bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nimbolide, a Limonoid Triterpene, Inhibits Growth of Human Colorectal Cancer Xenografts by Suppressing the Proinflammatory Microenvironment
Authors: Gupta Subash C. , Prasad Sahdeo , Sethumadhavan Dhanya R. , Nair Mangalam S. , Mo Yin-Yuan , Aggarwal Bharat B. 
Published: June 2013

Abstract
Purpose: Extensive research over the past decade has revealed that the proinflammatory microenvironment plays a critical role in the development of colorectal cancer. Whether nimbolide, a limonoid triterpene, can inhibit the growth of colorectal cancer was investigated in the present study.
Experimental Design: The effect of nimbolide on proliferation of colorectal cancer cell lines was examined by MTT assay, apoptosis by caspase activation and poly-ADP ribose polymerase cleavage, NF-κB activation by DNA-binding assay, and protein expression by Western blotting. The effect of nimbolide on the tumor growth in vivo was examined in colorectal cancer xenografts in a nude mouse model.
Results: Nimbolide inhibited proliferation, induced apoptosis, and suppressed NF-κB activation and NF-κB–regulated tumorigenic proteins in colorectal cancer cells. The suppression of NF-κB activation by nimbolide was caused by sequential inhibition of IκB kinase (IKK) activation, IκBα phosphorylation, and p65 nuclear translocation. Furthermore, the effect of nimbolide on IKK activity was found to be direct. In vivo, nimbolide (at 5 and 20 mg/kg body weight), injected intraperitoneally after tumor inoculation, significantly decreased the volume of colorectal cancer xenografts. The limonoid-treated xenografts exhibited significant downregulation in the expression of proteins involved in tumor cell survival (Bcl-2, Bcl-xL, c-IAP-1, survivin, and Mcl-1), proliferation (c-Myc and cyclin D1), invasion (MMP-9, ICAM-1), metastasis (CXCR4), and angiogenesis (VEGF). The limonoid was found to be bioavailable in the blood plasma and tumor tissues of treated mice.
Conclusions: Our studies provide evidence that nimbolide can suppress the growth of human colorectal cancer through modulation of the proinflammatory microenvironment. Clin Cancer Res; 19(16); 4465–76. ©2013 AACR.
Perivascular Delivery of Encapsulated Mesenchymal Stem Cells Improves Postischemic Angiogenesis Via Paracrine Activation of VEGF-A
Authors: Katare Rajesh , Riu Federica , Rowlinson Jonathan , Lewis Andrew , Holden Rachel , Meloni Marco , Reni Carlotta , Wallrapp Christine , Emanueli Costanza , Madeddu Paolo 
Published: June 2013

Objective—
To test the therapeutic activity of perivascular transplantation of encapsulated human mesenchymal stem cells (MSCs) in an immunocompetent mouse model of limb ischemia.

Approach and Results—
CD1 mice underwent unilateral limb ischemia, followed by randomized treatment with vehicle, alginate microbeads (MBs), MB-encapsulated MSCs (MB-MSCs), or MB-MSCs engineered with glucagon-like peptide-1. Treatments were applied directly in the perivascular space around the femoral artery. Laser Doppler and fluorescent microsphere assessment of blood flow showed a marked improvement of perfusion in the MB-MSCs and MB-MSCs engineered with glucagon-like peptide-1 groups, which was associated with increased foot salvage particularly in MB-MSCs engineered with glucagon-like peptide-1–treated mice. Histological analysis revealed increased capillary and arteriole density in limb muscles of the 2 MSC groups. Furthermore, MB-MSCs engineered with glucagon-like peptide-1 and, to a lesser extent, MB-MSC treatment increased functional arterial collaterals alongside the femoral artery occlusion. Analysis of expressional changes in ischemic muscles showed that MB-MSC transplantation activates a proangiogenic signaling pathway centered on vascular endothelial growth factor A. In contrast, intramuscular MB-MSCs caused inflammatory reaction, but no improvement of reparative vascularization. Importantly, nonencapsulated MSCs were ineffective either by intramuscular or perivascular route.

Conclusions—
Perivascular delivery of encapsulated MSCs helps postischemic reperfusion. This novel biological bypass method might be useful in patients not amenable to conventional revascularization approaches.
Usefulness of Exercise Test and Myocardial Perfusion–Gated Single Photon Emission Computed Tomography to Improve the Prediction of Major Events
Authors: Candell-Riera Jaume , Ferreira-González Ignacio , Marsal Josep R. , Aguadé-Bruix Santiago , Cuberas-Borrós Gemma , Pujol Paula , Romero-Farina Guillermo , Nazarena-Pizzi María , de León Gustavo , Castell-Conesa Joan , García-Dorado David 
Published: June 2013

Background—
The incremental prognostic value of myocardial perfusion–gated single photon emission computed tomography (MPGS) compared with exercise test has not yet been properly evaluated.

Methods and Results—

Five thousand six hundred seventy-two consecutive patients with known or suspected coronary disease undergoing exercise MPGS between 1997 and 2007 were included. Three-year predictive models for total death and death from cardiovascular causes or acute myocardial infarction (ie, major cardiovascular events [MCE]) were built using Cox-regression modeling, including only the clinical information. Then the exercise and MPGS information was sequentially added. The added discriminative ability of exercise test information and MPGS was assessed by net reclassification improvement and integrated discrimination improvement. The increase in predictive ability of exercise information for death and MCE was high as assessed by net reclassification improvement (0.199 and 0.263) and integrated discrimination improvement (0.042 and 0.021). The only variable of MPGS associated with total death was ejection fraction (hazard ratio, 0.84; 95% confidence interval, 0.79–0.89;
P
<0.001). Global stress ischemic score emerged as an additional variable associated with MCE (hazard ratio, 1.07; 95% confidence interval, 1.02–1.12;
P
=0.007). Adding MPGS information barely improved the prognostic value for total death (net reclassification improvement, 0.017; integrated discrimination improvement, 0.013), but it increased for MCE (net reclassification improvement, 0.122; integrated discrimination improvement, 0.033).

Conclusions—
Adding MPGS information to exercise information does not improve prediction of total death, although it allows a more accurate prediction of MCE.
Early New Diffusion-Weighted Imaging Lesions Appear More Often in Stroke Patients With a Multiple Territory Lesion Pattern
Authors: Braemswig Tim Bastian , Usnich Tatiana , Albach Fredrik N. , Brunecker Peter , Grittner Ulrike , Scheitz Jan F. , Fiebach Jochen B. , Nolte Christian H. 
Published: June 2013

Background and Purpose—
New diffusion-weighted imaging (DWI) lesions are common in patients with acute ischemic stroke. They are associated with an initial nonsingle lesion pattern. Previous studies have not analyzed this association in detail. We differentiated nonsingle lesions in 1 vascular supply territory only (scattered lesion pattern) from nonsingle lesions in ≥2 vascular supply territory (multiple territory lesion -pattern).

Methods—
Patients with an acute ischemic stroke underwent 3 MRI (3T) examinations: on admission, on the following day, and 4 to 7 days after symptom onset. First, DWI lesions were delineated manually by raters blinded to clinical details. Second, DWI images were coregistered and analyzed visually for new hyperintensities. The initial lesion pattern was categorized as single, scattered, or multiple territory.

Results—

Of 340 patients enrolled, 43% had a single lesion pattern, 40% had a scattered lesion pattern, and 17% had a multiple territory lesion pattern. In multivariable analysis, the categorical variable lesion pattern was independently associated with new DWI lesions (odds ratio
multiple territory lesion pattern
, 3.64 [95% confidence interval, 1.75–7.58]; odds ratio
scattered lesion pattern
, 1.96 [95% confidence interval, 1.09–3.56]). Patients with multiple territory lesion pattern had significantly more often diabetes mellitus, and their new lesions were more often located remotely from the initial area of hypoperfusion compared with patients with scattered lesion pattern.

Conclusion—
Lesion pattern on initial image is an independent risk factor for new DWI lesions. The risk for new DWI lesions is highest in patients with multiple territory lesion pattern.
Impact of Rossby Wave Breaking on U.S. West Coast Winter Precipitation during ENSO Events
Authors: Ryoo Ju-Mee , Kaspi Yohai , Waugh Darryn W. , Kiladis George N. , Waliser Duane E. , Fetzer Eric J. , Kim Jinwon 
Published: June 2013

Abstract
This study demonstrates that water vapor transport and precipitation are largely modulated by the intensity of the subtropical jet, transient eddies, and the location of wave breaking events during the different phases of ENSO. Clear differences are found in the potential vorticity (PV), meteorological fields, and trajectory pathways between the two different phases. Rossby wave breaking events have cyclonic and anticyclonic regimes, with associated differences in the frequency of occurrence and the dynamic response. During La Niña, there is a relatively weak subtropical jet allowing PV to intrude into lower latitudes over the western United States. This induces a large amount of moisture transport inland ahead of the PV intrusions, as well as northward transport to the west of a surface anticyclone. During El Niño, the subtropical jet is relatively strong and is associated with an enhanced cyclonic wave breaking. This is accompanied by a time-mean surface cyclone, which brings zonal moisture transport to the western United States. In both (El Niño and La Niña) phases, there is a high correlation (&gt;0.3–0.7) between upper-level PV at 250 hPa and precipitation over the west coast of the United States with a time lag of 0–1 days. Vertically integrated water vapor fluxes during El Niño are up to 70 kg m−1 s−1 larger than those during La Niña along the west coast of the United States. The zonal and meridional moist static energy flux resembles wave vapor transport patterns, suggesting that they are closely controlled by the large-scale flows and location of wave breaking events during the different phase of ENSO.
A Physical Basis for the Probabilistic Prediction of the Accumulated Tropical Cyclone Kinetic Energy in the Western North Pacific
Authors: Kim Hye-Mi , Lee Myong-In , Webster Peter J. , Kim Dongmin , Yoo Jin Ho 
Published: June 2013

Abstract
The relationship between El Niño–Southern Oscillation (ENSO) and tropical storm (TS) activity over the western North Pacific Ocean is examined for the period from 1981 to 2010. In El Niño years, TS genesis locations are generally shifted to the southeast relative to normal years and the passages of TSs tend to recurve to the northeast. TSs of greater duration and more intensity during an El Niño summer induce an increase of the accumulated tropical cyclone kinetic energy (ACE). Based on the strong relationship between the TS properties and ENSO, a probabilistic prediction for seasonal ACE is investigated using a hybrid dynamical–statistical model. A statistical relationship is developed between the observed ACE and large-scale variables taken from the ECMWF seasonal forecast system 4 hindcasts. The ACE correlates positively with the SST anomaly over the central to eastern Pacific and negatively with the vertical wind shear near the date line. The vertical wind shear anomalies over the central and western Pacific are selected as predictors based on sensitivity tests of ACE predictive skill. The hybrid model performs quite well in forecasting seasonal ACE with a correlation coefficient between the observed and predicted ACE at 0.80 over the 30-yr period. A relative operating characteristic analysis also indicates that the ensembles have significant probabilistic skill for both the above-normal and below-normal categories. By comparing the ACE prediction over the period from 2003 to 2011, the hybrid model appears more skillful than the forecast from the Tropical Storm Risk consortium.
Limitations of the CIBSE design summer year approach for delivering representative near-extreme summer weather conditions
Authors: Jentsch Mark F , Levermore Geoff J , Parkinson John B , Eames Matt E 
Published: June 2013

Representative, site-specific weather data is a key requirement for building performance simulation. In the UK, such data is available in two formats, Test Reference Years for analysing building services loads under ‘typical’ year conditions and Design Summer Years for estimating summer discomfort of naturally ventilated and free-running buildings. Currently, Design Summer Years are determined as a complete year based on the rank of the average dry bulb temperature from April to September. The simplicity of this approach does not take into account extreme temperature values in individual months or the incident solar radiation, both of which are however of great significance for the summer overheating performance of a building. This paper analyses the implications of this simplified approach for the resulting data. It is shown that there is no consistent relation between the Design Summer Years and the corresponding Test Reference Years and that, for some sites, building performance simulations using Design Summer Year files deliver unreliable results. Practical application: This paper demonstrates that the current approach for deriving Design Summer Years (DSYs) can lead to data series that are not representative for near-extreme summer conditions at a given location. It highlights that a new approach for deriving near-extreme summer years for building performance simulation is needed in order to overcome the inherent shortfalls of the current DSY data.
Detection of the Petrosquamosal Sinus in Chronic Otitis Media Using High‐Resolution CT
Authors: Hiraumi Harukazu , Yamamoto Akira , Yamamoto Norio , Sakamoto Tatsunori , Ito Juichi 
Published: June 2013

ObjectiveTo evaluate the prevalence of the persistent petrosquamosal venous sinus in patients with chronic otitis media using a high‐resolution CT scan.Study DesignRetrospective chart review.SettingTertiary referral center.Subjects and MethodsEighty‐four patients older than 6 years of age underwent surgery (in a total of 92 ears) for chronic otitis media at Kyoto University Hospital, Department of Otolaryngology‐Head and Neck Surgery. We used high‐resolution CT scans to evaluate the prevalence and size of persistent petrosquamosal sinuses, as well as their relative position to the middle fossa.ResultsA petrosquamosal sinus was detected in 42 (45.7%), a higher frequency than in ears without chronic otitis media (10.3%). The diameter of the sinuses was <1.0 mm in 20 ears, 1.0 mm to 2.0 mm in 17 ears, and >2.0 mm in 5 ears. The petrosquamosal sinus was positioned inferior to the lowest part of the middle fossa in 10 ears.ConclusionThe petrosquamosal sinus was detected frequently in high‐resolution CT scans in patients with chronic otitis media. In approximately half of the patients, the sinus was larger than 1 mm in diameter and may be encountered during mastoidectomy.
Ramosetron, midazolam, and combination of ramosetron and midazolam for prevention of postoperative nausea and vomiting: A prospective, randomized, double-blind study
Authors: Kim Won Joong , Kang Hyun , Shin Hwa Yong , Baek Chong Wha , Jung Yong Hun , Woo Young Cheol , Kim Jin Yun , Koo Gil Hoi 
Published: June 2013

Objective To compare the efficacy of ramosetron, midazolam, and the combination of ramosetron and midazolam in the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing thyroidectomy. Methods Patients were randomized to receive 0.3 mg ramosetron (Group R), 75 µg/kg midazolam (Group M) or 0.3 mg ramosetron combined with 75 µg/kg midazolam (Group RM) before the induction of anaesthesia. PONV, use of rescue antiemetics, pain severity and fentanyl consumption were assessed for 24 h after thyroidectomy. Results A total of 100 patients were enrolled; 94 patients completed the study. The severity of nausea was statistically significantly reduced at 0–2 h in Group RM compared with Groups R and M, and at 2–6 h in Group RM compared with Group M. The incidence of retching and vomiting was significantly lower at 0–2 h, 2–6 h, 6–12 h in Group RM than in Group M, and lower in Group R than Group M at 6–12 h. The requirement for rescue antiemetics was significantly lower at 0–2 h in group RM than in group M. Conclusion The combination therapy of ramosetron and midazolam provided superior antiemetic efficacy compared with midazolam single therapy, but did not show any significant additional benefits compared with ramosetron single therapy.
Outpatient management of primary spontaneous pneumothorax: a prospective study
Authors: Massongo Massongo , Leroy Sylvie , Scherpereel Arnaud , Vaniet Fabien , Dhalluin Xavier , Chahine Bachar , Sanfiorenzo Céline , Genin Michaël , Marquette Charles-Hugo 
Published: June 2013

We prospectively assessed the safety and cost saving of a small-bore drain based procedure for outpatient management of first episodes of primary spontaneous pneumothorax.Patients were managed by observation alone or insertion of an 8.5-F “pig-tail” drain connected to a one-way valve, according to size and clinical tolerance of the pneumothorax. All patients were reassessed after 4 h, on the first working day after discharge and on day 7. Patients still exhibiting air leak on day 4 underwent thoracoscopy. The primary end-point was complete lung re-expansion at day 7.60 consecutive patients entered the study. 48 (80%) met the definition of large pneumothorax. The success rate was 83%. The 1-year recurrence rate was 17%. 36 (60%) patients were discharged after 4 h and 50% had full outpatient management. No severe complication was observed. The mean±sdlength of hospitalisation was 2.3±3.1 days. This policy resulted in about a 40% reduction in hospital stay-related costs.The present study supports the use of a single system combined with a well-defined management algorithm including safe discharge criteria, as an alternative to manual aspiration or chest tube drainage. This approach participates in healthcare cost-savings.
Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort
Authors: Agusti Alvar , Edwards Lisa D. , Celli Bartolomé , MacNee William , Calverley Peter M. A. , Müllerova Hana , Lomas David A. , Wouters Emiel , Bakke Per , Rennard Steve , Crim Courtney , Miller Bruce E. , Coxson Harvey O. , Yates Julie C. , Tal-Singer Ruth , Vestbo Jørgen 
Published: June 2013

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) into four groups (A to D).We explored the characteristics, stability and relationship to outcomes of these groups within the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (n = 2101).Main results showed that: 1) these groups differed in several clinical, functional, imaging and biological characteristics in addition to those used for their own definition; 2) A and D groups were relatively stable over time, whereas groups B and C showed more temporal variability; 3) the risk of exacerbation over 3 years increased progressively from A to D, whereas that of hospitalisation and mortality were lowest in A, highest in D and intermediate and similar in B and C, despite the former having milder airflow limitation. The prevalence of comorbidities and persistent systemic inflammation were highest in group B.The different longitudinal behaviour of group AversusB and CversusD (each pair with similar forced expiratory volume in1 s (FEV1) values supports the 2011 GOLD proposal of assessing COPD patients by more than FEV1only. However the assumption that symptoms do not equate to risk appears to be naïve, as groups B and C carry equally poor clinical outcomes, though for different reasons.
Adaptive mechanisms of Campylobacter jejunito erythromycin treatment
Authors: Xia Qingqing , Muraoka Wayne T , Shen Zhangqi , Sahin Orhan , Wang Hongning , Wu Zuowei , Liu Peng , Zhang Qijing 
Published: June 2013

Abstract

Background
Macrolide is the drug of choice to treat human campylobacteriosis, but Campylobacter resistance to this antibiotic is rising. The mechanisms employed by Campylobacter jejuni to adapt to erythromycin treatment remain unknown and are examined in this study. The transcriptomic response of C. jejuni NCTC 11168 to erythromycin (Ery) treatment was determined by competitive microarray hybridizations. Representative genes identified to be differentially expressed were further characterized by constructing mutants and assessing their involvement in antimicrobial susceptibility, oxidative stress tolerance, and chicken colonization.

Results
Following the treatment with an inhibitory dose of Ery, 139 genes were up-regulated and 119 were down-regulated. Many genes associated with flagellar biosynthesis and motility was up-regulated, while many genes involved in tricarboxylic acid cycle, electron transport, and ribonucleotide biosynthesis were down-regulated. Exposure to a sub-inhibitory dose of Ery resulted in differential expression of much fewer genes. Interestingly, two putative drug efflux operons (cj0309c-cj0310c and cj1173-cj1174) were up-regulated. Although mutation of the two operons did not alter the susceptibility of C. jejuni to antimicrobials, it reduced Campylobacter growth under high-level oxygen. Another notable finding is the consistent up-regulation of cj1169c-cj1170c, of which cj1170c encodes a known phosphokinase, an important regulatory protein in C. jejuni. Mutation of the cj1169c-cj1170c rendered C. jejuni less tolerant to atmospheric oxygen and reduced Campylobacter colonization and transmission in chickens.

Conclusions
These findings indicate that Ery treatment elicits a range of changes in C. jejuni transcriptome and affects the expression of genes important for in vitro and in vivo adaptation. Up-regulation of motility and down-regulation of energy metabolism likely facilitate Campylobacter to survive during Ery treatment. These findings provide new insight into Campylobacter adaptive response to antibiotic treatment and may help to understand the mechanisms underlying antibiotic resistance development.
BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families
Authors: Berzina Dace , Nakazawa-Miklasevica Miki , Zestkova Jekaterina , Aksenoka Karina , Irmejs Arvids , Gardovskis Andris , Kalniete Dagnija , Gardovskis Janis , Miklasevics Edvins 
Published: June 2013

Abstract

Background
The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5–10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.

Methods
50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.

Results
Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.

Conclusions
Molecular screening of sequential cancer patients is an important tool to identify HBOC families.