bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Deficiency in Plasma Protein HRG Enhances Tumor Growth and Metastasis by Exacerbating Immune Escape and Vessel Abnormalization
Authors: Tugues Sònia , Honjo Satoshi , König Christian , Noguer Oriol , Hedlund Marie , Botling Johan , Deschoemaeker Sofie , Wenes Mathias , Rolny Charlotte , Jahnen-Dechent Wilhelm , Mazzone Massimiliano , Claesson-Welsh Lena 
Published: February 2012

Abstract
Histidine-rich glycoprotein (HRG) is a 75-kDa heparin-binding plasma protein implicated in the regulation of tumor growth and vascularization. In this study, we show that hrg−/− mice challenged with fibrosarcoma or pancreatic carcinoma grow larger tumors with increased metastatic properties. Compared with wild-type mice, fibrosarcomas in hrg−/− mice were more hypoxic, necrotic, and less perfused, indicating enhanced vessel abnormalization. HRG deficiency was associated with a suppressed antitumor immune response, with both increased infiltration of M2 marker–expressing macrophages and decreased infiltration of dendritic cells and cytotoxic T cells. Analysis of transcript expression in tumor-associated as well as peritoneal macrophages from hrg−/− mice revealed an increased expression of genes associated with a proangiogenic and immunoinhibitory phenotype. In accordance, expression arrays conducted on HRG-treated peritoneal macrophages showed induction of genes involved in extracellular matrix biology and immune responsiveness. In conclusion, our findings show that macrophages are a direct target of HRG. HRG loss influences macrophage gene regulation, leading to excessive stimulation of tumor angiogenesis, suppression of tumor immune response, and increased tumor growth and metastatic spread. Cancer Res; 72(8); 1953–63. ©2012 AACR.
HER2 As Therapeutic Target for Overcoming ATP-Binding Cassette Transporter–Mediated Chemoresistance in Small Cell Lung Cancer
Authors: Minami Toshiyuki , Kijima Takashi , Otani Yasushi , Kohmo Satoshi , Takahashi Ryo , Nagatomo Izumi , Hirata Haruhiko , Suzuki Mayumi , Inoue Koji , Takeda Yoshito , Kida Hiroshi , Tachibana Isao , Kumanogoh Atsushi 
Published: March 2012

Abstract
Small cell lung cancer (SCLC) easily acquires multidrug resistance after successful initial therapy. Overexpression of ATP-binding cassette (ABC) transporters is important for the multidrug resistance. Among them, ABCB1 and ABCG2 are known to be upregulated in chemoresistant SCLC cells. We found that human epidermal growth factor receptor 2 (HER2) expressions are also upregulated in chemoresistant SBC-3/ETP, SBC-3/SN-38, and SBC-3/CDDP cells, compared with chemosensitive SBC-3 cells. Lapatinib, a tyrosine kinase inhibitor of HER2, could not suppress proliferation of these HER2-positive SCLC cells alone but successfully restored chemosensitivity to etoposide and SN-38 with a clinically applicable concentration. The reversal effect of lapatinib was thought to be caused by inhibition of drug efflux pump functions of ABC transporters, although lapatinib itself has been reported to be a substrate for them. Moreover, knocking down of HER2 by an short interfering RNA weakened the effect of lapatinib on ABCB1, indicating the involvement of HER2 in the inhibitory mechanisms. Notably, we showed that caveolin-1 and Src play key roles in modulating ABCB1 function via HER2 inactivation. In SBC-3/ETP cells, dephosphorylation of HER2 by lapatinib activates Src and successively leads to increased caveolin-1 phosphorylation. Through this process, caveolin-1 dissociates from HER2 and strengthens association with ABCB1, and finally impairs the pump functions. Furthermore, we showed that treatment by lapatinib in combination with etoposide or irinotecan significantly suppresses the growth of subcutaneous SBC-3/ETP and SBC-3/SN-38 tumors in mice, respectively. Collectively, these results indicate that combination therapy with lapatinib and cytotoxic agents could conquer ABC transporter–mediated chemoresistance especially in HER2-positive SCLC. Mol Cancer Ther; 11(4); 830–41. ©2012 AACR.
Cause and Circumstance of In-Hospital Mortality Among Patients Undergoing Contemporary Percutaneous Coronary Intervention
Authors: Valle Javier A. , Smith Dean E. , Booher Anna M. , Menees Daniel S. , Gurm Hitinder S. 
Published: February 2012

Background—
Prior studies suggest that most deaths in patients undergoing percutaneous coronary intervention (PCI) are related to procedural complications. Mortality associated with PCI has steadily declined during the past decade, and the cause and circumstance of death among patients undergoing PCI in the contemporary era remain unknown.

Methods and Results—
We evaluated all patients undergoing PCI at the University of Michigan from 2001 to 2009. There were 85 deaths among a total of 5520 patients undergoing PCI during this time period. By using a standardized data collection form, 3 cardiologists (2 interventional, H.S.G. and D.S.M.; 1 noninvasive, A.M.B.) determined the cause and circumstance of death, in addition to grading the preventability of death. Left ventricular failure was the most common cause of death (35.3%, n=30), followed by neurological compromise (16.5%, n=14) and arrhythmia (12.1%, n=12). The circumstance of death was mostly acute cardiac (52.9%, n=45), with a procedural complication composing a small fraction (7.1%, n=6). Reviewers determined 93% of deaths to be mostly or entirely unpreventable.

Conclusions—
Procedural complications are responsible for a small fraction of deaths among patients undergoing contemporary PCI. Measures to further enhance procedural safety are unlikely to translate into meaningful reductions in PCI mortality.
Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation
Authors: Hijazi Ziad , Oldgren Jonas , Andersson Ulrika , Connolly Stuart J. , Ezekowitz Michael D. , Hohnloser Stefan H. , Reilly Paul A. , Vinereanu Dragos , Siegbahn Agneta , Yusuf Salim , Wallentin Lars 
Published: February 2012

Background—
Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.

Methods and Results—

Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS
2
and CHA
2
DS
2
-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17–3.39];
P
=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41–4.07];
P
=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05–6.29];
P
<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95–11.49];
P
<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72,
P
<0.0001, for a composite of thromboembolic events.

Conclusions—
Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00262600.
Islamic Finance in the Western Balkans: Prospects and Regulatory Challenges
Authors: Jusic Asim , Ismail Ashraf M. 
Published: March 2012

Abstract
In this article the authors contend that the murabaḥa debt-contract is over-emphasized, inefficient, and of questionable value with regards to creating Shariʿah-compliant alternatives to ribā-based finance. Instead, they argue that mushārakah, or equity-participation, should be the focus of Islamic financial innovation. They propose the creation of a new mushārakah market that would allow investors to bid for participation in investment projects, which would be distinguished from existing equity markets by requiring the direct participation of investors in a project’s management. Second, the authors address the legal and regulatory reforms necessary for mushārakah financing to succeed in the Western Balkans. They recommend the protection of property rights through financial arbitration mechanisms rather than court litigation. Arbitration resolves the conflict of laws inherent to Islamic finance, by providing a means of negotiating disputes between Islamic and secular sources of law. These measures reduce transaction costs associated with equity participation and thereby increase investor confidence.
Labral Penetration Rate in a Consecutive Series of 300 Hip Arthroscopies
Authors: Domb Benjamin , Hanypsiak Bryan , Botser Itamar 
Published: February 2012

Background: Intraoperative labral injury during the establishment of the first portal in hip arthroscopy has been reported to be as high as 20%. Purpose: The purpose of the study was to prospectively identify the incidence of acetabular labral injuries that occurred while using a current technique for the establishment of portals during hip arthroscopy. Study Design: Case series; Level of evidence, 4. Methods: Between the years 2008 and 2010, data were prospectively collected for all patients undergoing hip arthroscopic surgery. Patients with previous labral resection or Tonnis grade greater than 1 were excluded. Patients were positioned supine, traction was applied, and portals were established. The anterolateral portal was created first by venting the joint with a spinal needle and then re-entering the joint with the same needle with the bevel side facing the labrum. Next, the midanterior portal was created under vision. A thorough examination of the acetabular labrum was conducted arthroscopically through multiple viewing portals, and labral injuries related to the establishment of portals were identified and noted. Results: A total of 300 patients were included in the study; only 2 patients (0.67%) suffered intraoperative labral injuries at the study period. One injury occurred during revision arthroscopy, while the second involved a hyperplastic labrum in a dysplastic hip. No patient with normal hip morphological characteristics undergoing a hip arthroscopy suffered a labral tear as a result of portal placement. Conclusion: The incidence of iatrogenic labral injury during hip arthroscopy can be as low as 0.67% when using the described technique.
Stability of Double-Row Rotator Cuff Repair Is Not Adversely Affected by Scaffold Interposition Between Tendon and Bone
Authors: Beitzel Knut , Chowaniec David M. , McCarthy Mary Beth , Cote Mark P. , Russell Ryan P. , Obopilwe Elifho , Imhoff Andreas B. , Arciero Robert A. , Mazzocca Augustus D. 
Published: February 2012

Background: Rotator cuff reconstructions may be improved by adding growth factors, cells, or other biologic factors into the repair zone. This usually requires a biological carrier (scaffold) to be integrated into the construct and placed in the area of tendon-to-bone healing. This needs to be done without affecting the constructs mechanics. Hypothesis/Purpose: The hypothesis was that scaffold placement, as an interposition, has no adverse effects on biomechanical properties of double-row rotator cuff repair. The purpose of this study was to examine the effect of scaffold interposition on the initial strength of rotator cuff repairs. Study Design: Controlled laboratory study. Methods: Twenty-five fresh-frozen shoulders (mean age: 65.5 ± 8.9 years) were randomly assigned to 5 groups. Groups were chosen to represent a broad spectrum of commonly used scaffold types: (1) double-row repair without augmentation, (2) double-row repair with interposition of a fibrin clot (Viscogel), (3) double-row repair with interposition of a collagen scaffold (Mucograft) between tendon and bone, (4) double-row repair with interposition of human dermis patch (ArthroFlex) between tendon and bone, and (5) double-row repair with human dermis patch (ArthroFlex) placed on top of the repair. Cyclic loading to measure displacement was performed to 3000 cycles at 1 Hz with an applied 10- to 100-N load. The ultimate load to failure was determined at a rate of 31 mm/min. Results: There were no significant differences in mean displacement under cyclic loading, slope, or energy absorbed to failure between all groups ( P = .128, P = .981, P = .105). Ultimate load to failure of repairs that used the collagen patch as an interposition (573.3 ± 75.6 N) and a dermis patch on top of the reconstruction (575.8 ± 22.6 N) was higher compared with the repair without a scaffold (348.9 ± 98.8 N; P = .018 and P = .025). No significant differences were found for repairs with the fibrin clot as an interposition (426.9 ± 103.6 N) and the decellularized dermis patch as an interposition (469.9 ± 148.6 N; P = .73 and P = .35). Conclusion: Scaffold augmentation did not adversely affect the zero time strength of the tested standard double-row rotator cuff repairs. An increased ultimate load to failure was observed for 2 of the augmentation methods (collagen patch as an interposition and decellularized dermis patch on top of the reconstruction) compared with the nonaugmented repairs. Clinical Relevance: Scaffolds intended for application of growth factors or cellular components in a repair situation did not adversely jeopardize the stability of the operative construct.
A study of successful applicants’ views of a social work admissions process
Authors: Campbell Jim , Campbell Anne , Das Chaitali 
Published: February 2012

• Summary: There are substantial variations in the way that applicants are selected for social work programmes in the UK and across the world. This article begins by reviewing the literature in this field, revealing debates about how effective and reliable are methods of assessment used during admission processes. It then describes a cross-sectional survey of new social work applicants ( n = 203) to two programme providers, describing demographic characteristics and their experiences of the admissions process. • Findings: A number of themes emerged from two sets of findings. There were variations in demographic characteristics, particularly in terms of gender and religion. The study was particularly interested in how students viewed the admissions process. Most students were satisfied with admissions processes, and there were some differences in views about the methods used. The article concludes by describing changes to the admissions system that were partly informed by the study. The article acknowledges the expected bias in the methodology, given that successful applicants were surveyed and not those who were not successful. • Applications: The authors discuss the study findings in the context of national and international literature and suggest that more rigorous attention should be paid to such evaluations to enable this important area of education and workforce development to be better understood.
A comparison of family-of-origin perception of undergraduates: Social work students and students in other fields
Authors: Doron Hadas , Bar-On Amitai , Tal Degani , Adi Alharar , Hadas Kotnick , Orli Yigar , Einav Gefen , Noah Piler , Galit Ben-Dovid 
Published: February 2012

• Summary: In order to better understand the principal influences that cause social work professionals to choose their profession, an empirical research using the circumplex model for family evaluation was conducted, measuring perceived aspects of cohesion and change in the families-of-origin of social work students versus students from other disciplines. A total of 306 undergraduate students from social work, education, biotechnology, computer science, and economics participated. Students filled in questionnaires measuring their perception of families-of-origin, and their influential figure in choosing their profession. • Findings: Social work students were found to perceive significantly more extreme views of their families-of-origin, compared to students from other disciplines, while the latter scored higher in the category of ‘balanced family’. Finally, students of therapeutic disciplines, both males and females, rated a stronger influence of their mothers on their choice of profession, compared to students from non-therapeutic professions. • Applications: The findings indicate that students who train for therapeutic professions have presumably experienced more hardships in their families-of-origin compared to students who choose non-therapeutic studies. On the one hand, this may equip them with higher helping skills; on the other hand, being raised in a troubled family may render the future therapist more vulnerable to potential pitfalls in the helping relationship or impair the therapeutic process. Social work training institutions should therefore pay attention to their students’ perception of families-of-origin and allow for a conscious and structured processing of past experiences during the years of training.
Through-knee amputation in peripheral vascular disease
Authors: Jackson Andrew J , Coburn Gerald , Morrison David , Mrozinski Sarah , Reidy John 
Published: March 2012

Through-knee amputation accounts for just 2.8% of annual amputations in England. Traditionally it is viewed as an operation with poor outcomes, and its use limited. We present a case series and review of articles published on through knee amputation. The literature review covers the 17 papers identified on through-knee amputation in peripheral vascular disease. The results are summarised and discussed, with favourable outcomes in terms of perioperative mortality and primary healing demonstrated in the majority of papers. In the case series, 14 patients who underwent through knee amputation were retrospectively reviewed. Peri- operative mortality was 7%. Primary healing was achieved in 79% of cases. Functional outcomes were excellent, with predicted functional activity achieved in 81% of survivors, with 34% ambulating regularly. In conclusion, through-knee amputation should be considered as an alternative to transfemoral amputation, as perioperative mortality, healing rates and functional outcomes appear excellent, both in this series and the majority of others published.
Mcl-1 and Bcl-xL coordinately regulate megakaryocyte survival
Authors: Debrincat Marlyse A. , Josefsson Emma C. , James Chloé , Henley Katya J. , Ellis Sarah , Lebois Marion , Betterman Kelly L. , Lane Rachael M. , Rogers Kelly L. , White Michael J. , Roberts Andrew W. , Harvey Natasha L. , Metcalf Donald , Kile Benjamin T. 
Published: February 2012

Abstract
Mature megakaryocytes depend on the function of Bcl-xL, a member of the Bcl-2 family of prosurvival proteins, to proceed safely through the process of platelet shedding. Despite this, loss of Bcl-xL does not prevent the growth and maturation of megakaryocytes, suggesting redundancy with other prosurvival proteins. We therefore generated mice with a megakaryocyte-specific deletion of Mcl-1, which is known to be expressed in megakaryocytes. Megakaryopoiesis, platelet production, and platelet lifespan were unperturbed in Mcl-1Pf4Δ/Pf4Δ animals. However, treatment with ABT-737, a BH3 mimetic compound that inhibits the prosurvival proteins Bcl-2, Bcl-xL, and Bcl-w resulted in the complete ablation of megakaryocytes and platelets. Genetic deletion of both Mcl-1 and Bcl-xL in megakaryocytes resulted in preweaning lethality. Megakaryopoiesis in Bcl-xPf4Δ/Pf4ΔMcl-1Pf4Δ/Pf4Δ embryos was severely compromised, and these animals exhibited ectopic bleeding. Our studies indicate that the combination of Bcl-xL and Mcl-1 is essential for the viability of the megakaryocyte lineage.
Guidelines for the management of work-related asthma
Authors: Baur X. , Sigsgaard T. , Aasen T.B. , Burge P.S. , Heederik D. , Henneberger P. , Maestrelli P. , Rooyackers J. , Schlünssen V. , Vandenplas O. , Wilken D. 
Published: February 2012

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder.A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners’ three-star system.Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.
Repeated cross-sectional survey of patient-reported asthma control in Europe in the past 5 years
Authors: Demoly P. , Annunziata K. , Gubba E. , Adamek L. 
Published: February 2012

Although the main goal of asthma management guidelines is to achieve and maintain clinical control, reported levels of not well-controlled asthma remain high. The aim of this analysis was to compare the levels of asthma control and the associated impact on patients' health status in Europe in 2006, 2008 and 2010. An additional outcome was the comparison of the burden of asthma with diabetes.Data were obtained from the cross-sectional, self-reported, European National Health and Wellness Surveys conducted in France, Germany, Italy, Spain and the UK. Asthma control (Asthma Control Test™; QualityMetric, Inc., Lincoln, RI, USA) and health status (Short Form (SF)-12 health survey and the Work Productivity Loss and Activity Impairment questionnaire) were assessed.In 2010, the proportion of treated asthma patients assessed as having not well-controlled asthma was 53.5%, compared with 56.6% and 55.0% in 2008 and 2006, respectively. A significant reduction in not well-controlled asthma was observed in Germany between 2006 (72.3%) and 2010 (62.5%; p=0.005). Fluctuations in control levels were observed in other countries. For all surveys, having at least well-controlled asthma was associated with a significantly lower number of healthcare contacts in the previous 6 months, better mean±sdSF-12 scores for the physical (data for 2010: not well controlled 39.9±11.38, at least well-controlled 48.0±9.89; p<0.001) and mental (data for 2010: not well-controlled 40.6±10.95, at least well-controlled 45.0±10.91; p<0.001) components, and significantly less impact on Work Productivity Loss and Activity Impairment. Asthma and diabetes were associated with a similar overall negative impact on health status.A substantial proportion of asthmatics remain not well-controlled across five European countries, resulting in a significant impact on health resources and patients' health status. The overall burden of asthma appears to be similar to that of diabetes.