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Background: The optimal sampling techniques for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remain unclear and have not been standardized. The aim of this study was to compare the wet-suction and dry-suction techniques for sampling solid lesions in the pancreas, mediastinum, and abdomen., Methods: This was a multicenter, crossover, randomized controlled trial with randomized order of sampling techniques. The 296 consecutive patients underwent EUS-FNA with 22G needles and were randomized in a ratio of 1:1 into two separate groups that received the dry-suction and wet-suction techniques in a different order. The primary outcome was to compare the histological diagnostic accuracy of dry suction and wet suction for malignancy. The secondary outcomes were to compare the cytological diagnostic accuracy and specimen quality., Results: Among the 269 patients with pancreatic (n = 161) and non-pancreatic (n = 108) lesions analyzed, the wet-suction technique had a significantly better histological diagnostic accuracy (84.9 % [95 % confidence interval (CI) 79.9 % - 89.0 %] vs. 73.2 % [95 %CI 67.1 % - 78.7 %]; P  = 0.001), higher specimen adequacy (94.8 % vs. 78.8 %; P  < 0.001), and less blood contamination ( P  < 0.001) than the dry-suction technique. In addition, sampling non-pancreatic lesions with two passes of wet suction provided a histological diagnostic accuracy of 91.6 %., Conclusions: The wet-suction technique in EUS-FNA generates better histological diagnostic accuracy and specimen quality than the dry-suction technique. Furthermore, sampling non-pancreatic lesions with two passes of EUS-FNA with wet suction may provide a definitive histological diagnosis when rapid on-site evaluation is not routinely available., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin., Aim: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients., Methods: We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1 st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed., Results: A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I 2 =0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I 2 =0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I 2 =0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I 2 =0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02)., Conclusion: Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Aim: The purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases., Materials and Methods: PubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk., Results: Our results indicated positive associations between periodontal disease and non-alcoholic fatty liver disease (NAFLD) (OR = 1.19, 95% CI = 1.06-1.33), liver cirrhosis (OR = 2.28, 95% CI = 1.50-3.48) and elevated transaminase level risk (OR = 1.08, 95% CI = 1.02-1.15). Moreover, tooth loss could increase NAFLD (OR = 1.33, 95% CI = 1.12- 1.56) and liver cancer risk (OR = 1.34, 95% CI = 1.04-1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR = 1.05, 95% CI = 1.01 - 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR = 2.03, 95% CI = 0.85-4.85) although there was no statistical significance., Conclusion: Periodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tumor-specific metabolic rewiring, acquired to confer a proliferative and survival advantage over nontransformed cells, represents a renewed focus in cancer therapy development. Hepatocellular carcinoma (HCC), a malignancy that has hitherto been resistant to compounds targeting oncogenic signaling pathways, represents a candidate cancer to investigate the efficacy of selectively antagonizing such adaptive metabolic reprogramming. To this end, we sought to characterize metabolic changes in HCC necessary for tumorigenesis. We analyzed gene expression profiles in three independent large-scale patient cohorts who had HCC. We identified a commonly deregulated purine metabolic signature in tumors with the extent of purine biosynthetic enzyme up-regulation correlated with tumor grade and a predictor of clinical outcome. The functional significance of enhanced purine metabolism as a hallmark in human HCC was then validated using a combination of HCC cell lines, patient-derived xenograft (PDX) organoids, and mouse models. Targeted ablation of purine biosynthesis by knockdown of the rate-limiting enzyme inosine-5'-monophosphate dehydrogenase ( IMPDH ) or using the drug mycophenolate mofetil (MMF) reduced HCC proliferation in vitro and decreased the tumor burden in vivo . In comparing the sensitivities of PDX tumor organoids to MMF therapy, we found that HCC tumors defined by high levels of IMPDH and guanosine nucleosides were most susceptible to treatment. Mechanistically, a phosphoinositide 3-kinase (PI3K)-E2F transcription factor 1 (E2F1) axis coordinated purine biosynthetic enzyme expression, deregulation of which altered the activity of mitogen-activated protein kinase/RAS signaling. Simultaneously abolishing PI3K signaling and IMPDH activity with clinically approved inhibitors resulted in greatest efficacy in reducing tumor growth in a PDX mouse model. Conclusion: Enhanced purine metabolic activity regulated by PI3K pathway-dependent activation of E2F1 promotes HCC carcinogenesis, suggesting the potential for targeting purine metabolic reprogramming as a precision therapeutic strategy for patients with HCC., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Pancreatic islet transplantation into the liver is an effective treatment for type 1 diabetes but has some critical limitations. The subcutaneous site is a potential alternative transplant site, requiring minimally invasive procedures and allowing frequent graft monitoring; however, hypoxia is a major drawback. Our previous study without scaffolding demonstrated post-transplant graft aggregation in the subcutaneous site, which theoretically exacerbates lethal intra-graft hypoxia. In this study, we introduce a clinically applicable subcutaneous islet transplantation platform using a biodegradable Vicryl mesh scaffold to prevent aggregation in a diabetic rat model. Islets were sandwiched between layers of clinically proven Vicryl mesh within thrombin-fibrin gel. In vitro, the mesh prevented islet aggregation and intra-islet hypoxia, which significantly improved islet viability. In vivo rat syngeneic islet transplantations into a prevascularized subcutaneous pocket demonstrated that the mesh significantly enhanced engraftment, as measured by assays for graft survival and function. Histological examination at 6 weeks showed well-vascularized grafts sandwiched in a flat shape between the mesh layers. The biodegradable mesh was fully absorbed by three months, which alleviated chronic foreign body reaction and fibrosis, and supported long-term graft maintenance. This simple graft shape modification approach is an effective and clinically applicable strategy for improved subcutaneous islet transplantation., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background/objective: Productivity and monetary loss due to migraine in the workplace may be substantial. This study aimed to determine the impact of migraine on productivity and monetary lost among employees in the banking sectors, in a multiethnic middle income country., Methods: A cross-sectional online survey was conducted among employees in two multinational banks in Malaysia between April and July 2019. Screening for migraine was conducted using the self-administered ID-Migraine™ questionnaire. Migraine-related disability (MIDAS) and headache frequency were recorded. Impact of migraine on work productivity and activities were evaluated using the Work Productivity and Activity Impairment (WPAI) questionnaire., Results: Of the 1268 employees who submitted complete responses, 47.2% (n = 598) were screened positive for migraine. Strikingly, the mean percent productivity loss at work (presenteeism) was almost 20-fold higher than the mean percent work time missed due to migraine (absenteeism) (39.1% versus 1.9%). The mean percent productivity loss in regular activity (activity impairment) and overall work productivity loss (work impairment) was 38.4% and 39.9%, respectively. It was also found that the costs related to presenteeism (MYR 5392.6) (US$1296) was 3.5-fold higher than absenteeism (MYR1,548.3) (US$370). Highest monetary loss related to presenteeism was reported in migraineurs with frequency of headache of above 3 days (MYR 25,691.2) (US$6176), whereas highest monetary loss related to absenteeism was reported in migraineurs with MIDAS grade IV (MYR 12,369.1) (US$2973). Only 30% of migraineurs of MIDAS grade IV reported taking prescribed medication. Notably, a vast majority (96%) of migraineurs who had three or lower episodes of migraine per month did not seek treatment., Conclusion: The significant impact of migraine on work productivity and regular activity, appears to lead to substantial monetary loss attributed to not only absenteeism, but more importantly to presenteeism. This study also highlights the unmet needs in migraine management among employees in the banking sector.

Hyperuricemia has been associated with chronic kidney disease (CKD) progression. The antihyperuricemic febuxostat's potential renoprotective effect has been demonstrated in stage 1-3 CKD. Large-scale studies comparing the renoprotective potential of febuxostat and allopurinol in advanced CKD are lacking. We exclusively selected 6,057 eligible patients with predialysis stage 5 CKD prescribed either febuxostat or allopurinol using the National Health Insurance Research Database in Taiwan during 2012-2015. There were 69.57% of allopurinol users and 42.01% febuxostat users who required long-term dialysis (P < 0.0001). The adjusted hazard ratio (HR) of 0.65 (95% confidence interval (CI) 0.60-0.70) indicated near 35% lower hazards of long-term dialysis with febuxostat use. The renal benefit of febuxostat was consistent across most patient subgroups and/or using the propensity score-matched cohort. The adjusted HR was 0.66 (95% CI, 0.61-0.70) for long-term dialysis or death. In conclusion, lower risk of progression to dialysis was observed in predialysis stage 5 CKD febuxostat users without compromising survival., (© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Very few studies have been published on the hemodynamic changes associated with spinal anesthesia induced with ropivacaine during cesarean deliveries in preeclamptic women., Aim: To record and analyze hemodynamic data in women with preeclampsia undergoing cesarean delivery after spinal anesthesia induced with ropivacaine., Methods: Ten eligible women with preeclampsia were enrolled in this prospective observational study. Spinal anesthesia was performed with 2.4 mL of 0.5% ropivacaine. Hemodynamic changes were then analyzed at multiple time points. The hemodynamic responses to vasopressor interventions and uterotonic agents, as well as maternal and neonatal outcomes were also recorded., Results: Stable hemodynamic trends were observed in this study. Cardiac output (CO) and stroke volume increased mildly during surgery. In contrast, mean arterial pressure and systemic vascular resistance showed a moderate decrease from induction until the end of surgery. Central venous pressure dramatically increased after delivery. Oxytocin administration was associated with the most significant hemodynamic fluctuations during surgery, namely, an increase in CO and heart rate. Phenylephrine intervention was only required in three patients, and caused an increase in mean arterial pressure and systemic vascular resistance along with a decrease in heart rate, stroke volume, and CO. No maternal and neonatal complications were observed during this study, except transient episodes of hypotension., Conclusion: Spinal anesthesia for caesarian delivery with ropivacaine in women with preeclampsia is linked to modest hemodynamic changes of no clinical significance in this study. Careful cardiovascular monitoring is still recommended, particularly after the delivery of the fetus or the use of oxytocin., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: This study aimed to elucidate the regulatory role and molecular regulation mechanism of miR-130b gene in the process of invasion and metastasis of hepatocarcinoma, and provide a theoretical basis for seeking of effective prevention and treatment of new targets for hepatocellular carcinoma. Materials and methods: The expression level of miR-130b gene in hepatocarcinoma tissues was determined by qRT-PCR. The biological function and mechanism of miR-130b gene were verified by cell and animal models, and the target gene was verified by double luciferase assay. Results: In the liver cancer tissues of patients with metastasis, the expression level of miR-130b gene was increased, and the difference was significantly significant ( p  < 0.05). Evaluation of independent risk factors for overall survival showed significant difference ( p  < 0.01). Up-regulation of miR-130b in MHCC97L- subpopulation cells significantly enhanced the invasion and migration ability, and the difference was statistically significant ( p  < 0.05). The invasion and migration ability of MHCC97H + subpopulation cells with increased expression of miR-130b was significantly decreased, and the difference was notably significant ( p  < 0.05). When the expression of miR-130b in MHCC97H + subpopulation cells was inhibited, the expressions of Notch-Dll1 and SOX2, Nanog and E2F3 proteins in transplanted tumor tissues were significantly higher than those in other groups ( p  < 0.05). When miR-130b in MHCC97L- subpopulation cells was up-regulated, the expressions of Notch-Dll1 and Bcl-2, CCND1, Nanog and MET proteins in transplanted tumor tissues were significantly increased than those in other groups ( p  < 0.05). The prediction results of bioinformatics data suggest that the target gene of miR-130b may be Notch-Dll1 gene. The experiment of luciferase reporter gene confirmed that miR-130b gene can be inhibited and contains fluorescent reporter gene with complementary binding site, lost activity. Conclusion: The miR-130b gene can inhibit the protein expression of Notch-Dll1, and it can promote the invasion and metastasis of liver cancer cells.

Escherichia coli is a common inhabitant of the human microbiota and a beacon model organism in biology. However, an understanding of its signaling systems that regulate population-level phenotypes known as quorum sensing remain incomplete. Here, we define the structure and biosynthesis of autoinducer-3 (AI-3), a metabolite of previously unknown structure involved in the pathogenesis of enterohemorrhagic E. coli (EHEC). We demonstrate that novel AI-3 analogs are derived from threonine dehydrogenase (Tdh) products and "abortive" tRNA synthetase reactions, and they are distributed across a variety of Gram-negative and Gram-positive bacterial pathogens. In addition to regulating virulence genes in EHEC, we show that the metabolites exert diverse immunological effects on primary human tissues. The discovery of AI-3 metabolites and their biochemical origins now provides a molecular foundation for investigating the diverse biological roles of these elusive yet widely distributed bacterial signaling molecules., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Given the importance of undergrowth vegetation to plantation ecosystem, this study analyzed the effects of three kinds of understory management measures, including understory preservation, understory removal, and interplanting, on the soil bacterial diversity, community structure and relative abundance under large diameter timber plantation of Cunninghamia lanceolata using high-throughput sequencing technology. The relationship between soil physical and chemical properties and bacterial community diversity were analyzed. The results showed that Chao1, Ace and Shannon indices of soil bacterial communities of understory preservation were higher than those of understory removal and interplanting. Actinobacteria, Acidobacteria and Chloroflexi were the dominant bacteria groups in the soil of C. lanceolata plantation. Compared with understory removal and interplanting, the relative abundance of Proteobacteria, Planctomycetes, Firmicutes and Verrucomicrobia in the soil of understory preservation was relatively high, while that of Actinobacteria, Acidobacteria and Chloroflexi was relatively low. There were significant differences in the relative abundance of Firmicutes, Planctomycetes, Verrucomicrobia, Parcubacteria and Actinobacteria among three understory management measures. The contents of moisture, total nitrogen, total phosphorus, hydrolyzed nitrogen and available phosphorus in the soil were important factors affecting soil bacterial community structure. Soil bacterial diversity indices had significant positive correlation with the contents of total nitrogen, total phosphorus, total potassium, hydrolyzed nitrogen and available potassium in the soil.

We study whether humans or machine learning (ML) classification models are better at classifying scientific research abstracts according to a fixed set of discipline groups. We recruit both undergraduate and postgraduate assistants for this task in separate stages, and compare their performance against the support vectors machine ML algorithm at classifying European Research Council Starting Grant project abstracts to their actual evaluation panels, which are organised by discipline groups. On average, ML is more accurate than human classifiers, across a variety of training and test datasets, and across evaluation panels. ML classifiers trained on different training sets are also more reliable than human classifiers, meaning that different ML classifiers are more consistent in assigning the same classifications to any given abstract, compared to different human classifiers. While the top five percentile of human classifiers can outperform ML in limited cases, selection and training of such classifiers is likely costly and difficult compared to training ML models. Our results suggest ML models are a cost effective and highly accurate method for addressing problems in comparative bibliometric analysis, such as harmonising the discipline classifications of research from different funding agencies or countries., (© The Author(s) 2020.)

Background: The impact of preoperative glycemic control on the survival outcomes of patients undergoing a radical hysterectomy (RH) for cervical cancer has not been investigated., Patients and Methods: We reviewed patients who underwent a type III RH for cervical cancer between January 2004 and June 2011 in our institution., Results: A total of 431 patients were included and 83 (19.3%) were diagnosed with diabetes mellitus (DM). Poorly controlled DM (preoperative hemoglobin A1c [HbA1c] ≥7.0%) was observed in 49 (59.0%) diabetic patients. Compared to patients without DM and diabetic patients with good glycemic control (preoperative HbA1c <7.0%), diabetic patients with poor glycemic control had significantly higher risks of tumor recurrence, cervical cancer-specific death, and overall death. In multivariate analysis, DM with poor glycemic control independently predicted recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). We excluded patients without DM and performed a sensitivity analysis. When HbA1c levels were treated as a dichotomous variable, preoperative HbA1c ≥7.0% was independently associated with RFS, CSS, and OS. When HbA1c level was treated as a continuous variable, it remained an independent predictor of RFS, CSS, and OS., Conclusion: DM with poor glycemic control prior to RH was significantly associated with an increased risk of recurrence and mortality in cervical cancer patients. These results underscore the importance of intensive glycemic control and close follow-up for diabetic patients., (© 2019 S. Karger AG, Basel.)

Purpose: Liver fibrosis is the hallmark of chronic nonalcoholic steatohepatitis (NASH) and is characterised by the excessive deposition of extracellular matrix proteins. Early detection and accurate staging of liver fibrosis is critically important for patient management. One of the earliest pathological markers in NASH is the activation of hepatic stellate cells (HSCs) which may be exploited as a marker of fibrogenesis. Activated HSCs secreting factors such as integrin α v β 3 propagate fibrosis. The purpose of the current study was to assess the utility of the integrin α v β 3 imaging agent [ 18 F]FtRGD for the early detection of fibrosis in a diet-induced model of NASH longitudinally using PET imaging., Procedures: Mice were fed with either standard chow diet (SD), high-fat diet (HFD), or a choline-deficient, L-amino acid-defined high-fat fibrogenic diet (CDAHFD) to mimic the clinical pathology of liver disease and followed longitudinally for 10 weeks to assess the development of liver fibrosis using [ 18 F]FtRGD positron emission tomography (PET) imaging. Standard blood biochemistry, histological measures, and qPCR were used to quantify integrin α v β 3 , smooth muscle actin, and collagen types 1 and 6 to assess the extent of NASH pathology and accurately stage liver fibrosis., Results: The CDAHFD fibrogenic diet predictably developed hepatic inflammation and steatosis over the 10 weeks studied with little NASH pathology detected in high fat diet-treated animals. Stage 1 fibrosis was detected early by histology at day 21 and progressed to stage 2 by day 35 and stage 3 by day 56 in mice fed with CDAHFD diet only. Noninvasive imaging with [ 18 F]FtRGD correlated well with integrin α v β 3 and was able to distinguish early mild stage 2 fibrosis in CDAHFD animals compared with standard chow diet-fed animals at day 35. When compared with high fat diet-fed animals, [ 18 F]FtRGD was only able to distinguish later moderate stage 2 fibrosis in CDAHFD animals at day 49., Conclusions: The diet-induced progression of liver fibrosis was confirmed using histology and correlated well with the mRNA of integrin α v β 3 and extracellular matrix protein expression. [ 18 F]FtRGD showed very good correlation between liver uptake and integrin α v β 3 expression and similar detection sensitivity to the current clinical gold standard modalities for staging of liver fibrosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 S. V. Hartimath et al.)

Although in recent years there has been an increased awareness of the widespread nature of biofluorescence in the marine environment, the diversity of the molecules responsible for this luminescent phenotype has been mostly limited to green fluorescent proteins (GFPs), GFP-like proteins, and fluorescent fatty acid-binding proteins (FABPs). In the present study, we describe a previously undescribed group of brominated tryptophan-kynurenine small molecule metabolites responsible for the green biofluorescence in two species of sharks and provide their structural, antimicrobial, and spectral characterization. Multi-scale fluorescence microscopy studies guided the discovery of metabolites that were differentially produced in fluorescent versus non-fluorescent skin, as well as the species-specific structural details of their unusual light-guiding denticles. Overall, this study provides the detailed description of a family of small molecules responsible for marine biofluorescence and opens new questions related to their roles in central nervous system signaling, resilience to microbial infections, and photoprotection., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer, the most common invasive cancer of women, is a malignant neoplasm and the second main cause of cancer death. Resistance to paclitaxel (Taxol), one of the frequently used chemotherapy agents for breast cancer, presents a major clinical challenge. Recent studies revealed that metabolic alterations of cancer cells play important roles in chemo-resistance., Materials and Methods: In this study, Human breast cancer cells, BT474, SKBR3 and MCF7 were used to study the causal relationship between the lactate exporter, MCT1 (SLC16A1)-modulated glucose metabolism and Taxol resistance of breast cancer cells. Taxol resistant breast cancer cells were established. The intracellular lactate and extracellular lactate levels as well glucose uptake and oxygen consumption were measured. MicroRNA-124 expressions were detected by qRT-PCR from both breast cancer patient samples and breast cancer cells. Target of miR-124 was predicted and verified by Western blot and luciferase assay. An xenograft mice model was established and evaluated for the in vivo tumor therapeutic effects of MCT1 inhibitor plus microRNA-124 treatments., Results: Low toxic Taxol treatments promoted cellular glucose metabolism and intracellular lactate accumulation with upregulated lactate dehydrogenase-A (LDHA) and MCT1 expressions. By establishing Taxol resistant breast cancer cell line, we found Taxol resistant cells exhibit upregulated LDHA and MCT1 expressions. Furthermore, glucose consumption, lactate production and intracellular ATP were elevated in Taxol resistant MCF7 cells compared with their parental cells. The miR-124, a tumor suppressive miRNA, was significantly downregulated in Taxol resistant cells. Luciferase assay and q-RT-PCR showed MCT1 is a direct target of miR-124 in both breast cancer cell lines and patient specimens. Moreover, co-treatment of breast cancer cells with either MCT1 inhibitor or miR-124 plus Taxol led to synergistically cytotoxic effects. Importantly, based on in vitro and in vivo results, inhibition of MCT1 significantly sensitized Taxol resistant cells. Finally, rescue experiments showed restoration of MCT1 in miR-124 overexpressing cells promoted Taxol resistance., Conclusions: This study reveals a possible role of miRNA-214-mediated Taxol resistance, contributing to identify novel therapeutic targets against chemoresistant breast cancers., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Ulcerative colitis, one of the most important inflammatory bowel diseases, affects millions of people worldwide. The aim of this study was to investigate the effects of Saikosaponin A on dextran sulfate sodium (DSS)-induced colitis in mice. The mice were treated with 2.5% DSS for 5 d to induce acute colitis. Saikosaponin A was given 3 d before and during DSS treatment by intragastric administration. The results showed that Saikosaponin A significantly inhibited DSS-induced body weight loss and shortening of colon length. DSS-induced colonic histological changes and MPO activity were also prevented by treatment of Saikosaponin A. The levels of TNF-α and IL-1ß were increased by DSS and dose-dependently inhibited by Saikosaponin A. Furthermore, Saikosaponin A significantly inhibited DSS-induced NF-κB activation and up-regulated the expression of LXRα. Taken together, our results indicated that Saikosaponin A had protective effects against DSS-induced colitis. Saikosaponin A protected DSS-induced colitis through inhibiting inflammatory response., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanosize semiconductors have been used as active sensitizers for the application of quantum dot-sensitized solar cells (QDSSC). "Green" sensitizers are introduced as an alternative for the toxic Cd and Pb based compounds. In this work, Bi₂S₃ quantum dots (QDs) were fabricated and used as sensitizers in QDSSC. QDs were grown on TiO₂ electrode via solution dipping process. Although the performance of "green" QDSSC is not as high as that of CdS or CdSe based QDSSCs, its performance can be enhanced with post heat treatment. The effect is dependent on the heat treatment temperature profile where gradual increase of sintering temperature is preferred. The effects of post heat treatment on Bi₂S₃ sensitized TiO₂ electrodes are investigated and discussed.

Background: Numerous patients suffer from chronic wounds and wound infections nowadays. Until now, the care for wounds after surgery still remain a tedious and challenging work for the medical personnel and patients. As a result, with the help of the hand-held mobile devices, there is high demand for the development of a series of algorithms and related methods for wound infection early detection and wound self monitoring., Methods: This research proposed an automated way to perform (1) wound image segmentation and (2) wound infection assessment after surgical operations. The first part describes an edge-based self-adaptive threshold detection image segmentation method to exclude nonwounded areas from the original images. The second part describes a wound infection assessment method based on machine learning approach. In this method, the extraction of feature points from the suture area and an optimal clustering method based on unimodal Rosin threshold algorithm that divides feature points into clusters are introduced. These clusters are then merged into several regions of interest (ROIs), each of which is regarded as a suture site. Notably, a support vector machine (SVM) can automatically interpret infections on these detected suture site., Results: For (1) wound image segmentation, boundary-based evaluation were applied on 100 images with gold standard set up by three physicians. Overall, it achieves 76.44% true positive rate and 89.04% accuracy value. For (2) wound infection assessment, the results from a retrospective study using confirmed wound pictures from three physicians for the following four symptoms are presented: (1) Swelling, (2) Granulation, (3) Infection, and (4) Tissue Necrosis. Through cross-validation of 134 wound images, for anomaly detection, our classifiers achieved 87.31% accuracy value; for symptom assessment, our classifiers achieved 83.58% accuracy value., Conclusions: This augmentation mechanism has been demonstrated reliable enough to reduce the need for face-to-face diagnoses. To facilitate the use of this method and analytical framework, an automatic wound interpretation app and an accompanying website were developed., Trial Registration: 201505164RIND , 201803108RSB .

Avian infectious bronchitis virus (IBV) causes considerable economic losses in the poultry industry worldwide, including Taiwan. IBV is among the most important pathogens in chickens, and it spreads rapidly among flocks. In addition to dozens of known serotypes, new viral variants have emerged due to the viral evolution and antigenic variation in IBVs. Therefore, the development of a sensitive, specific, and easily performed assay is crucial for the rapid detection and surveillance of IBV infections. A rapid and simple immunochromatographic strip (ICS) was developed in this study by employing monoclonal antibodies against spike and nucleocapsid proteins of IBV as the tracer and the capture antibody. The ICS showed high specificity in detecting IBV antigens, including several IBV genotypes and novel variants, as opposed to three other common avian respiratory viruses. The detection limit of the strip reached 10 4.4 50% embryo-infective dose. Moreover, in the experimental chicken model, the strip test demonstrated consistency in detecting IBV with RT-PCR gene detection. Taken together, this antigen detection strip has the potential to serve as an on-farm rapid test for IBV; therefore, it may facilitate surveillance and control of the disease.

The static magnetic field (SMF) in human exposure has become a health risk concern, especially with respect to prolonged exposure. The International Commission on Non-Ionizing Radiation Protection (ICNIRP) has been considering cell or animal models to be adopted to estimate the possible human health impacts after such exposure. The medaka fish is a good animal model for human-related health assessment studies; this paper examines both the embryo development and behavioral responses in medaka fish in vivo to long-term SMF exposure at the mT level. SMF exposure was examined for the complete developmental period of embryos until hatched; the embryos were monitored and recorded every 24 h for different morphological abnormalities in their developmental stages. The behavioral response of adult fish was also examined by analyzing their swimming velocities and positioning as compared with that of the control group. It was observed that there were no impacts on embryo development under prolonged exposure up to about 100 mT while the swimming behavior of the adult fish under exposure was different to the control group-the swimming movement of the treated group was more static, with an average velocity of 24.6% less as observed over a 24-h duration.

Background/purpose: Pleurodesis with biomaterial implant is an emerging treatment method for pleural diseases. However, the ideal biomaterial or the optimal form for the common diseases is still under investigation. In our previous study, Poly-ε-caprolactone (PCL) membrane produces significant pleurodesis in New Zealand White rabbit animal models., Methods: We investigate the Poly-ε-caprolactone (PCL) gel pleurodesis by animal models using New Zealand White rabbits, which were sacrificed for examination after one month. Thirty-Six New Zealand White rabbits were randomized into three groups equally to undergo procedures. Gross pleurodesis scoring was evaluated. Additionally, inflammation and fibrosis scoring were done under microscopic evaluation, as well as Western blot analysis., Results: Gross evaluation of pleurodesis score revealed that lower concentrated PCL gel (10%) produced moderate pleural adhesion, while higher concentrated PCL gel (25%) showed significantly higher pleurodesis scores. (P < 0.05) Control group with thoracostomy alone produced almost no pleurodesis (P < 0.05). Western blot showed fibronectin expression was more evident in the 25% PCL gel than 10% one., Conclusion: PCL gel induced significant degree of pleurodesis in the rabbits. The 25% PCL gel produces more intensive adhesion than 10% one. Fibronectin plays an important role in the process of pleurodesis. Further study is required for the clinical application of the promising biomaterial with gel form., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Obesity increases the risk of hepatocellular carcinoma (HCC), but precise identification and characterization of druggable oncogenic pathways that contribute to the progression of NAFLD to HCC, and hence to the increased incidence and aggressiveness of HCC in obese individuals is lacking. In this regard, we demonstrate that the Indian Hedgehog (Ihh) signaling pathway is upregulated in the fatty livers of mice consuming a high fat diet, and furthermore sustained in HCC tumors specifically within the context of a NAFLD microenvironment. Using a diet-induced mouse model of HCC wherein only obese mice develop HCC, targeted ablation of hepatocyte-secreted Ihh results in a decreased tumor burden and lower grade tumors. Ihh activation regulates the transdifferentiation of ciliated stellate cells and proliferation of Epcam + ductal cells to promote fibrosis. Mechanistically, increased expression of hitherto uncharacterized effectors of Hh pathway, namely Myc and Tgf-β2 is critical to the observed physiology. This pro-tumorigenic response is driven by increased expression of Wnt5a to effect a poorly-differentiated and invasive tumor phenotype. Wnt5a secreted from activated stellate cells act on Ror2-expressing hepatocytes. We further demonstrate that Wnt5a expression is also elevated in poorly-differentiated HCC cells, suggesting that these ligands are also able to function in an autocrine positive feedback manner to sustain poorly-differentiated tumors. Taken together, our study provides a mechanistic understanding for how Ihh signaling promotes HCC tumorigenesis specifically in obese mice. We propose that therapeutic targeting of the Hh pathway offers benefit for patients with dietary / NAFLD-driven steatotic HCC.

To further dissect the mechanism of salt tolerance in Malus, the comparison was made regarding the differences between the salt-tolerant and salt-sensitive species in sodium accumulation and extrusion capability in the roots and stem base as well as the sodium re-transportation from shoot to roots by using 22 Na labeling-based feeding of leaves and roots-split experiments. The results demonstrated that the salt-tolerant Malus species could accumulate more 22 Na in the main roots, lateral roots, stem base phloem and xylem, and extrude more sodium out than the salt-sensitive one. In addition, the salt-tolerant Malus species had the higher sodium re-transportation rate from shoot to roots. Altogether, it is concluded that the stronger sodium accumulation and extrusion in the roots and the stronger sodium re-transportation from shoot to roots in the salt-tolerant species play important roles in salt tolerance of Malus species., (Copyright © 2019. Published by Elsevier Masson SAS.)

Islet transplantation is a promising treatment for type-1 diabetes; however, donor shortage is a concern. Even when a pancreas is available, low islet yield limits the success of transplantation. Islet culture enables pooling of multiple low-yield isolations into an effective islet mass, but isolated islets rapidly deteriorate under conventional culture conditions. Oxygen (O2) depletion in the islet core, which leads to central necrosis and volume loss, is one of the major reasons for this deterioration., Methods: To promote long-term culture of human islets in PIM-R medium (used for islet research), we adjusted temperature (12°C, 22°C, and 37°C) and O2 concentration (21% and 50%). We simulated the O2 distribution in islets based on islet O2 consumption rate and dissolved O2 in the medium. We determined the optimal conditions for O2 distribution and volume maintenance in a 2-week culture and assessed viability and insulin secretion compared to noncultured islets. In vivo islet engraftment was assessed by transplantation into diabetic nonobese diabetic-severe combined immunodeficiency mouse kidneys. We validated our results using CMRL 1066 medium (used for clinical islet transplantation)., Results: Simulation revealed that 12°C of 50% O2 PIM-R culture supplied O2 effectively into the islet core. This condition maintained islet volume at greater than 90% for 2 weeks. There were no significant differences in viability and function in vitro or diabetic reversal rate in vivo between 2-week cultured and noncultured islets. Similar results were obtained using CMRL 1066., Conclusions: By optimizing temperature and O2 concentration, we cultured human islets for 2 weeks with minimal loss of volume and function.

Background/purpose: Far-infrared (FIR) therapy is a safe and noninvasive source for medical applications. Animal study has shown the effects of FIR in promoting nerve repair. However, the cellular mechanism is not well known. Nerve growth factor (NGF) treated neuron-like PC12 cells for neurite outgrowth have been widely employed as the in vitro model for neural regeneration., Methods: In this study, we tried to evaluate the potential of FIR in promoting neurite outgrowth and related mechanism by using NGF-treated neuron-like PC12 cells as a cellular model. We found that FIR could promote neurites outgrowth of neuron-like PC12 cells at earlier culture period., Results: The neurite outgrowth-enhancing effect of FIR irradiation was more obvious when lower NGF concentration (1 ng/ml and 10 ng/ml) was added into the medium. We also found that FIR had no thermal effects on culture medium. The effects of FIR in promoting neurite outgrowth were dose dependent, and higher power density of FIR provided more effects for improving neurite outgrowth. The mechanism of FIR in promoting neurite outgrowth was through AKT1 pathway., Conclusion: The effects of FIR irradiation on promoting neurite outgrowth and neural regeneration of NGF-treated neuron-like PC12 cells are dose dependent and through activation of AKT1 phosphorylation. This study provided important information for understanding the cellular mechanism of FIR in promoting neurite outgrowth and possible neural regeneration for further clinical applications., (Copyright © 2018. Published by Elsevier B.V.)

Background: The prognostic value of preoperative anemia in gastric cancer remains unclear. Therefore, the purpose of the present study is to evaluate the prognostic value of preoperative anemia in gastric cancer., Methods: We searched Embase and PubMed databases for relevant studies from inception to March 2018. The prognostic value of preoperative anemia in gastric cancer was determined by calculating the hazard ratio (HR) and the corresponding 95% confidence interval (CI) as effect measures. A random effect model was used in cases in which there was significant heterogeneity; otherwise, a fixed effect model was used. Statistical analyses were performed using Stata software., Results: Seventeen studies involving 13,154 gastric cancer patients were included. The estimated rate of preoperative anemia was 36% (95%CI = 27-44%). The overall survival of preoperative anemia was poor (HR = 1.33, 95%CI = 1.21-1.45). Moreover, disease-free survival was significantly lower in patients with preoperative anemia compared with those without this condition (HR = 1.62, 95%CI = 1.13-2.32). These findings were corroborated by the results of subgroup analyses., Conclusions: The results indicate that preoperative anemia predicts poor prognosis in gastric cancer, including overall survival and disease-free survival. Therefore, preoperative anemia may be a convenient and cost-effective blood-derived prognostic marker for gastric cancer.

Cell transplantation is a promising treatment for complementing lost function by replacing new cells with a desired function, e.g. pancreatic islet transplantation for diabetics. To prevent cell obliteration, oxygen supply is critical after transplantation, especially until the graft is sufficiently re-vascularized. To supply oxygen during this period, we developed a chemical-/electrical-free implantable oxygen transporter that delivers oxygen to the hypoxic graft site from ambient air by diffusion potential. This device is simply structured using a biocompatible silicone-based body that holds islets, connected to a tube that opens outside the body. In computational simulations, the oxygen transporter increased the oxygen level to >120 mmHg within grafts; in contrast, a control device that did not transport oxygen showed <6.5 mmHg. In vitro experiments demonstrated similar results. To test the effectiveness of the oxygen transporter in vivo, we transplanted pancreatic islets, which are susceptible to hypoxia, subcutaneously into diabetic rats. Islets transplanted using the oxygen transporter showed improved graft viability and cellular function over the control device. These results indicate that our oxygen transporter, which is safe and easily fabricated, effectively supplies oxygen locally. Such a device would be suitable for multiple clinical applications, including cell transplantations that require changing a hypoxic microenvironment into an oxygen-rich site.

A number of previous studies have reported that numerous long non-coding RNAs (lncRNAs) are dysregulated in gastric cancer (GC) and are involved in a series of biological and pathological processes. Total RNA was extracted from the cancerous tissues and matched normal adjacent tissues (NATs) of 96 patients with GC. The expression level of AB007962, a novel lncRNA, was determined by reverse transcription-quantitative polymerase chain reaction. The association between AB007962 expression levels and clinicopathological features were analyzed. Kaplan-Meier curves were also constructed in order to evaluate prognosis. Finally, publicly accessible data from The Cancer Genome Atlas was used to further verify the expression levels and clinical significance of AB007962. In conclusion, it was determined that the expression level of AB007962 was significantly reduced, compared with matched NATs in GC tissues (P=0.003). Survival analysis indicated that patients with intestinal-type GC with a reduced expression of AB007962 had a reduced prognosis, compared with those with an increased expression. AB007962 may be involved in the progression of GC and act as a novel prognostic biomarker for patients with GC, particularly in intestinal-type GC.

Group A Streptococcus (GAS; Streptococcus pyogenes ) causes a wide range of infections, including pharyngitis, impetigo, and necrotizing fasciitis, and results in over half a million deaths annually. GAS ScpC (SpyCEP), a 180-kDa surface-exposed, subtilisin-like serine protease, acts as an essential virulence factor that helps S. pyogenes evade the innate immune response by cleaving and inactivating C-X-C chemokines. ScpC is thus a key candidate for the development of a vaccine against GAS and other pathogenic streptococcal species. Here, we report the crystal structures of full-length ScpC wild-type, the inactive mutant, and the ScpC-AEBSF inhibitor complex. We show ScpC to be a multi-domain, modular protein consisting of nine structural domains, of which the first five constitute the PR + A region required for catalytic activity. The four unique C-terminal domains of this protein are similar to collagen-binding and pilin proteins, suggesting an additional role for ScpC as an adhesin that might mediate the attachment of S. pyogenes to various host tissues. The Cat domain of ScpC is similar to subtilisin-like proteases with significant difference to dictate its specificity toward C-X-C chemokines. We further show that ScpC does not undergo structural rearrangement upon maturation. In the ScpC-inhibitor complex, the bound inhibitor breaks the hydrogen bond between active-site residues, which is essential for catalysis. Guided by our structure, we designed various epitopes and raised antibodies capable of neutralizing ScpC activity. Collectively, our results demonstrate the structure, maturation process, inhibition, and substrate recognition of GAS ScpC, and reveal the presence of functional domains at the C-terminal region., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The Hippo tumor suppressor pathway is an important regulator of cell proliferation and apoptosis, and signal transduction occurs through phosphorylation of the effector protein TAZ by the serine/threonine kinase LATS1/2. Here, we report the biophysical and computational studies to characterize the interaction between TAZ and LATS1/2 through WW domain-PPxY motif binding. We show that the TAZ WW domain exhibits a binding preference for the second of the two PPxY motifs of LATS1 in vitro. We modelled the structure of the domain in complex with LATS1 PPxY2 peptide and, through molecular dynamics simulations, show that WW domain-PPxY2 complex is stable with some flexibility in the peptide region. Next, we predict and verify that L143 and T150 of the WW domain are important for TAZ binding with the PPxY2 peptide using mutational and isothermal titration calorimetric studies. Furthermore, we suggest that the electrostatic potential of charged residues within the binding pocket may influence the ligand affinity among otherwise highly similar WW domains., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Realization of shape memory process in polymeric hydrogels at ambient condition is a significant development to shape memory materials. The sound understanding of the dynamic shape memory process is fundamentally important but limited. Here, a novel shape memory hydrogel with simultaneously switchable fluorescence behavior is developed. The hydrogel is prepared by incorporating a pH-responsive fluorescent molecule, perylene tetracarboxylic acid, into chitosan-based hydrogel, and the assembly and disassembly of chitosan chains into microcrystals upon the trigger of pH are applied as reversible crosslinks to achieve shape memory effect. Therefore, the formation and disassociation of microcrystalline chitosan, and the switchable fluorescence performance happen concurrently, which bring convenience to monitoring the shape memory process by fluorescent imaging. Moreover, the erasable fluorescence behavior also gives the hydrogel potential applications in information storage., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: A plethora of new biomaterials and dedicated rib fixator implant systems have been introduced into the field of chest wall reconstruction. The aim of our study is to evaluate the surgical outcomes of a novel combination of the anatomically contoured titanium rib implant and porcine dermal collagen patch for chest wall reconstruction., Methods: We performed a retrospective review of eight consecutive patients who underwent chest wall resection and reconstruction between January 2014 to August 2015 in a single institution. MatrixRib Fixation System and Permacol Surgical Implant were utilized to achieve chest wall reconstruction., Results: The indication for reconstruction was malignant infiltration in 50% of patients. Three other subjects (37.5%) had chest wall resections to achieve adequate and safe surgical exposure. One patient had a right lung apical mycetoma with chest wall invasion. All patients underwent lung resections with the removal of 2 to 6 (median 3) ribs. Reconstruction was performed using the MatrixRib system, with a median of 2.5 (range, 2-4) ribs fixed in each patient. There was no post-operative mortality. One patient had a superficial wound infection which resolved with one week of oral antibiotics. Upon discharge, the pain scores were near zero with minimal analgesic requirements. None of the patients required repeat surgery or removal of their implants., Conclusions: Our early experience indicates that the combination of the MatrixRib system and Permacol patch for chest wall reconstruction is safe and feasible with promising results in terms of anatomical restoration of the chest wall mechanics, infection and pain., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Although shape memory polymers have been highlighted widely and developed rapidly, it is still a challenging task to realize complex temporary shapes automatically in practical applications. Herein, a novel shape memory hydrogel with the ability of self-deformation is presented. Through constructing an anisotropic poly(acrylic acid)-polyacrylamide (PAAc-PAAm) structure, the obtained hydrogel exhibits stable self-deformation behavior in response to pH stimulus, and the shapes that formed automatically can be fixed by the coordination between carboxylic groups and Fe 3+ ; therefore, self-deformation and shape memory behaviors are integrated in one system. Moreover, the magnitude of auto-deformation and shape memory could be adjusted with the concentration of corresponding ions, leading to programmable shape memory and shape recovery processes., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet ( p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²). Conclusion : We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of nonsmall cell lung cancer (NSCLC) predominantly reported in East Asia. We aimed to evaluate clinical characteristics, diagnosis, treatment, and prognosis of PPLELC in Singapore., Methods: Retrospective review of all patients diagnosed with PPLELC at our center between 2000 and 2014., Results: All 28 patients were Chinese, 67.9% were female, and the median age was 58 years (range37-76 years). Majority (89.3%) were never smokers and 53.6% asymptomatic at diagnosis. About 28.6% presented with Stage I/II disease, 25% had Stage III disease, and 46.4% had Stage IV disease. All patients with Stage I/II disease underwent lobectomy without adjuvant treatment. Four out of 7 patients with Stage III disease underwent surgery with or without adjuvant therapy while the rest received chemoradiation. Twelve out of 13 patients with Stage IV disease received chemotherapy with or without radiotherapy. At the end of 2016, survival data were available for all 28 patients. Two-year survival rates for Stage I/II, Stage III, and Stage IV disease were 100%, 85.7%, and 61.5%, respectively, while survival was 100%, 85.7%, and 9.6%, respectively, at five years., Conclusion: The majority (46.4%) of patients presented with metastatic disease. For those with Stage I-III disease, 5-year survival for PPLELC was better than other NSCLC subtypes. Multimodality treatment including surgery could be considered in locally advanced disease. In Stage IV disease, it tended to approximate that of NSCLC., Competing Interests: There are no conflicts of interest.

In breast cancer 1 (BRCA) gene mutation carriers, mastectomy is still the mainstay of treatment for breast cancers due to the increased risk of local recurrence. It is performed as a therapeutic, as well as prophylactic procedure. However, mastectomy with removal of nipple areolar complex (NAC) is associated with adverse cosmetic outcome. NAC sparing mastectomy (NSM), which results in better cosmetic outcome, has been performed in non-BRCA mutation carriers. While studies have shown that NSM is a oncologically safe in sporadic breast cancers, its application in BRCA mutation carriers is still controversial. Here we review the existing evidence of NSM and its application in BRCA mutation carriers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study examined vegetable and fruit (VF) consumption rate and its associated factors among Chinese adults., Methods: Nationally representative data from the 2013 China Chronic Disease Surveillance survey were used. Dietary intake data, including VF consumption during the last 12 months, were collected. All analyses were weighted to obtain nationally representative estimates. Associations between VF consumption and other factors (e.g., meal frequency and physical activity) were examined through logistic regression analysis., Results: The average fruit consumption was 102.3 g/day (95% CI: 97.0-107.6) and the average vegetable consumption was 350.6 g/day (95% CI: 339.3-361.8). Over half (53.2%, 95% CI: 50.9-55.4) of Chinese adults met the VF consumption of 400 g/day recommended by the World Health Organization (WHO). Rural residents had a higher prevalence of low VF consumption rate than urban residents [49.20% (95% CI: 46.2%-52.2%) vs. 44.0% (95% CI: 41.7%-46.3%) P < 0.01]. Old age (OR = 1.01, 95% CI: 1.00-1.01), low educational level, low income, minority ethnicity (OR = 1.41, 95% CI: 1.15-1.74), underweight (OR = 1.17, 95% CI: 1.03-1.33), single marital status (OR = 1.20, 95% CI: 1.08-1.33), low health literacy, irregular breakfast (OR = 1.20, 95% CI: 1.04-1.38) or lunch (OR = 1.58, 95% CI: 1.26-1.99) habits, and no leisure-time physical activity were associated with low VF consumption., Conclusion: Only half of Chinese adults met the VF consumption recommended by the WHO. Low socio-economic status, irregular diet, and poor health literacy were likely associated with low VF consumption. National efforts and programs are needed to promote VF consumption., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background/purpose: Pleurodesis with biomaterial membrane is an emerging treatment method for pneumothorax. However, the ideal one for the common disease is still under debate., Methods: We investigate the Poly-ε-caprolactone (PCL) membrane pleurodesis by using New Zealand White rabbits, which was sacrificed for examination one month later. Moreover, inflammation and fibrosis scoring were done under microscopic evaluation, as well as Western blot analysis in vitro and in vivo., Results: Gross evaluation of pleurodesis score revealed that dense PCL membrane produced moderate pleural adhesion, while porous PCL membrane exhibited significantly higher pleurodesis scores., Conclusion: PCL membrane induced significant degree of adhesion, both within the abdomen and chest of the rabbits. The porous PCL membrane produces more intensive adhesion than dense one. Fibronectin plays an important role in the process of pleurodesis. Further study is required for the clinical application of the promising material., (Copyright © 2017. Published by Elsevier B.V.)

Background: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE)., Methods: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques., Results: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0-1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure., Conclusion: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.

Background: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency., Methodology: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model. In vitro human islet viability was also assessed after culturing in different oxygen conditions. Correlation between simulation data and experimentally measured islet viability was examined. Using these in vitro viability data of human islets, the effect of islet diameter and oxygen tension of the culture environment on islet viability was also analyzed using a logistic regression model., Principal Findings: Computational simulation clearly revealed the oxygen gradient inside the islet structure. We found that oxygen tension in the islet core was greatly lower (hypoxic) than that on the islet surface due to the oxygen consumption by the cells. The hypoxic core was expanded in the larger islets or in lower oxygen cultures. These findings were consistent with results from in vitro islet viability assays that measured central necrosis in the islet core, indicating that hypoxia is one of the major causes of central necrosis. The logistic regression analysis revealed a negative effect of large islet and low oxygen culture on islet survival., Conclusions/significance: Hypoxic core conditions, induced by the oxygen gradient inside islets, contribute to the development of central necrosis of human isolated islets. Supplying sufficient oxygen during culture could be an effective and reasonable method to maintain isolated islets viable.

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Evaluate parylene scaffold feasibility in cartilage lesion treatment, introducing a novel paradigm combining a reparative and superficial reconstructive procedure. Fifteen rabbits were used. All animals had both knees operated and the same osteochondral lesion model was created bilaterally. The parylene scaffold was implanted in the right knee, and the left knee of the same animal was used as control. The animals were euthanized at different time points after surgery: four animals at three weeks, three animals at six weeks, four animals at nine weeks, and four animals at 12 weeks. Specimens were analyzed by International Cartilage Repair Society (ICRS) macroscopic evaluation, modified Pineda histologic evaluation of cartilage repair, and collagen II immunostaining. Parylene knees were compared to its matched contra-lateral control knees of the same animal using the Wilcoxon matched-pairs signed rank. ICRS mean ± SD values for parylene versus control, three, six, nine and twelve weeks, respectively: 7.83 ± 1.85 versus 4.42 ± 1.08, p = 0.0005; 10.17 ± 1.17 versus 6.83 ± 1.17, p = 0.03; 10.89 ± 0.60 versus 7.33 ± 2.18, p = 0.007; 10.67 ± 0.78 versus 7.83 ± 3.40, p = 0.03. Modified Pineda mean ± SD values for parylene versus control, six, nine and twelve weeks, respectively: 3.37 ± 0.87 versus 6.94 ± 1.7, p < 0.0001; 5.73 ± 2.05 versus 6.41 ± 1.7, p = 0.007; 3.06 ± 1.61 versus 6.52 ± 1.51, p < 0.0001. No inflammation was seen. Parylene implanted knees demonstrated higher collagen II expression via immunostaining in comparison to the control knees. Parylene scaffolds are a feasible option for cartilage lesion treatment and the combination of a reparative to a superficial reconstructive procedure using parylene scaffolds led to better results than the reparative procedure alone.