bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Selection and Volume in the Era Surrounding Implementation of Medicare Conditions of Participation for Transplant Programs
Authors: White Sarah L. , Zinsser Dawn M. , Paul Matthew , Levine Gregory N. , Shearon Tempie , Ashby Valarie B. , Magee John C. , Li Yi , Leichtman Alan B. 
Published: May 2014

ObjectiveTo evaluate evidence of practice changes affecting kidney transplant program volumes, and donor, recipient and candidate selection in the era surrounding the introduction of Centers for Medicare and Medicaid Services (CMS) conditions of participation (CoPs) for organ transplant programs.DataScientific Registry of Transplant Recipients; CMS ESRD and Medicare claims databases.DesignRetrospective analysis of national registry data.MethodsA Cox proportional hazards model of 1‐year graft survival was used to derive risks associated with deceased‐donor kidney transplants performed from 2001 to 2010.FindingsAmong programs with ongoing noncompliance with the CoPs, kidney transplant volumes declined by 38 percent (n = 766) from 2006 to 2011, including a 55 percent drop in expanded criteria donor transplants. Volume increased by 6 percent (n = 638) among programs remaining in compliance. Aggregate risk of 1‐year graft failure increased over time due to increasing recipient age and obesity, and longer ESRD duration.ConclusionsAlthough trends in aggregate risk of 1‐year kidney graft loss do not indicate that the introduction of the CoPs has systematically reduced opportunities for marginal candidates or that there has been a systematic shift away from utilization of higher risk deceased donor kidneys, total volume and expanded criteria donor utilization decreased overall among programs with ongoing noncompliance.
ERK1/2 participates in regulating the expression and distribution of tight junction proteins in the process of reflux esophagitis
Authors: Tan Jia Cheng , Cui Wen Xia , Heng Ding , Lin Lin 
Published: May 2014

ObjectiveTo investigate the alterations of esophageal epithelial barrier during the process of reflux esophagitis (RE).MethodsIn total, 85 Sprague‐Dawley rats were randomly divided into two groups, the sham‐operation group (n = 25) and the RE group induced by incomplete pyloric ligation (n = 60). The establishment of RE model and the severity of esophagitis were evaluated by hematoxylin and eosin stain. Dilated intercellular spaces (DIS) in the esophageal epithelium were observed by transmission electron microscopy. The cellular distributions of ZO‐1, occludin and claudin‐1 were assessed by immunohistochemical stain. The expressions of these tight junction (TJ) proteins and the phosphorylation of extracellular signal‐regulated kinase 1/2 (ERK1/2), myosin light chain (MLC) and nonmuscular myosin light chain kinase (nmMLCK) were analyzed by Western blot.ResultsDIS occurred gradually in the RE group. ZO‐1, occludin and claudin‐1 were incompletely or even not expressed in the RE group. TJ proteins were expressed in the membrane instead of the cytoplasm in many epithelial cells in RE. With Western, the expression of ZO‐1, occludin and claudin‐1 was increased gradually in the RE group (P < 0.05). The phosphorylation levels of nmMLCK, MLC and ERK1/2 were also increased (P < 0.05). There was no marked changes in the esophageal epithelium in the sham‐operation group.ConclusionsTJ proteins could be used as sensitive markers of RE instead of DIS. ERK1/2 may participate in regulating TJ proteins in esophageal epithelia in RE.
The room temperature preservation of filtered environmental DNA samples and assimilation into a phenol–chloroform–isoamyl alcohol DNA extraction
Authors: Renshaw Mark A. , Olds Brett P. , Jerde Christopher L. , McVeigh Margaret M. , Lodge David M. 
Published: May 2014

AbstractCurrent research targeting filtered macrobial environmental DNA (eDNA) often relies upon cold ambient temperatures at various stages, including the transport of water samples from the field to the laboratory and the storage of water and/or filtered samples in the laboratory. This poses practical limitations for field collections in locations where refrigeration and frozen storage is difficult or where samples must be transported long distances for further processing and screening. This study demonstrates the successful preservation of eDNA at room temperature (20 °C) in two lysis buffers, CTAB and Longmire's, over a 2‐week period of time. Moreover, the preserved eDNA samples were seamlessly integrated into a phenol–chloroform–isoamyl alcohol (PCI) DNA extraction protocol. The successful application of the eDNA extraction to multiple filter membrane types suggests the methods evaluated here may be broadly applied in future eDNA research. Our results also suggest that for many kinds of studies recently reported on macrobial eDNA, detection probabilities could have been increased, and at a lower cost, by utilizing the Longmire's preservation buffer with a PCI DNA extraction.
Population pharmacokinetic−pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post‐transplant period
Authors: Dong Min , Fukuda Tsuyoshi , Cox Shareen , de Vries Marij T. , Hooper David K. , Goebel Jens , Vinks Alexander A. 
Published: May 2014

AimThe purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK−PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post‐transplant period.MethodsA total of 214 MPA plasma concentrations−time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK−PD modelling. The PK−PD model was developed using non‐linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK−PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co‐medication and clinical laboratory data. Non‐parametric bootstrapping and prediction‐corrected visual predictive checks were performed to evaluate the final models.ResultsA two compartment model with a transit compartment absorption best described MPA PK. A non‐linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h−1 70 kg−1; Vc/F, 45.4 (29.6, 55.6) l; Vp/F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h−1; Ka, 2.5 (1.45, 4.93) h−1. Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK−PD parameter estimates (and their 95% confidence intervals) were: E0, 3.45 (2.61, 4.56) nmol h−1 mg−1 protein and EC50, 1.73 (1.16, 3.01) mg l−1. Emax was fixed to 0. There were two African‐American patients in our study cohorts and both had low IMPDH baseline activities (E0) compared with Caucasian patients (mean value 2.13 mg l−1 vs. 3.86 mg l−1).ConclusionAn integrated population PK−PD model of MPA has been developed in paediatric renal transplant recipients. The current model provides information that will facilitate future studies and may be implemented in a Bayesian algorithm to allow a PK−PD guided therapeutic drug monitoring strategy.
Progress in central nervous system lymphomas
Authors: Wang Chia‐Ching , Carnevale Julia , Rubenstein James L. 
Published: May 2014

SummaryUntil recently, primary central nervous system lymphoma (PCNSL) was associated with a uniformly dismal prognosis. It is now reasonable to anticipate long‐term survival and possibly cure for a significant proportion of patients diagnosed with PCNSL. Accumulated data generated over the past 10 years has provided evidence that long‐term progression‐free survival (PFS) can reproducibly be attained in a significant fraction of PCNSL patients that receive dose‐intensive chemotherapy consolidation, without whole brain radiotherapy. One consolidative regimen that has reproducibly demonstrated promise is the combination of infusional etoposide plus high‐dose cytarabine (EA), administered in first complete remission after methotrexate, temozolomide and rituximab‐based induction. Given evolving principles of management and the mounting evidence for reproducible improvements in survival rates in prospective clinical series, our goal in this review is to highlight and update principles in diagnosis, staging and management as well as to review data regarding the pathogenesis of central nervous system lymphomas, information that is likely to constitute a basis for the implementation of novel therapies that are requisite for further progress in this unique phenotype of non‐Hodgkin lymphoma.
Phase II study of zoledronic acid combined with docetaxel for non‐small‐cell lung cancer: West Japan Oncology Group
Authors: Murakami Haruyasu , Yamanaka Takeharu , Seto Takashi , Sugio Kenji , Okamoto Isamu , Sawa Toshiyuki , Hirashima Tomonori , Takeda Koji , Atagi Shinji , Fukuoka Masahiro , Nakanishi Yoichi , Nakagawa Kazuhiko , Yamamoto Nobuyuki 
Published: May 2014

The aim of this open‐label, multicenter, randomized phase II trial was to evaluate the efficacy and safety of zoledronic acid in combination with docetaxel in previously treated patients with non‐small‐cell lung cancer (NSCLC) and bone metastases. In this study, patients randomly received docetaxel (60 mg/m2) with (group DZ) or without (group D) zoledronic acid every 21 days. There were 50 patients in each group, and the primary endpoint was progression‐free survival. In an efficacy analysis of 94 patients (DZ, 48; D, 46), the median progression‐free survival was 2.7 months (95% confidence interval [CI], 1.5–3.5 months) for the DZ group and 2.6 months (95% CI, 1.5–3.4 months) for the D group (stratified log‐rank test, P = 0.89). The median overall survival was 10.4 months (95% CI, 7.0–15.8 months) for the DZ group and 9.7 months (95% CI, 6.1–12.5 months) for the D group (stratified log‐rank test, P = 0.62). There were no clinically relevant differences in the frequencies of grade 3 or 4 adverse events between the two groups. No treatment‐related deaths occurred in the DZ group. Zoledronic acid combined with docetaxel was well tolerated but did not meet the primary endpoint of demonstrating a longer progression‐free survival in advanced NSCLC patients with bone metastases compared with docetaxel alone. This trial was registered with the University Hospital Medical Information Network (UMIN000001098).
Procognitive Properties of Drugs with Single and Multitargeting H3 Receptor Antagonist Activities
Authors: Nikolic Katarina , Filipic Slavica , Agbaba Danica , Stark Holger 
Published: May 2014

SummaryThe histamine H3 receptor (H3R) is an important modulator of numerous central control mechanisms. Novel lead optimizations for H3R antagonists/inverse agonists involved studies of structure–activity relationships, cross‐affinities, and pharmacokinetic properties of promising ligands. Blockade of inhibitory histamine H3 autoreceptors reinforces histaminergic transmission, while antagonism of H3 heteroreceptors accelerates the corticolimbic liberation of acetylcholine, norepinephrine, glutamate, dopamine, serotonin and gamma‐aminobutyric acid (GABA). The H3R positioned at numerous neurotransmission crossroads indicates therapeutic applications of small‐molecule H3R modulators in a number of psychiatric and neurodegenerative diseases with various clinical candidates available. Dual target drugs displaying H3R antagonism/inverse agonism with inhibition of acetylcholine esterase (AChE), histamine N‐methyltransferase (HMT), or serotonin transporter (SERT) are novel class of procognitive agents. Main chemical diversities, pharmacophores, and pharmacological profiles of procognitive agents acting as H3R antagonists/inverse agonists and dual H3R antagonists/inverse agonists with inhibiting activity on AChE, HMT, or SERT are highlighted here.
Vagomimetic Effects of Fingolimod: Physiology and Clinical Implications
Authors: Vanoli Emilio , Pentimalli Francesco , Botto Gianluca 
Published: May 2014

SummaryFingolimod is a sphingosine 1‐phosphate (S1P) receptor modulator approved to treat relapsing‐remitting multiple sclerosis (MS). Initiation of treatment with fingolimod has been found to produce transient bradycardia and/or slowing of atrioventricular impulse conduction in a small proportion of patients. This effect is thought to be due to the interaction of fingolimod with S1P receptors on the surface membrane of atrial myocytes causing a vagomimetic effect, similar to the action of acetylcholine on muscarinic receptors. As a precaution, patients are under electrocardiogram (ECG) monitoring for 6 h after receiving their first dose. Fingolimod is contraindicated in patients with overt or concealed cardiac diseases. However, the Fingolimod Initiation and caRdiac Safety Trial (FIRST), which was designed specifically to investigate the cardiac profile of fingolimod, did not show an increased risk of clinically relevant cardiac events with fingolimod. This review examines the electrophysiology and pathophysiology of cardiac impulse formation in the context of fingolimod. It concludes that these vagomimetic effects should be considered benign and should not prevent the effective use of fingolimod in the treatment of patients withMS.
Modeling Mental Spatial Reasoning About Cardinal Directions
Authors: Schultheis Holger , Bertel Sven , Barkowsky Thomas 
Published: May 2014

AbstractThis article presents research into human mental spatial reasoning with orientation knowledge. In particular, we look at reasoning problems about cardinal directions that possess multiple valid solutions (i.e., are spatially underdetermined), at human preferences for some of these solutions, and at representational and procedural factors that lead to such preferences. The article presents, first, a discussion of existing, related conceptual and computational approaches; second, results of empirical research into the solution preferences that human reasoners actually have; and, third, a novel computational model that relies on a parsimonious and flexible spatio‐analogical knowledge representation structure to robustly reproduce the behavior observed with human reasoners.
Agents and Causes: Dispositional Intuitions As a Guide to Causal Structure
Authors: Mayrhofer Ralf , Waldmann Michael R. 
Published: May 2014

AbstractCurrently, two frameworks of causal reasoning compete: Whereas dependency theories focus on dependencies between causes and effects, dispositional theories model causation as an interaction between agents and patients endowed with intrinsic dispositions. One important finding providing a bridge between these two frameworks is that failures of causes to generate their effects tend to be differentially attributed to agents and patients regardless of their location on either the cause or the effect side. To model different types of error attribution, we augmented a causal Bayes net model with separate error sources for causes and effects. In several experiments, we tested this new model using the size of Markov violations as the empirical indicator of differential assumptions about the sources of error. As predicted by the model, the size of Markov violations was influenced by the location of the agents and was moderated by the causal structure and the type of causal variables.
Performance of EGFR mutant‐specific antibodies in different cytological preparations: a validation study
Authors: Bellevicine C. , Bianco A. , Malapelle U. , De Luca C. , Vigliar E. , Cacciola N. A. , Pallante P. , Troncone G. 
Published: May 2014

ObjectivesMolecular testing for epidermal growth factor receptor (EGFR) mutations is required to select the most appropriate treatment for advanced‐stage non‐small cell lung cancer (NSCLC). In routine practice, cytological samples are often the only specimens available for testing. When the number of neoplastic cells is large, DNA‐based assays are the gold standard. When cytological samples contain only a few neoplastic cells, immunocytochemistry (ICC) using anti‐EGFR mutant‐specific antibodies may be more effective. We aim to assess the specificity and sensitivity of IHC staining in cytological specimens using mutated cell lines subjected to different cytopreparations and staining methods.MethodsHCC827 (exon 19 p.E746‐A750 del) and H3255 (exon 21 p.L858R) cell lines were subjected to different fixation (air dried, alcohol or CytoLyt®), staining (Diff‐Quik® or Papanicolaou) and preparation (smears or cell blocks) methods before ICC. In a second set of experiments, mutated cells were mixed with EGFR wild‐type cells to obtain low‐level (10%) mutated cytological samples. The intensity and percentage of cells stained were evaluated against validated molecular techniques. Moreover, the cell lines were subjected to poor growing conditions to simulate routine specimens that are less optimal than in vitro samples.ResultsThe cytological preparations showing the most intense staining were formalin‐fixed cell blocks and samples fixed with CytoLyt or alcohol, including Papanicolaou‐destained samples. Conversely, air‐dried slides showed the least intense staining. Mutant antibodies allowed the detection of mutated cells, even when representing only 10% of the total population. Although, in necrotic specimens, an aspecific background signal appeared, the viable cells still retained anti‐mutant EGFR positivity.ConclusionsAll cytological preparations are suitable for ICC using anti‐EGFR mutant‐specific antibodies, in particular formalin‐fixed cell blocks and alcohol‐ or CitoLyt‐fixed samples. the method is also validated to detect even a few mutant cells in less than optimal samples.
Mucosal healing of ileal lesions is associated with long‐term clinical remission after infliximab maintenance treatment in patients with Crohn's disease
Authors: Beppu Takahiro , Ono Yoichiro , Matsui Toshiyuki , Hirai Fumihito , Yano Yutaka , Takatsu Noritaka , Ninomiya Kazeo , Tsurumi Kozue , Sato Yuho , Takahashi Haruhiko , Ookado Yuuki , Koga Akihiro , Kinjo Ken , Nagahama Takashi , Hisabe Takashi , Takaki Yasuhiro , Yao Kenshi 
Published: May 2014

Background and AimThe aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients.MethodsThis study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow‐up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long‐term follow up, correlations between mucosal healing and long‐term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated.ResultsIleal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long‐term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044).ConclusionsComplete mucosal healing after 1–2 years was a predictive factor for long‐term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long‐term prognosis of Crohn's disease patients.
Reducing an in‐group bias in preschool children: the impact of moral behavior
Authors: Hetherington Chelsea , Hendrickson Caroline , Koenig Melissa 
Published: May 2014

AbstractHow impressionable are in‐group biases in early childhood? Previous research shows that young children display robust preferences for members of their own social group, but also condemn those who harm others. The current study investigates children's evaluations of agents when their group membership and moral behavior conflict. After being assigned to a minimal group, 4‐ to 5‐year‐old children either saw their in‐group member behave antisocially, an out‐group member act prosocially, or control agents, for whom moral information was removed. Children's explicit preference for and willingness to share with their in‐group member was significantly attenuated in the presence of an antisocial in‐group member, but not a prosocial out‐group member. Interestingly, children's learning decisions were unmoved by a person's moral behavior, instead being consistently guided by group membership. This demonstrates that children's in‐group bias is remarkably flexible: while moral information curbs children's in‐group bias on social evaluations, social learning is still driven by group information.
Competitive release modifies the impacts of hydrologic alteration for a partially migratory stream predator
Authors: Hartson Richard B. , Kennedy Brian P. 
Published: May 2014

AbstractUnderstanding ecological effects of altered stream flows is an essential objective. In a comparative field study of juvenile steelhead trout (Oncorhynchus mykiss) that compared natural‐ and reduced‐flow sites, we used mark–recapture modelling and information theory to quantify spatially and temporally explicit patterns of density, specific growth rate, survival and outmigration; and test predictions for biotic and abiotic drivers. Densities were lower in water withdrawal treatments, resulting in lower intraspecific competition and, higher specific growth rate and survival. We observed yearly differences in density and intraspecific competition, with a negative relationship between density and specific growth rate over a wide range of densities, but reductions in survival only at the highest densities. Moreover, individual variability within sites was important. At high density (sites and years), survival related negatively to body size. In contrast, when overall density was lower, specific growth rate was negatively related to body size. Lastly, individuals were more likely to outmigrate when they had larger body size, lower survival or reared in habitats with reduced flows, and these patterns appeared mediated by the intensity of intraspecific competition. Our results underscore the harsh bioenergetic conditions induced by higher temperatures and densities during summer baseflow (relative to other seasons), particularly for larger fish demanding more resources, and suggest a density‐dependent mechanism for why this period is important for regulating salmonid populations. We found that a complex combination of natural (e.g., density) and anthropogenic (e.g., withdrawal) factors affected juvenile salmon populations and life history expression in the face of altered flows.