Effect of Cl2 Radical on Dry Development of Spin-Coated Metal Oxide Resist.

In this study, the effects of Cl2 radicals on dry development of spin-coated metal oxide resist (MOR) and changes in its surface binding states were investigated to verify the mechanism of dry development. Dry development characteristics of tin hydroxide (Tin OH), which is one of the MOR candidates for next generation lithography, were investigated as functions of process time and temperature using a Cl2 radicals source. Non-UV-exposed Tin OH film showed a linear etch rate (1.77 nm/min) from the initial thickness of ∼50 nm, while the UV-exposed film showed slower etch behavior (1.46 nm/min) in addition to the increase of film thickness for up to 3 min during the Cl2 radical dry development. UV-exposed photoresist (PR) contained more oxygen (Sn-O bonding) in the film due to the removal of butyl compounds from the clusters during the UV exposure process. Therefore, due to the lower reaction of chlorine radicals with Sn-O in the UV-exposed Tin OH than the other bindings, the non-UV-exposed PR was preferentially removed compared to the UV-exposed PR. As the temperature decreases, the overall etch rate decreases, but the difference in etch rate between exposed and unexposed Tin OH becomes larger. Finally, at a substrate temperature of -20 °C, the non-UV-exposed Tin OH with a thickness of 50 nm was completely removed, while ∼30 nm thick PR remained for UV-exposed Tin OH. Eventually, a negative tone development was possible with Cl2 radical plasma due to the difference in activation energy between the UV-exposed and non-UV-exposed films. It is believed that dry development using Cl2 radicals will be one of the most important process techniques for next-generation patterning to remove problems such as pattern leaning, line edge roughness, residue, etc., caused by wet development.

Evaluation of the Properties of 3D-Printed Onyx-Fiberglass Composites.

This study evaluated the properties of 3D-printed Onyx-fiberglass composites. These composites were 3D-printed with zero, one, two, three, and four layers of fiberglass. Ten samples of each configuration were printed for the tensile and flexural tests. The average tensile strength of the Onyx specimens was calculated to be 44.79 MPa, which increased linearly by approximately 20-25 MPa with each additional fiberglass layer. The elastic moduli calculated from the micromechanics models were compared with the experimental values obtained from the tensile tests. The experimental elastic modulus increased more significantly than the model prediction when more fiberglass layers were added. The flexural modulus of Onyx was 17.6 GPa, which increased with each additional fiberglass layer. This quantitative analysis of composites fabricated using 3D printing highlights their potential for commercialization and industrial applications.

A multi-biomarker panel for predicting Tocilizumab response in Rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients.

Kinetic and competitive effects of sorption on multi-element migration through crushed granite and biotite gneiss in Ca-HCO3-SO4 type groundwater.

Crystalline rock is used as the host rock for the disposal of high-level radioactive waste. Two cationic elements (Cs(I) and Ni(II)) and three anionic elements (Se(IV/VI), Mo(VI), and U(VI)) were selected to comprehensively evaluate the sorption behaviors of these radionuclides on crystalline granite and biotite gneiss. The anionic elements showed weak sorption (log Kd (L·kg-1) < 1) and little competition effect, while the cationic elements (log Kd (L·kg-1) = 2-3) showed clear competition (18-98% in Kd values) even at low concentrations. Analysis by pseudo-second-order kinetics showed that Cs(I) sorbed at similar rates on both rocks (20% faster on biotite gneiss), but Ni(II) sorbed 190% faster on biotite gneiss than on granite. That is why the retardation factors for Cs(I) and Ni(II) were reversed in the biotite gneiss column compared to their distribution coefficients. Therefore, the sorption kinetics cannot be neglected in groundwater systems with high flow rates. In the desorption column test, the retardation followed the order of the distribution coefficient. The desorption column test revealed that the distribution coefficient determines the strength of sorption on crystalline rocks.

Clinical characteristics and courses of Korean patients with giant cell arteritis: a multi-center retrospective study.

Objective: Giant cell arteritis (GCA) is a large-vessel vasculitis that primarily affects elderly individuals. However, data regarding Korean patients with GCA are scarce owing to its extremely low prevalence in East Asia. This study aimed to investigate the clinical characteristics of Korean patients with GCA and their outcomes, focusing on relapse. Methods: The medical records of 27 patients with GCA treated at three tertiary hospitals between 2007 and 2022 were retrospectively reviewed. Results: Seventeen (63.0%) patients were females, and the median age at diagnosis was 75 years. Large vessel involvement (LVI) was detected in 12 (44.4%) patients, and polymyalgia rheumatica (PMR) was present in 14 (51.9%) patients. Twelve (44.4%) patients had fever at onset. The presence of LVI or concurrent PMR at diagnosis was associated with a longer time to normalization of the C-reactive protein level (p=0.039) or erythrocyte sedimentation rate (p=0.034). During follow-up (median 33.8 months), four (14.8%) patients experienced relapse. Kaplan-Meier analyses showed that relapse was associated with visual loss (p=0.008) and the absence of fever (p=0.004) at onset, but not with LVI or concurrent PMR. Conclusion: Concurrent PMR and LVI were observed in approximately half of Korean patients with GCA, and the elapsed time to normalization of inflammatory markers in these patients was longer. The relapse rate in Korean GCA is lower than that in Western countries, and afebrile patients or patients with vision loss at onset have a higher risk of relapse, suggesting that physicians should carefully monitor patients with these characteristics.

Corticosteroid-free adalimumab-cyclophosphamide combination therapy for acute phase neuro-Behçet's disease: a case report.

Neuro-Behçet's disease (NBD) represents a significant complication of Behçet's syndrome, potentially leading to elevated mortality and disability rates. The standard treatment for parenchymal NBD typically entails administering high-dose corticosteroids to prompt rapid-onset effects, coupled with immunosuppressants to prevent subsequent relapses. A 48-year-old male with NBD presented with progressively worsening dysarthria over 9 months. This patient experienced increased intraocular pressure while using glucocorticoids, which worsened his pre-existing glaucoma. The patient had a prior diagnosis of NBD and presented with progressive dysarthria over a period of nine months, leading to a brain magnetic resonance imaging (MRI) scan. The brain MRI revealed multifocal punctate high signal intensities in the left frontoparietal area, insula, and basal ganglia. Instead of the standard steroid pulse therapy, the patient received adalimumab-cyclophosphamide combination as an alternative induction therapy. Subsequent serial brain MRI scans exhibited no emergence of new lesions, and the patient remained devoid of clinical relapses even after 17 months from the commencement of induction treatment. Adalimumab-cyclophosphamide combination could be used as a corticosteroid-free induction strategy for NBD. Further investigations are warranted to establish the most suitable combination regimen.

SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.

The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.

Laser Ablation Saturated Absorption Spectroscopy (LA-SAS) for In Situ Detection of Neodymium Isotopes.

This study introduces a novel optical system integrating laser ablation with saturated absorption spectroscopy (LA-SAS) for the detection of neodymium isotopes, crucial for the characterization process in nuclear forensics. Conventional methods for isotope analysis have encountered challenges, such as the inability to perform on-site detection or difficulty in distinguishing minor isotope differences. The LA-SAS system overcomes these limitations by combining pulsed laser for ablation and counter-propagated diode laser for saturated absorption, enabling preparation-free detection with enhanced spectral resolution. The analytical capability was demonstrated through the successful detection of seven neodymium isotopes (142Nd, 143Nd, 144Nd, 145Nd, 146Nd, 148Nd, and 150Nd) with a line width narrowed to 0.1 pm, significantly improving upon the resolution limit of conventional LA-based methods. In addition, quantitative analysis of isotope abundance was facilitated by evaluating the signals from saturated absorption spectra. Special attention was given to the hyperfine structure of odd isotopes, which was resolved by multiple fitting in spectra, thereby refining the accuracy of isotope quantification up to an average bias of 0.45%. The established LA-SAS system offers on-site detection capability based on LA, and also the high resolution from SAS, making it a promising method for in situ nuclear forensics. Consequently, the study enhances the academic understanding of neodymium isotopes and underscores the potential of LA-SAS in fields requiring detailed isotopic information.

Effectiveness and safety of traditional herbal medicine on cardiac arrhythmic condition: A systematic review and meta-analysis of randomized control clinical trial.

INTRODUCTION: The prevalence of cardiac arrhythmia, which can lead to cardiac death, heart failure, and cardioembolic stroke, is increasing. Although various Western medicines for cardiac arrhythmias have been developed, there are still various difficulties in the management of arrhythmias. Traditional herbal medicines (THM) are widely used to manage arrhythmia in East Asia. Therefore, this study aimed to assess the effectiveness and safety of THM in the treatment of arrhythmia. METHOD: Using a systematic review methodology, we searched for randomized clinical trials on herbal medicines for arrhythmia without complications in 4 databases up to September 2022. The literature search was carried out again, targeting papers published until April 2024.We conducted a risk-of-bias assessment and meta-analysis. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eighty-two randomized clinical trials were included in this meta-analysis. Total effective rate was significantly better in unspecified arrhythmia (risk ratio [RR]: 1.20, 95% confidence interval [CI]: 1.13-1.26), premature ventricular contraction (RR: 1.29, 95% CI: 1.29-1.33), sinus bradycardia (RR: 1.26, 95% CI: 1.17-1.36), tachycardia (RR: 1.23 95% CI: 1.15-1.32), and atrial fibrillation (RR: 1.17, 95% CI: 1.07-1.27). No severe adverse events were associated with THM. The overall risk of bias was relatively high. The total effective rate was the most frequently assessed clinical outcome variable. Most outcomes were surrogates and not clinical endpoints. CONCLUSION: THM, alone or in combination with Western medicine, has therapeutic effects on cardiac arrhythmic diseases. However, additional disease-specific clinical outcome variables are required for further studies on THM. Owing to the low quality of the included studies and their small sample sizes, additional large-scale, long-term follow-up, and well-designed randomized controlled clinical trials are required. SYSTEMATIC REVIEW REGISTRATION NUMBER: Details of the protocol for this systematic review and meta-analysis were registered on the Open Science Framework (OSF. io). (https://osf.io/7r8kn/).

Risk of urolithiasis associated with allopurinol versus benzbromarone among patients with gout: a population-based cohort study.

OBJECTIVES: To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric. METHODS: Using the 2011-20 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the first-line urate-lowering treatment. The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazard models with a 5:1 ratio propensity-score matching on >80 variables. Subgroup analyses were done by age, sex, thiazide use and cardiovascular risk. RESULTS: 61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51-0.80). Approximately 44% of urinary stones required intervention with a HR of 0.61 (95% CI, 0.43-0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high cardiovascular risk subgroup (P for interaction = 0.02). CONCLUSION: This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high cardiovascular risk. This finding provides important safety information for clinicians' decision-making on urate-lowering treatments of different mechanisms of action.

Capsaicin induces ATP-dependent thermogenesis via the activation of TRPV1/ß3-AR/α1-AR in 3T3-L1 adipocytes and mouse model.

Capsaicin (CAP) is a natural bioactive compound in chili pepper that activates the transient receptor potential vanilloid subfamily 1 (TRPV1) and is known to stimulate uncoupling protein 1 (UCP1)-dependent thermogenesis. However, its effect on ATP-dependent thermogenesis remains unknown. In this study, we employed qRT-PCR, immunoblot, staining method, and assay kit to investigate the role of CAP on ATP-dependent thermogenesis and its modulatory roles on the TRPV1, ß3-adrenergic receptor (ß3-AR), and α1-AR using in vitro and in vivo models. The studies showed that CAP treatment in high-fat diet-induced obese mice resulted in lower body weight gain and elevated ATP-dependent thermogenic effectors' protein and gene expression through ATP-consuming calcium and creatine futile cycles. In both in vitro and in vivo experiments, CAP treatment elevated the protein and gene expressions of sarcoendoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2), ryanodine receptor 2 (RYR2), creatine kinase B (CKB), and creatine kinase mitochondrial 2 (CKMT2) mediated by the activation of ß3-AR, α1-AR, and TRPV1. Our study showed that CAP increased intracellular Ca2+ levels and the expression of voltage-dependent anion channel (VDAC) and mitochondrial calcium uniporter (MCU) which indicates that increased mitochondrial Ca2+ levels lead to increased expression of oxidative phosphorylation protein complexes as a result of ATP-futile cycle activation. A mechanistic study in 3T3-L1 adipocytes revealed that CAP induces UCP1- and ATP-dependent thermogenesis mediated by the ß3-AR/PKA/p38MAPK/ERK as well as calcium-dependent α1-AR/TRPV1/CaMKII/AMPK/SIRT1 pathway. Taken together, we identified CAP's novel functional and modulatory roles in UCP1- and ATP-dependent thermogenesis, which is important for developing therapeutic strategies for combating obesity and metabolic diseases.

Adipose Tissue Quantification Improves the Prognostic Value of GLIM Criteria in Advanced Gastric Cancer Patients.

The present study investigated whether the risk of recurrence after curative surgery could be further stratified by combining the Global Leadership Initiative on Malnutrition (GLIM) criteria and changes in subcutaneous (SAT) and visceral (VAT) adipose tissue mass after surgery in patients with advanced gastric cancer (AGC). This study retrospectively analyzed 302 patients with AGC who underwent curative surgery. Based on the GLIM criteria, patients were classified into malnourished and non-malnourished groups. The cross-sectional areas of SAT and VAT were measured from preoperative and 6-month post-operative computed tomography (CT) images. Multivariate survival analyses demonstrated that GLIM-defined malnutrition (p = 0.008) and loss of VAT after surgery (p = 0.008) were independent risk factors for recurrence-free survival (RFS). Evaluation of the prognostic value of combining the two independent predictors showed that malnourished patients with a marked loss of VAT had the worst 5-year RFS rate of 35.2% (p < 0.001). Preoperative GLIM-defined malnutrition and a loss of VAT during the first 6 months after surgery were independent predictors for RFS in patients with AGC. Changes in the VAT area after surgery could further enhance the prognostic value of the GLIM criteria for predicting the risk of gastric cancer recurrence.

Impact of socioeconomic status on biologics utilization in rheumatoid arthritis: revealing inequalities and healthcare efficiency.

BACKGROUND/AIMS: This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES). METHODS: Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis. RESULTS: Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60-0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use. CONCLUSION: The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.

All-cause and cause-specific mortality in patients with Behçet disease versus the general population.

BACKGROUND: The comparative risk of cause-specific mortality in patients with Behçet disease (BD) vs. the general population is not known. OBJECTIVES: To compare the risk of all-cause and cause-specific mortality in patients with BD vs. the general population. METHODS: Using data from the Korea National Health Insurance Service database for the period 2002-20, we conducted a cohort study comparing patients with BD with the general population, matched according to age and sex (1 : 4 ratio). We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analyses by age and sex were done. RESULTS: We included 24 669 patients with BD and 98 676 age- and sex-matched controls [mean (SD) age 40.5 (12.9) years; 34% male]. During a mean follow-up of 11.9 years, the incidence rate (IR) of death per 100 person-years was 0.36 in patients with BD and 0.29 in controls [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.20-1.38]. The risk of mortality was highest in the first year after BD diagnosis (HR 2.66, 95% CI 2.09-3.40). Patients with BD died more often in this period as a result of malignancy (HR 1.96, 95% CI 1.30-2.98); cardiovascular (HR 2.68, 95% CI 1.45-4.97), gastrointestinal (HR 3.50, 95% CI 1.35-9.07) and respiratory disease (HR 5.00, 95% CI 1.34-18.62); and infection (HR 3.33, 95% CI 1.02-10.92). Mortality as a result of neurological (HR 1.58, 95% CI 1.06-2.35) or genitourinary disease (HR 2.20, 95% CI 1.43-3.37) was also more common in patients with BD during the overall follow-up. Subgroup analyses showed consistent results. The risk of cardiovascular mortality vs. the general population was higher in younger patients (P = 0.006) and the risk of gastrointestinal mortality was increased in women vs. men (P = 0.04). CONCLUSIONS: This population-based cohort study revealed that the first year after diagnosis is the highest risk period for excess mortality in people with BD. The mortality burden in BD derives from a wide spectrum of organ involvement and should serve as a warning to clinicians about the systemic nature of the disease.

Behçet disease (BD) is a multisystem vasculitis (inflammation of the blood vessels) of unknown origin that commonly results in oral and genital ulcers, uveitis (eye inflammation) and skin lesions. BD is most prevalent in people from the Mediterranean to East Asia, affecting 0.4% of people in this area. Most lesions go away with time, but more severe forms that involve the cardiovascular and neurological systems can lead to death. It is estimated that people with BD have 1.4 times the risk of dying than the general population. Using large insurance databases in Korea, we investigated the risk of death in people with BD versus age- and sex-matched controls (i.e. people without the disease) from the general population. We found that patients with BD had a 28% greater risk of death than controls over 11.9 years of follow-up, with the highest risk being in first year after diagnosis. Top causes of death in people with BD included cancer, and cardiovascular, gastrointestinal, neurological, genitourinary, respiratory and infectious disease. Further analyses of the data showed that the risk of death in BD is affected by age and sex. In particular, younger patients were more susceptible to death as a result of cardiovascular disease and women were more susceptible to dying of gastrointestinal disease. Our study suggests that there could be an increased risk of death within the first year of being diagnosed with BD and highlights how BD is a systemic disease (i.e. the involvement of any internal organ system could lead to an increase in mortality). Finally, there were unique patterns of cause-specific deaths across subgroups of people with BD.

Attention-guided jaw bone lesion diagnosis in panoramic radiography using minimal labeling effort.

Developing a deep-learning-based diagnostic model demands extensive labor for medical image labeling. Attempts to reduce the labor often lead to incomplete or inaccurate labeling, limiting the diagnostic performance of models. This paper (i) constructs an attention-guiding framework that enhances the diagnostic performance of jaw bone pathology by utilizing attention information with partially labeled data; (ii) introduces an additional loss to minimize the discrepancy between network attention and its label; (iii) introduces a trapezoid augmentation method to maximize the utility of minimally labeled data. The dataset includes 716 panoramic radiograph data for jaw bone lesions and normal cases collected and labeled by two radiologists from January 2019 to February 2021. Experiments show that guiding network attention with even 5% of attention-labeled data can enhance the diagnostic accuracy for pathology from 92.41 to 96.57%. Furthermore, ablation studies reveal that the proposed augmentation methods outperform prior preprocessing and augmentation combinations, achieving an accuracy of 99.17%. The results affirm the capability of the proposed framework in fine-grained diagnosis using minimally labeled data, offering a practical solution to the challenges of medical image analysis.

Comparative Analysis of Integrated Filtering Methods Using UWB Localization in Indoor Environment.

This research delves into advancing an ultra-wideband (UWB) localization system through the integration of filtering technologies (moving average (MVG), Kalman filter (KF), extended Kalman filter (EKF)) with a low-pass filter (LPF). We investigated new approaches to enhance the precision and reduce noise of the current filtering methods-MVG, KF, and EKF. Using a TurtleBot robotic platform with a camera, our research thoroughly examines the UWB system in various trajectory situations (square, circular, and free paths with 2 m, 2.2 m, and 5 m distances). Particularly in the square path trajectory with the lowest root mean square error (RMSE) values (40.22 mm on the X axis, and 78.71 mm on the Y axis), the extended Kalman filter with low-pass filter (EKF + LPF) shows notable accuracy. This filter stands out among the others. Furthermore, we find that integrated method using LPF outperforms MVG, KF, and EKF consistently, reducing the mean absolute error (MAE) to 3.39% for square paths, 4.21% for circular paths, and 6.16% for free paths. This study highlights the effectiveness of EKF + LPF for accurate indoor localization for UWB systems.

Resolving the non-uniformity in the feature space of age estimation: A deep learning model based on feature clusters of panoramic images.

Age estimation is important in forensics, and numerous techniques have been investigated to estimate age based on various parts of the body. Among them, dental tissue is considered reliable for estimating age as it is less influenced by external factors. The advancement in deep learning has led to the development of automatic estimation of age using dental panoramic images. Typically, most of the medical datasets used for model learning are non-uniform in the feature space. This causes the model to be highly influenced by dense feature areas, resulting in adequate estimations; however, relatively poor estimations are observed in other areas. An effective solution to address this issue can be pre-dividing the data by age feature and training each regressor to estimate the age for individual features. In this study, we divide the data based on feature clusters obtained from unsupervised learning. The developed model comprises a classification head and multi-regression head, wherein the former predicts the cluster to which the data belong and the latter estimates the age within the predicted cluster. The visualization results show that the model can focus on a clinically meaningful area in each cluster for estimating age. The proposed model outperforms the models without feature clusters by focusing on the differences within the area. The performance improvement is particularly noticeable in the growth and aging periods. Furthermore, the model can adequately estimate the age even for samples with a high probability of classification error as they are located at the border of two feature clusters.

Compensating isotope effect on molecular emission of hydroxyl and imidogen isotopologues in laser-induced plasma.

BACKGROUND: The molecular isotopologues in laser-induced plasma exhibit riddling emission behaviors in terms of wavelength, intensity, and temporal evolution of spectra due to the isotope effect. Although this phenomenon introduces uncertainty to isotope analyses based on molecular spectra, its underlying mechanism remains undisclosed. RESULTS: In this study, laser-induced breakdown spectroscopy (LIBS) is employed to identify the emission behavior of hydrogen, oxygen, and nitrogen isotopologues in a plasma plume. The goal is to discern the details of the isotope effect and mitigate resulting uncertainty. The molecular emissions of hydroxyl (OH) and imidogen (NH) were measured from plasma ablated on isotopically enriched water samples. Time-resolved detection clearly reveals distinct isotopic disparities in intensity variation and optimum gate delay, which were attributed to plasma thermo-hydrodynamics. Lighter isotopologues exhibit earlier and faster associations than their heavier counterparts due to their fast reaction rates and expansion velocities. The extent of the isotope effect hinged on plasma characteristics governed by measurement conditions. Consequently, comparing spectral intensity between molecular isotopologues cannot directly indicate the nominal isotope abundance of the sample. To address it, a compensation strategy has been devised, quantifying isotope effects through parameters like the slope and optimum delay of time-resolved detection. The approach successfully predicts nominal isotope abundance using compensated intensity ratios, with an absolute bias of less than 3 %. SIGNIFICANCE: This study not only offered fundamental insights into the isotope effect in laser-induced plasma but also proposed an alternative method for isotope quantification that circumvents complicated calibration processes.

Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?

The three arms of the unfolded protein response (UPR) surveil the luminal environment of the endoplasmic reticulum (ER) and transmit information through the lipid bilayer to the cytoplasm to alert the cell of stress conditions within the ER lumen. That same lipid bilayer is the site of de novo synthesis of phospholipids and sphingolipids. Thus, it is no surprise that lipids are modulated by and are modulators of ER stress. Given that sphingolipids have both prosurvival and proapoptotic effects, they also exert opposing effects on life/death decisions in the face of prolonged ER stress detected by the UPR. In this review, we will focus on several recent studies that demonstrate how sphingolipids affect each arm of the UPR. We will also discuss the role of sphingolipids in the process of immunogenic cell death downstream of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiating factor 2α (eIF2α) arm of the UPR. Furthermore, we will discuss strategies to target the sphingolipid metabolic pathway that could potentially act synergistically with agents that induce ER stress as novel anticancer treatments. SIGNIFICANCE STATEMENT: This review provides the readers with a brief discussion of the sphingolipid metabolic pathway and the unfolded protein response. The primary focus of the review is the mechanism(s) by which sphingolipids modulate the endoplasmic reticulum (ER) stress response pathways and the critical role of sphingolipids in the process of immunogenic cell death associated with the ER stress response.