bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of anesthesia practice reduces catheter‐associated bloodstream infections: a quality improvement initiative
Authors: Martin Lizabeth D. , Rampersad Sally E. , Geiduschek Jeremy M. , Zerr Danielle M. , Weiss Gillian K. , Martin Lynn D. 
Published: April 2013

SummaryBackgroundA major strategic hospital goal is the prevention of catheter associated bloodstream infections (CABSI). In 2009, at our institution, the CABSI rate for patients who traveled out of the ICU to the operating room and other procedural areas under the care of an anesthesiologist was increased compared to patients who remained on the unit.AimsOur objective was to develop countermeasures to improve intraoperative cleanliness by anesthesia providers, minimize contamination of intravenous access points, and ultimately reduce CABSIs.Materials & MethodsA multidisciplinary team identified barriers to following best practices for reducing contamination of intravenous line entry‐ports. Using Continuous Performance Improvement (CPI) or Lean techniques, staff directly impacted by the changes developed countermeasures to improve anesthesia practice. Compliance with the new “best practices” improved with coaching and feedback.ResultsPostimplementation, CABSI rates for patients traveling off the ICU with anesthesiology providers decreased from 14.1 per thousand trips off the ICU preintervention in 2009 to 9.7 per 1000 trips in 2010 and to 0 per 1000 trips in 2011 postintervention. Hospital‐wide CABSI rates decreased from 3.5 per 1000 central line days preintervention to 2.2 per 1000 central line days after.ConclusionPractice modification by anesthesiology providers in the operating room can decrease workspace contamination and is associated with decreased CABSI rates.
Translatability and the scripting of other peoples’ souls
Authors: Wierzbicka Anna 
Published: April 2013

If anthropology aims at ‘understanding “others” ’, then obviously anthropologists must be interested in the meaning of what those ‘others’ say. But to understand what speakers of a language other than our own say, we need to know what exactly the words and grammatical categories of that other language mean. This article argues that translating indigenous categories into academic English does not allow us to capture indigenous perspectives and leads to what Geertz calls ‘scripting other people's souls’. Focusing on cognitive and cultural categories from Australian Aboriginal languages usually linked with English labels such as ‘kinship obligations’ and ‘odd‐numbered generations’, the article shows how the ways of thinking encoded in these languages can be explicated from the insider's point of view, in simple words and simple sentences directly cross‐translatable into the indigenous languages themselves.
Home Firm Performance After Foreign Investments and Divestitures
Authors: Engel Dirk , Procher Vivien 
Published: April 2013

AbstractAn almost undisputed aim for firms in today's globalised world is to operate internationally. Several papers find a positive relationship between foreign direct investment (FDI) and the domestic performance of firms. In this paper, we address the ‘FDI – export’ relationship to better understand this trend. Furthermore, by presenting results on firm's post‐divestiture employment growth at home, we are able to provide a more comprehensive view on firm performance after stepping in and out of foreign markets. We apply a propensity score matching technique in combination with a difference‐in‐difference estimator to analyse the performance dynamics of French firms that either invested abroad or carried out foreign divestitures during the period 2000–2007. FDI has, on average, a positive effect in terms of export share, operating turnover and employment in firm's domestic market. Industry differences reveal that firms in high‐tech industries experience a strong increase in their domestic performance, whereas firm performance in low‐tech industries increases only moderately in post‐investment periods. In contrast, the divestiture impact on the post‐divestiture performance is rather negligible.
The voltage‐dependent L‐type Ca2+ (CaV1.2) channel C‐terminus fragment is a bi‐modal vasodilator
Authors: Bannister John P. , Leo Marie Dennis , Narayanan Damodaran , Jangsangthong Wanchana , Nair Anitha , Evanson Kirk W. , Pachuau Judith , Gabrick Kyle S. , Boop Frederick A. , Jaggar Jonathan H. 
Published: April 2013

Key points
Voltage‐dependent L‐type Ca2+ (CaV1.2) channels are the major Ca2+ influx pathway and are central to contractility regulation in arterial smooth muscle cells.
CaV1.2 exists as a full‐length channel and undergoes cleavage to a short CaV1.2 and a C‐terminus (CCt) fragment in rat and human arterial smooth muscle cells.
CCt decreases CaV1.2 transcription and shifts the voltage dependence of current activation and inactivation to more depolarized potentials in arterial smooth muscle cells.
CCt reduces pressure‐ and depolarization‐induced vasoconstriction.
CCt is a bi‐modal vasodilator.
Abstract  Voltage‐dependent L‐type Ca2+ channels (CaV1.2) are the primary Ca2+ entry pathway in vascular smooth muscle cells (myocytes). CaV1.2 channels control systemic blood pressure and organ blood flow and are pathologically altered in vascular diseases, which modifies vessel contractility. The CaV1.2 distal C‐terminus is susceptible to proteolytic cleavage, which yields a truncated CaV1.2 subunit and a cleaved C‐terminal fragment (CCt). Previous studies in cardiac myocytes and neurons have identified CCt as both a transcription factor and CaV1.2 channel inhibitor, with different signalling mechanisms proposed to underlie some of these effects. CCt existence and physiological functions in arterial myocytes are unclear, but important to study given the functional significance of CaV1.2 channels. Here, we show that CCt exists in myocytes of both rat and human resistance‐size cerebral arteries, where it locates to both the nucleus and plasma membrane. Recombinant CCt expression in arterial myocytes inhibited CaV1.2 transcription and reduced CaV1.2 protein. CCt induced a depolarizing shift in the voltage dependence of both CaV1.2 current activation and inactivation, and reduced non‐inactivating current in myocytes. Recombinant truncated CCt lacking a putative nuclear localization sequence (Δ92CCt) did not locate to the nucleus and had no effect on arterial CaV1.2 transcription or protein. However, Δ92CCt shifted the voltage dependence of CaV1.2 activation and inactivation similarly to CCt. CCt and Δ92CCt both inhibited pressure‐ and depolarization‐induced vasoconstriction, although CCt was a far more effective vasodilator. These data demonstrate that endogenous CCt exists and reduces both CaV1.2 channel expression and voltage sensitivity in arterial myocytes. Thus, CCt is a bi‐modal vasodilator.
Metabolomics Guides Rational Development of a Simplified Cell Culture Medium for Drug Screening against Trypanosoma brucei
Authors: Creek Darren J. , Nijagal Brunda , Kim Dong-Hyun , Rojas Federico , Matthews Keith R. , Barrett Michael P. 
Published: April 2013

ABSTRACT

In vitro
culture methods underpin many experimental approaches to biology and drug discovery. The modification of established cell culture methods to make them more biologically relevant or to optimize growth is traditionally a laborious task. Emerging metabolomic technology enables the rapid evaluation of intra- and extracellular metabolites and can be applied to the rational development of cell culture media. In this study, untargeted semiquantitative and targeted quantitative metabolomic analyses of fresh and spent media revealed the major nutritional requirements for the growth of bloodstream form
Trypanosoma brucei
. The standard culture medium (HMI11) contained unnecessarily high concentrations of 32 nutrients that were subsequently removed to make the concentrations more closely resemble those normally found in blood. Our new medium, Creek's minimal medium (CMM), supports
in vitro
growth equivalent to that in HMI11 and causes no significant perturbation of metabolite levels for 94% of the detected metabolome (<3-fold change; α = 0.05). Importantly, improved sensitivity was observed for drug activity studies in whole-cell phenotypic screenings and in the metabolomic mode of action assays. Four-hundred-fold 50% inhibitory concentration decreases were observed for pentamidine and methotrexate, suggesting inhibition of activity by nutrients present in HMI11. CMM is suitable for routine cell culture and offers important advantages for metabolomic studies and drug activity screening.
Increased Resistance to Staphylococcus aureus Endophthalmitis in BALB/c Mice: Fas Ligand Is Required for Resolution of Inflammation but Not for Bacterial Clearance
Authors: Sugi Norito , Whiston Emily A. , Ksander Bruce R. , Gregory Meredith S. 
Published: April 2013

ABSTRACTFasL was recently shown be required for bacterial clearance in C57BL/6 mice that express the FasL.1 allotype. The FasL.2 allotype is expressed in BALB/c mice and exhibits increased binding affinity to and increased cytotoxic activity against Fas+target cells. Therefore, we hypothesized that BALB/c mice would be more resistant toStaphylococcus aureus-induced endophthalmitis. To test this hypothesis, C57BL/6, BALB/c, and BALB(gld) mice received intravitreal injections of 2,500 CFU ofS. aureus(RN6390). Clinical examinations, electroretinography (ERG), histology, and bacterial quantification were performed at 24, 48, 72, and 96 h postinjection. The myeloperoxidase (MPO) assay was used to quantitate neutrophil infiltration. At 96 h postinfection, 86% of C57BL/6 mice presented with complete destruction of the eye, compared to only 29% of BALB/c mice with complete destruction. To our surprise, in the absence of Fas ligand, BALB(gld) mice showed no difference in bacterial clearance compared to BALB/c mice. However, histology and ERG analysis revealed increased retinal damage and significant loss of retinal function. MPO analysis revealed equal numbers of neutrophils in BALB(gld) and BALB/c mice at 24 h postinfection. However, at 48 h, the neutrophil numbers remained significantly elevated in BALB(gld) mice, correlating with the increased retinal damage observed in BALB(gld) mice. We conclude that the increased resistance toS. aureusinduced endophthalmitis in BALB/c mice is not dependent upon the FasL. However, in contrast to C57BL/6 mice, FasL is required for resolution of inflammation and protecting host tissue from nonspecific damage in BALB/c mice.
High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis
Authors: Gaddy Jennifer A. , Radin Jana N. , Loh John T. , Zhang Feng , Washington M. Kay , Peek Richard M. , Algood Holly M. Scott , Cover Timothy L. 
Published: April 2013

ABSTRACT

Persistent colonization of the human stomach with
Helicobacter pylori
is a risk factor for gastric adenocarcinoma, and
H. pylori
-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT)
cagA
+
H. pylori
strain or an isogenic
cagA
mutant strain and maintained the animals on a regular diet or a high-salt diet. At 4 months postinfection, gastric adenocarcinoma was detected in 100% of the WT-infected/high-salt-diet animals, 58% of WT-infected/regular-diet animals, and none of the animals infected with the
cagA
mutant strain (
P
< 0.0001). Among animals infected with the WT strain, those fed a high-salt diet had more severe gastric inflammation, higher gastric pH, increased parietal cell loss, increased gastric expression of interleukin 1β (IL-1β), and decreased gastric expression of hepcidin and hydrogen potassium ATPase (H,K-ATPase) compared to those on a regular diet. Previous studies have detected upregulation of CagA synthesis in response to increased salt concentrations in the bacterial culture medium, and, concordant with the
in vitro
results, we detected increased
cagA
transcription
in vivo
in animals fed a high-salt diet compared to those on a regular diet. Animals infected with the
cagA
mutant strain had low levels of gastric inflammation and did not develop hypochlorhydria. These results indicate that a high-salt diet potentiates the carcinogenic effects of
cagA
+
H. pylori
strains.
T Cells Expressing Chimeric Antigen Receptors Can Cause Anaphylaxis in Humans
Authors: Maus Marcela V. , Haas Andrew R. , Beatty Gregory L. , Albelda Steven M. , Levine Bruce L. , Liu Xiaojun , Zhao Yangbing , Kalos Michael , June Carl H. 
Published: April 2013

AbstractT cells can be redirected to overcome tolerance to cancer by engineering with integrating vectors to express a chimeric antigen receptor (CAR). In preclinical models, we have previously shown that transfection of T cells with mRNA coding for a CAR is an alternative strategy that has antitumor efficacy and the potential to evaluate the on-target off-tumor toxicity of new CAR targets safely due to transient mRNA CAR expression. Here, we report the safety observed in four patients treated with autologous T cells that had been electroporated with mRNA coding for a CAR derived from a murine antibody to human mesothelin. Because of the transient nature of CAR expression on the T cells, subjects in the clinical study were given repeated infusions of the CAR-T cells to assess their safety. One subject developed anaphylaxis and cardiac arrest within minutes of completing the third infusion. Although human anti-mouse immunoglobulin (Ig)G antibodies have been known to develop with CAR-transduced T cells, they have been thought to have no adverse clinical consequences. This is the first description of clinical anaphylaxis resulting from CAR-modified T cells, most likely through IgE antibodies specific to the CAR. These results indicate that the potential immunogenicity of CARs derived from murine antibodies may be a safety issue for mRNA CARs, especially when administered using an intermittent dosing schedule. Cancer Immunol Res; 1(1); 26–31. ©2013 AACR.
Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo
Authors: Lanitis Evripidis , Poussin Mathilde , Klattenhoff Alex W. , Song Degang , Sandaltzopoulos Raphael , June Carl H. , Powell Daniel J. 
Published: April 2013

Abstract
Adoptive immunotherapy using T lymphocytes genetically modified to express a chimeric antigen receptor (CAR-T) holds considerable promise for the treatment of cancer. However, CAR-based therapies may involve on-target toxicity against normal tissues expressing low amounts of the targeted tumor-associated antigen (TAA). To specify T cells for robust effector function that is selective for tumor but not normal tissue, we developed a trans-signaling CAR strategy, whereby T-cell activation signal 1 (CD3ζ) is physically dissociated from costimulatory signal 2 (CD28) in two CARs of differing antigen specificity: mesothelin and a-folate receptor (FRa). Human T cells were genetically modified to coexpress signal 1 (anti-Meso scFv-CD3ζ) and signal 2 (anti-FRa scFv-CD28) CARs in trans. Trans-signaling CAR-T cells showed weak cytokine secretion against target cells expressing only one TAA in vitro, similar to first-generation CAR-T cells bearing CD3ζ only, but showed enhanced cytokine secretion upon encountering natural or engineered tumor cells coexpressing both antigens, equivalent to that of second-generation CAR-T cells with dual signaling in cis. CAR-T cells with dual specificity also showed potent anticancer activity and persistence in vivo, which was superior to first-generation CAR-T cells and equivalent to second-generation CARs. Importantly, second-generation CAR-T cells exhibited potent activity against cells expressing mesothelin alone, recapitulating normal tissue, whereas trans-signaling CAR-T cells did not. Thus, a dual specificity, trans-signaling CAR approach can potentiate the therapeutic efficacy of CAR-T cells against cancer while minimizing parallel reactivity against normal tissues bearing single antigen. Cancer Immunol Res; 1(1); 43–53. ©2013 AACR.
Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances
Authors: Keenan Bridget P. , Jaffee Elizabeth M. , Armstrong Todd D. 
Published: April 2013

Abstract
The fourth AACR Special Conference “Tumor Immunology: Basic and Clinical Advances” was held in Miami, FL in December 2012. The overall objective of this meeting was to discuss emerging concepts in cancer immunology and immunotherapy. The key findings that emerged from this meeting included: (i) multiple immune checkpoints should be inhibited to increase effective T-cell therapy, (ii) successful adoptive T-cell therapy will rely on obtaining the proper T-cell phenotype, (iii) chimeric antigen receptors have shown promise in treating some B-cell malignancies, and (iv) multiple pathways of inflammation within the tumor microenvironment are immunotherapy targets. Cancer Immunol Res; 1(1); 16–23. ©2013 AACR.
Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella Pneumoniae in mice
Authors: Patterson Craig M , Morrison Richard L , D’Souza Alain , Teng Xu S , Happel Kyle I 
Published: April 2013

Abstract

Background
Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia.

Methods
C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.

Results
Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model.

Conclusions
Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.
Identification of drought-responsive and novel Populus trichocarpamicroRNAs by high-throughput sequencing and their targets using degradome analysis
Authors: Shuai Peng , Liang Dan , Zhang Zhoujia , Yin Weilun , Xia Xinli 
Published: April 2013

Abstract

Background
MicroRNAs (miRNAs) are endogenous small RNAs (sRNAs) with a wide range of regulatory functions in plant development and stress responses. Although miRNAs associated with plant drought stress tolerance have been studied, the use of high-throughput sequencing can provide a much deeper understanding of miRNAs. Drought is a common stress that limits the growth of plants. To obtain more insight into the role of miRNAs in drought stress, Illumina sequencing of Populus trichocarpa sRNAs was implemented.

Results
Two sRNA libraries were constructed by sequencing data of control and drought stress treatments of poplar leaves. In total, 207 P. trichocarpa conserved miRNAs were detected from the two sRNA libraries. In addition, 274 potential candidate miRNAs were found; among them, 65 candidates with star sequences were chosen as novel miRNAs. The expression of nine conserved miRNA and three novel miRNAs showed notable changes in response to drought stress. This was also confirmed by quantitative real time polymerase chain reaction experiments. To confirm the targets of miRNAs experimentally, two degradome libraries from the two treatments were constructed. According to degradome sequencing results, 53 and 19 genes were identified as targets of conserved and new miRNAs, respectively. Functional analysis of these miRNA targets indicated that they are involved in important activities such as the regulation of transcription factors, the stress response, and lipid metabolism.

Conclusions
We discovered five upregulated miRNAs and seven downregulated miRNAs in response to drought stress. A total of 72 related target genes were detected by degradome sequencing. These findings reveal important information about the regulation mechanism of miRNAs in P. trichocarpa and promote the understanding of miRNA functions during the drought response.
The relationship between obesity and neurocognitive function in Chinese patients with schizophrenia
Authors: Guo Xiaofeng , Zhang Zhanchou , Wei Qinling , Lv Hailong , Wu Renrong , Zhao Jingping 
Published: April 2013

Abstract

Background
Studies have reported that up to 60% of individuals with schizophrenia are overweight or obese. This study explored the relationship between obesity and cognitive performance in Chinese patients with schizophrenia.

Methods
Outpatients with schizophrenia aged 18–50 years were recruited from 10 study sites across China. Demographic and clinical information was collected. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was used to assess cognitive function, and these 4 individual domains were transformed into a neurocognitive composite z score. In addition, height and weight were measured to calculate body mass index (BMI). Patients were categorized into 4 groups (underweight, normal weight, overweight and obese) based on BMI cutoff values for Asian populations recommended by the World Health Organization.

Results
A total number of 896 patients were enrolled into the study. Fifty-four percent of participants were overweight or obese. A higher BMI was significantly associated with lower scores on the Wechsler Memory Scale-Revised (WMS-R) Visual Reproduction subscale, the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol subscale, and the composite z score (p’s ≤ 0.024). Obese patients with schizophrenia had significantly lower scores than normal weight patients on the Trail Making Test B, the WMS-R Visual Reproduction subscale, the WAIS Digit Symbol subscale, and the composite z score (p’s ≤ 0.004).

Conclusions
Our study suggests that, in addition to its well established risk for various cardiometabolic conditions, obesity is also associated with decreased cognitive function in Chinese patients with schizophrenia. Future studies should explore if weight loss and management can improve cognitive function in obese patients who suffer from schizophrenia.