bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forest water use and water use efficiency at elevated CO2: a model‐data intercomparison at two contrasting temperate forest FACE sites
Authors: De Kauwe Martin G. , Medlyn Belinda E. , Zaehle Sönke , Walker Anthony P. , Dietze Michael C. , Hickler Thomas , Jain Atul K. , Luo Yiqi , Parton William J. , Prentice I. Colin , Smith Benjamin , Thornton Peter E. , Wang Shusen , Wang Ying‐Ping , Wårlind David , Weng Ensheng , Crous Kristine Y. , Ellsworth David S. , Hanson Paul J. , Seok Kim Hyun‐ , Warren Jeffrey M. , Oren Ram , Norby Richard J. 
Published: February 2013

AbstractPredicted responses of transpiration to elevated atmospheric CO2 concentration (eCO2) are highly variable amongst process‐based models. To better understand and constrain this variability amongst models, we conducted an intercomparison of 11 ecosystem models applied to data from two forest free‐air CO2 enrichment (FACE) experiments at Duke University and Oak Ridge National Laboratory. We analysed model structures to identify the key underlying assumptions causing differences in model predictions of transpiration and canopy water use efficiency. We then compared the models against data to identify model assumptions that are incorrect or are large sources of uncertainty. We found that model‐to‐model and model‐to‐observations differences resulted from four key sets of assumptions, namely (i) the nature of the stomatal response to elevated CO2 (coupling between photosynthesis and stomata was supported by the data); (ii) the roles of the leaf and atmospheric boundary layer (models which assumed multiple conductance terms in series predicted more decoupled fluxes than observed at the broadleaf site); (iii) the treatment of canopy interception (large intermodel variability, 2–15%); and (iv) the impact of soil moisture stress (process uncertainty in how models limit carbon and water fluxes during moisture stress). Overall, model predictions of the CO2 effect on WUE were reasonable (intermodel μ = approximately 28% ± 10%) compared to the observations (μ = approximately 30% ± 13%) at the well‐coupled coniferous site (Duke), but poor (intermodel μ = approximately 24% ± 6%; observations μ = approximately 38% ± 7%) at the broadleaf site (Oak Ridge). The study yields a framework for analysing and interpreting model predictions of transpiration responses to eCO2, and highlights key improvements to these types of models.
Efficient TALEN construction and evaluation methods for human cell and animal applications
Authors: Sakuma Tetsushi , Hosoi Sayaka , Woltjen Knut , Suzuki Ken‐ichi , Kashiwagi Keiko , Wada Housei , Ochiai Hiroshi , Miyamoto Tatsuo , Kawai Narudo , Sasakura Yasunori , Matsuura Shinya , Okada Yasushi , Kawahara Atsuo , Hayashi Shigeo , Yamamoto Takashi 
Published: February 2013

Transcription activator–like effector nucleases (TALENs) have recently arisen as effective tools for targeted genome engineering. Here, we report streamlined methods for the construction and evaluation of TALENs based on the ‘Golden Gate TALEN and TAL Effector Kit’ (Addgene). We diminished array vector requirements and increased assembly rates using six‐module concatemerization. We altered the architecture of the native TALEN protein to increase nuclease activity and replaced the final destination vector with a mammalian expression/in vitro transcription vector bearing both CMV and T7 promoters. Using our methods, the whole process, from initiating construction to completing evaluation directly in mammalian cells, requires only 1 week. Furthermore, TALENs constructed in this manner may be directly applied to transfection of cultured cells or mRNA synthesis for use in animals and embryos. In this article, we show genomic modification of HEK293T cells, human induced pluripotent stem cells, Drosophila melanogaster, Danio rerio and Xenopus laevis, using custom‐made TALENs constructed and evaluated with our protocol. Our methods are more time efficient compared with conventional yeast‐based evaluation methods and provide a more accessible and effective protocol for the application of TALENs in various model organisms.
Novel coagulation factor concentrates: Issues relating to their clinical implementation and pharmacokinetic assessment for optimal prophylaxis in haemophilia patients
Authors: Ljung R. , Auerswald G. , Benson G. , Jetter A. , Jiménez‐Yuste V. , Lambert T. , Morfini M. , Remor E. , Sørensen B. , Šalek S. Z. 
Published: February 2013

SummaryProphylaxis is considered the optimal treatment regimen for patients with severe haemophilia, and may be especially important in the prevention of joint disease. Novel coagulation factor concentrates with prolonged half‐lives promise to improve patient treatment by enabling prophylaxis with less frequent dosing. With the call to individualize therapy in haemophilia, there is growing awareness of the need to use pharmacokinetic (PK) assessments to tailor prophylaxis. However, for new factor concentrates, it is not yet known which PK values will be most informative for optimizing prophylaxis. This topic was explored at the Eighth Zurich Haemophilia Forum. On the basis of our clinical experience and a discussion of the literature, we report key issues relating to the PK assessment of new coagulation factors and include suggestions on the implementation of PK data to optimize therapy. As both inter‐ and intra‐individual variability in factor half‐life have been reported, we suggest that frequent PK assessments should be conducted. However, to diminish the burden of more frequent sampling, sparser sampling strategies and the use of population modelling should be considered. Guidelines on how to assay new factor concentrates, and which PK parameters should be measured, are needed. Concerns were raised regarding the possibility of breakthrough bleeding, and current thinking on how to prevent breakthrough bleeding may no longer be appropriate. Finally, as treatment adherence may be more important to ensure that a therapeutic level of a new coagulation factor concentrate is maintained, behavioural techniques could be implemented to help to improve treatment adherence.
Cytokine profile and FVIII inhibitors development in haemophilia A
Authors: Oliveira C. A. , Velloso‐Rodrigues C. , Machado F. C. J. , Carvalho B. N. , Gentz S. H. L. , Martins‐Filho O. A. , Chaves D. G. 
Published: February 2013

SummaryHaemophilia A is a hereditary bleeding disorder linked to the X chromosome characterized by a deficiency or defect in the coagulation factor VIII (FVIII). Individuals with this coagulopathy require constant infusions of FVIII to maintain their physical integrity and haemostasis. During treatment, some patients develop an immune response that produces antibodies to FVIII, also called inhibitors, affecting the pro‐coagulant activity of this protein. Despite the clinical relevance of FVIII inhibitors, the immune mechanisms that lead to their production are not known. This study investigated the immunological cytokine profile using plasma from HA patients which were either positive or negative for FVIII inhibitors and from healthy individuals. The results showed that healthy individuals and HA patients that do not develop FVIII inhibitors have a mixed immune response profile with high secretion of IFN‐γ, TNF‐α IL‐2 and IL‐5. In contrast, HA patients with FVIII inhibitors exhibited an anti‐inflammatory/regulatory immune response characterized by low levels of all measured cytokines except for IL‐4 and IL‐10. This profile may be related to the development and maintenance of the FVIII inhibitors. By comparing the cytokine profiles of the three different groups we have established a model explaining the immune activation resulting in the production of FVIII inhibitors in haemophilia A patients.
Transient elastography in hepatitis C virus‐infected patients with beta‐thalassemia for assessment of fibrosis
Authors: Poustchi Hossein , Eslami Masoomeh , Ostovaneh Mohammad Reza , Modabbernia Amirhossein , Saeedian Fatemeh Sima , Taslimi Shervin , George Jacob , Malekzadeh Reza , Zamani Farhad 
Published: February 2013

AimWe sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta‐thalassemia.MethodsSeventy‐six CHC patients with beta‐thalassemia underwent TE, liver biopsy, T2‐weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed.ResultsTE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2‐weighted MRI‐LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log‐transformed TE score(standardized β = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized β = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59–100%). A cut‐off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut‐off values for “TE‐FIB‐4 cirrhosis score” comprising TE and FIB‐4 and “TE‐APRI cirrhosis score” combining TE with aspartate aminotransferase‐to‐platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis.ConclusionRegardless of LIC, TE alone or when combined with FIB‐4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta‐thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB‐4 should be interpreted cautiously.
Silent information regulator 1 inhibition induces lipid metabolism disorders of hepatocytes and enhances hepatitis C virus replication
Authors: Sun Li‐Jie , Li Shu‐Chen , Zhao Yong‐Hua , Yu Jian‐Wu , Kang Peng , Yan Bing‐Zhu 
Published: February 2013

AimHepatic steatosis is an important histopathological feature of chronic hepatitis C virus (HCV) infection. Silent information regulator 1 (SIRT1) plays key role in regulation of hepatic lipid metabolism. We investigated the possible effect of HCV replication on lipid metabolism of hepatocytes and expression of SIRT1 using Huh‐7.5 cells harboring HCV replicon.MethodsThe level of reactive oxygen species (ROS) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the value of nicotinamide adenine dinucleotide (NAD+)/NADH was detected. The level of triacylglycerol (TG), total cholesterol (TC) and fatty acid β‐oxidation rate was detected. The activity and expression levels of SIRT1 and expression of its downstream lipid‐metabolism genes were measured.ResultsIn replicon cells, the level of ROS and MDA increased, SOD activity and the value of NAD+/NADH decreased, then the activity and expression level of mRNA and protein of SIRT1 reduced. Inhibition of SIRT1 decreased phosphorylation of forkhead box O1 (FoxO1), which not only upregulated SREBP‐1c, FAS, ACC, SREBP‐2, HMGR and HMGS genes and increased fatty acid synthesis; but also downregulated PPAR‐α and CPT1A genes and decreased fatty acid β‐oxidation. Interferon treatment restored aforementioned changes. SIRT1 activator improved lipid metabolism disorders by an increase in fatty acid β‐oxidation and a decrease in TG and TC synthesis and inhibited HCV replication.ConclusionHCV replication decreasing NAD+/NADH ratio may downregulate the activity and the expression of SIRT1, then change the expression profile of lipid metabolism‐related genes, thereby cause lipid metabolism disorders of hepatocytes and promote HCV replication. Treatment with SIRT1 activator ameliorates lipid metabolic disorders and inhibits HCV replication.
BioAggregate and iRoot BP Plus optimize the proliferation and mineralization ability of human dental pulp cells
Authors: Zhang S. , Yang X. , Fan M. 
Published: February 2013

AbstractAimTo investigate the cytotoxicity of BioAggregate and iRoot BP Plus root canal sealer (iRoot BP Plus) to human dental pulp cells (hDPCs) and their effect on proliferation and mineralization of hDPCs and to compare their performance with that of mineral trioxide aggregate (MTA).MethodologyHuman dental pulp cells were seeded onto the prepared BioAggregate, iRoot BP Plus and MTA, respectively. Cell proliferation was assessed by CCK‐8 cell proliferation kit on days 1, 3, 5 and 7. ALP activity was measured to evaluate the cell differentiation potential on days 1, 3, 5 and 7. The expression of odontoblastic differentiation‐related genes (dentine phosphoprotein, dentine matrix protein‐1 and osteocalcin) was measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). Statistical tests used were one‐way anova and post hoc Tukey's test.ResultsThe proliferation of hDPCs in the MTA group was suppressed throughout the culture period, whereas the BioAggregate group and the iRoot BP Plus group first significantly increased cell numbers on day 1 (P < 0.01) and then decreased on day 3 to day 7. ALP activity was enhanced in all the three groups from day 3, whilst iRoot BP Plus showed significantly higher ALP activity than MTA (P < 0.01). qRT‐PCR indicated that both BioAggregate and iRoot BP Plus groups were associated with a higher upregulation of mineralization and odontoblastic differentiation‐associated gene expressions as compared to MTA group (P < 0.05).ConclusionsBioAggregate and iRoot BP Plus were nontoxic and able to induce mineralization and odontoblastic differentiation‐associated gene expression in hDPCs.
Cystoscopic injection of N‐butyl‐2‐cyanoacrylate followed by fibrin glue for the treatment of persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy
Authors: Lim Ju Hyun , You Dalsan , Jeong In Gab , Park Hyung Keun , Ahn Hanjong , Kim Choung‐Soo 
Published: February 2013

ObjectivesVesicourethral anastomotic urine leak is a common postoperative complication of radical prostatectomy. Herein we describe a novel method for the treatment of this complication.MethodsIntervention for a prolonged or massive anastomotic urine leak was required in 10 out of 1828 patients (0.5%) submitted to radical prostatectomy between 2007 and 2011. N‐butyl‐2‐cyanoacrylate (Histoacryl) followed by fibrin glue (Greenplast) were injected under local anesthesia into vesicourethral anastomotic gaps under fluoroscopic guidance using a 20‐Fr rigid cystoscope. Cystograms were taken in all patients to confirm complete urine leak resolution before the removal of the urethral catheter.ResultsCystoscopic injection of Histoacryl followed by fibrin glue was technically successful and well tolerated in all patients. The mean time from radical prostatectomy to glue injection was 16.0 days (range 12–27 days). Urethral catheterization was required for an average of 7.7 days after cystoscopic injection of fibrin glue (range 3–13 days). These measures ultimately enabled complete resolution of the urine leak in all cases. At a mean follow up of 23.3 months, all 10 patients were fully continent. The mean time to recovery of urinary continence was 20.4 weeks (range 3.9–60.0 weeks).ConclusionsCystoscopic injection of N‐butyl‐2‐cyanoacrylate followed by fibrin glue into the anastomotic gap is both a feasible and effective solution in patients with a persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy.
Therapeutic options for intractable hematuria in advanced bladder cancer
Authors: Abt Dominik , Bywater Mirjam , Engeler Daniel Stephan , Schmid Hans‐Peter 
Published: February 2013

AbstractIntractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer‐reviewed papers published up toSeptember 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon‐aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side‐effects. Well‐designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy.
The characterization of the Phlebotomus papatasi transcriptome
Authors: Abrudan J. , Ramalho‐Ortigão M. , O'Neil S. , Stayback G. , Wadsworth M. , Bernard M. , Shoue D. , Emrich S. , Lawyer P. , Kamhawi S. , Rowton E. D. , Lehane M. J. , Bates P. A. , Valenzeula J. G. , Tomlinson C. , Appelbaum E. , Moeller D. , Thiesing B. , Dillon R. , Clifton S. , Lobo N. F. , Wilson R. K. , Collins F. H. , McDowell M. A. 
Published: February 2013

AbstractAs important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re‐emerging infectious diseases. The most devastating of the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the Old and New World. Here we present the first global transcriptome analysis of the Old World vector of cutaneous leishmaniasis, Phlebotomus papatasi (Scopoli) and compare this transcriptome to that of the New World vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed using pooled mRNA from Phlebotomus papatasi larvae, pupae, adult males and females fed sugar, blood, or blood infected with Leishmania major. A total of 47 615 generated sequences was cleaned and assembled into 17 120 unique transcripts. Of the assembled sequences, 50% (8837 sequences) were classified using Gene Ontology (GO) terms. This collection of transcripts is comprehensive, as demonstrated by the high number of different GO categories. An in‐depth analysis revealed 245 sequences with putative homology to proteins involved in blood and sugar digestion, immune response and peritrophic matrix formation. Twelve of the novel genes, including one trypsin, two peptidoglycan recognition proteins (PGRP) and nine chymotrypsins, have a higher expression level during larval stages. Two novel chymotrypsins and one novel PGRP are abundantly expressed upon blood feeding. This study will greatly improve the available genomic resources for P. papatasi and will provide essential information for annotation of the full genome.
Using decomposition to improve greedy solutions of the optimal diversity management problem
Authors: Agra Agostinho , Cerdeira Jorge Orestes , Requejo Cristina 
Published: February 2013

AbstractThe optimal diversity management problem is a special case of the p‐median problem, which arises in the production of wire harness for the automotive industry. Instances are typically very large and graphs consist of several nonconnected components. The greedy algorithm is normally applied to handle these large instances, producing solutions that are considered quite good. We design an approach that uses decomposition combined with a genetic algorithm and simulated annealing algorithm to improve greedy solutions of the optimal diversity management problem. We report computational results that render this approach as capable of improving greedy solutions on real instances from a company manufacturing wire harness for automobiles.
Attachment Style and Treatment Completion among Psychiatric Inpatients with Substance Use Disorders
Authors: Fowler James Christopher , Groat Michael , Ulanday Mike 
Published: February 2013

Background and ObjectivesA strong dose–response relationship exists for psychosocial treatments for co‐morbid substance abuse disorders; yet rates of attrition are exceedingly high for those seeking treatment in residential and hospital settings. This study examined patient characteristics, including attachment style as predictors of completing 42 contiguous days of inpatient dual‐diagnosis treatment among patients with substance use disorders.MethodsBaseline characteristics were assessed in 187 consecutively admitted patients with research diagnosis of substance use disorders. Hierarchical logistic regression analysis was used to examine predictors of treatment retention.ResultsResults indicated a two‐variable model consisting of total number of co‐occurring Axis I and II disorders, and pre‐occupied attachment style, accounting for 17% of the variance. Attachment status predicted retention above and beyond psychiatric co‐morbid disorders, demonstrating incremental predictive validity. Moderator analyses failed to detect an interaction.Conclusions and Scientific SignificanceAmong inpatients with substance abuse disorders, anxious‐preoccupied attachment style predicted treatment retention, reflecting the importance of interpersonal components of treatment relationships in completing treatment. This study adds to a growing body of evidence linking attachment style with treatment adherence. Further research is needed to examine possible mechanisms associated with this relationship. (Am J Addict 2013;22:14‐17)
Assessing Youth Participation in AA‐Related Helping: Validity of the Service to Others in Sobriety (SOS) Questionnaire in an Adolescent Sample
Authors: Pagano Maria E. , Kelly John F. , Scur Michael D. , Ionescu Rebecca A. , Stout Robert L. , Post Stephen G. 
Published: February 2013

Background and ObjectivesThe positive outcomes derived from participation in Alcoholics Anonymous‐related helping (AAH) found among adults has spurred study of AAH among minors with addiction. AAH includes acts of good citizenship in AA, formal service positions, public outreach, and transmitting personal experience to another fellow sufferer. Addiction research with adolescents is hindered by few validated assessments of 12‐step activity among minors. This study provides psychometric findings of the “Service to Others in Sobriety (SOS)” questionnaire as completed by youths.MethodsMulti‐informant data was collected prospectively from youth self‐reports, clinician‐rated assessments, biomarkers, and medical chart records for youths (N = 195) after residential treatment.ResultsFew youths (7%) did not participate in any AAH during treatment. Results indicated the SOS as a unidimensional scale with adequate psychometric properties, including inter‐informant reliability (r = .5), internal consistency (alpha = .90), and convergent validity (rs = −.3 to .3). Programmatic AAH activities distinguished abstinent youths in a random half‐sample, and replicated on the other half‐sample. The SOS cut‐point of 40 indicated high AAH participation.Conclusions and SignificanceThe SOS appears to be a valid measure of AAH, suggesting clinical utility for enhancing treatment and identifying service opportunities salient to sobriety. (Am J Addict 2013;22:60‐66)