bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment
In Vivo
Assay
Authors: Papadopoulou Maria V. , Bloomer William D. , Rosenzweig Howard S. , Mazzeti Ana Lia , Gonçalves Karolina Ribeiro , Mendes Priscila Fagundes , Bahia Maria Terezinha 
Published: February 2017

ABSTRACT

3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both
in vitro
and
in vivo
after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent
Trypanosoma cruzi
Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.
Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens
Authors: Hendrick William A. , Orr Mona W. , Murray Samantha R. , Lee Vincent T. , Melville Stephen B. 
Published: February 2017

ABSTRACT

The Gram-positive pathogen
Clostridium perfringens
possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in
C. perfringens
, called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the
pilB2
and
pilC2
genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected
in vivo
or
in vitro
even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from
C. perfringens
(CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels
in vivo
but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from
in vivo
studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium.

IMPORTANCE
Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species
Clostridium perfringens
was used to study proteins involved in polymerizing the pilin, PilA2, into a pilus. The assembly ATPase PilB2 and its cognate membrane protein partner, PilC2, were purified. PilB2 bound the intracellular signal molecule c-di-GMP. Increased levels of intracellular c-di-GMP led to increased polymerization of PilA2, indicating that Gram-positive bacteria use this molecule to regulate pilus synthesis. These findings provide valuable information for understanding how pathogenic clostridia regulate TFP to cause human diseases.
Understanding the Models of Community Hospital rehabilitation Activity (MoCHA): a mixed-methods study
Authors: Gladman John , Buckell John , Young John , Smith Andrew , Hulme Clare , Saggu Satti , Godfrey Mary , Enderby Pam , Teale Elizabeth , Longo Roberto , Gannon Brenda , Holditch Claire , Eardley Heather , Tucker Helen 
Published: February 2017

IntroductionTo understand the variation in performance between community hospitals, our objectives are: to measure the relative performance (cost efficiency) of rehabilitation services in community hospitals; to identify the characteristics of community hospital rehabilitation that optimise performance; to investigate the current impact of community hospital inpatient rehabilitation for older people on secondary care and the potential impact if community hospital rehabilitation was optimised to best practice nationally; to examine the relationship between the configuration of intermediate care and secondary care bed use; and to develop toolkits for commissioners and community hospital providers to optimise performance.Methods and analysis4 linked studies will be performed. Study 1: cost efficiency modelling will apply econometric techniques to data sets from the National Health Service (NHS) Benchmarking Network surveys of community hospital and intermediate care. This will identify community hospitals' performance and estimate the gap between high and low performers. Analyses will determine the potential impact if the performance of all community hospitals nationally was optimised to best performance, and examine the association between community hospital configuration and secondary care bed use. Study 2: a national community hospital survey gathering detailed cost data and efficiency variables will be performed. Study 3: in-depth case studies of 3 community hospitals, 2 high and 1 low performing, will be undertaken. Case studies will gather routine hospital and local health economy data. Ward culture will be surveyed. Content and delivery of treatment will be observed. Patients and staff will be interviewed. Study 4: co-designed web-based quality improvement toolkits for commissioners and providers will be developed, including indicators of performance and the gap between local and best community hospitals performance.Ethics and disseminationPublications will be in peer-reviewed journals, reports will be distributed through stakeholder organisations. Ethical approval was obtained from the Bradford Research Ethics Committee (reference: 15/YH/0062).
Research and analysis on the broadband dispersion tailoring of the sub-micro silicon-on-insulator waveguides
Authors: Wen Jin , Liu Wang , Liu Keyang , Fu Haiwei , Jia Zhenan 
Published: February 2017

High-order dispersions of the silicon-on-insulator (SOI) waveguides with different shapes (including slab, ridge and slot) have been obtained and compared using the finite element method (FEM). Through adjusting the geometrical parameters of the waveguides, single or dual zero-dispersion wavelengths (ZDWs) can be tuned in the broadband wavelength range. Differences of dispersion curves among these waveguides are analyzed from the viewpoint of structure and mechanism in detail. It is remarkably shown the number of ZDWs can be varied from 0 to 2 and the position of the ZDWs can be tuned from 1400 nm to 1900 nm flexibly. Moreover, the differences of dispersion features in short and long wavelength regions are also discussed deeply. Due to the dispersion of SOI waveguides playing a dominated role in many nonlinear optical effects, this research can make some contribution for dispersion tailoring and nonlinear optics.
A temperature characteristic research and compensation design for micro-machined gyroscope
Authors: Fu Qiang , Di Xin-Peng , Chen Wei-Ping , Yin Liang , Liu Xiao-Wei 
Published: February 2017

The all temperature range stability is the most important technology of MEMS angular velocity sensor according to the principle of capacity detecting. The correlation between driven force and zero-point of sensor is summarized according to the temperature characteristic of the air-damping and resonant frequency of sensor header. A constant trans-conductance high-linearity amplifier is designed to realize the low phase-drift and low amplitude-drift interface circuit at all-temperature range. The chip is fabricated in a standard 0.5 [Formula: see text] CMOS process. Compensation achieved by driven force to zero-point drift caused by the stiffness of physical construction and air-damping is adopted. Moreover, the driven force can be obtained from the drive-circuit to avoid the complex sampling. The test result shows that the zero-point drift is lower than 30[Formula: see text]/h (1-sigma) at the temperature range from −40[Formula: see text]C to 60[Formula: see text]C after three-order compensation made by driven force.
CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype
Authors: Lal Shruti , Cheung Edwin C. , Zarei Mahsa , Preet Ranjan , Chand Saswati N. , Mambelli-Lisboa Nicole C. , Romeo Carmella , Stout Matthew C. , Londin Eric , Goetz Austin , Lowder Cinthya Y. , Nevler Avinoam , Yeo Charles J. , Campbell Paul M. , Winter Jordan M. , Dixon Dan A. , Brody Jonathan R. 
Published: February 2017

Abstract
Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro, as HuR-deficient MIA PaCa-2 (MIA.HuR-KO(−/−)) cells had increased apoptosis when compared with isogenic wild-type (MIA.HuR-WT(+/+)) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a two-dimensional culture into three dimensional (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared with control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. Although not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO(−/−)) showed significantly reduced in vivo tumor growth compared with controls (HCT.HuR-WT(+/+)). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes.
Implications: The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. Mol Cancer Res; 15(6); 696–707. ©2017 AACR.
Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma
Authors: Mitsui Yozo , Shiina Hiroaki , Kato Taku , Maekawa Shigekatsu , Hashimoto Yutaka , Shiina Marisa , Imai-Sumida Mitsuho , Kulkarni Priyanka , Dasgupta Pritha , Wong Ryan Kenji , Hiraki Miho , Arichi Naoko , Fukuhara Shinichiro , Yamamura Soichiro , Majid Shahana , Saini Sharanjot , Deng Guoren , Dahiya Rajvir , Nakajima Koichi , Tanaka Yuichiro 
Published: February 2017

AbstractThe proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis (P &lt; 0.001) and worse 5-year overall survival after radical nephrectomy (P = 0.014). In vitro, VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling–related genes such as TNFα, BID, and BAK. Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies.Implications: This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer. Mol Cancer Res; 15(7); 884–95. ©2017 AACR.
Operationalizing the definition of e-leadership: identifying the elements of e-leadership
Authors: Van Wart Montgomery , Roman Alexandru , Wang XiaoHu , Liu Cheol 
Published: February 2017

The effects of the ongoing digital revolution have been profound and have been studied in many contexts such as government interaction with the public (e-participation) and administrative structures (e-administration). However, the study of how the digital revolution has changed leaders’ interactions with followers via information and communication technologies (ICTs) has been modest, and the theory building in organizational studies and public administration has been, for the most part, nonexistent. A major reason for this lack of progress is the inability to produce an operational definition of e-leadership that spans telework, team, and enterprise settings. The article examines an exploratory case study to propose an operational definition based on six factors (or broad e-competencies) for e-leadership. Research limitations and future research opportunities are discussed. Points for practitioners E-leadership, technology-mediated leadership, has become critically important for leaders at all levels, both inside and outside of the organization. E-leadership is as much about blending technologies and traditional communication as it is about simply using more ICT-mediated communication. While there is a lot of consistency in the types of leadership skills needed in traditional and virtual environments, they are not the same and the differences are critical to success and failure. The areas in which competence in e-skills were most important included: e-communication, e-social skills, e-team building, e-change management, e-technology skills, and e-trustworthiness.
Exploring Cognitive Decision-making Processes, Computer-focused Cyber Deviance Involvement and Victimization
Authors: Louderback Eric R. , Antonaccio Olena 
Published: February 2017

Objectives: Investigate the relationship between thoughtfully reflective decision-making (TRDM) and computer-focused cyber deviance involvement and computer-focused cybercrime victimization. Method: Survey data collected from samples of 1,039 employees and 418 students at a large private university were analyzed using ordinary least squares and negative binomial regression to test the effects of TRDM on computer-focused cyber deviance involvement and victimization. Results: TRDM reduces computer-focused cyber deviance involvement and computer-focused cybercrime victimization across measures and samples. The sensitivity analyses also indicated that TRDM is a more robust predictor of cyber deviance involvement than victimization. The results from moderation analyses showed that, whereas protective effects of TRDM are invariant across genders, they are less salient among older employees for the scenario-based measure of cybercrime victimization. Conclusions: Individual-level cognitive decision-making processes are important in predicting computer-focused cyber deviance involvement and victimization. These results can inform the development of targeted institutional and criminal justice policies aimed at reducing computer-focused cybercrime.
The silent world of young next of kin in mental healthcare
Authors: Martinsen Elin Håkonsen , Weimand Bente M , Pedersen Reidar , Norvoll Reidun 
Published: February 2017

Background: Young next of kin to patients with mental health problems are faced with many challenges. It is important to focus on the special needs of children and adolescents as next of kin to ensure their welfare and prevent harm. Research questions: We aimed to investigate young next of kin’s need for information and involvement, to examine the ways they cope with situations involving coercion related to the treatment of their relative, and to identify ethical challenges. Research design: We conducted a qualitative study based on semi-structured, individual interviews. Participants and research context: Seven young next of kin aged 14–22 years participated in the study. The informants were recruited from a regional hospital trust in Norway. Ethical considerations: The study was approved by the National Data Protection Official for Research and based upon informed consent and confidentiality. Findings: The adolescents wanted more information and described a need for increased interaction with their sick relative at the hospital. They struggled to keep their relationship with their relative intact, and they described communication problems in the family. Coercive treatment was perceived in a negative way. Discussion: The study finds that there are ethical challenges at stake for young next of kin and their families other than those that are often emphasized by traditional healthcare, which often focuses on the individual patient’s rights. These challenges are related to the young next of kin’s needs for interconnectedness and for the preservation of relationships as well as challenges related to family communication and the need for information. Conclusion: The study finds a need for more family-oriented perspectives in both mental healthcare practices and healthcare ethics.
Thinking on writing a critical essay
Authors: Ng Lillian Lywan 
Published: February 2017

Objective: To provide a strategy for writing a critical essay for the Royal Australian and New Zealand College of Psychiatrists examination using a sample question. Conclusion: To prepare for writing a critical essay, candidates are advised to read widely and critically, to practise writing essays with a clear structure under examination conditions and seek constructive critique from colleagues. This will help them to write succinctly and develop a reasoned argument that is relevant to the quotation.
Correlation between clot density and recanalization success or stroke etiology in acute ischemic stroke patients
Authors: Jagani Manoj , Kallmes David F , Brinjikji Waleed 
Published: February 2017

Background Predicting recanalization success for patients undergoing endovascular treatment for acute ischemic stroke is of significant interest. Studies have previously correlated the success of recanalization with the density of the clot. We evaluated clot density and its relationship to revascularization success and stroke etiology. Methods We conducted a retrospective review of 118 patients undergoing intra-arterial therapy for acute ischemic stroke. Mean and maximum thrombus density was measured by drawing a circular region of interest on an axial slice of a non-contrast computed tomography scan. T-tests were used to compare clot density to recanalization success or to stroke etiology, namely large artery atherosclerosis and cardioembolism. Recanalization success was compared in four device groups: aspiration, stent retriever, aspiration and stent retriever, and all other. Results There was no significant difference in the mean clot density in patients with successful ( n = 80) versus unsuccessful recanalization ( n = 38, 50.1 ± 7.4 Hounsfield unit (HU) vs. 53 ± 12.7 HU; P = 0.17). Comparing the large artery thromboembolism ( n = 35) to the cardioembolic etiology group ( n = 56), there was no significant difference in mean clot density (51.5 ± 7.7 HU vs. 49.7 ± 8.5 HU; P = 0.31). A subgroup analysis of middle cerebral artery occlusions ( n = 65) showed similar, non-statistically significant differences between groups. There was no difference in the rate of recanalization success in patients with a mean clot density greater than 50 HU or less than 50 HU in each of the four device groups. Conclusions There was no relationship between clot density and revascularization success or stroke etiology in our study. More research is needed to determine if clot density can predict recanalization rates or indicate etiology.
Utility of single-energy and dual-energy computed tomography in clot characterization: An in-vitro study
Authors: Brinjikji Waleed , Michalak Gregory , Kadirvel Ramanathan , Dai Daying , Gilvarry Michael , Duffy Sharon , Kallmes David F , McCollough Cynthia , Leng Shuai 
Published: February 2017

Background and purpose Because computed tomography (CT) is the most commonly used imaging modality for the evaluation of acute ischemic stroke patients, developing CT-based techniques for improving clot characterization could prove useful. The purpose of this in-vitro study was to determine which single-energy or dual-energy CT techniques provided optimum discrimination between red blood cell (RBC) and fibrin-rich clots. Materials and methods Seven clot types with varying fibrin and RBC densities were made (90% RBC, 99% RBC, 63% RBC, 36% RBC, 18% RBC and 0% RBC with high and low fibrin density) and their composition was verified histologically. Ten of each clot type were created and scanned with a second generation dual source scanner using three single (80 kV, 100 kV, 120 kV) and two dual-energy protocols (80/Sn 140 kV and 100/Sn 140 kV). A region of interest (ROI) was placed over each clot and mean attenuation was measured. Receiver operating characteristic curves were calculated at each energy level to determine the accuracy at differentiating RBC-rich clots from fibrin-rich clots. Results Clot attenuation increased with RBC content at all energy levels. Single-energy at 80 kV and 120 kV and dual-energy 80/Sn 140 kV protocols allowed for distinguishing between all clot types, with the exception of 36% RBC and 18% RBC. On receiver operating characteristic curve analysis, the 80/Sn 140 kV dual-energy protocol had the highest area under the curve for distinguishing between fibrin-rich and RBC-rich clots (area under the curve 0.99). Conclusions Dual-energy CT with 80/Sn 140 kV had the highest accuracy for differentiating RBC-rich and fibrin-rich in-vitro thrombi. Further studies are needed to study the utility of non-contrast dual-energy CT in thrombus characterization in acute ischemic stroke.