bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ObjectiveTo determine accuracy, safety and acceptability of the FreeStyle Libre Flash Glucose Monitoring System in the paediatric population.Design, setting and patientsEighty-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.ResultsClinical 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.ConclusionsAccuracy, 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 numberNCT02388815.
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

ObjectiveTo 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.DesignA prospective cohort study.ParticipantsAll 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.ResultsThe 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.ConclusionsThe 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

ObjectivesThe 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.DesignRetrospective study.SettingA secondary and tertiary referral centre in the Netherlands.Materials and methodsAll 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.ResultsIn 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).ConclusionsThis 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 purposeThe 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 methodsGEL 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.ResultsA 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).ConclusionsEndovascular 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 numberNCT01000675.
Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy
Authors: Baran Natalia , Konopleva Marina 
Published: January 2017

Abstract
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

Abstract
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

AbstractMetastatic 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.
Precocious mating in the freshwater crab Candidiopotamon rathbunae (De Man, 1914)
Authors: Liu Hung-Chang , Hartnoll Richard G. 
Published: January 2017

In Brachyura copulation prior to the instar in which females become fully morphologically and functionally mature (i.e., produce fertile eggs) is exceptional. However, in the freshwater crab Candidiopotamon rathbunae (family Potamidae), adult males frequently mate with immature females (precocious mating). The size of female functional maturity is 22-23 mm carapace width. Immature females larger than 15 mm carapace width are observed mating, usually have sperm in their seminal receptacles, and this sperm is retained through subsequent moults. Precocious mating in C. rathbunae could potentially increase the reproductive capacity of females. It could have evolved as an adaptation to a seasonally amphibious life, during which the mating opportunities are reduced compared to a permanently aquatic lifestyle. Data from the few other brachyuran taxa with precocious mating fail to indicate a common rationale.
On a new species of Shanphusa Yeo & Ng, 2007 (Brachyura, Potamoidea, Potamidae), from a cave in central Myanmar
Authors: Ng Peter K. L. , Whitten Anthony J. 
Published: January 2017

The potamid freshwater crab genus Shanphusa Yeo & Ng, 2007, currently contains two species from Shan State in Myanmar (= Burma): S. browneana (Kemp, 1918) (type species) and S. curtobates (Kemp, 1918). A third species, S. ywarngan sp. nov. is described from a cave in the region. The new species can easily be distinguished from its congeners by various carapace features, shape of the male telson, and structure of the male first gonopod.
NFLUX Satellite-Based Surface Radiative Heat Fluxes. Part II: Gridded Products
Authors: May Jackie C. , Rowley Clark , Barron Charlie N. 
Published: January 2017

AbstractThe Naval Research Laboratory (NRL) ocean surface flux (NFLUX) system provides near-real-time satellite-based gridded surface heat flux fields over the global ocean within hours of the observed satellite measurements. NFLUX can serve as an alternative to current numerical weather prediction models—in particular, the U. S. Navy Global Environmental Model (NAVGEM)—that provide surface forcing fields to operational ocean models. This study discusses the satellite-based shortwave and longwave global gridded analysis fields, which complete the full suite of NFLUX-provided ocean surface heat fluxes. A companion paper discusses the production of satellite swath-level surface shortwave radiation and longwave radiation estimates. The swath-level shortwave radiation estimates are converted into clearness-index values. Clearness index reduces the dependency on solar zenith angle, which allows for the assimilation of observations over a given time window. An automated quality-control process is applied to the swath-level estimates of clearness index and surface longwave radiation. Then 2D variational analyses of the quality-controlled satellite estimates with background atmospheric model fields form global gridded radiative heat flux fields. The clearness-index analysis fields are converted into shortwave analysis fields to be used in other applications. Three-hourly shortwave and longwave analysis fields are created from 1 May 2013 through 30 April 2014. These fields are validated against observations from research vessels and moored-buoy platforms and compared with NAVGEM. With the exception of the mean bias, the NFLUX fields have smaller errors when compared with those of NAVGEM.