bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alignment of systematic reviews published in the Cochrane Database of Systematic Reviews and the Database of Abstracts and Reviews of Effectiveness with global burden-of-disease data: a bibliographic analysis
Authors: Yoong Sze Lin , Hall Alix , Williams Christopher M , Skelton Eliza , Oldmeadow Christopher , Wiggers John , Karimkhani Chante , Boyers Lindsay N , Dellavalle Robert P , Hilton John , Wolfenden Luke 
Published: April 2015

BackgroundSystematic reviews of high-quality evidence are used to inform policy and practice. To improve community health, the production of such reviews should align with burden of disease. This study aims to assess if the volume of research output from systematic reviews proportionally aligns with burden of disease assessed using percentages of mortality and disability-adjusted life years (DALYs).MethodsA cross-sectional audit of reviews published between January 2012 and August 2013 in the Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of Effects (DARE) was undertaken. Percentages of mortality and DALYs were obtained from the 2010 Global Burden of Disease study. Standardised residual differences (SRD) based on percentages of mortality and DALYs were calculated, where conditions with SRD of more than or less than three were considered overstudied or understudied, respectively.Results1029 reviews from CDSR and 1928 reviews from DARE were examined. There was a significant correlation between percentage DALYs and systematic reviews published in CDSR and DARE databases (CDSR: r=0.68, p=0.001; DARE: r=0.60, p<0.001). There was no significant correlation between percentage mortality and number of systematic reviews published in either database (CDSR: r=0.34, p=0.14; DARE: r=0.22, p=0.34). Relative to percentage of mortality, mental and behavioural disorders, musculoskeletal conditions and other non-communicable diseases were overstudied. Maternal disorders were overstudied relative to percentages of mortality and DALYs in CDSR.ConclusionsThe focus of systematic reviews is moderately correlated with DALYs. A number of conditions may be overstudied relative to percentage of mortality particularly in the context of health and medical reviews.
The MITOS system predicts long-term survival in amyotrophic lateral sclerosis
Authors: Tramacere Irene , Dalla Bella Eleonora , Chiò Adriano , Mora Gabriele , Filippini Graziella , Lauria Giuseppe 
Published: April 2015

ObjectiveThe choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.MethodsAnalyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or >23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models.ResultsDisease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or >23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37/45) and 63% specificity (95% CI 55% to 71%, n=92/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50/70) and 68% specificity (95% CI 60% to 77%, n=76/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to predict survival at 12 and 18 months was 1 for the ALS-MITOS (ie, loss of at least one function) and a decline ranging from 6 to 9 points for the ALSFRS-R.ConclusionsThe ALS-MITOS system can reliably predict the course of ALS up to 18 months and can be considered a novel and valid outcome measure in RCTs.
Ocular manifestations of canine transmissible venereal tumour: a retrospective study of 25 cases in Greece
Authors: Komnenou A. Th , Thomas A. L. N. , Kyriazis A. P. , Poutahidis T. , Papazoglou L. G. 
Published: April 2015

Transmissible venereal tumour (TVT) is a sexually transmitted neoplasm that frequently affects dogs of either sex, in tropical and subtropical regions. TVT primarily involves the external genitalia, although extragenital sites have also been reported. This study describes the ocular manifestations of TVT in 25 naturally infected dogs and their response to treatment. Seventeen male and eight female dogs were included in the study. TVT ocular lesions were either unilateral (21 dogs) or bilateral (four dogs). Ocular lesions as the single manifestation of TVT were seen in 22 animals. One dog presented external genitalia involvement while two others were found to have tumours in the oral and nasal mucosa. Variably sized multilobular tumour masses with irregular surface were noticed on the bulbar conjunctiva of the nictitating membrane in 17 dogs, on the conjunctiva of the upper eyelid in five dogs and on the conjunctiva of the lower eyelid and adjacent skin in three dogs. Deep ulcerative keratitis was observed in eight animals. TVT diagnosis was based on cytology and histopathology. The large eye masses were surgically excised. All dogs were treated with a single chemotherapeutic agent (vincristine). After four weeks of treatment, complete remission of the tumours was evident in all but one animal. Extragenital primary ophthalmic TVT can be completely eliminated by vincristine chemotherapy, while any further ocular damage is prevented with the combination of the above treatment and surgical excision.
Resistance to weathering and retreatability of composite protective nanostructured coatings applied to Pendelikon marbles
Authors: Stefanidou M. , Matziaris K. , Karagiannis G. 
Published: April 2015

Abstract
The protection of Pendelikon marbles to weathering has been the main aim of numerous and longstanding studies. Latest scientific approaches in the field of conservation include methods for self-cleaning surfaces that mimic natural phenomena. In our research, we have critically studied and implemented by means of nanotechnology, the development of a biomimetic composite, protective, hybrid nanostructured film. The mineral substrates have been coated with a fluorosilanic base matrix and furthermore top-coated with a nanostructured synthesis made from amorphous silicon dioxide, sprayed using the ‘alla prima’ technique. The behaviour of the composite protective coating has been evaluated in terms of wettability, retreatability and resistance to weathering.
Xanthohumol-Mediated Suppression of Notch1 Signaling Is Associated with Antitumor Activity in Human Pancreatic Cancer Cells
Authors: Kunnimalaiyaan Selvi , Trevino Jose , Tsai Susan , Gamblin T. Clark , Kunnimalaiyaan Muthusamy 
Published: April 2015

Abstract
Pancreatic cancer remains a lethal disease with limited treatment options. At the time of diagnosis, approximately 80% of these patients present with unresectable tumors caused by either locally advanced lesions or progressive metastatic growth. Therefore, development of novel treatment strategies and new therapeutics is needed. Xanthohumol (XN) has emerged as a potential compound that inhibits various types of cancer, but the molecular mechanism underlying the effects of XN remains unclear. In the present study, we have assessed the efficacy of XN on pancreatic cancer cell lines (AsPC-1, PANC-1, L3.6pl, MiaPaCa-2, 512, and 651) against cell growth in real time and using colony-forming assays. Treatment with XN resulted in reduction in cellular proliferation in a dose- and time-dependent manner. The growth suppression effect of XN in pancreatic cancer cell lines is due to increased apoptosis via the inhibition of the Notch1 signaling pathway, as evidenced by reduction in Notch1, HES-1, and survivin both at mRNA as well as protein levels. Notch1 promoter reporter analysis after XN treatment indicated that XN downregulates Notch promoter activity. Importantly, overexpression of active Notch1 in XN-treated pancreatic cancer cells resulted in negation of growth suppression. Taken together, these findings demonstrate, for the first time, that the growth suppressive effect of XN in pancreatic cancer cells is mainly mediated by Notch1 reduction. Mol Cancer Ther; 14(6); 1395–403. ©2015 AACR.
Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca
2+
Channel Protein Stability
Authors: Pedrozo Zully , Criollo Alfredo , Battiprolu Pavan K. , Morales Cyndi R. , Contreras-Ferrat Ariel , Fernández Carolina , Jiang Nan , Luo Xiang , Caplan Michael J. , Somlo Stefan , Rothermel Beverly A. , Gillette Thomas G. , Lavandero Sergio , Hill Joseph A. 
Published: April 2015

Background—
L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress–induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein–coupled receptor–like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes.

Methods and Results—
We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown–dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction–induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction–elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals

Conclusion—
PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein.
Implications of the US Cholesterol Guidelines on Eligibility for Statin Therapy in the Community: Comparison of Observed and Predicted Risks in the Framingham Heart Study Offspring Cohort
Authors: Andersson Charlotte , Enserro Danielle , Larson Martin G. , Xanthakis Vanessa , Vasan Ramachandran S. 
Published: April 2015

Background

Concerns have been raised that the 2013 atherosclerotic cardiovascular disease (
ASCVD
) risk estimator overpredicts risk in contemporary cohorts. Whether suboptimal calibration will lead to overtreatment with statins is unknown. We investigated the numbers of people eligible for statin treatment in the Framingham Heart Study Offspring Cohort, based on the 2013 cholesterol guidelines, and estimated the proportion that may be overtreated as a result of potential miscalibration of the
ASCVD
estimator.

Methods and Results

During a median follow‐up of 10 years, we observed 285
ASCVD
events (8.4%; comprising ischemic stroke, myocardial infarction, and coronary artery disease death) among 3396 men and 112 events (2.9%) among 3838 women. Hosmer–Lemeshow chi‐square statistics were 16.3 in men (340 predicted versus 285 observed events) and 29.1 in women (166 predicted versus 112 observed events). Overprediction predominantly occurred among women in the highest risk decile and among men in the ≥7th risk deciles, for which observed
ASCVD
event rates were ≥7.5%. In total, 2615 participants (36%; 867 women) were eligible for statins based on the new guidelines. Of these, 171 women (20%) and 154 men (9%) were reclassified downward (as not eligible for statin therapy) using a recalibrated
ASCVD
estimator. In the latter group, 18 women (10.5%; 95% CI 5.9% to 15.2%) and 11 men (7.1%; 95% CI 3.0% to 11.3%) experienced
ASCVD
.

Conclusions

The risk estimator overpredicted
ASCVD
risk but did so mainly among high‐risk participants who would be considered eligible for statin use anyway. Our findings may mitigate concerns regarding the potential impact of miscalibration of the
ASCVD
estimator in contemporary cohorts.
Use of the Australian Therapy Outcome Measures for Occupational Therapy (AusTOMs-OT) in an early supported discharge programme for stroke patients in Singapore
Authors: Chen Zhenzhen , Eng Jia Yen 
Published: April 2015

Introduction This short report describes the use of the Australian Therapy Outcome Measures for Occupational Therapy (AusTOMs-OT) in an early supported discharge programme for stroke patients in Singapore. Method The Australian Therapy Outcome Measures for Occupational Therapy was assessed at the start and end of the early supported discharge programme and differences were statistically analysed. Findings All Australian Therapy Outcome Measures for Occupational Therapy scales demonstrated statistically significant change over time. The most commonly used scales were ‘Upper limb use’, ‘Functional walking and mobility’ and ‘Community life, recreation, leisure and play’, reflecting the pertinent types of occupational therapy intervention used in stroke rehabilitation in the home setting. Conclusion This study shows that the Australian Therapy Outcome Measures for Occupational Therapy is a useful outcome measure that can be used to articulate the administered occupational therapy interventions to members of the multi-disciplinary team and support the effectiveness of occupational therapy in stroke rehabilitation.
The Anterolateral Ligament
Authors: Kennedy Mitchell I. , Claes Steven , Fuso Fernando Augusto Freitas , Williams Brady T. , Goldsmith Mary T. , Turnbull Travis Lee , Wijdicks Coen A. , LaPrade Robert F. 
Published: April 2015

Background: Recent publications have described significant variability in the femoral attachment and overall anatomy of the anterolateral ligament (ALL). Additionally, there is a paucity of data describing its structural properties. Purpose: Quantitative data characterizing the anatomic and radiographic locations and the structural properties of the ALL may be used to guide graft selection and placement and to facilitate the future development of an evidence-based approach to ALL reconstructions. Study Design: Descriptive laboratory study. Methods: Identification of the ALL was performed by a combined outside-in and inside-out anatomic dissection of 15 nonpaired fresh-frozen cadaveric knees. Quantitative anatomic relationships were calculated using a 3-dimensional coordinate measuring device. Measurements on anteroposterior (AP) and lateral radiographs were obtained by use of a picture archiving and communications system program. Structural properties were characterized during a single pull-to-failure test using a tensile testing machine. All anatomic, radiographic, and biomechanical measurements were reported as mean values and 95% CIs. Results: The ALL was identified as a thickening of the lateral capsule coming under tension with an applied internal rotation at 30° of flexion. Its femoral attachment was located 4.7 mm (95% CI, 3.5-5.9 mm) posterior and proximal to the fibular collateral ligament attachment and coursed anterodistally to its anterolateral tibial attachment approximately midway between the center of the Gerdy tubercle and the anterior margin of the fibular head; the tibial attachment was located 24.7 mm (95% CI, 23.3-26.2 mm) and 26.1 mm (95% CI, 23.9-28.3 mm) from each structure, respectively. On the AP radiographic view, the ALL originated on the femur 22.3 mm (95% CI, 20.7-23.9 mm) proximal to the joint line and inserted on the tibia 13.1 mm (95% CI, 12.3-13.9 mm) distal to the lateral tibial plateau. On the lateral view, the femoral attachment was 8.4 mm (95% CI, 6.8-10.0 mm) posterior and proximal to the lateral epicondyle. The tibial attachment was 19.0 mm (95% CI, 17.1-20.9 mm) posterior and superior to the center of the Gerdy tubercle. The mean maximum load was 175 N (95% CI, 139-211 N) and the stiffness was 20 N/mm (95% CI, 16-25 N/mm). Failure occurred by 4 distinct mechanisms: ligamentous tear at the femoral (n = 4) or tibial (n = 1) attachment, midsubstance tear (n = 4), and bony avulsion of the tibial attachment (Segond fracture; n = 6). Conclusion: Defined ALL attachment locations can be reproducibly identified with intraoperative landmarks or radiographs. The biomechanical analysis suggests that most traditional soft tissue grafts are sufficient for ALL reconstruction. Clinical Relevance: The ALL was consistently found in all knees. Segond fractures appear to occur primarily from the avulsion of the ALL.
Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials
Authors: Korogiannaki Myrto , Guidi Giuliano , Jones Lyndon , Sheardown Heather 
Published: April 2015

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile.
Biomarkers for Prediction of Central Venous Catheter Related-Thrombosis in Patients With Hematological Malignancies
Authors: Boersma R. S. , Hamulyak K. , van Oerle R. , Tuinenburg A. , ten Cate-Hoek A. J. , Schouten H. C. 
Published: April 2015

Objective: In a prospective setting, we aimed to find associations between biomarkers of the hemostatic system and the occurrence of central venous catheter (CVC)-related thrombosis in patients with hematological malignancies undergoing intensive chemotherapy. Methods: The study was conducted between July 2006 and August 2010 at the University Hospital Maastricht, the Netherlands. Consecutive adult patients with hematological malignancies who were going to receive a CVC for intensive chemotherapy were included. The primary end points were (a) symptomatic CVC-related thrombosis and (b) CVC-related infections. Blood samples were taken directly after catheterization, and easy to determine biomarkers (platelet count, leukocyte count, and hemoglobin level) in combination with blood group, factor VIII (FVIII), plasminogen activator inhibitor 1 (PAI-1), activated protein C (APC) resistance, and free protein S antigen were determined. Results: Blood was collected and analyzed from 168 patients. The incidence of symptomatic CVC-related thrombosis was 9%. In univariate analysis, white blood cell count >10.6 × 109/L, mean FVIII activity, and PAI-1 >12.2 IU/mL were found to be associated with the development of symptomatic CVC-related thrombosis. Conclusion: Elevated leukocyte count, high PAI-1, and high FVIII were associated with an increased incidence of symptomatic CVC-related thrombosis. We hope in future that simple, easy to determine laboratory tests that reflect the hemostatic and fibrinolytic activity in combination with clinical parameters may help to identify hematological patients at highest risk of CVC-related thrombosis and help to tailor the management of thromboprophylaxis in hematological patients undergoing CVC placement.
Loss of Work Productivity and Quality of Life in Patients With Autoimmune Bullous Dermatoses
Authors: Heelan K. , Hitzig S. L. , Knowles S. , Drucker A. M. , Mittmann N. , Walsh S. , Shear N. H. 
Published: April 2015

Background: Little is known about quality of life and work productivity in autoimmune bullous dermatoses (AIBDs). Objective: To determine the impact of AIBDs on quality of life and work productivity. Methods: An observational cross-sectional study took place between February and May 2013 at an AIBD tertiary referral centre. Ninety-four patients were included. All participants completed the Dermatology Life Quality Index and the Work Productivity and Activity Impairment–Specific Health Problem questionnaires. Results: Responders to treatment had less impairment ( P < .001) than nonresponders. Patients with severe AIBD had significantly more impairment that those with mild ( P < .001) and moderate ( P = .002) AIBD. Greater impairment was associated with higher percentage of work missed. Those with a higher Dermatology Life Quality Index score had greater work impairment and overall activity impairment ( P = .041, P = .024). Nonresponders had increased impairment while working ( P < .001), overall work impairment ( P < .001), and activity impairment ( P < .001). Severely affected patients had worse impairment in all Work Productivity and Activity Impairment Questionnaire domains. Conclusions: AIBD has the potential to be a large burden on ability to work and quality of life. Larger studies are needed to clarify how these domains change over time and whether or not they improve with treatment.