Contribution of lncRNA CASC8, CASC11, and PVT1 Genetic Variants to the Susceptibility of Coronary Heart Disease.

ABSTRACT: The purpose of this study was to explore the relationship between lncRNA CASC8, CASC11, and plasmacytoma variant translocation 1 (PVT1). genetic variants and coronary heart disease (CHD) susceptibility among a Chinese Han population. Five single nucleotide polymorphisms were genotyped by Agena MassARRAY platform among 464 CHD patients and 510 healthy controls. Binary logistic regression models by calculating odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between selected single nucleotide polymorphisms and CHD risk. Multifactor dimensionality reduction analysis was performed to analyze gene-gene interaction. PVT1 rs4410871 (OR = 0.77, P = 0.040) was associated with a reduced risk of CHD occurrence in the Chinese population. CASC11 rs9642880 (OR = 1.49, P = 0.021) was a risk factor for increased CHD susceptibility in subjects over 60 years old, and PVT1 rs4410871 was a protective factor for CHD susceptibility in males (OR = 0.67, P = 0.015) and smokers (OR = 0.62, P = 0.047). Complications (hypertension or diabetes) of CHD influenced the association between CASC8, CASC11, and PVT1 genetic polymorphisms and CHD predisposition. Moreover, CASC8, CASC11, and PVT1 polymorphisms were related to the number of pathological branches and Gensini score in CHD patients. The study displayed the contribution of CASC8, CASC11, and PVT1 genetic polymorphisms to CHD predisposition, and these variants could serve as potential biomarkers of CHD susceptibility. These findings contribute to enhancing the understanding of the role of lncRNA polymorphisms in CHD risk.

Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.

A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.

Harmonization study between three laboratories for expression of malaria vaccine clinical trial IgG antibody ELISA data in µg/mL.

BACKGROUND: The ability to report vaccine-induced IgG responses in terms of µg/mL, as opposed arbitrary units (AU), enables a more informed interpretation of the magnitude of the immune response, and better comparison between vaccines targeting different antigens. However, these interpretations rely on the accuracy of the methodology, which is used to generate ELISA data in µg/mL. In a previous clinical trial of a vaccine targeting the apical membrane antigen 1 (AMA1) from Plasmodium falciparum, three laboratories (Oxford, NIH and WRAIR) reported ELISA data in µg/mL that were correlated but not concordant. This current study sought to harmonize the methodology used to generate a conversion factor (CF) for ELISA analysis of human anti-AMA1 IgG responses across the three laboratories. METHODS: Purified IgG was distributed to the three laboratories and, following a set protocol provided by NIH, AMA1-specific human IgG was affinity purified. A new "harmonized CF" was generated by each laboratory using their in-house ELISA, and the original clinical trial ELISA data were re-analysed accordingly. RESULTS: Statistical analysis showed that the data remained highly correlated across all three laboratories, although only Oxford and NIH were able to harmonize their CF for ELISA and generate concordant data. CONCLUSIONS: This study enabled two out of the three laboratories to harmonize their µg/mL readouts for the human anti-AMA1 IgG ELISA, but results reported from WRAIR are ~ twofold higher. Given the need to validate such information for each species and antigen of interest, it is important to bear in mind these likely differences when interpreting µg/mL ELISA data in the future.

IgE testing can predict food allergy status in patients with moderate to severe atopic dermatitis.

BACKGROUND: Diagnosing food allergy in patients with atopic dermatitis (AD) is complicated by their high rate of asymptomatic sensitization to foods, which can lead to misdiagnosis and unnecessary food avoidance. OBJECTIVE: We sought to determine whether food-specific (sIgE) or component immunoglobulin (Ig) E levels could predict allergic status in patients with moderate to severe AD and elevated total IgE. METHODS: Seventy-eight children (median age, 10.7 years) with moderate to severe AD were assessed for a history of clinical reactivity to milk, egg, peanut, wheat, and soy. The IgE levels for each food and its components were determined by ImmunoCAP. The level and pattern of IgE reactivity to each food and its components, and their ratio to total IgE, were compared between subjects who were allergic and tolerant to each food. RESULTS: Ninety-one percent of subjects were sensitized, and 51% reported allergic reactivity to at least 1 of the 5 most common food allergens. Allergy to milk, egg, and peanut were most common, and IgE levels to each of these foods were significantly higher in the allergic group. Component IgEs most associated with milk, egg, and peanut allergy were Bos d8, Gal d1, and Ara h2, respectively. The ratio of sIgE to total IgE offered no advantage to sIgE alone in predicting allergy. CONCLUSION: Specific IgE levels and the pattern of IgE reactivity to food components can distinguish AD subjects allergic vs tolerant to the major food allergens and may therefore be helpful in guiding the clinical management of these patients.

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy.

BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected. OBJECTIVE: We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. METHODS: Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4+ regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. RESULTS: Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. CONCLUSIONS: Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab.

GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity.

Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); and Emberger syndrome (primary lymphedema with MDS). A comprehensive examination of the clinical features of GATA2 deficiency is currently lacking. We reviewed the medical records of 57 patients with GATA2 deficiency evaluated at the National Institutes of Health from January 1, 1992, to March 1, 2013, and categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, pulmonary arterial hypertension 9%), dermatologic (warts 53%, panniculitis 30%), neoplastic (human papillomavirus+ tumors 35%, Epstein-Barr virus+ tumors 4%), vascular/lymphatic (venous thrombosis 25%, lymphedema 11%), sensorineural hearing loss 76%, miscarriage 33%, and hypothyroidism 14%. Viral infections and lymphedema were more common in individuals with null mutations (P = .038 and P = .006, respectively). Monocytopenia, B, NK, and CD4 lymphocytopenia correlated with the presence of disease (P < .001). GATA2 deficiency unites susceptibility to MDS/AML, immunodeficiency, pulmonary disease, and vascular/lymphatic dysfunction. Early genetic diagnosis is critical to direct clinical management, preventive care, and family screening.

Bone density and fractures in autosomal dominant hyper IgE syndrome.

PURPOSE: Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover. METHODS: Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately. RESULTS: Twenty-three AD-HIES children (6-18 years) and 33 AD-HIES adults (21-50 years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61%) had histories of minimal trauma fractures, as did 26 of the 33 adults (79%). Osteopenia or osteoporosis was found in 79% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures. CONCLUSIONS: Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.

Effects of exposure to high glucose on primary cultured hippocampal neurons: involvement of intracellular ROS accumulation.

Recent studies showed that hyperglycemia is the main trigger of diabetic cognitive impairment and can cause hippocampus abnormalities. The goal of this study is to explore the effects of different concentrations of high glucose for different exposure time on cell viability as well as intracellular reactive oxygen species (ROS) generation of primary cultured hippocampal neurons. Hippocampal neurons were exposed to different concentrations of high glucose (50, 75, 100, 125, and 150 mM) for 24, 48, 72 and 96 h. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. Intracellular ROS were monitored using the fluorescent probe DCFH-DA. The results showed that, compared with control group, the cell viability of all high glucose-treated groups decreased significantly after 72 h and there also was a significant increase of apoptotic nuclei in high glucose-treated groups from 72 to 96 h. Furthermore, 50 mM glucose induced a peak rise in ROS generation at 24 h and the intracellular ROS levels of 50 mM glucose group were significantly higher than the corresponding control group from 6 to 72 h. These results suggest that hippocampal neurons could be injured by high glucose exposure and the neuronal injury induced by high glucose is potentially mediated through intracellular ROS accumulation.

[Effect of ginsenoside Rb1 on insulin signal transduction pathway in hippocampal neurons of high-glucose-fed rats].

OBJECTIVE: To study the effect of ginsenoside Rb1 on GSKbeta/IDE signal transduction pathway and Abeta protein secretion in hippocampal neurons of high glucose-treated rats. METHOD: Hippocampal neurons of 24 h-old newly born SD rats were primarily cultured, inoculated in culture medium under different conditions, and then divided into the normal group, the high glucose group, the LiCl group and the Rb1 group. After being cultured for 72 h, the expressions of their phosphorylated GSK3beta, total GSK3beta and IDE protein were detected by Western blotting analysis. The mRNA expressions of GSK3beta and IDE were determined by RT-PCR. The ELISA assay was used to detect the secretion of Abeta protein in cell supernatant. RESULT: Compared with the normal group, the high glucose group showed increase in the p/tGSK3beta protein ratio and the secretion of Abeta protein and decrease in IDE protein and mRNA (P < 0.05). Compared with the high glucose group, both Rb1 and LiCl groups showed decrease in the p/tGSK3beta protein ratio and the expression of Abeta protein and increase in IDE protein and mRNA expression (P < 0.05). Compared with the LiCl group, the Rb1 group showed no significant difference in the expressions of p/tGSK3beta protein, IDE protein, mRNA and Abeta protein expression. In addition, the GSK3beta mRNA expression of the four groups had no significant difference. CONCLUSION: Ginsenoside Rb1 may reduce the secretion of Abeta protein in hippocampal neurons by reducing the phosphorylation of GSK3beta, down-regulating the ratio of pGSK3beta/GSK3beta and upregulating the expression of IDE.

Super-Resolution Reconstruction of CT Images Based on Multi-scale Information Fused Generative Adversarial Networks.

The popularization and widespread use of computed tomography (CT) in the field of medicine evocated public attention to the potential radiation exposure endured by patients. Reducing the radiation dose may lead to scattering noise and low resolution, which can adversely affect the radiologists' judgment. Hence, this paper introduces a new network called PANet-UP-ESRGAN (PAUP-ESRGAN), specifically designed to obtain low-dose CT (LDCT) images with high peak signal-to-noise ratio (PSNR) and high resolution (HR). The model was trained on synthetic medical image data based on a Generative Adversarial Network (GAN). A degradation modeling process was introduced to accurately represent realistic degradation complexities. To reconstruct image edge textures, a pyramidal attention model call PANet was added before the middle of the multiple residual dense blocks (MRDB) in the generator to focus on high-frequency image information. The U-Net discriminator with spectral normalization was also designed to improve its efficiency and stabilize the training dynamics. The proposed PAUP-ESRGAN model was evaluated on the abdomen and lung image datasets, which demonstrated a significant improvement in terms of robustness of model and LDCT image detail reconstruction, compared to the latest real-esrgan network. Results showed that the mean PSNR increated by 19.1%, 25.05%, and 21.25%, the mean SSIM increated by 0.4%, 0.4%, and 0.4%, and the mean NRMSE decreated by 0.25%, 0.25%, and 0.35% at 2[Formula: see text], 4[Formula: see text], and 8[Formula: see text] super-resolution scales, respectively. Experimental results demonstrate that our method outperforms the state-of-the-art super-resolution methods on restoring CT images with respect to peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and normalized root-mean-square error (NRMSE) indices.

Cyclin-dependent kinase 5 as a potential therapeutic target to alleviate high glucose-induced podocyte apoptosis and hyperglycemia-induced renal injury in mice.

BACKGROUND: Hyperglycemia is a risk factor for impaired renal function, including cellular metabolic disturbance, apoptosis, inflammation, and histologic lesion. This study aims to investigate the potential therapeutic targeting of cyclin-dependent kinase 5 (Cdk5) in hyperglycemia-induced podocyte dysfunction and renal damage. METHODS: Cell viability and apoptosis of podocytes were assessed through CCK-8 and TUNEL staining, respectively, following exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with Cdk5 inhibitors (trans-resveratrol, myricetin, salvianolic acid A, and BML-259). Diabetic mice were established by intraperitoneal injection of freshly streptozotocin (STZ), which was given at a dose of 35 mg/kg in five successive injections. Additionally, histochemical staining was employed to evaluate the morphologic lesion of the kidney. RESULTS: Cdk5 was found to be activated by HG stimulation both in vitro and in vivo. Notably, the inhibition of Cdk5 effectively mitigated the podocyte dysfunction induced by HG, including growth inhibition, membrane damage, and apoptosis. The compounds Trans-resveratrol, myricetin, salvianolic acid A, and BML-259 exhibited low binding energy values of -8.032 kcal/mol, -8.693 kcal/mol, -8.743 kcal/mol, and -10.952 kcal/mol, respectively, indicating strong and stable binding affinity between these candidates and Cdk5. The results of in vivo experimental analysis demonstrate that Cdk5 inhibitors, namely trans-resveratrol, myricetin, salvianolic acid A, and BML-259, confer protection against tubular and glomerular lesions induced by hyperglycemia. CONCLUSION: Both myricetin and BML-259 exhibit comparable protective effects on renal injury by inhibiting Cdk5.

Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

An audit strategy for time-to-event outcomes measured with error: application to five randomized controlled trials in oncology.

BACKGROUND: Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern. Blinded-independent central review (BICR) of all images from a trial is commonly undertaken to mitigate differential measurement-error bias that may be present in hazard ratios (HRs) based on local evaluations. Similar BICR and local evaluation HRs may provide reassurance about the treatment effect, but BICR adds considerable time and expense to trials. METHODS: We describe a BICR audit strategy [2] and apply it to five randomized controlled trials to evaluate its use and to provide practical guidelines. The strategy requires BICR on a subset of study subjects, rather than a complete-case BICR, and makes use of an auxiliary-variable estimator. RESULTS: When the effect size is relatively large, the method provides a substantial reduction in the size of the BICRs. In a trial with 722 participants and a HR of 0.48, an average audit of 28% of the data was needed and always confirmed the treatment effect as assessed by local evaluations. More moderate effect sizes and/or smaller trial sizes required larger proportions of audited images, ranging from 57% to 100% for HRs ranging from 0.55 to 0.77 and sample sizes between 209 and 737. LIMITATIONS: The method is developed for a simple random sample of study subjects. In studies with low event rates, more efficient estimation may result from sampling individuals with events at a higher rate. CONCLUSION: The proposed strategy can greatly decrease the costs and time associated with BICR, by reducing the number of images undergoing review. The savings will depend on the underlying treatment effect and trial size, with larger treatment effects and larger trials requiring smaller proportions of audited data.

Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial.

IMPORTANCE: The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations. OBJECTIVE: To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics. DESIGN, SETTING, AND PATIENTS: Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012). INTERVENTIONS: In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]). RESULTS: In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events. CONCLUSION AND RELEVANCE: In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01441180.

Urban scene segmentation model based on multi-scale shuffle features.

The monitoring of urban land categories is crucial for effective land resource management and urban planning. To address challenges such as uneven parcel distribution, difficulty in feature extraction and loss of image information in urban remote sensing images, this study proposes a multi-scale feature shuffle urban scene segmentation model. The model utilizes a deep convolutional encoder-decoder network with BlurPool instead of MaxPool to compensate for missing translation invariance. GSSConv and SE module are introduced to enhance information interaction and filter redundant information, minimizing category misclassification caused by similar feature distributions. To address unclear boundary information during feature extraction, the model applies multi-scale attention to aggregate context information for better integration of boundary and global information. Experiments conducted on the BDCI2017 public dataset show that the proposed model outperforms several established segmentation networks in OA, mIoU, mRecall, P and Dice with scores of 83.1%, 71.0%, 82.7%, 82.7% and 82.5%, respectively. By effectively improving the completeness and accuracy of urban scene segmentation, this study provides a better understanding of urban development and offers suggestions for future planning.

A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial.

BACKGROUND: West Nile virus (WNV) is a flavivirus that causes meningitis and encephalitis. There are no licensed vaccines to prevent WNV in humans. The safety and immunogenicity of a first-generation WNV DNA vaccine was demonstrated in a clinical trial and a similar DNA vaccine has been licensed for use in horses. METHODS: A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot. RESULTS: The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort. CONCLUSIONS: Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter. CLINICAL TRIALS REGISTRATION: NCT00300417.

[Effect of liver X receptor agonist T0901317 on endothelin-1 induced murine HL-1 cardiomyocytes hypertrophy].

OBJECTIVE: To investigate the role of liver X receptors (LXRs) on endothelin-1 (ET-1) induced murine HL-1 cardiomyocytes hypertrophy. METHODS: Cultured murine HL-1 cardiomyocytes were divided into four experiment groups: (1) CONTROL GROUP:treated with DMSO; (2) T0901317 group:treated with LXRs agonist T0901317 (1 µmol/L); (3) ET-1 group:treated with ET-1 (1 nmol/L); (4) T0901317 + ET-1 group:treated with T0901317 (1 µmol/L) for 8 hours, then treated with ET-1 (1 nmol/L). Twenty-four hours later, immunofluorescent staining was performed on HL-1 cells, the surface area of HL-1 cells was analyzed with NIH Image J software, and the synthetic rate of protein in HL-1 cells was detected by (3)H-leucine incorporation. The mRNA level of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (ß-MyHC) was measured by quantitative realtime PCR. The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing. RESULTS: The surface area of HL-1 cells, mRNA expression of ANP and ß-MyHC, and (3)H-leucine incorporation in ET-1 group were 2.00 ± 0.29, 1.98 ± 0.47, 2.13 ± 0.39 and 1.79 ± 0.17, respectively, which were significantly higher than those of control group (1.00 ± 0.26, 1.00 ± 0.21, 1.00 ± 0.31 and 1.00 ± 0.03, respectively, all P < 0.05). Compared with ET-1 group, the surface area of HL-1 cells, mRNA expression of ANP and ß-MyHC, and (3)H-leucine incorporation were significantly decreased in T0901317 + ET-1 group (1.24 ± 0.25, 1.19 ± 0.21, 1.48 ± 0.27 and 1.15 ± 0.11, respectively, all P < 0.05). After inhibition of LXRα/ß expression in HL-1 cardiomyocytes using the specific siRNAs, the mRNA expression of ANP in T0901317 + ET-1 group was 1.78 ± 0.05, which was similar as that in ET-1 group (1.94 ± 0.17, P > 0.05). CONCLUSION: T0901317, an agonist of LXRs, could inhibit ET-1 induced cardiac hypertrophy in vitro, and LXR ligand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.

Plant leaf veins coupling feature representation and measurement method based on DeepLabV3.

The plant leaf veins coupling feature representation and measurement method based on DeepLabV3+ is proposed to solve problems of slow segmentation, partial occlusion of leaf veins, and low measurement accuracy of leaf veins parameters. Firstly, to solve the problem of slow segmentation, the lightweight MobileNetV2 is selected as the extraction network for DeepLabV3+. On this basis, the Convex Hull-Scan method is applied to repair leaf veins. Subsequently, a refinement algorithm, Floodfill MorphologyEx Medianblur Morphological Skeleton (F-3MS), is proposed, reducing the burr phenomenon of leaf veins' skeleton lines. Finally, leaf veins' related parameters are measured. In this study, mean intersection over union (MIoU) and mean pixel accuracy (mPA) reach 81.50% and 92.89%, respectively, and the average segmentation speed reaches 9.81 frames per second. Furthermore, the network model parameters are compressed by 89.375%, down to 5.813M. Meanwhile, leaf veins' length and width are measured, yielding an accuracy of 96.3642% and 96.1358%, respectively.

Paucity of genotype-phenotype correlations in STAT3 mutation positive Hyper IgE Syndrome (HIES).

Autosomal dominant HIES (AD-HIES) is a primary immunodeficiency caused by dominant negative mutations in STAT3 clustered in the DNA binding and SH2 domains. Although in vitro differences in mutational constructs are observed, clinical phenotypic correlates of these genetic changes have not been described. We reviewed the charts of 65 AD-HIES patients (DNA binding n=35; SH2 n=30), recorded the components of the NIH HIES clinical scoring system as well as brain and coronary artery abnormalities and analyzed data by mutation region in adults and children. Patients with SH2 domain mutations had increased frequency of high palate, broad inter-alar distance, upper respiratory tract infections and, in the pediatric sub-group, significant scoliosis. There was suggestion of increased mortality for patients with DNA binding mutations. Although subtle differences in phenotype were observed to depend on the STAT3 genotype, overall the clinical phenotypes were similar between individuals with DNA binding and SH2 domain mutations.