain controversial. Here, we describe a case of mucopolysaccharidosis type II (MPS II) in which durable engraftment was successfully achieved following a second CBT using the same conditioning regimen as the initial transplantation. A 4-year-old boy with MPS II underwent unrelated CBT after undergoing a reduced-intensity conditioning regimen consisting of total abdominal irradiation, fludarabine, and melphalan. He acquired methicillin-resistant Staphylococcus aureus-associated sepsis early in the posttransplant period and developed graft failure on day 28, presumably due to drug-induced myelosuppression rather than insufficient conditioning intensity. Sixty-six days after the first transplantation, a second CBT was performed using the identical conditioning backbone but with antithymocyte globulin as immunosuppressant. The second course was complicated by severe hypercytokinemia with hemophagocytosis, cytomegalovirus antigenemia requiring preemptive antiviral therapy, and upper gastrointestinal bleeding. Nevertheless, donor chimerism remained high, and engraftment was confirmed on day 40 with transfusion independence on day 50. This case highlights the need for an etiological assessment of graft failure and demonstrates the viability of the initial conditioning regimen as a retransplantation strategy when inadequate conditioning is unlikely.
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.
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.
Density functional theory (DFT) calculations are employed to investigate the mechanism and selectivity of the oxygen reduction reaction (ORR) catalyzed by a dinuclear copper complex 1 [Cu2L2] (L = polypyridine-polyamide) in neutral aqueous solution. The ligand of complex 1 undergoes a protonation step to form the active species [LNHCuII---CuII]+ which initiates the catalytic cycle. This species undergoes a sequence of one-electron reduction, proton transfer, and another one-electron reduction to generate the reduced species [LNHCuI---CuILNH], which binds and activates O2 to form a peroxo-bridged intermediate [LNHCuII(μ-1,2-O22-)CuIILNH]. A two-proton-coupled one-electron transfer step followed by a one-electron reduction yields the key intermediate [LNHCuI(μ-1,1-HOOH)CuILNH], featuring a coordinated hydrogen peroxide unit. This species undergoes intramolecular O-O bond homolysis with a low overall barrier of 7.1 kcal/mol, producing the bis-hydroxo intermediate [OH-CuIILNH---LNHCuII-OH]. Notably, an extensive intramolecular hydrogen-bonding network within the [LNHCuI(μ-1,1-HOOH)CuILNH] intermediate kinetically suppresses the release of hydrogen peroxide, governing the high ORR selectivity of the catalyst. This study provides atomistic insights into O2 activation, the structural evolution of intermediates, and critical electron/proton transfer steps, establishing a theoretical blueprint for designing nonprecious metal ORR catalysts through the strategic integration of the second-sphere hydrogen-bonding network.
In underwater images, most useful features are occluded by water. The extent of the occlusion depends on imaging geometry and can vary even across a sequence of burst images. As a result, 3D reconstruction methods robust on in-air scenes, like Neural Radiance Field methods (NeRFs) or 3D Gaussian Splatting (3DGS), can degrade substantially on underwater scenes. While a recent underwater adaptation of NeRFs achieved high-quality results, it is impractically slow: reconstruction takes hours and its rendering rate, in frames per second (FPS), is less than 1. Here, we present a new method that takes only a few minutes for reconstruction and renders novel underwater scenes at 140 FPS. Named Gaussian Splashing, our method unifies the strengths and speed of 3DGS with an image formation model for capturing scattering, introducing innovations in the rendering and depth estimation procedures and in the 3DGS loss function. Across existing datasets and a new dataset we collected, Gaussian Splashing preserves competitive reconstruction quality while improving rendering speed, and it is particularly effective for distant scene details affected by backscatter.
Decision fatigue of nursing managers in stressful hospital environments is considered one of the fundamental challenges of healthcare management. It affects the quality of decisions and organizational outcomes. This study aimed to explore both the barriers that exacerbate decision fatigue and the protective factors and strategies that mitigate it from the perspective of clinical nursing managers during the COVID-19 pandemic. This qualitative study was conducted with a conventional content analysis approach. Participants consisted of 11 nursing managers working in the hospitals affiliated with Tehran University of Medical Sciences in Iran, who had been selected purposively and theoretically. Data were collected through semistructured, individual, and face-to-face interviews. MAXQDA software Version 18 was used for data management. Data validity was ensured according to the criteria of Lincoln and Guba (1985). The results revealed three main categories that encompassed both barriers (e.g., responsibility overload, organizational pressures) and protective factors (e.g., humanistic leadership, utilization of support resources), including organizational decision-making and leadership strategies, communication management and organizational interactions, and individual and organizational patterns in decision-making. Each of these categories consisted of two subcategories, including decision-making regulation and guidance, and humanistic management and leadership for the first category, activation of interaction and communication processes, and utilization of support resources for the second category, and finally independence and responsibility in decision-making, and organizational interest and commitment for the third category. Decision fatigue of nursing managers during the COVID-19 pandemic was shaped by a dynamic interplay of barriers and protective strategies. Clarifying these dual influences provides a coherent framework for understanding managerial decision-making under crisis conditions. Strengthening delegation, implementing decision pilots, and building organizational trust are effective strategies for reducing cognitive pressure and improving the quality of decision-making. Medical centers are suggested to reduce decision fatigue by addressing barriers such as organizational pressures and responsibility overload, while simultaneously strengthening protective factors such as supportive leadership, effective communication, and organizational trust.
The evaluation of disability grades in traffic accidents is a professional forensic clinical appraisal matter, and its results directly affect the fairness of judicial compensation. In the construction of automated disability grade evaluation models, the imbalanced distribution of disability cases leads to low recognition accuracy for minority categories, becoming a key bottleneck restricting the technology's implementation. In response, this paper proposes an imbalanced data classification method based on a hybrid parameter scaling weight optimization mechanism. First, a loss weight calculation model is constructed based on category proportion, category sparsity, and category diversity. Second, the loss weight calculation model is designed by integrating the focal loss function's ability to focus on hard samples with the cross-entropy loss function's global gradient stability advantage. Then, at the early stages of training, the model proposed in this paper aligns sensitivity to imbalanced categories and constructs a low-computational-demand hybrid parameter scaling weight optimization mechanism. Experimental results show that, compared with the best-performing baseline methods, the proposed method significantly improves both accuracy and macro-F1 score on the traffic accident disability grade dataset. It can effectively enhance the classification performance of minority grade categories in imbalanced data and help improve the accuracy of automated appraisal in judicial identification of traffic accident disability grades. 交通事故伤残等级评定是专业的法医临床鉴定事项，其结果直接影响司法赔偿的公平性。在自动化伤残等级评定模型构建中，不平衡的伤残案例分布使模型对少数类别的识别准确率较低，成为制约技术落地的关键瓶颈。对此，本文提出一种基于混合参数缩放权重优化机制的不平衡数据分类方法。首先，基于类别比例、类别稀疏度和类别多样性构建损失权重计算模型；其次，融合焦点损失函数对难分类样本的聚焦能力与交叉熵损失函数的全局梯度稳定性，设计损失权重计算模型；然后，在训练初期对齐本文模型对不平衡类别的敏感度，构建低算力需求的混合参数缩放权重优化机制。实验结果表明，相较于性能最优的基线方法，本文所提方法在交通事故伤残等级数据集上的准确率与宏F1值均有较大幅度提升，能有效改善不平衡数据中少数类等级的分类性能，有助于提高交通事故伤残等级司法鉴定中自动化鉴定的准确率。.
This study investigated whether the Wide-Awake Local Anesthesia No Tourniquet (WALANT) technique, widely used in hand surgery, is safe and acceptable in elective hallux valgus (HV) surgery. A total of 83 patients were included in this cross-sectional retrospective study, 38 of whom underwent surgery with WALANT and 45 of whom underwent surgery with spinal anesthesia (SA). The 2 groups were compared regarding demographic data, clinical results, and radiological outcomes. Preoperative preparation time and hospital stay were shorter in the WALANT group compared to the SA group. Visual analogue scale (VAS) values at the first, sixth, and 72nd hours after surgery were lower in the WALANT group. Intraoperative VAS-Anxiety (VAS-A) values were higher in the WALANT group, while postoperative VAS-A values at the sixth hour were lower. In the WALANT group, American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Rating System (AOFAS Hallux MT-IP) postoperative second-week values were found to be higher and the time to return to work was shorter than in the SA group. The groups had no significant difference regarding other variables. The WALANT technique in HV surgery is a method that can be easily applied, is safe, and is not inferior to SA in terms of clinical results. The WALANT shortens preoperative patient-preparation time, hospital stay, operating room usage, and return-to-work time after HV surgery. It improves functional and clinical results with low postoperative complication rates.
First, to evaluate whether the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is associated with hemodynamic changes in ophthalmic artery (OA) Doppler in near-term pregnancy. Second, to assess the performance of OA Doppler to rule in and rule out angiogenic factor imbalance. This was a cross-sectional cohort study nested within the PE37 randomized controlled trial, involving nulliparous women recruited between January 2023 and January 2025 who underwent sFlt-1/PlGF ratio measurement between 35 + 0 and 36 + 6 weeks' gestation. We included a subsample of women who underwent OA Doppler evaluation, including measurement of OA peak systolic velocity (PSV) ratio and OA pulsatility index (PI), as well as assessment of mean arterial pressure (MAP) and mean uterine artery (UtA) PI. The operator was blinded to sFlt-1/PlGF ratio values. Trends in median values of OA and maternal-fetal Doppler parameters across sFlt-1/PlGF tertiles were analyzed using the Jonckheere-Terpstra test and quantile regression, adjusting for maternal body mass index, age and smoking status. The predictive performance of the OA-PSV ratio for sFlt-1/PlGF ratio ≥ 38 was evaluated using receiver-operating-characteristics-curve analysis. We included 203 women, of whom 62, 71 and 70 were in the lowest, middle and highest tertiles of the sFlt-1/PlGF ratio, respectively. With increasing sFlt-1/PlGF ratio tertile, there was a significant increase in the OA-PSV ratio (median, 0.45 (interquartile range (IQR), 0.39-0.53) vs 0.48 (IQR, 0.41-0.58) vs 0.59 (IQR, 0.50-0.66); adjusted P < 0.001), a significant decrease in OA-PI (median, 2.20 (IQR, 1.92-2.61) vs 2.13 (IQR, 1.86-2.37) vs 1.86 (IQR, 1.60-2.26); adjusted P = 0.031) and a significant increase in MAP (median, 87.0 (IQR, 82.7-92.0) mmHg vs 88.7 (IQR, 83.7-93.7) mmHg vs 94.7 (IQR, 89.3-100.0) mmHg; adjusted P < 0.001). In contrast, no significant trend was observed in mean UtA-PI across sFlt-1/PlGF ratio tertiles. Among those individuals with an OA-PSV ratio < 0.61, 90.5% truly had a sFlt-1/PlGF ratio < 38, at a 15% false-positive rate. This study provides new evidence of a significant association between the sFlt-1/PlGF ratio and OA Doppler parameters in near-term pregnancies, suggesting that OA Doppler indices, particularly the PSV ratio, reflect angiogenic imbalance. Given its non-invasive nature, accessibility and low cost, OA Doppler emerges as a promising surrogate tool for ruling out angiogenic imbalance. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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.
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.
The aim of this study was to clarify the effects of reduced frame rates in videofluoroscopic swallowing studies (VFSS) on aspiration assessment. The consecutive key frames (CKFs), that is, the range of key frames that are essential for penetration-aspiration scale (PAS) scoring of abnormal laryngeal penetration (ALP) and aspiration, was defined using retrospective 30-frames/second (fps) VFSS records for 50 adult dysphagia patients at an acute care university hospital. The results showed that the CKFs was larger in 24 aspiration patients than in 26 ALP patients, and its distribution was wider. The minimum CKFs that included no trace of residual liquid (TRL) was 8 for aspiration. When reducing the frame rate in seven steps to 3.75 fps, the complete disappearance of CKFs with no TRL was seen in only four ALP patients. With partial disappearance of CKFs, the PAS scoring of ALP and aspiration even with a reduction to 3.75 fps agreed consistently and almost completely with that at 30 fps, and high reliability was obtained. This study was exploratory, but 3.75 fps was the lower limit that satisfied the criteria in analyses after defining the acceptable level for frame rate reductions in assessing aspiration.
This study focused on the critical environmental problem of harmful synthetic dyes being discharged into aquatic environments, which cannot be purified by conventional methods. We investigated the removal of methyl orange (MO) using Ceriporia lacerata RF-7, a recently discovered white-rot fungus, as a potent bioadsorbent. SEM and BET analyses of the biomass structure and texture revealed a complex, porous hyphae with sufficient surface area for dye adsorption, as well as a large specific surface area and mesoporous structure that promotes molecular diffusion. The efficiency of bioadsorption was significantly influenced by pH and temperature, achieving a maximum removal rate of 95.0% at pH 4. High removal efficiency was maintained up to 40°C, and at 30°C, the adsorption process was found to be thermodynamically spontaneous. This thermal stability shows that treating industrial wastewater does not require rigorous temperature control and is an energy-efficient method. Equilibrium results confirmed the Langmuir adsorption isotherm model (R2 > 0.999) and demonstrated a significant maximum monolayer adsorption capacity q max $$ {q}_{max} $$ of 185.10 mg/g, surpassing many commercially available and biological adsorbents. Kinematic studies demonstrated that the bioadsorption process adheres to a pseudo-second-order reaction mechanism, indicating that the rate-limiting step is influenced by both definite chemisorption and surface interactions. Thermodynamic studies show that the process is spontaneous (∆G° < 0), is endothermic (∆H° = +58.20 kJ/mol), and leads to greater disorder at the solid-liquid interface (∆S° = +224.0 J/mol·K). These findings underscore RF-7 as a strong, environmentally friendly, and highly effective biosorbent, providing a sustainable approach for the efficient treatment of industrial wastewater contaminated with dyes.
We evaluated clinical characteristics, response to therapy, event-free and overall survival (EFS and OS), patterns of recurrence/progression, and factors associated with survival in patients with metastatic non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) treated on the Children's Oncology Group ARST0332 trial. All patients with metastatic disease enrolled in ARST0332 were included. Treatment involved multimodal therapy with ifosfamide and doxorubicin, surgery ± radiotherapy. EFS was time from enrollment to progression, recurrence, second malignancy, or death; OS was defined as the time to death from any cause. The analysis included 80 patients, with synovial sarcoma as the most common histology (n = 21, 26%). Two-thirds of patients (n = 60) had >1 metastatic site, with the lung being the most common site of metastasis. At the week 13 therapy timepoint, response rate [complete or partial response (CR/PR)] was 41%, and 11% of patients had progressive disease. At a median follow-up of 7.5 years, 61 patients had relapse or progression, most commonly occurring at metastatic sites present at diagnosis (41%), followed by new metastatic sites (11%). The 5-year EFS and OS were 21% [95% Confidence Intervals (CI), 11 to 31] and 36% (95% CI, 24 to 47), respectively. In univariable analysis, histologic subtype was associated with EFS, whereas having a single metastatic site and achieving CR or PR at week 13 were associated with improved EFS and OS (p < 0.05). Survival of pediatric metastatic NRSTS remained dismal on ARST0332. Prognosis varied by histology, metastatic burden, and early treatment response, underscoring the urgent need for novel biologically informed, response-adapted treatment strategies.