bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic Lethality Screens Reveal RPS6 and MST1R as Modifiers of Insulin-like Growth Factor-1 Receptor Inhibitor Activity in Childhood Sarcomas
Authors: Potratz Jenny C. , Saunders Darren N. , Wai Daniel H. , Ng Tony L. , McKinney Steven E. , Carboni Joan M. , Gottardis Marco M. , Triche Timothy J. , Jürgens Heribert , Pollak Michael N. , Aparicio Samuel A. , Sorensen Poul H.B. 
Published: October 2010

Abstract
The insulin-like growth factor-1 receptor (IGF1R) is emerging as a promising therapeutic target in human cancers. In the high-risk childhood sarcomas Ewing family tumor and rhabdomyosarcoma, IGF1R-blocking antibodies show impressive antitumor activity in some but not all patients, and acquired resistance is observed. Because tumor IGF1R mutations are not described, the basis of IGF1R inhibitor resistance remains unknown. We hypothesized that compensatory signaling cascades bypassing targeted IGF1R inhibition might be involved. To test this systematically, we performed small interfering RNA (siRNA) screens in sarcoma cell lines to identify IGF1R pathway components or related protein tyrosine kinase (PTK) networks that modulate the antitumor efficacy of the BMS-536924 IGF1R kinase inhibitor. This strategy revealed (a) that sarcoma cells are exquisitely sensitive to loss of distal rather than proximal IGF1R signaling components, such as ribosomal protein S6 (RPS6); (b) that BMS-536924 fails to block RPS6 activation in resistant sarcoma cell lines; and (c) that siRNA knockdown of the macrophage-stimulating 1 receptor tyrosine kinase (MST1R; also known as RON) restores BMS-536924 efficacy, even in highly drug-resistant cell lines. We confirmed MST1R expression across a broad panel of childhood sarcomas, and found that loss of MST1R by RNA interference blocks downstream RPS6 activation when combined with BMS-536924 in vitro. These findings underscore the importance of fully understanding PTK networks for successful clinical implementation of kinase inhibitor strategies. Cancer Res; 70(21); 8770–81. ©2010 AACR.
FTY720 (Fingolimod) Sensitizes Prostate Cancer Cells to Radiotherapy by Inhibition of Sphingosine Kinase-1
Authors: Pchejetski Dmitri , Bohler Torsten , Brizuela Leyre , Sauer Lysann , Doumerc Nicolas , Golzio Muriel , Salunkhe Vishal , Teissié Justin , Malavaud Bernard , Waxman Jonathan , Cuvillier Olivier 
Published: October 2010

Abstract
Radiotherapy is widely used as a radical treatment for prostate cancer, but curative treatments are elusive for poorly differentiated tumors where survival is just 15% at 15 years. Dose escalation improves local response rates but is limited by tolerance in normal tissues. A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for treatment of multiple sclerosis, has been found to be a potent apoptosis inducer in prostate cancer cells. Using in vitro and in vivo approaches, we analyzed the impact of FTY720 on sphingolipid metabolism in hormone-refractory metastatic prostate cancer cells and evaluated its potential as a radiosensitizer on cell lines and prostate tumor xenografts. In prostate cancer cell lines, FTY720 acted as a sphingosine kinase 1 (SphK1) inhibitor that induced prostate cancer cell apoptosis in a manner independent of sphingosine-1-phosphate receptors. In contrast, γ irradiation did not affect SphK1 activity in prostate cancer cells yet synergized with FTY720 to inhibit SphK1. In mice bearing orthotopic or s.c. prostate cancer tumors, we show that FTY720 dramatically increased radiotherapeutic sensitivity, reducing tumor growth and metastasis without toxic side effects. Our findings suggest that low, well-tolerated doses of FTY720 could offer significant improvement to the clinical treatment of prostate cancer. Cancer Res; 70(21); 8651–61. ©2010 AACR.
Warfarin Discontinuation After Starting Warfarin for Atrial Fibrillation
Authors: Fang Margaret C. , Go Alan S. , Chang Yuchiao , Borowsky Leila H. , Pomernacki Niela K. , Udaltsova Natalia , Singer Daniel E. 
Published: October 2010

Background—
Although warfarin is widely recommended to prevent atrial fibrillation-related thromboembolism, many eligible patients do not take warfarin. The objective of this study was to describe factors associated with warfarin discontinuation in patients newly starting warfarin for atrial fibrillation.

Methods and Results—

We identified 4188 subjects newly starting warfarin in the Anticoagulation and Risk Factors in Atrial Fibrillation Study and tracked longitudinal warfarin use through pharmacy and laboratory databases. Data on patient characteristics, international normalized ratio (INR) tests, and incident hospitalizations for hemorrhage were obtained from clinical and laboratory databases. Multivariable Cox regression analysis was used to identify independent predictors of prolonged warfarin discontinuation, defined as ≥180 consecutive days off warfarin. Within 1 year after warfarin initiation, 26.3% of subjects discontinued therapy despite few hospitalizations for hemorrhage (2.3% of patients). The risk of discontinuation was higher in patients aged <65 years (adjusted hazard ratio [HR], 1.33 [95% CI, 1.03 to 1.72] compared to those aged ≥85 years), patients with poorer anticoagulation control (HR, 1.46 [95% CI, 1.42 to 1.49] for every 10% decrease in time in therapeutic INR range), and patients with lower stroke risk (HR, 2.54 [95% CI, 1.86 to 3.47] for CHADS
2
stroke risk index of 0 compared to 4 to 6).

Conclusions—
More than 1 in 4 patients newly starting warfarin for atrial fibrillation discontinued therapy in the first year despite a low overall hemorrhage rate. Individuals deriving potentially less benefit from warfarin, including those with younger age, fewer stroke risk factors, and poorer INR control, were less likely to remain on warfarin. Maximizing the benefits of anticoagulation for atrial fibrillation depends on determining which patients are most appropriately initiated and maintained on therapy.
Age and Sex Differences and 20-Year Trends (1986 to 2005) in Prehospital Delay in Patients Hospitalized With Acute Myocardial Infarction
Authors: Nguyen Hoa L. , Gore Joel M. , Saczynski Jane S. , Yarzebski Jorge , Reed George , Spencer Frederick A. , Goldberg Robert J. 
Published: October 2010

Background—
The prompt administration of coronary reperfusion therapy for patients with an evolving acute myocardial infarction (AMI) is crucial in reducing mortality and the risk of serious clinical complications in these patients. However, long-term trends in extent of prehospital delay and factors affecting patient's care-seeking behavior remain relatively unexplored, especially in men and women of different ages. The objectives of this study were to examine the overall magnitude and 20-year trends (1986 to 2005) in duration of prehospital delay in middle-aged and elderly men and women hospitalized with AMI.

Methods and Results—
The study sample consisted of 5967 residents of the Worcester, Mass, metropolitan area hospitalized at all greater Worcester medical centers for AMI between 1986 and 2005 who had information available about duration of prehospital delay. Compared with men <65 years, patients in other age-sex strata exhibited longer prehospital delays over the 20-year period under study. The multivariable-adjusted medians of prehospital delay were 1.96, 2.07, and 2.57 hours for men <65 years, men 65 to 74 years, and men ≥75 years and 2.08, 2.33, and 2.27 hours for women <65 years, women 65 to 74 years, and women ≥75 years, respectively. These age and sex differences have narrowed over time, which has been largely explained by changes in patient's comorbidity profile and AMI-associated characteristics.

Conclusions—
Our results suggest that duration of prehospital delay in persons with symptoms of AMI has remained essentially unchanged during the 20-year period under study and elderly individuals are more likely to delay seeking timely medical care than younger persons.
Pins and Rubber Band Traction System and Osteosynthesis With a Hook Plate for the Treatment of Old Fracture-Dislocation of a Toe Application of Hand Operative Techniques in a Foot Operation
Authors: Tonogai Ichiro , Hamada Yoshitaka , Kashima Masahiro , Takahashi Masami , Kanematsu Yoshiji , Henmi Tatsuhiko 
Published: October 2010

The treatment of old fracture-dislocation of a toe is usually difficult. The authors used 2 techniques that are commonly used in finger operations: One is the pins and rubber band traction system, and the other is the hook plate osteosynthesis. They treated a 56-year-old woman using these methods, and obtained a good result. Levels of Evidence: Therapeutic, Level IV
Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities
Authors: Marcucci Fabrizio , Mele Alfonso 
Published: October 2010

AbstractOver the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis viruses may contribute to lymphomagenesis, and discuss the therapeutic fallouts from this knowledge. Most of this evidence is on HCV, and this is the main focus of the review. Moreover, we mainly address the association with NHL, the most prevalent hematologic malignancy, and the most extensively investigated with regard to an association with hepatitis viruses. Available evidence on the association with other hematologic malignancies is also addressed briefly.
Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse
Authors: Choi Inho , Chung Hee Kyoung , Ramu Swapnika , Lee Ha Neul , Kim Kyu Eui , Lee Sunju , Yoo Jaehyuk , Choi Dongwon , Lee Yong Suk , Aguilar Berenice , Hong Young-Kwon 
Published: October 2010

Abstract
Although the blood vessel-specific fluorescent transgenic mouse has been an excellent tool to study vasculogenesis and angiogenesis, a lymphatic-specific fluorescent mouse model has not been established to date. Here we report a transgenic animal model that expresses the green fluorescent protein under the promoter of Prox1, a master control gene in lymphatic development. Generated using an approximately 200-kb-long bacterial artificial chromosome harboring the entire Prox1 gene, this Prox1-green fluorescent protein mouse was found to faithfully recapitulate the expression pattern of the Prox1 gene in lymphatic endothelial cells and other Prox1-expressing organs, and enabled us to conveniently visualize detailed structure and morphology of lymphatic vessels and networks throughout development. Our data demonstrate that this novel transgenic mouse can be extremely useful for detection, imaging, and isolation of lymphatic vessels and monitoring wound-associated lymphangiogenesis. Together, this Prox1-green fluorescent protein transgenic mouse will be a great tool for the lymphatic research.
Use of consensus sequences for the design of high density resequencing microarrays: the influenza virus paradigm
Authors: Leclercq India , Berthet Nicolas , Batéjat Christophe , Rousseaux Claudine , Dickinson Philip , Old Iain G , Kong Katherine , Kennedy Giulia C , Cole Stewart T , Manuguerra Jean-Claude 
Published: October 2010

Abstract

Background
A resequencing microarray called PathogenID v2.0 has been developed and used to explore various strategies of sequence selection for its design. The part dedicated to influenza viruses was based on consensus sequences specific for one gene generated from global alignments of a large number of influenza virus sequences available in databanks.

Results
For each HA (H1, H2, H3, H5, H7 and H9) and NA (N1, N2 and N7) molecular type chosen to be tested, 1 to 3 consensus sequences were computed and tiled on the microarray. A total of 12 influenza virus samples from different host origins (humans, pigs, horses and birds) and isolated over a period of about 50 years were used in this study. Influenza viruses were correctly identified, and in most cases with the accurate information of the time of their emergence.

Conclusions
PathogenID v2.0 microarray demonstrated its ability to type and subtype influenza viruses, often to the level of viral variants, with a minimum number of tiled sequences. This validated the strategy of using consensus sequences, which do not exist in nature, for our microarray design. The versatility, rapidity and high discriminatory power of the PathogenID v2.0 microarray could prove critical to detect and identify viral genome reassortment events resulting in a novel virus with epidemic or pandemic potential and therefore assist health authorities to make efficient decisions about patient treatment and outbreak management.
Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity
Authors: Preza Ana M , Jaramillo María E , Puebla Ana M , Mateos Juan C , Hernández Rodolfo , Lugo Eugenia 
Published: October 2010

Abstract

Background
Recently, proteins and peptides have become an added value to foodstuffs due to new knowledge about its structural analyses as related to antioxidant and anticancer activity. Our goal was to evaluate if protein fractions from cacao seeds show antitumor activity on lymphoma murine L5178Y model. The antioxidant activity of these fractions was also evaluated with the aim of finding a correlation with the antitumor activity.

Methods
Differential extraction of proteins from unfermented and semi-fermented-dry cacao seeds was performed and characterized by SDS-PAGE and FPLC size-exclusion chromatography. Antitumor activity was evaluated against murine lymphoma L5178Y in BALB/c mice (6 × 104 cells i.p.), with a treatment oral dose of 25 mg/kg/day of each protein fraction, over a period of 15 days. Antioxidant activity was evaluated by the ABTS+ and ORAC-FL assays.

Results
Albumin, globulin and glutelin fractions from both cacao seed type were obtained by differential solubility extraction. Glutelins were the predominant fraction. In the albumin fraction, polypeptides of 42.3 and 8.5 kDa were found in native conditions, presumably in the form of two peptide chains of 21.5 kDa each one. The globulin fraction presented polypeptides of 86 and 57 kDa in unfermented cacao seed that produced the specific-cacao aroma precursors, and after fermentation the polypeptides were of 45 and 39 kDa. The glutelin fraction presented proteins >200 kDa and globulins components <100 KDa in lesser proportion. Regarding the semifermented-dry cacao seed, it was observed that the albumin fraction showed antitumoral activity, since it caused significant decreases (p < 0.05) in the ascetic fluid volume and packed cell volume, inhibiting cell growth in 59.98 ± 13.6% at 60% of the population; while the greatest antioxidant capacity due to free radical scavenging capacity was showed by the albumin and glutelin fraction in both methods assayed.

Conclusion
This study is the first report on the biological activity of semifermented-dry cacao protein fractions with their identification, supporting the traditional use of the plant. The albumin fraction showed antitumor and free radical scavenging capacity, however both activities were not correlated. The protein fractions could be considered as source of potential antitumor peptides.
Categorizing and comparing psychophysical detection strategies based on biomechanical responses to short postural perturbations
Authors: Bhatkar Viprali V , Skufca Joseph D , Pilkar Rakesh B , Storey Christopher M , Robinson Charles J 
Published: October 2010

Abstract

Background
A fundamental unsolved problem in psychophysical detection experiments is in discriminating guesses from the correct responses. This paper proposes a coherent solution to this problem by presenting a novel classification method that compares biomechanical and psychological responses.

Methods
Subjects (13) stood on a platform that was translated anteriorly 16 mm to find psychophysical detection thresholds through a Adaptive 2-Alternative-Forced-Choice (2AFC) task repeated over 30 separate sequential trials. Anterior-posterior center-of-pressure (APCoP) changes (i.e., the biomechanical response RB) were analyzed to determine whether sufficient biomechanical information was available to support a subject's psychophysical selection (RΨ) of interval 1 or 2 as the stimulus interval. A time-series-bitmap approach was used to identify anomalies in interval 1 (a1) and interval 2 (a2) that were present in the resultant APCoP signal. If a1 > a2 then RB = Interval 1. If a1 < a2, then RB= Interval 2. If a2 - a1 < 0.1, RB was set to 0 (no significant difference present in the anomaly scores of interval 1 and 2).

Results
By considering both biomechanical (RB) and psychophysical (RΨ) responses, each trial run could be classified as a: 1) HIT (and True Negative), if RB and RΨ both matched the stimulus interval (SI); 2) MISS, if RB matched SI but the subject's reported response did not; 3) PSUEDO HIT, if the subject signalled the correct SI, but RB was linked to the non-SI; 4) FALSE POSITIVE, if RB = RΨ, and both associated to non-SI; and 5) GUESS, if RB = 0, if insufficient APCoP differences existed to distinguish SI. Ensemble averaging the data for each of the above categories amplified the anomalous behavior of the APCoP response.

Conclusions
The major contributions of this novel classification scheme were to define and verify by logistic models a 'GUESS' category in these psychophysical threshold detection experiments, and to add an additional descriptor, "PSEUDO HIT". This improved classification methodology potentially could be applied to psychophysical detection experiments of other sensory modalities.
Consumption of diets high in prebiotic fiber or protein during growth influences the response to a high fat and sucrose diet in adulthood in rats
Authors: Maurer Alannah D , Eller Lindsay K , Hallam Megan C , Taylor Kim , Reimer Raylene A 
Published: October 2010

Abstract

Background
Early dietary exposure can influence susceptibility to obesity and type 2 diabetes later in life. We examined the lasting effects of a high protein or high prebiotic fiber weaning diet when followed by a high energy diet in adulthood.

Methods
At birth, litters of Wistar rats were culled to 10 pups. At 21 d pups were weaned onto control (C), high prebiotic fiber (HF) or high protein (HP) diet. Rats consumed the experimental diets until 14 wk when they were switched to a high fat/sucrose (HFHS) diet for 6 wk. Body composition and energy intake were measured and an oral glucose tolerance test (OGTT) performed. Blood was analyzed for satiety hormones and tissues collected for real-time PCR.

Results
Weight gain was attenuated in male rats fed HF from 12 wk until study completion. In females there were early reductions in body weight that moderated until the final two wk of HFHS diet wherein HF females weighed less than HP. Final body weight was significantly higher following the high fat challenge in male and female rats that consumed HP diet from weaning compared to HF. Lean mass was higher and fat mass lower with HF compared to HP and compared to C in males. Energy intake was highest in HP rats, particularly at the start of HFHS feeding. Plasma glucose was higher in HP rats compared to HF during an OGTT. Plasma amylin was higher in HF females compared to C and glucagon-like peptide-1 (GLP-1) was higher in HF rats during the OGTT. Leptin was higher in HP rats during the OGTT. HF upregulated GLUT 5 mRNA expression in the intestine and downregulated hepatic hydroxymethylglutaryl coenzyme A reductase. Male rats fed HP had higher hepatic triglyceride content than C or HF.

Conclusion
These data suggest that while a long-term diet high in protein predisposes to an obese phenotype when rats are given a high energy diet in adulthood, consumption of a high fiber diet during growth may provide some protection.
‘Choosing shoes’: a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients
Authors: Silvester Renee N , Williams Anita E , Dalbeth Nicola , Rome Keith 
Published: October 2010

AbstractBackgroundFootwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA.MethodsEighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre‐determined criteria for assessing footwear type, based on a previous study of foot pain.ResultsThe patients had longstanding RA with moderate‐to severe disability and impairment. The foot and ankle assessment demonstrated a low‐arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were open‐type footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear.ConclusionsThe majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA.
The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome
Authors: Herst Patries M , Howman Rebecca A , Neeson Paul J , Berridge Michael V , Ritchie David S 
Published: October 2010

ABSTRACTThis research investigated the level of glycolytic metabolism in leukemic blasts as a prognostic marker in AML. Using an in vitro dye-reduction assay, we determined the level of glycolytic metabolism in 26 BM samples taken from 23 adult patients with newly diagnosed (n=19) or relapsed (n=4) AML, and AML blasts stratified into two distinct cohorts of moderate (&lt;70%) or high (&gt;80%) levels of glycolytic metabolism. All samples taken at relapse were moderately glycolytic. However, nine of the 19 samples taken at diagnosis were highly glycolytic, and 10 were moderately glycolytic. Three patients had paired samples taken at diagnosis and relapse, and the glycolytic metabolism of these samples did not alter between the two time-points. The level of glycolytic metabolism did not correlate with the percentage of marrow blasts, patient age, or CG/molecular risk group. Highly glycolytic AML blasts were more resistant to apoptosis induced by ATRA and/or ATO in vitro, suggesting potential resistance to induction chemotherapy, as has been observed in solid tumors. Despite this, high levels of glycolytic metabolism at diagnosis were predictive of a significantly improved duration of CR1 and OS following AML remission induction chemotherapy. In conclusion, we found that the extent of myeloblast glycolysis may be an effective and easily applied method to determine the pretreatment prognosis of AML.