bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death
Authors: Chen Christopher T. , Li Ling , Brooks Gabriel , Hassett Michael , Schrag Deborah 
Published: July 2017

ObjectiveTo characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer.Data Sources/Study Setting/Study Design2007–2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee‐for‐service claims.Data Collection/Extraction MethodsWe calculate per‐patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death.Principal FindingsOver the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis.ConclusionsCharacterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost‐effectiveness models.
Fatal Fat Embolism After Penis Enlargement by Autologous Fat Transfer: A Case Report and Review of the Literature
Authors: Zilg Brita , Råsten‐Almqvist Petra 
Published: July 2017

AbstractFat embolism is an incidental finding in cases of long bone fractures or other trauma, but it is also associated with liposuction and autologous fat transfer, a procedure where fat from liposuction is injected back into the same patient's face, breast, buttocks or penis. We here present a case of sudden death by fat embolism in a healthy young male, caused by a simple penis enlargement procedure, in which fat was injected into the penis shaft. We suggest that the risk of fat embolization might be higher when pretraumatized tissue is subjected to fat injection, like in this case, where a penis elongation was performed before the fat injection.
Microcatheter balloon pinning technique to facilitate wiring of a left circumflex chronic total occlusion
Authors: Oguayo Kevin N. , Oguayo Chris C. , Vallabhan Ravi , Choi James W. 
Published: July 2017

SummaryIntroductionCoronary chronic total occlusions (CTOs) are commonly encountered during diagnostic angiograms. With recent advances, especially in experienced centers, success rates with CTO percutaneous coronary intervention (PCI) have approached 80% or higher. It is important to note that despite these advancements in techniques, CTOs remain difficult to treat. We present a case of a left circumflex artery (LCX) CTO that was successfully revascularized using a microcatheter balloon pinning technique that allowed additional wire support.Case ReportA 77‐year‐old woman status post‐two‐vessel coronary artery bypass graft surgery presented with new onset angina at rest and was found to have a patent graft to the left anterior descending artery, and an unrevascularized proximal LCX CTO. PCI was attempted with a microcatheter using an antegrade approach. This approach was unsuccessful due to the lack of support and the left circumflex angle. As a result, we used a balloon to pin the microcatheter to the wall of the left main to allow for successful wiring of the LCX. A stent was successfully deployed in the LCX, and the patient was discharged from the hospital 2 days later. At follow‐up, the patient was asymptomatic and returned to her usual activity.DiscussionAfter conducting a thorough literature search, it appears that this is the first case that a microcatheter has been pinned with a balloon. We believe that in LCX CTOs that require support, the microcatheter pinning technique can provide adequate support in wiring CTO's. LCX CTOs can be very difficult to treat, we present a case of a LCX CTO that required the use of the microcatheter balloon pinning technique to allow additional wire support for successful wiring and ultimately treatment.
Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N‐acetyl‐ß‐D‐glucosaminidase
Authors: Lannemyr L. , Lundin E. , Reinsfelt B. , Bragadottir G. , Redfors B. , Oras J. , Ricksten S.‐E. 
Published: July 2017

BackgroundAcute kidney injury (AKI) is a common complication with a major impact on morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB). The aim of the present study was to perform a detailed analysis on the release of the tubular injury biomarker N‐acetyl‐b‐D‐glucosaminidase (NAG) during and early after CPB and to describe independent predictors of maximal tubular injury. We hypothesized that renal tubular injury occurs early after the onset of CPB.MethodsIn this prospective observational study, we included 61 patients undergoing open cardiac surgery with an expected CPB duration exceeding 60 min. The urinary NAG levels were measured at 30 min intervals during CPB, as well as early (30 min) after CPB and post‐operatively. Independent predictors of tubular injury were identified using an Interquantile multivariate regression model.ResultsAlready 30 min after the onset of CPB, NAG excretion was significantly increased (P < 0.001), followed by a sixfold peak increase after discontinuation of CPB (P < 0.001). In the multivariable regression model, CPB duration (P < 0.05) and the degree of rewarming during CPB (P < 0.05), were independent predictors of peak NAG excretion.ConclusionIn cardiac surgery, a renal tubular cell injury is seen early after onset of CPB with a peak biomarker increase early after end of CPB. The magnitude of this tubular injury is independently related to CPB duration and the degree of rewarming. Efforts made to decrease the CPB duration and to avoid hypothermia and the need for rewarming may decrease the risk for tubular injury.
Use of the Control of Allergic Rhinitis and Asthma Test and pulmonary function tests to assess asthma control in pregnancy
Authors: Amaral Luís , Martins Carla , Coimbra Alice 
Published: July 2017

IntroductionAsthma is one of the most prevalent chronic medical conditions to complicate pregnancy. Similarly, active management strategies that prioritise asthma control in this vulnerable population can have a far‐reaching impact.AimTo describe lung function parameters and results of the Control of Allergic Rhinitis and Asthma Test (CARAT) questionnaire in pregnant asthmatics and to analyse correlations between lung function tests and CARAT results.MethodsAll pregnant asthmatics who performed spirometry and CARAT between September 2014 and August 2015 were included. A medical records review was performed and data regarding demographics, sensitisation and medical prescriptions were recorded. Control of asthma and rhinitis was defined by CARAT total score (CARAT (T)) ≥ 24; upper airways (U) control if CARAT (U) > 8; lower airways (L) control if CARAT (L) > 15.ResultsForty‐two pregnant asthmatics were included, with a median age (interquartile range)of 32 (27–34) years; all had a previous medical diagnosis of asthma and rhinitis, 76% were atopic, 94% sensitised to dust mites and 43% were polissensitised. More than 80% presented poor control (CARAT (T) < 24) in the first assessment and 15% had a percentage forced expiratory volume in the first second < 80%. There were significant negative correlations between CARAT (L) and CARAT (T) scores and step‐up of controller medication, (correlation coefficients = −0.453 and −0.392, respectively).ConclusionThe use of tools such as spirometry and validated questionnaires to objectively assess asthma control during pregnancy should be routinely applied to assist in the management of these patients. These data reinforce the importance of close monitoring of pregnant asthmatics to achieve and maintain better disease control.
Factors related to recurrence of idiopathic granulomatous mastitis: what do we learn from a multicentre study?
Authors: Uysal Erdal , Soran Atilla , Sezgin Efe ,   Granulomatous Mastitis Study Group
Published: July 2017

BackgroundIdiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of the breast with unknown aetiology. Its treatment is controversial and the recurrence rate is high. The objectives of this study were to examine the demographic, sociocultural and clinical characteristics observed among a large cohort of IGM patients from Turkey and to identify factors related to the recurrence of IGM.MethodsThe study was designed as a multicentre retrospective study including 22 breast centres in Turkey. A total of 720 IGM patients are included in the study. Patient data were obtained from the patient's files and electronic records based on the study protocol. Patients’ demographic, clinical, radiological, treatment and recurrence of IGM related characteristics were recorded.ResultsOur results revealed a statistically significant association between IGM recurrence and history of pregnancy, breastfeeding, breast infection and smoking (P < 0.05). Having a chronic systematic disease, oral contraceptive, analgesic and herbal medicine consumptions, treatment choice, education, place of birth and current residence were not found to be associated with IGM recurrence (P > 0.05).ConclusionOur findings show that history of pregnancy, breastfeeding, breast infection and smoking were the risk factors for IGM recurrence. As current treatment methods did not affect IGM recurrence, recurrence‐related factors, such as breast infection and smoking, should be considered to eliminate while focusing on less invasive local treatment research.
Apelin‐induced cardioprotection against ischaemia/reperfusion injury: roles of epidermal growth factor and Src
Authors: Folino A. , Accomasso L. , Giachino C. , Montarolo P. G. , Losano G. , Pagliaro P. , Rastaldo R. 
Published: July 2017

AbstractAimApelin, the ligand of the G‐protein‐coupled receptor (GPCR) APJ, exerts a post‐conditioning‐like protection against ischaemia/reperfusion injury through activation of PI3K‐Akt‐NO signalling. The pathway connecting APJ to PI3K is still unknown. As other GPCR ligands act through transactivation of epidermal growth factor receptor (EGFR) via a matrix metalloproteinase (MMP) or Src kinase, we investigated whether EGFR transactivation is involved in the following three features of apelin‐induced cardioprotection: limitation of infarct size, suppression of contracture and improvement of post‐ischaemic contractile recovery.MethodIsolated rat hearts underwent 30 min of global ischaemia and 2 h of reperfusion. Apelin (0.5 μm) was infused during the first 20 min of reperfusion. EGFR, MMP or Src was inhibited to study the pathway connecting APJ to PI3K. Key components of RISK pathway, namely PI3K, guanylyl cyclase or mitochondrial K+‐ATP channels, were also inhibited. Apelin‐induced EGFR and phosphatase and tensing homolog (PTEN) phosphorylation were assessed. Left ventricular pressure and infarct size were measured.ResultsApelin‐induced reductions in infarct size and myocardial contracture were prevented by the inhibition of EGFR, Src, MMP or RISK pathway. The involvement of EGFR was confirmed by its phosphorylation. However, neither direct EGFR nor MMP inhibition affected apelin‐induced improvement of early post‐ischaemic contractile recovery, which was suppressed by Src and RISK inhibitors only. Apelin also increased PTEN phosphorylation, which was removed by Src inhibition.ConclusionWhile EGFR and MMP limit infarct size and contracture, Src or RISK pathway inhibition suppresses the three features of cardioprotection. Src does not only transactivate EGFR, but also inhibits PTEN by phosphorylation thus playing a crucial role in apelin‐induced cardioprotection.
Artificial infection of sheep with multiple strains ofDichelobacter nodosusto induce footrot
Authors: Allworth MB , Egerton JR 
Published: July 2017

ObjectivesTo establish multiple strains ofDichelobacter nodosusin two flocks of sheep and to assess the virulence of five of these strains.MethodsIn experiment 1, sheep were challenged with fiveD. nodosusstrains, which varied in both virulence and serotype. In experiment 2, consisting of four replicates (paddock groups), sheep were challenged with seven different strains ofD. nodosus. In experiment 3, sheep were challenged with one of fiveD. nodosusstrains.ResultsIn experiment 1, at 28 days post challenge, four of the five challenge strains were present. Multiple‐strain infections were present in 27 feet, with isolates from three serogroups being recovered from 5 feet, and four serogroups from 1 foot. Challenged hind feet were more frequently affected (P < 0.001). In experiment 2, four of the seven strains were recovered from one replicate and three strains from the remaining three replicates. Significantly more hind feet were affected (262/471, 55.6%) than front feet (198/481, 42%) (P < 0.001). Clinically, in both experiments 1 and 2 the footrot resembled an intermediate form, despite the inclusion of a virulent strain ofD. nodosus.In experiment 3, this virulent strain caused a higher prevalence of more severe footrot, a greater mean total foot score and, in Merino sheep, resulted in significantly lower weight gains (P < 0.05). Interaction betweenD. nodosusstrain and breed occurred, with Polwarth sheep being significantly more severely affected by one strain than Merino sheep.DiscussionThe clinical expression of multiple‐strain infections has implications for both research and control of footrot. A novel method of control is proposed.
Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy
Authors: Kitamura Hidemitsu , Ohno Yosuke , Toyoshima Yujiro , Ohtake Junya , Homma Shigenori , Kawamura Hideki , Takahashi Norihiko , Taketomi Akinobu 
Published: July 2017

Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)‐6, a pleiotropic cytokine, is highly produced in the tumor‐bearing host. Previous studies have indicated that IL‐6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL‐6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor‐infiltrating CD11b+CD11c+ cells isolated from colorectal cancer tissues showed strong induction of the IL‐6 gene, downregulated surface expression of human leukocyte antigen (HLA)‐DR, and an attenuated T cell‐stimulating ability compared with those from peripheral blood mononuclear cells, suggesting that the tumor microenvironment suppresses antitumor effector cells. In vitro experiments revealed that IL‐6‐mediated STAT3 activation reduced surface expression of HLA‐DR on CD14+ monocyte‐derived DC. Moreover, we confirmed that cyclooxygenase 2, lysosome protease and arginase activities were involved in the IL‐6‐mediated downregulation of the surface expression levels of HLA class II on human DC. These findings suggest that IL‐6‐mediated STAT3 activation in the tumor microenvironment inhibits functional maturation of DC to activate effector T cells, blocking introduction of antitumor immunity in cancers. Therefore, we propose in this review that blockade of the IL‐6/STAT3 signaling pathway and target molecules in DC may be a promising strategy to improve the efficacy of immunotherapies for cancer patients.
Prediction of Transporter‐Mediated Drug‐Drug Interactions for Baricitinib
Authors: Posada Maria M. , Cannady Ellen A. , Payne Christopher D. , Zhang Xin , Bacon James A. , Pak Y. Anne , Higgins J. William , Shahri Nazila , Hall Stephen D. , Hillgren Kathleen M. 
Published: July 2017

AbstractBaricitinib, an oral selective Janus kinase 1 and 2 inhibitor, undergoes active renal tubular secretion. Baricitinib was not predicted to inhibit hepatic and renal uptake and efflux drug transporters, based on the ratio of the unbound maximum eliminating‐organ inlet concentration and the in vitro half‐maximal inhibitory concentrations (IC50). In vitro, baricitinib was a substrate for organic anion transporter (OAT)3, multidrug and toxin extrusion protein (MATE)2‐K, P‐glycoprotein (P‐gp), and breast cancer resistance protein (BCRP). Probenecid, a strong OAT3 inhibitor, increased the area under the concentration‐time curve from time zero to infinity (AUC[0–∞]) of baricitinib by twofold and decreased renal clearance to 69% of control in healthy subjects. Physiologically based pharmacokinetic (PBPK) modeling reproduced the renal clearance of baricitinib and the inhibitory effect of probenecid using the in vitro IC50 value of 4.4 μM. Using ibuprofen and diclofenac in vitro IC50 values of 4.4 and 3.8 μM toward OAT3, 1.2 and 1.0 AUC(0–∞) ratios of baricitinib were predicted. These predictions suggest clinically relevant drug‐drug interactions (DDIs) with ibuprofen and diclofenac are unlikely.
Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis
Authors: Conrado Daniela J. , Nicholas Timothy , Tsai Kuenhi , Macha Sreeraj , Sinha Vikram , Stone Julie , Corrigan Brian , Bani Massimo , Muglia Pierandrea , Watson Ian A. , Kern Volker D. , Sheveleva Elena , Marek Kenneth , Stephenson Diane T. , Romero Klaus ,   on behalf of the Critical Path for Parkinson's (CPP) Parkinson's Disease Modeling and Simulation Working Group
Published: July 2017

AbstractGiven the recognition that disease‐modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient‐level longitudinal data of 672 subjects with early‐stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP‐1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed‐effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was –3.16 (90% confidence interval [CI] = –0.96 to –5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size.
Differences in brain morphology and working memory capacity across childhood
Authors: Bathelt Joe , Gathercole Susan E. , Johnson Amy , Astle Duncan E. 
Published: July 2017

AbstractWorking memory (WM) skills are closely associated with learning progress in key areas such as reading and mathematics across childhood. As yet, however, little is known about how the brain systems underpinning WM develop over this critical developmental period. The current study investigated whether and how structural brain correlates of components of the working memory system change over development. Verbal and visuospatial short‐term and working memory were assessed in 153 children between 5.58 and 15.92 years, and latent components of the working memory system were derived. Fractional anisotropy and cortical thickness maps were derived from T1‐weighted and diffusion‐weighted MRI and processed using eigenanatomy decomposition. There was a greater involvement of the corpus callosum and posterior temporal white matter in younger children for performance associated with the executive part of the working memory system. For older children, this was more closely linked with the thickness of the occipitotemporal cortex. These findings suggest that increasing specialization leads to shifts in the contribution of neural substrates over childhood, moving from an early dependence on a distributed system supported by long‐range connections to later reliance on specialized local circuitry. Our findings demonstrate that despite the component factor structure being stable across childhood, the underlying brain systems supporting working memory change. Taking the age of the child into account, and not just their overall score, is likely to be critical for understanding the nature of the limitations on their working memory capacity.
Modelling regional imbalances in English plebeian migration to late eighteenth‐century London†
Authors: Crymble Adam , Dennett Adam , Hitchcock Tim 
Published: July 2017

AbstractUsing a substantial set of vagrancy removal records for Middlesex (1777–86) giving details of the place of origin of some 11,500 individuals, and analysing these records using a five‐variable gravity model of migration, this article addresses a simple question: from which parts of England did London draw its lower‐class migrants in the late eighteenth century? It concludes, first, that industrializing areas of the north emerged as a competitor for potential migrants—contributing relatively fewer migrants than predicted by the model. Rising wage rates in these areas appear to explain this phenomenon. Second, it argues that migration from urban centres in the west midlands and parts of the West Country, including Bristol, Birmingham, and Worcester, was substantially higher than predicted, and that this is largely explained by falling wage rates and the evolution of an increasingly efficient travel network. Third, for the counties within about 130 kilometres of the capital, this article suggests that migration followed the pattern described in the current literature, with London drawing large numbers of local women in particular. It also argues that these short‐distance migrants came from a uniquely wide number of parishes, suggesting a direct rural‐to‐urban path.
Molecular dynamics simulation of crack initiation and propagation in bcc iron under load within spur gear tooth root
Authors: Zhao Z. , Chu F. 
Published: July 2017

AbstractSpur gears are widely used in practice, and one of their typical failures is tooth breakage. In general, the tooth breakage occurs at tooth root, and the amount of crack growth during a meshing cycle is in atomistic scale. This work aims at identifying the mechanisms of crack initiation and propagation at tooth root by using molecular dynamics simulation. The results prove that there are phase transition regions and edge dislocations at crack tips. According to the distribution characteristic of the atomic potential, its concentration can be observed obviously by visualization software. In these concentration regions, microvoids come into being and expand gradually, which results in the subcrack initiation. Additionally, the microvoids and subcracks propagate along the high potential direction and then come together to accelerate the crack growth. Through carrying out a comparative simulation, the effects of heavy load at single meshing area on crack initiation and propagation are addressed.