bluuebunny/crossref_metadata_2025 huggingface dataset:
A Whole-Genome Sequencing Approach To Study Cefoxitin-Resistant Salmonella enterica Serovar Heidelberg Isolates from Various Sources
Authors: Edirmanasinghe Romaine , Finley Rita , Parmley E. Jane , Avery Brent P. , Carson Carolee , Bekal Sadjia , Golding George , Mulvey Michael R.
Published: January 2017

This study characterized cefoxitin-resistant and -susceptible
Salmonella enterica
serovar Heidelberg strains from humans, abattoir poultry, and retail poultry to assess the molecular relationships of isolates from these sources in Québec in 2012. Isolates were collected as part of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). All isolates were subjected to antimicrobial susceptibility testing, PCR for CMY-2, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS). A total of 113
S
. Heidelberg isolates from humans (
n
= 51), abattoir poultry (
n
= 18), and retail poultry (
n
= 44) were studied. All cefoxitin-resistant isolates (
n
= 65) were also resistant to amoxicillin-clavulanic acid, ampicillin, ceftiofur, and ceftriaxone, and all contained the CMY-2 gene. PFGE analysis showed that 111/113 (98.2%) isolates clustered together with ≥90% similarity. Core genome analysis using WGS identified 13 small clusters of isolates with 0 to 4 single nucleotide variations (SNVs), consisting of cefoxitin-resistant and -susceptible human, abattoir poultry, and retail poultry isolates. CMY-2 plasmids from cefoxitin-resistant isolates all belonged to incompatibility group I1. Analysis of IncI1 plasmid sequences revealed high identity (95 to 99%) to a previously described plasmid (pCVM29188_101) found in
Salmonella
Kentucky. When compared to pCVM29188_101, all sequenced cefoxitin-resistant isolates were found to carry 1 of 10 possible variant plasmids. Transmission of
S
. Heidelberg may be occurring between human, abattoir poultry, and retail poultry sources, and transmission of a common CMY-2 plasmid may be occurring among
S
. Heidelberg strains with variable genetic backgrounds.
Use of Optical Imaging Technology in the Validation of a New, Rapid, Cost-Effective Drug Screen as Part of a TieredIn VivoScreening Paradigm for Development of Drugs To Treat Cutaneous Leishmaniasis
Authors: Caridha Diana , Parriot Sandi , Hudson Thomas H. , Lang Thierry , Ngundam Franklyn , Leed Susan , Sena Jenell , Harris Michael , O'Neil Michael , Sciotti Richard , Read Lisa , Lecoeur Herve , Hickman Mark , Grogl Max
Published: January 2017

In any drug discovery and development effort, a reduction in the time of the lead optimization cycle is critical to decrease the time to license and reduce costs. In addition, ethical guidelines call for the more ethical use of animals to minimize the number of animals used and decrease their suffering. Therefore, any effort to develop drugs to treat cutaneous leishmaniasis requires multiple tiers ofin vivotesting that start with higher-throughput efficacy assessments and progress to lower-throughput models with the most clinical relevance. Here, we describe the validation of a high-throughput, first-tier, noninvasive model of lesion suppression that uses anin vivooptical imaging technology for the initial screening of compounds. A strong correlation between luciferase activity and the parasite load at up to 18 days postinfection was found. This correlation allows the direct assessment of the effects of drug treatment on parasite burden. We demonstrate that there is a strong correlation between drug efficacy measured on day 18 postinfection and the suppression of lesion size by day 60 postinfection, which allows us to reach an accurate conclusion on drug efficacy in only 18 days. Compounds demonstrating a significant reduction in the bioluminescence signal compared to that in control animals can be tested in lower-throughput, more definitive tests of lesion cure in BALB/c mice and Golden Syrian hamsters (GSH) using Old World and New World parasites.
Antimicrobial Activity of High-Proportion Cefepime-Tazobactam (WCK 4282) against a Large Number of Gram-Negative Isolates Collected Worldwide in 2014
Authors: Sader Helio S. , Castanheira Mariana , Mendes Rodrigo E. , Flamm Robert K. , Jones Ronald N.
Published: January 2017

Cefepime-tazobactam (WCK 4282) is currently under clinical development for use at a dosage of 2 g/2 g every 8 h. A total of 7,981 isolates were collected from 146 medical centers (39 countries) in 2014 as a part of the SENTRY Antimicrobial Surveillance Program, and their susceptibilities to cefepime-tazobactam (with tazobactam at fixed concentrations of 4 and 8 μg/ml) were tested by a reference broth microdilution method. Isolates were mainly from patients with pneumonia (29.5%) and bloodstream infections (26.9%). Cefepime-tazobactam (with tazobactam at a fixed concentration of 8 μg/ml) and cefepime inhibited 96.9 and 87.9% of
Enterobacteriaceae
strains at ≤8 μg/ml. The activity of cefepime-tazobactam against
Enterobacteriaceae
strains was comparable to that of meropenem (96.7% of isolates were susceptible) and greater than that of piperacillin-tazobactam (87.7% susceptible). All
Enterobacteriaceae
species from the United States except
Klebsiella pneumoniae
had >99.0% of isolates inhibited by cefepime-tazobactam at ≤8/8 μg/ml. The prevalence of the extended-spectrum β-lactamase (ESBL)-screening-positive phenotype was the highest among
Escherichia coli
isolates in China (66.3%) and among
K. pneumoniae
isolates (58.0%) in Latin America. Cefepime-tazobactam at ≤8/8 μg/ml inhibited 98.7 and 71.3% of ESBL-screening-positive phenotype
E. coli
strains and
K. pneumoniae
strains, respectively. Meropenem showed limited activity against ESBL-screening-positive phenotype
K. pneumoniae
strains (69.6% susceptible). Cefepime-tazobactam was active against
Enterobacter
spp. (MIC
50
and MIC
90
, 0.06 and 0.5 μg/ml, respectively), including ceftazidime-nonsusceptible isolates (96.1% of isolates were inhibited by cefepime-tazobactam at ≤8/8 μg/ml). The activity of cefepime-tazobactam against
Pseudomonas aeruginosa
(82.4 and 91.6% of isolates were inhibited by cefepime-tazobactam at ≤8/8 and ≤16/8 μg/ml, respectively) was comparable to that of meropenem and piperacillin-tazobactam (79.2% susceptible). In summary, cefepime-tazobactam was highly active against
P. aeruginosa
and
Enterobacteriaceae
strains, including ESBL-screening-positive phenotype
E. coli
strains and ceftazidime-nonsusceptible
Enterobacter
spp. These results support the further clinical development of the cefepime-tazobactam combination.
Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters
Authors: Dangtakot Rungtiwa , Pinlaor Somchai , Itthitaetrakool Upsornsawan , Chaidee Apisit , Chomvarin Chariya , Sangka Arunnee , Wilailuckana Chotechana , Pinlaor Porntip
Published: January 2017

Persistent infection with
Opisthorchis viverrini
causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition,
Helicobacter pylori
is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with
H. pylori
and
O. viverrini
on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii)
H. pylori
infected (HP), (iii)
O. viverrini
infected (OV), and (iv)
O. viverrini
and
H. pylori
infected (OV+HP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of
H. pylori
in the stomach, gallbladder, and liver. In the liver,
H. pylori
was detected in the following order: OV+HP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%).
H. pylori
was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [
IL-1
],
IL-6
, and tumor necrosis factor alpha) were also observed in the OV+HP group. These results suggest that coinfection with
H. pylori
and
O. viverrini
increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did.
Cellular Uptake of Clostridium botulinum C2 Toxin Requires Acid Sphingomyelinase Activity
Authors: Nagahama Masahiro , Takehara Masaya , Takagishi Teruhisa , Seike Soshi , Miyamoto Kazuaki , Kobayashi Keiko
Published: January 2017

Clostridium botulinum
C2 toxin consists of an enzyme component (C2I) and a binding component (C2II). Activated C2II (C2IIa) binds to a cell receptor, giving rise to lipid raft-dependent oligomerization, and it then assembles with C2I. The whole toxin complex is then endocytosed into the cytosol, resulting in the destruction of the actin cytoskeleton and cell rounding. Here, we showed that C2 toxin requires acid sphingomyelinase (ASMase) activity during internalization. In this study, inhibitors of ASMase and lysosomal exocytosis blocked C2 toxin-induced cell rounding. C2IIa induced Ca
2+
influx from the extracellular medium to cells. C2 toxin-induced cell rounding was enhanced in the presence of Ca
2+
. ASMase was released extracellularly when cells were incubated with C2IIa in the presence of Ca
2+
. Small interfering RNA (siRNA) knockdown of ASMase reduced C2 toxin-induced cell rounding. ASMase hydrolyzes sphingomyelin to ceramide on the outer leaflet of the membrane at acidic pH. Ceramide was detected in cytoplasmic vesicles containing C2IIa. These results indicated that ASMase activity is necessary for the efficient internalization of C2 toxin into cells. Inhibitors of ASMase may confer protection against infection.
Genetic and Mechanistic Analyses of the Periplasmic Domain of the Enterohemorrhagic Escherichia coli QseC Histidine Sensor Kinase
Authors: Parker Christopher T. , Russell Regan , Njoroge Jacqueline W. , Jimenez Angel G. , Taussig Ron , Sperandio Vanessa
Published: January 2017

The histidine sensor kinase (HK) QseC senses autoinducer 3 (AI-3) and the adrenergic hormones epinephrine and norepinephrine. Upon sensing these signals, QseC acts through three response regulators (RRs) to regulate the expression of virulence genes in enterohemorrhagic
Escherichia coli
(EHEC). The QseB, QseF, and KdpE RRs that are phosphorylated by QseC constitute a tripartite signaling cascade having different and overlapping targets, including flagella and motility, the type three secretion system encoded by the locus of enterocyte effacement (LEE), and Shiga toxin. We modeled the tertiary structure of QseC's periplasmic sensing domain and aligned the sequences from 12 different species to identify the most conserved amino acids. We selected eight amino acids conserved in all of these QseC homologues. The corresponding QseC site-directed mutants were expressed and still able to autophosphorylate; however, four mutants demonstrated an increased basal level of phosphorylation. These mutants have differential flagellar, motility, LEE, and Shiga toxin expression phenotypes. We selected four mutants for more in-depth analyses and found that they differed in their ability to phosphorylate QseB, KdpE, and QseF. This suggests that these mutations in the periplasmic sensing domain affected the region downstream of the QseC signaling cascade and therefore can influence which pathway QseC regulates.

IMPORTANCE
In the foodborne pathogen EHEC, QseC senses AI-3, epinephrine, and norepinephrine, increases its autophosphorylation, and then transfers its phosphate to three RRs: QseB, QseF, and KdpE. QseB controls expression of flagella and motility, KdpE controls expression of the LEE region, and QseF controls the expression of Shiga toxin. This tripartite signaling pathway must be tightly controlled, given that flagella and the type three secretion system (T3SS) are energetically expensive appendages and Shiga toxin expression leads to bacterial cell lysis. Our data suggest that mutations in the periplasmic sensing loop of QseC differentially affect the expression of the three arms of this signaling cascade. This suggests that these point mutations may change QseC's phosphotransfer preferences for its RRs.
An alternative sensor-based method for glucose monitoring in children and young people with diabetes
Authors: Edge Julie , Acerini Carlo , Campbell Fiona , Hamilton-Shield Julian , Moudiotis Chris , Rahman Shakeel , Randell Tabitha , Smith Anne , Trevelyan Nicola
Published: January 2017

Objective

To determine accuracy, safety and acceptability of the FreeStyle Libre Flash Glucose Monitoring System in the paediatric population.

Design, setting and patients

Eighty-nine study participants, aged 4–17 years, with type 1 diabetes were enrolled across 9 diabetes centres in the UK. A factory calibrated sensor was inserted on the back of the upper arm and used for up to 14 days. Sensor glucose measurements were compared with capillary blood glucose (BG) measurements. Sensor results were masked to participants.

Results

Clinical accuracy of sensor results versus BG results was demonstrated, with 83.8% of results in zone A and 99.4% of results in zones A and B of the consensus error grid. Overall mean absolute relative difference (MARD) was 13.9%. Sensor accuracy was unaffected by patient factors such as age, body weight, sex, method of insulin administration or time of use (day vs night). Participants were in the target glucose range (3.9–10.0 mmol/L) ∼50% of the time (mean 12.1 hours/day), with an average of 2.2 hours/day and 9.5 hours/day in hypoglycaemia and hyperglycaemia, respectively. Sensor application, wear/use of the device and comparison to self-monitoring of blood glucose were rated favourably by most participants/caregivers (84.3–100%). Five device related adverse events were reported across a range of participant ages.

Conclusions

Accuracy, safety and user acceptability of the FreeStyle Libre System were demonstrated for the paediatric population. Accuracy of the system was unaffected by subject characteristics, making it suitable for a broad range of children and young people with diabetes.

Trial registration number

NCT02388815.
2016 Rio Olympics: an epidemiological study of the men’s and women’s Rugby-7s tournaments
Authors: Fuller Colin W , Taylor Aileen , Raftery Martin
Published: January 2017

Objective

To determine the incidence, severity and nature of injuries sustained during the men’s and women’s 2014/2015 and 2015/2016 Sevens World Series (SWS) and 2016 Olympic Games Rugby Sevens tournaments.

Design

A prospective cohort study.

Participants

All players from the core teams competing in the men’s and women’s 2014/2015 and 2015/2016 SWS (men: 15 teams; women: 11 teams) and all players from the men’s (12 teams) and women’s (12 teams) 2016 Rio Olympics tournaments.

Results

The gold, silver and bronze medal-winning women’s teams contained bigger players (body mass and stature) than other teams but the men’s medal winning teams came from across the size spectrum of men’s teams competing at Rio 2016. The incidences of injury in the men’s tournaments (2014/2015 SWS: 107.7 injuries/1000 player-match-hours (95% CI 90.9 to 127.4); 2015/2016 SWS: 109.7 (95% CI 93.7 to 128.6); Rio 2016: 124.5 (95% CI 73.7 to 210.2)) were higher but not statistically significant than those in the equivalent women’s tournaments (2014/2015 SWS: 88.5 (95% CI 68.4 to 114.5), p=0.250; 2015/2016 SWS: 109.4 (95% CI 84.2 to 142.2), p=0.984; Rio 2016: 71.1 (95% CI 35.6 to 142.2), p=0.208). There were no statistically significant differences between the incidences of injury at the men’s and women’s 2016 Rio Olympics and the equivalent 2014/2015 (men: p=0.603; women: p=0.562) and 2015/2016 (men: p=0.652; women: p=0.254) SWS.

Conclusions

The incidence, severity and nature of the injuries sustained during the men’s and women’s Rio 2016 Rugby-7s tournaments fell within the normal range of values for international Rugby-7s tournaments.
Prognostic value of plasma lactate levels in a retrospective cohort presenting at a university hospital emergency department
Authors: van den Nouland Danith P A , Brouwers Martijn C G J , Stassen Patricia M
Published: January 2017

Objectives

The prognostic value of lactate in the setting of an emergency department (ED) has not been studied extensively. The goal of this study was to assess 28-day mortality in ED patients in whom lactate was elevated (≥4.0 mmol/L), <4.0 mmol/L or not determined and to study the impact of the underlying cause of hyperlactatemia, that is, type A (tissue hypoxia) or type B (non-hypoxia), on mortality.

Design

Retrospective study.

Setting

A secondary and tertiary referral centre in the Netherlands.

Materials and methods

All internal medicine patients with hyperlactatemia (≥4.0 mmol/L) at the ED between January 2011 and October 2014 were included in this study. Samples of patients with lactate levels <4.0 mmol/L and of patients in whom no lactate was measured were included as a reference.

Results

In 1144 of 19 822 patients (5.8%), lactate was measured. Hyperlactatemia (n=197) was associated with a higher 28-day mortality than in those with lactate <4.0 mmol/L (40.6% vs 18.5%; p<0.001) and in those without lactate measurements (9.5%). Type A hyperlactatemia, present in 84% of those with hyperlactatemia, was associated with higher mortality than type B hyperlactatemia (45.8% vs 12.5%, p=0.001).

Conclusions

This study demonstrates that the prognostic value of lactate depends largely on the underlying cause and the population in whom lactate has been measured. Prospective studies are required to address the true added value of lactate at the ED.
GEL THE NEC: a prospective registry evaluating the safety, ease of use, and efficacy of the HydroSoft coil as a finishing device
Authors: Brinjikji Waleed , Amar Arun P , Delgado Almandoz Josser E , Diaz Orlando , Jabbour Pascal , Hanel Ricardo , Hui Ferdinand , Kelly Michael , Layton Kennith D , Miller Jeffrey W , Levy Elad , Moran Christopher , Suh Dae C , Woo Henry , Sellar Robin , Ho Brian , Evans Avery , Kallmes David F
Published: January 2017

Background and purpose

The HydroSoft coil was developed as a finishing coil, ideally to be placed along the aneurysm neck to enhance intracranial aneurysm healing. The GEL THE NEC (Gaining Efficacy Long Term: Hydrosoft, an Emerging, New, Embolic Coil) multicenter registry was developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We report angiographic and clinical results of this prospective registry.

Materials and methods

GEL THE NEC was performed at 27 centers in five countries. Patients aged 21–90 years with a ruptured or unruptured aneurysm 3–15 mm in size were eligible for enrollment. The following variables were obtained: demographics/comorbidities, aneurysm geometry, adjunctive devices used, proportion of patients in whom HydroSoft coils were successfully placed, and long-term angiographic outcomes (graded by an independent core laboratory using the Modified Raymond Scale), and procedure-related adverse events. Predictors of good angiographic outcome were studied using χ2and t-tests.

Results

A total of 599 patients with 599 aneurysms were included in this study. HydroSoft coils were successfully deployed in 577 (96.4%) patients. Procedure-related major morbidity and mortality were 0.5% (3/599) and 1.3% (8/599), respectively. The most common perioperative complications were iatrogenic vasospasm (30/599, 5.0%), thromboemboli (27/599, 4.5%), and aneurysm perforation (16/599, 2.7%). At last angiographic follow-up (mean 9.0±6.3 months), the complete occlusion rate was 63.2% (280/442) and near complete occlusion rate was 25.2% (107/442). The core laboratory read recanalization rate was 10.8% (46/425) and the retreatment rate was 3.4% (20/599).

Conclusions

Endovascular treatment of intracranial aneurysms with HydroSoft coils resulted in complete/near complete occlusion rates of 88% and a major complication rate of 1.8%.

Trial registration number

NCT01000675.
The Rab-GTPase activating protein, TBC1D1, is critical for maintaining normal glucose homeostasis and β-cell mass
Authors: Paglialunga Sabina , Simnett Genevieve , Robson Holly , Hoang Monica , Pillai Renjitha , Arkell Alicia M. , Simpson Jeremy A. , Bonen Arend , Huising Mark , Joseph Jamie W. , Holloway Graham P.
Published: January 2017

Tre-2/USP6, BUB2, cdc16 domain family, member 1 (TBC1D1), a Rab-GTPase activating protein, is a paralogue of AS160, and has been implicated in the canonical insulin-signaling cascade in peripheral tissues. More recently, TBC1D1 was identified in rat and human pancreatic islets; however, the islet function of TBC1D1 remains not fully understood. We examined the role of TBC1D1 in glucose homeostasis and insulin secretion utilizing a rat knockout (KO) model. Chow-fed TBC1D1 KO rats had improved insulin action but impaired glucose-tolerance tests (GTT) and a lower insulin response during an intraperitoneal GTT compared with wild-type (WT) rats. The in vivo data suggest there may be an islet defect. Glucose-stimulated insulin secretion was higher in isolated KO rat islets compared with WT animals, suggesting TBC1D1 is a negative regulator of insulin secretion. Moreover, KO rats displayed reduced β-cell mass, which likely accounts for the impaired whole-body glucose homeostasis. This β-cell mass reduction was associated with increased active caspase 3, and unaltered Ki67 or urocortin 3, suggesting the induction of apoptosis rather than decreased proliferation or dedifferentiation may account for the decline in islet mass. A similar phenotype was observed in TBC1D1 heterozygous animals, highlighting the sensitivity of the pancreas to subtle reductions in TBC1D1 protein. An 8-week pair-fed high-fat diet did not further alter β-cell mass or apoptosis in KO rats, suggesting that dietary lipids per se, do not lead to a further impairment in glucose homeostasis. The present study establishes a fundamental role for TBC1D1 in maintaining in vivo β-cell mass.
Automated Fuzzy System Based on Feature Extraction and Selection for Opinion Classification Across Different Domains
Authors: Cardoso Matheus , Loula Angelo , Pires Matheus Giovanni
Published: January 2017

Opinions have a relevant inuence on people’s behavior. The Internet and the Web have made it possible for people to share their opinions and for other people and organizations find out more about opinions and experiences from individuals. Still, opinions involve sentiments that are vague and imprecise textual descriptions. Hence, due to the nature of the data, Fuzzy Logic can be a promising approach. This paper proposes a method to automatically build a fuzzy system, based on features extracted and selected from documents, to perform classification of sentiment in opinions across different domains. Almost 60 features were extracted from documents and multiple feature selection algorithms were applied. Over the selected features, the Wang-Mendel (WM) method was used to generate fuzzy rules and classify documents. Variations on fuzzy set modeling, on the use of weights in the rules and on fuzzy inference mechanisms were considered. The classifier fuzzy system based achieved 71,25% of accuracy in a 10-fold cross-validation, comparable to a SVM classifier.
Nonlinear optical properties of dielectric nanocolloids: Particle size and concentration effects
Authors: Salazar-Romero M. Y. , Alvarez-Ortiz M. , Balbuena Ortega A. , Ayala Y. A. , Arzola A. V. , Hernández-Cordero J. , Volke-Sepulveda K.
Published: January 2017

The nonlinear optical properties of different samples of dielectric nanocolloids and their application to generate optical spatial solitons in two transverse dimensions are investigated. Each sample is constituted by a suspension of polystyrene nanospheres in water, and we analyze four cases with two different particle sizes (62[Formula: see text]nm and 77[Formula: see text]nm in diameter) and concentrations (0.5% and 1.0% solids). The z-scan technique is used to evaluate and compare the nonlinear refractive index of the nanocolloids. A detailed experimental study on the formation of soliton-like beams as a function of different parameters is also presented. Importantly, the generated solitons propagate along distances exceeding by one order of magnitude the propagation distances observed previously in the same kind of media.
An Analytical Solution for Predicting the Vibration-Fatigue-Life in Bimodal Random Processes
Authors: Han Chaoshuai , Ma Yongliang , Qu Xianqiang , Yang Mindong
Published: January 2017

Predicting the vibration-fatigue-life of engineering structures subjected to random loading is a critical issue for. Frequency methods are generally adopted to deal with this problem. This paper focuses on bimodal spectra methods, including Jiao-Moan method, Fu-Cebon method, and Modified Fu-Cebon method. It has been proven that these three methods can give acceptable fatigue damage results. However, these three bimodal methods do not have analytical solutions. Jiao-Moan method uses an approximate solution, Fu-Cebon method, and Modified Fu-Cebon method needed to be calculated by numerical integration which is obviously not convenient in engineering application. Thus, an analytical solution for predicting the vibration-fatigue-life in bimodal spectra is developed. The accuracy of the analytical solution is compared with numerical integration. The results show that a very good agreement between an analytical solution and numerical integration can be obtained. Finally, case study in offshore structures is conducted and a bandwidth correction factor is computed through using the proposed analytical solution.
Application of Spontaneous Photon Emission in the Growth Ages and Varieties Screening of Fresh Chinese Herbal Medicines
Authors: Zhao Xiaolei , Pang Jingxiang , Fu Jialei , Yang Meina , Van Wijk Eduard , Liu Yanli , Fan Hua , Zhang Yufeng , Han Jinxiang
Published: January 2017

Ultraweak photon emission emitted by all living organisms has been confirmed to be a noninvasive indicator for their physiological and pathological characteristics. In this study, we investigated the characteristics of spontaneous photon emission (SPE) and the contents of specific active compounds of roots and flowers buds of several fresh Chinese herbal medicines (natural medicines) with different growth ages and varieties. The results revealed that the contents of specific active compounds from same species herbs with different growth ages and varieties were significantly different, and this difference could be reflected by their SPE. Because the contents of specific bioactive constituents in Chinese herbs are closely related to their quality and curative effect, the SPE measurement technique may contribute to the quality control of Chinese herbal medicine in the future.
Evaluation of Parotid Salivary Glucose Level for Clinical Diagnosis and Monitoring Type 2 Diabetes Mellitus Patients
Authors: Wang Beibei , Du Juan , Zhu Zhao , Ma Zhihong , Wang Songlin , Shan Zhaochen
Published: January 2017

Background. To investigate the relationships among blood glucose, mixed saliva glucose, and parotid glucose in type 2 diabetes patients and to evaluate the diagnostic and monitoring value of salivary gland glucose in patients with type 2 diabetes (type 2DM). Material and Methods. Thirty patients with type 2DM and 30 healthy age- and sex-matched individuals were included in this study. Glucose levels in unstimulated mixed saliva and in unstimulated parotid saliva were measured by the glucose oxidase peroxidase method. Results. The blood glucose and parotid salivary glucose levels in type 2DM patients were significantly higher than those in the controls (P<0.05). The blood glucose, parotid salivary glucose, and mixed salivary glucose were 7.46±1.44 mmol/L, 0.18±0.19 mmol/L, and 3.17×10-2±2.84×10-2 mmol/L, respectively, in the type 2DM group; the corresponding glucose levels in the control group were 5.56±0.71 mmol/L, 7.70×10-2±6.02×10-2 mmol/L, and 3.47×10-2±2.79×10-2 mmol/L. The parotid salivary and blood glucose levels in type 2DM patients were strongly correlated; the linear regression equation for blood glucose and parotid salivary glucose was Y=6.267X+6.360, with r=0.810. However, mixed salivary glucose levels were not significantly different in the type 2 diabetes group compared with the control group. Conclusion. Our results suggest that parotid salivary glucose has potential as a biomarker to monitor type 2DM and as a painless, noninvasive method for the management of type 2DM.
Meretoja’s Syndrome: Lattice Corneal Dystrophy, Gelsolin Type
Authors: Casal I. , Monteiro S. , Abreu C. , Neves M. , Oliveira L. , Beirão M.
Published: January 2017

Lattice corneal dystrophy gelsolin type was first described in 1969 by Jouko Meretoja, a Finnish ophthalmologist. It is caused by an autosomal dominant mutation in gelsolin gene resulting in unstable protein fragments and amyloid deposition in various organs. The age of onset is usually after the third decade of life and typical diagnostic triad includes progressive bilateral facial paralysis, loose skin, and lattice corneal dystrophy. We report a case of a 53-year-old female patient referred to our Department of Ophthalmology by severe dry eye and incomplete eyelid closure. She had severe bilateral facial paresis, significant orbicularis, and perioral sagging as well as hypoesthesia of extremities and was diagnosed with Meretoja’s syndrome at the age of 50, confirmed by the presence of gelsolin mutation. At our observation she had bilateral diminished tear film break-up time and Schirmer test, diffuse keratitis, corneal opacification, and neovascularization in the left eye. She was treated with preservative-free lubricants and topical cyclosporine, associated with nocturnal complete occlusion of both eyes, and underwent placement of lacrimal punctal plugs. Ocular symptoms are the first to appear and our role as ophthalmologists is essential for the diagnosis, treatment, and monitoring of ocular alterations in these patients.
An Efficient Approach in Analysis of DNA Base Calling Using Neural Fuzzy Model
Authors: Hameed Safa A. , Hamed Raed I.
Published: January 2017

This paper presented the issues of true representation and a reliable measure for analyzing the DNA base calling is provided. The method implemented dealt with the data set quality in analyzing DNA sequencing, it is investigating solution of the problem of using Neurofuzzy techniques for predicting the confidence value for each base in DNA base calling regarding collecting the data for each base in DNA, and the simulation model of designing the ANFIS contains three subsystems and main system; obtain the three features from the subsystems and in the main system and use the three features to predict the confidence value for each base. This is achieving effective results with high performance in employment.
Alternative to Water Based Fabric Cleaner in Textile and Detergent Processes
Authors: Jain Arpan
Published: January 2017

Three different detergent formulations, (1) ethyl-hydro-oxides (EHOs, using ethanol + H2O2 + KOH + water, without pH adjustment, at 60°C for 1 h), (2) modified EHOs (using ethanol + H2O2 + KOH + water, with pH adjustment, at 40°C for 1 h), and (3) water based detergent (WBD, using commercial detergent T + water, at 40°C for 1 h), were analyzed for cleaning of dried biodiesel soaked cotton cloth (DBSCC) samples. The effects of detergent formulations were analyzed based on cloth sample weights (residual and intact) and visual (through photographic images) examinations. With EHOs formulations, the increasing concentration of KOH and H2O2 had a significant effect on increasing both brightness and residual content of DBSCC samples. On the contrary, the controlled pH environments (as with modified EHOs formulations) had a significant effect in decreasing residual content and increasing brightness of DBSCC samples. The implications of EHOs formulations (with and without modification) are discussed with respect to current water based textile and detergent industries practices.
Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases
Authors: Madeira Maria H. , Boia Raquel , Ambrósio António F. , Santiago Ana R.
Published: January 2017

Caffeine is the major component of coffee and the most consumed psychostimulant in the world and at nontoxic doses acts as a nonselective adenosine receptor antagonist. Epidemiological evidence suggests that caffeine consumption reduces the risk of several neurological and neurodegenerative diseases. However, despite the beneficial effects of caffeine consumption in human health and behaviour, the mechanisms by which it impacts the pathophysiology of neurodegenerative diseases still remain to be clarified. A promising hypothesis is that caffeine controls microglia-mediated neuroinflammatory response associated with the majority of neurodegenerative conditions. Accordingly, it has been already described that the modulation of adenosine receptors, namely, theA2Areceptor, affords neuroprotection through the control of microglia reactivity and neuroinflammation. In this review, we will summarize the main effects of caffeine in the modulation of neuroinflammation in neurodegenerative diseases.
Analysis of the Dynamic Influence of Social Network Nodes
Authors: Yin Hong-Jian , Yu Hai , Zhao Yu-Li , Zhu Zhi-Liang , Zhang Wei
Published: January 2017

In recent years, with the development of the social network theories, how to find or mining the most significant node in social network for understanding or controlling the information dissemination has become a hot topic and a series of effective algorithms have been presented. In this paper, a new scheme to measure the dynamic influence of the nodes in a social network is proposed, in which the sum of trust values of the propagation nodes is used. Simulations have been carried out and the results show that our scheme is stable and accurate.
Evaluating Adherence to Antiretroviral Therapy Using Pharmacy Refill Records in a Rural Treatment Site in South Africa
Authors: Gachara George , Mavhandu Lufuno G. , Rogawski Elizabeth T. , Manhaeve Cecile , Bessong Pascal O.
Published: January 2017

Optimal adherence to combination antiretroviral therapy (cART) is critical to maintain virologic suppression, thereby ensuring the global success of HIV treatment. We evaluated adherence to cART using pharmacy refill records and determined the adherence threshold resulting in >90% virologic suppression in a community run treatment site in South Africa. Additionally, we analysed factors associated with adherence using univariable and multivariable logistic regression models. Logistic regression was also performed to determine the relationship between adherence and virologic suppression and the adherence threshold resulting in <10% virologic failure. The overall median (interquartile range) adherence was 95% (88.6–98.4%). Out of the study participants, 210/401 (52.4%) had optimal (≥95%) adherence while only 37/401 (9.2%) had poor (≤80%) adherence. The majority (90.5%) of patients with optimal adherence had virologic suppression. Having TB at registration into care was found to be negatively associated with adherence (adjusted odds ratio [AOR], 0.382; p≤.05). Compared to nonadherent individuals, optimally adherent participants were more likely to achieve virologic suppression (OR 2.92; 95% CI: 1.63–5.22). Only adherence rates above 95% were observed to lead to <10% virologic failure. cART adherence measured by pharmacy refill records could serve as a useful predictor of virologic failure; adherence rates >95% are needed to maintain optimal virologic suppression.
SAR Reduction Using Integration of PIFA and AMC Structure for Pentaband Mobile Terminals
Authors: Lee Jae-Gon , Lee Jeong-Hae
Published: January 2017

In this paper, a capacitive grating artificial magnetic conductor (AMC) is presented to reduce the specific absorption rate (SAR) in pentaband mobile terminals. The AMC structure is implemented using a dielectric film with the printed arrays of the metal strips placed at the top and the bottom of the dielectric. It is difficult to design the AMC structure to operate at low (824~960 MHz) and high bands (1710~2170 MHz) simultaneously, because of the limited space available for the antenna. Hence, we have designed the capacitive grating AMC to operate at a high band. Then, we attached a PIFA to the AMC structure to cover low and high bands. As the AMC structure is operated as a perfect electric conductor (PEC) in low band, the radiating branches of the PIFA for the low and high bands should be located on the non-AMC and the AMC structures, respectively. Even though the AMC structure is operated at a high band, the effect against the head could be reduced in the pentaband due to the spreading effect of the electromagnetic (EM) field at lower bands. From measured results, the 1 g SAR in the case of the AMC antenna is significantly lower than that in the case where only the PIFA is present in the pentaband.
Optimal Container Routing in Liner Shipping Networks Considering Repacking 20 ft Containers into 40 ft Containers
Authors: Wang Shuaian , Qu Xiaobo , Wang Tingsong , Yi Wen
Published: January 2017

The volume of a 40 ft container is twice as large as that of a 20 ft container. However, the handling cost (loading, unloading, and transshipment) of a 40 ft container is much lower than twice the corresponding handling cost of two 20 ft containers. Enlightened by this observation, we propose a novel container routing with repacking problem in liner shipping, where two 20 ft containers can be repacked to a 40 ft container in order to reduce the handling cost. We develop a mixed-integer linear programming model that formulates the routing decisions and the repacking decisions in a holistic manner. An illustrative example is reported to demonstrate the applicability of the model. Results show that the benefit of repacking is the most significant when containers are transshipped several times.
Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes
Authors: Duan Peng , Yang Min , Wei Meilin , Liu Jia , Tu Ping
Published: January 2017

The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (n=93), impaired glucose regulation (IGR) (n=90), and normal glucose regulation group (NGR) (n=88), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) (p=0.031) and T2DM group (183.20 ± 56.53 pg/mL) (p<0.01), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009,p=0.006) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.
The Performance and Mechanism Analysis of Cement Pastes Added to Aluminum Sulfate-Based Low-Alkali Setting Accelerator
Authors: Lv Xingdong , Shi Yan , Dong Yun , Gao Zhiyang , Li Beixing
Published: January 2017

We proposed a type of low-alkali liquid state setting accelerator, named HLSA; it was environmentally friendly product. To investigate the temperature adaptation and cement flexibilities of HLSA, the setting time and strength development properties of cement with HLSA were discussed in this paper. The effects of HLSA on hydration process, hydration products, and microstructure were studied by means of X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscope (SEM), and mercury intrusion porosimetry (MIP). The results show that four typical 42.5-grade ordinary Portland cement types with 6–8% HLSA could satisfy the first-grade requirements according to JC477-2005 even at a lower temperature (e.g., 10°C). Further, the percentage ratio of 28 d compressive strength of cement with 6–8% HLSA was over 90%; the XRD diffraction peak of AFt integrated area of cement with 7% HLSA was 3818 at 5 min of hydration; SEM observation revealed that AFt crystals were filled in the pore of cement at 28 d of hydration; the temperature adaptation and cement flexibilities of HLSA were excellent; the cement with HLSA coagulating in a short time attributed to promoting the formation of abundant AFt and the hydration of C3S.
Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy
Authors: Baran Natalia , Konopleva Marina
Published: January 2017

Hypoxia is a known feature of aggressive solid tumors as well as a critical hallmark of the niche in aggressive hematologic malignances. Hypoxia is associated with insufficient response to standard therapy, resulting in disease progression and curtailed patients' survival through maintenance of noncycling cancer stem–like cells. A better understanding of the mechanisms and signaling pathways induced by hypoxia is essential to overcoming these effects. Recent findings demonstrate that bone marrow in the setting of hematologic malignancies is highly hypoxic, and that progression of the disease is associated with expansion of hypoxic niches and stabilization of the oncogenic hypoxia-inducible factor-1alpha (HIF1α). Solid tumors have also been shown to harbor hypoxic areas, maintaining survival of cancer cells via the HIF1α pathway. Developing new strategies for targeting hypoxia has become a crucial approach in modern cancer therapy. The number of preclinical and clinical trials targeting low-oxygen tumor compartments or the hypoxic bone marrow niche via hypoxia-activated prodrugs is increasing. This review discusses the development of the hypoxia-activated prodrugs and their applicability in treating both hematologic malignancies and solid tumors. Clin Cancer Res; 23(10); 2382–90. ©2017 AACR.
The TLR3 Agonist Inhibit Drug Efflux and Sequentially Consolidates Low-Dose Cisplatin-Based Chemoimmunotherapy while Reducing Side Effects
Authors: Ding Liang , Ren Jing , Zhang Dongya , Li Yi , Huang Xiaofeng , Ji Jianjian , Hu Qingang , Wang Hui , Ni Yanhong , Hou Yayi
Published: January 2017

The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n = 166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine–polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo. The results in vitro indicated that preculture with PIC downregulated drug transporters (e.g., P-gp and MRP-1) and increased the cytoplasmic residence of cisplatin, and dramatically strengthened the low-dose cisplatin-induced cell death in TLR3- and caspase-3–dependent manner. Meanwhile, the spleen immunocytes were activated but the immunosuppressive cancer-associated fibroblasts (CAF) were dampened. These findings were confirmed in human tumor models in vivo. Pretreatment with PIC promoted the low-dose cisplatin residence for tumor regression with decreased myeloid-suppressive cells (MDSC), tumor-associated macrophages (TAM) and CAFs, and alleviated adverse side effects in the OSCC model, which was further enhanced by the Cetuximab safely. This strategy also repressed the progression of melanoma and lymphoma. Moreover, TLR3 negatively manipulated the inflammation-related long noncoding RNA lnc-IL7R, which was upregulated during this chemotherapy. Knockdown of lnc-IL7R improved the chemotherapy sensitivity. Overall, this study provided preclinically new instructions for the PIC/cisplatin utilization to target tumor microenvironment and strengthen the low-dose cisplatin-based chemotherapy with reduced side effects. Mol Cancer Ther; 16(6); 1068–79. ©2017 AACR.
Targeted Treatment of Metastatic Breast Cancer by PLK1 siRNA Delivered by an Antioxidant Nanoparticle Platform
Authors: Morry Jingga , Ngamcherdtrakul Worapol , Gu Shenda , Reda Moataz , Castro David J. , Sangvanich Thanapon , Gray Joe W. , Yantasee Wassana
Published: January 2017

Metastatic breast cancer is developed in about 20% to 30% of newly diagnosed patients with early-stage breast cancer despite treatments. Herein, we report a novel nanoparticle platform with intrinsic antimetastatic properties for the targeted delivery of Polo-like kinase 1 siRNA (siPLK1). We first evaluated it in a triple-negative breast cancer (TNBC) model, which shows high metastatic potential. PLK1 was identified as the top therapeutic target for TNBC cells and tumor-initiating cells in a kinome-wide screen. The platform consists of a 50-nm mesoporous silica nanoparticle (MSNP) core coated layer-by-layer with bioreducible cross-linked PEI and PEG polymers, conjugated with an antibody for selective uptake into cancer cells. siRNA is loaded last and fully protected under the PEG layer from blood enzymatic degradation. The material has net neutral charge and low nonspecific cytotoxicity. We have also shown for the first time that the MSNP itself inhibited cancer migration and invasion in TNBC cells owing to its ROS- and NOX4-modulating properties. In vivo, siPLK1 nanoconstructs (six doses of 0.5 mg/kg) knocked down about 80% of human PLK1 mRNA expression in metastatic breast cancer cells residing in mouse lungs and reduced tumor incidence and burden in lungs and other organs of an experimental metastasis mouse model. Long-term treatment significantly delayed the onset of death in mice and improved the overall survival. The platform capable of simultaneously inhibiting the proliferative and metastatic hallmarks of cancer progression is unique and has great therapeutic potential to also target other metastatic cancers beyond TNBC. Mol Cancer Ther; 16(4); 763–72. ©2017 AACR.