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For dupilumab, real-world long-term follow-up data remain scarce, and studies on optimized treatment modes as well as drug survival rate and its predictors are lacking. To explore the effectiveness of different treatment modes of dupilumab and to understand the drug survival rates of dupilumab in China and its predictive factors. This retrospective study included patients with moderate-to-severe AD who received dupilumab treatment. Their clinical data were collected and analyzed. Compared with baseline, the SCORing Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), numerical rating scale (NRS), and Atopic Dermatitis Control Tool (ADCT) scores significantly decreased at 12, 24, and 52 weeks (p < 0.0001), and the continuous medication group had more significant improvements in SCORAD, EASI, NRS, and ADCT scores at 52 weeks than the noncontinuous medication group (p < 0.05). The 6-month and 1-year drug survival rates of dupilumab were 59.7% and 51.9%, respectively. The most common reason for treatment discontinuation was the satisfactory control of AD. Patients with adult-onset AD (adjusted odds ratio [OR]: 0.15, 95% confidence interval [CI]: 0.03–0.73) , not complicated by other systemic diseases (adjusted OR: 0.17, 95% CI: 0.04–0.84) and eosinophilia at baseline (adjusted OR: 3.71, 95% CI: 1.12–12.26) had a higher probability of drug discontinuation. In real-world practice in China, dupilumab has exhibited good long-term effectiveness and safety for the treatment of moderate-to-severe AD, and continuous administration can benefit patients in the long term. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated. Methods: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach. Results: [18F]FDG (2‐deoxy‐2‐[fluorine‐18]fluoro‐d‐glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one‐carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade. Conclusion: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism. [ABSTRACT FROM AUTHOR]

In this paper, two new fault-tolerant interior permanent magnet (FT-IPM) motors are proposed and compared for achieving high fault tolerance and sensorless operating capacity under multiple operations. Most previous studies regarding FT-IPM motors aim to improve fault-tolerant capability but suffer from the saliency characteristic problem, which is unfavorable for sensorless control. To overcome this issue, the design idea of flux-intensifying effect is innovatively proposed. Based on this, two new FT-IPM motors with different rotor structures and slot-pole combinations are developed to achieve flux-intensifying effect. To explore the impact of different motor structures and slot-pole combinations on motor performances, the simulation and experimental results of the two motors are compared and discussed in detail. The comparison results indicate that good fault tolerance and sensorless operating performances need tradeoffs, which provide a reference for balancing the fault tolerance and sensorless operating capacity. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

• Atopic dermatitis significantly affects patients' quality of life. • Some patients are resistant to monotherapy for atopic dermatitis. • Combining dupilumab and subcutaneous immunotherapy may improve patients' responses. Subcutaneous immunotherapy (SCIT) and dupilumab are important treatments for patients with moderate to severe atopic dermatitis (AD). However, in clinical practice, poor response to allergen immunotherapy (AIT) or dupilumab has been observed in some patients. It is unknown whether combining dupilumab and SCIT can improve treatment responses in patients with moderate to severe AD that is resistant to dupilumab or SCIT monotherapy. This single-centre, retrospective, observational, real-world study evaluated the efficacy and safety of dupilumab and SCIT for refractory moderate to severe AD. The data of ten patients with moderate to severe atopic dermatitis who were treated with dupilumab and SCIT were retrospectively analysed. The scoring atopic dermatitis (SCORAD) score, numerical rating scale (NRS), and atopic dermatitis control test (ADCT) scores and eosinophil and total IgE levels before and after add-on therapy were compared and analysed. The SCORAD, NRS, and ADCT scores decreased significantly at four and 12 weeks after the initiation of add-on therapy and plateaued during maintenance treatment. The eosinophil and total IgE levels were not significantly different before and after add-on therapy. No serious adverse reactions were reported in any patient during add-on therapy. This study indicates that the combination of dupilumab and SCIT safely improves the treatment response of patients with moderate to severe AD who are resistant to dupilumab or SCIT monotherapy. [ABSTRACT FROM AUTHOR]

Low‐cost, low‐power wireless sensor nodes that operate in Cauchy noise are required for applications that are located near highly trafficked roads, highways, and bridges, where solar or other green power operation is desirable. A novel suboptimal Cauchy detector of notable simplicity, suitable for low‐power sensor nodes, is proposed. The novel suboptimal detector approaches the performance of the optimal detector very closely while surpassing the performance of popular previously published suboptimal Cauchy detectors by 1–4 dB. [ABSTRACT FROM AUTHOR]

Odorant-binding proteins (OBPs) are found in both insects and vertebrates, and it is believed that they are involved in chemical communication. In this study, we identify and express 2 OBPs from the scarab beetle, Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae). HoblOBP1 shows more similarities with other scarab beetle OBPs, whereas HoblOBP2 is more diverse. N-phenyl-1-naphthylamine (1-NPN) is used as a fluorescent probe in ligand-binding experiment, and results indicate that both HoblOBPs prefer plant volatiles to putative H. oblita sex pheromones. HoblOBP1 shows binding affinity to a wider range of test compounds, but HoblOBP2 displays more specific binding affinity. Cinnamaldehyde and 2,4-di-tert-butylphenol bind to HoblOBP1 can elicit strong electrophysiological responses of the antennae from female H. oblita adults, respectively. Methyl salicylate also shows good affinity to HoblOBP2 and it can elicit moderate electrophysiological responses. Although, b-ionone is one of the ligands of the strongest binding, it elicits a weak electrophysiological response. In the immunocytochemical analysis, we observe that HoblOBP1 and HoblOBP2 are coexpressed in sensilla basiconica and placodea in both sexes. [ABSTRACT FROM AUTHOR]

Background: Gynecological cancer will become a more important public health problem in future years but limited evidence on gynecological cancer burden in China. Methods: We extracted age-specific rate of cancer cases and deaths during 2007–2016 from the Chinese Cancer Registry Annual Report, and estimated age-specific population size using the data released by National Bureau of Statistics of China. Cancer burden were calculated by multiplying the rates with the population size. Temporal trends of the cancer cases, incidence, deaths, and mortality during 2007–2016 were calculated by JoinPoint Regression Program, and from 2017 to 2030 were projected by grey prediction model GM (1,1). Results: In China, total gynecological cancer cases increased from 177,839 to 241,800, with the average annual percentage change of 3.5% (95% CI: 2.7–4.3%) during 2007–2016. Cervical, uterine, ovarian, vulva, and other gynecological cancer cases increased by 4.1% (95% CI: 3.3–4.9%), 3.3% (95% CI: 2.6–4.1%), 2.4% (95% CI: 1.4–3.5%), 4.4% (95% CI: 2.5–6.4%), and 3.6% (95% CI: 1.4–5.9%) respectively. From 2017 to 2030, projected gynecological cancer cases are changing from 246,581 to 408,314. Cervical, vulva and vaginal cancers showed evident upward trend, while uterine and ovarian cancer cases are slightly increasing. The increases for age-standardized incidence rates were similar with that of cancer cases. Temporal trends of cancer deaths and mortality were similar with that of cancer cases and incidence during 2007–2030, except that uterine cancer deaths and mortality were declined. Conclusions: With the aging of population and other increased risk factors, the burden of gynecological cancers in China is likely to be grew rapidly in the future, comprehensive gynecological cancer control should be concerned. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized as a distinct onset and progression of cognitive and functional decline associated with age, as well as a specific neuropathology. It has been discovered that glutamine (Gln) metabolism plays a crucial role in cancer. However, a full investigation of its role in Alzheimer's disease is still missing. This study intended to find and confirm potential Gln-related genes associated with AD using bioinformatics analysis. The discovery of GlnMgs was made possible by the intersection of the WGCNA test and 26 Gln-metabolism genes (GlnMgs). GlnMgs' putative biological functions and pathways were identified using GSVA. The LASSO method was then used to identify the hub genes as well as the diagnostic efficiency of the four GlnMgs in identifying AD. The association between hub GlnMgs and clinical characteristics was also studied. Finally, the GSE63060 was utilized to confirm the levels of expression of the four GlnMgs. Four GlnMgs were discovered (ATP5H, NDUFAB1, PFN2, and SPHKAP). For biological function analysis, cell fate specification, atrioventricular canal development, and neuron fate specification were emphasized. The diagnostic ability of the four GlnMgs in differentiating AD exhibited a good value. This study discovered four GlnMgs that are linked to AD. They shed light on potential new biomarkers for AD and tracking its progression. [ABSTRACT FROM AUTHOR]

Background A previous validation study showed a very low sensitivity and higher specificity associated with Hanifin and Rajka criteria (H&R) and the UK Working Party criteria (UKWP) in diagnosing AD vs. the Chinese criteria of atopic dermatitis (AD) for children (CCAD). However, their diagnostic efficacy in adult and elderly Chinese populations remains unknown. Objectives To validate the diagnostic efficacy of three sets of AD criteria in adult and elderly Chinese populations in a hospital setting. Methods A total of 1034 patients (aged 19–95 years) from five university hospital dermatological clinics were recruited. Medical history, dermatological examination, AD diagnosis and evaluation of AD severity were done by dermatologists. Each patient was investigated by two dermatologist panels, one to establish a clinical diagnosis, and the other to identify and record the major or minor signs of H&R criteria, UKWP criteria and CCAD. Taking clinical diagnosis as the reference, the diagnostic efficacy of three sets of diagnostic criteria was evaluated. The χ2 test or rank sum test were used for between-groups comparisons. Results CCAD had a higher sensitivity (84.0%), especially among mild and moderate cases of AD (72.7% and 90.3%, respectively), than the H&R (58.0%; P < 0.001) and UKWP criteria (56.0%; P < 0.001) in diagnosing AD. The specificity of CCAD (92.7%) was slightly lower than the H&R (97.3%; P < 0.001) or UKWP criteria (97.4%; P < 0.001). The CCAD had the highest Youden index (0.77), accuracy rate (0.90) and Kappa value (0.76) of the three sets of diagnostic criteria. Conclusions Consistent with results in a population of Chinese children, although the H&R and UKWP criteria had a high specificity for diagnosing AD, their low sensitivity limited their use in adult and elderly Chinese patients. Based on the high sensitivity and favourable diagnostic efficacy, the CCAD is proposed for AD diagnosis in adult and elderly Chinese populations, especially for cases of mild and moderate AD. [ABSTRACT FROM AUTHOR]

Polypyrrole (PPy)/montmorillonite (MMT) nanocompounds were prepared by in situ chemical oxidative polymerization of pyrrole in the presence of MMT. The results indicate PPy is intercalated into MMT interlayers and the morphology of obtained PPy in nanocompounds is changed to flake-like rather than granular particles as pristine PPy. The resultant PPy/MMT nanocompounds and pristine PPy were used as microwave absorbing filler separately to prepare microwave absorbing PPy/MMT and PPy epoxy composites. The results indicate PPy/MMT epoxy composites exhibit much better microwave absorbing properties than those filled by pristine PPy. The maximum reflection loss of 20 wt% PPy/MMT filled composite is −32.63 dB at 10.55 GHz with a matching thickness of 2.8 mm, and the effective absorption bandwidth with the reflection loss below −10 dB is from 8.6 GHz to 12.4 GHz, which almost covers the whole X-band. We postulated that the morphology change of PPy in PPy/MMT and its better dispersion may be responsible for the enhancement of microwave absorption. POLYM. COMPOS., 37:532-538, 2016. © 2014 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Abstract: Odorant-binding proteins (OBPs) are important parts of insect olfactory systems, and sensitive olfaction is vital for phytophagous insects in host foraging. Electrophysiological studies are helpful in understanding olfactory sensing in Sitobion avenae (Hemiptera: Aphididae), but the functions of odorant-binding proteins in this insect are poorly understood. In this study, we used fluorescence competition assays to measure the binding specificities of SaveOBPs. The results showed that both SaveOBP2 and SaveOBP3 were superior to SaveOBP7 in binding green leaf volatiles. It was unexpected that SaveOBP7 bound trans-β-farnesene strongly, which was known as alarm pheromone of this species. Host volatiles were recognized much more easily by SaveOBP2, and the observed binding activity of SaveOBP2 equaled for tested green leaf volatiles. Our results imply that SaveOBP7 might play a more important role in aphid alarm pheromone discrimination. [Copyright &y& Elsevier]

Background: Osteosarcoma is a primary malignant tumor originating from mesenchymal tissue, with a poor distant metastasis prognosis. The molecular mechanisms of osteosarcoma metastasis are extremely complicated.Methods: A public data series (GSE21257) was used to identify differentially expressed genes (DEGs) in osteosarcoma patients that did, or did not, develop metastases. Functional enrichment analysis, a protein-protein interaction network, and survival analysis of DEGs were performed. DEGs with a prognostic value were considered as candidate genes and their functional predictions, different expression in normal and malignant tissues, and immune infiltration were analyzed.Results: The DEGs were mainly enriched in the immune response. Three candidate genes (ALOX5AP, CD74, and FCGR2A) were found, all of which were expressed at higher levels in lungs and lymph nodes than in matched cancer tissues and were probably expressed in the microenvironment.Conclusions: Candidate genes can help us understand the molecular mechanisms underlying osteosarcoma metastasis and provide targets for future research. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel hetero-aromatic moieties substituted α-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure–activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004–113.6 μM). Moreover, compounds 6h (IC50 = 0.004 μM) and 6n (IC50 = 0.01 μM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t 1/2 = 1.45 h; compound 6n, F% = 16.8%, t 1/2 = 3.64 h). [Copyright &y& Elsevier]