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As a diverse and complex food matrix, the animal food microbiota and repertoire of antimicrobial resistance (AMR) genes remain to be better understood. In this study, 16S rRNA gene amplicon sequencing and shotgun metagenomics were applied to three types of animal food samples (cattle feed, dry dog food, and poultry feed). ZymoBIOMICS mock microbial community was used for workflow optimization including DNA extraction kits and bead-beating conditions. The four DNA extraction kits (AllPrep PowerViral DNA/RNA Kit, DNeasy Blood & Tissue Kit, DNeasy PowerSoil Kit, and ZymoBIOMICS DNA Miniprep Kit) were compared in animal food as well as the use of peptide nucleic acid blockers for 16S rRNA gene amplicon sequencing. Distinct microbial community profiles were generated, which varied by animal food type and DNA extraction kit. Employing peptide nucleic acid blockers prior to 16S rRNA gene amplicon sequencing was comparable with post-sequencing in silico filtering at removing chloroplast and mitochondrial sequences. There was a good agreement between 16S rRNA gene amplicon sequencing and shotgun metagenomics on community profiles in animal feed data sets; however, they differed in taxonomic resolution, with the latter superior at resolving at the species level. Although the overall prevalence of AMR genes was low, resistome analysis of animal feed data sets by shotgun metagenomics revealed 10 AMR gene/protein families, including beta-lactamases, erythromycin/lincomycin/pristinamycin/tylosin, fosfomycin, phenicol, and quinolone. Future expansion of microbiome and resistome profiling in animal food will help better understand the bacterial and AMR gene diversity in these commodities and help guide pathogen control and AMR prevention efforts.IMPORTANCEWith the growing interest and application of metagenomics in understanding the structure/composition and function of diverse microbial communities along the One Health continuum, this study represents one of the first attempts to employ these advanced sequencing technologies to characterize the microbiota and AMR genes in animal food. We unraveled the effects of DNA extraction kits on sample analysis by 16S rRNA gene amplicon sequencing and showed similar efficacies of two strategies at removing chloroplast and mitochondrial reads. The in-depth analysis using shotgun metagenomics shed light on the community compositions and the presence of an array of AMR genes in animal food. This exploration of microbiomes and resistomes in representative animal food samples by both sequencing approaches laid important groundwork for future metagenomic investigations to gain a better understanding of the baseline/core microbiomes and associated AMR functions in these diverse commodities and help guide pathogen control and AMR prevention efforts.

Importance: Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones., Competing Interests: The authors declare no conflict of interest.

Background: Recent guidelines suggest that coronary angiography (CAG) should be considered for out-of-hospital cardiac arrest (OHCA) survivors, including those without ST elevation (STE) and without shockable rhythms. However, there is no prospective data to support CAG for survivors with nonshockable rhythms and no STE post resuscitation., Methods: This was a re-analysis of the PEARL study (randomized OHCA survivors without STE to early CAG versus not). Patients were subdivided by initial rhythm as nonshockable (Nsh) vs shockable (Sh). The primary outcome was coronary angiographic evidence of acute culprit lesion, with secondary outcomes being survival to hospital discharge and neurological recovery., Results: The PEARL study included 99 patients with OHCA from a presumed cardiac etiology, 24 with nonshockable and 75 with shockable rhythms. There was no difference in the frequency of CAG between the two groups [71% (Nsh) and 75% (Sh); p = 0.79], presence of CAD [81% (Nsh) and 68% (sh); p = 0.37, or culprit lesions identified in each group [50% (Nsh) and 45% (Sh); p = 0.78. Nonshockable patients had worse discharge survival [33% (Nsh) vs 57% (Sh); p = 0.04] and those survived, had worse neurological recovery [30% (Nsh) vs 54% (Sh); p = 0.02] compared to shockable patients., Conclusions: OHCA survivors presenting with nonshockable rhythms and no STE post resuscitation had similar prevalence of culprit coronary lesions to those with shockable rhythms. CAG may be considered in patients with OHCA without STE regardless of initial presenting rhythm. There was no benefit of emergent CAG both in shockable and non-shockable rhythms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study., Patients and Methods: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level., Results: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively., Conclusions: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC., Competing Interests: Disclosure YC, SQ, SL, ZL, YC, YF, YS, XY, XY, WL, TL, XL, JZ, YB, CB, KG, H-MP, LB, J-WY, JC have declared no conflicts of interest. C-HH reports honoraria and fees for consulting and lecture from Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Ono Pharmaceutical, and Roche; fees for consulting from Merck Serono; and grants from AstraZeneca and BeiGene. S-BK reports grants (to institution) from DongKook Pharm Co., Novartis, and Sanofi Genzyme; and personal fees (advisory) for Dae Hwa Pharma Co. Ltd, Daiichi-Sankyo, ISU Abxis. TK reports grants and personal fees from Astellas Amgen BioPharma, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Ono Pharmaceutical; grants from Shionogi and Taiho Pharmaceutical; and personal fees from Astellas Pharma, Bristol Myers Squibb, and Oncolys BioPharma. S-HL reports personal fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme Corp., and Roche; and grants from Merck Sharp & Dohme Corp., KM reports research funding for Amgen, Daiichi-Sankyo, Merck Serono, Merck Sharp & Dohme Corp., Ono, Parexel International, Pfizer, Sanofi, Solasia Pharma, and Taiho; personal fees (consulting fee and/or honorarium) for Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly, Ono, Sanofi, Taiho, and Takeda. TD reports grants from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Eisai, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Novartis, Pfizer, Quintile (IQVIA), Sumitomo Dainippon, and Taiho; and personal fees from AbbVie, Amgen, Astellas Pharma, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharma, Daiichi Sankyo, Janssen, Merck Sharp & Dohme Corp., Novartis, Oncolys BioPharma, Ono Pharmaceutical, Otsuka Pharma, Rakuten Medical, Sumitomo Dainippon, Taiho, and Takeda. YC is an employee of MSD China, Shanghai, China. WL is an employee of MSD China, Shanghai, China., (Copyright © 2021 Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA, The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to build a hemogram-based decision tree to evaluate the association between current probability of metabolic syndrome (MetS) and prediction of future hypertension, type 2 diabetes and cardiovascular diseases (CVD) risk., Methods: A total of 40 395 elder participants (≥60 years) were enrolled in a standard health examination program in Taiwan from January 1999 to December 2014. A decision tree classification of the presence or absence of MetS at baseline, using age, sex and hemogram (white blood cell, hemoglobin and platelet) as independent variables, was conducted for the randomly assigned training (70%) and validation (30%) groups. Participants without MetS at baseline (n = 25 643) were followed up to observe whether they developed MetS, hypertension, type 2 diabetes or CVD in the future., Results: Modest accuracy of the decision tree in the training and validation groups with area under the curves of 0.653 and 0.652, respectively, indicated an acceptable generalizability of results. The predicted probability of baseline MetS was obtained from decision tree analysis. Participants without MetS at baseline were categorized into three equally sized groups according to the predicted probability. Participants in the third tertile had significantly higher risks of future MetS (hazard ratio 1.40, 95% confidence interval 1.25-1.58); type 2 diabetes (1.46, 1.17-1.83); hypertension (1.14, 1.01-1.28); and CVD (1.21, 1.01-1.44), compared with those in the first tertile., Conclusions: Execution of hemogram-based decision tree analysis can assist in early identification and prompt management of elderly patients at a high risk of future hypertension, type 2 diabetes and CVD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome., Methods: A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks., Results: Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p < 0.001), waist (41.3 vs. 38.8 inches, p < 0.001), systolic BP (144.1 vs. 133.4 mm of Hg, p = 0.014), diastolic BP (83.3 vs. 76.2 mm of Hg, p = 0.0056), TG (146.0 vs. 113.8 mg/dl, p = 0.022), HDL (51.1 vs. 55.0 mg/dl, p = 0.012), and serum glucose (114.0 vs. 103.2 mg/dl, p = 0.013)., Conclusion: CLIPP demonstrates feasibility and early efficacy of a multicomponent lifestyle modification intervention toward addressing obesity as well as components of metabolic syndrome in men on ADT for prostate cancer. This study provides strong preliminary data to develop future clinical trials in this population., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer., Methods: The primary aim of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2) is to test the feasibility of conducting a 24-week lifestyle modification intervention in men on ADT for prostate cancer. Additionally, it will also determine the effect of this intervention on weight loss, cardiometabolic markers (secondary aim and markers of interest: serum glucose, insulin resistance, hemoglobin A1C and lipid panel), and QoL (tertiary aim). The intervention will be delivered weekly via telephone for the first 10 weeks and bi-weekly for the remaining 14 weeks. Questionnaires and serum samples will be collected at baseline, week 12, and week 24. Anthropometric measurements will be collected at baseline, week 6, week 12, week 18 and week 24., Results: We hypothesize that the CLIPP2 intervention will produce a 7% weight loss that will result in improved markers associated with cardiometabolic disease and type 2 diabetes in the study population., Conclusion: Results will provide insight into the role of lifestyle modification in addressing ADT adverse effects as well as provide preliminary data to inform the development of future lifestyle interventions in this area., Trial Registration: NCT04228055 Clinicaltrials. gov., (© 2021 Published by Elsevier Inc.)

CeTe 3 is a unique platform to investigate the itinerant magnetism in a van der Waals (vdW) coupled metal. Despite chemical pressure being a promising route to boost quantum fluctuation in this system, a systematic study on the chemical pressure effect on Ce 3+ (4f 1 ) states is absent. Here, we report on the successful growth of a series of Se doped single crystals of CeTe 3 . We found a fluctuation driven exotic magnetic rotation from the usual easy-axis ordering to an unusual hard-axis ordering. Unlike in localized magnetic systems, near-critical magnetism can increase itinerancy hand-in-hand with enhancing fluctuation of magnetism. Thus, seemingly unstable hard-axis ordering emerges through kinetic energy gain, with the self-consistent observation of enhanced magnetic fluctuation (disorder). As far as we recognize, this order-by-disorder process in fermionic system is observed for the first time within vdW materials. Our finding opens a unique experimental platform for direct visualization of the rich quasiparticle Fermi surface deformation associated with the Fermionic order-by-disorder process. Also, the search for emergent exotic phases by further tuning of quantum fluctuation is suggested as a promising future challenge.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries., Competing Interests: Disclosure GSB has received fees for consultancy/advisory roles from VICUS Therapeutics, Mylan, Biocon, Cipla, Boehringer Ingelheim, Novartis, GlaxoSmithKline and MSD, and research funding from VICUS Therapeutics and Cipla. AC has received fees for consultancy/advisory roles from Merck Serono, Roche, Beigene, Bayer, Servier, Eli Lilly, Novartis, Takeda, Astelas and Pierre Fabre, and research funding from Genentech, Merck Serono, Roche, Beigene, Bayer, Servier, Eli Lilly, Novartis, Takeda, Astelas, Fibrogen, Amcure, Sierra Oncology, AstraZeneca, Medimmune, Bristol-Myers Squibb and MSD. A-LC has received fees for consultancy/advisory roles from Bayer Schering Pharma, Bristol-Myers Squibb, Eisai, Merck Serono, Novartis, Ono Pharmaceutical, Exelixis, Nucleix Ltd., Roche/Genentech and IQVIA. L-TC has received research funding from Novartis, Merck Serono, TTY, Polaris, SyncorePharm, Pfizer and Bristol-Myers Squibb, honoraria from ONO, Eli Lilly, MSD, PharmaEngine, TTY, SyncorePharm, Novartis, AstraZeneca and Ipsen, patents and royalties for ENO-1 mAb from HuniLife, and is a Scientific Advisory Board member at PharmaEngine and a board member at SinoPharm Taiwan, Ltd. SPC has received fees for consultancy/advisory roles from Sirtex, Bristol-Myers Squibb, Bayer, Eisai, Ipsen, Celgene and Eli Lilly, and research funding from Sirtex and Bristol-Myers Squibb. CHH has received fees for consultancy/advisory roles from Ono Pharmaceutical, Bristol-Myers Squibb, Merck Sharp & Dohme and Merck Serono, and research funding from AstraZeneca, Genentech and Merck Sharp & Dohme. MI has received research funding from Eli Lilly Japan, Bayer, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, AstraZeneca and Merck Serono. H-YL has received fees for consultancy/advisory roles from Bayer, Bristol-Myers Squibb and Eisai. EM has received fees for consultancy/advisory roles from Amgen, Bayer, Merck Serono, Roche, Servier, AstraZeneca and Pierre Fabre. HM has received fees for consultancy/advisory roles from Mylan, Cipla, Pfizer, Eli Lilly, Novartis and AstraZeneca, and research funding from Novartis. GP has received fees for consultancy/advisory roles from Roche, Amgen, MSD, Boehringer and Bristol-Myers Squibb, and research funding from Roche, Amgen, Astellas, Pfizer and Novartis. DT has received fees for consultancy/advisory roles from Novartis, Celgene and MSD, and research funding from Novartis, Sirtex and Bristol-Myers Squibb. JT has received fees for consultancy/advisory roles from Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Infection Biosciences Limited, Ipsen, Kura Oncology, Eli Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd., Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. MU has received research funding from Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte, ASLAN Pharmaceuticals and Yakult Honsha. AV has received fees for consultancy/advisory roles from Bayer, Merck Serono, Roche, Servier, AstraZeneca, Pierre Fabre, Bristol-Myers Squibb, MSD, Celgene, Beigene, EISAI, INCYTE, Eli Lilly and BTG, and research funding from INCYTE. TY has received research funding from Novartis Pharma K.K., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., Sanofi K.K., Daiichi Sankyo Co., Ltd., Parexel International Inc., Ono Pharmaceutical Co., Ltd., GlaxoSmithKline K.K. and Boehringer Ingelheim Japan, Inc. S-CC, J-YD, CH, GFH, Y-HH, TCK, S-NL, SQ, B-YR, ZR, Y-CS, C-JY and YY have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Abstract: Antimicrobial-resistant bacteria are a major public health problem. Of particular importance in the context of food safety is the prevalence of antimicrobial resistance (AMR) genes within nontyphoidal Salmonella, which is a leading bacterial cause of foodborne disease. We determined the prevalence of AMR genes across a very large number of Salmonella genomes (n = 25,647) collected from isolates from 16 common food sources. The average percentage of isolates from nonanimal foods, such as fruit, nuts and seeds, and vegetables, harboring at least one AMR gene was only marginally lower (72%) than that observed in isolates from animal foods such as beef, chicken, turkey, and pork (74%). This high prevalence of AMR genes was primarily driven by the high prevalence of aminoglycoside resistance genes in nearly all food isolates; genes for resistance to tetracycline and sulfonamide also were highly prevalent. However, evaluation of the number of genes per isolate revealed that the prevalence of AMR genes was higher in animal food isolates than in nonanimal food isolates (P = 0.018). A random forest analysis provided evidence that within a given serovar, resistance gene profiles differed according to isolate food source. AMR gene profiles could be used to correctly predict the food of origin for 71% of the isolates, but success differed according to serovar. This information can help inform AMR risk assessments of food commodities and refine processes for targeting interventions to limit the spread of AMR through the food supply., (Published 2020 by the International Association for Food Protection Not subject to U.S. Copyright. This is an open access.)

Avilamycin-resistant Enterococcus spp. have never been reported in the United States. Here, we report the complete genome sequences of two avilamycin-resistant (Avi r ) Enterococcus faecium strains isolated from a retail chicken and a cecal sample from a young chicken. Both isolates are multidrug resistant (MDR) and carry emtA on MDR plasmids.

Background: The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings., Aims: This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study., Methods: A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC., Results: The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection., Conclusions: Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Natural killer (NK) cells play a crucial role in regulating immune functions. Few studies have characterized canine NK cells. We previously demonstrated that canine peripheral blood lymphocytes (PBLs) with a low surface CD5 density (CD5lo) are considered a critical NK population. Natural killer cells in most mammals do not express T-cell markers, but canine CD5lo cells express surface molecules, such as CD3 T-cell receptors. These features make canines unique models for the study of comparative immunology in NK cells. In this study, we discovered that CD5lo and CD21 double-negative (CD5lo-ne/CD2 - ) cells were originally low in NK cytotoxicity and their NK cytotoxicity was highly activated when co-cultured with CD5lo NK cells. The cytotoxicity was not activated when co-cultured with other cell types, such as high surface CD5 density (CD5hi) cells. The CD5lo-negative (CD5lo-ne) population comprises CD5 - and CD5hi cells. CD5-cells were low in NK cytotoxicity initially or after culturing with interleukin-2 (IL-2) without CD5lo cells; however, the addition of CD5lo cells in a similar medium markedly enhanced the NK activity. By contrast, CD5hi cells were always NK inactive, irrespective of them being cultured with CD5lo cells or not. We further verified that only the CD5 - CD21 - cells, which were separated from CD5 - CD21 + cells in the entire CD5 - population, showed activated NK activity through CD5lo cell induction. This study is the first to reveal that canine NK cells enhanced NK-inert cells to become NK-cytotoxic cells. Additionally, it is concluded that in beagles, except for CD5lo cells, CD5 - CD21 - cells show NK activity.

Objectives: Abdominal fat may be a better predictor than body mass index (BMI) for risk of metabolically-related diseases, such as diabetes, cardiovascular disease, and some cancers. We sought to validate the percent fat reported on dual energy X-ray absorptiometry (DXA) regional spine scans (spine fat fraction, SFF) against abdominal fat obtained from total body scans using the iDXA machine (General Electric, Madison, WI), as previously done on the Prodigy model., Methods: Total body scans and regional spine scans were completed on the same day (N = 50). In alignment with the Prodigy-based study, the following regions of interest (ROI) were assessed from total body scans and compared to the SFF from regional spine scans: total abdominal fat at (1) lumbar vertebrae L2-L4 and (2) L2-Iliac Crest (L2-IC); (3) total trunk fat; and (4) visceral fat in the android region. Separate linear regression models were used to predict each total body scan ROI from SFF; models were validated by bootstrapping., Results: The sample was 84% female, a mean age of 38.5 ± 17.4 years, and mean BMI of 23.0 ± 3.8 kg/m 2 . The SFF, adjusted for BMI, predicted L2-L4 and L2-IC total abdominal fat (%; Adj. R 2 : 0.90) and total trunk fat (%; Adj. R 2 : 0.88) well; visceral fat (%) adjusted R 2 was 0.83. Linear regression models adjusted for additional participant characteristics resulted in similar adjusted R 2 values., Conclusions: This replication of the strong correlation between SFF and abdominal fat measures on the iDXA in a new population confirms the previous Prodigy model findings and improves generalizability., (© 2017 Wiley Periodicals, Inc.)

Overexpression of Cys2His2 zinc-finger 322A (ZNF322A) oncogenic transcription factor is associated with lung tumorigenesis. However, the mechanism of ZNF322A overexpression remains poorly understood. Here, we discover that protein stability of ZNF322A is regulated by coordinated phosphorylation and ubiquitination through the CK1δ/GSK3β/FBXW7α axis. CK1δ and GSK3β kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7α leading to ZNF322A protein destruction. Overexpression of FBXW7α induces ZNF322A protein degradation, thereby blocks ZNF322A transcription activity and suppresses ZNF322A-induced tumor growth and metastasis in vitro and in vivo. Clinically, overexpression of ZNF322A correlates with low FBXW7α or defective CK1δ/GSK3β-mediated phosphorylation in lung cancer patients. Multivariate Cox regression analysis indicates that patients with ZNF322A high/FBXW7 low expression profile can be used as an independent factor to predict the clinical outcome in lung cancer patients. Our results reveal a new mechanism of ZNF322A oncoprotein destruction regulated by the CK1δ/GSK3β/FBXW7α axis. Deregulation of this signaling axis results in ZNF322A overexpression and promotes cancer progression.

Background: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC., Methods: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in K trans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed., Results: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042)., Conclusions: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804)., (© 2017 John Wiley & Sons Ltd.)

Current guidelines in the setting of exposures to potentially rabid bats established by the Advisory Committee on Immunization Practices (ACIP) address post-exposure prophylaxis (PEP) administration in situations where a person may not be aware that a bite or direct contact has occurred and the bat is not available for diagnostic testing. These include instances when a bat is discovered in a room where a person awakens from sleep, is a child without an adult witness, has a mental disability or is intoxicated. The current ACIP guidelines, however, do not address PEP in the setting of multiple persons exposed to a bat or a bat colony, otherwise known as mass bat exposure (MBE) events. Due to a dearth of recommendations for response to these events, the reported reactions by public health agencies have varied widely. To address this perceived limitation, a survey of 45 state public health agencies was conducted to characterize prior experiences with MBE and practices to mitigate the public health risks. In general, most states (69% of the respondents) felt current ACIP guidelines were unclear in MBE scenarios. Thirty-three of the 45 states reported prior experience with MBE, receiving an average of 16.9 MBE calls per year and an investment of 106.7 person-hours annually on MBE investigations. PEP criteria, investigation methods and the experts recruited in MBE investigations varied between states. These dissimilarities could reflect differences in experience, scenario and resources. The lack of consistency in state responses to potential mass exposures to a highly fatal disease along with the large contingent of states dissatisfied with current ACIP guidance warrants the development of national guidelines in MBE settings., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Zoonoses and Public Health published by Blackwell Verlag GmbH.)

A cross-sectional cohort study was conducted to investigate whether ghrelin level in obese women predicts the quality of life (QOL). A total of 307 subjects fulfilled the criteria: (1) age between 20 and 65 years old, (2) body mass index ≥27 kg/m 2 (3) waist circumference ≥80 cm were enrolled in the study. All subjects were assigned to one of the plasma ghrelin level categories according to the quartiles. The median of age and BMI of the 307 obese women were 45 ± 18 years and 29.9 ± 4.1 kg/m 2 , respectively. The main outcome evaluated is the associations of plasma ghrelin level and QOL, which were evaluated using multiple linear regression analysis. Results of linear trend test show significant statistical difference in plasma lipoproteins (triglyceride, cholesterol, HDL-cholestero and LDL-cholesterol = and levels of obesity-related hormone peptides, including leptin, adiponectin, insulin among quartiles of ghrelin. Multiple liner regression analysis of serum obesity-related hormone peptide level and QOL using stepwise method shows ghrelin concentration was the only predictor of QOL, including PCS-12 level (β = -0.18, p = 0.001), MCS-12 level (β = -0.14, p = 0.009), WHOQOL-BREF scores: physical (β = -0.13, p = 0.03), psychological (β = -0.16, p = 0.007), social (β = -0.21, p =  < 0.001), and environmental (β = -0.22, p =  <0.001), after adjusting other factors for obese female subjects. This study demonstrated that ghrelin concentration is strongly associated with QOL level among obese women. Hence, ghrelin concentration might be a valuable marker to be monitored in obese women.

Body composition may be a better predictor of chronic disease risk than body mass index (BMI) in older populations., Objectives: We sought to validate spine fat fraction (%) from dual energy X-ray absorptiometry (DXA) spine scans as a proxy for total abdominal fat., Methods: Total body DXA scan abdominal fat regions of interest (ROI) that have been previously validated by magnetic resonance imaging were assessed among healthy, postmenopausal women who also had antero-posterior spine scans (n = 103). ROIs were (1) lumbar vertebrae L2-L4 and (2) L2-Iliac Crest (L2-IC), manually selected by two independent raters, and (3) trunk, auto-selected by DXA software. Intra-class correlation coefficients evaluated intra and inter-rater reliability on a random subset (N = 25). Linear regression models, validated by bootstrapping, assessed the relationship between spine fat fraction (%) and total abdominal fat (%) ROIs., Results: Mean age, BMI, and total body fat were 66.1 ± 4.8 y, 25.8 ± 3.8 kg/m 2 and 40.0 ± 6.6%, respectively. There were no significant differences within or between raters. Linear regression models adjusted for several participant and scan characteristics were equivalent to using only BMI and spine fat fraction. The model predicted L2-L4 (Adj. R 2 : 0.83) and L2-IC (Adj. R 2 : 0.84) abdominal fat (%) well; the adjusted R 2 for trunk fat (%) was 0.78. Model validation demonstrated minimal over-fitting (Adj. R 2 : 0.82, 0.83, and 0.77 for L2-L4, L2-IC, and trunk fat, respectively)., Conclusions: The strong correlation between spine fat fraction and DXA abdominal fat measures make it suitable for further development in postmenopausal chronic disease risk prediction models. Am. J. Hum. Biol. 28:918-926, 2016. © 2016Wiley Periodicals, Inc., Competing Interests: Statement: The authors have declared no conflicts of interest., (© 2016 Wiley Periodicals, Inc.)

Introduction: Acute neck swelling with pharyngeal signs often triggers emergency consultation. Treatment and diagnosis are usually multidisciplinary. Failing to find a possible etiology may lead to misdiagnosis., Case Presentation: A young man presented to the emergency room with a 4-day history of cough, neck swelling and sore throat. Laboratory testing showed a leukocyte count of 9200 without left shift. Mild elevated CRP with 1.7 was noted and computed tomography (CT) showed fluid accumulation in the retropharyngeal space and neck edema down to thyroid region. Antibiotic was prescribed and admitted to infection ward under the impression of deep neck infection. During hospitalization, needle aspiration was performed where water fluid was collected without pus. Investigations showed massive proteinuria, hypoalbuminemia and hypercholesterolemia. The early focal segmental glomerulosclerosis was found by renal biopsy. After prednisolone 60mg daily and albumin supplement, the neck swelling, swallowing pain and general edema had completely resolved., Discussion: The purpose of this case is to raise awareness of nephrotic syndrome as an unusual but possibly cause of retropharyngeal edema. We highlight the diagnostic features that will allow the physicians to make the correct diagnosis, avoid unnecessary incision and drainage, and commence effective treatment early in the disease course., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Green tea is believed to have beneficial effects in the prevention and treatment of acne., Objective: To examine the effects of a decaffeinated green tea extract (GTE), providing a daily dose of 856 mg of epigallocatechin gallate (EGCG) upon women with post-adolescent acne., Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from May 2012 through October 2013. A final group of 80 subjects were randomly assigned to receive either 1500 mg of decaffeinated GTE or placebo (cellulose) daily for 4 weeks. Inflammatory lesion counts were used as the major outcome measurement. At baseline and after 4 weeks of treatment, anthropometric measurements, fasting glucose levels and a lipid profile were measured from both groups., Results: Sixty-four of 80 women, from 25 to 45 years of age with moderate-to-severe acne completed the study. Statistically significant differences were noted in inflammatory lesion counts distributed on the nose, periorally and on the chin between the two groups. However, there were no significant differences between groups for total lesion counts. Within-group comparison revealed that the GTE group had significant reductions in inflammatory lesions distributed on the forehead and cheek, and significant reductions in total lesion counts. GTE resulted in significant reductions in total cholesterol levels within the GTE group., Conclusions: GTE resulted in significant reductions in lesions located on the nose, perioral area and chin. More research is required to determine whether a decaffeinated GTE standardized for EGCG content will provide clinical benefits in women with post-adolescent acne., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Acne in adult women tends to be chronic, refractory to treatment and associated with psychosocial problems. Body mass index (BMI) has been reported to be a risk factor for acne in school children and adolescents, but not in adult women., Objectives: The aim of this study was to demonstrate the relationship between BMI and acne lesion counts in women with post-adolescent acne., Methods: Hundred and four women between 25 and 45 years of age, with moderate or severe acne vulgaris were enrolled in this study. The main outcome evaluated was the number of acne lesions, which were then assessed using multiple linear regression analysis., Results: The coefficients of multiple regression analysis with stepwise model showed that BMI (β = -0.36; p = 0.001) and family history (β = 0.21; p = 0.04) were the main predictors of the number of acne lesions., Conclusion: Initial findings indicate that BMI is negatively associated with the number of acne lesions in Taiwanese women with moderate to severe post-adolescent acne., (© 2014 European Academy of Dermatology and Venereology.)

Introduction: It is well known that higher fasting plasma glucose (FPG) is associated with metabolic syndrome (MetS). This relationship still exists even the FPG is within the normal range. However, most of these studies did not exclude subjects who were on medications which would affect the results of the studies. At the same time, there is no longitudinal study done to validate this correlation, especially in elderly. In this study, the relationships between normal FPG and MetS were evaluated., Method: We randomly selected 57,517 subjects who were ≥ 60-years old from health screening centre. In the first part of study, subjects were enrolled in the cross-sectional study to find out the optimal cut-off value of FPG with higher chances to have MetS. In the second part of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 5.3-year longitudinal study., Results: There were 18,287 subjects enrolled in this study. In the first part of study, the cross-sectional study, optimal cut-off values of FPG were determined by the ROC curve and the sensitivity for these cut-off values were 56.6% in men and 60.9% in women, respectively. The result showed that lower FPG is healthier than the higher (log-rank test, p < 0.001). During the follow-up period, 5039 subjects showed hazard ratios of 2.09 for men and 1.884 for women developing future MetS., Conclusion: Our study is the first longitudinal design in elderly and showed that older subjects with higher FPG proved to have higher risk of Mets even the FPG is still within its normal range., (© 2015 John Wiley & Sons Ltd.)

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA., (©2015 The British Editorial Society of Bone & Joint Surgery.)

Introduction: Hyperlactatemia may occur early after cardiac surgery and is correlated with prognosis. This study was conducted to analyze the perioperative variables and postoperative outcomes among heart transplant recipients with extremely high lactate levels (>15 mmol/L)., Methods: The single-center medical records of heart transplantation from June 2006 to May 2013 were retrospectively reviewed for patient characteristics, perioperative hemodynamic variables, arterial blood gas analysis data, and postoperative mortality., Results: Among 58 consecutive heart transplant recipients, lactate levels over the detectable upper limit (>15 mmol/L) were identified in 12 patients after intensive care unit admission, with peak time at 1.9 ± 2.0 (range 0-6.1) hours. The maximal preoperative lactate level was 3.1 mmol/L, and most (11/12) postoperative lactate levels returned to <4 mmol/L at 27.5 ± 12.8 hours after surgery (range 15-58, median 24), displaying a trend toward delayed extubation time in 10 recipients (P < .01). Blood glucose levels elevated significantly from preoperative 148.9 ± 45.2 to 375.7 ± 96.9 mg/dL at peak lactate level (P < .01). Four patients died in the ICU (range 5-32 days), 4 died after discharge (range 5-57 months), with 6 in total surviving over 1 year., Conclusion: Extreme hyperlactatemia commonly occurred early after heart transplantation and mostly recovered within 30 hours; however, with delayed extubation time after operation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In Taiwan, persons over 65 years old have higher prevalence of hepatitis C. Among these patients, around 50% have non-alcoholic fatty liver disease (NAFLD). Since cardiovascular diseases and diabetes are main causes of death in this age group, in this cross-sectional study, we tried to evaluate the effects of NAFLD and hepatitis C on the risk of metabolic syndrome (MetS)., Methods: In total, 25 116 subjects over 65 years old who presented for routine health check-ups were enrolled. From the results of seropositivity for hepatitis C and abnormal echogenicity, they were classified into four groups: normal (N), subjects with only hepatitis C (C), subjects with only abnormal echogenicity (E) and subjects with both hepatitis C and abnormal echogenicity (CE)., Results: Subjects in both groups E and CE had higher abnormal MetS components than group C. Among all five components, triglyceride (TG) was the one having the highest odds ratio (OR) in determining the incidence of MetS in groups C and E. Finally, compared to group N, both groups E and CE had significantly higher OR for having MetS. However, after adjusting for confounding factors, only the significance between groups E and N remained. In other words, higher MetS was noted in group E compared to group N and there was no difference in incidence of MetS between group CE and group N., Conclusions: Chronic hepatitis C is a protective factor against having MetS and this effect might be due to lower TG level in the elderly. Further studies are warranted for the underlying mechanisms.

Background and Aim: The influenza A virus (IAV) is an important zoonotic pathogen with infections also reported in dogs. IAV infections can be detected through the presence of antibodies using the enzyme-linked immunosorbent assay (ELISA). Serum is the only standard sample source; however, there is no information on the availability of other sample sources for IAV antibody detection in dogs. Compared with serum, plasma is more widely employed in most animal hospitals. The object of this study is to investigate whether plasma collected in ethylenediaminetetraacetic acid (EDTA) tubes (EDTA plasma) or heparin tubes (heparin plasma) could be used in the ELISA protocol instead of serum for IAV antibody detection in dogs., Materials and Methods: Totally, 82 matched EDTA plasma and serum sample pairs and 79 matched heparin plasma and serum sample pairs were employed using blocking enzyme-linked immunosorbent assay (bELISA). The agreement and correlation between the plasma (EDTA or heparin plasma) and serum were assessed using the agreement index kappa (kD) calculation and Pearson correlation coefficient, respectively., Results: The agreement index kD of EDTA plasma and serum was 1.0, and that of heparin plasma and serum was 0.85. The Pearson correlation coefficient of EDTA plasma and serum was 0.87 (p<0.01), and that of heparin plasma and serum was 0.82 (p<0.01)., Conclusion: The results proved that plasma, especially EDTA plasma, could be substituted for serum in the bELISA test. This might greatly expand the clinical applicability of IAV antibody detection in dogs.

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted.

Objectives: To determine the effect of selenium supplementation on the human proteomic profile., Design: Serum samples were collected in this pilot study from a randomized placebo controlled Phase 2 clinical trial (Watchful Waiting (WW))., Setting: Subjects were followed every three months for up to five years at the University of Arizona Prostate Cancer Prevention Program., Participants: One hundred and forty men (age < 85 years) had biopsy-proven prostate cancer, a Gleason sum score less than eight, no metastatic cancer, and no prior treatment for prostate cancer., Intervention: As part of the WW trial, men were randomized to placebo, selenium 200 μg/day or selenium 800 μg/day. For the purpose of the current study, 40 subjects enrolled in the WW study (20 from the placebo group and 20 from Se 800 μg/day group) were selected., Measurements: Baseline serum samples were collected at each follow-up visit and stored at -80 degrees Celsius. A multiplexed proteomic panel investigated changes in 120 proteins markers simultaneously., Results: Thirteen proteins (Apolipoprotein J, IL-10, IL-1 alpha, MMP-3, IL-12p70, IL-2 receptor alpha, cathepsin B, eotaxin, EGFR, FGF-basic, myeloperoxidase, RANTES, TGF-beta) were determined to be either statistically (p-value < 0.05) or marginally significantly (0.05 < p-value <0.1) changed in the selenium supplemented group as compared to placebo., Conclusion: Although independent validation of these results is needed, this study is the first of its kind to utilize high throughput fluorescence based protein multiplex panel in analyzing changes in the proteomic profile due to selenium supplementation. Results from this study provide insight into the ability of selenium to modulate numerous protein markers and thus impact various biological processes in humans.

Using a step-graded (SG) buffer structure via metal-organic chemical vapor deposition, we demonstrate a high suitability of In0.5Ga0.5As epitaxial layers on a GaAs substrate for electronic device application. Taking advantage of the technique's precise control, we were able to increase the number of SG layers to achieve a fairly low dislocation density (∼10(6) cm(-2)), while keeping each individual SG layer slightly exceeding the critical thickness (∼80 nm) for strain relaxation. This met the demanded but contradictory requirements, and even offered excellent scalability by lowering the whole buffer structure down to 2.3 μm. This scalability overwhelmingly excels the forefront studies. The effects of the SG misfit strain on the crystal quality and surface morphology of In0.5Ga0.5As epitaxial layers were carefully investigated, and were correlated to threading dislocation (TD) blocking mechanisms. From microstructural analyses, TDs can be blocked effectively through self-annihilation reactions, or hindered randomly by misfit dislocation mechanisms. Growth conditions for avoiding phase separation were also explored and identified. The buffer-improved, high-quality In0.5Ga0.5As epitaxial layers enabled a high-performance, metal-oxide-semiconductor capacitor on a GaAs substrate. The devices displayed remarkable capacitance-voltage responses with small frequency dispersion. A promising interface trap density of 3 × 10(12) eV(-1) cm(-2) in a conductance test was also obtained. These electrical performances are competitive to those using lattice-coherent but pricey InGaAs/InP systems.

Background: The discovery of asynchronous or synchronous double or multiple malignancies in patients is not uncommon. The co-occurrence of second primary malignancy (SPM) could be randomly occurring or association with risk factors such as environmental, genetic predisposition and therapy-related., Materials and Methods: We retrieved ∼782 million claim records consisting of 10.8 million males and 10.6 million females from Taiwan's National Health Insurance, which were collected for a period of 3 years (January 2000-December 2002). All the patient records were stratified by gender and ages at a 20-year interval with SPMs and specific groups. Interestingness or Q-value was used to measure strength of the disease-disease associations., Results: A total of 9423 thyroid cancer (female: 7483, male: 1940), 276 184 SPM (female: 141 023, male: 135 161) and 861 co-occurrence cases (female: 583, male: 278) were recorded. The co-occurrence incidence rate of head and neck, breast, digestive system and lung was 1.93%, 1.59%, 1.44% and 1.18%, respectively. Malignancy of salivary glands, laryngx, sarcoma, lymphoid tissue, mouth, central nervous system and lungs found Q-value >10. Malignancies with intermediate Q-values (5.0-9.9) were observed in nasopharynx, kidney and ureter, breast, stomach and skin. Prostate, leukemia, urinary bladder, ovary, colon, liver and uterine cervix cancer have lower Q-values (1.0-4.9)., Conclusion: Co-occurrence ratio of thyroid cancer and SPM was high, occurred in all organ systems. We postulated that the aggressive use of modern diagnostic modalities, aggressive radioiodine treatment, pre-existing molecular oncogen mutations, and thyroid hormone for simultaneously supple-mentary and suppressive therapies were responsible., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours., Methods: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course., Results: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile., Conclusions: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.

MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that regulate protein synthesis through posttranscriptional modifications. In this study, we found significant upregulation of miR-18a in prostate cancer specimens and prostate cancer cell lines compared with the normal controls. MiRNAs can be separated into two groups based on whether they regulate tumor suppressors or oncogenes. In our previous study, we found that miR-18a, which belongs to the miR17-92 cluster, is upregulated in prostate cancer; the objective of this study was to investigate the associated regulatory mechanisms. We found that miR-18a is upregulated in clinical tumor specimens and cancer cell lines. Our bioinformatics analysis showed that the serine/threonine-protein kinase 4 (STK4) 3' untranslated region contains a highly conserved binding site for the miR-18a seed region. Luciferase reporter assays were performed to indicate that STK4 is a direct target of miR-18a. Interestingly, miR-18a knockdown decreased cell growth in prostate cancer cells and significantly decreased prostate tumor growth in in vivo nude mice experiments through STK4-mediated dephosphorylation of AKT and thereby inducing apoptosis. Our results suggest that miR-18a acts as an oncomiR targeting STK4 in prostate cancer, and inhibition of miR-18a expression may offer therapeutically beneficial option for prostate cancer treatment.

Certain complexities, such as extensive vena caval injury, unexpected dense adhesions between liver and retrohepatic vena cava, and liver tumor abutting retrohepatic vena cava, sometimes warrant resection of vena cava during living-donor liver transplantation. Because the donor graft is devoid of vena cava, reconstruction of the retrohepatic cava is required, which can be done with the use of either a cryopreserved venous graft or an artificial conduit. With only a few published reports, the experience in vena cava reconstruction with the use of expanded polytetrafluoroethylene (ePTFE) during living-donor liver transplantation remains limited. We present our experience of 4 patients who successfully underwent vena caval resection during liver transplantation for various indications, which was subsequently reconstructed with the use of ePTFE grafts. All of these patients except 1 recovered well without any undue complications, such as thrombosis or outflow inadequacies, thus proving this extensive surgical treatment to be a successful and life-saving procedure, though meticulous skills are prerequisite., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: Periodontal disease encompasses gingivitis and periodontitis, which exerts systemic effects. We conducted a population-based study to evaluate the association between periodontal disease and the risk of cancer., Methods: We used insurance claims data from 1997 to 2010, accessing a database of 1 million randomly selected insurants in Taiwan. All patients were older than 20 and newly diagnosed with periodontitis between 1 January 1997 and 31 December 2010. The comparison cohort comprised patients older than 20, who were newly diagnosed with gingivitis in the same period. Both cohorts were followed until a cancer diagnosis, lost to follow-up, death, termination of insurance, or the end of 2010., Results: The incidence rate of cancer was 1.14 times higher in the study cohort than in the comparison cohort [confidence interval (CI) = 1.11-1.17]. The adjusted hazard ratio (HR) was 1.05 (95% CI = 1.00-1.11). A multivariable analysis showed that the periodontitis patients exhibited an elevated risk of developing oral cancer (adjusted HR = 1.79, 95% CI = 1.42-2.25)., Conclusion: The findings indicated that patients in the periodontitis cohort exhibited a higher risk of developing oral cancer than those in the gingivitis cohort.

Objectives: The aim of our study was to review the experience of early use of everolimus for recipients after adult-to-adult living donor liver transplantation., Methods: From February 2012 to December 2012, 80 recipients underwent living donor liver transplantation. Forty-three of them used everolimus as an adjunct to the calcineurin inhibitors (CNIs) in the early postoperative period. Thirty-nine patients had hepatocellular carcinoma (HCC) and poor renal function was noted in 9 patients. Ten of them were females and 33 were males. The age varied from 39 to 75 years old. The starting date of use was within 1 week in 33 patients, 2 weeks in 9 patients, and 1 patient was administered on postoperative day 20. The initial doses of everolimus were 0.25 mg every 12 hours and increased to 0.5 mg every 12 hours to target the level at 3-5 ng/mL. Doppler ultrasound was performed regularly postoperative days 1, 4, and 14., Results: The mean time between liver transplantation and everolimus treatment was 12 ± 8 days. The maximum dose of everolimus used was 1 mg/d with a target trough level between 3 and 5 ng/mL. At 3 months, a target trough level of 3 ng/mL was achieved. Six of 9 renal failure patients showed significant recovery of renal function, whereas 3 of them showed further deterioration and 1 required hemodialysis. During the follow-up period of 9 ± 6 months, all showed good patency of hepatic artery without thrombosis. Three patients (7%) developed HCC recurrence, whereas 1 patient died at the 10th month postoperative due to sepsis. Elevation of lipid profile was noted in 5 patients. Stomatitis was the most frequent side effect and occurred in 15 patients., Conclusions: The early use of everolimus was safe and feasible. Also, it can be safely used in patients with prior renal failure while reducing the doses of CNIs. Although the recurrence rate of HCC was reduced, further study is ongoing to evaluate the long-term impact of everolimus on prevention of HCC recurrence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Type-2 diabetes is mainly the metabolic defect involving multiple organs. To conclude their intricate relationships, the term 'ominous octet' had been proposed to denote this phenomenon. In this study, we enrolled older men without any medications for MetS components to further elucidate the relationships between normoglycaemic state and MetS., Methods: We enrolled male subjects with FPG less than 100 mg/dl and aged 65 and older undergoing routine health check-ups in Taiwan. After excluding subjects taking medications that might affect the components of MetS, a total of 6679 men were eligible for the analysis. Study subjects were further grouped into FPG tertiles (< 91 mg/dl, 92-95 mg/dl and > 95 mg/dl for tertil 1, tertil 2 and tertil 3, respectively)., Results: There was a significant trend between the FPG and percentages of subjects having MetS (p = 0.009). The relationships between the MetS components were higher in FPG 2 and FPG 3 than FPG 1. In simple correlation, all of the MetS and LDL-C were positively correlated with FPG level and multiple regression further confirmed the same result except for HDL-C that became non-significant. Subjects in FPG3 had significantly higher ORs (ORs = 1.19) for having MetS than those in FPG1., Conclusions: In conclusion, higher FPG still had higher risk of having MetS in normoglycaemic range in elderly male. More strict FPG level control may be valuable in CVD prevention and warrants further investigations., (© 2013 John Wiley & Sons Ltd.)

The amphidromous goby Sicyopterus japonicus is distributed throughout southern Taiwan and Japan. Larvae of this freshwater fish go through a long marine stage. This migratory mode influences population genetic structure. We examined the genetic diversity, population differentiation, and demographic history of S. japonicus based on the mitochondrial DNA control region. We identified 102 haplotypes from 107 S. japonicus individuals from 22 populations collected from Taiwan and Islet Lanyu. High mean haplotype diversity (h = 0.999) versus low nucleotide diversity (θπ = 0.008) was detected across populations. There was low correspondence between clusters identified in the neighbor-joining tree and geographical region, as also indicated by AMOVA and pairwise F(ST) estimates. Both mismatch distribution analysis and Tajima's D test indicated that S. japonicus likely experienced a demographic expansion. Using a Bayesian skyline plot approach, we estimated the time of onset of the expansion of S. japonicus at 135 kyr (during the Pleistocene) and the time of stable effective population size at approximately 2.5 kyr (last glacial maximum). Based on these results, we suggest 1) a panmictic population at the oceanic planktonic larval stage, mediated by the Kuroshio current; 2) a long planktonic marine stage and long period of dispersal, which may have permitted efficient tracking of environmental shifts during the Pleistocene; and 3) a stable, constant population size ever since the last glacial maximum.

Structural allografts may be used to manage uncontained bone defects in revision total knee replacement (TKR). However, the availability of cadaver grafts is limited in some areas of Asia. The aim of this study was to evaluate the mid-term outcome of the use of femoral head allografts for the reconstruction of uncontained defects in revision TKR, focusing on complications related to the graft. We retrospectively reviewed 28 patients (30 TKRs) with Anderson Orthopaedic Research Institute (AORI) type 3 bone defects, who underwent revision using femoral head allografts and stemmed components. The mean number of femoral heads used was 1.7 (1 to 3). The allograft-host junctions were packed with cancellous autograft. At a mean follow-up of 76 months (38 to 136) the mean American Knee Society knee score improved from 37.2 (17 to 60) pre-operatively to 90 (83 to 100) (p < 0.001). The mean function score improved from 26.5 (0 to 50) pre-operatively to 81 (60 to 100) (p < 0.001). All the grafts healed to the host bone. The mean time to healing of the graft was 6.6 months (4 to 16). There have been no complications of collapse of the graft, nonunion, infection or implant loosening. No revision surgery was required. The use of femoral head allografts in conjunction with a stemmed component and autogenous bone graft in revision TKR in patients with uncontained bone defects resulted in a high rate of healing of the graft with minimal complications and a satisfactory outcome. Longer follow-up is needed to observe the evolution of the graft.

Two different types of lasing modes, vertical Fabry-Perot cavity and random lasing, were observed in ZnO epi-films of different thicknesses grown on Si (111) substrates. Under optical excitation at room temperature by a frequency tripled Nd:YVO₄ laser with wavelength of 355 nm, the lasing thresholds are low due to high crystalline quality of the ZnO epitaxial films, which act as microresonators. For the thick ZnO layer (1,200 nm), its lasing action is originated from the random scattering due to the high density of crack networks developed in the thick ZnO film. However, the low crack density of the thin film (555 nm) fails to provide feedback loops essential for random scattering. Nevertheless, even the lower threshold lasing is achieved by the Fabry-Perot cavity formed by two interfaces of the thin ZnO film. The associated lasing modes of the thin ZnO film can be characterized as the transverse Gaussian modes attributed to the smooth curved surfaces.

Background: Patients enrolled in clinical trials of advanced hepatocellular carcinoma (HCC) are usually required to have good liver reserve and organ function. However, their outcomes are still highly variable. We aimed to examine whether current staging systems can predict the survival of these highly selected patients., Methods: Patients from clinical trials involving first-line anti-angiogenic therapy were assigned to different stage groups using the American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), China integrated score, Cancer of the Liver Italian Program (CLIP) score, Chinese University Prognostic Index (CUPI), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH), Japan Integrated Staging (JIS) score, Okuda, Tokyo score, and a new staging system recently proposed. Survival prediction by the 10 systems was then compared by both univariate and multivariate analyses., Results: A total of 157 patients were selected for this study. In univariate analysis, all staging systems can predict patient survival except AJCC, BCLC, and JIS score. Concordance indexes for CLIP score, CUPI, and GETCH (0.752, 0.775, and 0.791, respectively) were significantly higher than those obtained for other staging systems. In multivariate analysis, the CLIP score and CUPI (P<0.001 and 0.009, respectively) predicted survival more accurately than did the other tested staging systems. Hepatitis B infection and poor performance status were also associated with poor survival., Conclusion: Several HCC staging systems, especially the CLIP score and CUPI, can predict prognosis of patients who are enrolled in clinical trials of advanced HCC.

High-quality m-plane orientated ZnO films have been successfully grown on m-plane sapphire by using radio frequency magnetron sputtering deposition. The introduction of a nanometer-thick, low-temperature-grown ZnO buffer layer effectively eliminates inclusions of other undesirable orientations. The structure characteristics of the ZnO epi-layers were thoroughly studied by synchrotron X-ray scattering and transmission electron microscopy (TEM). The in-plane epitaxial relationship between ZnO and sapphire follows (0002)(ZnO) [parallel] (112[overline]0)(sapphire) and (112[overline]0)(ZnO) [parallel] (0006)(sapphire) and the ZnO/sapphire interface structure can be described by the domain matching epitaxy along the [112[overline]0](ZnO) direction. The vibrational properties of the films were investigated by polarization dependent micro-Raman spectroscopy. Both XRD and micro-Raman results reveal that the obtained m-ZnO layers are under an anisotropic biaxial strain but still retains a hexagonal lattice.

Tranexamic acid (TEA), an inhibitor of fibrinolysis, reduces blood loss after routine total knee replacement (TKR). However, controversy persists regarding the dosage and timing of administration of this drug during surgery. We performed a prospective randomised controlled study to examine the optimum blood-saving effect of TEA in minimally invasive TKR. We randomly assigned 151 patients who underwent unilateral minimally invasive TKR to three groups: 1) a placebo group (50 patients); 2) a one-dose TEA group (52 patients), who received one injection of TEA (10 mg/kg) intra-operatively on deflation of the tourniquet; and 3) a two-dose TEA group (49 patients), who received two injections of TEA (10 mg/kg) given pre-operatively and intra-operatively. Total blood loss was calculated from the maximum loss of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism (VTE). The mean total blood loss was significantly higher in the placebo group than in the other two groups (1222 ml (845 to 2043) versus 1035 ml (397 to 1934) and 986 ml (542 to 1811), respectively (both p < 0.0001)). The mean blood loss was not significantly different between the one- and two-TEA groups (p = 0.148). The mean transfusion rate was higher in the placebo group than in the other two groups (22% versus 3.8% (p = 0.006) and 6.1% (p = 0.041), respectively) and there was no statistically significant difference in the mean transfusion rate between the one- and two-TEA groups (p = 0.672). Only one patient, in the two-dose group, had a radiologically confirmed deep venous thrombosis. Our prospective randomised controlled study showed that one intra-operative injection of TEA is effective for blood conservation after minimally invasive TKR.