Alzheimer's disease early screening and staged detection with plasma proteome using machine learning and convolutional neural network.

Alzheimer's disease (AD) stands as the prevalent progressive neurodegenerative disease, precipitating cognitive impairment and even memory loss. Amyloid biomarkers have been extensively used in the diagnosis of AD. However, amyloid proteins offer limited information about the disease process and accurate diagnosis depends on the presence of a substantial accumulation of amyloid deposition which significantly impedes the early screening of AD. In this study, we have combined plasma proteomics with an ensemble learning model (CatBoost) to develop a cost-effective and non-invasive diagnostic method for AD. A longitudinal panel has been identified that can serve as reliable biomarkers across the entire progression of AD. Simultaneously, we have developed a neural network algorithm that utilizes plasma proteins to detect stages of Alzheimer's disease. Based on the developed longitudinal panel, the CatBoost model achieved an area under the operating curve of at least 0.90 in distinguishing mild cognitive impairment from cognitively normal. The neural network model was utilized for the detection of three stages of AD, and the results demonstrated that the neural network model exhibited an accuracy as high as 0.83, surpassing that of the traditional machine learning model.

The Value of Contrast-Enhanced Ultrasound in the Detection of Sentinel Lymph Nodes in Malignant Melanoma.

OBJECTIVE: To evaluate the location and characterization value of contrast-enhanced ultrasound (CEUS) in the detection of sentinel lymph nodes (SLNs) in malignant melanoma. METHODS: SLNs and the lymph node network were tracked by subcutaneous injection of ultrasonic contrast agent around the tumor and preoperative localization, and qualitative analyses were performed. The SLNs were also detected by the intraoperative subcutaneous injection of carbon nanoparticles, and the findings were compared with lymph nodes located by CEUS. The accuracy of the preoperative lymph node identification was evaluated by the results of postoperative pathology, which served as the gold standard of detection. RESULTS: In 47 patients with malignant melanoma, the mean number of SLNs detected by CEUS was 1.72 ± 0.10, while that by carbon nanoparticle administration it was 1.79 ± 1.07 (P = .371 > .05). Seven cases of lymph node metastasis were detected by CEUS, with a sensitivity of 70.0%, specificity of 97.3%, positive predictive value of 87.5%, negative predictive value of 92.3%, and accuracy of 91.5%. There was high consistency between the findings of CEUS and pathology in differentiating benign and malignant lymph nodes (kappa = 0.726, χ2  = 25.243, P < .001). CONCLUSIONS: CEUS can localize and differentiate SLNs in malignant melanoma, and thus, may potentially guide clinical treatment in the future.

Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway.

Persistent chronic inflammation of the lungs and airway remodeling are important pathological features that cannot be ignored in patients with chronic asthma. Apigenin (API) is a natural small molecule compound with good anti-inflammatory and antioxidant activity that has been widely reported in recent years, but its role in chronic asthma is not well defined. Our study began with oral gavage intervention using API (10, 20 mg/kg) or dexamethasone (DEX, 2 mg/kg) in a BALB/c mouse model of ovalbumin (OVA) sensitization. Different doses of API intervention effectively reduced airway resistance in the administered group. Additionally, inflammation was downregulated, mucus secretion was reduced, and airway remodeling was inhibited in the API intervention group compared with the model group. Asthma-related inflammatory cytokines, such as IgE, IL-4, IL-5, IL-13, and IL-17, were downregulated in alveolar lavage fluid. Moreover, the apoptosis level of the administered group was found to be lower than that of the model group in the Tunel staining experiment. By analyzing transcriptome sequencing results, we found that API may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK pathway. Our subsequent results supported this conclusion, showing that the phosphorylation levels of ERKs, JNKs, and p38 MAPKs were inhibited in the administered group relative to the model group. Downstream expression of the apoptosis-related protein B-cell lymphoma-2 (Bcl-2) was upregulated, and the expression of Bcl-2-associated × protein (Bax) and cleaved caspase-3 was downregulated. To further investigate the specific mechanism by which API acted, we established an in vitro model with house dust mite (HDM) stimulation, using API (10, 20 µM) for administration intervention. The results showed that API was able to improve cell viability, inhibit ROS production, and reverse HDM-induced decreases in mitochondrial membrane potential (MMP) and apoptosis in airway epithelial cells via the MAPK pathway.

Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with polycystic ovary syndrome: a cross-sectional study.

PURPOSE: Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic ß cell function index (HOMA-ß) among women with PCOS. METHODS: Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-ß were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-ß) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed with the quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables. RESULTS: BMI was positively associated with ln (HOMA-IR) and ln (HOMA-ß) (ß = 0.090, p < 0.001; ß = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-ß) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-ß, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-ß. CONCLUSION: Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-ß among women with PCOS.

Comparison of the saccules and lagenae in six macrourid fishes from different deep-sea habitatsa).

There are substantial interspecific differences in the morphology of the ears of the more than 34 000 living fish species. However, almost nothing is known about the functional significance of these differences. One reason is that most comparative studies have been conducted on shallow-water species with far less focus on the numerous species that inhabit the depths of the oceans. Thus, to get a better sense of ear diversity in fishes and its potential role in hearing, this study focuses on the saccule and lagena, the primary auditory end organs, in six species of the family Macrouridae (rattails), a large group of fishes that typically inhabit depths from 1000 to 4000 m. The inner ears and, particularly, the saccules and lagenae in these species are large with the saccule resembling that of other Gadiformes. The lagenae of all macrourids studied here have serrated edge otoliths and highly diverse hair cell ciliary bundle shapes. The differences found in the inner ear anatomy of macrourids likely reflect the sensory advantages in different habitats that are related to the benefits and constraints at different depths, the fish's particular lifestyle, and the trade-off among different sensory systems.

Delegated Proof of Stake Consensus Mechanism Based on Community Discovery and Credit Incentive.

Consensus algorithms are the core technology of a blockchain and directly affect the implementation and application of blockchain systems. Delegated proof of stake (DPoS) significantly reduces the time required for transaction verification by selecting representative nodes to generate blocks, and it has become a mainstream consensus algorithm. However, existing DPoS algorithms have issues such as "one ballot, one vote", a low degree of decentralization, and nodes performing malicious actions. To address these problems, an improved DPoS algorithm based on community discovery is designed, called CD-DPoS. First, we introduce the PageRank algorithm to improve the voting mechanism, achieving "one ballot, multiple votes", and we obtain the reputation value of each node. Second, we propose a node voting enthusiasm measurement method based on the GN algorithm. Finally, we design a comprehensive election mechanism combining node reputation values and voting enthusiasm to select secure and reliable accounting nodes. A node credit incentive mechanism is also designed to effectively motivate normal nodes and drive out malicious nodes. The experimental simulation results show that our proposed algorithm has better decentralization, malicious node eviction capabilities and higher throughput than similar methods.

Angiotensin Receptor Blockers vs. Beta-Blocker Therapy for Marfan Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVE: Several RCTs have been conducted to assess the efficacy and safety of angiotensin receptor blocker (ARB) and beta-blocker (BB) therapy for Marfan syndrome (MFS), but the existing evidence is limited and conflicting. This study aimed to compare the efficacy and safety of different therapies. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were electronically searched up to March 2021 to retrieve randomized controlled trials regarding the efficacy and safety of ARB-related (including ARB-only and ARB+BB treatment) and BB-only treatment for treating patients with MFS. The revised risk-of-bias tool was used for quality assessment. The odds ratio (OR) and standard mean difference (SMD) with 95% confidence interval (CI) were used to estimate the pooled effect size. RESULTS: Fourteen reports of 9 trials involving 1,449 patients were included in the meta-analysis. Regarding aortic root dilation, the ARB-related regimen has efficacy comparable with that of the BB-only regimen in patients with MFS (pooled SMD = -0.16, 95% CI [-0.33; 0.01]; P = 0.06), while in the ARB+BB vs. BB-only subgroup, a significant difference was observed (pooled SMD = -0.26; 95% CI [-0.40; -0.11]; P < 0.01). In addition, there were no significant differences in other aortic dilation-related measures (aortic root Z scores, ascending aorta, pulmonary artery, aortic annulus, sinotubular junction, aortic arch, thoracic aorta, and abdominal aorta diameter change) or cardiovascular events (aortic dissection, aortic surgery, and death) between the 2 regimens. CONCLUSION: Our results showed that the clinical efficacy of ARB-only therapy is not inferior to that of BB-only therapy. Moreover, ARB+BB therapy showed superior therapeutic effects without significant adverse effects.

A new strategy for quality evaluation and control of Chinese patent medicine based on chiral isomer ratio analysis: With Yuanhuzhitong tablet as an example.

Chiral compounds commonly exist in traditional Chinese medicine (TCM), but little research on the quality control of TCM has been conducted. In this study, a new strategy is proposed, taking Yuanhuzhitong tablet [YHZT, consisting of Radix Angelicae Dahuricae and Rhizoma Corydalis (Yan Hu Suo, YHS)] for example, which is based on chiral isomer ratio analysis to monitor the production process of Chinese patent medicine companies. In the process of content determination for tetrahydropalmatine (THP) in YHZT from different companies, noticeable differences were observed in their chromatographic behaviors. It is known that THP has two enantiomers, naturally coexisting in YHS as a racemic mixture, so we prepared THP twice and subsequently performed chiral separation analysis using supercritical fluid chromatography. As a result, the peak area ratios of two enantiomers from different companies varied remarkably, demonstrating that some companies did not probably manufacture YHZT products in accordance with the prescription proportion, used inferior or extracted YSH crude materials in the production process, and added raw chemical medicine in the production to reach the standard and lower the costs. In conclusion, the peak area ratio of chiral isomers could be taken as a key quality index.

Preimplantation genetic diagnosis for a carrier with m.3697G > A mitochondrial DNA mutation.

OBJECTIVE: To explore inheritance of the m.3697G > A mitochondrial DNA (mtDNA) mutation and the effectiveness of preimplantation genetic diagnosis (PGD) for the carrier. METHODS: The study encompassed a pedigree of m.3697G > A mtDNA mutation, including one asymptomatic patient who pursued for PGD treatment. Twelve cumulus oocyte complexes (COCs) were collected in the first PGD cycle and 11 COCs in the second cycle. The efficiency of cumulus cells, polar bodies, and trophectoderm (TE) in predicting the m.3697G > A heteroplasmy of embryos was analyzed. RESULTS: From 23 COCs, 20 oocytes were fertilized successfully. On day 5 and 6 post-fertilization, 15 blastocysts were biopsied. The m.3697G > A mutation load of TE biopsies ranged from 15.2 to 100%. In the first cycle, a blastocyst with mutation load of 31.7% and chromosomal mosaicism was transferred, but failed to yield a clinical pregnancy. In the second cycle, a euploid blastocyst with mutation load of 53.9% was transferred, which gave rise to a clinical pregnancy. However, the pregnancy was terminated due to fetal cleft lip and palate. The mutation loads of different tissues (47.7 ± 1.8%) from the induced fetus were comparable to that of the biopsied TE and amniotic fluid cell (49.7%). The mutation load of neither cumulus cells (R2 = 0.02, p = 0.58) nor polar bodies (R2 = 0.33, p = 0.13) correlated with TE mutation load which was regarded as a gold standard. CONCLUSIONS: The m.3697G > A mutation showed a random pattern of inheritance. PGD could be used to reduce the risk of inheritance of a high mutation load. Cumulus cells are not a suitable predictor of blastocyst mutation load.

Association between mitochondrial DNA D-loop region polymorphisms and endometriosis in a Chinese population.

OBJECTIVE: To investigate the correlation between endometriosis and mitochondrial DNA (mtDNA) D-loop single nucleotide polymorphisms (SNPs) and haplotype, as well as the predictive power of certain SNPs in reproductive outcomes in a Chinese Han population. METHODS: A case-control study was conducted in which 125 endometriosis patients and 124 controls were recruited from an academic fertility center. The entire 1124-bp D-loop region of mtDNA of whole blood samples from all subjects was amplified, sequenced, and compared with the revised Cambridge Reference Sequence (rCRS) to identify SNPs and haplotypes. The association between D-loop SNPs and embryo quality and clinical outcome following in vitro fertilization (IVF) was also assessed. RESULTS: A total of 321 polymorphisms were identified by sequencing, allowing comparison of the D-loop between endometriosis patients and controls. The frequency of the AC523-524 del, T16172C, and C16290T variants were significantly higher, while the frequency of polymorphisms T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins were lower, in the endometriosis group compared with the control group (p < 0.05). Within the endometriosis group, the high-quality blastocyst rate in the 16,290T subgroup was significantly lower than that in the 16290C subgroup (p < 0.05). In the control group, 16519C carriers showed a lower rate of high-quality blastocyst development compared with 16519T (p < 0.05). In endometriosis patients clinical pregnancy rate was significantly lower in the 150T subgroup compared with the 150C subgroup (p < 0.05). DISCUSSION: Data confirms a correlation between D-loop polymorphisms and endometriosis. The polymorphisms AC523-524 del, T16172C, and C16290T are associated with increased risk of endometriosis, while T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins are associated with decreased risk of endometriosis. In addition, C16290T and T16519C can be associated with poor quality blastocyst development in population with and without endometriosis, respectively and C150T can be a predictor of poor IVF outcome.

Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses.

BACKGROUND: Amlexanox (ALX), a TBK1 inhibitor, can modulate immune responses and has anti-inflammatory properties. To investigate its role in regulating the progression of experimental autoimmune encephalomyelitis (EAE), we studied the effect of ALX on the maturation of dendritic cells (DCs) and the responses of effector and regulatory T cells (Tregs). METHODS: In vitro, bone marrow-derived DCs (BMDCs) were cultured and treated with ALX. Their proliferation, maturation, and their stimulatory function to induce T cells responses were detected. In vivo, the development of EAE from different groups was recorded. At the peak stage of disease, HE, LFB, and electronic microscope (EM) were used to evaluate inflammation and demyelination. Maturation of splenic DC and Th1/Th17/Treg response in the CNS and peripheral were also detected. To further explore the mechanism underlying the action of ALX in DC maturation, the activation of TBK1, IRF3, and AKT was analyzed. RESULTS: Our data indicated that ALX significantly inhibited the proliferation and maturation of BMDCs, characterized by the reduced MHCII, a co-stimulatory molecule, IL12, and IL-23 expression, along with morphological alterations. Co-culture of ALX-treated BMDCs inhibited allogeneic T cell proliferation and MOG-specific T cell response. In EAE mice, ALX significantly attenuated the EAE development by decreasing inflammatory infiltration and demyelination in the spinal cords, accompanied by reduced frequency of splenic pathogenic Th1 and Th17 cells and increased Tregs. Moreover, ALX treatment decreased Th1 and Th17 cytokines, but increased Treg cytokines in the CNS and spleen. Notably, ALX treatment reduced the frequency and expression of CD80 and CD86 on splenic DCs and lowered IL-12 and IL-23 secretion, further supporting an impaired maturation of splenic DCs. In addition, ALX potently reduced the phosphorylation of IRF3 and AKT in BMDC and splenic DCs, both of which are substrates of TBK1 and associated with DC maturation. CONCLUSIONS: ALX, a TBK1 inhibitor, mitigated EAE development by inhibiting DC maturation and subsequent pathogenic Th1 and Th17 responses while increasing Treg responses through attenuating the TBK1/AKT and TBK1/IRF3 signaling.

Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade.

The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 µM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 µM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.

[Effects of light intensity on growth and content of active components of Uncaria rhynchophyll].

The aim of this study was to study the effects of different light intensity on the growth,biomass accumulation and distribution,chlorophyll content and effective components of Uncaria rhynchophylla seedlings,and explore the suitable light intensity conditions for artificial cultivation of U. rhynchophylla seedlings. Three-year-old U. rhynchophylla seedlings were used as experimental materials. Four light intensity levels( 100%,70%-75%,30%-35%,5%-10%) were set up with different layers of black shading net. With the decrease of light intensity,the results showed that the plant height,basal diameter and biomass( root,stem,leaf and hook) of U.rhynchophylla seedlings exhibited the trend of " increase-decrease". Under 70%-75% light intensity,the plant height,basal diameter,biomass( root,stem,leaf,hook) of U. rhynchophylla seedlings were significantly higher than those of other treatments( P< 0. 05);under 5%-10% light intensity,the plant height,basal diameter and biomass( root,hook) of U. rhynchophylla seedlings were significantly lower than those of other treatments( P<0. 05). With the decrease of light intensity,the chlorophyll content of U. rhynchophylla seedlings increased gradually: under 100% light intensity,the chlorophyll content of U. rhynchophylla seedlings were the smallest,while under 100% light intensity,its chlorophyll content was the highest. With the decrease of light intensity,the contents of rhynchophylline and isorhynchophylline in different organs of U. rhynchophylla seedlings varied: under 30%-35% light intensity,the contents of rhynchophylline and isorhynchophylline in hooks and rhynchophylline content in stems were the highest; under 5%-10% light intensity,the contents of rhynchophylline and isorhynchophylline in leaves and stems of U. rhynchophylla were the highest. In conclusion,70%-75% light intensity is suitable for seedling growth and biomass accumulation,and 30%-35% light intensity is suitable for the accumulation of effective components in U. rhynchophylla seedlings.

Let-7e inhibits TNF-α expression by targeting the methyl transferase EZH2 in DENV2-infected THP-1 cells.

Tumor necrosis factor α (TNFα), an important inflammatory cytokine, is associated with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), a severe pathological manifestation of dengue virus (DENV) infection. However, the regulatory mechanism of microRNA on TNFα is currently unknown. Our study showed that the TNFα expression increased immediately and then later decreased, while a marked increase for the miRNA let-7e was detected in dengue virus type 2 (DENV2)-infected peripheral blood mononuclear cells (PBMCs). From this study, we found that let-7e was able to inhibit TNFα expression, but bioinformatics analysis showed that the enhancer of zeste homolog 2 (EZH2) was the potential direct target of let-7e instead of TNFα. EZH2 methyl transferase can produce H3K27me3 and has a negative regulatory role. Using a dual-luciferase reporter assay and Western blotting, we confirmed that EZH2 was a direct target of let-7e and found that siEZH2 could inhibit TNFα expression. In the further study of the regulatory mechanism of EZH2 on TNFα expression, we showed that siEZH2 promoted EZH1 and H3K4me3 expression and inhibited H3K27me3 expression. More importantly, we revealed that siEZH2 down-regulated NF-κB p65 within the nucleus. These findings indicate that the let-7e/EZH2/H3K27me3/NF-κB p65 pathway is a novel regulatory axis of TNFα expression. In addition, we determined the protein differences between siEZH2 and siEZH2-NC by iTRAQ and found a number of proteins that might be associated with TNFα.

Temporal coupling between specifications of neuronal and macular fates of the inner ear.

The inner ear is a complex organ comprised of various specialized sensory organs for detecting sound and head movements. The timing of specification for these sensory organs, however, is not clear. Previous fate mapping results of the inner ear indicate that vestibular and auditory ganglia and two of the vestibular sensory organs, the utricular macula (UM) and saccular macula (SM), are lineage related. Based on the medial-lateral relationship where respective auditory and vestibular neuroblasts exit from the otic epithelium and the subsequent formation of the medial SM and lateral UM in these regions, we hypothesized that specification of the two lateral structures, the vestibular ganglion and the UM are coupled and likewise for the two medial structures, the auditory ganglion and the SM. We tested this hypothesis by surgically inverting the primary axes of the otic cup in ovo and investigating the fate of the vestibular neurogenic region, which had been spotted with a lipophilic dye. Our results showed that the laterally-positioned, dye-associated, vestibular ganglion and UM were largely normal in transplanted ears, whereas both auditory ganglion and SM showed abnormalities suggesting the lateral but not the medial-derived structures were mostly specified at the time of transplantation. Both of these results are consistent with a temporal coupling between neuronal and macular fate specifications.

Metaphorical mapping between raw-cooked food and strangeness-familiarity in Chinese culture.

Previous research has demonstrated metaphorical mappings between physical coldness-warmth and social distance-closeness. Since the concepts of interpersonal warmth are frequently expressed in terms of food-related words in Chinese, the present study sought to explore whether the concept of raw-cooked food could be unconsciously and automatically mapped onto strangeness-familiarity. After rating the nutritive value of raw or cooked foods, participants were presented with morphing movies in which their acquaintances gradually transformed into strangers or strangers gradually morphed into acquaintances, and were asked to stop the movies when the combined images became predominantly target faces. The results demonstrated that unconscious and automatic metaphorical mappings between raw-cooked food and strangeness-familiarity exist. This study provides a foundation for testing whether Chinese people can think about interpersonal familiarity using mental representations of raw-cooked food and supports cognitive metaphor theory from a crosslinguistic perspective.

A Classification Tool for Differentiation of Kawasaki Disease from Other Febrile Illnesses.

OBJECTIVE: To develop and validate a novel decision tree-based clinical algorithm to differentiate Kawasaki disease (KD) from other pediatric febrile illnesses that share common clinical characteristics. STUDY DESIGN: Using clinical and laboratory data from 801 subjects with acute KD (533 for development, and 268 for validation) and 479 febrile control subjects (318 for development, and 161 for validation), we developed a stepwise KD diagnostic algorithm combining our previously developed linear discriminant analysis (LDA)-based model with a newly developed tree-based algorithm. RESULTS: The primary model (LDA) stratified the 1280 subjects into febrile controls (n = 276), indeterminate (n = 247), and KD (n = 757) subgroups. The subsequent model (decision trees) further classified the indeterminate group into febrile controls (n = 103) and KD (n = 58) subgroups, leaving only 29 of 801 KD (3.6%) and 57 of 479 febrile control (11.9%) subjects indeterminate. The 2-step algorithm had a sensitivity of 96.0% and a specificity of 78.5%, and correctly classified all subjects with KD who later developed coronary artery aneurysms. CONCLUSION: The addition of a decision tree step increased sensitivity and specificity in the classification of subject with KD and febrile controls over our previously described LDA model. A multicenter trial is needed to prospectively determine its utility as a point of care diagnostic test for KD.

Cerebrospinal fluid protein dynamic driver network: At the crossroads of brain tumorigenesis.

To get a better understanding of the ongoing in situ environmental changes preceding the brain tumorigenesis, we assessed cerebrospinal fluid (CSF) proteome profile changes in a glioma rat model in which brain tumor invariably developed after a single in utero exposure to the neurocarcinogen ethylnitrosourea (ENU). Computationally, the CSF proteome profile dynamics during the tumorigenesis can be modeled as non-smooth or even abrupt state changes. Such brain tumor environment transition analysis, correlating the CSF composition changes with the development of early cellular hyperplasia, can reveal the pathogenesis process at network level during a time before the image detection of the tumors. In our controlled rat model study, matched ENU- and saline-exposed rats' CSF proteomics changes were quantified at approximately 30, 60, 90, 120, 150 days of age (P30, P60, P90, P120, P150). We applied our transition-based network entropy (TNE) method to compute the CSF proteome changes in the ENU rat model and test the hypothesis of the critical transition state prior to impending hyperplasia. Our analysis identified a dynamic driver network (DDN) of CSF proteins related with the emerging tumorigenesis progressing from the non-hyperplasia state. The DDN associated leading network CSF proteins can allow the early detection of such dynamics before the catastrophic shift to the clear clinical landmarks in gliomas. Future characterization of the critical transition state (P60) during the brain tumor progression may reveal the underlying pathophysiology to device novel therapeutics preventing tumor formation. More detailed method and information are accessible through our website at http://translationalmedicine.stanford.edu.

Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: a preliminary study of the correlations between quantitative parameters and clinical stage.

PURPOSE: To evaluate the relationship between quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical stage of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-one newly diagnosed NPC patients received MRI examination on Philips Achieva 3.0 Tesla TX MR system. We used DCE-Tool (Philips Healthcare, Best, The Netherlands) to investigate parameters from primary tumors. Tumor/node/metastasis and corresponding clinical stages were determined based on 2009 UICC 7th edition. The correlations between quantitative parameters and clinical stage were correlated using Pearson correlation analysis. RESULTS: Mean K(trans) , Kep , ve , and vp for primary tumors were 0.500 ± 0.188/min, 0.744 ± 0.273/min, 0.986 ± 0.595, and 0.052 ± 0.071, respectively. Both K(trans) and Kep of tumors showed moderate negative correlation with clinical stage, T stage and N stage (P < 0.05), while ve showed moderate positive correlation with them (P < 0.05). vp revealed a moderate negative correlation with T stage (r = -0.369; P < 0.004). Kep and ve have significant differences between many early and advanced stages patients. CONCLUSION: DCE-MRI is feasible to assess vascular permeability of NPC patients. Our results first revealed that the quantitative parameters were significantly related to clinical stage of NPC. Thus, DCE-MRI may be valuable to add noninvasive prognostic indicators in evaluating NPC.