bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls
Authors: Verstovsek Srdan , Kantarjian Hagop M. , Estrov Zeev , Cortes Jorge E. , Thomas Deborah A. , Kadia Tapan , Pierce Sherry , Jabbour Elias , Borthakur Gautham , Rumi Elisa , Pungolino Ester , Morra Enrica , Caramazza Domenica , Cazzola Mario , Passamonti Francesco 
Published: June 2012

Abstract
Ruxolitinib is JAK1/JAK2 inhibitor with established clinical benefit in myelofibrosis (MF). We analyzed long-term outcomes of 107 patients with intermediate-2 or high-risk MF receiving ruxolitinib at MD Anderson Cancer Center (MDACC) on phase 1/2 trial. After a median of 32 months of follow-up, 58 patients (54%) were still receiving ruxolitinib, with overall survival (OS) of 69%. The splenomegaly and symptom reductions achieved with ruxolitinib were sustained with long-term therapy. Therapy was well tolerated; discontinuation rates at 1, 2, and 3 years were 24%, 36%, and 46%, respectively. OS of 107 MDACC patients was significantly better (P = .005) than that of 310 matched (based on trial enrollment criteria) historical control patients, primarily because of highly significant difference in OS in the high-risk subgroup (P = .006). Furthermore, among MDACC patients, those with high-risk MF experienced the same OS as those with intermediate-2 risk. Patients with ≥ 50% reduction in splenomegaly had significantly prolonged survival versus those with < 25% reduction (P < .0001). Comparison of discontinuation rates and reasons for stopping the therapy to those reported for other 51 patients in the phase 1/2 trial, and 155 ruxolitinib-treated patients in phase 3 COMFORT-I study, suggest that continued therapy with ruxolitinib at optimal doses contributes to the benefits seen, including OS benefit.
Generation and characterization of an inducible transgenic model for studying mouse esophageal biology
Authors: Roth Sabrina , Franken Patrick , Monkhorst Kim , Kong a San John , Fodde Riccardo 
Published: June 2012

Abstract

Background
To facilitate the in vivo study of esophageal (stem) cell biology in homeostasis and cancer, novel mouse models are necessary to elicit expression of candidate genes in a tissue-specific and inducible fashion. To this aim, we developed and studied a mouse model to allow labeling of esophageal cells with the histone 2B-GFP (H2B-GFP) fusion protein.

Results
First, we generated a transgenic mouse model expressing the reverse tetracycline transactivator rtTA2-M2 under control of the promoter (ED-L2) of the Epstein-Barr virus (EBV) gene encoding the latent membrane protein-1 (LMP-1). The newly generated ED-L2-rtTA2-M2 (ED-L2-rtTA) mice were then bred with the previously developed tetO-HIST1H2BJ/GFP (tetO-H2B-GFP) model to assess inducibility and tissue-specificity. Expression of the H2B-GFP fusion protein was observed upon doxycycline induction but was restricted to the terminally differentiated cells above the basal cell layer. To achieve expression in the basal compartment of the esophagus, we subsequently employed a different transgenic model expressing the reverse transactivator rtTA2S-M2 under the control of the ubiquitous, methylation-free CpG island of the human hnRNPA2B1-CBX3 gene (hnRNP-rtTA). Upon doxycycline administration to the compound hnRNP-rtTA/tetO-H2B-GFP mice, near-complete labeling of all esophageal cells was achieved. Pulse-chase experiments confirmed that complete turnover of the esophageal epithelium in the adult mouse is achieved within 7–10 days.

Conclusions
We show that the esophagus-specific promoter ED-L2 is expressed only in the differentiated cells above the basal layer. Moreover, we confirmed that esophageal turn-over in the adult mouse does not exceed 7–10 days.
Spatiotemporal analysis of indigenous and imported dengue fever cases in Guangdong province, China
Authors: Li Zhongjie , Yin Wenwu , Clements Archie , Williams Gail , Lai Shengjie , Zhou Hang , Zhao Dan , Guo Yansha , Zhang Yonghui , Wang Jinfeng , Hu Wenbiao , Yang Weizhong 
Published: June 2012

Abstract

Background
Dengue fever has been a major public health concern in China since it re-emerged in Guangdong province in 1978. This study aimed to explore spatiotemporal characteristics of dengue fever cases for both indigenous and imported cases during recent years in Guangdong province, so as to identify high-risk areas of the province and thereby help plan resource allocation for dengue interventions.

Methods
Notifiable cases of dengue fever were collected from all 123 counties of Guangdong province from 2005 to 2010. Descriptive temporal and spatial analysis were conducted, including plotting of seasonal distribution of cases, and creating choropleth maps of cumulative incidence by county. The space-time scan statistic was used to determine space-time clusters of dengue fever cases at the county level, and a geographical information system was used to visualize the location of the clusters. Analysis were stratified by imported and indigenous origin.

Results
1658 dengue fever cases were recorded in Guangdong province during the study period, including 94 imported cases and 1564 indigenous cases. Both imported and indigenous cases occurred more frequently in autumn. The areas affected by the indigenous and imported cases presented a geographically expanding trend over the study period. The results showed that the most likely cluster of imported cases (relative risk = 7.52, p < 0.001) and indigenous cases (relative risk = 153.56, p < 0.001) occurred in the Pearl River Delta Area; while a secondary cluster of indigenous cases occurred in one district of the Chao Shan Area (relative risk = 471.25, p < 0.001).

Conclusions
This study demonstrated that the geographic range of imported and indigenous dengue fever cases has expanded over recent years, and cases were significantly clustered in two heavily urbanised areas of Guangdong province. This provides the foundation for further investigation of risk factors and interventions in these high-risk areas.
Etiology of community-acquired pneumonia in a population-based study: Link between etiology and patients characteristics, process-of-care, clinical evolution and outcomes
Authors: Capelastegui Alberto , España Pedro P , Bilbao Amaia , Gamazo Julio , Medel Federico , Salgado Juan , Gorostiaga Iñaki , Lopez de Goicoechea Maria Jose , Gorordo Inmaculada , Esteban Cristobal , Altube Lander , Quintana Jose M 
Published: June 2012

AbstractBackgroundThe etiologic profile of community-acquired pneumonia (CAP) for each age group could be similar among inpatients and outpatients. This fact brings up the link between etiology of CAP and its clinical evolution and outcome. Furthermore, the majority of pneumonia etiologic studies are based on hospitalized patients, whereas there have been no recent population-based studies encompassing both inpatients and outpatients.MethodsTo evaluate the etiology of CAP, and the relationship among the different pathogens of CAP to patients characteristics, process-of-care, clinical evolution and outcomes, a prospective population-based study was conducted in Spain from April 1, 2006, to June 30, 2007. Patients (age >18) with CAP were identified through the family physicians and the hospital area.ResultsA total of 700 patients with etiologic evaluation were included: 276 hospitalized and 424 ambulatory patients. We were able to define the aetiology of pneumonia in 55.7% (390/700). The most frequently isolated organism wasS. pneumoniae(170/390, 43.6%), followed byC. burnetti(72/390, 18.5%),M. pneumoniae(62/390, 15.9%), virus as a group (56/390, 14.4%), Chlamydia species (39/390, 106%), andL. pneumophila(17/390, 4.4%). The atypical pathogens and theS. pneumoniaeare present in pneumonias of a wide spectrum of severity and age. Patients infected by conventional bacteria were elderly, had a greater hospitalization rate, and higher mortality within 30 days.ConclusionsOur study provides information about the etiology of CAP in the general population. The microbiology of CAP remains stable: infections by conventional bacteria result in higher severity, and theS. pneumoniaeremains the most important pathogen. However, atypical pathogens could also infect patients in a wide spectrum of severity and age.
Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density
Authors: Emmett Maxine S , Symonds Kirsty E , Rigby Howard , Cook Martin G , Price Rebecca , Metcalfe Chris , Orlando Antonio , Bates David O 
Published: June 2012

Abstract

Background
Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB), which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group.

Methods
Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators.

Results
The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis) was also effective when combined into the Shields index in a cohort of 24 patients.

Conclusions
These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.
Prediction of axillary lymph node metastasis in primary breast cancer patients using a decision tree-based model
Authors: Takada Masahiro , Sugimoto Masahiro , Naito Yasuhiro , Moon Hyeong-Gon , Han Wonshik , Noh Dong-Young , Kondo Masahide , Kuroi Katsumasa , Sasano Hironobu , Inamoto Takashi , Tomita Masaru , Toi Masakazu 
Published: June 2012

Abstract

Background
The aim of this study was to develop a new data-mining model to predict axillary lymph node (AxLN) metastasis in primary breast cancer. To achieve this, we used a decision tree-based prediction method—the alternating decision tree (ADTree).

Methods
Clinical datasets for primary breast cancer patients who underwent sentinel lymph node biopsy or AxLN dissection without prior treatment were collected from three institutes (institute A, n = 148; institute B, n = 143; institute C, n = 174) and were used for variable selection, model training and external validation, respectively. The models were evaluated using area under the receiver operating characteristics (ROC) curve analysis to discriminate node-positive patients from node-negative patients.

Results
The ADTree model selected 15 of 24 clinicopathological variables in the variable selection dataset. The resulting area under the ROC curve values were 0.770 [95% confidence interval (CI), 0.689–0.850] for the model training dataset and 0.772 (95% CI: 0.689–0.856) for the validation dataset, demonstrating high accuracy and generalization ability of the model. The bootstrap value of the validation dataset was 0.768 (95% CI: 0.763–0.774).

Conclusions
Our prediction model showed high accuracy for predicting nodal metastasis in patients with breast cancer using commonly recorded clinical variables. Therefore, our model might help oncologists in the decision-making process for primary breast cancer patients before starting treatment.
ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion
Authors: Li Hailing , Peng Wenhui , Jian Weixia , Li Yuanmin , Li Qi , Li Weiming , Xu Yawei 
Published: June 2012

Abstract

Background
Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1).

Methods
HUVECs were stimulated with high glucose (HG) or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples.

Results
Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 ± 7.5 ng/ml to 39.7 ± 5.6 ng/ml after fasudil treatment (P < 0.05).

Conclusions
Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.
Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay
Authors: Tyner Stuart D , Lon Chanthap , Se Youry , Bethell Delia , Socheat Doung , Noedl Harald , Sea Darapiseth , Satimai Wichai , Schaecher Kurt , Rutvisuttinunt Wiriya , Fukuda Mark M , Chaorattanakawee Suwanna , Yingyuen Kritsanai , Sundrakes Siratchana , Chaichana Panjaporn , Saingam Piyaporn , Buathong Nillawan , Sriwichai Sabaithip , Chann Soklyda , Timmermans Ans , Saunders David L , Walsh Douglas S 
Published: June 2012

Abstract

Background

In vitro drug susceptibility assay of Plasmodium falciparum field isolates processed “immediate ex vivo” (IEV), without culture adaption, and tested using histidine-rich protein-2 (HRP-2) detection as an assay, is an expedient way to track drug resistance.

Methods
From 2005 to 2010, a HRP-2 in vitro assay assessed 451 P. falciparum field isolates obtained from subjects with malaria in western and northern Cambodia, and eastern Thailand, processed IEV, for 50% inhibitory concentrations (IC50) against seven anti-malarial drugs, including artesunate (AS), dihydroartemisinin (DHA), and piperaquine.

Results
In western Cambodia, from 2006 to 2010, geometric mean (GM) IC50 values for chloroquine, mefloquine, quinine, AS, DHA, and lumefantrine increased. In northern Cambodia, from 2009–2010, GM IC50 values for most drugs approximated the highest western Cambodia GM IC50 values in 2009 or 2010.

Conclusions
Western Cambodia is associated with sustained reductions in anti-malarial drug susceptibility, including the artemisinins, with possible emergence, or spread, to northern Cambodia. This potential public health crisis supports continued in vitro drug IC50 monitoring of P. falciparum isolates at key locations in the region.
Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images
Authors: Pachiyappan Arulmozhivarman , Das Undurti N , Murthy Tatavarti VSP , Tatavarti Rao 
Published: June 2012

AbstractWe describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized.
Endotracheal intubation using the C-MAC® video laryngoscope or the Macintosh laryngoscope: A prospective, comparative study in the ICU
Authors: Noppens Ruediger R , Geimer Stephanie , Eisel Nicole , David Matthias , Piepho Tim 
Published: June 2012

Abstract
Introduction
Endotracheal intubation in the ICU is a challenging procedure and is frequently associated with life-threatening complications. The aim of this study was to investigate the effect of the C-MAC® video laryngoscope on laryngeal view and intubation success compared with direct laryngoscopy.

Methods
In a single-center, prospective, comparative before-after study in an anesthetist-lead surgical ICU of a tertiary university hospital, predictors of potentially difficult tracheal intubation, number of intubation attempts, success rate and glottic view were evaluated during a 2-year study period (first year, Macintosh laryngoscopy (ML); second year, C-MAC®).

Results
A total of 274 critically ill patients requiring endotracheal intubation were included; 113 intubations using ML and 117 intubations using the C-MAC® were assessed. In patients with at least one predictor for difficult intubation, the C-MAC® resulted in more successful intubations on first attempt compared with ML (34/43, 79% vs. 21/38, 55%; P = 0.03). The visualization of the glottis with ML using Cormack and Lehane (C&L) grading was more frequently rated as difficult (20%, C&L grade 3 and 4) compared with the C-MAC® (7%, C&L grade 3 and 4) (P < 0.0001).

Conclusion
Use of the C-MAC® video laryngoscope improved laryngeal imaging and improved the intubating success rate on the first attempt in patients with predictors for difficult intubation in the ICU setting. Video laryngoscopy seems to be a useful tool in the ICU where potentially difficult endotracheal intubations regularly occur.
Early developmental gene regulation in Strongylocentrotus purpuratus embryos in response to elevated CO2 seawater conditions
Authors: Hammond LaTisha M. , Hofmann Gretchen E. 
Published: June 2012

SUMMARY
Ocean acidification, or the increased uptake of CO2 by the ocean due to elevated atmospheric CO2 concentrations, may variably impact marine early life history stages, as they may be especially susceptible to changes in ocean chemistry. Investigating the regulatory mechanisms of early development in an environmental context, or ecological development, will contribute to increased understanding of potential organismal responses to such rapid, large-scale environmental changes. We examined transcript-level responses to elevated seawater CO2 during gastrulation and the initiation of spiculogenesis, two crucial developmental processes in the purple sea urchin, Strongylocentrotus purpuratus. Embryos were reared at the current, accepted oceanic CO2 concentration of 380 microatmospheres (μatm), and at the elevated levels of 1000 and 1350 μatm, simulating predictions for oceans and upwelling regions, respectively. The seven genes of interest comprised a subset of pathways in the primary mesenchyme cell gene regulatory network (PMC GRN) shown to be necessary for the regulation and execution of gastrulation and spiculogenesis. Of the seven genes, qPCR analysis indicated that elevated CO2 concentrations only had a significant but subtle effect on two genes, one important for early embryo patterning, Wnt8, and the other an integral component in spiculogenesis and biomineralization, SM30b. Protein levels of another spicule matrix component, SM50, demonstrated significant variable responses to elevated CO2. These data link the regulation of crucial early developmental processes with the environment that these embryos would be developing within, situating the study of organismal responses to ocean acidification in a developmental context.
Visual attention in a complex search task differs between honeybees and bumblebees
Authors: Morawetz Linde , Spaethe Johannes 
Published: June 2012

SUMMARYMechanisms of spatial attention are used when the amount of gathered information exceeds processing capacity. Such mechanisms have been proposed in bees, but have not yet been experimentally demonstrated. We provide evidence that selective attention influences the foraging performance of two social bee species, the honeybee Apis mellifera and the bumblebee Bombus terrestris. Visual search tasks, originally developed for application in human psychology, were adapted for behavioural experiments on bees. We examined the impact of distracting visual information on search performance, which we measured as error rate and decision time. We found that bumblebees were significantly less affected by distracting objects than honeybees. Based on the results, we conclude that the search mechanism in honeybees is serial like, whereas in bumblebees it shows the characteristics of a restricted parallel-like search. Furthermore, the bees differed in their strategy to solve the speed–accuracy trade-off. Whereas bumblebees displayed slow but correct decision-making, honeybees exhibited fast and inaccurate decision-making. We propose two neuronal mechanisms of visual information processing that account for the different responses between honeybees and bumblebees, and we correlate species-specific features of the search behaviour to differences in habitat and life history.
High speed galloping in the cheetah (Acinonyx jubatus) and the racing greyhound (Canis familiaris): spatio-temporal and kinetic characteristics
Authors: Hudson Penny E. , Corr Sandra A. , Wilson Alan M. 
Published: June 2012

SUMMARYThe cheetah and racing greyhound are of a similar size and gross morphology and yet the cheetah is able to achieve a far higher top speed. We compared the kinematics and kinetics of galloping in the cheetah and greyhound to investigate how the cheetah can attain such remarkable maximum speeds. This also presented an opportunity to investigate some of the potential limits to maximum running speed in quadrupeds, which remain poorly understood. By combining force plate and high speed video data of galloping cheetahs and greyhounds, we show how the cheetah uses a lower stride frequency/longer stride length than the greyhound at any given speed. In some trials, the cheetahs used swing times as low as those of the greyhounds (0.2 s) so the cheetah has scope to use higher stride frequencies (up to 4.0 Hz), which may contribute to it having a higher top speed that the greyhound. Weight distribution between the animal's limbs varied with increasing speed. At high speed, the hindlimbs support the majority of the animal's body weight, with the cheetah supporting 70% of its body weight on its hindlimbs at 18 m s–1; however, the greyhound hindlimbs support just 62% of its body weight. Supporting a greater proportion of body weight on a particular limb is likely to reduce the risk of slipping during propulsive efforts. Our results demonstrate several features of galloping and highlight differences between the cheetah and greyhound that may account for the cheetah's faster maximum speeds.