bluuebunny/crossref_metadata_2025_split huggingface dataset:
How we manage patients with hereditary haemochromatosis
Authors: Rombout‐Sestrienkova Eva , van Kraaij Marian G. J. , Koek Ger H. 
Published: October 2016

SummaryA number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment. Recent publications suggest that erythrocytapheresis, as a more individualized treatment, can provide a good balance between effectiveness, tolerability and costs. Other treatments like oral chelators and proton pomp inhibitors, which are used in selected patients, create the possibility to further individualize treatment of hereditary haemochromatosis. In the future, hepcidin‐targeted therapy could provide a more fundamental approach to treatment.
Multicentre, randomised phaseIIIstudy of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia
Authors: Yang Renchi , Li Junmin , Jin Jie , Huang Meijuan , Yu Ziqiang , Xu Xiaojun , Zhang Xiaohui , Hou Ming 
Published: October 2016

SummaryEltrombopag, a thrombopoietin receptor agonist, raises platelet counts and reduces bleeding in patients with immune thrombocytopenia (ITP). In Chinese patients, eltrombopag was evaluated at an initial dose of 25 mg, vs. 50 mg for non‐Asians, because the plasma exposure of eltrombopag is higher in East Asians. A multicentre, double‐blind, randomised, placebo‐controlled, 8‐week, phaseIIIstudy enrolled 155 patients with chronic, previously treatedITP. Dosage could be adjusted (25–75 mg/day) to maintain platelet counts 50–250 × 109/l. The primary efficacy endpoint was the proportion of patients with a platelet count ≥50 × 109/l after Day 42. Pharmacokinetics and pharmacodynamics of eltrombopag were analysed in an open‐label extension. After Day 42, 57·7% of eltrombopag‐treated and 6·0% of placebo‐treated patients achieved platelet counts ≥50 × 109/l. Odds of achieving a platelet count ≥50 × 109/l were 26·08 times greater with eltrombopag than placebo (P < 0·001). Compared with placebo, time to response and duration of response were better with eltrombopag (P < 0·001) and the odds of any bleeding were reduced by 72% (P = 0·001). Tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics were similar to previous findings in East Asian patients. In conclusion, in Chinese patients with chronicITP, eltrombopag 25 mg once daily, elevated platelet counts to a safe range and reduced bleeding.
Development of a stretch‐induced neurotrauma model for medium‐throughput screening in vitro: identification of rifampicin as a neuroprotectant
Authors: López‐García Isabel , Gerő Domokos , Szczesny Bartosz , Szoleczky Petra , Olah Gabor , Módis Katalin , Zhang Kangling , Gao Jungling , Wu Ping , Sowers Lawrence C , DeWitt Doug , Prough Donald S , Szabo Csaba 
Published: October 2016

Background and PurposeWe hypothesized that an in vitro, stretch‐based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma.Experimental ApproachWe screened three neural cell lines (B35, RN33B and SH‐SY5Y) subjected to two differentiation methods and selected all‐trans‐retinoic acid‐differentiated B35 rat neuroblastoma cells subjected to rapid stretch injury, coupled with a subthreshold concentration of H2O2, for the screen. The model induced marked alterations in gene expression and proteomic signature of the cells and culminated in delayed cell death (LDH release) and mitochondrial dysfunction [reduced 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) conversion]. Follow‐up studies utilized human stem cell‐derived neurons subjected to rapid stretch injury.Key ResultsFrom screening of a composite library of 3500 drugs, five drugs (when applied in a post‐treatment regimen relative to stretch injury) improved both LDH and MTT responses. The effects of rifampicin were investigated in further detail. Rifampicin reduced cell necrosis and apoptosis and improved cellular bioenergetics. In a second model (stretch injury in human stem cell‐derived neurons), rifampicin pretreatment attenuated LDH release, protected against the loss of neurite length and maintained neuron‐specific class III β‐tubulin immunoreactivity.Conclusions and ImplicationsWe conclude that the current model is suitable for medium‐throughput screening to identify compounds with neuroprotective potential. Rifampicin, when applied either in pre‐ or post‐treatment, improves the viability of neurons subjected to stretch injury and protects against neurite loss. Rifampicin may be a candidate for repurposing for the therapy of traumatic brain injury.Linked ArticlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Urbanizing physical geography
Authors: Ashmore Peter , Dodson Belinda 
Published: October 2016

The physical environment of cities and processes of urbanization have a long‐standing presence in the field of physical geography and can give physical geography a renewed relevance in urban sustainability and planning. Existing approaches in physical geography will be a valuable component of this work. New insights and understanding of urban environments may be gained by engaging with ideas of urban landscapes as socio‐natures; adopting critical, political, and reflexive modes of thought and practice; and thinking beyond the physical structures and spatial boundaries of the city to planetary urbanization. Thinking about urban environments in these ways also opens up possible changes in the scope of, and approaches to, physical geography as a whole.Urbaniser la géographie physiqueL'environnement physique des villes et les processus d'urbanisation sont des sujets bien établis dans le domaine de la géographie physique qui peuvent contribuer à assurer sa pertinence en regard du développement durable et de l'urbanisme. Les approches existantes en géographie physique constitueront un atout pour ce travail. De nouvelles connaissances sur les environnements urbains peuvent être obtenues en partant de l'idée que les paysages urbains sont une construction socio‐naturelle ; en adoptant une perspective critique, politique et réflexive des cadres de pensée et d'action ; et en posant un regard sur l'urbanisation planétaire au‐delà des structures physiques et des limites territoriales de la ville. Cette façon de concevoir les environnements urbains permet d'accroître la portée et de modifier les approches de la géographie physique dans son ensemble.
Negative income taxes, inequality and poverty
Authors: Angyridis Constantine , Thompson Brennan Scott 
Published: October 2016

AbstractWe use a neoclassical growth model with heterogeneous agents to analyze the redistributive effects of a negative income tax system, which combines a flat rate tax with a fully refundable credit (“demogrant”). We show that changing the demogrant‐to‐output ratio causes significant changes in the distribution of income. Specifically, we find that increasing the demogrant‐to‐output ratio sharply reduces the level of inequality as well as both relative and absolute poverty (all measured in terms of post‐tax total income). However, these reductions in inequality and poverty come at the expense of a significant reduction in output.
Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild‐type KRAS colorectal cancer‐WJOG 6210G
Authors: Shitara Kohei , Yonesaka Kimio , Denda Tadamichi , Yamazaki Kentaro , Moriwaki Toshikazu , Tsuda Masahiro , Takano Toshimi , Okuda Hiroyuki , Nishina Tomohiro , Sakai Kazuko , Nishio Kazuto , Tokunaga Shoji , Yamanaka Takeharu , Boku Narikazu , Hyodo Ichinosuke , Muro Kei 
Published: October 2016

This randomized phase II trial compared panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second‐line chemotherapy for wild‐type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory to first‐line chemotherapy containing oxaliplatin and bevacizumab were randomly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI. Of 121 randomly assigned patients, 117 were eligible. Median overall survival (OS) for panitumumab plus FOLFIRI and bevacizumab plus FOLFIRI were 16.2 and 13.4 months [hazard ratio (HR), 1.16; 95% CI, 0.76–1.77], respectively. Progression‐free survival (PFS) was also similar (HR, 1.14; 95% CI, 0.78–1.66). KRAS, NRAS, and BRAF status using ctDNA was successfully examined in 109 patients, and mutations were identified in 19 patients (17.4%). Panitumumab plus FOLFIRI showed favorable survival compared with bevacizumab plus FOLFIRI in WT patients and unfavorable survival in those with mutations (P for interaction = 0.026 in OS and 0.054 in PFS). OS with bevacizumab plus FOLFIRI was better than panitumumab plus FOLFIRI in patients with high serum vascular endothelial growth factor‐A (VEGF‐A) levels and worse in those with low levels (P for interaction = 0.016). Second‐line FOLFIRI plus panitumumab and FOLFIRI plus bevacizumab showed a similar efficacy in patients with WT KRAS exon 2 mCRC. RAS and BRAF mutation in ctDNA could be a negative predictive marker for panitumumab.
Lifecourse socioeconomic position indicators and tooth loss in Korean adults
Authors: Han Dong‐Hun , Khang Young‐Ho 
Published: October 2016

AbstractAimThe aim of this study was to assess the association between lifecourse socioeconomic position (SEP) indicators and tooth loss in a large representative sample of the Korean adult population.MethodsData from the Fourth and Fifth Korea National Health and Nutritional Examination Survey on 17,549 Korean adults aged 50 years or older were analyzed. The study design was cross‐sectional. Tooth loss was defined as either edentulism (0 teeth) or severe tooth loss (<20 teeth). Parental education, own education, and income were used as indicators of early childhood SEP, adolescent SEP, and adulthood SEP, respectively. The association between the lifecourse SEPs and tooth loss was estimated with three different lifecourse models: the independent impact model for three different lifecourse SEPs, the cumulative impact model using the sum of the three SEP scores, and the social mobility model using the pathway information of the three SEPs. The covariates were demographic factors and health behaviors. The prevalence ratios (PRs), slope index of inequality (SII), and relative index of inequality (RII) for tooth loss were estimated with log‐binomial regression analyses.ResultsIn the independent impact model, significant associations of each SEP with edentulism (SII=3.61%, 4.76%, 2.17% and RII=1.67, 1.52, 1.41 for parental education, own education, and income, respectively) and severe tooth loss (SII=8.03%, 17.73%, 12.73% and RII=1.26, 1.72, 1.42 for parental education, own education, and income, respectively) were found after adjusting for all covariates. For the cumulative impact model, stepwise patterns of PRs according to the summed SEP scores were found. In addition, in the social mobility model, the PR of tooth loss was greatest in the persistently low SEP group over the life course (PR=2.10 for edentulism and 2.33 for severe tooth loss). The other mobile groups in lifecourse SEPs also presented higher PRs of tooth loss than the persistently high SEP group.ConclusionParental education was independently associated with edentulism in later life, and own education showed the strongest associations with tooth loss. The cumulative and social mobility models for the social impacts of life course on oral health should be considered in oral epidemiological studies.
Localized bone regeneration around dental implants using recombinant bone morphogenetic protein‐2 and platelet‐derived growth factor‐BB in the canine
Authors: Thoma Daniel S. , Cha Jae‐Kook , Sapata Vitor M. , Jung Ronald E. , Hüsler Juerg , Jung Ui‐Won 
Published: October 2016

AbstractObjectivesTo test whether or not one of two biological mediators (recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human platelet‐derived growth factor (rhPDGF‐BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures.Materials and methodsBox‐type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine‐derived particulated bone mineral (DBBM) mixed with rhBMP‐2 and a collagen membrane (CM) (DBBM/BMP‐2), (ii) DBBM mixed with rhPDGF‐BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post‐surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed.ResultsThe mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP‐2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP‐2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP‐2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP‐2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone‐to‐implant contact values on the buccal side were minimal for DBBM/BMP‐2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks.ConclusionsThe use of biological mediators (rhBMP‐2 and rhPDGF‐BB) can increase the amount of bone regeneration at dehiscence‐type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes.
The importance of combined 24‐hour multichannel intraluminal impedance–pH monitoring in the evaluation of children with suspected laryngopharyngeal reflux
Authors: Pavić I. , Babić I. , Čepin Bogović J. , Hojsak I. 
Published: October 2016

ObjectiveThe aim of this study was to investigate the diagnostic usefulness of combined multichannel intraluminal impedance–pH (MII‐pH) monitoring in children with suspected laryngopharyngeal reflux (LPR).Design, setting and participantsA prospective study including children in whom, due to LPR suggestive symptoms, MII‐pH monitoring was performed at tertiary medical centre from February 2012 to July 2015.InterventionsAll included children underwent same diagnostic protocol which included examination by single pulmonologist and ENT specialist and underwent 24‐hour MII‐pH monitoring.Main outcomesPrimary outcome was to determine MII‐pH characteristics of the children in whom LPR was suspected based on symptoms and ENT examination.ResultsOne hundred and four patients (mean age 8.9 years; range 0.4–17.9 years; male/female 57/47) participated in the study. In children with signs and symptoms suggestive of LPR, MII‐pH monitoring found the median incidence of proximal gastro‐oesophageal reflux (GER) of 15 (range 0–129), proximal acidic GER of 6.5 (range 0–66) and weakly acidic GER of 5 (range 0–102). There were significant positive correlations between the number of GER (proximal total, acidic and weakly acid) with Reflux Finding Score, Reflux Symptom Index and presence of eosinophils in nasal swabs. The only endoscopy ENT finding which significantly correlated with total proximal GER, acid proximal GER and weakly acidic proximal GER was arytenoid hyperaemia.ConclusionBoth acid and non‐acid reflux seem to have a significant role in the pathogenesis of LPR.
Rank aggregation of local expert knowledge for conservation planning of the critically endangered saola
Authors: Wilkinson Nicholas M. , Van Duc Luong 
Published: October 2016

AbstractThere has been much recent interest in using local knowledge and expert opinion for conservation planning, particularly for hard‐to‐detect species. Although it is possible to ask for direct estimation of quantities such as population size, relative abundance is easier to estimate. However, an expert's knowledge is often geographically restricted relative to the area of interest. Combining (or aggregating) experts’ assessments of relative abundance is difficult when each expert only knows a part of the area of interest. We used Google's PageRank algorithm to aggregate ranked abundance scores elicited from local experts through a rapid rural‐appraisal method. We applied this technique to conservation planning for the saola(Pseudoryx nghetinhensis), a poorly known bovid. Near a priority landscape for the species, composed of 3 contiguous protected areas, we asked groups of local people to indicate relative abundances of saola and other species by placing beans on community maps. For each village, we used this information to rank areas within the knowledge area of that village for saola abundance. We used simulations to compare alternative methods to aggregate the rankings from the different villages. The best‐performing method was then used to produce a single map of relative abundance across the entire landscape, an area larger than that known to any one village. This map has informed prioritization of surveys and conservation action in the continued absence of direct information about the saola.
Low concentrations of TNF‐α promote osteogenic differentiation via activation of the ephrinB2‐EphB4 signalling pathway
Authors: Wang Limei , Zhang Jin , Wang Cunwei , Qi Yuping , Du Mi , Liu Wenhua , Yang Chengzhe , Yang Pishan 
Published: October 2016

AbstractObjectivesLow concentrations of tumour necrosis factor‐alpha (TNF‐α) have been reported to promote osteogenic differentiation. In this study, a series of in vitro experiments was performed to investigate underlying molecular mechanisms involved.Materials and methodsMC3T3‐E1 murine preosteoblasts were treated with TNF‐α at doses of 0, 0.1 or 1 ng/mL. The ephrinB2‐EphB4 signalling pathway was activated using ephrinB2‐fc, or inhibited using lentiviruses encoding siRNAs specifically targeting EphB4. Cell proliferation/survival was evaluated using the Cell Counting Kit‐8 (CCK‐8) assay, and expression levels of Runx2, BSP, ephrinB2 and EphB4 were determined using RT‐PCR and Western blotting. ALP activity in these cells was also determined, and mineral nodule formation was evaluated with alizarin red S staining.ResultsLow concentrations of TNF‐α had no influence on cell proliferation/survival. However, expression levels of Runx2, BSP, ephrinB2 and EphB4, as well as ALP activity and mineral nodule formation, were significantly enhanced in MC3T3‐E1 cells treated with low concentrations of TNF‐α. Moreover, activation of the ephrinB2‐EphB4 signalling pathway by ephrinB2‐fc enhanced TNF‐α‐induced osteogenic differentiation, while down‐regulation of EphB4 level reversed the positive effect of TNF‐α.ConclusionsLow concentrations of TNF‐α promoted osteogenic differentiation via activation of the ephrinB2‐EphB4 signalling pathway.
Clinical features in patients of cough variant asthma with normal and high level of exhaled fractional nitric oxide
Authors: Tang Wei , Zhou Jun , Miao Lili , Shi GuoCao 
Published: October 2016

AbstractObjectiveCough variant asthma (CVA) is a subtype of asthma that is characterized by a chronic cough. The clinical characteristics and pulmonary function in patients with CVA who had normal and high exhaled fractional nitric oxide (FeNO) levels were compared.MethodsThe clinical history and pulmonary function data from 99 patients with newly diagnosed CVA were collected.ResultNewly diagnosed subjects with CVA were divided into a high FeNO group (FeNO value over or equal to 25 ppb, n = 52) and a normal FeNO group (FeNO lower than 25 ppb, n = 47). There were more patients with coexistent allergic rhinitis or with family histories of allergic diseases in the high FeNO group. More patients in the high FeNO group reported that their chronic cough was triggered by allergen exposure. In the high FeNO group, the patients were younger than in the normal FeNO group. It was shown that baseline lung function tests were normal in all subjects, apart from a reduced midexpiratory flow rate (FEF25‐75). There was a significant decrease in FEF25‐75 in the high FeNO group compared with the normal FeNO group. No difference was found in the PD20 or the maximal FEV1 drop between the two groups. The multi‐factor logistic regression analysis showed that concomitant with allergic rhinitis was the high risk factor of a high FeNO in these subjects with CVA (OR = 5.03, 95% CI, 1.88‐13.49).ConclusionCVA patients showed heterogeneity according to FeNO level. Patients with high FeNO level are more likely to experience symptoms associated with allergies.
Mutation analysis of the EGFR gene and its downstream signaling pathway in thymic carcinoma patients from a Chinese Han population
Authors: Zhan Ping , Chen Xiao , Wu Xiao‐Yuan , Hou Zhi‐Bo , Qian Qian , Zhang Yu , Zou Jue , Zhang Yuan‐Qing , Wan Ming‐Yue , Wang Jian‐Dong , Yu Li‐Ke , Xie Hai‐yan 
Published: October 2016

AbstractIntroductionFor thymic carcinoma (TC), which is a rare epithelial neoplasm of the thymus gland, median survival with current treatments is only 2 years.ObjectivesMutations in the epidermal growth factor receptor (EGFR) gene or its downstream effectors may cause constitutive activation that leads to cell proliferation and metastases. Thus, molecular profiling is essential for selecting TC patients who may respond to anti‐EGFR therapies.MethodsGenomic DNA was extracted from 61 histological samples of TCs. Real‐time polymerase chain reaction (PCR) and direct sequencing were used to assess the mutations in the EGFR downstream pathway.ResultsGene mutations were identified in seven patients (11.5%). In particular, the identified mutations included four mutations in the KRAS gene, one mutation in the BRAF gene, one mutation in the PIK3CA gene, and only one mutation in the EGFR gene itself. Gene mutations in the EGFR downstream pathway were associated with shorter survival time and were observed to be an independent prognostic factor for TC patients.ConclusionMutations in the EGFR downstream pathway are not rare in TCs. These data offer interesting possibilities for the future management of TCs, particularly in the era of new targeted therapies.