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Abstract To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 years. Forty-one proteins were associated with obesity (FDR

The association among sugar sweetened beverages (SSB) consumption, addiction and depression in adults, children and adolescents is widely reported. Dieting patterns during pregnancy is complicated by maternal fetal concerns. Specifically, restrained use of SSB might be potentially a source of perinatal distress. The current study modified diagnostic criteria for Substance Use Disorder (SUD) in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into SSB-specific questions to assess SSB use tendency. Edinburgh Postpartum Depression Scores (EPDS) is used to assess maternal distress during pregnancy. One hundred and ninety-six consecutive pregnant women receiving antenatal care at Kaohsiung Medical University Hospital were invited to participate in this study. In the first trimester, 46.6% of women had none or 1 DSM-5 symptom, 27.0% had 2–3 symptoms, while 26.4% had ≥ 4 symptoms. The mean numbers of DSM-5 symptoms in each trimester were found to be 2.5 ± 2.25, 2.6 ± 2.45, 2.4 ± 2.43 for the first, second and third trimester, respectively, p = 0.750. While EPDS score showed no difference among DSM-5 symptoms 0–1, 2–3 and ≥ 4 groups in the first trimester (8.1 ± 4.59, 8.4 ± 5.00, 8.8 ± 4.82, p = 0.343), women with ≥ 4 DSM-symptoms was found significantly higher EPDS scores than those with < 4 DSM-symptoms in the second (7.2 ± 4.81, 7.7 ± 4.98, 8.8 ± 4.33, p = 0.030) and third trimester (6.8 ± 5.00, 7.2 ± 4.63, 8.7 ± 5.24, p = 0.019). The relationship remained significant after adjusting for covariates including actual SSB amount consumed (adjusted β = 0.25 with 95% confident interval (CI) 0.04–0.45 and 0.21 with 95% CI 0.04–0.38 for the second and third trimesters, respectively). Overall, the study is the first to characterize the positive relationship between SSB use tendency and antenatal distress in pregnancy, independent of actual SSB amount consumed. The observational nature of the study design precludes inferences of its underlying socio-psychomotor mechanisms, although restrained SSB use in pregnancy is suspected to contribute. The novel employment of modified SSB-specific DSM-5 scores and EPDS in this setting is feasible and further validation is promising. With better understanding and awareness, pregnant women with increased SSB use tendency should be properly counseled with special attention to their mental state. [ABSTRACT FROM AUTHOR]

Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli. These responses improved after MAC treatment. The PD-1 and PD ligand expressions and apoptosis were higher in the lymphocytes of the patients with MAC-LD compared to the controls. Both PD-1 and apoptosis on T lymphocytes were significantly increased in the patients with MAC-LD, either by direct MAC stimulation or by MAC-primed macrophage activation. Partially blocking PD-1 and the PD ligand with antagonizing antibodies in the stimulation assay significantly increased the cytokine production of IFN-γ and decreased the apoptosis on T lymphocytes. In conclusion, the patients with MAC-LD have attenuated lymphocyte immunity, which might be associated with increasing activation of PD-1 and PD-1 ligand. Regulating such activation might improve the lymphocytic secretion of IFN-γ and reduce apoptosis. [ABSTRACT FROM AUTHOR]

Abstract Autologous liver transplantation (ALT) to cure end-stage hepatic alveolar echinococcosis (HAE) requires that hepatobiliary surgeons understand the invasion of intrahepatic structure and adjacent tissues or organs. Triphase contrast-enhanced CT of the liver has been widely used for diagnosis and preoperative evaluation of HAE. Three-dimensional (3D) reconstruction allows for accurate measurement of remnant liver volume (RLV). The objective of the study was to evaluate value of triphase contrast-enhanced CT together with 3D reconstruction in preoperative evaluation of indications for ALT in patients with end-stage HAE. This cohort include twenty-one consecutive patients with end-stage HAE, who preoperatively underwent triphase enhanced CT together with 3D reconstruction for ALT. To depict the indications, the 2D image data were reviewed statistically focusing on porta hepatis invasion, retrohepatic vena cava (RHVC) involvement and degrees of intrahepatic vessel invasion, and the 3D reconstruction was performed to obtain ratio of RLV to standard liver volume (SLV). The results showed that 95.24% patients (20/21) had porta hepatis invasion. When lesions located in right liver lobe, porta hepatis invasion occurred most commonly in the second and third porta hepatis (7/10), whereas the first, second and third porta hepatis were most commonly invaded by lesions in the right and caudate / left medial liver lobes (7/11) (P

Abstract Expanding bile leaks after blunt liver trauma require more aggressive treatment than contained bile leaks. In this retrospective study approved by institution review board, we analyzed if non-invasive contrast-enhanced magnetic resonance cholangiography (CEMRC) using hepatocyte-specific contrast agent (gadoxetic acid disodium) could detect and characterize traumatic bile leaks. Between March 2012 and December 2014, written informed consents from 22 included patients (17 men, 5 women) with a median age of 24.5 years (IQR 21.8, 36.0 years) were obtained. Biliary tree visualization and bile leak detection on CEMRC acquired at 10, 20, 30, 90 minutes time points were independently graded by three radiologists on a 5-point Likert scale. Intraclass Correlation (ICC) was computed as estimates of interrater reliability. Accuracy was measured by area under receiver operating characteristic curves (AUROC). Biliary tree visualization was the best on CEMRC at 90 minutes (score 4.30) with excellent inter-rater reliability (ICC = 0.930). Of 22 CEMRC, 15 had bile leak (8 expanding, 7 contained). The largest AUROC of bile leak detection by three radiologists were 0.824, 0.914, 0.929 respectively on CEMRC at 90 minutes with ICC of 0.816. In conclusion, bile leaks of blunt liver trauma can be accurately detected and characterized on CEMRC.

Abstract In this study, four canine distemper virus (CDV) strains were isolated from captive Siberian tigers (Panthera tigris altaica) and red pandas (Ailurus fulgens) during two separate CDV outbreaks in a zoo in Guangdong province, China. Sequence alignment and phylogenetic analyses based on the full-length hemagglutinin (H) and fusion (F) genes showed that they were closely identical to genotype Asia-1. Prior to confirmation of CDV in Siberian tigers, to control spread of the disease, a live attenuated combination CDV vaccine was used among almost all carnivore animals except for red pandas in which another recombinant combination CDV vaccine was used. However, about two months later, CDV re-emerged and caused the death among red pandas. Based on the vaccination records, the live combination vaccine could be considered an ideal weapon against CDV in zoo carnivore animals. Although the recombinant combination CDV vaccine was safe for red pandas, its protection effectiveness remains to be further investigated. Moreover, according to the outbreak interval time and sequence characterization, we suspected that stray cats circulating in the zoo were the intermediate host, which contributed to CDV spread from stray dogs to zoo animals. This study revealed the importance of vaccination and biosecurity for zoo animals.

Emerging evidences addressed an association between phosphate and muscle function. Because little attention was focused on this issue, the objective of our study was to explore the relationship of phosphate with muscle strength, dynapenia, and sarcopenia. From the National Health and Nutrition Examination Survey, a total of 7421 participants aged 20 years or older were included in our study with comprehensive examinations included anthropometric parameters, strength of the quadriceps muscle, and appendicular lean masses. Within the normal range of serum phosphate, we used quartile-based analyses to determine the potential relationships of serum phosphate with dynapenia, and sarcopenia through multivariate regression models. After adjusting for the pertinent variables, an inverse association between the serum phosphate quartiles and muscle strength was observed and the linear association was stronger than other anthropometric parameters. Notably, the significant association between phosphate and muscle strength was existed in >65 years old age group, not in 20-65 years old. The higher quartiles of phosphate had higher likelihood for predicting the presence of dynapenia rather than sarcopenia in entire population. Our study highlighted that higher quartiles of phosphate had significant association with lower muscle strength and higher risks for predicting the presence of dynapenia.

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A sensitive and specific liquid chromatographic/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantifying total and unbound docetaxel drug concentrations in plasma. Calibration curves for unbound and total docetaxel were linear over the respective ranges of 0.108~10.8 and 0.54~216 ng/mL. The intra- and interday assay accuracy and precision did not exceed 15%. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of docetaxel in the matrices tested. In addition, this method is fast and simple with a short run time of 4.5 min and a small plasma sample volume (500 µL). The validated method was successfully applied to a pharmacokinetic study of a docetaxel micelle formulation in rat plasma after intravenous administration at a dose of 10 mg/kg. Docetaxel micelles slowly released their drug payload, and protein-bound, unbound, and micellar drug pools existed simultaneously. These various forms in plasma pools were also measured in the study. We confirmed that most of the docetaxel in plasma was micelle-associated (96.52% at 24 h and 83.14% at 72 h) after micellar docetaxel administration, as a result of sequestration of the drug in long-circulating micelles.

This study aimed to explore the clinical applications of multimodal navigation combined with indocyanine green (ICG) fluorescein angiography in microsurgical treatment of cerebral arteriovenous malformations (AVMs). We retrospectively collected 52 patients with AVMs. Assisted by anatomic image, we reestablished three-dimensional structure using preoperative functional magnetic resonance imaging (fMRI) and Diffusion tensor imaging (DTI). The operation for lesion resection was finished under the assistance of neuro-navigation. ICG fluorescein angiography was performed for 16 of the study subjects, meanwhile, FLOW800 was used to rebuild blood vessel color visual image. Brain angiography was performed 1 week after the operation to check residual malformations. The patients' status was estimated by Modified Rankin Scale score. Of the AVMs, 92.3% (48/52) were totally removed, without severe side events. Among the patients, fluorescein angiography was carried out up to 58 times for 16 cases. All of these 16 cases were confirmed with malformations and 14 of them had draining vein. The total resection rate of these 16 cases reached 100%, and the occurrence rate of postoperative complications was not significantly increased. During the operation of lesion resection, the application of multimodal navigation could effectively protect functional cortex and conduction pathway.

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.

Tamoxifen is the standard first-line hormonal therapy for premenopausal women with estrogen receptor (ER)-positive metastatic breast cancer (BC). One of the crucial mechanisms underlying hormonal therapy resistance is the collateral activation of the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. We explored whether PI3K inhibitors, buparlisib and alpelisib, enhance the efficacy of tamoxifen against ER-positive BC cells. We have observed a synergism between alpelisib or buparlisib and tamoxifen in the treatment for ER-positive BC cell lines harboring different PI3K alterations. Immunoblotting analysis showed alpelisib, buparlisib, or either drug in combination with tamoxifen downregulated the PI3K downstream targets in the MCF-7 and ZR75-1 cells. In the MCF-7 cells transfected with a constitutive active (myristoylated) AKT1 construct or mutant ER, the synergistic effect between alpelisib and tamoxifen was markedly attenuated, indicating that synergism depends on AKT inhibition or normally functioning ER. Combining alpelisib or buparlisib with tamoxifen also attenuated MCF-7 tumor growth in Balb/c nude mice. Our data suggest that additional PI3K blockade might be effective in enhancing the therapeutic effect of tamoxifen in ER-positive BC and support the rationale combination in clinical trials.

Autosomal dominant non-syndromic hearing loss (ADNSHL) is genetically heterogeneous with more than 35 genes identified to date. Using a massively parallel sequencing panel targeting 159 deafness genes, we identified a novel missense variant of POU4F3 (c.982A>G, p.Lys328Glu) which co-segregated with the deafness phenotype in a three-generation Taiwanese family with ADNSHL. This variant could be classified as a "pathogenic variant" according to the American College of Medical Genetics and Genomics guidelines. We then performed subcellular localization experiments and confirmed that p.Lys328Glu compromised transportation of POU4F3 from the cytoplasm to the nucleus. POU3F4 p.Lys328Glu was located within a bipartite nuclear localization signal (NLS), and was the first missense variant in bipartite NLS of POU4F3 validated in functional studies. These findings expanded the mutation spectrum of POU4F3 and provided insight into the pathogenesis associated with aberrant POU4F3 localization.

Lipid bodies (LBs) in the coral gastrodermal tissues are key organelles in the regulation of endosymbiosis and exhibit a diel rhythmicity. Using the scleractinian Euphyllia glabrescens collected across the diel cycle, we observed temporally dynamic lipid profiles in three cellular compartments: host coral gastrodermal cells, LBs, and in hospite Symbiodinium. Particularly, the lipidome varied over time, demonstrating the temporally variable nature of the coral-Symbiodinium endosymbiosis. The lipidome-scale data highlight the dynamic, light-driven metabolism of such associations and reveal that LBs are not only lipid storage organelles but also act as a relay center in metabolic trafficking. Furthermore, lipogenesis in LBs is significantly regulated by coral hosts and the lipid metabolites within holobionts featured predominantly triacylglycerols, sterol esters, and free fatty acids. Given these findings through a time-varied lipidome status, the present study provided valuable insights likely to be crucial to understand the cellular biology of the coral-Symbiodinium endosymbiosis.

To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m 2 ) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.

Abundant and low-cost Ce has attracted considerable interest as a prospective alternative for those critically relied Nd/Pr/Dy/Tb in the 2:14:1-type permanent magnets. The (Nd, Ce)2Fe14B compound with inferior intrinsic magnetic properties to Nd2Fe14B, however, cannot provide an equivalent magnetic performance. Since Ce valence is sensitive to local steric environment, manipulating it towards the favorable trivalent state provides a way to enhance the magnetic properties. Here we report that such a desirable Ce valence can be induced by La-Ce co-doping into [(Pr, Nd)1-x(La, Ce)x]2.14Fe14B (0 ≤ x ≤ 0.5) compounds via strip casting. As verified by X-ray photoelectron spectroscopy results, Ce valence shifts towards the magnetically favorable Ce(3+) state in the composition range of x > 0.3, owing to the co-doping of large radius La(3+) into 2:14:1 phase lattice. As a result, both crystallographic and magnetic anomalies are observed in the same vicinity of x = 0.3, above which lattice parameters a and c, and saturation magnetization Ms increase simultaneously. Over the whole doping range, 2:14:1 tetragonal structure forms and keeps stable even at 1250 K. This finding may shed light on obtaining a favorable Ce valence via La-Ce co-doping, thus maintaining the intrinsic magnetic properties of 2:14:1-type permanent magnets.

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.