bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global prevalence and incidence of surgical site infections after appendectomy: a systematic review and meta-analysis protocol
Authors: Danwang Celestin , Mazou Temgoua Ngou , Tochie Joel Noutakdie , Nzalie Rolf Nyah Tuku , Bigna Jean Joel 
Published: August 2018

IntroductionAcute appendicitis is a surgical emergency and the most frequent aetiology of acute surgical abdominal pain in developed countries. Universally, its widely approved treatment is appendectomy. Like all surgical procedures, appendectomy can be associated with many complications among which are surgical site infections (SSIs).Despite the increasing number of appendectomies done around the world and the associated morbidities related to SSI after appendectomy, there is still scarcity of data concerning the global epidemiology of SSI after appendectomy. The current review aims at providing a summary of the published data on epidemiology of SSI after appendectomy.Methods and designWe will include randomised controlled trials, cohort studies, case–control and cross-sectional studies. Electronic databases including Embase, MEDLINE and ISI Web of Science (Science Citation Index) will be searched for relevant abstracts of studies published between 1 January 2000 and 30 December 2017, without language restriction. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of abstracts, study selection, data extraction and assessment of risk of bias, we shall assess the studies individually for clinical and statistical heterogeneity. Appropriate meta-analytic techniques will then be used to pool studies judged to be clinically homogenous. Visual inspection of funnel plots and Egger’s test will be used to detect publication bias. Results will be presented by country and continent.Ethics and disseminationSince primary data are not collected in this study, ethical approval is not required. This review is expected to provide relevant data to help in quantifying the global burden of SSI after appendectomy. The final report will be published in a peer-reviewed journal.Trial registration numberCRD42017075257.
Factors influencing the decision to convey or not to convey elderly people to the emergency department after emergency ambulance attendance: a systematic mixed studies review
Authors: Oosterwold Johan , Sagel Dennis , Berben Sivera , Roodbol Petrie , Broekhuis Manda 
Published: August 2018

BackgroundThe decision over whether to convey after emergency ambulance attendance plays a vital role in preventing avoidable admissions to a hospital’s emergency department (ED). This is especially important with the elderly, for whom the likelihood and frequency of adverse events are greatest.ObjectiveTo provide a structured overview of factors influencing the conveyance decision of elderly people to the ED after emergency ambulance attendance, and the outcomes of these decisions.Data sourcesA mixed studies review of empirical studies was performed based on systematic searches, without date restrictions, in PubMed, CINAHL and Embase (April 2018). Twenty-nine studies were included.Study eligibility criteriaOnly studies with evidence gathered after an emergency medical service (EMS) response in a prehospital setting that focused on factors that influence the decision whether to convey an elderly patient were included.SettingPrehospital, EMS setting; participants to include EMS staff and/or elderly patients after emergency ambulance attendance.Study appraisal and synthesis methodsThe Mixed Methods Appraisal Tool was used in appraising the included articles. Data were assessed using a ‘best fit’ framework synthesis approach.ResultsED referral by EMS staff is determined by many factors, and not only the acuteness of the medical emergency. Factors that increase the likelihood of non-conveyance are: non-conveyance guidelines, use of feedback loop, the experience, confidence, educational background and composition (male–female) of the EMS staff attending and consulting a physician, EMS colleague or other healthcare provider. Factors that boost the likelihood of conveyance are: being held liable, a lack of organisational support, of confidence and/or of baseline health information, and situational circumstances. Findings are presented in an overarching framework that includes the impact of these factors on the decision’s outcomes.ConclusionMany non-medical factors influence the ED conveyance decision after emergency ambulance attendance, and this makes it a complex issue to manage.
Association between type 1 diabetes mellitus and educational attainment in childhood: a systematic review protocol
Authors: Oakley Natalie Jayne , Kneale Dylan , Mann Mala , Hilliar Mariann , Tan Jeanette , Dayan Colin , Gregory John W , French Robert 
Published: August 2018

IntroductionType 1 diabetes has the potential to significantly impact children’s educational attainment. With the increase in incidence, quantifying this effect would be useful to assess how much additional support should be focused on children with type 1 diabetes in school.Methods and analysisWe will conduct a systematic review of all observational studies and randomised controlled trials, including individuals both with and without a diagnosis of type 1 diabetes who have undertaken high stakes testing at the end of compulsory schooling when under 18 years of age. The search will cover both peer-reviewed and grey literature available from January 2004 to January 2018. The following seven databases will be searched: Ovid MEDLINE (1946 to present), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid EMBASE (1947 to present), Thomson Reuters Web of Science, EBSCO Education Resources Information Center, EBSCO British Education Index and EBSCO Cumulative Index to Nursing and Allied Health Literature. Study selection and data extraction will be performed independently by two reviewers with any disagreements resolved via a third reviewer. The quality and risk of bias in the observational studies included in this review will be assessed using the Newcastle-Ottawa Scale. We aim to conduct a meta-analysis and will assess heterogeneity between the included studies and potential for publication bias if sufficient (>10) studies are included.Results and disseminationFormal ethical approval is not required as individual patient data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42017084078.
Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran
Authors: Goshayeshi Ladan , Ghaffarzadegan Kamran , Khooei Alireza , Esmaeilzadeh Abbas , Rahmani Khorram Mahla , Mosannen Mozaffari Hooman , Kiani Behzad , Hoseini Benyamin 
Published: August 2018

ObjectivesLynch syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform a universal strategy to assess the prevalence and clinicopathological characteristics of early onset CRCs at high risk of LS versus late-onset ones in the Iranian population.SettingA local population-based study from Northeastern Iran.Participants321 consecutive CRCs and pathology specimen screened between 2013 and 2016.Primary and secondary outcome measuresRetrospectively, information regarding the clinical criteria was obtained by interviewing the patients with CRC or, their families. Pathologists tested tumours with immunohistochemistry (IHC) staining of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6andPMS2). Tumours with absent IHC staining ofMLH1were tested for BRAF mutations to exclude sporadic CRCs. Prevalence of early onset CRCs at high risk of LS and familial CRC type X were assessed as primary and secondary outcome measures, respectively.ResultsOf 321 CRCs (13/123 (10.57%), early onset vs 21/198 (10.6%) late-onset) were detected to be MMR-deficient (dMMR). Nine early onset cases and 14 late-onset ones with a loss ofMLH1underwent testing for the BRAF mutation, none of the early onset and four (2.02%) late-onset were recognised as sporadic. The difference in the outcome of IHC-analysis between early and late-onset CRCs at high risk of LS was not statistically significant (p=0.34). Majority of the suspected LS tumours from early onset patients had arisen in distal part (8/11 (72.72%) vs 8/14 (57.14%)), all of which were occurred in the rectum or sigmoid.ConclusionClinically, these findings suggest that in case of limitation for BRAF testing, the practitioner in Iran may consider managing early onset dMMR cases like LS until access to BRAF testing becomes available to them, before germline testing to accurately diagnose LS.
Tectonic evolution of the Himalayan syntaxes: the view from Nanga Parbat
Authors: Butler Robert W. H. 
Published: August 2018

Abstract
Current tectonic understanding of the Nanga Parbat–Haramosh massif (NPHM) is reviewed, developing new models for the structure and deformation of the Indian continental crust, its thermorheological evolution, and its relationship to surface processes. Comparisons are drawn with the Namche Barwa–Gyala Peri massif (NBGPM) that cores an equivalent syntaxis at the NE termination of the Himalayan arc. Both massifs show exceptionally rapid active denudation and riverine downcutting, identified from very young cooling ages measured from various thermochronometers. They also record relicts of high-pressure metamorphic conditions that chart early tectonic burial. Initial exhumation was probably exclusively by tectonic processes but the young, and continuing emergence of these massifs reflects combined tectonic and surface processes. The feedback mechanisms implicit in aneurysm models may have been overemphasized, especially the role of synkinematic granites as agents of rheological softening and strain localization. Patterns of distributed ductile deformation exhumed within the NPHM are consistent with models of orogen-wide gravitation flow, with the syntaxes forming the lateral edges to the flow beneath the Himalayan arc.
Dependable Model-driven Development of CPS
Authors: Jiang Yu , Song Houbing , Yang Yixiao , Liu Han , Gu Ming , Guan Yong , Sun Jiaguang , Sha Lui 
Published: August 2018

Simulink is widely used for model-driven development (MDD) of cyber-physical systems. Typically, the Simulink-based development starts with Stateflow modeling, followed by simulation, validation, and code generation mapped to physical execution platforms. However, recent trends have raised the demands of rigorous verification on safety-critical applications to prevent intrinsic development faults and improve the system dependability, which is unfortunately challenging. Even though the constructed Stateflow model and the generated code pass the validation of Simulink Design Verifier and Simulink Polyspace, respectively, the system may still fail due to some implicit defects contained in the design model (design defect) and the generated code (implementation defects).
In this article, we bridge the Stateflow-based MDD and a well-defined rigorous verification to reduce development faults. First, we develop a self-contained toolkit to translate a Stateflow model into timed automata, where major advanced modeling features in Stateflow are supported. Taking advantage of the strong verification capability of Uppaal, we can not only find bugs in Stateflow models that are missed by Simulink Design Verifier but also check more important temporal properties. Next, we customize a runtime verifier for the generated non-intrusive VHDL and C code of a Stateflow model for monitoring. The major strength of the customization is the flexibility to collect and analyze runtime properties with a pure software monitor, which offers more opportunities for engineers to achieve high reliability of the target system compared with the traditional act that only relies on Simulink Polyspace. In this way, safety-critical properties are both verified at the model level and at the consistent system implementation level with physical execution environment in consideration. We apply our approach to the development of a typical cyber-physical system-train communication controller based on the IEC standard 61375. Experiments show that more ambiguousness in the standard are detected and confirmed and more development faults and those corresponding errors that would lead to system failure have been removed. Furthermore, the verified implementation has been deployed on real trains.
Assessment of liver fibrosis progression and regression by a serological collagen turnover profile
Authors: Karsdal Morten A. , Hjuler Sara T. , Luo Yi , Rasmussen Daniel G. K. , Nielsen Mette J. , Holm Nielsen Signe , Leeming Diana J. , Goodman Zachary , Arch Robert H. , Patel Keyur , Schuppan Detlef 
Published: August 2018

There is a need for noninvasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to antifibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be included in clinical studies with fibrosis as end point. Circulating biomarkers, originating from defined fragments of the scar tissue itself, may serve as valuable tools for this aspect of precision medicine. We investigated a panel of serological collagen formation and degradation markers to identify patients likely to regress or progress in absence of a therapeutic intervention. Plasma samples from patients with moderate-stage hepatitis C receiving placebo treatment in a phase II trial of the peroxisome proliferator-activated receptor agonist farglitazar were included. The patients had matched liver biopsies at baseline and 52 wk of follow-up. Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C5) and collagen degradation (C3M, C4M, and C6M) were analyzed. Logistic regression analysis including PRO-C3 and C6M identified subjects with progressive liver fibrosis with an AUROC of 0.91 ( P < 0.0001) and positive and negative predictive values (PPV/NPV) of 75.0%/88.6%. Low levels of PRO-C5 predicted a spontaneous regression phenotype, with an odds ratio of 33.8 times higher compared with patients with high levels ( P < 0.0025) with an AUROC of 0.78 ( P < 0.0001) and PPV/NPV of 60.0%/95.7%. Two collagen fragments (PRO-C3 and C6M) identified liver fibrosis progressors, and one collagen fragment (PRO-C5) identified liver fibrosis regressors. These biomarkers may improve patient stratification and monitor treatment efficacy in studies with fibrosis as clinical end point.NEW & NOTEWORTHY In this study we report two biomarkers of collagen fragments (PRO-C3 and C6M) that are able to identify liver fibrosis progressors while one biomarker (PRO-C5) identified liver fibrosis regressors. In particular, we present three noninvasive biomarkers that can be used to identify patients with progressive liver fibrosis, monitor response to antifibrotic therapy, and also identify the spontaneous liver fibrosis regression phenotype.
Intestinal IMINO transporter SIT1 is not expressed in human newborns
Authors: Meier C. , Camargo S. M. , Hunziker S. , Moehrlen U. , Gros S. J. , Bode P. , Leu S. , Meuli M. , Holland-Cunz S. , Verrey F. , Vuille-dit-Bille R. N. 
Published: August 2018

The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion.
Role of P53-Senescence Induction in Suppression of LNCaP Prostate Cancer Growth by Cardiotonic Compound Bufalin
Authors: Zhang Yong , Dong Yinhui , Melkus Michael W. , Yin Shutao , Tang Su-Ni , Jiang Peixin , Pramanik Kartick , Wu Wei , Kim Sangyub , Ye Min , Hu Hongbo , Lu Junxuan , Jiang Cheng 
Published: August 2018

Abstract
Bufalin is a major cardiotonic compound in the traditional Chinese medicine, Chansu, prepared from toad skin secretions. Cell culture studies have suggested an anticancer potential involving multiple cellular processes, including differentiation, apoptosis, senescence, and angiogenesis. In prostate cancer cell models, P53-dependent and independent caspase-mediated apoptosis and androgen receptor (AR) antagonism have been described for bufalin at micromolar concentrations. Because a human pharmacokinetic study indicated that single nanomolar bufalin was safely achievable in the peripheral circulation, we evaluated its cellular activity within range with the AR-positive and P53 wild-type human LNCaP prostate cancer cells in vitro. Our data show that bufalin induced caspase-mediated apoptosis at 20 nmol/L or higher concentration with concomitant suppression of AR protein and its best-known target, PSA and steroid receptor coactivator 1 and 3 (SRC-1, SRC-3). Bufalin exposure induced protein abundance of P53 (not mRNA) and P21CIP1 (CDKN1A), G2 arrest, and increased senescence-like phenotype (SA-galactosidase). Small RNAi knocking down of P53 attenuated bufalin-induced senescence, whereas knocking down of P21CIP1 exacerbated bufalin-induced caspase-mediated apoptosis. In vivo, daily intraperitoneal injection of bufalin (1.5 mg/kg body weight) for 9 weeks delayed LNCaP subcutaneous xenograft tumor growth in NSG SCID mice with a 67% decrease of final weight without affecting body weight. Tumors from bufalin-treated mice exhibited increased phospho-P53 and SA-galactosidase without detectable caspase-mediated apoptosis or suppression of AR and PSA. Our data suggest potential applications of bufalin in therapy of prostate cancer in patients or chemo-interception of prostate precancerous lesions, engaging a selective activation of P53 senescence. Mol Cancer Ther; 17(11); 2341–52. ©2018 AACR.
Apontamentos sobre as Cantigas de Santa Maria de D. Afonso X
Authors: Silva Alex Rogério 
Published: August 2018

Este artigo se propõe a apresentar a composição medieval intitulada Cantigas de Santa Maria, de autoria de D. Afonso X, rei de Leão e Castela. Tal obra foi empreendida em seu reinado (1252-1284), em concomitância com outros trabalhos de cunho científico e jurídico, influenciando a cultura do século XIII. D. Afonso X é tido como um mecenas do seu tempo, tendo adquirido o cognome de “O Sábio”.
Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients
Authors: Hajialilo M , Tayari P , Ghorbanihaghjo A , Khabbazi A , Malek Mahdavi A , Rashtchizadeh N 
Published: August 2018

Background Endothelial dysfunction plays an important role in pathogenesis of systemic lupus erythematosus (SLE). Considering the importance of serum soluble vascular cell adhesion molecule-1 as the most abundant of the circulating adhesion molecules increased as a result of endothelial dysfunction and the role of endothelin-1 in pathophysiology of SLE, this study aimed to evaluate serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy subjects. Methods In this cross-sectional study, 60 SLE patients according to the Systemic Lupus International Collaborating Clinics classification criteria for SLE and 40 age and sex-matched healthy controls were included. In patients, clinical examination was performed and SLE disease activity index was assessed. Serum endothelin-1 and soluble vascular cell adhesion molecule-1 levels were measured using ELISA kits. Results The mean ± standard deviation age of patients and controls was 31.91 ± 7.66 and 33.20 ± 10.08 years, respectively. Compared to healthy controls, serum soluble vascular cell adhesion molecule-1 (1023.8 ± 352.96 vs. 866.06 ± 109.91) and endothelin-1 (77.83 ± 16.27 vs. 54.45 ± 12.01) was significantly higher in SLE patients ( P = 0.003 and P < 0.001, respectively). The most common organs involved in patients were skin, joint and kidney. There were no significant differences in serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels according to organ involvement, activity of disease and the conventional serum markers of disease activity ( P > 0.05). There was no significant correlation between disease activity, organ involvement and negative or positivity of autoantibodies as well as serum complement with endothelin-1 and vascular cell adhesion molecule-1 levels ( P > 0.05). Conclusions Although our study revealed higher serum soluble vascular cell adhesion molecule-1 and endothelin-1 levels in SLE patients compared to healthy controls, there were no significant correlations between their serum levels with organ involvement and disease activity.
Operative Treatment of the Malunited Fibula Fracture
Authors: Egger Anthony C. , Berkowitz Mark J. 
Published: August 2018

Failure to anatomically reduce and stabilize the fractured distal fibula can result in malunion of the fibula and malreduction of the ankle mortise. Fibular malunion results in altered ankle joint biomechanics which often leads to the development of pain, stiffness, and premature joint degeneration. Fortunately, many fibular malunions can be successfully salvaged using osteotomy techniques to restore anatomic fibular length and rotation. Different osteotomy techniques are indicated depending on the location and characteristics of the malunion. In this review, the oblique fibular osteotomy is described for the reconstruction of SER-type fibular fractures. For more proximal fibular malunion, the transverse osteotomy technique with lengthening and structural bone graft is reviewed. Level of Evidence: Level V, expert opinion.