bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yersinia pestis YopK Inhibits Bacterial Adhesion to Host Cells by Binding to the Extracellular Matrix Adaptor Protein Matrilin-2
Authors: Tan Yafang , Liu Wanbing , Zhang Qingwen , Cao Shiyang , Zhao Haihong , Wang Tong , Qi Zhizhen , Han Yanping , Song Yajun , Wang Xiaoyi , Yang Ruifu , Du Zongmin 
Published: May 2017

ABSTRACT

Pathogenic yersiniae harbor a type III secretion system (T3SS) that injects
Yersinia
outer protein (Yop) into host cells. YopK has been shown to control Yop translocation and prevent inflammasome recognition of the T3SS by the innate immune system. Here, we demonstrate that YopK inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (MATN2). YopK binds to MATN2, and deleting amino acids 91 to 124 disrupts binding of YopK to MATN2. A
yopK
null mutant exhibits a hyperadhesive phenotype, which could be responsible for the established Yop hypertranslocation phenotype of
yopK
mutants. Expression of YopK, but not YopK
Δ91–124
, in a
yopK
mutant restored the wild-type phenotypes of adhesion and Yop translocation, suggesting that binding to MATN2 might be essential for YopK to inhibit bacterial adhesion and negatively regulate Yop translocation. A green fluorescent protein (GFP)-YopK fusion specifically binds to the endogenous MATN2 on the surface of HeLa cells, whereas GFP-YopK
Δ91–124
cannot. Addition of purified YopK protein during infection decreased adhesion of
Y. pestis
to HeLa cells, while YopK
Δ91–124
protein showed no effect. Taking these results together, we propose a model that the T3SS-secreted YopK hinders bacterial adhesion to HeLa cells by binding to MATN2, which is ubiquitously exposed on eukaryotic cells.
Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans
Authors: Vesga Boris , Hernandez Hector , Higuera Sergio , Gasior Pawel , Echeveri Dario , Delgado Juan A , Dager Antonio , Arana Camilo , Simonton Charles , Maehara Akiko , Palmaz Julio , Granada Juan F 
Published: May 2017

ObjectiveTo evaluate the biological effect of microengineered stent grooves (MSG) on early strut healing in humans by performing optical coherence tomography (OCT) analysis 3 weeks following the implantation.BackgroundIn the experimental setting, MSG accelerate endothelial cell migration and reduce neointimal proliferation compared with bare metal stent (BMS).MethodsA total of 37 patients undergoing percutaneous coronary intervention with de novo coronary lesions were randomly assigned to either MSG (n=19) or an identical BMS controls (n=18). All patients underwent OCT imaging at 3 weeks. A total of 7959 struts were included in the final analysis.ResultsAt 3 weeks following stent implantation, almost all struts analysed (~97%) had evidence of tissue coverage. The percentage of partially covered struts was comparable between both groups. However, the percentage of fully embedded struts was higher in the BMS group (81.22%, 49.75–95.52) compared with the MSG group (74.21%, 58.85–86.38). The stent-level analysis demonstrated reduction in neointimal formation (neointimal hyperplasia area and volume reduction of ~14% and ~19%, respectively) in the MSG versus the BMS group. In the strut-level analysis, an even greater reduction (~22% in neointimal thickness) was seen in the MSG group. Layered neointimal was present in ~6% of the OCT frames in the BMS group while it was not present in the MSG group.ConclusionsMSG induced a more homogeneous and predictable pattern of surface healing in the early stages following stent implantation. The biological effect of MSG on stent healing has the potential to improve the safety profile of current generation drug-eluting stents.ClassificationsBMS, OCT, clinical trials.
Characteristics, management and response to alteplase in China versus non-China participants of the ENCHANTED trial
Authors: Song Lily , Wang Xia , Robinson Thompson , Lindley Richard I , Arima Hisatomi , Lavados Pablo M , Chen Xiaoying , Chalmers John , Anderson Craig S 
Published: May 2017

BackgroundThe characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS.MethodsENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS.ResultsParticipants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2–6 (55.6% vs 47.8%; OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07; p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8%; p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants.ConclusionPatients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.
Production of copper-64 and gallium-68 with a medical cyclotron using liquid targets
Authors: Alves F. , Alves V. H. P. , Do Carmo S. J. C. , Neves A. C. B. , Silva M. , Abrunhosa A. J. 
Published: May 2017

This work describes the production of two clinically relevant metal radioisotopes [Formula: see text] and [Formula: see text] with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched [Formula: see text] and [Formula: see text] were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/([Formula: see text]Ah ⋅ mg) and 1.5 MBq/([Formula: see text]Ah ⋅ mg)) of [Formula: see text] and [Formula: see text]; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched material. Purified solutions containing [Formula: see text] and [Formula: see text] were obtained within 30 min after EOB and used to produce [Formula: see text]-ATSM and [Formula: see text]–DOTA–NOC, respectively, with quality parameters suitable for human use.
Conformally non-flat spacetime representing dense compact objects
Authors: Singh Ksh. Newton , Bhar Piyali , Rahaman Farook , Pant Neeraj , Rahaman Mansur 
Published: May 2017

A new conformally non-flat interior spacetime embedded in five-dimensional (5D) pseudo Euclidean space is explored in this paper. We proceed our calculation with the assumption of spherically symmetric anisotropic matter distribution and Karmarkar condition (necessary condition for class one). This solution is free from geometrical singularity and well-behaved in all respects. We ansatz a new type of metric potential [Formula: see text] and solve for the metric potential [Formula: see text] via Karmarkar condition. Further, all the physical parameters are determined from Einstein’s field equations using the two metric potentials. All the constants of integration are determined using boundary conditions. Due to its conformally non-flat character, it can represent bounded configurations. Therefore, we have used it to model two compact stars Vela X-1 and Cyg X-2. Indeed, the obtained masses and radii of these two objects from our solution are well matched with those observed values given in [T. Gangopadhyay et al., Mon. Not. R. Astron. Soc. 431, 3216 (2013)] and [J. Casares et al., Mon. Not. R. Astron. Soc. 401, 2517 (2010)]. The equilibrium of the models is investigated from generalized TOV-equation. We have adopted [L. Herrera’s, Phys. Lett. A 165, 206 (1992)] method and static stability criterion of Harisson–Zeldovich–Novikov [B. K. Harrison et al., Gravitational Theory and Gravitational Collapse (University of Chicago Press, 1965); Ya. B. Zeldovich and I. D. Novikov, Relativistic Astrophysics, Vol. 1, Stars and Relativity (University of Chicago Press, 1971)] to analyze the stability of the models.
Fractionated Radiation Therapy Stimulates Antitumor Immunity Mediated by Both Resident and Infiltrating Polyclonal T-cell Populations when Combined with PD-1 Blockade
Authors: Dovedi Simon J. , Cheadle Eleanor J. , Popple Amy L. , Poon Edmund , Morrow Michelle , Stewart Ross , Yusko Erik C. , Sanders Catherine M. , Vignali Marissa , Emerson Ryan O. , Robins Harlan S. , Wilkinson Robert W. , Honeychurch Jamie , Illidge Timothy M. 
Published: May 2017

Abstract
Purpose: Radiotherapy is a highly effective anticancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. Radiotherapy is known to enhance tumor immunogenicity; however, the contribution and mechanisms of radiotherapy-induced immune responses are unknown.
Experimental Design: The impact of low-dose fractionated radiotherapy (5 × 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing of the T-cell receptor (TCR) repertoire. A dual-tumor model was used, with fractionated radiotherapy delivered to a single tumor site to enable evaluation of the local and systemic response to treatment and ability to induce abscopal responses outside the radiation field.
Results: We show that fractionated radiotherapy leads to T-cell infiltration at the irradiated site; however, the TCR landscape remains dominated by polyclonal expansion of preexisting T-cell clones. Adaptive resistance via the PD-1/PD-L1 pathway restricts the generation of systemic anticancer immunity following radiotherapy, which can be overcome through combination with αPD-1 mAb leading to improved local and distal tumor control. Moreover, we show that effective clearance of tumor following combination therapy is dependent on both T cells resident in the tumor at the time of radiotherapy and infiltrating T cells.
Conclusions: These data provide evidence that radiotherapy can enhance T-cell trafficking to locally treated tumor sites and augment preexisting anticancer T-cell responses with the capacity to mediate regression of out-of-field tumor lesions when delivered in combination with αPD-1 mAb therapy. Clin Cancer Res; 23(18); 5514–26. ©2017 AACR.
Multifunctional Effects of a Small-Molecule STAT3 Inhibitor on NASH and Hepatocellular Carcinoma in Mice
Authors: Jung Kwang Hwa , Yoo Wonbeak , Stevenson Heather L. , Deshpande Dipti , Shen Hong , Gagea Mihai , Yoo Suk-Young , Wang Jing , Eckols T. Kris , Bharadwaj Uddalak , Tweardy David J. , Beretta Laura 
Published: May 2017

Abstract
Purpose: The incidence of hepatocellular carcinoma is increasing in the United States, and liver cancer is the second leading cause of cancer-related mortality worldwide. Nonalcoholic steatohepatitis (NASH) is becoming an important risk for hepatocellular carcinoma, and most patients with hepatocellular carcinoma have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat hepatocellular carcinoma in the context of NASH and cirrhosis are urgently needed.
Experimental Design: Constitutive activation of STAT3 is frequently detected in hepatocellular carcinoma tumors. STAT3 signaling plays a pivotal role in hepatocellular carcinoma survival, growth, angiogenesis, and metastasis. We identified C188-9, a novel small-molecule STAT3 inhibitor using computer-aided rational drug design. In this study, we evaluated the therapeutic potential of C188-9 for hepatocellular carcinoma treatment and prevention.
Results: C188-9 showed antitumor activity in vitro in three hepatocellular carcinoma cell lines. In mice with hepatocyte-specific deletion of Pten (HepPten− mice), C188-9 treatment blocked hepatocellular carcinoma tumor growth, reduced tumor development, and reduced liver steatosis, inflammation, and bile ductular reactions, resulting in improvement of the pathological lesions of NASH. Remarkably, C188-9 also greatly reduced liver injury in these mice as measured by serum aspartate aminotransferase and alanine transaminase levels. Analysis of gene expression showed that C188-9 treatment of HepPten− mice resulted in inhibition of signaling pathways downstream of STAT3, STAT1, TREM-1, and Toll-like receptors. In contrast, C188-9 treatment increased liver specification and differentiation gene pathways.
Conclusions: Our results suggest that C188-9 should be evaluated further for the treatment and/or prevention of hepatocellular carcinoma. Clin Cancer Res; 23(18); 5537–46. ©2017 AACR.
Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient–Derived Xenografts
Authors: Mohamed Suhaimi Nur-Afidah , Phyo Wai Min , Yap Hao Yun , Choy Sharon Heng Yee , Wei Xiaona , Choudhury Yukti , Tan Wai Jin , Tan Luke Anthony Peng Yee , Foo Roger Sik Yin , Tan Suzanne Hui San , Tiang Zenia , Wong Chin Fong , Koh Poh Koon , Tan Min-Han 
Published: May 2017

Abstract
There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P &lt; 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035–44. ©2017 AACR.
Comparison and the Spectre of Perennialism: A Reply to Craig Martin
Authors: Blum Jason 
Published: May 2017

AbstractCraig Martin accuses me of repeating the mistakes of perennialism, perpetuating an irresponsible and covertly theological approach to research that rushes to identify dubious “similarities” in religious experience across culture and history. While it is true that I identify cross-cultural similarities in the accounts of mystical experience that I examine inZen and the Unspeakable God, that argument is based on historical evidence, and does not imply the questionable theological conclusions for which classical perennialism has been criticized. Learning from the mistakes of perennialism does not mean dismissing comparison as an illegitimate enterprise or rejecting cross-cultural similarities asprima facieimpossible; it means insisting on evidentially-grounded and historically sensitive research that is willing and able to identify both differences and similarities. It also means resisting the temptation to oversimplify our task by reducing all research on religion to one preferred analytical category.
Intranasal Steroid Use for Otitis Media with Effusion: Ongoing Opportunities for Quality Improvement
Authors: Wang David E. , Lam Derek J. , Bellmunt Angela M. , Rosenfeld Richard M. , Ikeda Allison K. , Shin Jennifer J. 
Published: May 2017

ObjectivesOur objectives were (1) to assess patterns of intranasal steroid administration when otitis media with effusion (OME) has been diagnosed in children, (2) to investigate whether usage varies according to visit setting, and (3) to determine if practice gaps are such that quality improvement could be tracked.Study DesignCross‐sectional analysis of an administrative database.Subjects and MethodsNational Ambulatory and Hospital Ambulatory Medical Care Surveys, 2005 to 2012; univariate, multivariate, and stratified analyses of intranasal steroid usage were performed. The primary outcome was intranasal steroid administration, and the primary predictor was a diagnosis of OME. The impact of location of service was also analyzed.ResultsData representing 1,943,177,903 visits demonstrated that intranasal steroids were administered in 10.0% of visits in which OME was diagnosed, in comparison to 3.5% of visits in which OME was not diagnosed (univariate odds ratio, 3.07; 95% confidence interval [CI], 1.85‐5.08; P <. 001). After adjusting for age, sex, race/ethnicity, and other confounding conditions, multivariate analysis demonstrated that OME remained associated with an increase in intranasal steroid usage (odds ratio, 3.58; 95% CI, 1.60‐8.01; P =. 002). This practice pattern was more prevalent in the ambulatory office setting (risk difference 6.6%, P <. 001) and less seen in a hospital‐based office or emergency department.ConclusionDespite randomized controlled trials showing a lack of efficacy for isolated OME, nasal steroids continue to be used in treating children with OME in the United States. Related quality improvement opportunities to prevent usage of an ineffective treatment exist.
Tympanostomy Tube Placement vs Medical Management for Recurrent Acute Otitis Media in TRICARE‐Insured Children
Authors: Raol Nikhila , Sharma Meesha , Boss Emily F. , Jiang Wei , Scott John W. , Learn Peter , Weissman Joel S. 
Published: May 2017

ObjectiveTo compare number of infections and health care utilization in children insured by TRICARE with recurrent acute otitis media (RAOM) managed surgically with tympanostomy tube (TT) placement compared with those managed medically.Study DesignRetrospective matched cohort study.SettingTRICARE claims database from 2006 to 2010.Subjects and MethodsWe matched TRICARE beneficiaries ≤5 years of age diagnosed with RAOM who underwent TT placement with those managed medically using 1:1 coarsened‐exact matching on age, sex, race, sponsor rank, and region. We used multivariable negative binomial regression to compare number of infections and health care utilization at 1 and 2 years. Outcomes were adjusted for rate of infection before treatment for RAOM, season of either TT placement or establishment of candidacy for TT placement, and comorbidities.ResultsAmong 6659 pairs identified at 1‐year follow‐up, the TT group had fewer infections (1.96 vs 2.18, P <. 001) and oral antibiotic prescriptions (1.52 vs 1.67, P <. 001) but more visits to primary care physicians (4.36 vs 4.06, P <. 0001) and otolaryngologists (1.21 vs 0.44, P <. 0001) compared with the medically managed group. At 2‐year follow‐up, the benefits of TT placement were no longer seen.ConclusionTT placement for RAOM is associated with fewer infections and oral antibiotic prescriptions in the first year after surgery but more doctor visits. Benefits of TT placement do not appear to extend through the second year. Future research should investigate costs associated with TT placement vs medical management, as well as real‐time health care utilization with impact on patient symptoms and quality of life.
Factors affecting recovery from anaesthesia with propofol–remifentanil target-controlled infusion in laparoscopic surgery
Authors: Liu Shao-hua , Tian Ming 
Published: May 2017

Objective This study was performed to analyse factors influencing the effect-site concentration (Ce) of propofol at return of consciousness (ROC) with target-controlled infusion of propofol–remifentanil after laparoscopic surgery. Methods In total, 112 patients who underwent laparoscopic surgery under general anaesthesia were given propofol at the target concentration of 3.5 µg/ml. Remifentanil (Ce: 4.0 ng/ml) and 0.9 mg/kg of rocuronium were administered when the Observer’s Assessment of Alertness/Sedation score reached 1. Two minutes after injection of rocuronium, tracheal intubation was initiated. The bispectral index (BIS) was maintained between 45 and 55. Results Ce values of propofol at loss of consciousness (LOC) and ROC were significantly correlated. Age was significantly correlated with Ce of propofol at ROC. At LOC, propofol Ce values of patients aged 65–80, 45–64, and 20–44 years were 1.8 ± 0.8, 2.2 ± 0.7, and 2.3 ± 0.8 µg/ml, respectively, and the BIS was 70 ± 10, 68 ± 7, and 69 ± 10, respectively. At ROC, the propofol Ce values of the three groups were 1.2 ± 0.3, 1.4 ± 0.3, and 1.5 ± 0.3 µg/ml, respectively, and the BIS was 80 ± 5, 82 ± 6, and 83 ± 6, respectively. Conclusions The concentration of propofol at ROC was significantly affected by age, and ROC of propofol–remifentanil anaesthesia after laparoscopic surgery was well predicted by the concentration at LOC.
Chlorhexidine and silver sulfadiazine coating on central venous catheters is not sufficient for protection against catheter-related infection: Simulation-based laboratory research with clinical validation
Authors: Choi Yoon Ji , Lim Jae Kwan , Park Jeong Jun , Huh Hyub , Kim Dong-Joo , Gong Chang-Hoon , Yoon Seung Zhoo 
Published: May 2017

Objective The efficacy of chlorhexidine- and silver sulfadiazine-coated central venous catheters (CSS-CVC) against catheter-related infection remains controversial. We hypothesized that the loss of silver nanoparticles may reduce the antibacterial efficacy of CSS-CVCs and that this loss could be due to the frictional force between the surface of the CVC and the bloodstream. The objective of this study was to investigate whether the antimicrobial effect of CSS-CVCs decreases with increasing exposure time in a bloodstream model and quantitatively assay the antimicrobial effect of CSS-CVCs compared with polyurethane and antiseptic-impregnated CVCs. Methods Each CVC was subjected to 120 hours of saline flow and analyzed at intervals over 24 hours. The analyses included energy-dispersive X-ray spectroscopy, scanning electron microscopy, and optical density after a Staphylococcus aureus incubation test. Results The weight percentage of silver in the CSS-CVCs significantly decreased to 56.18% (44.10% ± 3.32%) with 48-hour catheterization and to 18.88% (14.82% ± 1.33%) with 120-hour catheterization compared with the initial weight percentage (78.50% ± 6.32%). In the S. aureus incubation test, the antibacterial function of CSS-CVCs was lost after 48 hours [3 (N/D) of OD]. Similar results were observed in a pilot clinical study using 18 CSS-CVCs. Conclusions We found that the efficacy of CSS-CVCs decreased over time and that the antibacterial function was lost after 48 hours of simulated wear-out. Therefore, antibiotic-impregnated CVCs may be a better option when longer (>48 hours) indwelling is needed.