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This study investigates the influence of different levels of urbanization, built environment, and socio-demographic features on the frequency of vehicle crashes associated with distracted driving (...

We compared the therapeutic effects of topical 8-oxo-2′-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p p p

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated

The ocular surface is continuously exposed to various environmental factors, and innate and adaptive immunity play crucial roles in ocular surface diseases (OSDs). Previously, we have reported that the topical application of RCI001 affords excellent anti-inflammatory and antioxidant effects in dry eye disease and ocular chemical burn models. In this study, we examined the inhibitory effects of RCI001 on the Rac1 and NLRP3 inflammasomes in vitro and in vivo. Following RCI001 application to RAW264.7 and Swiss 3T3 cells, we measured Rac1 activity using a glutathione-S-transferase (GST) pull-down assay and G-protein activation assay kit. In addition, we quantified the expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells using ELISA and real-time PCR. In the mouse ocular alkali burn model, RCI001 was administered via eye drops (10 mg/mL, twice daily) for 5 days, and 1% prednisolone acetate (PDE) ophthalmic suspension was used as a positive control. Corneal epithelial integrity (on days 0-5) and histological examinations were performed, and transcript and protein levels of Rac1, NLRP3, caspase-1, and IL-1β were quantified using real-time PCR and western blotting in corneal tissues collected on days 3 and 5. We observed that RCI001 dose-dependently inhibited Rac1 activity and various inflammatory cytokines in LPS-stimulated murine macrophages. Furthermore, RCI001 restored corneal epithelial integrity more rapidly than corticosteroid treatment in chemically injured corneas. Compared to the saline group, activation of Rac1 and the NLRP3 inflammasome/IL-1β axis was suppressed in the RCI001 group, especially during the early phase of the ocular alkali burn model. Topical RCI001 suppressed the expression of activated Rac1 and inflammatory cytokines in vitro and rapidly restored the injured cornea by inhibiting activation of Rac1 and the NLRP inflammasome/IL-1β axis in vivo. Accordingly, RCI001 could be a promising therapeutic agent for treating OSDs.

This study examines the latent influence of spatial locations on the relative risks of crash injuries associated with distracted driving (DD) and identifies regions of excess risks for policy intervention. Using a sample of aggregated injury and fatal DD crash records for the period 2015-2019 across 1,024 census block groups in Central Ohio (i.e., the Columbus Metropolitan Area) in the United States, we investigate the role of latent effects along with several covariates such as land-use mix, sociodemographic features, and the built environment. To this end, we specifically leverage a full Bayesian hierarchical formulation with conditional autoregressive priors to account for uncertainty (i.e., spatially structured random effects) stemming from adjacent census block groups. Furthermore, we consider uncorrelated random effects from upper-level administrative units within which each block group is nested (i.e., census tracts and counties). Our analysis reveals that (1) addressing spatial correlation improves the model's performance, (2) block-group-level variability substantially explains the residual random fluctuation, and (3) intersection density appears negatively associated with the relative risks of crash injuries, while more diversified land use can increase injury risk. Based on these findings, we present spatial clusters with twice the relative risks compared to other block groups, suggesting that policies be devised to mitigate severe injuries due to DD and therefore enhance public health.

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Kyung Jae Ryu,1 Seunghoon Kim,2 Mee Kum Kim,3 Hae Jung Paik,1 Dong Hyun Kim1 1Department of Ophthalmology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea; 2RudaCure Co., LTD, Incheon, Korea; 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Dong Hyun KimDepartment of Ophthalmology, Gachon University College of Medicine, Gil Medical Center, 1198, Guwol-dong, Namdong-Gu, Incheon, 21565, KoreaEmail amidfree@gmail.comPurpose: To compare the short-term therapeutic effects of topical corticosteroids in patients with refractory dry eye disease (DED) according to the tear matrix metalloproteinase 9 (MMP-9) point-of-care positivity.Methods: This study was conducted on 137 patients who were referred from other eye clinics, complaining of irresponsive DED or acute DED flares despite routine treatment with topical cyclosporin or diquafosol. The patients received treatment with topical corticosteroids for 1 month. DED was evaluated by SANDE (Symptom Assessment in Dry Eye) questionnaire, tear film breakup time, ocular surface staining score, and meibomian gland dysfunction stage. The InflammaDry MMP-9 immunoassay was conducted in more symptomatic eyes of all patients. The changes in the subjective symptoms were additionally surveyed as symptom improvement score.Results: The mean age of the patients was 57.8± 13.4 years, and the tear MMP-9 positivity was 73.0%. Topical corticosteroids treatment showed significant improvement of symptoms and signs in the patients with refractory DED irrespective of the positivity of MMP-9 (each p< 0.001). The changes in SANDE score and OSS, and symptom improvement score were higher in the MMP-9 positive group than in the MMP-9 negative group (p=0.002/0.010/0.011). The overall rates of subjective symptoms improvement and SANDE reduction were 73.0% and 90.6% after topical corticosteroids treatment, respectively.Conclusion: Short-term topical corticosteroids had excellent therapeutic effects in patients with refractory DED or acute DED flares, irrespective of the tear MMP-9 level. Tear MMP-9 positivity may serve as a reliable response predictor of topical corticosteroids treatment in DED.Keywords: dry eye disease, ocular surface inflammation, tear MMP-9 positivity, corticosteroid

Along with the rapid demographic change, there has been increased attention to the risk of vehicle crashes relative to older drivers. Due to senior involvement and their physical vulnerability, it is crucial to develop models that accurately predict the severity of senior-involved crashes. However, the challenge is how to cope with an imbalanced severity class distribution and the ordered nature of crash severities, as these can complicate the classification of the severity of crashes. In that regard, this study investigates the influence of implementing ordinal nature and handling imbalanced class distribution on the prediction performance. Using vehicle crash data in Ohio, U.S., as an example, the eight machine learning classifiers (logistic and ordered logistic regressions and random forest and ordered random forest with or without handling imbalanced classes) are suggested and then compared with their respective performances. The analysis outcomes show that balancing strategy enhances performance in predicting severe crashes. In contrast, the effects of implementing ordinal nature vary across models. Specifically, the ordered random forest classifier without balancing appears to be superior in terms of overall prediction accuracy, and the ordered random forest with balancing outperforms others in predicting severer crashes.

Transit-oriented development (TOD) is often considered a solution for automobile dependency in the pursuit of sustainability. Although TOD has shown various benefits as sustainable development and smart growth, there are potential downsides, such as transit-induced gentrification (TIG). Even if there were no displacement issues with TIG, existing residents could be disadvantaged by a TOD due to affordability problems. This study focuses on these potential affordability issues and aims to evaluate the effects of TOD using residents&rsquo, discretionary income (DI) as an indicator of affordability. The light rail transit-oriented development (LRTOD) in Phoenix, AZ, is selected because of the timing of the introduction of development and the simplicity of the light rail transit line. In order to counteract problems induced by a non-random location of TODS, propensity score matching is used. The results indicate that LRTOD can give benefit to all TOD residents. Moreover, the effects of LRTOD on discretionary income of various types of households are not statistically significantly different. We have identified the different magnitudes of the effects of TOD between propensity score matching (PSM)-controlled and uncontrolled models. These indicate the existence of the selection bias of TOD implementation, justifying the adoption of the PSM method.

Periodontitis is a widespread chronic inflammatory disease caused by interactions between periodontal bacteria and homeostasis in the host. We aimed to investigate the performance and reliability of machine learning models in predicting the severity of chronic periodontitis. Mouthwash samples from 692 subjects (144 healthy controls and 548 generalized chronic periodontitis patients) were collected, the genomic DNA was isolated, and the copy numbers of nine pathogens were measured using multiplex qPCR. The nine pathogens are as follows: Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Aggregatibacter actinomycetemcomitans (Aa), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec). By adding the species one by one in order of high accuracy to find the optimal combination of input features, we developed an algorithm that predicts the severity of periodontitis using four machine learning techniques. The accuracy was the highest when the models classified “healthy” and “moderate or severe” periodontitis (H vs. M-S, average accuracy of four models: 0.93, AUC = 0.96, sensitivity of 0.96, specificity of 0.81, and diagnostic odds ratio = 112.75). One or two red complex pathogens were used in three models to distinguish slight chronic periodontitis patients from healthy controls (average accuracy of 0.78, AUC = 0.82, sensitivity of 0.71, and specificity of 0.84, diagnostic odds ratio = 12.85). Although the overall accuracy was slightly reduced, the models showed reliability in predicting the severity of chronic periodontitis from 45 newly obtained samples. Our results suggest that a well-designed combination of salivary bacteria can be used as a biomarker for classifying between a periodontally healthy group and a chronic periodontitis group.

The initial phase of the Korean Genome Project (Korea1K) releases 1094 whole genomes, along with data of 79 clinical traits., We present the initial phase of the Korean Genome Project (Korea1K), including 1094 whole genomes (sequenced at an average depth of 31×), along with data of 79 quantitative clinical traits. We identified 39 million single-nucleotide variants and indels of which half were singleton or doubleton and detected Korean-specific patterns based on several types of genomic variations. A genome-wide association study illustrated the power of whole-genome sequences for analyzing clinical traits, identifying nine more significant candidate alleles than previously reported from the same linkage disequilibrium blocks. Also, Korea1K, as a reference, showed better imputation accuracy for Koreans than the 1KGP panel. As proof of utility, germline variants in cancer samples could be filtered out more effectively when the Korea1K variome was used as a panel of normals compared to non-Korean variome sets. Overall, this study shows that Korea1K can be a useful genotypic and phenotypic resource for clinical and ethnogenetic studies.

Dental caries are one of the chronic diseases caused by organic acids made from oral microbes. However, there was a lack of knowledge about the oral microbiome of Korean children. The aim of this study was to analyze the metagenome data of the oral microbiome obtained from Korean children and to discover bacteria highly related to dental caries with machine learning models. Saliva and plaque samples from 120 Korean children aged below 12 years were collected. Bacterial composition was identified using Illumina HiSeq sequencing based on the V3–V4 hypervariable region of the 16S rRNA gene. Ten major genera accounted for approximately 70% of the samples on average, including Streptococcus, Neisseria, Corynebacterium, and Fusobacterium. Differential abundant analyses revealed that Scardovia wiggsiae and Leptotrichia wadei were enriched in the caries samples, while Neisseria oralis was abundant in the non-caries samples of children aged below 6 years. The caries and non-caries samples of children aged 6–12 years were enriched in Streptococcus mutans and Corynebacterium durum, respectively. The machine learning models based on these differentially enriched taxa showed accuracies of up to 83%. These results confirmed significant alterations in the oral microbiome according to dental caries and age, and these differences can be used as diagnostic biomarkers.

Background Papillary renal cell carcinoma type 2 (PRCC2) is refractory to systemic treatment and has a dismal prognosis. Previous studies showed that genetic alterations in PRCC2 were heterogeneous regardless of germline or somatic mutations. In this study, we aimed to perform precision treatment of PRCC2 based on genetic information. Methods We performed exome and genome sequencing of tumor tissues and matched normal samples. Based on sequencing data, we treated patients with metastatic PRCC2 using precision oncology. Results Four patients underwent curative surgery of PRCC2 and three patients had metastatic PRCC2. All PRCC2 heterogeneously harbored own driver mutations. Two out of the three patients with metastatic disease had fumarate hydratase (FH) germline mutations. One patient with a germline FH mutation was diagnosed with hereditary leiomyomatosis RCC. He was treated with bevacizumab and erlotinib combination and showed a durable response. The other metastatic PRCC2 patient harboring a germline FH mutation had an additional somatic FH mutation and was durably controlled with pazopanib. Other metastatic PRCC2 patient with somatic PBRM1 and SETD2 mutations had over 5 years of overall survival with axitinib treatment. Conclusions We performed precision systemic treatment based on genetic information. Genome sequencing could help identify candidates for targeted therapy in PRCC2, a genetically heterogeneous disease.

A growing number of studies examine the affordability benefits of living near transit, especially fixed-rail, with the assumption that transportation benefits of transit neighborhoods outweigh increasing housing costs. Yet these studies only compare housing and transportation costs. This study adds to the existing literature by investigating the influence of new light rail on changes in discretionary income in urbanized areas. We examine such changes from 2000 to 2010 at the block group level, comparing light rail neighborhoods (LRNs) and Non-LRNs, across 20 U.S. urban areas that opened light rail stations between this time period. Using descriptive statistical measures and OLS regressions, we find that while discretionary income decreased overall, neighborhoods with light rail provide a positive influence on discretionary income. Overall, our findings suggest light rail neighborhoods provide greater affordability benefits than non-light rail neighborhoods.

e14623 Background: Poly-gamma-glutamic acid (γ-PGA), as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to induce innate immune responses. In previous non-clinical study, we showed that γ-PGA induces signaling pathway of Type 1 interferon, which consequently eliminates various viruses such as SARS, hepatitis C virus, influenza virus, etc. To evaluate the clinical efficacy of γ-PGA, we’ve investigated the antiviral effect of γ-PGA on human. In retrospective study to evaluate, the clinical significance of g-PGA treatment for vaginal intraepithelial neoplasia (VAIN), γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN. Since previous human studies showed the possibility of a drug, we have completed a phase I dose escalation study to determine the safety, tolerance and pharmacokinetics of γ-PGA in healthy adult male subjects. Methods: In the current study, we designed a human study of γ-PGA orally treated daily (75 mL) for 24 weeks to demonstrate the antiviral effect of γ-PGA in female HPV-positive patients. HPV viral load and cell-mediated immune responses were measured during 24 weeks to compare HPV clearance rates between the γ-PGA-treated group and the placebo-controlled group and to evaluate immunological parameters, respectively. Results: . In phase IIb clinical trial to evaluate the efficacy and safety of γ-PGA for the fertile women with cervical intraepithelial neoplasia grade 1 (CIN1) patients, regression rate by the treatment of γ-PGA was 45.65%, whereas the placebo controls were 30.23% in ITT group with statistically significance ( p= 0.0247). Conclusions: γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive CIN I.

In this letter, new two-way and four-way power dividers are proposed using quarter-wave long multi-conductor coupled lines. The design equations for a two-way power divider are derived by analyzing a three-conductor coupled line. Then, the structure is extended to propose a planar four-way power divider with compact size. The fabricated two-way and four-way power dividers at 2.0 GHz show an excellent performance in the insertion loss, impedance matching at all ports and isolation between output ports.

A cyclic 10-bit D/A converter based on a Johnson counter and a capacitor swapping technique is described. To reduce capacitor mismatching errors, two capacitors are alternately swapped according to input data. Further, a half differential architecture to reduce offset errors and a Johnson counter to improve the digital logic performance are proposed. With a 0.35μm Samsung CMOS technology, the measured SFDR is about 65dB, when the input frequency is 1MHz at a clock frequency of 2MHz. The power consumption is only 310μW at 3.3V power supply. The measured INL and DNL are within ±0.7LSB and ±0.75LSB, respectively.

In battery-powered embedded systems, dedicated circuitry is used to convert stored energy into a form that can be directly used by processors. These power regulation devices seek to mask non-ideal aspects of the battery and present an ideal, fixed-voltage power source to the processor. However, this comes at a high price in terms of form factor, component cost, and energy efficiency. We describe and evaluate a new method for eliminating voltage regulation circuitry from battery-powered embedded systems. This method makes use of power gating, frequency scaling, and thread migration in chip-level multiprocessors to dynamically adjust to varying battery voltage. The key advantages of this approach are reduction in printed circuit board area (by 1/3 in many embedded applications) and the elimination of bulky unreliable discrete components such as electrolytic capacitors while maintaining similar battery lifespan. We have evaluated the power consumption, performance, and reliability implications of the proposed method using analytical techniques, power models, and detailed full-system simulation of numerous benchmarks from the ALPBench and Me-diaBench benchmark suites. For a number of battery technologies, the proposed technique holds the potential to eliminate power regulation circuitry and maintain battery lifespan while maintaining the same performance as systems using Buck-Boost voltage regulators.