bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies
Authors: Chen Yi , Liu Lingxiao , Wang Xiaolin , Wang Jianhua , Yan Zhiping , Cheng Jieming , Gong Gaoquan , Li Guoping 
Published: May 2013

Abstract
Background: To provide a quantitative assessment of the association between body mass index (BMI) and the risk of gastric cancer, we summarized the evidence from prospective studies.
Methods: Eligible studies published up to November 30, 2012, were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Summary relative risks (SRR) with their corresponding 95% confidence intervals (CI) were calculated using a random-effects model.
Results: A total of 24 prospective studies of BMI and gastric cancer risk with 41,791 cases were included in our analysis. Overall, both overweight (BMI, 25–30 kg/m2) and obesity (BMI, ≥30 kg/m2) were not associated with risk of total gastric cancer (overweight: SRR, 1.01; 95% CI, 0.96–1.07; obesity: SRR, 1.06; 95% CI, 0.99–1.12). Furthermore, we found increased BMI was positively associated with the risk of gastric cardia cancer (GCC; SRR = 1.21 for overweight and 1.82 for obesity), but not with gastric non-cardia cancer (GNCC; SRR = 0.93 for overweight and SRR = 1.00 for obesity). Similar results were observed in a linear dose–response analysis.
Conclusion: On the basis of meta-analysis of prospective studies, we find high BMI is positively associated with the risk of GCCs but not with GNCCs.
Impact: (i) On the basis of more definite and quantitative evidence than previously available, we found that increasing BMI was not a clear risk factor for total gastric cancer. (ii) Increased BMI was positively associated with risk of GCC but not with GNCCs. Cancer Epidemiol Biomarkers Prev; 22(8); 1395–408. ©2013 AACR.
Preclinical Evaluation of the WEE1 Inhibitor MK-1775 as Single-Agent Anticancer Therapy
Authors: Guertin Amy D. , Li Jing , Liu Yaping , Hurd Melissa S. , Schuller Alwin G. , Long Brian , Hirsch Heather A. , Feldman Igor , Benita Yair , Toniatti Carlo , Zawel Leigh , Fawell Stephen E. , Gilliland D. Gary , Shumway Stuart D. 
Published: May 2013

Abstract
Inhibition of the DNA damage checkpoint kinase WEE1 potentiates genotoxic chemotherapies by abrogating cell-cycle arrest and proper DNA repair. However, WEE1 is also essential for unperturbed cell division in the absence of extrinsic insult. Here, we investigate the anticancer potential of a WEE1 inhibitor, independent of chemotherapy, and explore a possible cellular context underlying sensitivity to WEE1 inhibition. We show that MK-1775, a potent and selective ATP-competitive inhibitor of WEE1, is cytotoxic across a broad panel of tumor cell lines and induces DNA double-strand breaks. MK-1775–induced DNA damage occurs without added chemotherapy or radiation in S-phase cells and relies on active DNA replication. At tolerated doses, MK-1775 treatment leads to xenograft tumor growth inhibition or regression. To begin addressing potential response markers for MK-1775 monotherapy, we focused on PKMYT1, a kinase functionally related to WEE1. Knockdown of PKMYT1 lowers the EC50 of MK-1775 by five-fold but has no effect on the cell-based response to other cytotoxic drugs. In addition, knockdown of PKMYT1 increases markers of DNA damage, γH2AX and pCHK1S345, induced by MK-1775. In a post hoc analysis of 305 cell lines treated with MK-1775, we found that expression of PKMYT1 was below average in 73% of the 33 most sensitive cell lines. Our findings provide rationale for WEE1 inhibition as a potent anticancer therapy independent of a genotoxic partner and suggest that low PKMYT1 expression could serve as an enrichment biomarker for MK-1775 sensitivity. Mol Cancer Ther; 12(8); 1442–52. ©2013 AACR.
Alternative Cytotoxic Effects of the Postulated IGF-IR Inhibitor Picropodophyllin In Vitro
Authors: Wu Xuping , Sooman Linda , Wickström Malin , Fryknäs Mårten , Dyrager Christine , Lennartsson Johan , Gullbo Joachim 
Published: May 2013

Abstract
The insulin-like growth factor-1 (IGF-I) and its receptors play an important role in transformation and progression of several malignancies. Inhibitors of this pathway have been developed and evaluated but generally performed poorly in clinical trials, and several drug candidates have been abandoned. The cyclolignan picropodophyllin (PPP) has been described as a potent and selective IGF-IR inhibitor and is currently undergoing clinical trials. We investigated PPP's activity in panels of human cancer cell lines (e.g., esophageal squamous carcinoma cell lines) but found no effects on the phosphorylation or expression of IGF-IR. Nor was the cytotoxic activity of PPP related to the presence or spontaneous phosphorylation of IGF-IR. However, its activity correlated with that of known tubulin inhibitors, and it destabilized microtubule assembly at cytotoxic concentrations also achievable in patients. PPP is a stereoisomer of podophyllotoxin (PPT), a potent tubulin inhibitor, and an equilibrium between the two has previously been described. PPP could thus potentially act as a reservoir for the continuous generation of low doses of PPT. Interestingly, PPP also inhibited downstream signaling from tyrosine kinase receptors, including the serine/threonine kinase Akt. This effect is associated with microtubule-related downregulation of the EGF receptor, rather than the IGF-IR. These results suggest that the cytotoxicity and pAkt inhibition observed following treatment with the cyclolignan PPP in vitro result from microtubule inhibition (directly or indirectly by spontaneous PPT formation), rather than any effect on IGF-IR. It is also suggested that PPT should be used as a reference compound in all future studies on PPP. Mol Cancer Ther; 12(8); 1526–36. ©2013 AACR.
Cost-Effectiveness of Ventricular Assist Device Therapy as a Bridge to Transplantation Compared With Nonbridged Cardiac Recipients
Authors: Alba Ana C. , Alba Luis F. , Delgado Diego H. , Rao Vivek , Ross Heather J. , Goeree Ron 
Published: May 2013

Background—
Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)–VAD approach relative to direct heart transplantation in transplant-eligible patients.

Methods and Results—
A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients’ baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio.

Conclusions—
BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.
Economic Evaluation of Percutaneous Left Atrial Appendage Occlusion, Dabigatran, and Warfarin for Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation
Authors: Singh Sheldon M. , Micieli Andrew , Wijeysundera Harindra C. 
Published: May 2013

Background—
Percutaneous left atrial appendage (LAA) occlusion and novel pharmacological therapies are now available to manage stroke risk in patients with nonvalvular atrial fibrillation; however, the cost-effectiveness of LAA occlusion compared with dabigatran and warfarin in patients with nonvalvular atrial fibrillation is unknown.

Methods and Results—
Cost-utility analysis using a patient-level Markov microsimulation decision analytic model with a lifetime horizon was undertaken to determine the lifetime costs, quality-adjusted life years, and incremental cost-effectiveness ratio of LAA occlusion in relation to dabigatran and warfarin in patients with nonvalvular atrial fibrillation at risk for stroke without contraindications to oral anticoagulation. The analysis was performed from the perspective of the Ontario Ministry of Health and Long Term Care, the third-party payer for insured health services in Ontario, Canada. Effectiveness and utility data were obtained from the published literature. Cost data were obtained from the Ontario Drug Benefits Formulary and the Ontario Case Costing Initiative. Warfarin therapy had the lowest discounted quality-adjusted life years at 4.55, followed by dabigatran at 4.64 and LAA occlusion at 4.68. The average discounted lifetime cost was $21 429 for a patient taking warfarin, $25 760 for a patient taking dabigatran, and $27 003 for LAA occlusion. Compared with warfarin, the incremental cost-effectiveness ratio for LAA occlusion was $41 565. Dabigatran was extendedly dominated.

Conclusions—
Percutaneous LAA occlusion represents a novel therapy for stroke reduction that is cost-effective compared with warfarin for patients at risk who have nonvalvular atrial fibrillation.
On the Exchange of Momentum over the Open Ocean
Authors: Edson James B. , Jampana Venkata , Weller Robert A. , Bigorre Sebastien P. , Plueddemann Albert J. , Fairall Christopher W. , Miller Scott D. , Mahrt Larry , Vickers Dean , Hersbach Hans 
Published: May 2013

AbstractThis study investigates the exchange of momentum between the atmosphere and ocean using data collected from four oceanic field experiments. Direct covariance estimates of momentum fluxes were collected in all four experiments and wind profiles were collected during three of them. The objective of the investigation is to improve parameterizations of the surface roughness and drag coefficient used to estimate the surface stress from bulk formulas. Specifically, the Coupled Ocean–Atmosphere Response Experiment (COARE) 3.0 bulk flux algorithm is refined to create COARE 3.5. Oversea measurements of dimensionless shear are used to investigate the stability function under stable and convective conditions. The behavior of surface roughness is then investigated over a wider range of wind speeds (up to 25 m s−1) and wave conditions than have been available from previous oversea field studies. The wind speed dependence of the Charnock coefficient α in the COARE algorithm is modified to , where m = 0.017 m−1 s and b = −0.005. When combined with a parameterization for smooth flow, this formulation gives better agreement with the stress estimates from all of the field programs at all winds speeds with significant improvement for wind speeds over 13 m s−1. Wave age– and wave slope–dependent parameterizations of the surface roughness are also investigated, but the COARE 3.5 wind speed–dependent formulation matches the observations well without any wave information. The available data provide a simple reason for why wind speed–, wave age–, and wave slope–dependent formulations give similar results—the inverse wave age varies nearly linearly with wind speed in long-fetch conditions for wind speeds up to 25 m s−1.
Biomechanical Analysis of Distal Clavicle Excision With Acromioclavicular Joint Reconstruction
Authors: Beaver Andrew B. , Parks Brent G. , Hinton Richard Y. 
Published: May 2013

Background: Acromioclavicular (AC) joint separation is a common injury, usually affecting young adults. Controversy exists regarding whether to excise the distal clavicle when surgical intervention is required. Purpose: To evaluate the biomechanical strength of AC and coracoclavicular (CC) ligament reconstruction with and without concurrent distal clavicle excision. Study Design: Controlled laboratory study. Methods: Nine matched pairs of cadaver shoulders were used. All shoulders were tested with intact CC and AC ligaments, and the ligaments were sectioned. For 1 shoulder in each pair, a 7-mm distal clavicle excision was performed. The contralateral distal clavicle was left intact. Single-tunnel CC ligament reconstruction was performed, and excess graft length was extended and secured across the AC joint to reconstruct the superior AC joint ligaments in all specimens. Specimens were then potted and cyclically loaded for 500 cycles in the anterior-posterior and superior-inferior planes using an MTS Minibionix load frame to evaluate displacement across the AC joint. Results: Regarding the clavicle–intact reconstructed versus the intact state, there was significantly greater AC joint translation in the reconstructed state in the anterior-posterior (20.2 ± 7.0 mm vs 6.0 ± 1.5 mm; P < .001) and superior-inferior directions (12.3 ± 3.3 mm vs 4.2 ± 1.2 mm; P < .001). In the clavicle–excised reconstructed versus the intact state, there was also significantly greater translation in the reconstructed state in the anterior-posterior (21.7 ± 5.1 mm vs 8.9 ± 4.3 mm; P < .001) and superior-inferior directions (12.3 ± 6.1 mm vs 5.8 ± 3.1 mm; P < .001). When the difference in translation between the reconstructed and intact groups in the clavicle-intact versus the clavicle-excised group was compared, no statistically significant difference was noted in anterior-posterior (14.2 ± 7.8 mm vs 12.8 ± 5.0 mm; P = .67) or superior-inferior translation (8.1 ± 2.9 mm vs 6.6 ± 3.9 mm; P = .39). Conclusion: Excision of the distal clavicle did not have a significant effect on anterior-posterior or superior-inferior motion at the AC joint following single-tunnel CC and AC ligament reconstruction. Clinical Relevance: The study suggests that excision of the distal clavicle in this procedure is not associated with increased anterior-posterior or superior-inferior instability in this model.
Blood biomarkers in metal scrap workers accidentally exposed to ionizing radiation
Authors: Gupta ML , Srivastava NN , Dutta S , Shukla SK , Dutta A , Verma S , Devi M 
Published: May 2013

The detrimental effect of nuclear accidents due to localized or whole body radiation exposure results in severe cellular damage. The current study was carried out to evaluate radiation-mediated variability in blood components of metal scrap workers exposed accidently to cobalt-60 source. Blood samples collected initially from five hospitalized patients, coded P1–P5, were processed for total leukocyte counts (TLC), platelet (PLT) counts, haemoglobin, estimation of DNA double strand breaks by measuring phosphorylated form of H2AX (γ-H2AX) and chromosomal aberrations (dicentrics). Blood cells count (TLC), in all the patients except P2, was found decreased. Dicentrics increased in all the five patients. γ-H2AX was found significantly elevated in patients P2 and P4. After 3 days, 21 subjects working in close vicinity of accident site were evaluated for the above-mentioned markers to confirm their possibility of radiation exposure; however, all the parameters in these subjects were found within normal limits. Blood from patients P1–P5 was collected again after 11 days. Studies revealed exorbitant increase in γ-H2AX in lymphocytes and monocytes of patients P1, P4 and P5. TLC and PLT count in these patients had fallen further. Dicentrics declined with time in all the five patients. Based on the studied blood biomarkers, we conclude that the five subjects showed signs of radiation exposure. Measurement on radiation dose could not be performed in the current study; however, the generated data particularly on dicentrics provide ample evidence of radiation exposure.
The Efficacy and Safety of Oral Anticoagulants in Warfarin-Suitable Patients With Nonvalvular Atrial Fibrillation
Authors: Mitchell Stephen A. , Simon Teresa A. , Raza Syed , Jakouloff David , Orme Michelle E. , Lockhart Ian , Drost Pieter 
Published: May 2013

The novel oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban have been recently indicated for stroke prevention in patients with atrial fibrillation (AF) . Due to a lack of direct head-to-head trials comparing the NOACs, the current systematic review and network meta-analysis (NMA) were conducted to assess their relative efficacy and safety. Three phase III randomized controlled trials enrolling 50 578 patients were included. Results of the NMA show a clear trend favoring NOACs over warfarin with regard to the key outcomes of stroke/systemic embolism and all-cause mortality, with apixaban also showing a favorable response for major bleeding and total discontinuations. Although there were few significant differences among the NOACS with regard to efficacy outcomes, apixaban and dabigatran 110 mg were associated with significantly lower hazards of major bleeding compared with dabigatran 150 mg and rivaroxaban. The NOACs offer a therapeutic advance over standard warfarin treatment in stoke prevention in patients with nonvalvular AF.
Oxidative Stress, Trace Elements, and Circulating Microparticles in Patients With Gaucher Disease Before and After Enzyme Replacement Therapy
Authors: Zahran Asmaa M. , Elsayh Khalid I. , El-Deek Sahar E.M. , El-Baz Mona A.H. 
Published: May 2013

We studied the level of lipid peroxide, nitric oxide (NO), trace elements (TEs), and microparticles (MPs) in Gaucher disease (GD) before and after 1 year of enzyme replacement therapy (ERT). A total of 15 children with GD and 15 healthy controls were enrolled in this study. Serum level of lipid peroxide, NO, and TEs was determined. The MPs were detected by flow cytometry. The level of lipid peroxide was significantly higher in the patients than in the controls even after ERT. Although NO level was normalized in the patients after ERT, zinc and copper were still lower in the patients after ERT. The percentages of various MPs were significantly higher in the patients than in the controls both before and after ERT. There were positive correlations between chitotriosidase and both lipid peroxide and total MPs. Conclusion: The GD is associated with alteration in oxidant and antioxidant status and high level of circulating MPs.
First-line urological evaluation in multiple sclerosis: validation of a specific decision-making algorithm
Authors: Amarenco Gérard , Chartier-Kastler Emmanuel , Denys Pierre , Jean Jacques Labat , de Sèze Marianne , Lubetzski Catherine 
Published: May 2013

Background: Urinary disorders that lead to urological complications are frequent in multiple sclerosis, resulting in diminished quality of life. Urinary management guidelines are scarce and targeted to neuro-urology specialists. Objective: This study aimed to construct and validate an algorithm dedicated to neurologists and general practitioners to facilitate first-line evaluation and treatment of urinary disorders associated with multiple sclerosis. Methods: 49 items concerning urological symptom evaluation and therapeutic strategies were derived from literature analysis and evaluated by an expert panel. The Delphi method established consensus between the experts and allowed development of the First-Line Urological Evaluation in Multiple Sclerosis (FLUE-MS) algorithm. Two questions from the Urinary Bothersome Questionnaire in Multiple Sclerosis were included and their validation to verify comprehensiveness and acceptability was also conducted. Results: Three rounds of expert review obtained consensus of all 49 items and allowed finalisation of the algorithm. Comprehension and acceptability of two Urinary Bothersome Questionnaire in Multiple Sclerosis questions were verified (mean comprehensiveness score: 1.99/2 [99.7% total comprehensiveness], mean acceptability score: 1.99/2 [99.1% complete acceptability]). Conclusion: The FLUE-MS algorithm was designed for neurologists and general practitioners, enabling identification of ‘red flags’, timely patient referral to specialist neuro-urology units, and appropriate first-line therapy.
Predictors of HIV Serodiscordance among Couples in Southwestern Ethiopia
Authors: Habte Ermias , Yami Alemeshet , Alemseged Fissahye , Abdissa Yishak , Deribe Kebede , Memiah Peter , Biadgilign Sibhatu 
Published: May 2013

Background: With transmission of HIV occurring mainly through heterosexual contact, it is paramount to identify serodiscordant couples and implement preventive strategies that will protect the negative partner. The burden of serodiscordance and its predictors in Ethiopia is not clearly understood due to the dearth of data. Objective: To assess the prevalence and predictors of HIV serodiscordance among couples tested in Jimma University Specialized Hospital (JUSH) Voluntary Counseling and Testing (VCT) center. Methods: The study employed a case–control study design conducted at VCT center of JUSH in all registered serodiscordant couples and seroconcordant couples that were selected from the registered clients in the period from 2003 to 2010. A pretested structured questionnaire was used for data collection using medical chart abstraction. Data were entered, cleaned, and coded using Statistical Package of Social Sciences (SPSS) version 16. Results: The prevalence of serodiscordance in the study population was found to be 8.4%. Male and female discordants accounted for 5.8% (137) and 2.6% (62), respectively. Rare use of condom (adjusted odds ratio [AOR] = 7.2; 95% confidence interval [CI] = 1.59-32.54) and active tuberculosis (TB) at enrollment (AOR= 17.7; 95% CI = 2.3-139.2) were significantly found to be the predictors of serodiscordance. Conclusion: The prevalence of serodiscordance in the study area was found to be low, but it contributes to a clinically significant population that mandates implementation of preventive strategy. Sero-positive individuals who use condoms rarely should be encouraged to have their partners tested, and the association between active TB and serodiscordance underscores the need for further study.
Oxidized low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase–signaling pathways
Authors: Wraith Katie S. , Magwenzi Simbarashe , Aburima Ahmed , Wen Yichuan , Leake David , Naseem Khalid M. 
Published: May 2013

Key PointsOxidized LDL stimulates rapid change in platelet shape through ligation of CD36. Ligation of CD36 by oxidized LDL simultaneously activates tyrosine and Rho kinase–dependent signaling pathways.