bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathological assessment of tumour regression, nodal stage and status of resection margins determines prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy
Authors: Wedemeyer I , Kreppel M , Scheer M , Zöller JE , Büttner R , Drebber U 
Published: May 2013

ObjectivesIn advanced oral squamous cell carcinoma (OSCC), tumour regression after neoadjuvant radiochemotherapy seems to be an important prognostic factor. In this study, we intended to compare regression grading according to two previously described regression models and to analyse the association of tumour regression and other tumour characteristics with patients' characteristics and overall survival.MethodsThe retrospective study included 63 treatment‐naive patients with primary OSCC of stages II‐IV, who were treated with a concomitant neoadjuvant radiochemotherapy followed by radical surgery. Assessment of histopathological features was performed, there under regression grading according to two previously described regression models.ResultsBoth tumour regression models provided comparable results in terms of distribution of different regression grades. In univariate analysis regression gradings (P = 0.003 and P = 0.007), ypT‐stage, ypN‐stage and status of resection margins (P < 0.001) were significantly associated with the 5‐year overall survival (OS). None of the pretreatment clinicopathological parameters showed association with histopathological tumour regression. Multivariate analysis revealed the status of resection margins and of lymph node metastasis as statistically significant features for OS (P = 0.020 and P = 0.003, respectively).ConclusionTumour regression grading, nodal stage and status of resection margins predict prognosis in patients after neoadjuvant treatment. Currently, there are no pretreatment clinicopathological parameters, which predicting good tumour response to therapy. Thus, identifying non‐responding patients, which might benefit from an intensified systemic therapy, requires surgical resection and consecutive histopathological assessment. Therefore, further investigation and validation of new, especially, molecular predictors of tumour response to radiochemotherapy remains an unmet, future clinical need.
Melanoma inhibitory activity promotes melanoma development through activation of YBX1
Authors: Schmid Rainer , Meyer Katharina , Spang Rainer , Schittek Birgit , Bosserhoff Anja‐Katrin 
Published: May 2013

SummaryMelanoma inhibitory activity (MIA), a small soluble secreted protein, is functionally important for progression of malignant melanoma. We recently revealed that p54nrb acts as a mediator of MIA action. In this study, we characterize the transcriptional regulation of p54nrb by MIA to explain MIA's molecular action. We identified one highly conserved region in the p54nrb promoter that is necessary and sufficient for MIA‐dependent activation. Functional promoter analysis identified the transcription factor YBX1 as the mediator of MIA activation of p54nrb transcription. We screened the genome for further potential MIA‐regulated genes carrying the element in their promoter regions. Integrating our sequence data with expression data from human melanomas identified a list of 23 potential MIA‐YBX1 targets in melanomas. In summary, we present for the first time effects of MIA on transcriptional regulation. Uncovering new potential downstream effectors working via activation of YBX1 supports the important role of MIA in melanoma.
Utilization of frozen plasma in Ontario: a provincewide audit reveals a high rate of inappropriate transfusions
Authors: Tinmouth Alan , Thompson Troy , Arnold Donald M. , Callum Jeannie L. , Gagliardi Kate , Lauzon Deborah , Owens Wendy , Pinkerton Peter 
Published: May 2013

BackgroundFrozen plasma (FP) is frequently transfused inappropriately, an intervention that results in risk without benefit for the patient. To better understand current utilization practices in our region, we undertook a provincewide prospective audit to evaluate the clinical indications and appropriateness of FP transfusion.Study Design and MethodsAll hospitals in the Canadian province of Ontario with transfusion medicine services were invited to participate in a 5‐day audit of FP utilization. FP dose, indication, and clinical patient data were collected for each transfusion request. Indications for FP transfusions were independently adjudicated as appropriate, inappropriate, or indeterminate based on predefined criteria.ResultsSeventy‐six (49%) of 155 invited hospitals participated in the audit, which included 573 requests for 2012 units of FP. A total of 559 transfusions (1909 units) were administered. Of 573 requests, 164 (28.6%) were deemed inappropriate most often because: 1) they were administered to patients with an international normalized ratio below 1.5 or 2) they were administered in absence of bleeding or emergency surgery. The most frequent indications for FP transfusions were before surgery and warfarin reversal. Overall, patients admitted to the clinical areas of surgery, internal medicine, and the emergency department represented the largest users of FP, but this varied by hospital type (community vs. academic). The most frequently requested doses of FP were 2 and 4 units.ConclusionThis point‐prevalence hospital audit revealed that transfusion of FP is frequently inappropriate. Focusing on reducing the two most common reasons for inappropriate FP transfusions could lead to a significant improvement in FP utilization.
Reovirus Activates a Caspase-Independent Cell Death Pathway
Authors: Berger Angela K. , Danthi Pranav 
Published: May 2013

ABSTRACT
Virus-induced apoptosis is thought to be the primary mechanism of cell death following reovirus infection. Induction of cell death following reovirus infection is initiated by the incoming viral capsid proteins during cell entry and occurs via NF-κB-dependent activation of classical apoptotic pathways. Prototype reovirus strain T3D displays a higher cell-killing potential than strain T1L. To investigate how signaling pathways initiated by T3D and T1L differ, we methodically analyzed cell death pathways activated by these two viruses in L929 cells. We found that T3D activates NF-κB, initiator caspases, and effector caspases to a significantly greater extent than T1L. Surprisingly, blockade of NF-κB or caspases did not affect T3D-induced cell death. Cell death following T3D infection resulted in a reduction in cellular ATP levels and was sensitive to inhibition of the kinase activity of receptor interacting protein 1 (RIP1). Furthermore, membranes of T3D-infected cells were compromised. Based on the dispensability of caspases, a requirement for RIP1 kinase function, and the physiological status of infected cells, we conclude that reovirus can also induce an alternate, necrotic form of cell death described as necroptosis. We also found that induction of necroptosis requires synthesis of viral RNA or proteins, a step distinct from that necessary for the induction of apoptosis. Thus, our studies reveal that two different events in the reovirus replication cycle can injure host cells by distinct mechanisms.

IMPORTANCE
Virus-induced cell death is a determinant of pathogenesis. Mammalian reovirus is a versatile experimental model for identifying viral and host intermediaries that contribute to cell death and for examining how these factors influence viral disease. In this study, we identified that in addition to apoptosis, a regulated form of cell death, reovirus is capable of inducing an alternate form of controlled cell death known as necroptosis. Death by this pathway perturbs the integrity of host membranes and likely triggers inflammation. We also found that apoptosis and necroptosis following viral infection are activated by distinct mechanisms. Our results suggest that host cells can detect different stages of viral infection and attempt to limit viral replication through different forms of cellular suicide. While these death responses may aid in curbing viral spread, they can also exacerbate tissue injury and disease following infection.
Sex differences in the risk of injury in World Cup alpine skiers: a 6-year cohort study
Authors: Bere Tone , Flørenes Tonje Wåle , Nordsletten Lars , Bahr Roald 
Published: May 2013

BackgroundIn competitive alpine skiing, there is a controversy regarding the sex-related risk of injury.ObjectiveTo compare the risk of injury in female versus male World Cup (WC) alpine skiers.MethodsInjuries were recorded through the International Ski Federation Injury Surveillance System for six consecutive winter seasons (2006–2012), based on retrospective interviews with athletes from 10 teams at the end of each season. All acute training and competition injuries which required medical attention were recorded. Race exposure was calculated based on the exact number of runs started in the WC for each of the interviewed athletes each season.ResultsMen had a higher overall rate of injury (relative risk (RR) 1.24, 95% CI 1.05 to 1.47), as well as a higher rate of time-loss injury (RR 1.23, 95% CI 1.03 to 1.48) than women in training and competitions, expressed as injuries/100 athletes/season. These sex differences were even more pronounced during WC races (RR 1.58, 95% CI 1.22 to 2.04 and RR 1.72, 95% CI 1.29 to 2.31, for overall and time-loss injuries, respectively). There was no sex difference in the risk of knee/anterior cruciate ligament (ACL) injuries.ConclusionsNo previous studies from competitive skiing have reported a significantly higher risk of injuries in men than women. In contrast to recreational skiing and team sports, there was no sex difference in the risk of knee/ACL injuries and prevention efforts should be directed as much towards male as female competitive skiers.
Determinants of vulnerability in early childhood development in Ireland: a cross-sectional study
Authors: Curtin Margaret , Madden Jamie , Staines Anthony , Perry Ivan J 
Published: May 2013

ObjectivesEarly childhood development strongly influences lifelong health. The Early Development Instrument (EDI) is a well-validated population-level measure of five developmental domains (physical health and well-being, social competence, emotional maturity, language and cognitive skills, and communication skills and general knowledge) at school entry age. The aim of this study was to explore the potential of EDI as an indicator of early development in Ireland.DesignA cross-sectional design was used.SettingThe study was conducted in 42 of 47 primary schools in a major Irish urban centre.ParticipantsEDI (teacher completed) scores were calculated for 1243 children in their first year of full-time education. Contextual data from a subset of 865 children were collected using a parental questionnaire.Primary and secondary outcome measuresChildren scoring in the lowest 10% of the population in one or more domains were deemed ‘developmentally vulnerable’. Scores were correlated with contextual data from the parental questionnaire.ResultsIn the sample population, 29% of children were not developmentally ready to engage in school. Factors associated with increased risk of vulnerability were being male OR 2.1 (CI 1.6 to 2.7); under 5 years OR 1.5 (CI 1.1 to 2.1) and having English as a second language OR 3.7 (CI 2.6 to 5.2). Adjusted for these demographics, low birth weight, poor parent/child interaction and mother's lower level of education showed the most significant ORs for developmental vulnerability. Calculating population attributable fractions, the greatest population-level risk factors were being male (35%), mother's education (27%) and having English as a second language (12%).ConclusionsThe EDI and linked parental questionnaires are promising indicators of the extent, distribution and determinants of developmental vulnerability among children in their first year of primary school in Ireland.
Cost-effectiveness of a telephone-delivered education programme to prevent early childhood caries in a disadvantaged area: a cohort study
Authors: Pukallus Margaret , Plonka Kathryn , Kularatna Sanjeewa , Gordon Louisa , Barnett Adrian G , Walsh Laurence , Seow W Kim 
Published: May 2013

ObjectivesEarly childhood caries is a highly destructive dental disease which is compounded by the need for young children to be treated under general anaesthesia. In Australia, there are long waiting periods for treatment at public hospitals. In this paper, we examined the costs and patient outcomes of a prevention programme for early childhood caries to assess its value for government services.DesignCost-effectiveness analysis using a Markov model.SettingPublic dental patients in a low socioeconomic, socially disadvantaged area in the State of Queensland, Australia.ParticipantsChildren aged 6 months to 6 years received either a telephone prevention programme or usual care.Primary and secondary outcome measuresA mathematical model was used to assess caries incidence and public dental treatment costs for a cohort of children. Healthcare costs, treatment probabilities and caries incidence were modelled from 6 months to 6 years of age based on trial data from mothers and their children who received either a telephone prevention programme or usual care. Sensitivity analyses were used to assess the robustness of the findings to uncertainty in the model estimates.ResultsBy age 6 years, the telephone intervention programme had prevented an estimated 43 carious teeth and saved £69 984 in healthcare costs per 100 children. The results were sensitive to the cost of general anaesthesia (cost-savings range £36 043–£97 298) and the incidence of caries in the prevention group (cost-savings range £59 496–£83 368) and usual care (cost-savings range £46 833–£93 328), but there were cost savings in all scenarios.ConclusionsA telephone intervention that aims to prevent early childhood caries is likely to generate considerable and immediate patient benefits and cost savings to the public dental health service in disadvantaged communities.
Falling sex ratios and emerging evidence of sex-selective abortion in Nepal: evidence from nationally representative survey data
Authors: Frost Melanie Dawn , Puri Mahesh , Hinde Peter Richard Andrew 
Published: May 2013

ObjectivesTo quantify trends in changing sex ratios of births before and after the legalisation of abortion in Nepal. While sex-selective abortion is common in some Asian countries, it is not clear whether the legal status of abortion is associated with the prevalence of sex-selection when sex-selection is illegal. In this context, Nepal provides an interesting case study. Abortion was legalised in 2002 and prior to that, there was no evidence of sex-selective abortion. Changes in the sex ratio at birth since legalisation would suggest an association with legalisation, even though sex-selection is expressly prohibited.DesignAnalysis of data from four Demographic and Health Surveys, conducted in 1996, 2001, 2006 and 2011.SettingNepal.Participants31 842 women aged 15–49.Main outcome measureConditional sex ratios (CSRs) were calculated, specifically the CSR for second-born children where the first-born was female. This CSR is where the evidence of sex-selective abortion will be most visible. CSRs were looked at over time to assess the impact of legalisation as well as for population sub-groups in order to identify characteristics of women using sex-selection.ResultsFrom 2007 to 2010, the CSR for second-order births where the first-born was a girl was found to be 742 girls per 1000 boys (95% CI 599 to 913). Prior to legalisation of abortion (1998–2000), the same CSR was 1021 (906–1150). After legalisation, it dropped most among educated and richer women, especially in urban areas. Just 325 girls were born for every 1000 boys among the richest urban women.ConclusionsThe fall in CSRs witnessed post-legalisation indicates that sex-selective abortion is becoming more common. This change is very likely driven by both supply and demand factors. Falling fertility has intensified the need to bear a son sooner, while legal abortion services have reduced the costs and risks associated with obtaining an abortion.
Organising a manuscript reporting quality improvement or patient safety research
Authors: Holzmueller Christine G , Pronovost Peter J 
Published: May 2013

BackgroundPeer-reviewed publication plays important roles in disseminating research findings, developing generalisable knowledge and garnering recognition for authors and institutions. Nonetheless, many bemoan the whole manuscript writing process, intimidated by the arbitrary and somewhat opaque conventions.MethodsThis paper offers practical advice about organising and writing a manuscript reporting quality improvement or patient safety research for submission to a peer-reviewed journal.ResultsEach section of the paper discusses a specific manuscript component—from title, abstract and each section of the manuscript body, through to reference list and tables and figures—explaining key principles, offering content organisation tips and providing an example of how this section may read. The paper also offers a checklist of common mistakes to avoid in a manuscript.
Stable isotope chemostratigraphy in lacustrine strata of the Xiagou Formation, Gansu Province, NW China
Authors: Suarez Marina B. , Ludvigson Gregory A. , González Luis A. , Al-Suwaidi Aisha H. , You Hai-Lu 
Published: May 2013

Abstract

Two sections from Early Cretaceous lacustrine strata of the Xiagou Formation from the Changma Basin in Gansu Province, China, are correlated based on their carbon isotopic compositions of bulk sedimentary organic matter and carbonate, as well as carbonate oxygen-isotopic compositions. The samples were collected from fossiliferous strata, which contain well-preserved Cretaceous bird remains. The sections are primarily correlated based on a two-step increase in δ
13
C
org
with an overall magnitude of
c.
12.5‰. The stratigraphic variations in carbon isotopes within the two lacustrine sections are correlated with global carbon isotope variations C3–C7 based on marine carbon isotope records. This correlation places the Xiagou lacustrine strata in this locality within the early Aptian Stage, specifically, the Selli Equivalent, which is associated with Ocean Anoxic Event 1a.
KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells
Authors: Xu Yong , Fang Fang , Miriyala Sumitra , Crooks Peter A. , Oberley Terry D. , Chaiswing Luksana , Noel Teresa , Holley Aaron K. , Zhao Yanming , Kiningham Kelley K. , Clair Daret K. St. , Clair William H. St. 
Published: May 2013

Abstract
Elevated oxidative stress is observed more frequently in cancer cells than in normal cells. It is therefore expected that additional exposure to a low level of reactive oxygen species (ROS) will push cancer cells toward death, whereas normal cells might maintain redox homeostasis through adaptive antioxidant responses. We previously showed that parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase. The present study identifies KEAP1 as the downstream redox target that contributes to parthenolide's radiosensitization effect in prostate cancer cells. In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury. Mechanistically, parthenolide increases the level of cellular ROS and causes oxidation of thioredoxin (TrX) in prostate cancer cells, leading to a TrX-dependent increase in a reduced state of KEAP1, which in turn leads to KEAP1-mediated PGAM5 and Bcl-xL (BCL2L1) degradation. In contrast, parthenolide increases oxidation of KEAP1 in normal prostate epithelial cells, leading to increased Nrf2 (NFE2L2) levels and subsequent Nrf2-dependent expression of antioxidant enzymes. These results reveal a novel redox-mediated modification of KEAP1 in controlling the differential effect of parthenolide on tumor and normal cell radiosensitivity. Furthermore, they show it is possible to develop a tumor-specific radiosensitizing agent with radioprotective properties in normal cells. Cancer Res; 73(14); 4406–17. ©2013 AACR.
Optical Image-Guided Cancer Surgery: Challenges and Limitations
Authors: Keereweer Stijn , Van Driel Pieter B.A.A. , Snoeks Thomas J.A. , Kerrebijn Jeroen D.F. , Baatenburg de Jong Robert J. , Vahrmeijer Alexander L. , Sterenborg Henricus J.C.M. , Löwik Clemens W.G.M. 
Published: May 2013

Abstract
Optical image-guided cancer surgery is a promising technique to adequately determine tumor margins by tumor-specific targeting, potentially resulting in complete resection of tumor tissue with improved survival. However, identification of the photons coming from the fluorescent contrast agent is complicated by autofluorescence, optical tissue properties, and accurate fluorescent targeting agents and imaging systems. All these factors have an important influence on the image that is presented to the surgeon. Considering the clinical consequences at stake, it is a prerequisite to answer the questions that are essential for the surgeon. What is optical image-guided surgery and how can it improve patient care? What should the oncologic surgeon know about the fundamental principles of optical imaging to understand which conclusions can be drawn from the images? And how do the limitations influence clinical decision making? This article discusses these questions and provides a clear overview of the basic principles and practical applications. Although there are limitations to the intrinsic capacity of the technique, when practical and technical surgical possibilities are considered, optical imaging can be a very powerful intraoperative tool in guiding the future oncologic surgeon toward radical resection and optimal clinical results. Clin Cancer Res; 19(14); 3745–54. ©2013 AACR.
Implantable Cardioverter Defibrillators in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Schinkel Arend F.L. 
Published: May 2013

Background—
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a cardiomyopathy characterized by ventricular arrhythmias and an abnormal right ventricle. Implantable cardioverter defibrillator (ICD) therapy may prevent sudden cardiac death in patients with ARVD/C. Currently, an overview of outcomes, appropriate and inappropriate interventions, and complications of ICD therapy in ARVD/C is lacking.

Methods and Results—
A literature search was performed to identify studies reporting outcome and complications in patients with ARVD/C who underwent ICD implantation. Of 641 articles screened, 24 studies on 18 cohorts were eligible for inclusion. In case of multiple publications on a cohort, the most recent publication was included in the meta-analysis. There were 610 patients (mean age, 40.4 years; 42% women), who had an ICD for primary or secondary prevention of sudden cardiac death. Risk factors for sudden cardiac death were presyncope (61%), syncope (31%), previous cardiac arrest (14%), ventricular tachycardia (58%), and ventricular fibrillation (6%). Antiarrhythmic medication consisted mostly of β-blockers (38%), amiodarone (14%), or sotalol (30%). During the 3.8-year follow-up, annualized cardiac mortality rate was 0.9%, annualized noncardiac mortality rate was 0.8%, and annualized heart transplant rate was 0.9%. The annualized appropriate and inappropriate ICD intervention rates were 9.5% and 3.7%, respectively. ICD-related complications consisted of difficult lead placement (18.4%), lead malfunction (9.8%), infection (1.4%), lead displacement (3.3%), and any complication (20.3%).

Conclusions—
Cardiac and noncardiac mortality rates after ICD implantation in patients with ARVD/C are low. Appropriate ICD interventions occur at a rate of 9.5%/y. Inappropriate ICD interventions and complications lead to considerable ICD-related morbidity.