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Abstract Background The Integrated Palliative care Outcome Scale (IPOS) is a key tool for assessing the quality of palliative care using patient-reported outcomes. This study aimed to culturally adapt and translate the IPOS to Korean and verify its psychometric properties for use in palliative care settings. Methods The IPOS was translated and culturally adapted, followed by validation in 119 terminally ill cancer patients and 28 healthcare providers across six Hospice and Palliative Care Units from September 2023 to January 2024. Reliability was assessed using internal consistency, test-retest reliability, and inter-rater reliability. Concurrent validity was assessed using Spearman’s correlation coefficients between the IPOS items and the corresponding EORTC QLQ-C15-PAL and the corresponding FACIT-Sp-12. Results The Korean IPOS demonstrated good internal consistency, with Cronbach’s alphas of 0.74 for patients and 0.81 for staff. The test-retest reliability showed moderate-to-good stability, with an intra-class correlation coefficient of 0.722 for the IPOS total score. Concurrent validity was supported by moderate correlations with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and Functional Assessment of Chronic Illness Therapy-Spiritual Well-being Scale (FACIT-Sp-12). Known-group validity was demonstrated by significant differences in the IPOS scores across Phase of Illness. Conclusion The Korean IPOS is reliable and valid for assessing palliative care outcomes. This validation supports its use in clinical practice and research and provides a robust framework for evaluating and improving palliative care delivery in Korea.

The production of strawberries (Fragaria ×ananassa) in hydroponic systems has been increasing. In hydroponic systems, precise nutrient management is crucial for optimal plant growth and fruit production. Among essential elements, potassium (K) is a key nutrient that affects fruit yield and quality in fruiting crops. The objective of this study was to investigate whether increasing the K concentration in the Yamazaki strawberry nutrient solution could enhance plant growth, fruit yield, and fruit quality in hydroponic strawberries. Bare-root plants of strawberry ‘Monterey’ and ‘San Andreas’ were planted in a deep water culture hydroponic system and grown with initial K concentrations of 117, 194, 271, and 348 mg·L−1 under the same initial nitrogen concentration of 77 mg·L−1. As the K concentration increased from 117 to 348 mg·L−1, the nutrient solution electrical conductivity increased from 1.0 to 1.9 dS·m−1. The experiment was conducted inside an indoor vertical farm at a 23 °C air temperature with an extended photon flux density (400–750 nm) of 350 µmol·m−2·s−1 under an 18-hour photoperiod. Increasing the K concentration from 117 to 348 mg·L−1 had minimal effects on plant growth characteristics of both cultivars, although root dry mass of ‘Monterey’ increased linearly with increasing K. Increasing the K concentration from 117 to 348 mg·L−1 did not affect the total fruit number or total fruit fresh mass of ‘Monterey’, but for ‘San Andreas’, it reduced the total fruit number by 34% and total fruit fresh mass by 45%. Additionally, increasing the K concentration from 117 to 348 mg·L−1 reduced the individual fruit mass, fruit length, and fruit diameter and increased titratable acidity in both cultivars. These results indicate that increasing the K concentration in the Yamazaki strawberry nutrient solution did not benefit plant growth, fruit yield, or fruit quality of the hydroponically grown strawberries ‘Monterey’ or ‘San Andreas’.

Metalens design and optimization software (MetaCraft) is a Python-based software that generates a variety of metalens designs based on the user preferences. The design of metalenses involves the time-wise and computationally expensive tasks of searching for the appropriate components. Additionally, designers must ensure that the generated designs are compatible with fabrication capabilities, given that optical metalenses consist of nanoscale structures and elements. Currently, there is a shortage of dedicated software for metalens designs, and even fewer tools are available that can customize designs based on specific requests. MetaCraft is designed with an intuitive interface to allow users unfamiliar with coding to easily navigate through the graphical user interface. This study describes the basic usage of MetaCraft, elucidates its compositional framework, and substantiates the software's performance by comparing the results with the previously reported ones in metalens research.

Introduction Pediatric extracorporeal membrane oxygenation (ECMO) management presents unique challenges in acute care settings, requiring specialized expertise to manage critically ill children. Medical and surgical fellows often manage these patients, but prior residency training rarely provides sufficient ECMO exposure. We developed and evaluated a multimodal pediatric ECMO boot camp for new fellows. Methods This boot camp was implemented during 5-hour sessions in August 2021, August 2022, and August 2023. The curriculum included a 45-minute introductory didactics session, 30-minute hands-on circuit demonstration, and four 30-minute small-group activity stations. To assess knowledge acquisition, pre- and posttests were administered; participants also completed a post–boot camp survey to evaluate their confidence and provide feedback. Results Forty-nine participants completed the boot camp, including 18 critical care, four cardiology, 11 pediatric surgery, 12 cardiothoracic surgery, and four pediatric emergency medicine fellows. Pre- and posttests demonstrated significant improvement in knowledge of ECMO circuit components and pressures (56% vs. 76%, p < .001). All of our participants agreed or strongly agreed that participating in the boot camp increased their confidence in troubleshooting ECMO emergencies. The inclusion of fellows from various clinical disciplines, offering a rich diversity of perspectives, was particularly valued by participants. Discussion Our results demonstrate the feasibility and effectiveness of establishing a pediatric ECMO boot camp to train new surgical and medical fellows. The curriculum not only improved ECMO knowledge but also boosted learners’ confidence in managing ECMO-related challenges.

Abstract Background Given the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population. Methods A retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged

Background: The data on the association between alcohol intake and sleep quality in a community-based setting are lacking. This study examined overall sleep difficulty according to alcohol habits among Korean adults. Materials and Methods: We analyzed data from 4937 adults who responded to questions about sleep difficulty and drinking habits from the 2019 Korea National Health and Nutrition Examination Survey. Multivariate logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for substantial sleep difficulty based on the frequency or amount of alcohol consumption in total and age- and sex-stratified subgroup analyses. Results: Approximately 8.5% of the study population had substantial sleep difficulty. Individuals who drank

Background Individuals increasingly turn to the Internet for health information, with YouTube being a prominent source. However, the quality and reliability of the health information vary widely, potentially affecting health literacy and behavioural intentions. Methods To analyse the impact of health information quality on health literacy and behavioural intention, we conducted a randomized controlled trial using a quality-controlled YouTube intervention. Health information quality on YouTube was evaluated using the Global Quality Score and DISCERN. We randomly allocated (1 : 1) to the intervention group to watch the highest quality-evaluated content and to the control group to watch the lowest quality-evaluated content. Health literacy and health behavioural intention were assessed before and after watching YouTube. The trial was set for two different topics: interpreting laboratory test results from health check-up and information about inflammatory bowel disease (IBD). Results From 8 April 2022 to 15 April 2022, 505 participants were randomly assigned to watch either high-quality content (intervention group, n = 255) or low-quality content (control group, n = 250). Health literacy significantly improved in the intervention group (28.1 before and 31.8 after; p

Strawberries (Fragaria ×ananassa) are being produced increasingly in indoor vertical farms, where the light quality of sole-source lighting is a primary factor that influences the outcomes of crop production. Far-red (FR) light (700–750 nm) has been shown to promote plant responses such as leaf expansion, biomass accumulation, and flowering in some long-day plant species. However, the impacts of including FR light in sole-source lighting on strawberries have not been fully understood. This study investigated the impacts of FR light on the growth and development of long-day strawberries ‘Albion’ and ‘Monterey’ in an indoor vertical farm. We hypothesized that the addition of FR light under a long photoperiod would promote leaf expansion, biomass accumulation, flowering, and fruit production in long-day strawberries. Bare-root strawberry plants were grown in a deep-water-culture hydroponic system at an air temperature of 22 °C and an 18-hour photoperiod using 90 μmol⋅m–2⋅s–1 of blue (peak = 455 nm) + 250 μmol⋅m–2⋅s–1 of red (peak = 660 nm) light-emitting diodes (LEDs) with or without adding 50 μmol⋅m–2⋅s–1 of FR (peak = 730 nm) LEDs. After 5 weeks of lighting treatments, additional FR light increased the leaf area and shoot dry mass of strawberry ‘Monterey’ by 74% and 73%, respectively, and the number of crowns per plant of strawberry ‘Albion’ by 33%. However, FR light did not influence flowering time in either cultivar. Adding FR light increased the number of fruit harvested per plant by 36%, the total fruit yield by 48%, and the total soluble solids of fruit by 12% in strawberry ‘Albion’, but not in ‘Monterey’. In both cultivars, FR light did not affect the individual fruit mass. Our results suggest that the addition of FR light in sole-source lighting can promote leaf expansion, biomass accumulation, fruit yield, and fruit quality in at least some long-day strawberry cultivars.

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO4. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200–670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1–15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver–Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Background: Obstructive sleep apnea (OSA) commonly coexists with lung disease. However, the association between OSA components and lung function remains unclear. This study estimated STOP-BANG scores according to lung function using nationwide Korean data. Materials and Methods: Three thousand and two hundred eighty adults with available STOP-BANG scores and spirometry data were analyzed. Multivariate regression models were applied to estimate STOP-BANG scores according to lung function. Results: Approximately 28% of participants had abnormal lung function, and the characteristics were diverse. The significant factors associated with abnormal lung function included the STOP-BANG score. In multivariate regression analyses, individuals with abnormal lung function had significantly higher STOP-BANG scores than those with normal lung function (odds ratio: 1.19; 95% confidence interval: 1.10– 1.29; P < 0.001), and this difference was remarkable in men. Conclusion: Our results suggest that screening and management of OSA components are warranted to prevent impaired lung function.

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1–8 were prepared as potential tyrosinase inhibitors. Four analogs (1–3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

BackgroundAs cancer treatment methods have diversified and the importance of self-management, which lowers the dependence rate on direct hospital visits, has increased, effective cancer care education and management for health professionals and patients have become necessary. The metaverse is in the spotlight as a means of digital health that allows users to engage in cancer care education and management beyond physical constraints. However, it is difficult to find a multipurpose medical metaverse that can not only be used in the field but also complements current cancer care. ObjectiveThis study aimed to develop an integrated metaverse cancer care platform, Dr. Meta, and examine its usability. MethodsWe conducted a multicenter, cross-sectional survey between November and December 2021. A descriptive analysis was performed to examine users’ experiences with Dr. Meta. In addition, a supplementary open-ended question was used to ask users for their suggestions and improvements regarding the platform. ResultsResponses from 70 Korean participants (male: n=19, 27% and female: n=51, 73%) were analyzed. More than half (n=37, 54%) of the participants were satisfied with Dr. Meta; they responded that it was an interesting and immersive platform (n=50, 72%). Less than half perceived no discomfort when using Dr. Meta (n=34, 49%) and no difficulty in wearing and operating the device (n=30, 43%). Furthermore, more than half (n=50, 72%) of the participants reported that Dr. Meta would help provide non–face-to-face and noncontact services. More than half also wanted to continue using this platform in the future (n=41, 59%) and recommended it to others (n=42, 60%). ConclusionsWe developed a multidomain metaverse cancer care platform that can support both health professionals and patients in non–face-to-face cancer care. The platform was uniquely disseminated and implemented in multiple regional hospitals and showed the potential to perform successful cancer care.

As a key modifiable risk factor, alcohol consumption is clinically crucial information that allows medical professionals to further understand their patients’ medical conditions and suggest appropriate lifestyle modifying interventions. However, identifying alcohol-related information from unstructured free-text clinical notes is often challenging. Not only are the formats of the notes inconsistent, but they also include a massive amount of non-alcohol-related information. Furthermore, for medical institutions outside of English-speaking countries, these clinical notes contain both a mixture of English and local languages, inducing additional difficulty in the extraction. Thanks to the increasing availability of electronic medical record (EMR), several previous works explored the idea of using natural language processing (NLP) to train machine learning models that automatically identify alcohol-related information from unstructured clinical notes. However, all these previous works are limited to English clinical notes, thereby able to leverage various large-scale external ontologies during the text preprocessing. Furthermore, they rely on simple NLP techniques such as the bag-of-words models that suffer from high dimensionality and out-of-vocabulary issues. Addressing these issues, we adopt fine-tuning multilingual transformers. By leveraging their linguistically rich contextual information learned during their pre-training, we are able to extract alcohol-related information from unstructured clinical notes without preprocessing the clinical notes on any external ontologies. Furthermore, our work is the first to explore the use of transformers in bilingual clinical notes to extract alcohol-related information. Even with minimal text preprocessing, we achieve extraction accuracy of 84.70% in terms of macro F-1 score.

Objectives As climate change deepened, the concept of 2050 carbon neutrality was introduced. The COP 26 Glasgow Agreement strengthened the national greenhouse gases (GHGs) target of 2030. However, there are controversies over the feasibility of these GHGs reduction goals, considering the economic sectors energy policy and the attributes of GHGs emissions. Taking this into consideration, this study aimed to formulate the 2017 Environmentally Expanded Input-output Table to analyze the characteristics of GHGs emissions in Korea's economic sectors. Methods The carbon dioxide emission was calculated by multiplying carbon dioxide emission factors to fuel consumption in the 2017 energy balance table, while other GHGs emissions are taken from the national GHGs inventory. All the GHGs emissions calculated and taken were allocated to 381 basic sectors of the Input-Output Table to represent each sector's characteristics of GHGs emissions. Then 381 sectors are combined into a large category of 35 sectors to formulate the 2017 Republic of Korea Environmentally Extended Input-Output Table (ROKEEIOT). Using this ROKEEIOT, the emission of Scope 1. 2, and 3 by economic sectors were estimated, and the GHGs emissions and GHGs intensity by economic sectors. Results and Discussion The carbon dioxide emissions calculated by the 2017 ROKEEIOT prepared in this study showed a difference of 2% from the 2017 national GHGs emission statistics, confirming that the 2017 ROKEEIOT is very effective. The three economic sectors with the highest direct GHGs emissions were electricity, steam, chilled or hot water, air conditioning supply (262,280 kt CO2eq.), primary metal products (117.098 kt CO2eq.), and transportation equipment (58,332 kt CO2eq.). However, the total GHGs emissions were different in the order of construction (151,476 kt CO2eq.), transportation equipment (112,168 kt CO2eq.), computer, and electronic and optical instruments (107,868 kt CO2eq.). As a result of classifying the scope of GHGs emissions, 6 industries exceeded 50% in Scope 1, and 29 sectors exceeded 50% in Scope 3, indicating that GHGs reduction measures were necessary for the supply chain in consideration of the GHGs emissions characteristics by economic sectors. In particular, 41.68% of GHGs emissions induced by final demand were generated by exports confirming, confirming the urgent need to strengthen the carbon competitiveness of export industry in preparation for the introduction of the carbon border adjustment mechanism. Conclusion The economic contribution, direct GHGs emissions of industries, and the amount of GHGs emissions induced by supply chains and value chains show very different patterns by economic sectors. Therefore, it was confirmed that scientific policies to reduce GHGs emissions, such as net-zero and climate change measures, should reflect the characteristics of Scope 1, which is direct emission by industry, Scope 2 emissions caused by electricity and steam consumption and scope 3 emissions generated along the supply chain or value chain.

Natural killer (NK) cells play an important role in immune rejection in solid organ transplantation. To mitigate human NK cell activation in xenotransplantation, introducing inhibitory ligands on xenografts via genetic engineering of pigs may protect the graft from human NK cell-mediated cytotoxicity and ultimately improve xenograft survival. In this study, non-classical HLA class I molecules HLA-E and HLA-G were introduced in an immortalized porcine liver endothelial cell line with disruption of five genes (GGTA1, CMAH, β4galNT2, SLA-I α chain, and β-2 microglobulin) encoding three major carbohydrate xenoantigens (αGal, Neu5Gc, and Sda) and swine leukocyte antigen class I (SLA-I) molecules. Expression of HLA-E and/or HLA-G on pig cells were confirmed by flow cytometry. Endogenous HLA-G molecules as well as exogenous HLA-G VL9 peptide could dramatically enhance HLA-E expression on transfected pig cells. We found that co-expression of HLA-E and HLA-G on porcine cells led to a significant reduction in human NK cell activation compared to the cells expressing HLA-E or HLA-G alone and the parental cell line. NK cell activation was assessed by analysis of CD107a expression in CD3-CD56+ population gated from human peripheral blood mononuclear cells. CD107a is a sensitive marker of NK cell activation and correlates with NK cell degranulation and cytotoxicity. HLA-E and/or HLA-G on pig cells did not show reactivity to human sera IgG and IgM antibodies. This in vitro study demonstrated that co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells provided a superior inhibition in human xenoreactive NK cells, which may guide further genetic engineering of pigs to prevent human NK cell mediated rejection.

ABSTRACT There is an unmet medical need for effective treatments against Mycobacterium abscessus infections. Although advanced molecular genetic tools to validate drug targets and resistance of M. abscessus exist, the practical design and construction of plasmids are relatively laborious and time-consuming. Thus, for this purpose, we used CRISPR interference (CRISPRi) combined with catalytically deactivated Cas9 to inhibit the gene expression of a predicted LysR-type transcriptional regulator gene, MAB_0055c, in M. abscessus and evaluated its contribution to the development of drug resistance. Our results showed that silencing the MAB_0055c gene lead to increased rifamycin susceptibility depending on the hydroquinone moiety. These results demonstrate that CRISPRi is an excellent approach for studying drug resistance in M. abscessus. IMPORTANCE In this study, we utilized CRISPR interference (CRISPRi) to specifically target the MAB_0055c gene in M. abscessus, a bacterium that causes difficult-to-treat infections. The study found that silencing the gene lead to increased rifabutin and rifalazil susceptibility. This study is the first to establish a link between the predicted LysR-type transcriptional regulator gene and antibiotic resistance in mycobacteria. These findings underscore the potential of using CRISPRi as a tool for elucidating resistance mechanisms, essential drug targets, and drug mechanisms of action, which could pave the way for more effective treatments for M. abscessus infections. The results of this study could have important implications for the development of new therapeutic options for this challenging-to-treat bacterial infection.

The 3.5 keV line is a purported emission line observed in galaxies, galaxy clusters, and the Milky Way whose origin is inconsistent with known atomic transitions and has previously been suggested to arise from dark matter decay. We systematically reexamine the bulk of the evidence for the 3.5 keV line, attempting to reproduce six previous analyses that found evidence for the line. We only reproduce one of the analyses; in the other five, we find no significant evidence for a 3.5 keV line when following the described analysis procedures on the original data sets. For example, previous results claimed 4 σ evidence for a 3.5 keV line from the Perseus cluster; we dispute this claim, finding no evidence for a 3.5 keV line. We find evidence for background mismodeling in multiple analyses. We show that analyzing these data in narrower energy windows diminishes the effects of mismodeling but returns no evidence for a 3.5 keV line. We conclude that there is little robust evidence for the existence of the 3.5 keV line. Some of the discrepancy of our results from those of the original works may be due to the earlier reliance on local optimizers, which we demonstrate can lead to incorrect results. For ease of reproducibility, all code and data are publicly available.

In Republic of Korea, pronounced seasonal precipitation variability poses substantial challenges for stream water quality management and the effective utilization of water resources. Ecologically degraded streams are particularly vulnerable to these fluctuations, which can exacerbate their already fragile condition. We assessed the resilience of reference and impaired streams in response to rainfall through water quality system performance (WQSP). The WQSP is quantified as the concentration of BOD, T-N, and T-P, which represent streams’ eutrophication and anaerobic conditions and respond quickly to disturbances. Reference and impaired streams are classified according to the biological condition and habitat environment of the streams in the Han River watershed of Republic of Korea. The resilience of the stream ecosystem was estimated using WQSP, the linear multiple regression model, and the generalized additive model for rainfall and WQSP. The WQSP reference streams have a lower sensitivity to disturbance and recover more quickly from the influence of rainfall; therefore, they have higher resilience than impaired streams to rainfall events. This study facilitates understanding changes in stream ecosystems of varying conditions in response to rainfall for ensuring long-term stability and adaptability.

Climate change is expected to result in increased occurrences of extreme weather events such as heat waves and cold spells. Urban planning responses are crucial for improving the capacity of cities and communities to deal with significant temperature variations across seasons. This study aims to investigate the relationship between urban temperature fluctuations and urban morphology throughout the four seasons. Through quadrant and statistical analyses, built-environment factors are identified that moderate or exacerbate seasonal land surface temperatures (LSTs). The focus is on Seoul, South Korea, as a case study, and seasonal LST values are calculated at both the grid (100 m × 100 m) and street block levels, incorporating factors such as vegetation density, land use patterns, albedo, two- and three-dimensional building forms, and gravity indices for large forests and water bodies. The quadrant analysis reveals a spatial segregation between areas demonstrating high LST adaptability (cooler summers and warmer winters) and those displaying LST vulnerability (hotter summers and colder winters), with significant differences in vegetation and building forms. Spatial regression analyses demonstrate that higher vegetation density and proximity to water bodies play key roles in moderating LSTs, leading to cooler summers and warmer winters. Building characteristics have a constant impact on LSTs across all seasons: horizontal expansion increases the LST, while vertical expansion reduces the LST. These findings are consistent for both grid- and block-level analyses. This study emphasizes the flexible role of the natural environment in moderating temperatures.

Abstract We investigate regional features nearby the subway station using the clustering method called the funFEM and propose a two-step procedure to predict a subway passenger transport flow by incorporating the geographical information from the cluster analysis to functional time series prediction. A massive smart card transaction dataset is used to analyze the daily number of passengers for each station in Seoul Metro. First, we cluster the stations into six categories with respect to their patterns of passenger transport. Then, we forecast the daily number of passengers with respect to each cluster. By comparing our predicted results with the actual number of passengers, we demonstrate the predicted number of passengers based on the clustering results is more accurate in contrast to the result without considering the regional properties. The result from our data-driven approach can be applied to improve the subway service plan and relieve infectious diseases as we can reduce the congestion by controlling train intervals based on the passenger flow. Furthermore, the prediction result can be utilized to plan a ‘smart city’ which seeks shorter commuting time, comfortable ridership, and environmental sustainability.

Health information exchange can improve health outcomes and reduce unnecessary medical expenses. An important task in health information exchange is to prove data integrity and strengthen the right to self-determination of individuals. This can be addressed using blockchain technology and dynamic consents. We aimed to develop a blockchain-based mobile platform called HealthPocket to exchange reliable health information with proven integrity through a dynamic consent system based on the HL7 FHIR standards. Through HealthPocket, subjects can selectively provide their consent to share specific medical and PGHD through proper authorization, and each response is converted into the JSON format with FHIR compatibility. We conducted a usability test to demonstrate health information exchange between primary and tertiary medical institutions. A total of 116 subjects used the HealthPocket mobile application to selectively share health information for at least one month, and conducted a questionnaire about their experience. In addition, medical staff of the institution could access the medical information shared by the participants and use it for treatment. The user surveys for patients examined the perceived usefulness, perceived ease of use, and overall service satisfaction. The mean overall satisfaction with the health information exchange service was the highest (4.67 out of 5 points). As security, personal information protection, and interoperability are main concerns related to health information exchange, blockchain technology can provide suitable solutions. For instance, when health information is exchanged using blockchain technology, it is impossible to alter data blocks. Therefore, by using a blockchain-based platform and dynamic consent system, we ensured the integrity of medical data.

As part of our continuous search for novel tyrosinase inhibitors, we designed 5,6-dihydroimindazo[2,1-b]thiazol-3(2H)-one (DHIT) derivatives based on the structure of MHY773; a potent tyrosinase inhibitor with a 2-iminothiazolidin-4-one template. Of the 11 DHIT derivatives synthesized using a Knoevenagel condensation, three DHIT derivatives 1a (IC50 = 36.14 ± 3.90 μM), 1b (IC50 = 0.88 ± 0.91 μM), and 1f (IC50 = 17.10 ± 1.01 μM) inhibited mushroom tyrosinase more than kojic acid (IC50 = 84.41 ± 2.87 μM). Notably, compound 1b inhibited mushroom tyrosinase around 100- and 3.3-fold more potently than kojic acid and MHY773, respectively. Lineweaver-Burk plots demonstrated that compounds 1b and 1f competitively inhibited mushroom tyrosinase, and in silico docking results supported our kinetic results and indicated that these two compounds bind more strongly to the active site of tyrosinase than kojic acid. Docking simulation results using a human tyrosinase homology model confirmed the abilities of 1b and 1f to strongly inhibit human tyrosinase. B16F10 murine melanoma cells were used to investigate whether these two compounds display tyrosinase inhibitory activities and anti-melanogenesis effects in cells. Both compounds were found to significantly and dose-dependently inhibit cellular tyrosinase activity and intracellular and extracellular melanin production more potently than kojic acid. The similarities observed between the cellular tyrosinase and melanogenesis inhibitory effects of 1b and 1f suggest their observed anti-melanogenic effects were due to tyrosinase inhibition. These results indicate that compounds 1b and 1f, which possess the DHIT template, are promising candidates as anti-browning agents and therapeutic agents for hyperpigmentation disorders.

Although green (G, 500 to 600 nm) and far-red (FR, 700 to 800 nm) light play important roles in regulating plant growth and development, they are often considered less useful at stimulating photosynthesis than red (R, 600 to 700 nm) and blue (B, 400 to 500 nm) light. Based on this perception, approaches to modifying the transmission of greenhouse glazing materials include (1) conversion of G photons from sunlight into R photons and (2) exclusion of the near-infrared (>700 nm) fraction of sunlight. We evaluated these approaches using simulated scenarios with light-emitting diodes to determine how partial and complete substitution of G with R light and exclusion of FR light affected the growth of lettuce and tomato grown indoors. The substitution of G with R light had little or no effect on fresh and dry mass of tomato. However, with the presence of FR light, fresh and dry mass of lettuce increased by 22–26% as G light was increasingly substituted with R light. In tomato, excluding FR inhibited plant height, leaf area, and dry mass by 60–71%, 10–37%, and 20–44%, respectively. Similarly, in lettuce, excluding FR inhibited plant diameter, leaf length, and dry mass by 15–23%, 23–33%, or 28–48%, respectively. We conclude that the spectral conversion of G-to-R photons can promote plant growth in at least some crop species, such as lettuce, while the exclusion of FR decreases crop growth and yield.

Ten 2-mercaptobenzimidazole (2-MBI) analogs were synthesized as potential tyrosinase inhibitors because mercapto-containing compounds can bind to copper ions at the active site of tyrosinase to inhibit enzyme activity. Nine 2-MBI analogs showed sub-micromolar IC50 values for mushroom tyrosinase monophenolase activity; analog 4 was 280-fold more potent than kojic acid, and in diphenolase activity, 6 was 970-fold more potent than kojic acid. The inhibition mode of the 2-MBI analogs was investigated using kinetic studies supported by docking simulations. Benzimidazoles without the 2-mercapto substituent of the 2-MBI analogs lost their tyrosinase inhibitory activity, implying that the 2-mercapto substituent plays an important role in tyrosinase inhibition. The 2-MBI analogs exerted potent antioxidant effects against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reactive oxygen species (ROS). The results obtained from apple slices and human embryonic kidney cells (HEK-293) suggest that most 2-MBI analogs are sufficiently safe candidates to delay the browning of apple slices effectively. Thus, these results support the potential use of 2-MBI analogs as anti-browning agents in foods such as mushrooms, vegetables, and fruits.

Eliminating major xenoantigens in pig cells has drastically reduced human antibody-mediated hyperacute xenograft rejection (HXR). Despite these advancements, acute xenograft rejection (AXR) remains one of the major obstacles to clinical xenotransplantation, mediated by innate immune cells, including macrophages, neutrophils, and natural killer (NK) cells. NK cells play an ‘effector’ role by releasing cytotoxicity granules against xenogeneic cells and an ‘affecter’ role on other immune cells through cytokine secretion. We highlight the key receptor-ligand interactions that determine the NK cell response to target cells, focusing on the regulation of NK cell activating receptor (NKG2D, DNAM1) and inhibitory receptor (KIR2DL1-4, NKG2A, and LIR-1) signaling pathways. Inhibition of NK cell activity may protect xenografts from cytotoxicity. Recent successful approaches to reducing NK cell-mediated HXR and AXR are reviewed, including genetic modifications of porcine xenografts aimed at improving pig-to-human compatibility. Future directions to promote xenograft acceptance are discussed, including NK cell tolerance in pregnancy and NK cell evasion in viral infection.

Xylella fastidiosa is the most damaging pathogen in many parts of the world. To increase diagnostic capability of X. fastidiosa in the field, the loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assay were developed to mqsA gene of citrate-synthase (XF 1535) X. fastidiosa and evaluated for specificity and sensitivity. Both assays were more robust than current published tests for detection of X. fastidiosa when screened against 16 isolates representing the four major subgroups of the bacterium from a range of host species. No cross reaction with DNA from healthy hosts or other species of bacteria has been observed. The LAMP and PCR assays could detect 10-4 pmol and 100 copies of the gene, respectively. Hydroxynaphthol blue was evaluated as an endpoint detection method for LAMP. There was a significant color shift that signaled the existence of the bacterium when at least 100 copies of the target template were present.

The β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold confers tyrosinase inhibitory activity, and in the present study, 16 (Z)-5-(substituted benzylidene)-3-phenyl-2-thioxooxazolidin-4-one analogues containing this scaffold were synthesized. Mushroom tyrosinase inhibitory activities were examined. Compound 1c (IC50 = 4.70 ± 0.40 μM) and compound 1j (IC50 = 11.18 ± 0.54 μM) inhibited tyrosinase by 4.9 and 2.1-fold, respectively, and did so more potently than kojic acid (IC50 = 23.18 ± 0.11 μM). Kinetic analysis of tyrosinase inhibition revealed that 1c and 1j inhibited tyrosinase competitively. Results of docking simulation with mushroom tyrosinase using four docking programs suggested that 1c and 1j bind more strongly than kojic acid to the active site of tyrosinase and supported kinetic findings that both compounds are competitive inhibitors. The docking results of human tyrosinase homology model indicated that 1c and 1j can also strongly inhibit human tyrosinase. EZ-cytox assays revealed 1c and 1j were not cytotoxic to B16F10 melanoma cells. The effects of 1c and 1j on cellular tyrosinase activity and melanin production were also investigated in α-MSH- and IBMX-co-stimulated these cells. Both compounds significantly and dose-dependently reduced tyrosinase activity, and at 10 µM were more potent than kojic acid at 20 µM. Compounds 1c and 1j also inhibited melanogenesis, which suggested that the inhibitory effects of these compounds on melanin production were mainly attributable to their inhibitions of tyrosinase. These results indicate that compounds 1c and 1j with the PUSC scaffold have potential use as whitening agents for the treatment of hyperpigmentation-associated diseases.

Background: Aromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen. Methods: We analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE. Results: We included 47,569 women for the final analysis. Patients were classified into ‘No hormonal treatment (n = 18,807), ‘Switch (n = 2097)’, ‘Tamoxifen (n = 7081)’ and ‘AI (n = 19,584)’. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84–1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47–0.84). Conclusions: Our results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.

Objective Early diagnosis of ankylosing spondylitis (AS) remains challenging because of the high prevalence of chronic back pain in patients initially treated by nonrheumatology health care providers (HCPs). We assessed the patient pathway to rheumatology referral, including HCP recognition of inflammatory back pain (IBP) and other features suggestive of AS, diagnostic workup, treatment, and referral to a specialist with the goal of identifying barriers to patient referral to a rheumatologist. Methods US HCPs from 10 specialties were invited to participate in a cross‐sectional web‐based survey on clinical characteristics and diagnostic measures leading to IBP suspicion and the subsequent referral process. Eligible HCPs were actively practicing and had referred a patient with suspected IBP or ocular findings (ophthalmology only) within 12 months. Data were analyzed descriptively. Results Of 1690 HCPs, 61% identified morning stiffness lasting more than 30 minutes, 29% sleep disturbance due to back pain, and 28% pain that improves with activity as features suggestive of IBP. Nearly two‐thirds of primary care HCPs reported that they were the first HCPs consulted by patients with suspected IBP. Among HCPs ordering diagnostic blood work, approximately 90% selected antinuclear antibody and rheumatoid factor, whereas 76% selected human leukocyte antigen B27. Almost 40% would treat patients with suspected IBP themselves. HCPs cited lack of adequate specialists nearby (35.1%), insurance restrictions (47.1%), and long wait time (77.0%) as barriers to early referral. Conclusion Most HCPs had difficulty identifying features suggestive of IBP and indicated insurance restrictions and long wait times as barriers to early referral of patients with potential AS.

Objective The number of therapies for axial spondyloarthritis (axSpA) is increasing. Thus, it has become more challenging for patients and physicians to navigate the risk‐benefit profiles of the various treatment options. In this study, we used conjoint analysis—a form of trade‐off analysis that elucidates how people make complex decisions by balancing competing factors—to examine patient decision‐making surrounding medication options for axSpA. Methods We conducted an adaptive choice‐based conjoint analysis survey for patients with axSpA to assess the relative importance of medication attributes (eg, chance of symptom improvement, risk of side effects, route of administration, etc) in their decision‐making. We also performed logistic regression to explore whether patient demographics and disease characteristics predicted decision‐making. Results Overall, 397 patients with axSpA completed the conjoint analysis survey. Patients prioritized medication efficacy (importance score 26.8%), cost (26.3%), and route of administration (13.9%) as most important in their decision‐making. These were followed by risk of lymphoma (9.5%), dosing frequency (7.2%), risk of serious infection (6.0%), tolerability of side effects (5.3%), and clinic visit and laboratory test frequency (4.8%). In regression analyses, there were few significant associations between patients’ treatment preferences and sociodemographic and axSpA characteristics. Conclusions Treatment decision‐making in axSpA is highly individualized, and demographics and baseline disease characteristics are poor predictors of individual preferences. This calls for the development of online shared decision‐making tools for patients and providers, with the goal of selecting a treatment that is consistent with patients’ preferences.

Objective To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis. Methods This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank‐sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables. Results Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA than those without enthesitis (both P < 0.05). Additionally, higher proportions of patients with enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease‐modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without enthesitis. Patients with enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without enthesitis (all P < 0.05). Conclusion In this US‐based real‐world study, enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no enthesitis.

Human mesenchymal stromal cells are a promising source for cell-based therapies. Here the authors use Cas9 to engineer lines that secrete PDGF-BB and VEFGA for improving wound healing.

Preclinical trials of pig-to-nonhuman primate liver xenotransplantation have recently achieved longer survival times. However, life-threatening thrombocytopenia and coagulation dysregulation continue to limit preclinical liver xenograft survival times to less than one month despite various genetic modifications in pigs and intensive pharmacological support. Transfusion of human coagulation factors and complex immunosuppressive regimens have resulted in substantial improvements in recipient survival. The fundamental biological mechanisms of thrombocytopenia and coagulation dysregulation remain incompletely understood. Current studies demonstrate that porcine von Willebrand Factor binds more tightly to human platelet GPIb receptors due to increased O-linked glycosylation, resulting in increased human platelet activation. Porcine liver sinusoidal endothelial cells and Kupffer cells phagocytose human platelets in an asialoglycoprotein receptor 1-dependent and CD40/CD154-dependent manner, respectively. Porcine Kupffer cells phagocytose human platelets via a species-incompatible SIRPα/CD47 axis. Key drivers of coagulation dysregulation include constitutive activation of the extrinsic clotting cascade due to failure of porcine tissue factor pathway inhibitor to repress recipient tissue factor. Additionally, porcine thrombomodulin fails to activate human protein C when bound by human thrombin, leading to a hypercoagulable state. Combined genetic modification of these key genes may mitigate liver xenotransplantation-induced thrombocytopenia and coagulation dysregulation, leading to greater recipient survival in pig-to-nonhuman primate liver xenotransplantation and, potentially, the first pig-to-human clinical trial.

Background. There has been a dramatic increase in obesity in the United States. Several studies have reported conflicting results for the impact of obesity on outcomes of liver transplantation (LT). This study aims to assess the impact of obesity on LT and changes in body mass index (BMI) after transplantation. Methods. All adult LTs performed at Indiana University between 2001 and 2018 were reviewed. BMIs of recipients were subdivided into 6 categories. Survival outcomes were compared across the subgroup. BMI was followed up in a cohort of patients from 2008 to 2018. Results. Among 2024 patients, 25% were in class I obesity, 9.3% were in class II obesity, and 1.1% were in class III obesity. There was no significant difference in patient and graft survival at 10-y follow-up with respect to BMI. Among 1004 patients in the subgroup, BMI of all groups except the underweight group declined in the first 3 mo postoperatively; however, the BMI of all groups except the class III obesity group returned to the pre-LT level by 2 y and reached a plateau by 5 y. In the class III obesity group, there was a significant increase in body weight at 5 y. Conclusions. Class III obesity was not associated with higher mortality in our cohort. Because our cohort is small, it may be underpowered to detect a smaller difference in outcome. From our observation, obesity should not be considered a contraindication for LT. Post-LT interventions are required to prevent significant weight gain for the class III obesity group.

(Z)-5-Benzylidene-2-phenylthiazol-4(5H)-one ((Z)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (Z)-BPTs 1–14, was determined based on the 3JC,Hβ coupling constant of 1H-coupled 13C NMR spectra. Three (Z)-BPT derivatives (1–3) showed stronger tyrosinase inhibitory activities than kojic acid; in particular, 2 was to be 189-fold more potent than kojic acid. Kinetic analysis using mushroom tyrosinase indicated that 1 and 2 were competitive inhibitors, whereas 3 was a mixed-type inhibitor. The in silico results revealed that 1–3 could strongly bind to the active sites of mushroom and human tyrosinases, supporting the kinetic results. Derivatives 1 and 2 decreased the intracellular melanin contents in a concentration-dependent manner in B16F10 cells, and their anti-melanogenic efficacy exceeded that of kojic acid. The anti-tyrosinase activity of 1 and 2 in B16F10 cells was similar to their anti-melanogenic effects, suggesting that their anti-melanogenic effects were primarily owing to their anti-tyrosinase activity. Western blotting of B16F10 cells revealed that the derivatives 1 and 2 inhibited tyrosinase expression, which partially contributes to their anti-melanogenic ability. Several derivatives, including 2 and 3, exhibited potent antioxidant activities against ABTS cation radicals, DPPH radicals, ROS, and peroxynitrite. These results suggest that (Z)-BPT derivatives 1 and 2 have promising potential as novel anti-melanogenic agents.

Beyond producing leafy greens, there is a growing interest in strawberry production on indoor vertical farms. Considering that sole-source lighting is one of the most important components for successful indoor crop production, we investigated how photosynthetic photon flux density (PPFD) and the photoperiod of sole-source lighting affected plant growth, flowering, and fruit production in strawberry ‘Albion.’ Bare-rooted strawberry plants were grown in deep water culture hydroponics inside an indoor vertical farm at 21 °C under white + blue + red light-emitting diodes at a PPFD of 200, 300, or 450 µmol∙m−2∙s−1 with a 12-h or 16-h photoperiod. Under both photoperiods, increasing PPFD from 200 to 450 µmol∙m−2∙s−1 linearly increased crown diameter by 18–64%, shoot fresh and dry mass by 38–80%, and root fresh and dry mass by 19–48%. Under a PPFD ≥ 300 µmol∙m−2∙s−1, root fresh and dry biomass increased by 95–108% and 41–44%, respectively, with an increasing photoperiod from 12 to 16 h. In addition, increasing the photoperiod from 12 to 16 h accelerated flowering by 17–21 days under a PPFD ≥ 300 µmol∙m−2∙s−1 and first fruit harvest by 17 days at a PPFD of 450 µmol∙m−2∙s−1. Regardless of PPFD, strawberry fruit production (g·m−2·month−1) increased by 372–989% under a 16-h photoperiod in comparison to under a 12-h photoperiod. In contrast, there was little effect of PPFD on fruit production. Our results suggest that increasing the PPFD or photoperiod can increase strawberry plant growth, but increasing the photoperiod can have a dominant effect on increasing early fruit production in strawberry ‘Albion’.

Mycobacterium abscessus is a difficult respiratory pathogen to treat, when compared to other nontuberculus mycobacteria (NTM), due to its drug resistance. In this study, we aimed to find a new clarithromycin partner that potentiated strong, positive, synergy against M. abscessus among current anti-M. abscessus drugs, including omadacycline, amikacin, rifabutin, bedaquiline, and cefoxitine. First, we determined the minimum inhibitory concentrations required of all the drugs tested for M. abscessus subsp. abscessus CIP104536T treatment using a resazurin microplate assay. Next, the best synergistic partner for clarithromycin against M. abscessus was determined using an in vitro checkerboard combination assay. Among the drug combinations evaluated, omadacycline showed the best synergistic effect with clarithromycin, with a fractional inhibitory concentration index of 0.4. This positive effect was also observed against M. abscessus clinical isolates and anti-M. abscessus drug resistant strains. Lastly, this combination was further validated using a M. abscessus infected zebrafish model. In this model, the clarithromycin-omadacyline regimen was found to inhibit the dissemination of M. abscessus, and it significantly extended the lifespan of the M. abscessus infected zebrafish. In summation, the synergy between two anti-M. abscessus compounds, clarithromycin and omadacycline, provides an attractive foundation for a new M. abscessus treatment regimen.

In this study, (Z)-2-(benzylamino)-5-benzylidenethiazol-4(5H)-one (BABT) derivatives were designed as tyrosinase inhibitors based on the structure of MHY2081, using a simplified approach. Of the 14 BABT derivatives synthesized, two derivatives ((Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one [7] and (Z)-2-(benzylamino)-5-(2,4-dihydroxybenzylidene)thiazol-4(5H)-one [8]) showed more potent mushroom tyrosinase inhibitory activities than kojic acid, regardless of the substrate used; in particular, compound 8 was 106-fold more potent than kojic acid when l-tyrosine was used as the substrate. Analysis of Lineweaver–Burk plots for 7 and 8 indicated that they were competitive inhibitors, which was confirmed via in silico docking. In experiments using B16F10 cells, 8 exerted a greater ability to inhibit melanin production than kojic acid, and it inhibited cellular tyrosinase activity in a concentration-dependent manner, indicating that the anti-melanogenic effect of 8 is attributable to its ability to inhibit tyrosinase. In addition, 8 exhibited strong antioxidant activity to scavenge 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and peroxynitrite and inhibited the expression of melanogenesis-associated proteins (tyrosinase and microphthalmia-associated transcription factor). These results suggest that BABT derivative 8 is a promising candidate for the treatment of hyperpigmentation-related diseases, owing to its inhibition of melanogenesis-associated protein expression, direct tyrosinase inhibition, and antioxidant activity.

Abstract Introduction Few studies have evaluated the impact of delayed diagnosis of axial spondyloarthritis (axSpA) on the overall burden of disease. The objective of this review was to evaluate the available literature on the clinical, economic, and humanistic burden of delayed diagnosis in patients with axSpA. Methods This systematic literature review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the MEDLINE and Embase databases for English-language publications of original research articles (up to July 12, 2018) and conference abstracts (January 1, 2014, to July 12, 2018) reporting studies of adult patients with delayed diagnosis of axSpA associated with clinical, economic, or humanistic burden. Retrieved publications were screened for eligibility by two independent reviewers; discrepancies were resolved by a third independent reviewer. Data were extracted by one reviewer and validated by a second independent reviewer. Results A total of 1391 publications were retrieved, of which 21 met the inclusion criteria and were included in the analysis. Of these, 15 reported data on clinical burden, nine on economic burden, and six on humanistic burden, with eight studies reporting a combination of clinical, economic, and/or humanistic burden. Patients with a delayed diagnosis of axSpA generally had higher disease activity, worse physical function, and more structural damage than those who received an earlier diagnosis. Patients with a delayed diagnosis also had a greater likelihood of work disability and higher direct and indirect healthcare costs than those who received an earlier diagnosis. Delayed diagnosis was associated with a greater likelihood for depression, negative psychological impacts, and worse quality of life. Conclusions Delayed axSpA diagnosis was associated with more functional impairment, higher healthcare costs, and worse quality of life, highlighting the importance of early recognition of axSpA to reduce extensive burden on patients and society. Plain Language Summary Plain language summary available for this article.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Abstract Introduction Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are three common inflammatory rheumatic diseases that can lead to deformities and joint destruction. Few studies have compared disease burden across patients with these diseases. The objective of this study was to compare disease burden in patients with RA, PsA, or axSpA in routine US clinical practice. Methods This study included adults with RA, PsA, or axSpA enrolled in the Corrona RA and PsA/SpA registries between March 2013 and March 2018. Patient and clinical characteristics at enrollment were compared between patients with RA vs. PsA and RA vs. axSpA using t tests or Wilcoxon rank-sum tests for continuous variables and χ 2 or Fisher’s exact tests for categorical variables. Results A total of 11,350 patients with RA, 2003 with PsA, and 495 with axSpA were included. Patients with RA had shorter mean symptom and disease duration (9.4 and 7.6 years, respectively) than those with PsA (11.2 and 8.4 years) or axSpA (16.7 and 9.8 years). Patients with PsA had lower mean physician global assessment (18.6 vs. 27.3), higher patient global assessment (43.2 vs. 36.9), comparable pain (38.9 vs. 39.5), and lower fatigue (41.1 vs. 43.4) scores than those with RA. Patients with axSpA had comparable mean physician global assessment (25.5 vs. 27.3) and higher patient global assessment (50.2 vs. 36.9), pain (46.1 vs. 39.5), and fatigue (48.3 vs. 43.4) scores than those with RA. Conclusions Disease burden in patients with PsA or axSpA was comparable to or greater than that in patients with RA on the basis of common patient-reported outcome measures but appeared lower when assessed using RA disease activity measures, suggesting that disease-specific approaches to care are needed to optimize disease management. Funding This study was sponsored by Corrona, LLC, and financial support was provided by Novartis. The Rapid Service Fee was funded by Novartis. Plain Language Summary Plain language summary available for this article.

Abstract Purpose This real-world study evaluated the feasibility of assessing patient-reported symptom improvement and treatment satisfaction using a web-based survey among patients with ankylosing spondylitis (AS) treated with secukinumab. Methods This cross-sectional, web-based survey collected data on demographics, symptoms, treatment history, and treatment satisfaction from US patients with AS who were receiving secukinumab at survey participation. Patients reported AS symptoms experienced before and after secukinumab initiation, time to symptom improvement, and satisfaction with secukinumab treatment. Results Of 2755 patients screened, 200 with AS were included in the analysis. The mean (SD) age of patients was 34.4 (10.6) years; 86.5% were biologic experienced. Most (74.0%) reported overall improvement (“a little,” “moderately,” or “much better”) in AS symptoms since secukinumab initiation compared with before secukinumab initiation; a similar trend was observed for all the individual symptoms analyzed (pain disrupting sleep, fatigue, morning stiffness, pain and stiffness in lower back or neck, sore areas other than joints, and ankle or heel pain [indicating enthesitis]). Approximately 41.9% of patients reported overall symptom improvement within 4 weeks of secukinumab treatment. Most expressed overall satisfaction (“very,” “mostly,” or “somewhat satisfied”) with secukinumab regarding symptom improvement (99.0%), speed of symptom improvement (97.0%), frequency and method of administration (96.0% and 91.5%, respectively), ease of use (93.5%), patient support services (97.0%), and side effects, if any (93.0%). Conclusion Most patients reported overall symptom improvement and satisfaction with treatment. Our study indicates that patient-reported perspectives may be feasibly collected using a web-based survey to provide insights into treatment experience and satisfaction.

Abstract Introduction We aim to assess the real-world, US patient-reported impact of ankylosing spondylitis (AS) on quality of life (QOL) across physical, discomfort, social, and emotional domains. Methods Demographic and QOL data were collected from a random sample of patients associated with the Spondylitis Association of America (SAA) from July to December 2017. QOL measures were based on the Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL) questionnaire. The survey evaluated AS impact on the physical domain on the day of survey participation and impact on the discomfort, social, and emotional domains within the week before participation. A 3:1 (male to female) weighting was performed to reflect the reported prevalence of AS in US adults. Results Of 820 respondents who completed the survey, 716 self-reported receiving an AS diagnosis from their doctor and were included in this analysis (mean age, 55.5 years; 46.9% male). The mean total EASi-QoL score was 28.9 (weighted); overall, 33.7%, 31.7%, and 34.7% of respondents, respectively, reported a low (EASi-QoL score 0–17), a medium (18–35), and a high (≥ 36) impact of AS on QOL. The physical domain was most impacted; 41.9% of respondents had an EASi-QoL score ≥ 10 (weighted). Women were significantly more likely than men to report a high impact of AS on all QOL domains. Biologic users reported an impact on QOL comparable with the impact on QOL of nonsteroidal anti-inflammatory drug use. AS also impacted lifestyle characteristics, including career choice and sports participation. Conclusion AS negatively impacted all QOL domains analyzed. The incorporation of subjective measures of disease into disease evaluation should be considered. Funding Novartis Pharmaceuticals Corporation and UCB, Inc. Plain Language Summary Plain language summary available for this article.

Abstract Introduction We describe the journey to diagnosis of ankylosing spondylitis (AS) from the patient perspective and examine differences in this journey by sex. Methods US adults aged ≥ 18 years with a self-reported AS diagnosis were recruited online through CreakyJoints, a patient support community, and ArthritisPower, a patient research registry. Respondents completed a web-based survey on sociodemographics, disease burden, and diagnosis history. Results were stratified by sex and time to diagnosis using two-sample t tests and χ 2 tests, respectively, to observe differences across the groups; P

Many compounds containing the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, including cinnamamide derivatives, have been shown to inhibit tyrosinase potently in vitro and in vivo. Structural changes to cinnamamide derivatives were produced by adding a dithionate functional group to provide eight (Z)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs with high log p values for skin. These analogs were synthesized using a two-step reaction, and their stereochemistry was confirmed using the 3JC4-Hβ values of C4 measured in proton-coupled 13C mode. Analogs 2 (IC50 = 5.21 ± 0.86 µM) and 3 (IC50 = 1.03 ± 0.14 µM) more potently inhibited mushroom tyrosinase than kojic acid (IC50 = 25.26 ± 1.10 µM). Docking results showed 2 binds strongly to the active site of tyrosinase, while 3 binds strongly to an allosteric site. Kinetic studies using l-tyrosine as substrate indicated 2 and 3 competitively and non-competitively inhibit tyrosinase, respectively, which was supported by our docking results. In B16F10 cells, 3 significantly and concentration-dependently reduced α–MSH plus IBMX induced increases in cellular tyrosinase activity and melanin production and the similarity between these inhibitory patterns implied that the anti-melanogenic effect of 3 might be due to its tyrosinase-inhibitory ability. In addition, 2 and 3 exhibited strong antioxidant effects; for example, they reduced ROS and ONOO– levels and exhibited radical scavenging activities, suggesting that these effects might underlie their anti-melanogenic effects. Furthermore, 3 suppressed the expressions of melanogenesis-associated proteins and genes in B16F10 cells. These results suggest (Z)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs offer a means of producing novel anti-melanogenesis agents.

This scoping review explored the trends in open educational resources (OER) that support the interactions of learners with disabilities and the challenges of supporting these interactions in such environments. Emerging OER and open educational practices allow learners to interact with digital learning resources in self-regulated learning. Since OER assume learners’ self-regulation, research has explored how to promote learner interactions to facilitate better engagement and motivation. Emerging research on OER-enabled pedagogy corroborate this trend. However, despite increasing interest in OER and open educational practices, few studies have demonstrated how OER support various types of interactions for learners with disabilities. Learners with disabilities are likely to experience challenges in interacting with OER due to their modality constraints. A comprehensive literature synthesis is essential to investigate the needs of learners with disabilities in their interactions in OER. In this study, we reviewed and synthesized existing research on how OER and open educational practices support the interactions of learners with disabilities across different OER platforms. Our findings suggest both research and design implications for future OER designs suited for learners with disabilities.

Tyrosinase is a key enzyme responsible for melanin biosynthesis and is effective in protecting skin damage caused by ultraviolet radiation. As part of ongoing efforts to discover potent tyrosinase inhibitors, we systematically designed and synthesized thirteen (E)-benzylidene-1-indanone derivatives (BID1–13) and determined their inhibitory activities against tyrosinase. Among the compounds evaluated, BID3 was the most potent inhibitor of mushroom tyrosinase (IC50 = 0.034 µM, monophenolase activity; IC50 = 1.39 µM, diphenolase activity). Kinetic studies revealed that BID3 demonstrated a mixed type of tyrosinase inhibition with Ki value of 2.4 µM using l-DOPA as a substrate. In silico molecular docking simulations demonstrated that BID3 can bind to the catalytic and allosteric sites of tyrosinase to inhibit enzyme activity which confirmed in vitro experimental studies between BID3 and tyrosinase. Furthermore, melanin contents decreased and cellular tyrosinase activity was inhibited after BID3 treatment. These observations revealed that BID3 is a potent tyrosinase inhibitor and potentially could be used as a whitening agent for the treatment of pigmentation-related disorders. Keywords: 1-Indanone, 2,4-Dihydroxy benzylidene, Melanin, Tyrosinase inhibitor

Abstract Objectives To characterize US patients with ankylosing spondylitis (AS) who were treated with secukinumab and to assess rheumatologist-reported reasons for prescribing treatment in clinical practice. Methods This descriptive analysis of data from a US retrospective medical chart review included patients aged ≥ 18 years diagnosed with AS who initiated secukinumab after 15 January 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, co-morbidity profile, and treatment history prior to or on the index date, defined as the date of the first secukinumab prescription recorded in the medical chart. Information on physician-level characteristics and reasons for secukinumab prescription and dosing were also collected. Results Medical charts from 78 patients with AS who initiated secukinumab were reviewed by 25 rheumatologists between 7 July 2017 and 11 August 2017. Overall, 76.9% of patients were male, mean (SD) age was 39.8 (10.8) years, and 34.6% were biologic naïve. The most common reasons for secukinumab initiation among biologic-naïve and biologic-experienced patients, respectively, were efficacy/effectiveness (77.8%) and failure of other prior biologics (84.3%). Nearly all patients (94.9%) received a loading dose, including 150 mg every week (39.7%), 300 mg every week (53.8%), and other (1.3%). Overall, 73 patients (93.6%) received ≥ 1 maintenance secukinumab dose, of whom 56.2% and 43.8% received 150 mg and 300 mg, respectively, every 4 weeks. Conclusions In this US medical chart review of patients with AS who initiated secukinumab, approximately one-third were biologic naïve, and secukinumab efficacy/effectiveness and failure of other biologics were the most common reasons for initiating secukinumab.