bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis
Authors: Kalil Andre C , Klompas Michael , Haynatzki Gleb , Rupp Mark E 
Published: October 2013

ObjectiveHospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin.DesignSystematic review and meta-analysis.Data sourcesPubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013.Eligibility criteria for selecting studiesAll randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia.Data extractionPreferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data.ResultsNine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI −2.1% to 2.1%; p=0.992; I2=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI −1.2% to 3.1%; p=0.409; I2=0%. The risk of both microbiological (RD=5.6%, 95% CI −2.2% to 13.3%; p=0.159; I2=0%) and methicillin-resistantStaphylococcus aureus(RD=6.4%, 95% CI −4.1% to 16.9%; p=0.230; I2=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality.ConclusionsLinezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia.
Republished: Interprofessional education in team communication: working together to improve patient safety
Authors: Brock Douglas , Abu-Rish Erin , Chiu Chia-Ru , Hammer Dana , Wilson Sharon , Vorvick Linda , Blondon Katherine , Schaad Douglas , Liner Debra , Zierler Brenda 
Published: October 2013

Abstract

Background
Communication failures in healthcare teams are associated with medical errors and negative health outcomes. These findings have increased emphasis on training future health professionals to work effectively within teams. The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) communication training model, widely employed to train healthcare teams, has been less commonly used to train student interprofessional teams. The present study reports the effectiveness of a simulation-based interprofessional TeamSTEPPS training in impacting student attitudes, knowledge and skills around interprofessional communication.

Methods
Three hundred and six fourth-year medical, third-year nursing, second-year pharmacy and second-year physician assistant students took part in a 4 h training that included a 1 h TeamSTEPPS didactic session and   three 1 h team simulation and feedback sessions. Students worked in groups balanced by a professional programme in a self-selected focal area (adult acute, paediatric, obstetrics). Preassessments and postassessments were used for examining attitudes, beliefs and reported opportunities to observe or participate in team communication behaviours.

Results
One hundred and forty-nine students (48.7%) completed the preassessments and postassessments. Significant differences were found for attitudes toward team communication (p&lt;0.001), motivation (p&lt;0.001), utility of training (p&lt;0.001) and self-efficacy (p=0.005). Significant attitudinal shifts for TeamSTEPPS skills included, team structure (p=0.002), situation monitoring (p&lt;0.001), mutual support (p=0.003) and communication (p=0.002). Significant shifts were reported for knowledge of TeamSTEPPS (p&lt;0.001), advocating for patients (p&lt;0.001) and communicating in interprofessional teams (p&lt;0.001).

Conclusions
Effective team communication is important in patient safety. We demonstrate positive attitudinal and knowledge effects in a large-scale interprofessional TeamSTEPPS-based training involving four student professions.
Novel cancer therapies: treatments driven by tumour biology
Authors: Ramaswami Ramya , Harding Victoria , Newsom-Davis Thomas 
Published: October 2013

Abstract
The traditional view is that treatments within oncology largely consist of chemotherapy, which aims to maximise damage to the rapidly dividing cancer cells but often at the expense of normal cells and overall quality of life for the patient. The development of anticancer drugs has changed from the serendipitous discoveries of the past, to today's purposeful targeting of cancer cells which takes advantage of novel technological developments and a greater understanding of tumour biology. The aim of these new treatments is to affect the essential function of the cancer cell while sparing normal cells, and limiting side effects. The phenotypic characteristics of tumours, such as unregulated growth signalling, development of new vascular systems and the evasion of immune destruction are used to identify potential drug targets. Here we review the clinical evidence and molecular mechanisms for novel therapies that are currently in use and those that are in development.
Republished: Whipple's disease
Authors: Puéchal Xavier 
Published: October 2013

Abstract
Whipple's disease is a chronic, systemic infection caused by Tropheryma whipplei. Gene amplification, isolation and DNA sequencing of T whipplei have extended our knowledge of this pathogen, which is now recognised as a ubiquitous commensal bacterium. The spectrum of signs associated with T whipplei has now been extended beyond the classic form, which affects middle-aged men, and begins with recurrent arthritis followed several years later by digestive problems associated with other diverse clinical signs. Children may present an acute primary infection, but only a small number of people with a genetic predisposition subsequently develop authentic Whipple's disease. This bacterium may also cause localised chronic infections with no intestinal symptoms: endocarditis, central nervous system involvement, arthritis, uveitis and spondylodiscitis. An impaired TH1 immune response is seen. T whipplei replication in vitro is dependent on interleukin 16 and is accompanied by the apoptosis of host cells, facilitating dissemination of the bacterium. In patients with arthritis, PCR with samples of joint fluid, saliva and stools has become the preferred examination for diagnosis. Immunohistochemical staining is also widely used for diagnosis. Treatment is based on recent microbiological data, but an immune reconstitution syndrome and recurrence remain possible. The future development of serological tests for diagnosis and the generalisation of antigen detection by immunohistochemistry should make it possible to obtain a diagnosis earlier and thus to decrease the morbidity, and perhaps also the mortality, associated with this curable disease which may, nonetheless, be fatal if diagnosed late or in an extensive systemic form.
Understanding and controlling the ingress of driven rain through exposed, solid wall masonry structures
Authors: Laycock Elizabeth A. , Wood Christopher 
Published: October 2013

Abstract
Long-term performance of historic buildings can be affected by many environmental factors, some of which become more apparent as the competence of the fabric deteriorates. Many tall historic buildings suffer from water ingress when exposed to driving rain conditions, particularly church towers in the SW of England. It is important to recognize that leakage can occur not only through flaws in the roof of a building but also through significant thicknesses of solid masonry. Identification of the most appropriate intervention requires an understanding of the way in which water might enter the structure and the assessment of potential repair options. While the full work schedule used an integrated assessment involving laboratory, field and archival work to assess the repairs that might be undertaken on these solid wall structures, this paper focuses on the laboratory work carried out to inform the writing of a Technical Advice Note on the effects of wind-driven rain and moisture movement in historic structures. The laboratory work showed that grouting and rendering were effective at reducing water penetration without retarding drying rates, and that use of internal plastering also had a very beneficial effect.
Building stone as a part of a World Heritage Site: ‘Piedra Pajarilla’ Granite and the city of Salamanca, Spain
Authors: Pereira Dolores , Cooper Barry J. 
Published: October 2013

Abstract
Building stone is a significant product in most human communities. While some civilizations paid more attention to the aesthetics of the stone, others focused more on physical properties, especially durability, as well as the ease of transportation to construction sites. These latter issues determined which rocks were exploited, in preference to others, for centuries. Ancient Roman society became expert in constructing durable engineering projects (e.g. roads, bridges and aqueducts). Most of their projects were realized using local granites and most remain in excellent condition today. The historic cores of many European cities need to preserve their integrity, using the original building stone of the city both for new construction and for restoration. A supply of the original material should be preserved in order to avoid use of alternative building stones when restoring old monuments. In Salamanca, a specific unique granite was used to build many of its monuments that are now preserved as part of the UNESCO World Heritage Site. An attempt to preserve this architecture and restore it, when needed, with the original material is the main focus of our paper, as some experiences using other types of rocks have led to unfortunate results.
Impact of cement repointing on rates of sandstone decay in medieval churches of the French Massif Central
Authors: André Marie-Françoise , Voldoire Olivier , Vautier Franck , Roussel Erwan , Phalip Bruno , Morel David 
Published: October 2013

Abstract
Three Romanesque churches of the Bourbonnais region in the French Massif Central have been investigated. These date back to the twelfth century, and are mainly built of red and white sandstones. Their ashlar blocks were extensively repointed in the mid-twentieth century with cement-rich mortar. In order to quantitatively assess the impact of repointing on the decay rates of the sandstones, the following methods have been used: dating of reference surfaces (‘zero datum levels’) based on stone-dressing marks, stone-by-stone and terrestrial LiDAR (Light Detection And Ranging) surveys, and petrographical analyses including on-site non-destructive tests. This study reveals that, between the twelfth century and the mid-twentieth century, intrinsic geological factors have been a key control on weathering rates. Stone surface recession has proceeded, on average, 500 times faster in the poorly cemented soft white sandstone compared to the iron-cemented red sandstone (4 mm/century v. 0.008 mm/century). Since the mid-twentieth century, the replacement of the original lime mortar with a cement-rich mortar has resulted in a marked increase in weathering rates and resulting surface recession of the poorly cemented white sandstone: this increase is fivefold where cement-lime mortar (‘bastard mortar’) has been used and 10-fold where harder cement-rich mortar has been applied. By contrast, the application of cement-lime mortar between the ashlars composed of iron-cemented red sandstone had no deleterious effects. This study confirms that the use of cement-based mortar should be avoided on soft and porous masonries. It also stresses the fact that accelerated stone surface recession rates are systematically associated with heritage sites that are subject to significant anthropogenic effects caused by inappropriate interventions or excessive pressure on the monuments or their environment.
Low PIP4K2B Expression in Human Breast Tumors Correlates with Reduced Patient Survival: A Role for PIP4K2B in the Regulation of E-Cadherin Expression
Authors: Keune Willem-Jan , Sims Andrew H. , Jones David R. , Bultsma Yvette , Lynch James T. , Jirström Karin , Landberg Goran , Divecha Nullin 
Published: October 2013

Abstract
Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase β (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan–Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-β–induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-β–induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival. Cancer Res; 73(23); 6913–25. ©2013 AACR.
Prostate-Specific Membrane Antigen Protein Expression in Tumor Tissue and Risk of Lethal Prostate Cancer
Authors: Kasperzyk Julie L. , Finn Stephen P. , Flavin Richard , Fiorentino Michelangelo , Lis Rosina , Hendrickson Whitney K. , Clinton Steven K. , Sesso Howard D. , Giovannucci Edward L. , Stampfer Meir J. , Loda Massimo , Mucci Lorelei A. 
Published: October 2013

Abstract
Background: Overexpression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but none of the studies have assessed its association with disease-specific mortality.
Methods: We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two U.S.-based cohorts (n = 902, diagnosed 1983–2004). We used Cox proportional hazards regression to calculate multivariable HRs and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n = 95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers.
Results: During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1 = 2.42; Ptrend &lt; 0.01). This association was attenuated and nonsignificant (multivariable-adjusted HRQ4vs.Q1 = 1.01; Ptrend = 0.52) after further adjusting for Gleason score and prostate-specific antigen (PSA) at diagnosis. High PSMA expression was significantly (P &lt; 0.05) correlated with higher Gleason score and PSA at diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen receptor expression, and absence of ets-related gene (ERG) expression.
Conclusions: High tumor PSMA expression was not an independent predictor of lethal prostate cancer in the current study. PSMA expression likely captures, in part, malignant features of Gleason grade and tumor angiogenesis.
Impact: PSMA is not a strong candidate biomarker for predicting prostate cancer–specific mortality in surgically treated patients. Cancer Epidemiol Biomarkers Prev; 22(12); 2354–63. ©2013 AACR.
Redirecting Apoptosis to Aponecrosis Induces Selective Cytotoxicity to Pancreatic Cancer Cells through Increased ROS, Decline in ATP Levels, and VDAC
Authors: Dinnen Richard D. , Mao Yuehua , Qiu Wanglong , Cassai Nicholas , Slavkovich Vesna N. , Nichols Gwen , Su Gloria H. , Brandt-Rauf Paul , Fine Robert L. 
Published: October 2013

Abstract
Pancreatic cancer cell lines with mutated ras underwent an alternative form of cell death (aponecrosis) when treated concomitantly with clinically achievable concentrations of arsenic trioxide, ascorbic acid, and disulfiram (Antabuse; AAA). AAA's major effects are mediated through generation of intracellular reactive oxygen species (ROS) and more than 50% decline in intracellular ATP. N-acetyl cysteine and a superoxide dismutase mimetic prevented aponecrosis and restored intracellular ATP levels. DIDS (4,4′-diisothiocyanatostilbene-2, 2′ disulfonic acid), the pan- Voltage-Dependent Anion Channel (VDAC), -1, 2, 3 inhibitor and short hairpin RNA (shRNA) to VDAC-1 blocked cell death and ROS accumulation. In vivo exposure of AAA led to a 62% reduction in mean tumor size and eliminated tumors in 30% of nude mice with PANC-1 xenografts. We concluded that early caspase-independent apoptosis was shifted to VDAC-mediated “targeted” aponecrosis by the addition of disulfiram to arsenic trioxide and ascorbic acid. Conceptually, this work represents a paradigm shift where switching from apoptosis to aponecrosis death pathways, also known as targeted aponecrosis, could be utilized to selectively kill pancreatic cancer cells resistant to apoptosis. Mol Cancer Ther; 12(12); 2792–803. ©2013 AACR.
Long Pentraxin-3 Inhibits Epithelial–Mesenchymal Transition in Melanoma Cells
Authors: Ronca Roberto , Di Salle Emanuela , Giacomini Arianna , Leali Daria , Alessi Patrizia , Coltrini Daniela , Ravelli Cosetta , Matarazzo Sara , Ribatti Domenico , Vermi William , Presta Marco 
Published: October 2013

Abstract
During melanoma progression, malignant melanocytes are reprogrammed into mesenchymal-like cells through to an epithelial–mesenchymal transition (EMT) process associated with the acquisition of an invasive, prometastatic phenotype. The fibroblast growth factor-2 (FGF2)/FGF receptor (FGFR) system plays a pivotal role in melanoma, leading to autocrine/paracrine induction of tumor cell proliferation and angiogenesis. Long pentraxin-3 (PTX3) interacts with FGF2, and other FGF family members, inhibiting FGF-dependent neovascularization and tumor growth. Here, PTX3 protein and the PTX3-derived acetylated pentapeptide Ac-ARPCA-NH2 inhibit FGF2-driven proliferation and downstream FGFR signaling in murine melanoma B16-F10 cells. Moreover, human PTX3-overexpressing hPTX_B16-F10 cells are characterized by the reversed transition from a mesenchymal to an epithelial-like appearance, inhibition of cell proliferation, loss of clonogenic potential, reduced motility and invasive capacity, downregulation of various mesenchymal markers, and upregulation of the epithelial marker E-cadherin. Accordingly, PTX3 affects cell proliferation and EMT transition in human A375 and A2058 melanoma cells. Also, hPTX_B16-F10 cells showed a reduced tumorigenic and metastatic activity in syngeneic C57BL/6 mice. In conclusion, PTX3 inhibits FGF/FGFR-driven EMT in melanoma cells, hampering their tumorigenic and metastatic potential. These data represent the first experimental evidence about a nonredundant role of the FGF/FGFR system in the modulation of the EMT process in melanoma and indicate that PTX3 or its derivatives may represent the basis for the design of novel therapeutic approaches in FGF/FGFR-dependent tumors, including melanoma. Mol Cancer Ther; 12(12); 2760–71. ©2013 AACR.
Paradoxical Activation of T Cells via Augmented ERK Signaling Mediated by a RAF Inhibitor
Authors: Callahan Margaret K. , Masters Gregg , Pratilas Christine A. , Ariyan Charlotte , Katz Jessica , Kitano Shigehisa , Russell Valerie , Gordon Ruth Ann , Vyas Shachi , Yuan Jianda , Gupta Ashok , Wigginton Jon M. , Rosen Neal , Merghoub Taha , Jure-Kunkel Maria , Wolchok Jedd D. 
Published: October 2013

Abstract
RAF inhibitors selectively block extracellular signal–regulated kinase (ERK) signaling in BRAF-mutant melanomas and have defined a genotype-guided approach to care for this disease. RAF inhibitors have the opposite effect in BRAF wild-type tumor cells, where they cause hyperactivation of ERK signaling. Here, we predict that RAF inhibitors can enhance T-cell activation, based on the observation that these agents paradoxically activate ERK signaling in BRAF wild-type cells. To test this hypothesis, we have evaluated the effects of the RAF inhibitor BMS908662 on T-cell activation and signaling in vitro and in vivo. We observe that T-cell activation is enhanced in a concentration-dependent manner and that this effect corresponds with increased ERK signaling, consistent with paradoxical activation of the pathway. Furthermore, we find that the combination of BMS908662 with cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockade in vivo potentiates T-cell expansion, corresponding with hyperactivation of ERK signaling in T cells detectable ex vivo. Finally, this combination demonstrates superior antitumor activity, compared with either agent alone, in two transplantable tumor models. This study provides clear evidence that RAF inhibitors can modulate T-cell function by potentiating T-cell activation in vitro and in vivo. Paradoxical activation of ERK signaling in T cells offers one mechanism to explain the enhanced antitumor activity seen when RAF inhibitors are combined with CTLA-4 blockade in preclinical models. Cancer Immunol Res; 2(1); 70–79. ©2013 AACR.