bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Inhibition of Src Kinase with Dasatinib Blocks Thyroid Cancer Growth and Metastasis
Authors: Chan Christine M. , Jing Xia , Pike Laura A. , Zhou Qiong , Lim Dong-Jun , Sams Sharon B. , Lund Gregory S. , Sharma Vibha , Haugen Bryan R. , Schweppe Rebecca E. 
Published: May 2012

Abstract
Purpose: There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer. We therefore tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid cancer growth and metastasis.
Experimental Design: The effects of dasatinib on thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an orthotopic and a novel experimental metastasis model. Expression and activation of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib was determined using an Src gatekeeper mutant.
Results: Dasatinib treatment inhibited Src signaling, decreased growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004, respectively).
Conclusion: These data provide the first evidence that Src is a central mediator of thyroid cancer growth and metastasis, indicating that Src inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both antitumor and antimetastatic agents. Clin Cancer Res; 18(13); 3580–91. ©2012 AACR.
CTLA-4 Blockade Expands Infiltrating T Cells and Inhibits Cancer Cell Repopulation during the Intervals of Chemotherapy in Murine Mesothelioma
Authors: Wu Licun , Yun Zhihong , Tagawa Tetsuzo , Rey-McIntyre Katrina , de Perrot Marc 
Published: May 2012

Abstract
Cancer immunotherapy has shown promising results when combined with chemotherapy. Blocking CTLA-4 signaling by monoclonal antibody between cycles of chemotherapy may inhibit cancer cell repopulation and enhance the antitumoral immune reaction, thus improve the efficacy of chemotherapy in mesothelioma. The impact of CTLA-4 blockade on the early stage of tumor development was evaluated in a subcutaneous murine mesothelioma model. CTLA-4 blocking antibody was administered following each cycle of chemotherapy, and monotherapy was included as controls. Antitumor effect was evaluated by tumor growth delay and survival of the animals. Tumor cell repopulation was quantified by bromodeoxyuridine incorporation and Ki67 by immunohistochemistry and/or flow cytometry. In vitro cell killing was determined by classic chromium-released assay, and reverse transcription PCR (RT-PCR) was carried out to determine the gene expression of associated cytokines. Anti-CTLA-4 monoclonal antibody was able to inhibit tumor growth at early stage of tumor development. Antitumor effect was achieved by administration of CTLA-4 blockade between cycles of chemotherapy. Tumor cell repopulation during the intervals of cisplatin was inhibited by CTLA-4 blockade. Anti-CTLA-4 therapy gave rise to an increased number of CD4 and CD8 T cells infiltrating the tumor. RT-PCR showed that the gene expression of interleukin IL-2, IFN-γ, granzyme B, and perforin increased in the tumor milieu. Blockade of CTLA-4 signaling showed effective anticancer effect, correlating with inhibiting cancer cell repopulation between cycles of chemotherapy and upregulating tumor-infiltrating T lymphocytes, cytokines, and cytolytic enzymes in a murine mesothelioma model. Mol Cancer Ther; 11(8); 1809–19. ©2012 AACR.
The Effect of a Postoperative Course of Oral Prednisone on Postoperative Morbidity following Childhood Tonsillectomy
Authors: Macassey Emily , Dawes Patrick , Taylor Barry , Gray Andrew 
Published: May 2012

ObjectiveTonsillectomy is a common procedure with a wide range of described operative techniques and usage of perioperative medications. Single‐dose intraoperative dexamethasone has been shown to decrease postoperative nausea and pain and improve return to normal diet. The aim was to determine if a course of oral postoperative steroids would further decrease postoperative morbidity following tonsillectomy in children.Study DesignRandomized, placebo‐controlled, double‐blinded trial. Power analysis recommended 198 participants.SettingA university hospital and private hospital.Subjects and MethodsThe authors compared a 5‐day course of oral prednisolone with placebo in a pediatric population (3‐16 years) undergoing tonsillectomy to assess effects on postoperative pain, nausea, and vomiting and return to normal function. They also assessed the effect of corticosteroids on sleep duration and aspects of sleep quality.ResultsThe results showed no significant difference between the 2 groups when analyzed for differences in the above variables both overall and at each of the postoperative 10 time points (pain, P =. 478; nausea and vomiting, P =. 556; return to normal diet well, P =. 234; return to normal activity, P =. 668; bedtime, P =. 056; number of times awake during the night, P =. 593).ConclusionThere is no evidence of benefit from postoperative administration of corticosteroids in pediatric patients recovering from tonsillectomy.
The COPII pathway and hematologic disease
Authors: Khoriaty Rami , Vasievich Matthew P. , Ginsburg David 
Published: May 2012

AbstractMultiple diseases, hematologic and nonhematologic, result from defects in the early secretory pathway. Congenital dyserythropoietic anemia type II (CDAII) and combined deficiency of coagulation factors V and VIII (F5F8D) are the 2 known hematologic diseases that result from defects in the endoplasmic reticulum (ER)–to–Golgi transport system. CDAII is caused by mutations in the SEC23B gene, which encodes a core component of the coat protein complex II (COPII). F5F8D results from mutations in either LMAN1 (lectin mannose-binding protein 1) or MCFD2 (multiple coagulation factor deficiency protein 2), which encode the ER cargo receptor complex LMAN1-MCFD2. These diseases and their molecular pathogenesis are the focus of this review.
Hand hygiene instruction decreases illness-related absenteeism in elementary schools: a prospective cohort study
Authors: Lau Claudia H , Springston Elizabeth E , Sohn Min-Woong , Mason Iyana , Gadola Emily , Damitz Maureen , Gupta Ruchi S 
Published: May 2012

AbstractBackgroundIllness-related absences have been shown to lead to negative educational and economic outcomes. Both hand washing and hand sanitizer interventions have been shown to be effective in reducing illness-related absences. However, while the importance of hand hygiene in schools is clear, the role of instruction in use is less obvious. The purpose of this study was to compare absenteeism rates among elementary students given access to hand hygiene facilities versus students given both access and short repetitive instruction in use, particularly during influenza season when illness-related absences are at a peak.MethodsA hand hygiene intervention was implemented from October to May during the 2009/2010 academic year, including peak flu season, in two Chicago Public Elementary Schools among students grades pre-kindergarten to eighth grade (ages 4–14). Classrooms were systematically assigned to an intervention or control group by grade (cluster design). Hand hygiene facilities (sanitizer and soap) were made available to all students. Students in the intervention group also received short repetitive instruction in hand hygiene every 2 months. Only absences as a result of respiratory or gastrointestinal illness were used to establish illness-related absenteeism rates. Percent absent days were calculated and bivariate analyses were performed to compare percent absent days among students given access to hand hygiene facilities versus students given both access and instruction. Prior to the intervention, teachers’ perceptions of students’ hand hygiene were also evaluated. Teacher perceptions were analysed to describe attitudes and beliefs.ResultsData were collected and analysed for 773 students reporting 1,886 absences during the study period (1.73% of total school days). Both the percent total absent days and percent illness-related absent days were significantly lower in the group receiving short instruction during flu season (P = 0.002, P < 0.001, respectively). This difference peaked during the influenza season (when intervention began) and declined in the following months. Teachers (n = 23) agreed that hand hygiene is not performed properly among students and reported time constraints as a barrier to frequent hand washing.ConclusionsAdding hand hygiene instruction to existing hand hygiene practices improved attendance at public elementary schools during the flu season. Standardized and brief repetitive instruction in hand hygiene holds potential to significantly reduce absenteeism.
New cell line development for antibody-producing Chinese hamster ovary cells using split green fluorescent protein
Authors: Kim Yeon-Gu , Park Byoungwoo , Ahn Jung Oh , Jung Joon-Ki , Lee Hong Weon , Lee Eun Gyo 
Published: May 2012

Abstract

Background
The establishment of high producer is an important issue in Chinese hamster ovary (CHO) cell culture considering increased heterogeneity by the random integration of a transfected foreign gene and the altered position of the integrated gene. Fluorescence-activated cell sorting (FACS)-based cell line development is an efficient strategy for the selection of CHO cells in high therapeutic protein production.

Results
An internal ribosome entry site (IRES) was introduced for using two green fluorescence protein (GFP) fragments as a reporter to both antibody chains, the heavy chain and the light chain. The cells co-transfected with two GFP fragments showed the emission of green fluorescence by the reconstitution of split GFP. The FACS-sorted pool with GFP expression had a higher specific antibody productivity (q
Ab) than that of the unsorted pool. The q
Ab was highly correlated with the fluorescence intensity with a high correlation coefficient, evidenced from the analysis of median GFP and q
Ab in individual selected clones.

Conclusions
This study proved that the fragment complementation for split GFP could be an efficient indication for antibody production on the basis of high correlation of q
Ab with reconstitution of GFP. Taken together, we developed an efficient FACS-based screening method for high antibody-producing CHO cells with the benefits of the split GFP system.
Bariatric surgery and T2DM improvement mechanisms: a mathematical model
Authors: Toghaw Puntip , Matone Alice , Lenbury Yongwimon , De GAETANO Andrea 
Published: May 2012

Abstract

Background
Consensus exists that several bariatric surgery procedures produce a rapid improvement of glucose homeostasis in obese diabetic patients, improvement apparently uncorrelated with the degree of eventual weight loss after surgery. Several hypotheses have been suggested to account for these results: among these, the anti-incretin, the ghrelin and the lower-intestinal dumping hypotheses have been discussed in the literature. Since no clear-cut experimental results are so far available to confirm or disprove any of these hypotheses, in the present work a mathematical model of the glucose-insulin-incretin system has been built, capable of expressing these three postulated mechanisms. The model has been populated with critically evaluated parameter values from the literature, and simulations under the three scenarios have been compared.

Results
The modeling results seem to indicate that the suppression of ghrelin release is unlikely to determine major changes in short-term glucose control. The possible existence of an anti-incretin hormone would be supported if an experimental increase of GIP concentrations were evident post-surgery. Given that, on the contrary, collected evidence suggests that GIP concentrations decrease post-surgery, the lower-intestinal dumping hypothesis would seem to describe the mechanism most likely to produce the observed normalization of Type 2 Diabetes Mellitus (T2DM) after bariatric surgery.

Conclusions
The proposed model can help discriminate among competing hypotheses in a context where definitive data are not available and mechanisms are still not clear.
Standard abdominal wound edge protection with surgical dressings vs coverage with a sterile circular polyethylene drape for prevention of surgical site infections (BaFO): study protocol for a randomized controlled trial
Authors: Mihaljevic André L , Michalski Christoph W , Erkan Mert , Reiser-Erkan Carolin , Jäger Carsten , Schuster Tibor , Schuhmacher Christoph , Kleeff Jörg , Friess Helmut 
Published: May 2012

Abstract

Background
Postoperative surgical site infections cause substantial morbidity, prolonged hospitalization, costs and even mortality and remain one of the most frequent surgical complications. Approximately 14% to 30% of all patients undergoing elective open abdominal surgery are affected and methods to reduce surgical site infection rates warrant further investigation and evaluation in randomized controlled trials.

Methods/design
To investigate whether the application of a circular plastic wound protector reduces the rate of surgical site infections in general and visceral surgical patients that undergo midline or transverse laparotomy by 50%. BaFO is a randomized, controlled, patient-blinded and observer-blinded multicenter clinical trial with two parallel surgical groups. The primary outcome measure will be the rate of surgical site infections within 45 days postoperative assessed according to the definition of the Center for Disease Control. Statistical analysis of the primary endpoint will be based on the intention-to-treat population. The global level of significance is set at 5% (2 sided) and sample size (n = 258 per group) is determined to assure a power of 80% with a planned interim analysis for the primary endpoint after the inclusion of 340 patients.

Discussion
The BaFO trial will explore if the rate of surgical site infections can be reduced by a single, simple, inexpensive intervention in patients undergoing open elective abdominal surgery. Its pragmatic design guarantees high external validity and clinical relevance.

Trial registration

http://www.clinicaltrials.gov NCT01181206. Date of registration: 11 August 2010; date of first patient randomized: 8 September 2010
The space of linear maps into a Grassmann manifold
Authors: Ben Hammouda Walid , Kallel Sadok , Salvatore Paolo 
Published: May 2012

Abstract.
We show that the space of all holomorphic maps of
degree one from the Riemann sphere into a Grassmann manifold is a
sphere bundle over a flag manifold. Using the notions of “kernel” and
“span” of a map, we
completely identify the space of unparameterized maps as well. The illustrative case of maps into the quadric Grassmann manifold is
discussed in detail and the homology of the corresponding spaces is computed.
Lipid Profiles of Children With Down Syndrome Compared With Their Siblings
Authors: Adelekan Tahira , Magge Sheela , Shults Justine , Stallings Virginia , Stettler Nicolas 
Published: May 2012

OBJECTIVES:Our objective was to compare serum lipid profiles, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) between children with Down syndrome (DS) and their non-DS siblings. We hypothesized that the children with DS would have higher TC, LDL, and TG and lower HDL. The secondary aim was to explore if the difference in lipid profiles could be explained by differences in weight status.METHODS:This was a cross-sectional study. Fasting lipid profile was obtained from 27 children with DS and 31 siblings between 4 and 10 years of age with no severe comorbidities (heart disease, cancer, hypothyroidism, diabetes, or obesity). BMI was calculated and BMI z scores were used to account for differences in BMI throughout childhood.RESULTS:Children with DS had higher TC (difference, 11.2 mg/dL; 95% confidence interval: 2.5–19.9; P = .01), LDL (12.8 mg/dL; 7.2–18.4; P &lt; .001), TG (33.6 mg/dL; 11.1–56.1; P = .003), and lower HDL (−7.6 mg/dL; −12.1 to −3.0; P = .001) after adjustment for race, gender, age, and ethnicity. Results remained significant after additional adjustment for BMI z score: TC (14.9 mg/dL; 4.9–24.9; P = .003), LDL (16.6 mg/dL; 10.1–23.2; P &lt; .001), TG (32.7 mg/dL; 7.7–57.7; P = .01), and lower HDL (−6.4 mg/dL; −12.2 to −0.7; P = .03).CONCLUSIONS:Children with DS have less favorable lipid profiles than their siblings independent of weight status. These findings may have important implications for the screening and treatment of this large population at increased risk for ischemic heart disease.
Randomized Trial of Sumatriptan and Naproxen Sodium Combination in Adolescent Migraine
Authors: Derosier Frederick J. , Lewis Donald , Hershey Andrew D. , Winner Paul K. , Pearlman Eric , Rothner Arnold David , Linder Steven L. , Goodman David K. , Jimenez Theresa B. , Granberry Wendy K. , Runken M. Chris 
Published: May 2012

BACKGROUND:
Treatment of adolescent migraine remains a significant unmet medical need. We compared the efficacy and safety of 3 doses of sumatriptan and naproxen sodium (suma/nap) combination tablets to placebo in the acute treatment of adolescent migraine.

METHODS:
This randomized, parallel group study in 12 to 17 year olds required 2 to 8 migraines per month (typically lasting &gt;3 hours untreated) for ≥6 months. Subjects entered a 12-week run-in phase, treating 1 moderate-to-severe migraine (attack 1) with single-blind placebo. Subjects reporting headache pain 2 hours after dosing were randomly assigned into a 12-week double-blind phase, treating 1 moderate-to-severe migraine (attack 2) with placebo (n = 145), suma/nap 10/60 mg (n = 96), 30/180 mg (n = 97), or 85/500 mg (n = 152). The primary end point was the percentage of subjects pain-free at 2 hours.

RESULTS:
The attack 2 adjusted (age; baseline pain severity) 2-hour pain-free rates were higher with suma/nap 10/60 mg (29%; adjusted P = .003), 30/180 mg (27%; adjusted P = .003), and 85/500 mg (24%; adjusted P = .003) versus placebo (10%). Posthoc primary end-point analyses did not demonstrate differences among the 3 doses or an age-by-treatment interaction. Statistically significant differences were found for 85/500 mg versus placebo for sustained pain-free 2 to 24 hours (23% vs 9%; adjusted P = .008), 2-hour photophobia-free (59% vs 41%; adjusted P = .008), and 2-hour phonophobia-free (60% vs 42%; adjusted P = .008). Analyses of other pain, associated symptoms, rescue medication use, and health outcome end points supported higher efficacy for active doses versus placebo. All active doses were well tolerated.

CONCLUSIONS:
All doses of suma/nap were well tolerated, providing similarly effective acute treatment of adolescent migraine pain and associated symptoms, as compared with placebo.
Oral Dimenhydrinate Versus Placebo in Children With Gastroenteritis: A Randomized Controlled Trial
Authors: Gouin Serge , Vo Thuy-Tien , Roy Michel , Lebel Denis , Gravel Jocelyn 
Published: May 2012

OBJECTIVE:
To evaluate the efficacy and safety of oral dimenhydrinate in the treatment of acute gastroenteritis.

METHODS:
This was a randomized, double-blind, placebo-controlled trial conducted in the emergency department of a pediatric university-affiliated center. Children 1 to 12 years old who presented to the emergency department with at least 5 episodes of vomiting in the previous 12 hours and diagnosed with acute gastroenteritis were block-randomized to receive oral dimenhydrinate (1 mg/kg; maximum: 50 mg) every 6 hours for 4 doses or placebo for 4 doses. The primary outcome measure was treatment failure as defined by the occurrence of ≥2 episodes of vomiting in the 24 hours after administration of the first dose of the study medication.

RESULTS:
During the study period, 209 patients met inclusion criteria, but 50 refused to participate and 7 were missed. Eight participants were lost to follow-up, and 144 were thus included in the primary analysis. Of these patients, 74 were randomized to receive dimenhydrinate and 70 placebo. The proportions of patients showing failure of treatment were similar for both treatment groups: dimenhydrinate, 31% (23 of 74); placebo, 29% (20 of 70) (difference: 0.02 [95% confidence interval: –0.12 to 0.17]). There were no differences between the 2 groups in rates of intravenous cathether insertion, mean number of episodes of vomiting or diarrhea, abdominal pain, nausea, duration of symptoms, revisit rates, or parental absenteeism. The proportions of adverse effects were similar in both groups (53% vs 54%).

CONCLUSIONS:
The prescription of oral dimenhydrinate did not significantly decrease the frequency of vomiting in children with acute gastroenteritis compared with placebo.
La diplomatie française à l'épreuve de l'Iran
Authors: Therme Clément 
Published: May 2012

Résumé Du point de vue des révolutionnaires khomeynistes, la France est un pays de type « petit Satan », une catégorie à mettre en perspective avec le statut de « grand Satan » réservé aux États-Unis. Pour les élites politiques de la République islamique, ce statut se justifie avant tout par le soutien de Paris à Saddam Hussein pendant la guerre Iran-Irak (1980-1988) et par l’appartenance de la France au camp occidental. Cette vision de ce que représente la France et de sa politique sur la scène internationale doit être mise en regard avec la perception de l’Iran que développent les élites diplomatiques françaises. Selon ces dernières, la fermeté dans les négociations avec l’Iran est indispensable pour contrer ses ambitions nucléaires.
Value of 3-D CT in Classifying Acetabular Fractures During Orthopedic Residency Training
Authors: Garrett Jeffrey , Halvorson Jason , Carroll Eben , Webb Lawrence X. 
Published: May 2012

The complex anatomy of the pelvis and acetabulum have historically made classification and interpretation of acetabular fractures difficult for orthopedic trainees. The addition of 3-dimensional (3-D) computed tomography (CT) scan has gained popularity in preoperative planning, identification, and education of acetabular fractures given their complexity. Therefore, the authors examined the value of 3-D CT compared with conventional radiography in classifying acetabular fractures at different levels of orthopedic training. Their hypothesis was that 3-D CT would improve correct identification of acetabular fractures compared with conventional radiography.
The classic Letournel fracture pattern classification system was presented in quiz format to 57 orthopedic residents and 20 fellowship-trained orthopedic traumatologists. A case consisted of (1) plain radiographs and 2-dimensional axial CT scans or (2) 3-D CT scans. All levels of training showed significant improvement in classifying acetabular fractures with 3-D vs 2-D CT, with the greatest benefit from 3-D CT found in junior residents (postgraduate years 1–3).
Three-dimensional CT scans can be an effective educational tool for understanding the complex spatial anatomy of the pelvis, learning acetabular fracture patterns, and correctly applying a widely accepted fracture classification system.