bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations
Authors: Williams D. L. , Robinson J. C. , Lay E. , Field H. 
Published: October 2014

This study aimed to evaluate the efficacy of topical ophthalmic aciclovir applied five times daily as a treatment for feline herpesvirus type 1 (FHV‐1) keratitis in a group of cats in a first‐opinion practice setting. Cats with ocular signs indicative of FHV‐1 or Chlamydophila species infection, predominantly conjunctivitis and keratitis, were tested for FHV‐1 antigen using an immunofluorescent technique on air‐dried conjunctival swabs. They were first treated with topical chlortetracycline with efficacy against Chlamydophila species and then, in cases positive for FHV‐1, with topical aciclovir. The time to recovery was determined and illustrated using a Kaplan‐Meier plot. Three cats were infected with Chlamydophila species and showed a median time to recovery of 14 days (95 per cent confidence interval [CI] 10 to 18 days), while 30 cats infected with FHV‐1 showed a median time to recovery of 12 days (95 per cent CI 10 to 14 days). The drug dose at which 50 per cent plaque reduction (ED50) occurred in a standard plaque reduction assay was determined in an in vitro study. This showed a mean (sd) ED50 of aciclovir of 25 (3·5) mg/ml compared with 0·4 (0·05) mg/ml for trifluorothymidine, a drug known to be efficacious against FHV‐1. The study shows that even though aciclovir is generally considered to lack efficacy against ocular FHV‐1 infection, when used frequently it can have a beneficial effect in FHV‐1 conjunctivitis and keratitis
Oncogenic KRAS Confers Chemoresistance by Upregulating NRF2
Authors: Tao Shasha , Wang Shue , Moghaddam Seyed Javad , Ooi Aikseng , Chapman Eli , Wong Pak K. , Zhang Donna D. 
Published: October 2014

Abstract
Oncogenic KRAS mutations found in 20% to 30% of all non–small cell lung cancers (NSCLC) are associated with chemoresistance and poor prognosis. Here we demonstrate that activation of the cell protective stress response gene NRF2 by KRAS is responsible for its ability to promote drug resistance. RNAi-mediated silencing of NRF2 was sufficient to reverse resistance to cisplatin elicited by ectopic expression of oncogenic KRAS in NSCLC cells. Mechanistically, KRAS increased NRF2 gene transcription through a TPA response element (TRE) located in a regulatory region in exon 1 of NRF2. In a mouse model of mutant KrasG12D-induced lung cancer, we found that suppressing the NRF2 pathway with the chemical inhibitor brusatol enhanced the antitumor efficacy of cisplatin. Cotreatment reduced tumor burden and improved survival. Our findings illuminate the mechanistic details of KRAS-mediated drug resistance and provide a preclinical rationale to improve the management of lung tumors harboring KRAS mutations with NRF2 pathway inhibitors. Cancer Res; 74(24); 7430–41. ©2014 AACR.
Polyphosphate accelerates factor V activation by factor XIa
Authors: Choi Sharon , Smith Stephanie , Morrissey James 
Published: October 2014

SummaryFactor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532–1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.
Tumor Necrosis Factor Receptor–Associated Factor 2 Mediates Mitochondrial Autophagy
Authors: Yang Kai-Chun , Ma Xiucui , Liu Haiyan , Murphy John , Barger Philip M. , Mann Douglas L. , Diwan Abhinav 
Published: October 2014

Background—
Tumor necrosis factor (TNF) signaling protects against ischemia/reperfusion–induced cardiomyocyte death, in vitro, ex vivo, and in vivo. TNF-receptor–associated factor 2 (TRAF2), an E3 ubiquitin ligase, coordinates cytoprotective signaling downstream of both TNF receptors, via unclear mechanisms. Noting that TRAF2 is recruited to mitochondria, and that autophagic removal of ubiquitin-tagged damaged mitochondria is cytoprotective, we tested the hypothesis that TRAF2 mediates mitochondrial autophagy.

Methods and Results—
TRAF2 localizes to the mitochondria in neonatal rat cardiac myocytes, and TNF treatment transcriptionally upregulates TRAF2 abundance in the mitochondrial subfraction. TRAF2 colocalizes with ubiquitin, p62 adaptor protein, and mitochondria within LC3-bound autophagosomes; and exogenous TRAF2 enhances autophagic removal of mitochondria. TRAF2 knockdown with adenoviral shRNA transduction induces accumulation of depolarized mitochondria in resting neonatal rat cardiac myocytes, as well as in those treated with TNF or uncoupling agent carbonyl cyanide m-chlorophenyl hydrazone, suggesting an essential role for TRAF2 in homeostatic and stress-induced mitochondrial autophagy. TRAF2 also colocalizes and interacts with PARKIN, a previously described E3 ubiquitin ligase and mitophagy effector, on depolarized mitochondria in neonatal rat cardiac myocytes. Exogenous expression of TRAF2, but not its E3 ligase-deficient mutants, is sufficient to partially restore mitophagy in the setting of PARKIN knockdown, suggesting redundancy in their ubiquitin ligase roles. TRAF2 abundance increases in the mitochondrial subfraction of ischemia/reperfusion–modeled hearts; and exogenous TRAF2, but not its E3 ligase-deficient mutants, reduces depolarized mitochondria and rescues cell death in neonatal rat cardiac myocytes subjected to hypoxia/reoxygenation.

Conclusions—
Taken together, these data indicate an essential role for TRAF2 in concert with PARKIN as a mitophagy effector, which contributes to TRAF2-induced cytoprotective signaling.
Transition from Suppressed to Active Convection Modulated by a Weak Temperature Gradient–Derived Large-Scale Circulation
Authors: Daleu C. L. , Woolnough S. J. , Plant R. S. 
Published: October 2014

Abstract
Numerical simulations are performed to assess the influence of the large-scale circulation on the transition from suppressed to active convection. As a model tool, the authors used a coupled-column model. It consists of two cloud-resolving models that are fully coupled via a large-scale circulation that is derived from the requirement that the instantaneous domain-mean potential temperature profiles of the two columns remain close to each other. This is known as the weak temperature gradient approach.
The simulations of the transition are initialized from coupled-column simulations over nonuniform surface forcing, and the transition is forced in the dry column by changing the local and/or remote surface forcings to uniform surface forcing across the columns. As the strength of the circulation is reduced to zero, moisture is recharged into the dry column and a transition to active convection occurs once the column is sufficiently moistened to sustain deep convection. Direct effects of changing surface forcing occur over the first few days only. Afterward, it is the evolution of the large-scale circulation that systematically modulates the transition. Its contributions are approximately equally divided between the heating and moistening effects.
A transition time is defined to summarize the evolution from suppressed to active convection. It is the time when the rain rate in the dry column is halfway to the mean value obtained at equilibrium over uniform surface forcing. The transition time is around twice as long for a transition that is forced remotely compared to a transition that is forced locally. Simulations in which both local and remote surface forcings are changed produce intermediate transition times.
Monitoring Greek Seas Using Passive Underwater Acoustics
Authors: Nystuen Jeffrey A. , Anagnostou Marios N. , Anagnostou Emmanouil N. , Papadopoulos Anastasios 
Published: October 2014

AbstractThe Hellenic Center for Marine Research POSEIDON ocean monitoring and forecasting system has included passive underwater acoustic measurements as part of its real-time operations. Specifically, low-duty-cycle long-term passive acoustic listeners (PALs) are deployed on two operational buoys, one off Pylos in the Ionian Sea and the second off Athos in the northern Aegean Sea. The first step toward the quantitative use of passive ambient sound is the classification of the geophysical sources—for example, wind speed and rain rate—from the noise of shipping, from other anthropogenic activities, and from the natural sounds of marine animals. After classification, quantitative measurements of wind speed and precipitation are applied to the ambient sound data. Comparisons of acoustic quantitative measurements of wind speed with in situ buoy anemometer measurements were shown to be within 0.5 m s−1. The rainfall detection and quantification was also confirmed with collocated measurements of precipitation from a nearby coastal rain gauge and operational weather radar rainfall observations. The complicated condition of high sea states, including the influence of ambient bubble clouds, rain, and sea spray under high winds, was sorted acoustically, and shows promise for identifying and quantifying such conditions from underwater sound measurements. Long-term data were used in this study to derive sound budgets showing the percent occurrence of dominant sound sources (ships, marine mammals, wind, and rain), their relative intensity as a function of frequency, and statistical summaries of the retrieved rainfall amounts and wind speeds at the two buoy locations in the Aegean and Ionian Seas.
Probabilistic Voxel-Fe model for single cell motility in 3D
Authors: Borau Carlos , Polacheck William J , Kamm Roger D , García-Aznar José Manuel 
Published: October 2014

Abstract

Background
Cells respond to a variety of external stimuli regulated by the environment conditions. Mechanical, chemical and biological factors are of great interest and have been deeply studied. Furthermore, mathematical and computational models have been rapidly growing over the past few years, permitting researches to run complex scenarios saving time and resources. Usually these models focus on specific features of cell migration, making them only suitable to study restricted phenomena.

Methods
Here we present a versatile finite element (FE) cell-scale 3D migration model based on probabilities depending in turn on ECM mechanical properties, chemical, fluid and boundary conditions.

Results
With this approach we are able to capture important outcomes of cell migration such as: velocities, trajectories, cell shape and aspect ratio, cell stress or ECM displacements.

Conclusions
The modular form of the model will allow us to constantly update and redefine it as advancements are made in clarifying how cellular events take place.
Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support
Authors: Lin Yen-Hung , Huang Hui-Chun , Chang Yi-Chung , Lin Chen , Lo Men-Tzung , Liu Li-Yu Daisy , Tsai Pi-Ru , Chen Yih-Sharng , Ko Wen-Je , Ho Yi-Lwun , Chen Ming-Fong , Peng Chung-Kang , Buchman Timothy G 
Published: October 2014

Abstract
Introduction
Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission.

Methods
Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6–20, Area 6–40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated.

Results
Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment.

Conclusions
MSsE provides additional prognostic information in patients receiving ECLS.
Year in review 2013: Critical Care- metabolism
Authors: Lheureux Olivier , Preiser Jean-Charles 
Published: October 2014

AbstractNovel insights into the metabolic alterations of critical illness, including new findings on association between blood glucose at admission and poor outcome, were published in Critical Care in 2013. The role of diabetic status in the relation of the three domains of glycemic control (hyperglycemia, hypoglycemia, and glycemic variability) was clarified: the association between mean glucose, high glucose variability, and ICU mortality was stronger in the non-diabetic than in diabetic patients. Improvements in the understanding of pathophysiological mechanisms of stress hyperglycemia were presented. Novel developments for the management of glucose control included automated closed-loop algorithms based on subcutaneous glucose measurements and microdialysis techniques. In the field of obesity, some new hypotheses that could explain the `obesity paradox’ were released, and a role of adipose tissue in the response to stress was suggested by the time course of adipocyte fatty-acid binding protein concentrations. In the field of nutrition, beneficial immunological effects have been associated with early enteral nutrition. Early enteral nutrition was significantly associated with potential beneficial effects on the phenotype of lymphocytes. Uncertainties regarding the potential benefits of small intestine feeding compared with gastric feeding were further investigated. No significant differences were observed between the nasogastric and nasojejunal feeding groups in the incidence of mortality, tracheal aspiration, or exacerbation of pain. The major risk factors to develop diarrhea in the ICU were described. Finally, the understanding of disorders associated with trauma and potential benefits of blood acidification was improved by new experimental findings.
Year in review 2013: critical care - respiratory infections
Authors: Nair Girish B , Niederman Michael S 
Published: October 2014

AbstractInfectious complications, particularly in the respiratory tract of critically ill patients, are related to increased mortality. Severe infection is part of a multiple system illness and female patients with severe sepsis have a worse prognosis compared to males. Kallistatin is a protective hormokine released during monocyte activation and low levels in the setting of septic shock can predict adverse outcomes. Presepsin is another biomarker that was recently evaluated and is elevated in patients with severe sepsis patients at risk of dying. The Centers for Disease Control and Prevention has introduced new definitions for identifying patients at risk of ventilator-associated complications (VACs), but several other conditions, such as pulmonary edema and acute respiratory distress syndrome, may cause VACs, and not all patients with VACs may have ventilator-associated pneumonia. New studies have suggested strategies to identify patients at risk for resistant pathogen infection and therapies that optimize efficacy, without the overuse of broad-spectrum therapy in patients with healthcare-associated pneumonia. Innovative strategies using optimized dosing of antimicrobials, maximizing the pharmacokinetic and pharmacodynamic properties of drugs in critically ill patients, and newer routes of drug delivery are being explored to combat drug-resistant pathogens. We summarize the major clinical studies on respiratory infections in critically ill patients published in 2013.
Transducin (β)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling
Authors: Li Xinghua , Liang Weijiang , Liu Junling , Lin Chuyong , Wu Shu , Song Libing , Yuan Zhongyu 
Published: October 2014

Abstract
Introduction
Transducin (β)-like 1 X-linked receptor 1(TBLR1) is an F-box-like and WD repeat-containing protein which functions as a switch in transcriptional activation, However, the clinical significance and biological role of TBLR1 in breast cancer remains largely unknown.

Methods
Western blotting, immunocytochemistry and real-time PCR were used to evaluate TBLR1 expression in normal breast epithelial cells and breast cancer cell lines, clinical tissue samples and adjacent nontumor tissues, and in 214 paraffin-embedded specimens. Statistical analyses were used to test for the prognostic and diagnostic associations. The biological role of TBLR1 -induced proliferation and tumorigenicity in breast cancer cells was explored in vitro and in vivo. The effect of TBLR1 on the expression of cyclin D1 and β-catenin signaling was examined by Western blotting, luciferase reporter assay and by several immunoprecipitation techniques.

Results
TBLR1 was significantly upregulated in breast cancer cells and tissues compared to normal control samples. Immunohistochemical analysis revealed high expression of TBLR1 in 113 of 214 (52.8%) paraffin-embedded archival breast cancer. The overall expression level of TBLR1 was significantly correlated with clinical stage (P <0.001), the tumor classification (P <0.001), node classification (P =0.024), and metastasis classification (P = 0.004), histological grade (P = 0.044), as well as with the expression level of c-erbB2 (P = 0.036) and Ki-67 (P <0.001). Patients with higher TBLR1 expression had shorter overall survival time, whereas patients with lower TBLR1 expression had better survival. Multivariate analysis suggested that TBLR1 expression might be an independent prognostic indicator for the survival of breast cancer patients. TBLR1 overexpression promoted, whereas TBLR1 silencing inhibited, proliferation and tumorigenicity in breast cancer cells both in vitro and in vivo. We found that TBLR1 expression was implicated in the upregulation of cyclin D1, phosphorylation of cell-cycle control protein Rb (pRb) and activation of β-catenin signaling in breast cancer.

Conclusions
TBLR1 plays a key role in the development and progression of breast cancer cells via cyclin D1-transactivation and activation of the β-catenin signaling pathway. TBLR1 may be a novel prognostic marker and a potential therapeutic target in the treatment human breast cancer.
Down-regulating peroxisome proliferator-activated receptor-gamma coactivator-1beta alleviates the proinflammatory effect of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting extracellular signal-regulated kinase, p38 and nuclear factor-kappaB activation
Authors: Zhou Jing-Jing , Ma Jian-Da , Mo Ying-Qian , Zheng Dong-Hui , Chen Le-Feng , Wei Xiu-Ning , Dai Lie 
Published: October 2014

Abstract
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1β) is a transcriptional coactivator that plays important roles in regulating multiple aspects of energy metabolism and cytokine signaling pathways. PGC-1β overexpression leads to the attenuation of macrophage-mediated inflammation. In this study, we aimed to determine the expression of PGC-1β in RA synovium and fibroblast-like synoviocytes (FLS), and explore the mechanisms of PGC-1β on both the proinflammatory effects and apoptosis in RA-FLS.

Methods
Synovium was obtained from 31 patients with active RA, as well as 13 osteoarthritis (OA) and 10 orthopedic arthropathies (Orth.A) as "less inflamed" disease controls. FLS were then isolated and cultured. Synovial PGC-1β expression was determined by immunohistochemistry staining, while FLS PGC-1β expression was detected by immunofluorescence staining, quantitative real-time PCR (qPCR) assay and western blot. PGC-1β was depleted by lentivirus sh-RNA, and up-regulated by pcDNA3.1- PGC-1β. The expression of proinflammatory cytokines, matrix metalloproteinases and receptor activator of nuclear factor-kappaB ligand was analyzed by qPCR, cytometric bead array and western blot. The expression of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) was determined by qPCR and western blot. Besides, cell apoptosis was examined using flow cytometry. The interaction between PGC-1β and NF-κB was performed by dual-luciferase reporter gene assays.

Results
(A) Synovial PGC-1β was over-expressed in RA patients compared with OA or Orth.A patients. (B) PGC-1β expression significantly increased in RA-FLS compared with OA-FLS. (C) PGC-1β mediated the expression of proinflammatory cytokines and apoptosis through extracellular signal-regulated kinase (ERK), p38 and NF-κB in RA-FLS. (D) PGC-1β mediated NF-κB transcription in RA-FLS, but did not affect ERK and p38.

Conclusion
The results indicate that PGC-1β may play important roles in the proinflammatory effects and apoptosis of RA-FLS.
Information and Communication: to the Question about the Formation of Meaning
Authors: Решетников  , Reshetnikov Sergey 
Published: October 2014

The article continues the series of publications of the author, which take up
the conclusions, following from a very general definition of communication
as interaction. In this case we are talking about the problems of the sense
creation and scientific truths, which are considered from the point of view of
dualism logics of the cognizing subject: the logic of immobility, under which
the author refers to the thinking and the logic of motion, i.e. tacit knowledge,
a prerequisite for successful (appropriate) the use of which is to stop thinking.
The presented position allows you to take the issues raised in aporia
Zeno (the tasks they recognize insoluble) and a new angle of vision to see
the dichotomy of analysis and synthesis, rationality and irrationality, similarity
and hierarchy, as well as other concepts.