bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marginal Bayesian Nonparametric Model for Time to Disease Arrival of Threatened Amphibian Populations
Authors: Zhou Haiming , Hanson Timothy , Knapp Roland 
Published: July 2015

SummaryThe global emergence of Batrachochytrium dendrobatidis (Bd) has caused the extinction of hundreds of amphibian species worldwide. It has become increasingly important to be able to precisely predict time to Bd arrival in a population. The data analyzed herein present a unique challenge in terms of modeling because there is a strong spatial component to Bd arrival time and the traditional proportional hazards assumption is grossly violated. To address these concerns, we develop a novel marginal Bayesian nonparametric survival model for spatially correlated right-censored data. This class of models assumes that the logarithm of survival times marginally follow a mixture of normal densities with a linear-dependent Dirichlet process prior as the random mixing measure, and their joint distribution is induced by a Gaussian copula model with a spatial correlation structure. To invert high-dimensional spatial correlation matrices, we adopt a full-scale approximation that can capture both large- and small-scale spatial dependence. An efficient Markov chain Monte Carlo algorithm with delayed rejection is proposed for posterior computation, and an R package spBayesSurv is provided to fit the model. This approach is first evaluated through simulations, then applied to threatened frog populations in Sequoia-Kings Canyon National Park.
Synergistic effect of targeting the epidermal growth factor receptor and hyaluronan synthesis in oesophageal squamous cell carcinoma cells
Authors: Kretschmer I , Freudenberger T , Twarock S , Fischer J W 
Published: July 2015

Background and PurposeWorldwide, oesophageal cancer is the eighth most common cancer and has a very poor survival rate. In order to identify new tolerable treatment options for oesophageal squamous cell carcinoma (ESCC), erlotinib was tested with moderate efficacy in phase I and II studies. As 4‐methylumbelliferone (4‐MU), an hyaluronan (HA) synthesis inhibitor showed anti‐cancer effects in vitro, and in ESCC xenograft tumours, we investigated whether the anti‐cancer effects of erlotinib could be augmented by combining it with 4‐MU.Experimental ApproachESCC cell lines were treated with erlotinib or gefitinib (1 μmol·L−1) and 4‐MU (300 μmol·L−1), and the cell count, cell cycle progression and migration were determined as compared to the single agents and the solvent‐control.Key ResultsThe combination of erlotinib and 4‐MU synergistically inhibited the proliferation of ESCC cell lines. Furthermore, the migration speed of ESCC cell line KYSE‐410 in gap closure assays was significantly reduced by the combination of erlotinib and 4‐MU. Decreased ERK phosphorylation could explain the anti‐proliferative and anti‐migratory effects in the combined treatment group. Finally, the combination was additionally able to decrease the growth of multicellular tumour spheroids, a three‐dimensional cell culture model that was associated with sustained inhibition of ERK1/2 phosphorylation.Conclusions and ImplicationsThe combination of 4‐MU and erlotinib showed promising anti‐cancer efficacies in the ESCC cell lines.
Dysregulated post‐transcriptional control of COX‐2 gene expression in gestational diabetic endothelial cells
Authors: Di Francesco Luigia , Dovizio Melania , Trenti Annalisa , Marcantoni Emanuela , Moore Ashleigh , O'Gaora Peadar , McCarthy Cathal , Tacconelli Stefania , Bruno Annalisa , Alberti Sara , Gizzo Salvatore , Nardelli Giovanni Battista , Orso Genny , Belton Orina , Trevisi Lucia , Dixon Dan A , Patrignani Paola 
Published: July 2015

Background and PurposeHyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX‐2 expression in HUVEC in response to IL‐1β through the induction of long‐lasting epigenetic changes involving microRNA‐16 (miR‐16), a post‐transcriptional modulator of COX‐2 expression.Experimental ApproachStudies were performed on HUVEC collected from women with gestational diabetes mellitus (GDM) (dHUVEC) and normal women (nHUVEC).Key ResultsIn dHUVEC treated with IL‐1β, the expression of COX‐2 mRNA and protein was enhanced and generation of prostanoids increased (the most abundant was the promitogenic PGF2α). COX‐2 mRNA was more stable in dHUVEC and this was associated with miR‐16 down‐regulation and c‐Myc induction (a suppressor of miR expression). dHUVEC showed increased proliferation in response to IL‐1β, which was prevented by a COX‐2 inhibitor and PGF2α receptor antagonist. Comparable changes in COX‐2 mRNA, miR‐16 and c‐Myc detected in dHUVEC were produced in nHUVEC exposed to transient high glucose and then stimulated with IL‐1β under physiological glucose levels; superoxide anion production was enhanced under these experimental conditions.Conclusions and ImplicationsOur results describe a possible mechanism operating in GDM that links the enhanced superoxide anion production and epigenetic changes, associated with hyperglycaemic memory, to endothelial dysfunction through dysregulated post‐transcriptional control of COX‐2 gene expression in response to inflammatory stimuli. The association of conventional therapy for glycaemic control with agents affecting inflammatory responses and oxidative stress might lead to a more effective prevention of the complications associated with GDM.
Parent–adolescent relationship in youths with a chronic condition
Authors: Christin A. , Akre C. , Berchtold A. , Suris J. C. 
Published: July 2015

SummaryBackgroundSuffering from a chronic disease or disability (CDD) during adolescence can be a burden for both the adolescents and their parents. The aim of the present study is to assess how living with a CDD during adolescence, the quality of parent–adolescent relationship (PAR) and the adolescent's psychosocial development interact with each other.MethodsUsing the Swiss Multicenter Adolescent Survey on Health 2002 (SMASH02) database, we compared adolescents aged 16–20 years with a CDD (n = 760) with their healthy peers (n = 6493) on sociodemographics, adolescents' general and psychosocial health, interparental relationship and PAR.ResultsBivariate analyses showed that adolescents with a CDD had a poorer psychosocial health and a more difficult relationship with their parents.The log‐linear model indirectly linked CDD and poor PAR through four variables: two of the adolescents' psychosocial health variables (suicide attempt and sensation seeking), the need for help regarding difficulties with parents and a highly educated mother that acted as a protective factor, allowing for a better parent–adolescent with a CDD relationship.ConclusionIt is essential for health professionals taking care of adolescents with a CDD to distinguish between issues in relation with the CDD from other psychosocial difficulties, in order to help these adolescents and their parents deal with them appropriately and thus maintain a healthy PAR.
Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone children
Authors: Basha S , Pichichero M E 
Published: July 2015

Summary
We recently identified a cohort of children with recurrent episodes of acute otitis media (AOM) who fail to generate protective antibody titres to otopathogens and several vaccine antigens. In this study we determined the antibody levels against DTaP vaccine antigens, diphtheria toxoid (DT), tetanus toxoid (TT) and acellular pertussis toxoid (PT) in sera from 15 stringently defined otitis-prone (sOP) children and 20 non-otitis-prone (NOP) children. We found significantly lower concentrations of immunoglobulin (Ig)G antibodies against vaccine antigens in the serum of sOP children compared to age-matched NOP children. To elucidate immunological cellular responses to the vaccines in these children, we investigated memory B cell responses to DTaP vaccination. We used fluorescently conjugated vaccine antigens to label antigen receptors on the surface of memory B cells and examined the frequency of antigen-specific CD19+ CD27+ memory B cells in the peripheral blood. sOP children showed a significantly lower percentage of antigen-specific CD19+ CD27+ memory B cells than NOP children. We also found a linear correlation between the frequencies of memory B cells and circulating IgG titres for DT, TT and PT proteins. To our knowledge, this is the first study to show significant differences in memory B cell responses to DTaP vaccine antigens and their correlation with the circulating antibodies in young children with recurrent AOM.
Regulatory T cells and minimal change nephropathy: in the midst of a complex network
Authors: Bertelli R , Bonanni A , Di Donato A , Cioni M , Ravani P , Ghiggeri G M 
Published: July 2015

SummaryMinimal change nephrosis (MCN) is an important cause of morbidity in children. In spite of successful therapies having been developed in the last three decades, most aspects related to pathogenesis still remain poorly defined. Evolution in basic immunology and results deriving from animal models of the disease suggest a complex interaction of factors and cells starting from activation of innate immunity and continuing with antigen presentation. Oxidants, CD80 and CD40/CD40L have probably a relevant role at the start. Studies in animal models and in human beings also suggest the possibility that the same molecules (i.e. CD80, CD40) are expressed by podocytes under inflammatory stimuli, representing a direct potential mechanism for proteinuria. B and T cells could play a relevant role this contest. Implication of B cells is suggested indirectly by studies utilizing anti-CD20 monoclonal antibodies as the main therapy. The role of regulatory T cells (Tregs) is supported mainly by results in animal models of nephrotic syndrome (i.e. adriamycin, puromycin, lipopolysaccharide), showing a protective effect of direct Treg infusion or stimulation by interleukin 2 (IL-2). Limited studies have also shown reduced amounts of circulating Tregs in patients with active MCN cells. The route from bench to bedside would be reduced if results from animal models were confirmed in human pathology. The expansion of Tregs with recombinant IL-2 and new anti-CD20 monoclonal antibodies is the beginning. Blocking antigen-presenting cells with cytotoxic T lymphocyte antigen (CTLA-4)–Ig fusion molecules inhibiting CD80 and/or with blockers of CD40–CD40 ligand interaction represent potential new approaches. The hope is that evolution in therapies of MCN could fill a gap lasting 30 years.
New insight of functional molecular imaging into the atheroma biology: 18F‐NaF and 18F‐FDG in symptomatic and asymptomatic carotid plaques after recent CVA. Preliminary results
Authors: Quirce R. , Martínez‐Rodríguez I. , Banzo I. , Jiménez‐Bonilla J. , Martínez‐Amador N. , Ibáñez‐Bravo S. , López‐Defilló J. , Jiménez‐Alonso M. , Revilla M. A. , Carril J. M. 
Published: July 2015

SummaryAimThe identification of the vulnerable atheroma plaque could allow a more effective treatment of cerebrovascular accident (CVA). Active calcification and inflammation of the carotid atheroma were assessed and compared in symptomatic and asymptomatic plaques by 18F‐NaF and 18F‐FDG PET/CT.MethodsNine patients investigated for recent CVA and no preventive treatment with statins were enrolled. In each patient, at least one atheroma plaque was detected by CT angiogram. In total, 18 plaques were available: 9 symptomatic and 9 asymptomatic. 18F‐NaF uptake and 18F‐FDG uptake by each plaque were assessed visually and semiquantitatively by calculating target/background ratios (TBRs) and TBR indexes (TBR symptomatic/TBR asymptomatic and 18F‐NaF TBR/18F‐FDG TBR within each of the 2 clinical groups of plaques).ResultsAll plaques showed 18F‐NaF and 18F‐FDG uptake, and semiquantitation showed higher 18F‐NaF uptake by 11 of the 18 plaques, 6 symptomatic and 5 asymptomatic. In the symptomatic group, the mean 18F‐NaF TBR was 2·12 ± 0·44, and in the asymptomatic group, it was 1·85 ± 0·46. The 18F‐NaF/18F‐FDG showed that, overall, 18F‐NaF uptake is higher than 18F‐FDG. In the symptomatic plaques, the 18F‐NaF was higher for the low calcium content and the lowest for the high.ConclusionActive calcification and inflammation are simultaneous processes in the symptomatic and asymptomatic carotid atheroma. However, active calcification seems predominant over inflammation in both groups. In the symptomatic plaques, the highest 18F‐NaF uptake does not correspond with the largest calcium content. These patterns open new insights on the role of 18F‐NaF in the study of calcification and in the identification of the vulnerable carotid atheroma.
A diagnostic predicament: activated sarcoidosis or pulmonary histoplasmosis. A case report
Authors: Lingscheid Tilman , von Heinz Marie , Klages Birgit , Rickerts Volker , Tintelnot Kathrin , Gerhold Manuela , Oestmann Jörg‐Wilhelm , Becker Markus , Temmesfeld‐Wollbrück Bettina , Suttorp Norbert , Hübner Ralf‐Harto 
Published: July 2015

AbstractWe report a case of a 41‐year‐old man presenting with persisting fevers over 2 weeks. The patient had spent 4 weeks in Central America. He was in control of a stable stage II sarcoidosis. Laboratory and various microbiological tests as well as chest radiography led to no diagnosis. Activated sarcoidosis was hypothesized as the most likely diagnosis. However, we considered an infectious process as a differential diagnosis, in detail, the travel history imposed histoplasmosis. Chest‐CT documented localized interstitial consolidations. Bronchoscopy with bronchoalveolar lavage (BAL) and biopsy was performed. Results of BAL fluid, biopsy, distinct sarcoidosis serum markers and a borderline positive histoplasmosis‐serology yielded in a diagnostic dilemma as no distinct diagnosis was drawable. After the patient was already started on a prednisolone trial, the final diagnosis – pulmonary histoplasmosis – could be achieved via positive culture and PCR out of the BAL fluid. This case shows the difficult differentiation between an acute exacerbation of a chronic pulmonary disease and a concomitant infection, which was especially aggravated in this case as the histoplasmosis masqueraded an acute picture of sarcoidosis.
Computerized working memory training has positive long‐term effect in very low birthweight preschool children
Authors: Grunewaldt Kristine Hermansen , Skranes Jon , Brubakk Ann‐Mari , Lähaugen Gro C C 
Published: July 2015

AimWorking memory deficits are frequently found in children born preterm and have been linked to learning disabilities, and cognitive and behavioural problems. Our aim was to evaluate if a computerized working memory training program has long‐term positive effects on memory, learning, and behaviour in very‐low‐birthweight (VLBW) children at age 5 to 6 years.MethodThis prospective, intervention study included 20 VLBW preschool children in the intervention group and 17 age‐matched, non‐training VLBW children in the comparison group. The intervention group trained with the Cogmed JM working memory training program daily for 5 weeks (25 training sessions). Extensive neuropsychological assessment and parental questionnaires were performed 4 weeks after intervention and at follow‐up 7 months later. For most of the statistical analyses, general linear models were applied.ResultsAt follow‐up, higher scores and increased or equal performance gain were found in the intervention group than the comparison group on memory for faces (p=0.012), narrative memory (p=0.002), and spatial span (p=0.003). No group differences in performance gain were found for attention and behaviour.InterpretationComputerized working memory training seems to have positive and persisting effects on working memory, and visual and verbal learning, at 7‐month follow‐up in VLBW preschool children. We speculate that such training is beneficial by improving the ability to learn from the teaching at school and for further cognitive development.
Arteriosclerosis and vascular calcification: causes, clinical assessment and therapy
Authors: Tölle Markus , Reshetnik Alexander , Schuchardt Mirjam , Höhne Matthias , van der Giet Markus 
Published: July 2015

AbstractBackgroundArteriosclerosis is a pathological, structural (media vascular calcification) and physiological (modified vascular smooth vessel cells; increased arterial stiffness) alteration of the vessel wall. Through improved assessment methods (functional and imaging), it has become a well‐known phenomenon in recent decades. However, its clinical importance was underestimated until recently.Materials and methodsCurrently available English‐speaking data about conditions/diseases associated with arteriosclerosis, its clinical sequels, available diagnostic procedures and therapeutic modalities were reviewed and summarized.ResultsIn recent decades, emerging data have brought about a better understanding of causes and consequences of arteriosclerosis and highlight its growing clinical impact.ConclusionAlthough arteriosclerosis showed an independent clinical impact on cardiovascular morbidity and mortality, especially in patients with chronic kidney disease/end‐stage renal disease (CKD/ESRD) and diabetes mellitus, convincing clinical therapy concepts are not available until now. The establishment of novel therapeutic strategies derived from basic research is strongly needed.
Efficacy of phenytoin, valproic acid, carbamazepine and new antiepileptic drugs on control of late‐onset post‐stroke epilepsy in Taiwan
Authors: Huang Y.‐H. , Chi N.‐F. , Kuan Y.‐C. , Chan L. , Hu C.‐J. , Chiou H.‐Y. , Chien L.‐N. 
Published: July 2015

Background and purposeTo assess the efficacy of various antiepileptic drugs (AEDs) for controlling post‐stroke epilepsy.MethodsThis nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post‐stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan−Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs.ResultsIn all, 3622 late‐onset post‐stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person‐months based on ER visits [95% confidence interval (CI) 0.95–1.15] and hospitalizations (95% CI 0.62–0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person‐months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42–0.74; P < 0.001), 0.37 (95% CI 0.18–0.75; P = 0.006) and 0.28 (95% CI 0.15–0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results.ConclusionsThis large nationwide, population‐based study demonstrated that late‐onset post‐stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.
Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison
Authors: Alvarez Vincent , Lee Jong Woo , Drislane Frank W. , Westover M. Brandon , Novy Jan , Dworetzky Barbara A. , Rossetti Andrea O. 
Published: July 2015

SummaryObjectiveBenzodiazepines (BZD) are recommended as first‐line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date.MethodsWe identified all patients treated with CLZ, LZP, or MDZ as a first‐line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE.ResultsAmong 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66–15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8–10.49).SignificanceCLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice.
Time to get moving: assisted gene flow of forest trees
Authors: Aitken Sally N. , Bemmels Jordan B. 
Published: July 2015

AbstractGeographic variation in trees has been investigated since the mid‐18th century. Similar patterns of clinal variation have been observed along latitudinal and elevational gradients in common garden experiments for many temperate and boreal species. These studies convinced forest managers that a ‘local is best’ seed source policy was usually safest for reforestation. In recent decades, experimental design, phenotyping methods, climatic data and statistical analyses have improved greatly and refined but not radically changed knowledge of clines. The maintenance of local adaptation despite high gene flow suggests selection for local adaptation to climate is strong. Concerns over maladaptation resulting from climate change have motivated many new genecological and population genomics studies; however, few jurisdictions have implemented assisted gene flow (AGF), the translocation of pre‐adapted individuals to facilitate adaptation of planted forests to climate change. Here, we provide evidence that temperate tree species show clines along climatic gradients sufficiently similar for average patterns or climate models to guide AGF in the absence of species‐specific knowledge. Composite provenancing of multiple seed sources can be used to increase diversity and buffer against future climate uncertainty. New knowledge will continue to refine and improve AGF as climates warm further.