Arcadia

Dry eye disease (DED) has increasingly been linked to oxidative stress; however, the specific redox mechanisms underlying different clinical phenotypes remain incompletely understood. This study aimed to evaluate tear film oxidative stress profiles in patients with primary DED and sarcoidosis-associated DED (S-DED) by assessing lipid peroxidation, antioxidant enzyme activity, and total tear protein content, and to explore their relationship with clinical tear film dysfunction. Tear samples were analyzed for superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as for malondialdehyde (MDA) and total protein levels, alongside standard clinical tests of tear film stability and secretion. Both DED groups exhibited significant oxidative alterations compared to controls, but with distinct redox signatures. Primary DED was characterized by markedly increased tear MDA levels, indicating predominant lipid peroxidation, whereas S-DED showed a more pronounced impairment of antioxidant defense, reflected by preserved or increased SOD activity in the context of significantly reduced GPx activity. Total tear protein levels were reduced in both groups, with evidence suggesting qualitative protein alterations in S-DED. The tear collection method significantly influenced the measured levels of several oxidative stress markers, underscoring the importance of sampling technique when interpreting tear-based redox profiles. Oxidative stress markers correlated with clinical measures of tear film dysfunction, supporting their physiological relevance. These findings demonstrate that DED encompasses heterogeneous oxidative stress mechanisms and that sarcoidosis acts as a modifier of ocular surface redox homeostasis. Distinct tear-based redox profiles differentiate primary from sarcoidosis-associated dry eye, highlighting the potential value of oxidative biomarkers for phenotyping DED beyond tear deficiency alone.

This paper presents a rigorous geometric realization of Morse theory within the framework of singular ring topological spaces, resolving the long-standing theoretical obstacles in non-smooth manifolds due to the lack of metric regularity. By embedding the Iwahori-Hecke algebra into the stratified filtration structure, we utilize the Jucys-Murphy elements and the Casimir center to construct a class of canonical "Hecke-Morse potential functions". The study shows that the non-commutative braiding relations of the algebra intrinsically encode the bifurcation dynamics behavior of the gradient flow across Whitney stratifications, effectively quantizing the classical Morse critical point set. Further, using the derived category tools, we establish a spectral sequence that converges from the local homology of the critical sub-manifolds to the global homology of the space. The core theorem confirms that under geometric purity conditions, the resulting Morse-Witten complex is isomorphic to the induced module structure of the Hecke algebra, proving that the Betti numbers of the ring space are strictly controlled by the Kazhdan-Lusztig basis. This framework not only eliminates the ambiguity in the definition of the gradient flow in the singular domain but also provides an intuitive geometric realization for the representation theory of quantum groups.

In robotics-assisted surgery, accurate segmentation of surgical instruments from background pixels is crucial for the success of various downstream tasks. Currently, popular segmentation models such as the U-Net exhibit excellent performance under major surgical conditions. However, when benchmarking the segmentation models under unforeseen surgical complications such as overbleeding, concerns toward their robustness remain. In fact, due to the lack of training datasets for the surgical segmentation models under complications, these models often exhibit degraded performances and thus result in failures for conducting accurate segmentations at the pixel level. In this paper, we leverage the Generative Adversarial Network (GAN), specifically through generating realistic images that simulate the condition of overbleeding to enlarge the training datasets a process known as data augmentation. With more diverse training data from different scenarios, segmentation models can be trained better and reduce the risk of errors. In addition, a dataset consisting of 17 mock endoscopic video sequences with binary masks indicating ground truths was used for training/testing. With the dataset, a U-Net architecture is used to examine performance through metrics such as the Normalized Surface Distance (NSD) and Dice Similarity Coefficient (DSC). As a result, integrations with GAN-based data augmentation allow segmentation models performances to improve 9.07% for NSD and 6.63% for DSC. From the results, our GAN-based augmentation is proven to be effective, providing a novel direction for improving models robustness during the training procedure, paving the way for future exploration and clinical translation of the cutting-edge deep learning models into real robotics surgery.

Abstract. The roadmap to enable operational soil moisture (SM) monitoring for meteorologic and hydrological early warning depends on the capabilities of the available remote sensing and modelling products. Since each type of soil moisture product shows specific strengths and limitations due to their technical restrictions over certain environments, the detection of impactful anomalies across a wide range of conditions and scales is often challenging and incomplete without a combination of complemental data types of sufficient resolution, revisit time and coverage. This study evaluates the capabilities of SM products of different nature and their compatibility for combination, with special attention to their uncertainties in spatial consistency and in residual trends. While the first has been often revisited to validate remote sensing and modelling products against in situ data, the last is often overlooked in studies addressing SM changes despite its potential to disrupt the outcomes. To meet the demands of operational monitoring this study evaluated three SM products: (1) the Satellite Application Facility on Support to Operational Hydrology and Water Management (H SAF) active Advanced SCATterometer (ASCAT)-derived dataset, (2) the passive subset of the European Space Agency (ESA) – Climate Change Initiative (CCIp), and (3) the modelled dataset from the European Drought Observatory (EDO). The analysis was carried out over Europe in the period 2007–2022 at 10 d temporal scales and 5 km × 5 km spatial sampling. First, Pearson's correlation coefficient (R) is used to measure the correspondence between H120, H121, CCIp and EDO SM products. Then triplets of the active, passive and model-based products are applied triple collocation analysis (TCA) to assess their performance based on TCA metrics such as the correlation, error variance, sensitivity and signal-to-noise ratio. We obtained that these popular well-validated datasets are increasingly capable in view of the notable TCA scores obtained but still subject to patches of spatial inconsistency and residual trends when compared against in situ SM data of the International Soil Moisture Network (ISMN). These uncertainties have minimal impact on drought monitoring in most of Europe, except in snow prone regions and for the assessment of long-term soil moisture trends used to design climate adaptation policies. Furthermore, each type of soil moisture product prevails in terms of triple collocation scores over the others under specific environmental conditions of the European continent. In view of the synergies shown by the active and passive remote sensing and the modelled SM estimates, two merged products are proposed and tested against the in situ data. The merging of the products is conducted by combining the various products based on weights calculated proportionally to the R_TCA scores of the triplets equalized in dynamic range matching their cumulative distribution functions. Results indicate that combining H SAF ASCAT, CCIp and EDO equals or surpasses the spatial and temporal consistency of the individual SM products alone, even when only the near-real-time products of H SAF ASCAT and EDO are combined. The evaluation of the trends of the individual products also indicates that small residual trends remain despite the improved filtering of the uncertainties, but given their differing sign of the trend, once combined into merged products can provide improved temporal stability of the series. Thus, merging remote sensing and modelled SM products enhances spatial consistency, resolution, temporal coverage and near-real-time capabilities for better European-scale drought monitoring, strengthening the early warning and risk management systems devoted to improving societal and environmental resilience.

A method is proposed to build an advanced knowledge base for preventing trouble and quickly recovering from trouble, which will contribute to the safe and stable operation and maintenance of large-scale, complex technical systems. This was developed based on the authors' conceptual research into structuring past trouble knowledge and the findings of three years of joint experimental research conducted by the authors on heliotron fusion plasma experimental facility. In the future, the feasibility of the advanced intellectual infrastructure will be verified through the implementation of a system that applies a higher harmonics system for electrical equipment to diagnose deterioration of electric pumps that make up the cooling system of neutron beam injection equipment.

Radial fractures are relatively uncommon (0-1%) injuries in postmortem studies of racehorses, and few cases have been published. We describe here a series of 42 cases of radial fractures observed in California racehorses. Autopsy findings from all racehorses submitted for postmortem examination between 2006 July 1 and 2022 June 30 that had a recorded radial fracture were evaluated. We included 42 horses (30 Thoroughbreds, 12 Quarter Horses), most of which were 3-5-y-old. Catastrophic radial fracture was observed in 30 (71%) horses; in the remaining 12 (29%) horses, the fracture of the radius was considered an incidental finding. All of the catastrophic radial fractures were complete, displaced, and comminuted; 70% were articular and 30% were non-articular; 61% were open and 39% were closed; 83% were diaphyseal to distal epiphyseal and 17% were proximal epiphyseal. Nine of the 30 horses with catastrophic fracture had a preexisting periosteal callus associated with the main line of fracture. Among Quarter Horse racehorses, the frequency of callus in radial fractures tended to be higher (p = 0.083) in 3-y-olds compared with other ages. In 6 of these 9 cases, the callus was located along the cranial aspect of the distal third of the diaphysis. All incidental cases consisted of osteochondral fragmentations, which occurred most frequently on the cranial border of the intermediate facet of the distal articular surface of the radius. Knowledge of the common sites of stress fractures or osteochondral stress remodeling in the radius can help to focus autopsies and to improve the characterization and interpretation of those lesions.

We study the reduction from a bipartite Hermitian matrix H to two single-qubit reduced Hermitian matrices HA and HB and the inverse problem. The inverse problem extends the so-called marginal problem from quantum information theory. We explicitly obtain the expressions of the matrices mentioned above and then extend them to positive semidefinite matrices by showing several inequalities involving a few parameters from the matrices. We also extend our results to multi-quit matrices. Our study constructs the intimate connection between the generalized marginal problems in terms of Hermitian matrices and the traditional marginal problem in terms of positive semidefinite matrices.

BackgroundDespite the remarkable clinical outcomes of epidermal growth factor receptor (EGFR)-targeted therapies in patients with lung cancer, therapeutic resistance eventually develops. This study elucidates the role of galectin-9 (Gal-9), a TIM-3 immune checkpoint ligand, in facilitating tumor immune escape during EGFR tyrosine kinase inhibitor (TKI) therapy, and evaluates the therapeutic potential of combined EGFR-TKI and Gal-9 blockade in preclinical models.MethodsEGFR-TKI-mediated Gal-9 regulation was systematically investigated through multianalysis including RNA-seq transcriptomics, quantitative reverse transcription-PCR, immunoblotting, ELISA, flow cytometry, and immunohistochemical validation across human and murine lung/colorectal cancer cell lines, murine tumor tissues, and paired patient tumor tissues/serum samples. Therapeutic efficacy was evaluated in two syngeneic murine models, with comprehensive immune monitoring of tumor microenvironment (TME), tumor-draining lymph nodes (tdLNs), and splenic compartments. Mechanistic investigations employed CD8+ T-cell/macrophage depletion strategies (anti-CD8α monoclonal antibodies (mAbs)/PLX-3397), type I interferon (IFN-I) pathway inhibition (anti-IFNAR1 mAbs), and lymph node retention approaches (FTY720 administration).ResultsEGFR-TKI treatment significantly induced Gal-9 expression in both tumor cells and host immune cells, particularly myeloid cells. Clinical validation revealed elevated Gal-9 levels in EGFR-TKI-treated patient with lung cancer tumor tissues and serums, correlating with reduced progression-free survival. Mechanistically, EGFR-TKIs triggered DNA damage-potentiated cytosolic double-stranded DNA accumulation and activated tumor-intrinsic STING-IFN-I innate immune pathway that transcriptionally regulated Gal-9 expression. Notably, Gal-9-neutralizing antibodies synergized with EGFR-TKI to markedly inhibit tumor growth in two syngeneic mouse models, including the poorly immunogenic LLC lung tumor model unresponsive to programmed cell death protein-1/programmed death-ligand 1 blockade. The combination therapy remodeled myeloid landscapes toward antigen-presenting phenotypes, promoted dendritic cell accumulation in the tdLN and enhanced CD8+ T response in the TME. Depleting CD8+ T cells or macrophages/monocytes abrogated the therapeutic benefits. Blocking the IFN-I pathway attenuated Gal-9 expression and enhanced the antitumor immunity of afatinib in the LLC tumor model.ConclusionsThese findings identify Gal-9 upregulation as a key mechanism mediating immune evasion and limiting EGFR-TKI efficacy, providing a promising combinational therapeutic strategy of EGFR-TKI and Gal-9 blockade for the treatment of EGFR-driven cancers.

Graduates of U.S. dental schools must meet curriculum and competency requirements set by the school and by the Commission on Dental Accreditation. Little is known about the impact of this training on recent alumni in practice. This cross-sectional study surveyed recent alumni about their preparedness and comfort in treating the oral health needs of children before and after a curriculum change in the predoctoral pediatric dental clinical course. Results were used to inform future curriculum improvement. Five classes of dental school alumni were surveyed at least 6 mo after graduation. Information about their practice setting, patient pool demographics, comfort and preparedness in diagnosing and treating common pediatric oral health conditions, and open-ended thoughts on caring for the oral health needs of children were obtained. Responses were analyzed before and after a curriculum change that introduced predoctoral students to patient care in the graduate pediatric dental clinic. Electronic and mailed paper surveys were sent to 552 alumni, with 218 (39.3%) returned. A majority (91.1%) reported seeing pediatric dental patients in practice. There was no difference in the incidence of seeing pediatric patients before or after the curriculum change. Participants reported high comfort and confidence in diagnosing pediatric oral health conditions, and there were no significant differences seen pre or post intervention. Surveyed alumni reported similar comfort levels in diagnosing and treating common pediatric oral health conditions both before and after the curriculum change. General dentist alumni still struggle with recommending that the first dental visit happen at the eruption of the first tooth or the child's first birthday. More information is needed to assess how to educate competent clinicians in a predoctoral setting.Knowledge Transfer Statement:The recommendations from this article can be used by dental educators to improve clinical and didactic teaching and to ensure dental learners' education and competency.

10032 Background: Identifying clinical and biological factors associated with outcomes in localized Ewing sarcoma (ES) will enable risk-stratified clinical trials with the goal of improved outcomes for high-risk patients and decreased treatment toxicity for low-risk patients. The specific aims of this analysis in localized ES patients were 1) to classify extraosseous (EO) primary tumors with subdivisions into deep (viscera, glands, body cavities, muscle, nerves) and superficial (cutaneous and subcutaneous) sites, and 2) to understand the relationship between baseline clinical factors (age, sex, primary tumor site, size (maximum dimension and volume)) and event-free survival (EFS). Methods: The analytic cohort included ES patients treated with ICC on AEWS0031 and AEWS1031. Primary tumor sites were defined as pelvic, non-pelvic, and EO (deep vs. superficial). Post-enrollment EFS was the primary endpoint. Univariate analyses used the Kaplan–Meier method (logrank test). Multivariable analyses used Cox proportional hazards models. To assess the impact of tumor volume as a continuous variable, a subgroup analysis was conducted using AEWS1031 only, as tumor volumes were collected prospectively on this study. Visual exploration of effects of continuous variables on EFS event hazard used restricted cubic splines with 3 knots. Tests were performed at the 5% level. Results: AEWS0031 (n = 628) and AEWS1031 Regimen B (n = 283) yielded 911 patients. In univariate analyses, difference in risk of EFS event was observed between tumor sites ( P = 0.03). EO tumors had the highest estimated EFS compared to pelvic and non-pelvic (5 year EFS 84.7% vs. 72.4% and 75.9%). Superficial EO appeared to be a very low-risk group, albeit interpretations are limited by the small group size and singular event (one second malignant neoplasm among 15 patients). In multivariable analysis of the combined cohort, sex, race, and ethnicity were not prognostic. EO tumors may be associated with decreased hazard compared with non-pelvic bone primaries (HR 0.58, P = 0.07), and tumors ≥200 mL with increased hazard (HR 1.56, P < 0.01). In the subgroup analysis, tumor volume and age were prognostic and in visualizations age was non-linearly related to the hazard of EFS event, increasing until approximately 15 years. Tumor volume was non-linearly related to the hazard of EFS event and increased until approximately 400 mL. Conclusions: Patients with ES and primary tumors ≥200 mL continue to be at higher risk of an EFS event when treated with ICC, and EO tumors may be lower risk compared with other sites. Risk of an event appears to remain constant in ES patients ≥15 years or with primary tumors ≥400 mL. These findings should be validated in prospective trials and tumor biology integrated with clinical factors to improve risk stratification for localized ES.