bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subsequent treatment of epidermal growth factor receptor‐tyrosine kinase inhibitor failure in patients with advanced lung adenocarcinoma
Authors: Qiao Xiaojuan , Zhang Ye , Wang Jinghui , Nong Jingying , Li Xi , Yang Xinjie , Lv Jialin , Zhang Hui , Qin Na , Zhang Quan , Yue Wentao , Zhang Shucai 
Published: February 2015

AbstractBackgroundEpidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) effectively treat advanced non‐small cell lung cancer with EGFR‐mutation. However, most patients develop acquired resistance without effective therapy subsequent to EGFR‐TKI failure. We evaluated the efficacy of subsequent treatment strategies for EGFR‐TKI resistance.MethodsWe retrospectively analyzed 240 patients with advanced lung adenocarcinoma with EGFR‐TKI failure and following subsequent treatment. According to the first subsequent strategies after EGFR‐TKI failure, patients were divided into groups of EGFR‐TKI continuation (21 cases), EGFR‐TKI continuation with chemotherapy (23 cases), chemotherapy alone (143 cases), and best supportive care (BSC) (53 cases).ResultsExcept for 53 cases of BSC, the disease control rates (DCR) of the remaining 187 patients in the EGFR‐TKI continuation, EGFR‐TKI continuation with chemotherapy, and chemotherapy alone groups were 66.7%, 73.9%, and 44.8%, respectively. The median post‐progression progression‐free survival (PFS) for the three groups was 3.0, 3.3, and 2.0 months, respectively. The DCR for the EGFR‐TKI continuation with chemotherapy group was significantly higher than the chemotherapy alone group (P = 0.006). The post‐progression PFS of the EGFR‐TKI continuation with chemotherapy group was significantly longer than the chemotherapy alone group (P = 0.037). The median overall survival in the EGFR‐TKI continuation, EGFR‐TKI continuation with chemotherapy, chemotherapy alone, and BSC groups were 6.9, 11.6, 8.8, and 0.9 months, respectively. Compared to the BSC group, all groups achieved a survival benefit (P < 0.001).ConclusionsEGFR‐TKI continuation with chemotherapy could provide benefits for patients with acquired resistance to EGFR‐TKI.
Activated estrogen receptor‐mitogen‐activated protein kinases cross talk confer acquired resistance to lapatinib
Authors: Li Zhe , Yang Sheng‐Sheng , Yin Pei‐Hao , Chang Tao , Shi Lin‐Xiang , Fang Lin , Fang Guo‐En 
Published: February 2015

AbstractBackgroundThe efficacy of lapatinib is limited by the development of acquired resistance. The aim of this study was to investigate the role of estrogen receptor (ER) signaling compensatory activation in acquired resistance to lapatinib in breast cancer cells BT474 and the related mechanism.MethodsAcquired resistant cell model resistant (r)BT474 was generated with an increasing concentration of lapatinib. Real‐time polymerase chain reaction and Western blotting were used to determine the changes of human epidermal growth factor receptor (HER)2 and ER pathways in breast cancer cell BT474 after treatment with lapatinib and the distinction between BT474 and rBT474. Methyl thiazolyl tetrazolium and colony formation assays were employed to detect the proliferation of rBT474 and BT474 cells treated with lapatinib and/or an ER inhibitor, fulvestrant, respectively.ResultsLapatinib could inhibit phosphorylation of HER2 and induce expression of forkhead‐box protein O3a and progesterone receptor. Acquired resistant cell model rBT474 could grow in the presence of 5 μM lapatinib, with an apoptosis rate of only 5%. Significant inhibition of phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (AKT) pathway and the activation of the mitogen‐activated protein kinases (MAPK) and ER pathways were detected in rBT474, compared with BT474. Furthermore, the expressions of Src phosphorylation and caveolin‐1 were also upregulated. The viability of rBT474 was markedly suppressed by the lapatinib/fulvestrant combination in vitro, confirmed by the BT474 xenograft model.ConclusionER signaling compensatory activation may partly contribute to lapatinib acquired resistance in HER2‐overexpressing/ERα‐positive breast cancer cells, which might be related to PI3K/AKT inhibition and MAPK pathway activation.
Use of Prestudy Heparin Did Not Influence the Efficacy and Safety of Rivaroxaban in Patients Treated for Symptomatic Venous Thromboem‐bolism in the EINSTEIN DVT and EINSTEIN PE Studies
Authors: Prandoni Paolo , Prins Martin H. , Cohen Alexander T. , Müller Katharina , Pap Ákos F. , Tewes Miriam C. , Lensing Anthonie W. A. 
Published: February 2015

AbstractObjectivesIn the EINSTEIN DVT and EINSTEIN PE studies, the majority of patients received heparins to bridge the period during venous thromboembolism (VTE) diagnosis confirmation and the start of the study. In contrast to vitamin K antagonists (VKAs), rivaroxaban may not require initial heparin treatment.MethodsTo evaluate the effect of prestudy heparin on the efficacy and safety of rivaroxaban relative to enoxaparin/VKA, the 3‐month incidence of recurrent VTE, and the 14‐day incidence of major and nonmajor clinically relevant bleeding were compared in patients who did and did not receive prestudy heparin.ResultsOf the 8,281 patients randomized, 6,937 (83.8%) received prestudy heparin (mean ± SD duration = rivaroxaban: 1.04 [± 0.74] days; enoxaparin 1.03 [± 0.42] days), and 1,344 (16.2%) did not. In patients who did not receive prestudy heparin, the incidences of recurrent VTE were similar in rivaroxaban (15 of 649, 2.3%) and enoxaparin/VKA (13 of 695, 1.9%) patients (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 0.52 to 2.37). The incidences of recurrent VTE were also similar in rivaroxaban (54 of 3,501, 1.5%) and enoxaparin/VKA (69 of 3,436, 2.0%) patients who did receive prestudy heparin (adjusted HR = 0.74; 95% CI = 0.52 to 1.06; pinteraction = 0.32). The incidences of major or nonmajor clinically relevant bleeding with rivaroxaban were not significantly different from those with enoxaparin/VKA, either with (105 of 3,485, 3.0% vs. 104 of 3,428, 3.0%; adjusted HR = 0.98; 95% CI = 0.75 to 1.29) or without (24 of 645, 3.7% vs. 30 of 688, 4.4%; adjusted HR = 0.81; 95% CI = 0.46 to 1.40; pinteraction = 0.68) prestudy heparin.ConclusionsAlthough the majority of patients in the EINSTEIN studies received prestudy heparin, there were no notable differences in treatment effect of rivaroxaban versus enoxaparin/VKA in those who did and did not receive it.
The Development and Validation of Hand Motion Analysis to Evaluate Competency in Central Line Catheterization
Authors: Clinkard David , Holden Matthew , Ungi Tamas , Messenger David , Davison Colleen , Fichtinger Gabor , McGraw Robert 
Published: February 2015

AbstractObjectivesTraditionally, technical skills proficiency has been assessed by direct observation. While direct observation and feedback are essential components in technical skills learning, they demand considerable investment of faculty time, and as an assessment tool, direct observation is inherently subjective and has been criticized as unreliable. The purpose of this study was to determine if quantitative electromagnetic motion tracking is feasible and can discriminate between experts and nonexperts during simulated ultrasound (US)‐guided insertion of a central venous catheter (CVC) guidewire.MethodsTen nonexperts (junior emergency medicine residents) and 10 experts (critical care fellows or attending physicians) were recruited. Electromagnetic sensor probes were used to capture hand motion during an US‐guided internal jugular cannulation on a standardized manikin. Hand, US, and needle motion were analyzed for the following metrics: total path length, total time, translational movements, and rotational movements. Subjects were also videotaped and evaluated using a modified, validated global rating scale (GRS) by a blinded expert.ResultsThere was a significant difference in almost all examined motion parameters between experts and nonexperts. Experts took 66% less time (50.2 seconds vs. 148.7 seconds, p < 0.001) and had significantly less right‐hand and US motion (total path length and translational and rotational movements). Left‐hand total path length was the only parameter that was not significantly different between groups. Concurrent validity of motion parameters was established by strong correlations (r2 > 0.74) to a previously published, modified GRS.ConclusionsElectromagnetic hand and instrument motion analysis is technically feasible for assessing competence in US‐guided insertion of a CVC guidewire in a simulation setting. In showing that it discriminates between the performances of nonexperts and experts, this study has provided evidence for construct validity. It also shows excellent correlation with a modified version of a previously validated GRS, providing evidence of concurrent validity.
If a frog calls in the forest: Bioacoustic monitoring reveals the breeding phenology of the endangered Richmond Range mountain frog (Philoria richmondensis)
Authors: Willacy Rosalie J. , Mahony Michael , Newell David A. 
Published: February 2015

AbstractAmphibians are the most threatened vertebrate taxon of modern times. Baseline data and affordable methods to monitor populations are absent for many Australian frog species. Furthermore, some species are visually cryptic, and detection often relies upon male advertisement calls. Imperfect detection rates impede our ability to assess the status of populations over time. Understanding the factors that influence calling is essential to inform the timing of survey effort and increase survey efficiency. Automated recording systems offer considerable potential to determine calling phenology and establish the relationship between calling and abiotic factors. The mountain frogs (Philoria Myobatrachidae) of the Gondwana rainforests are considered susceptible to climate change impacts, such as shifts in the timing of calling. In order to describe the calling phenology of Philoria richmondensis, commercially available automated recording systems were deployed at five locations, and over 5000 h of sound recordings were captured and analysed. Peak calling activity occurred during morning and evening periods in the austral spring. Ambient temperature was found to significantly contribute to the probability of a call occurring, with the highest frequency of calls recorded occurring between 15°C and 16°C, and there was a negative relationship between precipitation and calling activity. The results allow future surveys to be better targeted and provide a benchmark with which to detect changes in calling phenology over time.
Doing Good and Doing Well: Prairie Wetlands, Private Property, and the Public Trust
Authors: Gewertz Deborah , Errington Frederick 
Published: February 2015

ABSTRACTIn this article, we focus on a gift of land and its restoration. The land is a 300‐acre lakeside family farm near Brookings, South Dakota. We gave this farm to the United States Fish and Wildlife Service in 2012 to be taken from cropland and restored to prairie wetland—and at a time when high commodity prices are encouraging many farmers to do precisely the opposite, albeit not without challenge. Our intent is to explore a range of critical values—values apparent under conditions of conflict—as they have been playing out in this portion of the U.S. heartland. By going against the grain of contemporary agricultural practice, we have inserted ourselves into this conflict and have become strategically placed to contribute ethnographically to ongoing anthropological, philosophical, and environmental discussions of what nature is worth, to whom (in the past, present, and future), and why. In so doing, we follow in the footsteps of Lewis Henry Morgan and Aldo Leopold, both of whom pondered similar issues in similar places.
Designer steroids – over‐the‐counter supplements and their androgenic component: review of an increasing problem
Authors: Rahnema C. D. , Crosnoe L. E. , Kim E. D. 
Published: February 2015

SummaryColloquially referred to by various misleading monikers (‘pro‐hormones’, ‘natural steroids’, ‘testosterone boosters’, etc.) designer anabolic steroids have been popular now for over a decade as a way to achieve classic anabolic steroid‐like results from products sold in the legal marketplace. Recent evidence suggests that anabolic steroid use may be the most common cause of hypogonadism in men of reproductive age. Despite recent regulatory efforts that have banned specific compounds, many anabolic‐androgenic steroids (AAS) remain available in over‐the‐counter dietary supplements that are legally sold in the United States. Severe side effects including hepatotoxicity, cholestasis, renal failure, hypogonadism, gynecomastia, and infertility have been reported secondary to the use of these products. While some of these side effects may be reversible, more aggressive use may result in more permanent end‐organ damage as has been previously described for the case of aggressive AAS users (Rahnema et al., Fertil Steril, 2014). Designer AAS remain easily available for purchase in over‐the‐counter bodybuilding supplements and these products appear to be increasingly popular, despite the known health risks associated with their use. We conducted a systematic search to identify the designer steroids that are most commonly sold in dietary supplements as of April 2014 and review what is known regarding their potency and toxicity. We propose that the impact of AAS use on the reproductive and hormonal health of men is underestimated in the literature owing to previous studies’ failure to account for designer steroid use. Lastly, we make clinical recommendations to help physicians steer patients away from potentially harmful supplements, and summarize key regulatory obstacles that have allowed potent androgens to remain unregulated in the legal marketplace.
Fetal pelvic index to predict cephalopelvic disproportion – a retrospective clinical cohort study
Authors: Korhonen Ulla , Taipale Pekka , Heinonen Seppo 
Published: February 2015

AbstractObjectiveTo investigate the diagnostic accuracy of the fetal pelvic index to predict cephalopelvic disproportion.DesignRetrospective observational cohort study.SettingPregnant women who had been examined by X‐ray or magnetic resonance imaging pelvimetry because of an increased risk of fetal–pelvic disproportion during 2000–2008 in North Karelia Central Hospital.PopulationA total of 274 pregnant women.MethodsUnivariable and multivariable regression analyses were carried out to identify risk factors for cesarean section. Diagnostic accuracy was tested with a receiver operating characteristic curve, and the optimal cut‐off value for fetal pelvic index was calculated.Main outcome measureCesarean section rates.ResultsA total of 242 women delivered vaginally, and 32 delivered with cesarean section caused by labor arrest. In multivariable modeling, the fetal pelvic index, maternal pelvic inlet size, fetal head circumference and maternal age were significantly associated with a risk of cesarean section. In the receiver operating characteristic analysis, the area under curve was 0.686 with a p‐value of 0.001 and a 95% confidence interval of 0.595–0.778. The optimal fetal pelvic index cut‐off value according to the receiver operating characteristic was −0.65. The cesarean section rate was 8% below the fetal pelvic index value of −0.65 and 20% above the fetal pelvic index value of −0.65.ConclusionsThe fetal pelvic index was not a clinically useful tool to predict the mode of delivery for patients at high risk of cephalopelvic disproportion. The pooled analysis of the current and previous studies strengthened this conclusion.
The increasing incidence and prevalence of eosinophilic oesophagitis outpaces changes in endoscopic and biopsy practice: national population‐based estimates from Denmark
Authors: Dellon E. S. , Erichsen R. , Baron J. A. , Shaheen N. J. , Vyberg M. , Sorensen H. T. , Pedersen L. 
Published: February 2015

SummaryBackgroundNational population‐based medical registries in Denmark offer a unique opportunity to study eosinophilic oesophagitis (EoE) epidemiology.AimTo determine the incidence and prevalence of EoE in Denmark, and evaluate whether an increase in endoscopy with biopsy activity explains changes in these trends.MethodsThe Danish National Pathology Registry, Danish National Patient Registry and Danish Registry of Medicinal Product Statistics were queried from 1997 to 2012. Using an EoE case‐finding algorithm validated for Danish patients, EoE cases were identified during each year of the study period; we also identified all patients with oesophageal eosinophilia. Using the known population of Demark, the annual incidence and prevalence of EoE were determined. We also determined the number of oesophageal biopsies performed each year in Denmark, and compared the change in the incidence rate to the change in biopsy rate.ResultsBetween 1997 and 2012, 1708 patients had oesophageal eosinophilia, of whom 844 met the case definition of EoE. There were seven new cases of EoE in 1997 and 145 new cases in 2012, corresponding to a 19.5‐fold increase in incidence (0.13/100 000 to 2.6/100 000). There were 769 total cases in 2012 (prevalence of 13.8/100 000). Over the same time frame, the oesophageal biopsy rate increased only 1.9 fold, from 91.1/100 000 to 175.3/100 000.ConclusionsThe incidence and prevalence of EoE markedly increased in Denmark over the past 15 years. This increase far outpaced the increase in oesophageal biopsy utilisation, indicating that changes in the frequency of EoE are not due to changes in biopsy rates alone.
Usefulness of laparoscopic cholecystostomy in children with complicated choledochal cyst
Authors: Yamoto Masaya , Urushihara Naoto , Fukumoto Koji , Miyano Go , Nouso Hiroshi , Morita Keiichi , Miyake Hiromu , Kaneshiro Masakatsu , Koyama Mariko 
Published: February 2015

AbstractIntroductionIn children with choledochal cysts (CC), obstruction of the discharge of bile or pancreatic juice is frequently observed, and biliary perforation and severe pancreatitis may occur. In such cases, temporary drainage is necessary to stabilize these patients. We employed laparoscopic cholecystostomy followed by laparoscopic cyst excision in cases with complicated CC.MethodsBetween 2009 and 2013, emergency laparoscopic cholecystostomy for bile drainage was performed in seven girls with complicated CC in whom conservative treatment failed to ameliorate abdominal pain, vomiting, and jaundice; among these seven patients included two with biliary perforation, one with a huge cyst, and four with peribiliary edema suggestive of impending biliary rupture. Protein plugs in the common channel or the terminal portion of the cyst were present in six patients.ResultsAmelioration of symptoms, such as abdominal pain and jaundice, was achieved in all patients after laparoscopic cholecystostomy. Saline irrigation of the bile duct via cholecystostomy was commenced 2 days postoperatively. All patients underwent laparoscopic cyst resection after improvement of their general condition and detailed evaluation of the intrahepatic and extrahepatic bile ducts and pancreaticobiliary maljunction. Impacted protein plugs or gallstones were eliminated in all patients by the time of laparoscopic cyst excision.ConclusionLaparoscopic cholecystostomy followed by laparoscopic cyst excision is a useful and safe procedure for the treatment of complicated CC. This technique is also favorable from a cosmetic viewpoint because the resultant wound can be reused as the trocar insertion site at the time of laparoscopic cyst excision.
Findings from an ovine parasitological monitoring service provided by a rural veterinary practice in New South Wales, Australia
Authors: Kozaruk MK , Churchill R , Windsor PA 
Published: February 2015

ObjectiveTo describe an ovine parasitological monitoring service delivered by a rural veterinary practice and determine associations between flock, anthelmintic and monitoring factors and worm control.DesignRetrospective study of records from a rural veterinary practice in south‐eastern Australia over an 8.75‐year period.MethodsRecords of sheep producers using veterinary services for gastrointestinal parasite management from 1 August 2003 to 30 April 2012 were analysed. Results from pre‐ (FECt1) and post‐treatment faecal egg counts (FECt2) were used to identify factors influencing anthelmintic effectiveness, calculated as faecal egg count reduction percentage (FECR%) by linear mixed model analyses. The trends in anthelmintic merchandising and uptake of veterinary services for parasite management were determined by logistic regression analyses.ResultsFECR% varied according to the treatment group used (P < 0.001), with an apparent decreasing effectiveness of the macrocylic lactone group over the duration of the study (P = 0.008). Wether and ram flocks displayed lower FECR% than ewe flocks (P < 0.05). Time between FECt1 and treatment (P = 0.031), as well as time between treatment and FECt2 (P < 0.001), had a significant negative association with FECR%. The proportion of properties purchasing 4‐way combination anthelmintics increased significantly over the study period (P < 0.001), with declines observed in other anthelmintics (P < 0.05). The proportion of properties performing FECR% monitoring to those that purchased anthelmintics increased significantly over the study period (P = 0.001).ConclusionAnthelmintic treatment type, sex of the flock and time between drenching and testing had the greatest influence on drench effectiveness (FECR%). An increasing reliance on 4‐way combination drenches to manage gastrointestinal parasitism was demonstrated. Benefits of parasitological monitoring include: appropriate advice on parasitological management; observations on trends in regional anthelmintic usage; estimation of drench effectiveness; early indication of anthelmintic resistance; and improved service provision by the rural veterinary practice.
On Bayesian Estimation of Marginal Structural Models
Authors: Saarela Olli , Stephens David A. , Moodie Erica E. M. , Klein Marina B. 
Published: February 2015

SummaryThe purpose of inverse probability of treatment (IPT) weighting in estimation of marginal treatment effects is to construct a pseudo-population without imbalances in measured covariates, thus removing the effects of confounding and informative censoring when performing inference. In this article, we formalize the notion of such a pseudo-population as a data generating mechanism with particular characteristics, and show that this leads to a natural Bayesian interpretation of IPT weighted estimation. Using this interpretation, we are able to propose the first fully Bayesian procedure for estimating parameters of marginal structural models using an IPT weighting. Our approach suggests that the weights should be derived from the posterior predictive treatment assignment and censoring probabilities, answering the question of whether and how the uncertainty in the estimation of the weights should be incorporated in Bayesian inference of marginal treatment effects. The proposed approach is compared to existing methods in simulated data, and applied to an analysis of the Canadian Co-infection Cohort.