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The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

To overcome the shortcomings of activated bleaching clay in the decolorization of edible oil industry, such as high operating temperature, large residual oil ratio, and difficulty in the disposal of waste bleaching clay, this work developed the super-strong adsorbent material, graphene, as a new type of adsorbent for the decolorization of rapeseed oil. Graphene nanoplatelets (GNP) and graphene oxide (GO) were characterized by scanning electron microscope. Fourier infrared spectrometer and Raman spectrometer, etc After clarifying the structural characteristics of graphene, they were used for the decolorization of rapeseed oil, and the effects of graphene species, addition amount, pressure, temperature, and reaction time on the decolorization of rapeseed oil were investigated. The results showed that GNP was more effective in rapeseed oil decolorization compared with GO and exhibited unique adsorption properties for chlorophyll in oil at low temperature (45 ℃). The one-factor results showed that GNP could remove 80.6% of chlorophyll in oil under the optimized conditions of GNP addition of 2.0%, temperature of 45 ℃ and adsorption time of 5 min. GNP as adsorbent for oil decolorization has the advantages of low reaction temperature and short adsorption time, which could have the potential application prospects in low temperature moderate processing of oils and fats.

Thermal cooking is one of the major application scenarios of edible oils in Chinese cooking. Cooking oil fume (COF), which is generated from edible oils during thermal cooking, is a complex mixture of solid particles, liquid droplets and gaseous volatile organic compounds (VOCs), and COF imposes adverse effects on both the indoor atmosphere and human health. In the present review, we first elucidate the compositional characteristics of the two major harmful substances in COF, particulate matter (PM) and VOCs and their emission status during the thermal cooking of edible oils, and then summarize the influences of COF exposure on human respiratory diseases and other related health risks. Next, the major factors that affect the composition and emission characteristics of COF are discussed from the perspectives of thermal cooking methods, types of cooking ingredients, and the quality and basic properties of edible oils. Finally, an outlook is given on the optimization of edible oil processing technologies based on the compositional characteristics of COF and the development of new processing technologies, raw materials and pathways for future edible oils in the future in order to achieve precise and moderate processing of edible oils that is green with low energy consumption and to produce high-quality, nutritious and healthy edible oils for use in Chinese cooking. This review could provide some references for the future development of edible oil and fat processing technologies, and may be of guiding significance to improving the nutritional quality and safety of edible oils and fats and even helping to achieve the national strategic goals of “Healthy China” and “Double Carbon”.

BackgroundSocial Media, such as Yelp, provides rich information of consumer experience. Previous studies suggest that Yelp can serve as a new source to study patient experience. However, the lack of a corpus of patient reviews causes a major bottleneck for applying computational techniques. ObjectiveThe objective of this study is to create a corpus of patient experience (COPE) and report descriptive statistics to characterize COPE. MethodsYelp reviews about health care-related businesses were extracted from the Yelp Academic Dataset. Natural language processing (NLP) tools were used to split reviews into sentences, extract noun phrases and adjectives from each sentence, and generate parse trees and dependency trees for each sentence. Sentiment analysis techniques and Hadoop were used to calculate a sentiment score of each sentence and for parallel processing, respectively. ResultsCOPE contains 79,173 sentences from 6914 patient reviews of 985 health care facilities near 30 universities in the United States. We found that patients wrote longer reviews when they rated the facility poorly (1 or 2 stars). We demonstrated that the computed sentiment scores correlated well with consumer-generated ratings. A consumer vocabulary to describe their health care experience was constructed by a statistical analysis of word counts and co-occurrences in COPE. ConclusionsA corpus called COPE was built as an initial step to utilize social media to understand patient experiences at health care facilities. The corpus is available to download and COPE can be used in future studies to extract knowledge of patients’ experiences from their perspectives. Such information can subsequently inform and provide opportunity to improve the quality of health care.

BackgroundA search engine to find physicians’ information is a basic but crucial function of a health care provider’s website. Inefficient search engines, which return no results or incorrect results, can lead to patient frustration and potential customer loss. A search engine that can handle misspellings and spelling variations of names is needed, as the United States (US) has culturally, racially, and ethnically diverse names. ObjectiveThe Marshfield Clinic website provides a search engine for users to search for physicians’ names. The current search engine provides an auto-completion function, but it requires an exact match. We observed that 26% of all searches yielded no results. The goal was to design a fuzzy-match algorithm to aid users in finding physicians easier and faster. MethodsInstead of an exact match search, we used a fuzzy algorithm to find similar matches for searched terms. In the algorithm, we solved three types of search engine failures: “Typographic”, “Phonetic spelling variation”, and “Nickname”. To solve these mismatches, we used a customized Levenshtein distance calculation that incorporated Soundex coding and a lookup table of nicknames derived from US census data. ResultsUsing the “Challenge Data Set of Marshfield Physician Names,” we evaluated the accuracy of fuzzy-match engine–top ten (90%) and compared it with exact match (0%), Soundex (24%), Levenshtein distance (59%), and fuzzy-match engine–top one (71%). ConclusionsWe designed, created a reference implementation, and evaluated a fuzzy-match search engine for physician directories. The open-source code is available at the codeplex website and a reference implementation is available for demonstration at the datamarsh website.

BackgroundThe Unified Medical Language System (UMLS) contains many important ontologies in which terms are connected by semantic relations. For many studies on the relationships between biomedical concepts, the use of transitively associated information from ontologies and the UMLS has been shown to be effective. Although there are a few tools and methods available for extracting transitive relationships from the UMLS, they usually have major restrictions on the length of transitive relations or on the number of data sources. ObjectiveOur goal was to design an efficient online platform that enables efficient studies on the conceptual relationships between any medical terms. MethodsTo overcome the restrictions of available methods and to facilitate studies on the conceptual relationships between medical terms, we developed a Web platform, onGrid, that supports efficient transitive queries and conceptual relationship studies using the UMLS. This framework uses the latest technique in converting natural language queries into UMLS concepts, performs efficient transitive queries, and visualizes the result paths. It also dynamically builds a relationship matrix for two sets of input biomedical terms. We are thus able to perform effective studies on conceptual relationships between medical terms based on their relationship matrix. ResultsThe advantage of onGrid is that it can be applied to study any two sets of biomedical concept relations and the relations within one set of biomedical concepts. We use onGrid to study the disease-disease relationships in the Online Mendelian Inheritance in Man (OMIM). By crossvalidating our results with an external database, the Comparative Toxicogenomics Database (CTD), we demonstrated that onGrid is effective for the study of conceptual relationships between medical terms. ConclusionsonGrid is an efficient tool for querying the UMLS for transitive relations, studying the relationship between medical terms, and generating hypotheses.

Edible oils and fats are the important dietary nutrients for human body, and play a vital roles in maintaining nutritional health for the hosts. Whereas, the unhealthy oils and fats intake would lead to the increase of the risks of chronic metabolic diseases, which has become a serious public health challenge for the present society. The oilomics, integrating genomics, transcriptomics, proteomics, metabolomics, lipomics as the major analytical methods, have been becoming on important approach to elucidate the host nutritional and metabolic regulation mechanisms, and realize the personalized nutrition of human body based on the functional characteristics of dietary factors. The present review manuscript illustrated the basic concepts of oilomics, and the major research approaches of oilomics in the areas of edible oil nutrition and human health. Moreover, the research progress of oilomics in oil nutrition and host health research were also summarized, primarily, focusing on elaborating the nutrients metabolic regulation, the enteral nutrition and gut homeostasis, as well as the personalized nutrition of the humans. In view of the current research status, the future trends of the development of oilomics were further prospected, at the aim of which is to provide references for expanding the applications of oilomics in lipid nutrition and human health. The overall nutrition level of the nationwide residents will be improved, and the construction of healthy China will be promoted.

Oil is a significant source of fatty acids and various trace functional components, and plays a vital role in regulating human health. The macro- and micro-components in oils are closely related to nutritional health. This paper introduces the future development goals and strategies of healthy oils from two aspects of precise nutrition and moderate processing. Firstly, precise nutrition based on life cycle and physiological state is a priority research area of lipid science. On the other hand, moderate processing will retain nutrients such as vitamin E, phytosterols, and squalene to a greater extent, and avoid the formation of risk factors such as trans fatty acids, 3-chloropropanol esters, and glycidyl esters. Moderate processing not only ensures the safety of oil, but also reduces the loss of healthy and beneficial fat concomitants, which is the development direction of oil engineering research. Therefore, under the dual demands of nutrition and safety, accurate nutrition and moderate processing of oils will help the implementation of "Healthy China" and "Double- Carbon" strategies. Future healthy oils will not only provide basic nutrition and flavor, but also give specific health functions to people with different life cycles, such as infants, children, adolescents, adults and the elderly, and maintain the homeostasis of people with different physiological states including pregnant and lactating women.

Selecting training samples is crucial in remote sensing image classification. In this paper, we selected three images—Sentinel-2, GF-1, and Landsat 8—and employed three methods for selecting training samples: grouping selection, entropy-based selection, and direct selection. We then used the selected training samples to train three supervised classification models—random forest (RF), support-vector machine (SVM), and k-nearest neighbor (KNN)—and evaluated the classification results of the three images. According to the experimental results, the three classification models performed similarly. Compared with the entropy-based method, the grouping selection method achieved higher classification accuracy using fewer samples. In addition, the grouping selection method outperformed the direct selection method with the same number of samples. Therefore, the grouping selection method performed the best. When using the grouping selection method, the image classification accuracy increased with the increase in the number of samples within a certain sample size range.

Abstract Background The coral-Symbiodiniaceae symbiosis is fundamental for the coral reef ecosystem. Corals provide various inorganic nutrients to their algal symbionts in exchange for the photosynthates to meet their metabolic demands. When becoming symbionts, Symbiodiniaceae cells show a reduced proliferation rate and a different life history. While it is generally believed that the animal hosts play critical roles in regulating these processes, far less is known about the molecular underpinnings that allow the corals to induce the changes in their symbionts. Results We tested symbiont cell proliferation and life stage changes in vitro in response to different nutrient-limiting conditions to determine the key nutrients and to compare the respective symbiont transcriptomic profiles to cells in hospite. We then examined the effects of nutrient repletion on symbiont proliferation in coral hosts and quantified life stage transitions in vitro using time-lapse confocal imaging. Here, we show that symbionts in hospite share gene expression and pathway activation profiles with free-living cells under nitrogen-limited conditions, strongly suggesting that symbiont proliferation in symbiosis is limited by nitrogen availability. Conclusions We demonstrate that nitrogen limitation not only suppresses cell proliferation but also life stage transition to maintain symbionts in the immobile coccoid stage. Nutrient repletion experiments in corals further confirmed that nitrogen availability is the major factor limiting symbiont density in hospite. Our study emphasizes the importance of nitrogen in coral-algae interactions and, more importantly, sheds light on the crucial role of nitrogen in symbiont life history regulation.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN‐825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open‐label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450‐mg single dose under fasted conditions or with a high‐fat meal. Multiple‐dose PKs for twice‐daily dosing of either 300 or 450 mg with low‐ or high‐fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose‐proportional manner from 150 to 450 mg. At 450 mg, a high‐fat meal increased the maximum observed concentration and area under the curve by approximately 1.9‐ and 2.1‐fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies. [ABSTRACT FROM AUTHOR]

Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

We hypothesized that generalized linear mixed models (GLMMs), which estimate the additive genetic variance underlying phenotype variability, would facilitate rapid characterization of clinical phenotypes from an electronic health record. We evaluated 1,288 phenotypes in 29,349 subjects of European ancestry with single-nucleotide polymorphism (SNP) genotyping on the Illumina Exome Beadchip. We show that genetic liability estimates are primarily driven by SNPs identified by prior genome-wide association studies and SNPs within the human leukocyte antigen (HLA) region. We identify 44 (false discovery rate q