bluuebunny/crossref_metadata_2025_split huggingface dataset:
FoxO3a modulation and promotion of apoptosis by interferon‐α2b in rat preneoplastic liver
Authors: Parody Juan P. , Ceballos Maria P. , Quiroga Ariel D. , Frances Daniel E. , Carnovale Cristina E. , Pisani Gerardo B. , Alvarez Maria L. , Carrillo Maria C. 
Published: November 2013

AbstractBackgroundFoxO3a, a member of the FOXO family of transcription factors, is expressed in adult liver and modulates the expression of genes involved in apoptosis. FoxO3a is post‐translationally regulated, negatively by PI3K/Akt and MAPK/Erk and positively by oxidative stress/JNK pathways. In previous works, we have demonstrated that interferon‐α2b (IFN‐α2b) induces apoptosis of hepatic preneoplastic foci through the production of reactive oxygen species (ROS).AimsTo investigate the post‐translational signal events triggered by the oxidative stress induced by IFN‐α2b and the modulation of FoxO3a transcriptional activity during these events in rat preneoplastic liver.MethodsAdult male Wistar rats were subjected to a two‐phase model of hepatocarcinogenesis. A group of animals received IFN‐α2b and another group received IFN‐α2b and ascorbic acid (ASC), by intraperitoneal injection. Lipid peroxidation, immunohistochemistry, immunoblotting, co‐immunoprecipitation and sqRT‐PCR assays were performed to explore the role of ROS, JNK, Akt, Erk, FoxO3a, β‐catenin and PUMA in the IFN‐α2b‐mediated apoptotic mechanism.ResultsIn vivo IFN‐α2b treatment induced endogenous production of ROS which activated JNK. IFN‐α2b blocked the activation of Akt and Erk, avoiding FoxO3a activity repression. Activated JNK was responsible for the nuclear translocation and transcriptional activity of FoxO3a which positively modulated the expression of PUMA, a proapoptotic player. In addition, nuclear FoxO3a competed for the nuclear β‐catenin associated to TCF, inhibiting the canonical Wnt signalling pathway.ConclusionsThe data presented here propose a model in which in vivo IFN‐α2b treatment induces nuclear translocation and transcriptional activity of FoxO3a, triggering the mitochondrial apoptotic pathway in hepatic preneoplastic foci.
Sphingolipid signalling mediates mitochondrial dysfunctions and reduced chronological lifespan in the yeast model of Niemann‐Pick type C1
Authors: Vilaça Rita , Silva Elísio , Nadais André , Teixeira Vítor , Matmati Nabil , Gaifem Joana , Hannun Yusuf A. , Sá Miranda Maria Clara , Costa Vítor 
Published: November 2013

SummaryThe Niemann‐Pick type C is a rare metabolic disease with a severe neurodegenerative phenotype characterized by an accumulation of high amounts of lipids (cholesterol and sphingolipids) in the late endosomal/lysosomal network. It is caused by loss‐of‐function point mutations in either NPC1 or NPC2, which seem to mediate proper intracellular lipid transport through endocytic pathway. In this study, we show that yeast cells lacking Ncr1p, an orthologue of mammalian NPC1, exhibited a higher sensitivity to hydrogen peroxide and a shortened chronological lifespan. These phenotypes were associated with increased levels of oxidative stress markers, decreased levels of antioxidant defences and mitochondrial dysfunctions. Moreover, we report that Ncr1p‐deficient cells displayed high levels of long chain bases (LCB), and that Sch9p‐phospho‐T570 and Sch9p levels increased in ncr1Δ cells through a mechanism regulated by Pkh1p, a LCB‐activated protein kinase. Notably, deletion of PKH1 or SCH9 suppressed ncr1Δ phenotypes but downregulation of de novo sphingolipid biosynthesis had no protective effect, suggesting that LCBs accumulation may result from an increased turnover of complex sphingolipids. These results suggest that sphingolipid signalling through Pkh1p‐Sch9p mediate mitochondrial dysfunction, oxidative stress sensitivity and shortened chronological lifespan in the yeast model of Niemann‐Pick type C disease.
The interplay between the GATA transcription factors AreA, the global nitrogen regulator and AreB in Fusarium fujikuroi
Authors: Michielse C. B. , Pfannmüller A. , Macios M. , Rengers P. , Dzikowska A. , Tudzynski B. 
Published: November 2013

SummaryNitrogen metabolite repression (NMR) in filamentous fungi is controlled by the GATA transcription factors AreA and AreB. While AreA mainly acts as a positive regulator of NMR‐sensitive genes, the role of AreB is not well understood. We report the characterization of AreB and its interplay with AreA in the gibberellin‐producing fungus Fusarium fujikuroi. The areB locus produces three different transcripts that each code for functional proteins fully complementing the areB deletion mutant that influence growth and secondary metabolism. However, under nitrogen repression, the AreB isoforms differ in subcellular localization indicating distinct functions under these conditions. In addition, AreA and two isoforms of AreB colocalize in the nucleus under low nitrogen, but their nuclear localization disappears under conditions of high nitrogen. Using a bimolecular fluorescence complementation (BiFC) approach we showed for the first time that one of the AreB isoforms interacts with AreA when starved of nitrogen. Cross‐species complementation revealed that some AreB functions are retained between F. fujikuroi and Aspergillus nidulans while others have diverged. By comparison to other fungi where AreB was postulated to function as a negative counterpart of AreA, AreB can act as both repressor and activator of transcription in F. fujikuroi.
Reduced E‐cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS
Authors: Wilcz‐Villega E. , McClean S. , O'Sullivan M. 
Published: November 2013

AbstractBackgroundIncreased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E‐cadherin and TJ proteins zonula occludens (ZO)‐1 and claudin (CLD)‐1 and associations with IBS symptoms.MethodsJunctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS‐A) and diarrhea predominant (IBS‐D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence.Key ResultsE‐cadherin and ZO‐1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS‐A and IBS‐D subtypes. CLD‐1 expression was not significantly altered compared with controls. On subtype analysis, ZO‐1 expression was significantly reduced in both IBS‐A and IBS‐D compared with controls, whereas E‐cadherin was reduced only in IBS‐A. Lower E‐cadherin expression was associated with longer symptoms duration specifically in IBS‐A patients (rs = −0.76, p = 0.004). Reduced E‐cadherin associated with abdominal pain severity in the overall IBS group (rs = −0.36, p = 0.041), but this association was unrelated to IBS subtype.Conclusions & InferencesE‐cadherin protein expression in the cecum was significantly lower in IBS‐A compared with controls and associated with longstanding symptoms. E‐cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E‐cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS.
Secondary learning and the unintended benefits of collaborative mechanisms: The Federal Aviation Administration's voluntary disclosure programs
Authors: Mills Russell W. , Reiss Dorit Rubinstein 
Published: November 2013

AbstractAlong with other types of process‐oriented regulation, voluntary disclosure programs are increasingly used by regulatory agencies to supplement traditional inspection activities. Voluntary disclosure programs provide incentives, such as immunity or reduced regulatory enforcement to those submitting reports, while providing regulatory agencies with valuable information on existing risks and areas of non‐compliance. This article contributes to the discussion of voluntary disclosure programs by highlighting an important unconsidered benefit of such programs: the secondary learning they generate, above and beyond information about violations. Beyond the information submitted by firms contained in the self‐disclosures, the programs generate information and insights about the usual practices of the industry, the division of labor, typical problems, and ways to handle them – those details often invisible to those outside an organization or inside the organization but not “on the ground.” This additional information provides important benefits to both industry management and agency officials. We demonstrate the existence of secondary learning and describe the effect of the structure of voluntary programs on secondary learning with evidence from two case studies of the Federal Aviation Administration's voluntary disclosure programs: the Aviation Safety Action Program and the Voluntary Disclosure Reporting Program.
Rituximab in severe, treatment‐refractory interstitial lung disease
Authors: Keir Gregory J. , Maher Toby M. , Ming Damien , Abdullah Reza , de Lauretis Angelo , Wickremasinghe M. , Nicholson Andrew G. , Hansell David M. , Wells Athol U. , Renzoni Elisabetta A. 
Published: November 2013

AbstractBackground and objectiveIn patients with severe interstitial lung disease (ILD) progressing despite conventional immunosuppression, rituximab, a B‐lymphocyte depleting monoclonal antibody, may offer an effective rescue therapy.MethodsRetrospective assessment of 50 patients with severe, progressive ILD (of varying aetiologies, excluding idiopathic pulmonary fibrosis (IPF)) treated with rituximab between 2010 and 2012. Change in pulmonary function tests compared with pre‐rituximab levels was assessed at 6–12 months post‐treatment.ResultsILD was associated with connective tissue disease in 33 patients, hypersensitivity pneumonitis in 6 patients and miscellaneous conditions in 11 patients. At the time of rituximab administration, patients had severe physiologic impairment with a median forced vital capacity (FVC) of 44.0% (24.0–99.0%) and diffusing capacity of carbon monoxide (DLCO) of 24.5% (11.4–67.0%). In contrast with a median decline in FVC of 14.3% and DLCO of 18.8% in the 6–12 months prior to rituximab, analysis of paired pulmonary function data revealed a median improvement in FVC of 6.7% (P < 0.01) and stability of DLCO (0% change; P < 0.01) in the 6–12 months following rituximab treatment. Two patients developed serious infections (pneumonia) requiring hospitalization following rituximab, and 10 patients died from progression of underlying ILD, a median of 5.1 (1.2–24.5) months after treatment.ConclusionsIn patients with severe, progressive non‐IPF ILD unresponsive to conventional immunosuppression, rituximab may offer an effective therapeutic intervention. Future prospective, controlled trials are warranted to validate these findings, and to assess safety outcomes.
Does Prior Acupuncture Exposure Affect Perception of Blinded Real Or Sham Acupuncture?
Authors: Dilli Caitlin R , Childs Rebecca , Berk Julie , Christian M K , Nguyen Nancy , Brown R Preston , Kluger Benzi M 
Published: November 2013

Objective To determine if acupuncture-exposed and naïve participants differ in their perceptions of real and sham acupuncture under blinded conditions. Methods The setting was an outpatient clinic at the Colorado School of Traditional Chinese Medicine. Participants were between the ages of 18 and 90 years. Acupuncture-exposed participants had at least five prior acupuncture treatments, with one treatment in the month prior to the study date. Acupuncture-naïve participants had experienced no prior acupuncture treatments. Participants with dementia, cognitive impairment, or neuropathy were excluded. In total, 61 acupuncture-exposed and 59 acupuncture-naïve participants were blindfolded and received either real acupuncture or toothpick sham acupuncture treatment. Following treatment, participants completed a questionnaire rating the realness of the acupuncture and were asked how they made this determination. We used a previously developed scale rating treatments from 1 (definitely real needle) to 5 (definitely imitation needle) to assess outcome. Results Perceptions of the real treatment were rated as more real than sham treatments for all participants. Further analysis revealed that prior acupuncture exposure did not influence ratings of real treatments, but exposed participants rated sham treatments as significantly less real than naïve participants. Conclusions Acupuncture-naïve and exposed participants both reported different perceptions of real and sham acupuncture using a blindfolded toothpick protocol. This suggests that future trials should carefully monitor participant perceptions of treatments received, even for naïve individuals. Differences between groups further suggest that participants with significant and/or recent exposure to real acupuncture may introduce bias to blinded clinical acupuncture trials.
Serum ferritin and nutritional status: insights from an eating disorders clinic population
Authors: Nemba Kuria , Lewis Barry , Watson Hunna , Hoiles Kimberley , Zhang Guicheng , Forbes David 
Published: November 2013

ObjectiveTo determine the relationship between serum ferritin and malnutrition in newly assessed patients at a paediatric eating disorders clinic.DesignThis was a prospectively assessed clinical cohort study.SettingIntake assessment clinic of a tertiary eating disorders service for children and adolescents.MethodsClinical, anthropometric and laboratory features of children and adolescents were systematically measured. The relationship of serum ferritin to other clinical, anthropometric and laboratory measures was determined using linear regression.ResultsA total of 121 female patients aged 9.5–17.6 years were included, with body mass index (BMI) z score −5.7 to 1.9 (median −1.3). Using multiple regression, serum ferritin was inversely associated with BMI z score (regression coefficient (β)=−0.234, 95% CI −0.413 to −0.055) and serum insulin-like growth factor 1 (IGF-1) (β=−0.476, 95% CI −0.884 to −0.068) and positively associated with alanine aminotransferase (β=0.357, 95% CI 0.055 to 0.659, controlling for age, pubertal stage and serum iron).ConclusionsIn malnourished adolescents with eating disorders increased serum ferritin is associated with lower BMI z score and serum IGF-1.
Association of note quality and quality of care: a cross-sectional study
Authors: Edwards Samuel T , Neri Pamela M , Volk Lynn A , Schiff Gordon D , Bates David W 
Published: November 2013

BackgroundWhile physician notes are known to vary in organisation, content and quality, the relationship between note quality and clinical quality is uncertain.MethodsWe performed a cross-sectional study of outpatient visit physician notes by adult patients with coronary artery disease or diabetes mellitus seen in 2010. We assessed physician note quality using the 9-item Physician Documentation Quality Instrument (PDQI-9) and compared this to disease-specific clinical quality scores constructed from data extracted from the electronic health record (EHR). We also assessed the presence of typical note subsections, and indicators of quality care in physician notes.ResultsWe evaluated 239 notes, written by 111 physicians; 110 notes were written by primary care physicians, 52 by cardiologists and 77 by endocrinologists. Reason for visit was absent in 10% of notes, medication list was not present in the note in 19.7% and timing for follow-up was absent in 18.0% of notes. Significant copy/pasted material was present in 10.5% of notes. Laboratory quality indicators were more often found in other EHR sections than in the physician note. Clinical quality scores for diabetes and coronary artery disease (CAD) showed no significant association with subjective note quality (diabetes: r −0.119, p=0.065, CAD: r −0.124, p=0.06).ConclusionsNotes varied in documentation method and length, and important note subsections were frequently missing. Key clinical data to support quality patient care were often not present in physician notes, but were often found elsewhere in the EHR. Subjective assessment of note quality did not correlate with clinical quality scores, suggesting that writing high-quality notes and meeting quality measures are not mutually reinforcing activities.
OCP-PLACE in Speech Segmentation
Authors: Boll-Avetisyan Natalie , Kager René 
Published: November 2013

OCP-Place, a cross-linguistically well-attested constraint against pairs of consonants with shared [place], is psychologically real. Studies have shown that the processing of words violating OCP-Place is inhibited. Functionalists assume that OCP arises as a consequence of low-level perception: a consonant following another with the same [place] cannot be faithfully perceived as an independent unit. If functionalist theories were correct, then lexical access would be inhibited if two homorganic consonants conjoin at word boundaries—a problem that can only be solved with lexical feedback. Here, we experimentally challenge the functional account by showing that OCP-Place can be used as a speech segmentation cue during pre-lexical processing without lexical feedback, and that the use relates to distributions in the input. In Experiment 1, native listeners of Dutch located word boundaries between two labials when segmenting an artificial language. This indicates a use of OCP-Labial as a segmentation cue, implying a full perception of both labials. Experiment 2 shows that segmentation performance cannot solely be explained by well-formedness intuitions. Experiment 3 shows that knowledge of OCP-Place depends on language-specific input: in Dutch, co-occurrences of labials are under-represented, but co-occurrences of coronals are not. Accordingly, Dutch listeners fail to use OCP-Coronal for segmentation.
The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks
Authors: Krystal Andrew D , Zhang Wei , Davidson Jonathan RT , Connor Kathryn M 
Published: November 2013

Introduction: We sought to test the hypothesis that improvements in sleep might mediate treatment-related improvements in daytime symptoms of post-traumatic stress disorder (PTSD). We evaluated whether changes in sleep occurring on the first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor) administration predicted subsequent PTSD response. Methods: This was an open-label three-week polysomnographic (PSG) study of nightly treatment with tiagabine dosing from 2–12 mg including 20 adults with PTSD with ≥30 min of self-reported and PSG wake time after sleep onset (WASO). Results: A treatment night 1 decrease in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the primary outcome measure ( p<0.001). Increased night 1 SWS also accounted for 91% of the variance in Work/School Impairment and 45% of the variance in Social Life Impairment as measured with the Sheehan Disability Scale ( p<0.001). These relationships were much stronger correlates of three-week outcome than three-week sleep effects. Conclusions: The initial sleep response to tiagabine may mediate or be an indicator of the subsequent PTSD response. The findings highlight the importance of sleep maintenance and SWS in the treatment of PTSD and also suggest a potential relationship between SWS and daytime function.
Correlation between plasma miR-122 expression and liver injury induced by hepatectomy
Authors: Ruoquan Yao , Wanpin Nie , Qiangsheng Xiao , Guodong Tian , Feizhou Huang 
Published: November 2013

Objective: This study aimed to define the correlation between microRNA-122 (miR-122) expression and hepatectomy-induced liver injury in patients with hepatocellular carcinoma (HCC). Methods: Plasma miR-122 expression in patients with HCC and healthy age-matched controls was determined, and correlated with plasma alanine transaminase activity (ALT) and bilirubin levels preoperatively and on days 1 and 7 postoperation. Correlations between plasma miR-122 and clinicopathological characteristics at 1 day postoperation were also determined. Results: This study included 80 patients with HCC and 80 controls. Baseline expression of miR-122 mRNA and ALT in patients with HCC was significantly higher than in controls. MiR-122 expression correlated with ALT and bilirubin levels preoperatively and on days 1 and 7 postoperatively. In patients with HCC who received a block of the first hepatic portal during surgery and those with excised tumour size >5 cm, plasma miR-122 expression was significantly increased on day 1 postoperatively, compared with expression levels in those who did not receive a block and those with smaller tumours. Conclusions: Plasma miR-122 expression is correlated with hepatectomy-induced liver injury in patients with HCC. Increase in miR-122 expression could be used as an index of such injury before and after hepatectomy in these patients.
Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients
Authors: Ye Changqing , Jin Haiqiang , Zhang Rui , Sun Yongan , Wang Zhaoxia , Sun Weiping , Sun Wei , Peng Qing , Liu Ran , Huang Yining 
Published: November 2013

Objective To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 ( CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 ( VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy. Methods Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated. Results Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 ± 0.14) than those with the VKORC1-1639 AG genotype (1.32 ± 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 ± 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 ± 0.70 mg/day). Conclusions Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.