bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble interleukin‐6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy
Authors: Makuuchi Yosuke , Honda Kazufumi , Osaka Yoshiaki , Kato Ken , Kojima Takashi , Daiko Hiroyuki , Igaki Hiroyasu , Ito Yoshinori , Hoshino Sumito , Tachibana Shingo , Watanabe Takafumi , Furuta Koh , Sekine Shigeki , Umaki Tomoko , Watabe Yukio , Miura Nami , Ono Masaya , Tsuchida Akihiko , Yamada Tesshi 
Published: May 2013

Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin‐6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.
Characterization of the EP receptor subtype that mediates the inhibitory effects of prostaglandin E2 on IgE‐dependent secretion from human lung mast cells
Authors: Kay L. J. , Gilbert M. , Pullen N. , Skerratt S. , Farrington J. , Seward E. P. , Peachell P. T. 
Published: May 2013

SummaryBackgroundProstaglandin E2 (PGE2) has been shown to inhibit IgE‐dependent histamine release from human lung mast cells. This effect of PGE2 is believed to be mediated by EP2 receptors. However, definitive evidence that this is the case has been lacking in the absence of EP2‐selective antagonists. Moreover, recent evidence has suggested that PGE2 activates EP4 receptors to inhibit respiratory cell function.ObjectiveThe aim of this study was to determine the receptor by which PGE2 inhibits human lung mast cell responses by using recently developed potent and selective EP2 and EP4 receptor antagonists alongside other established EP receptor ligands.MethodsThe effects of non‐selective (PGE2, misoprostol), EP2‐selective (ONO‐AE1‐259, AH13205, butaprost‐free acid) and EP4‐selective (L‐902,688, TCS251) agonists on IgE‐dependent histamine release and cyclic‐AMP generation in mast cells were determined. The effects of EP2‐selective (PF‐04418948, PF‐04852946) and EP4‐selective (CJ‐042794, L‐161,982) antagonists on PGE2 responses of mast cells were studied. The expression of EP receptor subtypes was determined by RT‐PCR.ResultsProstaglandin E2, EP2 agonists and EP4 agonists inhibited IgE‐dependent histamine release from mast cells. PGE2 and EP2 agonists, but not EP4 agonists, increased cyclic‐AMP levels in mast cells. EP4‐selective antagonists did not affect the PGE2 inhibition of histamine release, whereas EP2‐selective antagonists caused rightward shifts in the PGE2 concentration–response curves. RT‐PCR studies indicated that mast cells expressed EP2 and EP4 receptors.Conclusions and Clinical RelevanceAlthough human lung mast cells may express both EP2 and EP4 receptors, the principal mechanism by which PGE2 inhibits mediator release in mast cells is by activating EP2 receptors.
Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen‐induced disrupted tight junctions in the airway epithelium
Authors: Park S.‐W. , Lee E. H. , Lee E.‐J. , Kim H. J. , Bae D.‐J. , Han S. , Kim D. , Jang A. S. , Uh S.‐T. , Kim Y. H. , Erle D. J. , Park C.‐S. 
Published: May 2013

SummaryBackgroundAsthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A‐1 (ApoA1) or ApoA1 mimetics have demonstrated anti‐inflammatory activity and preventive effects in mouse models.ObjectiveWe investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma.MethodsApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)‐driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot.ResultsAsthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL‐25, IL‐33, and thymic stromal lymphopoietin levels in HDM‐challenged mice and inhibited allergen‐induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens‐1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1‐induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4).Conclusions and Clinical RelevanceApoA1 enhances resolution of allergen‐induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.
Age‐dependent sting recurrence and outcome in immunotherapy‐treated children with anaphylaxis to Hymenoptera venom
Authors: Stritzke A. I. , Eng P. A. 
Published: May 2013

SummaryBackgroundData on outcome of insect venom immunotherapy in children are rare.ObjectiveWe investigated the rate of sting recurrence and outcome of Hymenoptera venom anaphylaxis in children of different age groups treated with immunotherapy.MethodsData from children consecutively referred for anaphylaxis to Hymenoptera venom were collected using a standardized questionnaire.ResultsDuring mean follow‐up of 7.7 years after commencement of immunotherapy, 45 of 83 children (56%) were re‐stung 108 times by the insect they were allergic to. This corresponds to a rate of 0.23 stings per child and year of follow‐up. The younger the subject, the higher was the prevalence of re‐stings, with rates of 0.41 in children < 6 years, 0.21 at school age and 0.15 in adolescents (P = 0.001). In contrast, prevalence of systemic allergic reactions to field stings was significantly lower in pre‐school (3.4%) and school‐age children (4.3%) compared with adolescents (15.6%; P < 0.05). Overall, prevalence of systemic allergic reactions at re‐sting was 15.6% in the honey bee venom and 5.9% in the Vespula venom allergic group (P = ns). Younger boys with anaphylaxis to honey bee venom predominated in our cohort (P = 0.019).Conclusion and Clinical RelevanceA majority of children with anaphylaxis to Hymenoptera venom (56%) in our cohort were re‐stung, equally by honey bees or Vespula species. Younger children were more likely to be re‐stung, but less likely to have a systemic reaction. Venom immunotherapy induces long‐term protection in most children: 84.4% of subjects with anaphylaxis to honey bee and 94.1% of those to Vespula venom were completely protected at re‐stings.
Scalable Music: Automatic Music Retargeting and Synthesis
Authors: Wenner Simon , Bazin Jean‐Charles , Sorkine‐Hornung Alexander , Kim Changil , Gross Markus 
Published: May 2013

AbstractIn this paper we propose a method for dynamic rescaling of music, inspired by recent works on image retargeting, video reshuffling and character animation in the computer graphics community. Given the desired target length of a piece of music and optional additional constraints such as position and importance of certain parts, we build on concepts from seam carving, video textures and motion graphs and extend them to allow for a global optimization of jumps in an audio signal. Based on an automatic feature extraction and spectral clustering for segmentation, we employ length‐constrained least‐costly path search via dynamic programming to synthesize a novel piece of music that best fulfills all desired constraints, with imperceptible transitions between reshuffled parts. We show various applications of music retargeting such as part removal, decreasing or increasing music duration, and in particular consistent joint video and audio editing.
Trophic Flexibility and the Persistence of Understory Birds in Intensively Logged Rainforest
Authors: EDWARDS DAVID P. , WOODCOCK PAUL , NEWTON ROB J. , EDWARDS FELICITY A. , ANDREWS DAVID J. R. , DOCHERTY TEEGAN D. S. , MITCHELL SIMON L. , OTA TAKAHIRO , BENEDICK SUZAN , BOTTRELL SIMON H. , HAMER KEITH C. 
Published: May 2013

AbstractEffects of logging on species composition in tropical rainforests are well known but may fail to reveal key changes in species interactions. We used nitrogen stable‐isotope analysis of 73 species of understory birds to quantify trophic responses to repeated intensive logging of rainforest in northern Borneo and to test 4 hypotheses: logging has significant effects on trophic positions and trophic‐niche widths of species, and the persistence of species in degraded forest is related to their trophic positions and trophic‐niche widths in primary forest. Species fed from higher up the food chain and had narrower trophic‐niche widths in degraded forest. Species with narrow trophic‐niche widths in primary forest were less likely to persist after logging, a result that indicates a higher vulnerability of dietary specialists to local extinction following habitat disturbance. Persistence of species in degraded forest was not related to a species’ trophic position. These results indicate changes in trophic organization that were not apparent from changes in species composition and highlight the importance of focusing on trophic flexibility over the prevailing emphasis on membership of static feeding guilds. Our results thus support the notion that alterations to trophic organization and interactions within tropical forests may be a pervasive and functionally important hidden effect of forest degradation.Flexibilidad Trófica y la Persistencia de Aves de Sotobosque en un Bosque Lluvioso Talado Intensivamente
Restorative proctocolectomy in patients with ulcerative colitis: a cross‐sectional Danish population study on function and quality of life
Authors: Brandsborg S. , Tøttrup A. , Nicholls J. , Laurberg S. 
Published: May 2013

AbstractAimThe study evaluated function and quality of life (QoL) in all patients having restorative proctocolectomy (RPC) in Denmark for ulcerative colitis (UC) from 1980 to 2010. Inclusion of all patients in one country has never previously been achieved.MethodAll patients who had had a RPC in Denmark, from the first case in 1980 to the last case in 2010, were studied. A cross‐sectional questionnaire survey was performed, and function and QoL were assessed using a standardized questionnaire – the Short‐Form 36 (SF36) – and the inflammatory bowel disease questionnaire (IBDQ).ResultsThe median duration of follow up was 11 (range, 1–30) years. Apart from deaths, pouch failures and research protection, data on function and QoL were obtained from 1047 (85%) of 1229 patients who had a functioning pouch at the time of the investigation. More female patients than male patients experienced urgency (56% vs 44%, P = 0.0021). The median number of bowel movements per 24 h was 7 (range, 1–23) in female patients and 6 (range, 1–20) in male patients (P < 0.001). Pad usage was more frequent among female patients than among male patients (62% vs 38%, P < 0.001). A higher incidence of major incontinence (P = 0.009) and use of pads (P = 0.01) was found among patients who had been operated on 21–30 years previously compared with those operated on 11–20 years previously. The prevalence of urgency was higher in patients who received surgery 0–10 years previously compared with 11–20 years previously (P = 0.009). The total IBDQ score was higher in male patients than in female patients (P < 0.001). Male patients scored higher in five of eight SF36 domains (P < 0.001).ConclusionFemale patients had more urgency, a higher frequency of defaecation and higher pad usage. This was associated with a reduced QoL. Nevertheless, RPC resulted in good function and a high degree of satisfaction in most patients.
Evaluation of plasma treatment effects on improving adhesive–dentin bonding by using the same tooth controls and varying cross‐sectional surface areas
Authors: Dong Xiaoqing , Ritts Andrew C. , Staller Corey , Yu Qingsong , Chen Meng , Wang Yong 
Published: May 2013

The objective of this study was to evaluate and verify the effectiveness of plasma treatment for improving adhesive–dentin interfacial bonding by performing microtensile bond‐strength (μTBS) testing using the same‐tooth controls and varying cross‐sectional surface areas. Extracted unerupted human third molars were used after removal of the crowns to expose the dentin surface. One half of each dentin surface was treated with a non‐thermal argon plasma brush, whilst the other was shielded with glass slide and used as an untreated control. Adper Single Bond Plus adhesive and Filtek Z250 dental composite were then applied as directed. The teeth thus prepared were further cut into micro‐bar specimens, with cross‐sectional sizes of 1 × 1 mm2, 1 × 2 mm2, and 1 × 3 mm2, for μTBS testing. The test results showed that plasma‐treated specimens gave substantially stronger adhesive–dentin bonding than their corresponding same‐tooth controls. Compared with their untreated controls, plasma treatment gave statistically significant higher bonding strength for specimens with a cross‐sectional area of 1 × 1 mm2 and 1 × 2 mm2, with mean increases of 30.8% and 45.1%, respectively. Interface examination using optical and electron microscopy verified that plasma treatment improved the quality of the adhesive–dentin interface by reducing defects/voids and increasing the resin tag length in dentin tubules.
Patterns of tooth agenesis in patients with orofacial clefts
Authors: Hermus Ruurd R. , van Wijk Arjen J. , Tan Stephan P. K. , Kramer Gem J. C. , Ongkosuwito Edwin M. 
Published: May 2013

Orofacial clefts are a common oral disorder associated with tooth agenesis. As information on the simultaneous absence of teeth can be an aid in treatment planning, a large sample of orofacial cleft patients was examined. The sample consisted of 910 patients with cleft lip and palate. Tooth agenesis was assessed on the basis of at least two panoramic radiographs and patient records. Third‐molar agenesis was determined in 474 patients. Patterns of tooth agenesis were analysed using Tooth Agenesis Code (TAC) values, according to van Wijk & Tan. Per quadrant, at least 90% of patients could be described according to three different patterns. In the maxilla, 85% of patients with tooth agenesis had a TAC‐value of 2, 16, or 18 on either the left side, right side or bilaterally. In the mandible, 90% of patients with tooth agenesis had a TAC‐value of 16, 1 or 2 on either the left side, right side or bilaterally. In patients with tooth agenesis, patterns were symmetrical in the maxilla in 18.8% and in the mandible in 51%. More extended cleft types were associated with a higher prevalence of tooth agenesis. Third‐molar agenesis (prevalence = 22.4%) was significantly related to the prevalence of other absent teeth. These results show which patterns of tooth agenesis can be expected to occur in most orofacial cleft patients.
Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene
Authors: Naveenkumar Chandrashekar , Raghunandakumar Subramanian , Asokkumar Selvamani , Binuclara John , Rajan Balan , Premkumar Thandavamoorthy , Devaki Thiruvengadam 
Published: May 2013

AbstractThe lungs mainly serve as a primary site for xenobiotic metabolism and constitute an important defense mechanism against inhalation of carcinogens. Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice exposed to tobacco‐specific carcinogen benzo(a)pyrene [B(a)P] for its ability to mitigate pulmonary carcinogenesis. Here, we report that altered activities/levels of lysosomal enzymes (cathepsin‐D, cathepsin‐B, acid phosphatase, β‐D‐galactosidase, β‐D‐glucuronidase, and β‐D‐N‐acetyl glucosaminidase), phase I biotransformation enzymes (cytochrome P450, cytochrome b5, NADPH‐cytochrome P450 reductase, and NADH‐cytochrome b5 reductase), and phase II enzymes (glutathione S‐transferase, UDP‐glucuronyl transferase, and DT‐diaphorase) were observed in the B(a)P‐induced mice. Treatment with BE significantly restored back the activities/levels of lysosomal enzymes, phase I and phase II biotransformation enzymes. Moreover, assessment of lysosomal abnormalities by transmission electron microscopic examination revealed that BE treatment effectively counteract B(a)P‐induced oxidative damages. Protein expression levels studied by immunohistochemistry, immunofluorescence, and immunoblot analysis of CYP1A1 revealed that BE treatment effectively negate B(a)P‐induced upregulated expression of CYP1A1. Further analysis of scanning electron microscopic studies in lung was carried out to substantiate the anticarcinogenic effect of BE. The overall data suggest that BE treatment significantly inhibits lysosomal and microsomal dysfunction, thus revealing its potent anticarcinogenic effect.
Zinc‐induced modulation of SRSF6 activity alters Bim splicing to promote generation of the most potent apoptotic isoform BimS
Authors: Hara Hirokazu , Takeda Tatsuya , Yamamoto Nozomi , Furuya Keisuke , Hirose Kazuya , Kamiya Tetsuro , Adachi Tetsuo 
Published: May 2013

Bim is a member of the pro‐apoptotic BH3‐only Bcl‐2 family of proteins. Bim gene undergoes alternative splicing to produce three predominant splicing variants (BimEL, BimL and BimS). The smallest variant BimS is the most potent inducer of apoptosis. Zinc (Zn2+) has been reported to stimulate apoptosis in various cell types. In this study, we examined whether Zn2+ affects the expression of Bim in human neuroblastoma SH‐SY5Y cells. Zn2+ triggered alterations in Bim splicing and induced preferential generation of BimS, but not BimEL and BimL, in a dose‐ and time‐dependent manner. Other metals (cadmium, cobalt and copper) and stresses (oxidative, endoplasmic reticulum and genotoxic stresses) had little or no effect on the expression of BimS. To address the mechanism of Zn2+‐induced preferential generation of BimS, which lacks exon 4, we developed a Bim mini‐gene construct. Deletion analysis using the Bim mini‐gene revealed that predicted binding sites of the SR protein SRSF6, also known as SRp55, are located in the intronic region adjacent to exon 4. We also found that mutations in the predicted SRSF6‐binding sites abolished generation of BimS mRNA from the mutated Bim mini‐gene. In addition, a UV cross‐linking assay followed by Western blotting showed that SRSF6 directly bound to the predicted binding site and Zn2+ suppressed this binding. Moreover, Zn2+ stimulated SRSF6 hyper‐phosphorylation. TG003, a cdc2‐like kinase inhibitor, partially prevented Zn2+‐induced generation of BimS and SRSF6 hyper‐phosphorylation. Taken together, our findings suggest that Zn2+ inhibits the activity of SRSF6 and promotes elimination of exon 4, leading to preferential generation of BimS.
Different prognosis in hospitalized patients with influenza one season after the pandemic H1N1 influenza of 2009–2010 in Spain
Authors: Delgado‐Rodríguez Miguel , Castilla Jesús , Godoy Pere , Martín Vicente , Soldevila Nuria , Alonso Jordi , Astray Jenaro , Baricot Maretva , Galán Juan C. , Castro Ady , Gónzález‐Candelas Fernando , Mayoral José M. , Quintana José M. , Pumarola Tomás , Tamames Sonia , Sáez Marc , Domínguez Angela ,   the CIBERESP Cases and Controls in Pandemic Influenza Working Group, Spain
Published: May 2013

BackgroundThe present report compares prognosis in hospitalized cases with the H1N1 pandemic virus in two seasons.MethodsTwo series of hospitalized patients with laboratory‐confirmed H1N1 pandemic influenza have been compared: 813 in the season 2009–2010 and 707 in the season 2010–2011. A detailed history of variables preceding hospital admission and during hospitalization was obtained by interview and clinical charts. A combined endpoint of death admission to intensive care was used as outcome due to the low number of deaths. Logistic regression was applied in the analysis for adverse outcome.ResultsPatients of the second season had different characteristics than in the first one (older, more underlying conditions, more malfunctioning organs and more symptoms). Patients with H1N1 pandemic virus when hospitalized were more frequently directly admitted to ICU during the 2010–2011 season than in the previous season (RR = 2·10; 95% confidence intervals CI, 1·55–2·85), as a consequence of a higher presence of sepsis and respiratory distress. These patients also showed during hospitalization a higher risk of ICU admission or death (RR = 3·22, 95% CI, 2·15–4·83). After adjusting for the differences in risk factors of adverse outcome, patients in the second season showed a higher risk of ICU admission and/or in‐hospital death odds ratio (OR = 3·77, 95% CI, 2·30–6·18).ConclusionHospitalized patients with H1N1 pandemic influenza during the second season were more severely affected at hospital admission and showed a worse prognosis than in previous season, independently of the differences found at hospital admission.
Cleavage of GSK‐3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK‐3β activity induced by H2O2
Authors: Feng Ye , Xia Yiyuan , Yu Guang , Shu Xiji , Ge Haoliang , Zeng Kuan , Wang Jianzhi , Wang Xiaochuan 
Published: May 2013

AbstractGlycogen synthase kinase‐3 beta (GSK‐3β) dysfunction may play an essential role in the pathogenesis of psychiatric, metabolic, neurodegenerative diseases, in which oxidative stress exists concurrently. Some studies have shown that GSK‐3β activity is up‐regulated under oxidative stress. This study evaluated how oxidative stress regulates GSK‐3β activity in human embryonic kidney 293 (HEK293)/Tau cells treated with hydrogen peroxide (H2O2). Here, we show that H2O2 induced an obvious increase of GSK‐3β activity. Surprisingly, H2O2 dramatically increased phosphorylation of GSK‐3β at Ser9, an inactive form of GSK‐3β,while there were no changes of phosphorylation of GSK‐3β at Tyr216. Moreover, H2O2 led to a transient [Ca2+]i elevation, and simultaneously increased the truncation of GSK‐3β into two fragments of 40 kDa and 30 kDa, whereas inhibition of calpain decreased the truncation and recovered the activity of GSK‐3β. Furthermore, tau was hyperphosphorylated at Ser396, Ser404, and Thr231, three most common GSK‐3β targeted sites after 100 μM H2O2 administration in HEK293/Tau cells, whereas inhibition of calpain blocked the tau phosphorylation. In addition, we found that there were no obvious changes of Cyclin‐dependent kinase 5 (CDK5) expression (responsible for tau phosphorylation) and of p35 cleavage, the regulatory subunit of CDK5 in H2O2‐treated HEK293/Tau cells. In conclusion, Ca2+‐dependent calpain activation leads to GSK‐3β truncation, which counteracts the inhibitory effect of Ser9 phosphorylation, up‐regulates GSK‐3β activity, and phosphorylates tau in H2O2‐treated HEK293/Tau cells.