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Ella H Leung,1 Sahana Sharma,2 Ana Levie-Sprick,1 Gregory D Lee,1 Hyung Cho,1 Krishna Mukkamala1 1Georgia Retina, Atlanta, GA, USA; 2Vanderbilt University, Nashville, TN, USACorrespondence: Ella H LeungGeorgia Retina, 833 Campbell Hill St NW, Suite 300, Marietta, GA, 30060, USATel +1-770-218-1888Email eleung@garetina.comPurpose: To evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy.Patients and Methods: A retrospective chart review was performed of patients exposed to PPS who had a dilated fundus examination at a large retina-only practice from 2018– 21. Multimodal images were evaluated by masked reviewers.Results: A total of 148 patients were included, of whom 33 (22%) had PPS-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The PPS-associated retinopathy group had higher mean cumulative doses of PPS (1600g± 849 vs 864g± 852, P < 0.0001, Mann–Whitney test) and longer duration of PPS use (13.6 years vs 7.48, P < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with PPS-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance.Conclusion: A longer duration of PPS use and higher cumulative dosage of PPS were associated with an increased risk of developing PPS-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to PPS is still to be determined.Keywords: pentosan polysulfate sodium, pigmentary retinopathy, pharmacotoxicity, inherited retinal dystrophies, genetics

Travelers make different choices about their routes based on the perceived travel time. This study aims to analyze the route choice behaviors by grouping them according to their perceived travel times. Reliability preference is a behavioral characteristic for travelers’ on-time arrival according to stochastic travel time, and it is used to classify the travelers into four groups. From Dedicated Short Range Communication (DSRC) data in Daegu, 9,758 travelers are observed to analyze their route choice behaviors. A stochastic model with generated sets of choices is developed using the probabilistic characteristics of travel times. A route-choice model is also estimated for each group, and the travelers’ route-choice behaviors are analyzed using a mixed path-size correction logit (MPSCL) model. The statistical analysis indicates that there are different route-choice behaviors among the four groups. The different behaviors concerning the routes are analyzed by comparing the magnitude of the different coefficients. This study contributes to constructing different strategies for acquiring information considering the route-choice behaviors of each group. Providing travel information that considers individual preferences in travel choice is essential in smart mobility transportation systems.

This study was conducted to investigate the correlation between the microstructure/texture evolutions and the high temperature flow behavior of Mg-8.3Gd-3.6Y-1.6Zn-0.5Zr (wt. %) alloy containing long period stacking order (LPSO) phases. Toward this end, the hot tensile tests were conducted at 350 and 400 °C on two different starting microstructures: (i) as-extruded containing blocky LPSO, and (ii) as-annealed, which contained both blocky and lamellar LPSO phases. The peak stresses of the annealed microstructures at 350 and 400 °C, i.e. 200 and 80 MPa, were almost twice that of extruded ones at the same temperatures, i.e. 117 and 39 MPa, respectively. The annealing treatment effectively strengthened the alloy and decreased the ductility value. This was justified relying on the grain growth, deformation twinning and texture evolution, but a special emphasize was paid on the effect of lamellar and blocky LPSO phases. It was found that the blocky LPSO could assist the dynamic recrystallization through activation of particle stimulated nucleation (PSN) mechanism and effectively contributed in the formation of rare earth (RE)-texture component. This provided high Schmid factors for operation of basal slip and improved the ductility values. On the contrary, the fine lamellar LPSO effectively increased the strength of the alloy via texture hardening but reduced the ductility. The lamellar LPSO played a key role in the formation and strengthening of the fiber texture, retarded the recrystallization process and suppressed the formation of RE-texture component.

Crosstalk between post-translational modifications of histone proteins influences the regulation of chromatin structure and gene expression. Among such crosstalk pathways, the best-characterized example is H2B monoubiquitination-mediated H3K4 and H3K79 methylation, which is referred to as trans-tail regulation. Although many studies have investigated the fragmentary effects of this pathway on silencing and transcription, its ultimate contribution to transcriptional control has remained unclear. Recent advances in molecular techniques and genomics have, however, revealed that the trans-tail crosstalk is linked to a more diverse cascade of histone modifications and has various functions in cotranscriptional processes. Furthermore, H2B monoubiquitination sequentially facilitates H3K4 dimethylation and histone sumoylation, thereby providing a binding platform for recruiting Set3 complex proteins, including two histone deacetylases, to restrict cryptic transcription from gene bodies. The removal of both ubiquitin and SUMO, small ubiquitin-like modifier, modifications from histones also facilitates a change in the phosphorylation pattern of the RNA polymerase II C-terminal domain that is required for subsequent transcriptional elongation. Therefore, this review describes recent findings regarding trans-tail regulation-driven processes to elaborate on their contribution to maintaining transcriptional fidelity., Cell biology: Interaction of DNA-winding proteins ensures correct gene expression Crosstalk between different DNA-winding proteins, or histones, is a mechanism of molecular fidelity that helps prevent the initiation of aberrant gene expression, which may contribute to cancer and neurodegenerative disease. A team from South Korea, led by Jungmin Choi from the Korea University College of Medicine in Seoul and Hong-Yeoul Ryu from Kyungpook National University in Daegu, review the ways in which different histone proteins chemically modify parts of each other’s structure to regulate their functions. These modifications affect how histones interact with DNA, which in turn alters the dynamics of other factors implicated in gene expression. The correct interaction of histones is necessary to prevent the gene expression machinery from starting RNA synthesis from the wrong sites. Accurate control of these mechanisms is essential for cellular wellbeing

We carried out KF postdeposition treatment (PDT) on a Cu(In,Ga)Se2 (CIGS) layer with a process time varying from 50 to 200 s. The highest CIGS solar-cell efficiency was achieved at a KF PDT process time of 50 s; in this condition, we observed the highest level of K element at the near-surface of the CIGS layer and the perfectly passivated pinholes on the CIGS surface. At process times above 150 s, the oversupplied KF agglomerated into large islands and was subsequently eliminated during the deposition of the chemical bath deposition (CBD)-Zn(O,S) buffer layer owing to the islands' water-soluble characteristics. As a result, the growth mechanism of the CBD-Zn(O,S) layer varied as a function of KF PDT process time. X-ray photoemission spectroscopy (XPS) measurements were used to examine the dependency of the chemical state on the KF PDT process time, and from the results, we formulated a chemical reaction model based on the shift in the elemental binding energy following deposition of the CBD-Zn(O,S) buffer layer. The chemical states of the K-In-Se phase, which have a beneficial effect on the solar-cell performance owing to the formation of durable and improved p-n junctions, are formed only at a KF PDT process time of 50 s. We derived band alignments from the XPS depth profiles by extracting the conduction- and valence-band offsets, and we used optical-pump-THz-probe spectroscopy to measure the ultrafast photocarrier lifetimes related to the defect states following KF PDT. Our key findings can be summarized as follows: (i) photocarrier transport is beneficial at a low barrier height, and (ii) the photocarrier lifetime increases when the K-In-Se phases are formed on the CIGS surface, which allows K+ ions to be effectively substituted into Cu vacancies.

The purpose of this study was to identify the ego-resiliency of Taekwondo athletes and to develop a scale measuring such skills. We collected preliminary data using an open-ended online survey targeting Taekwondo athletes from nine countries (South Korea, China, Malaysia, United States, Spain, France, Brazil, United Kingdom, and Taiwan) who participated in international competitions between 2019 and 2020. We extracted participants’ ego-resiliency from 48 survey responses, guided by expert meetings and a thorough literature review. We verified our Taekwondo ego-resiliency scale’s construct validity using 741 survey responses. We utilized V coefficients, parallel analysis, an exploratory structural equation model, maximum likelihood, confirmatory factor analysis, and multi-group confirmatory factor analysis for data analysis. We identified four core ego-resiliency types: “empathy,” “coach support,” “care,” and “parent support/effort”. Our final measure, which demonstrated evidence of reliability and validity, comprises 18 items spanning 4 factors, with each item rated on a 3-point Likert scale.

Gut microbiota are known to play an important role in obesity. Enterobacter cloacae, a Gram-negative bacterium, has been considered a pathogenic bacterium related to obesity in the gut. In this study, we established an obesity model of C. elegans by feeding E. cloacae combined with a high glucose diet (HGD), which significantly induced lipid accumulation. An anti-lipid mechanism study revealed that the fatty acid composition and the expression level of fat metabolism-related genes were altered by feeding E. cloacae to C. elegans under HGD conditions. Lactic acid bacteria that showed antagonistic activity against E. cloacae were used to screen anti-obesity candidates in this model. Among them, L. pentosus MJM60383 (MJM60383) showed good antagonistic activity. C. eleans fed with MJM60383 significantly reduced lipid accumulation and triglyceride content. The ratio of C18:1Δ9/C18:0 was also changed in C. elegans by feeding MJM60383. In addition, the expression level of genes related to fatty acid synthesis was significantly decreased and the genes related to fatty acid β-oxidation were up-regulated by feeding MJM60383. Moreover, MJM60383 also exhibited a high adhesive ability to Caco-2 cells and colonized the gut of C. elegans. Thus, L. pentosus MJM60383 can be a promising candidate for anti-obesity probiotics. To the best of our knowledge, this is the first report that uses E. cloacae combined with a high-glucose diet to study the interactions between individual pathogens and probiotics in C. elegans.

Based on electron backscatter diffraction (EBSD), hollow structures of Ni foam struts fabricated by electroplating on a chemically removable template were observed. Three-dimensional (3D) pore structures of Ni foams were also obtained using X-ray computed tomography (CT), and microstructural features such as porosity, pore size and strut thickness were statistically quantified. Evolution of microstructure and mechanical properties during ex situ compression of open-cell Ni-foams was investigated based on X-ray CT, and experimental results were compared with predictions by the finite element method (FEM). 3D microstructures obtained by X-ray CT revealed that the stress drop started with the buckling of struts at the center of the Ni-foams. The flow stress increased after the buckling of the struts spreads to most of the regions. For effective simulation of the compressive deformation and determination of the microstructural evolution, small domains of interest were selected from the entire set of observed 3D microstructures based on X-ray CT, and struts of Ni foams with a hollow structure were simplified with relevant thin-solid struts. Numerical 3D modeling comprehensively disclosed that compression caused the transverse buckling of the struts, with the bending and buckling of struts thus reducing the stress. Thickness variation of the struts causes a change in the porosity of Ni-foams without a change in pore shape or connectivity. The overall range of strut thickness was from 59 to 133 μm, and the range of porosity values was from 80% to 93.7%. A stress drop was predicted with a decrease in the strut thickness or an increase in the porosity, as measured experimentally. It was also found that the stress drop contributed to an increase in the calculated energy absorption efficiency.

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Work in animals implicates the central extended amygdala (EAc), but the translational relevance of these discoveries remains speculative. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.

New shared mobility services have become increasingly common in many cities and shown potential to address urban transportation challenges. This study aims to analyze the mobility performance of integrating bike-sharing into multimodal transport systems and develop a machine learning model to predict the performance of intermodal trips with bike-sharing compared with those without bike-sharing for a given trip using transit smart card data and bike-sharing GPS data from the city of Seoul. The results suggest that using bike-sharing in the intermodal trips where it performs better than buses could enhance the mobility performance by providing up to 34% savings in travel time per trip compared with the scenarios in which bus is used exclusively for the trips and up to 33% savings when bike-sharing trips are used exclusively. The results of the machine learning models suggest that the random forest classifier outperformed three other classifiers with an accuracy of 90% in predicting the performance of bike-sharing and intermodal transit trips. Further analysis and applications of the mobility performance of bike-sharing in Seoul are presented and discussed.

Background/aim We evaluated the predictive value of candidate serum biomarkers for recurrence in stage II and III colorectal cancer (CRC) after curative surgery. Patients and methods A total of 33 and 120 patients with CRC with or without recurrence at 5 years after curative surgery were included in the training set and the validation set, respectively. Possible serum biomarkers were examined for associations with CRC recurrence using receiver operating characteristics (ROC) curve analysis. Results In the training set, the expression levels of the 14 biomarkers were compared according to recurrence. Among them, five biomarkers that had significantly different expression levels were validated in 60 patients with recurrence at 5 years after curative surgery and 60 patients without. Multivariate analysis showed that natural log-transformed values of carcinoembryonic antigen (CEA), cyclin-dependent kinase regulatory subunit 2 (CKS2), 2'-5'-oligoadenylate synthetase 2 (OAS2), and autophagy-related gene 5 (ATG5) in preoperative serum were significantly related to recurrence. ROC analysis showed that these biomarkers were able to discriminate patients with recurrence from those without (area under the curve=0.828, 95% confidence interval=0.755-0.990). Conclusion Preoperative serum levels of CEA, CKS2, OAS2 and ATG5 were independent risk factors for recurrence. A combination of serum CEA, CKS2, OAS2 and ATG5 predicted tumor recurrence well in patients with stage II and III CRC.

Transit accessibility is an explanatory variable evaluating the mobility of a region in consideration of the connectivity and demand among the regions, which has been used for an important index to determine transport policy on the transit network. This study aims to develop an accessibility index considering the two factors with a demand-weighted approach, that is, impedance and attraction level. Two variables, travel time and the ratio of trips, are employed to calculate the accessibility index, and comparative assessments between zones are conducted. The application of smart card data makes it possible to analyze travel information and reflect them empirically in the model. This study identifies zones with vulnerable accessibility and suggests criteria for transit investment plans with two aspects, that is, intensive transit area and spatial distribution of the accessibility index. These aspects contribute to transit planners by suggesting transit investment criteria and comprehensible statistics to evaluate accessibility. Since zones with low accessibility indexes are identified as being vulnerable to access from other zones, policymakers should focus on those zones to improve the overall transit network.

Background Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). Methods RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. Results Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. Conclusions Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.

To develop an in vitro culture system for tissue engineering to mimic the in vivo environment and evaluate the applicability of ultrasound and PLGA particle system. For tissue engineering, large molecules such as growth factors for cell differentiation should be supplied in a controlled manner into the culture system, and the in vivo microenvironment need to be reproduced in the system for the regulation of cellular function. In this study, portable prototype ultrasound with low intensity was devised and tested for protein release from bovine serum albumin (BSA)-loaded poly(lactic-co-glycolic acid) (PLGA) particles. BSA-loaded PLGA particles were prepared using various types of PLGA reagents and their physicochemical properties were characterized including particle size, shape, or aqueous wetting profiles. The BSA-loaded formulation showed nano-ranged size distribution with optimal physical stability during storage period, and protein release behaviors in a controlled manner. Notably, the application of prototype ultrasound with low intensity influenced protein release patterns in the culture system containing the BSA-loaded PLGA formulation. The results revealed that the portable ultrasound set controlled by the computer could contribute for the protein delivery in the culture medium. This study suggests that combined application with ultrasound and protein-loaded PLGA encapsulation system could be utilized to improve culture system for tissue engineering or cell regeneration therapy.

Background The ABC test measures serum pepsinogen and anti-Helicobacter pylori IgG antibody levels to predict precancerous conditions in the stomach and gastric cancer. However, a limitation of this test is that the gastric cancer risk is not negligible in patients with a negative result. Methods Based on their ABC results, 1157 patients were classified into Groups A (n = 392), B (n = 479), C (n = 247), and D (n = 39). In Group A, 24.2% of patients had atrophic gastritis and/or intestinal metaplasia and had thus been incorrectly assigned to Group A. Patients in Group A were then assigned to derivation (n = 236) and validation (n = 156) cohorts by 3:2 random sampling. Logistic regression analyses were performed to identify the factors discriminating between a correct (true) and incorrect (false) Group A classification. Results A 4-point discriminative model was constructed based on a high-negative H. pylori IgG antibody titer and the patient's age (50-64 and ≥65 years). The areas under the receiver operating characteristic curve for the derivation and validation cohorts were 0.868 and 0.894, respectively. In the validation cohort, the addition of a discriminative model score ≥2 to the ABC method showed a similar accuracy for predicting gastric cancer risk compared with the ABC method alone (93.8% vs. 92.4%). Conclusion The 4-point discriminative model may help identify patients with a normal serological test who are nonetheless at risk of developing gastric cancer.

Zonal express is an operational strategy for express transit service that only stops in the initial and final zones of its route while skipping stops in-between. Zonal express provides a service with less travel and transfer time by aggregating trip demands with similar origins, destinations, and departure times. In this study, new zonal express routes are designed to reduce the travel and transfer times of transit users efficiently. This study develops a methodology that considers demand diversion. To meet the purpose, the following are conducted: (1) estimation of zonal express demand; (2) clustering of demand with similar origins, destinations, and departure times; (3) selection of candidate clusters; (4) optimization of stops and routes of zonal express; and (5) determining zonal express routes in which the benefit from reduced time and transfers outweighs the cost. The methodology is applied to an actual transportation network in Seoul, South Korea, using smartcard, car navigation, and spatial information data. The result shows that zonal express can reduce users’ travel time and the number of transfers effectively. This study proposes that it is desirable to introduce the zonal express sequentially from the route with the highest net benefit under a budget constraint. This study also presents the results when fares change to provide implications for pricing strategies of the zonal express. Future studies can consider incorporating various objective functions or utilizing vehicles in different time slots.

The purpose of this study is to investigate the surface activity of starch nanocrystals (SNC), material derived from starch, and confirm their usefulness as a surfactant. In order to evaluate the surface activity, the surface tension change of suspended SNC solution via the Wilhelmy plate method was measured and the values were compared with various synthetic surfactants. The effect of SNC as emulsifier was evaluated on emulsion formation and physical stability. The surface tension of the SNC-dispersed solution was decreased while its concentration was increased. When the 5.0% (w/v) of SNC was added, the surface tension was decreased from 70.3 to 49.5 mN/m. It was confirmed that the physical stability of the emulsion prepared by adding the SNC was improved compared to that of surface inactivity material (PEG 400). The phase separation was observed within 1 hour after preparation of the emulsion containing PEG 400, but the emulsion containing SNC was stable for 5 hours or more. To summarize this study, SNC, a natural-derived and non-toxic material, exhibits sufficient surface activity, thereby confirming the possibility of being applied to the food and pharmaceutical industry.

Formation of an electrolyte complex using the electrostatic interactions between a polyanionic polymer and a cationic drug is a simple and efficient method of preparing a colloidal drug carrier system. Dextran sulfate, with a negatively charged sulfate group, was reacted in an acetate buffer solution of pH 3 with positively charged 1° amine, 2° amine, 3° amine, piperazine, and piperidine structures from 24 small-molecule drugs. The electrolyte complex was formed from 15 drugs, 63% of those tested. The tendency to form the electrolyte complex was in the order of piperazine and piperidine >3° amine >>2° amine. The drugs with the 1° amine structure failed to form an electrolyte complex. The mean particle sizes were in the range of 50-740 nm, and most of them showed a submicron colloidal dispersion of