bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Content Analysis/Screening for Predictive Toxicology: Application to Hepatotoxicity and Genotoxicity
Authors: Persson Mikael , Løye Anni F. , Jacquet Mélanie , Mow Natacha S. , Thougaard Annemette V. , Mow Tomas , Hornberg Jorrit J. 
Published: January 2014

AbstractHigh‐content imaging/analysis has emerged as a powerful tool for predictive toxicology as it can be used for identifying and mitigating potential safety risks during drug discovery. By careful selection of end‐points, some cellular assays can show better predictivity than routine animal toxicity testing for certain adverse events. Here, we present the perhaps most utilized high‐content screening assays for predictive toxicology in the pharmaceutical industry. Multi‐parametric imaging of cell health in simple and cost‐effective model systems can be used to predict human hepatotoxicity and elucidate mechanisms of toxicity, and imaging of bile salt transport inhibition in sandwich‐cultured hepatocytes can be used to predict cholestasis‐inducing compounds. Imaging of micronuclei formation in simple cell models can be used to detect genotoxic potential and elucidate anuegenic or clastogenic mode of actions. The hope is that application of these relatively predictive assays during drug discovery will reduce toxicity and safety‐related attrition of drug development programmes at later stages.
A Lectin from Spatholobus parviflorus Inhibits Aspergillus flavus α‐Amylase: Enzyme Kinetics and Thermodynamic Studies
Authors: Tintu Ignatius , Abhilash Joseph , Dileep Kalarickal V. , Augustine Anu , Haridas Madathilkovilakath , Sadasivan Chittalakkottu 
Published: January 2014

Aspergillus flavus is a commonly found fungal pathogen which produces structurally related and highly toxic secondary metabolites, aflatoxins. It has been proposed that α‐amylase inhibitors may limit the ability of the fungus to produce aflatoxins. Hence, this enzyme is a potent target for the development of antifungal agents. In this study, it was found that Spatholobus parviflorus seed lectin (SPL) can inhibit the growth of A. flavus with a MIC value of 1.5 mg/mL. The enzyme kinetics, molecular modeling and isothermal titration calorimetric studies suggest that SPL can inhibit α‐amylase with Ki value of 0.0042 mm. Hence, it is suggested that the antifungal activity of SPL might be partly due to its ability to inhibit the enzyme α‐amylase.
Decision making on detection and triage of oral mucosa lesions in community dental practices: screening decisions and referral
Authors: Laronde Denise M. , Williams P. M. , Hislop T. G. , Poh Catherine , Ng Samson , Zhang Lewei , Rosin Miriam P. 
Published: January 2014

AbstractOral cancer is a substantial, often unrecognized issue globally, with close to 300 000 new cases reported annually. It is a management conundrum: a cancer site that is easily examined; yet more than 40% of oral cancers are diagnosed at a late stage when prognosis is poor and treatment can be devastating. Opportunistic screening within the dental office could lead to earlier diagnosis and intervention with improved survival.ObjectiveTo describe how clinicians make decisions about referral based on the risk classification of the lesion.MethodsEighteen dentists from 15 dental offices participated in a 1‐day workshop on oral cancer screening. Participants then screened patients (medical history, conventional oral exam, fluorescent visualization examination) in‐office for 11 months, triaging patients by apparent clinical risk: low risk (common benign conditions, geographic tongue, candidiasis, trauma), intermediate risk (lichenoid lesions) and high risk (white or red lesions or ulcers without apparent cause). Clinicians made the decision on which lesions to reassess in 3 weeks based on risk assessment and clinical judgment. Lesions of concern were seen by a community facilitator or referred to an oral medicine specialist.ResultsOf 2542 patients were screened, and 389 lesions were identified (15% of patients). 350 were determined to be low risk (90%), 19 intermediate risk (IR) (5%), and 20 high risk (HR) (5%). One hundred and sixty‐six (43%) patients were recalled for 3‐week reassessment: 90% of HR lesions, 63% of IR lesions (63%), and 39% of low‐risk lesions. Compliance to recall was high (92% of cases). Reassessment eliminated the referral of 99/166 (60%) of lesions that had resolved. six lesions were biopsied with three low‐grade dysplasias identified.ConclusionsThree key decision points were tested: risk assessment, need for reassessment, and need for referral. A 3‐week reassessment appointment was invaluable to prevent the unnecessary referral due to confounders. There is a need for a well‐defined triage pathway to facilitate oral cancer screening and a methodical and consistent approach to opportunistic screening in the dental office.
Impact of dental caries and trauma on quality of life among 5‐ to 6‐year‐old children: perceptions of parents and children
Authors: Abanto Jenny , Tsakos Georgios , Paiva Saul Martins , Carvalho Thiago S. , Raggio Daniela P. , Bönecker Marcelo 
Published: January 2014

AbstractObjectiveTo assess the impact of dental caries and traumatic dental injuries (TDI) on the oral health‐related quality of life (OHRQoL) of 5‐ to 6‐year‐olds according to both self‐ and parental reports.MethodsA total of 335 pairs of parents and children who sought dental screening at the Dental School, University of São Paulo, completed the Scale of Oral Health Outcomes for 5‐year‐old children (SOHO‐5), which consists of a child self‐report and a parental proxy‐report version. Three calibrated examiners assessed the experience of caries according to primary teeth that were decayed, indicated for extraction due to caries, or filled (def‐t). TDI were classified into uncomplicated and complicated injuries. Poisson regression models were used to associate the different clinical and sociodemographic factors to the outcome.ResultsOverall, 74.6% of children reported an oral impact, and the corresponding estimate for parental reports was 70.5%. The mean (standard deviation) SOHO‐5 scores in child self‐report and parental versions were 3.32(3.22) and 5.18(6.28), respectively. In both versions, caries was associated with worse children's OHRQoL, for the total score and all SOHO‐5 items (P < 0.001). In contrast, TDI did not have a negative impact on children's OHRQoL, with the exception of two items of the parental version and one item of the child self‐report version. In the final multivariate adjusted models, there was a gradient in the association between caries experience and child's OHRQoL with worse SOHO‐5 score at each consecutive level with more severe caries experience, for both child and parental perceptions [RR (CI 95%) = 6.37 (4.71, 8.62) and 10.81 (7.65, 15.27)], respectively. A greater family income had a positive impact on the children's OHRQoL for child and parental versions [RR (CI 95%) = 0.68 (0.49, 0.94) and 0.70 (0.54, 0.90)], respectively.ConclusionsDental caries, but not TDI, is associated with worse OHRQoL of 5‐ to 6‐year‐old children in terms of perceptions of both children and their parents. Families with higher income report better OHRQoL at this age, independent of the presence of oral diseases.
An immune response study of oakmoss absolute and its constituents atranol and chloroatranol
Authors: Menné Bonefeld Charlotte , Nielsen Morten Milek , Gimenéz‐Arnau Elena , Lang Matthieu , Vennegaard Marie Torp , Geisler Carsten , Johansen Jeanne Duus , Lepoittevin Jean‐Pierre 
Published: January 2014

SummaryBackgroundAtranol and chloroatranol are the main allergens of oakmoss absolute. However, the immune responses induced by these substances are poorly characterized.ObjectivesTo characterize immune responses induced by atranol, chloroatranol and oakmoss absolute in mice.MethodsMice were sensitized and challenged with various concentrations of atranol, chloroatranol, and oakmoss absolute. The immune responses were analysed as B cell infiltration, T cell proliferation in the draining lymph nodes, and expression of interleukin (IL)‐18, IL‐1β and tumour necrosis factor‐α in skin. The cytotoxicity of atranol and chloroatranol against keratinocytes was determined.ResultsSensitization experiments showed that atranol, chloroatranol and oakmoss induced sensitization when applied in high concentrations. Challenge experiments showed that even low concentrations of atranol and chloroatranol induced sensitization. In parallel, atranol and chloroatranol elicited challenge reactions following sensitization with oakmoss. The magnitude of the immune response to the three allergens increased in the following order: atranol, chloroatranol, and oakmoss. The expression of proinflammatory cytokines was induced by chloroatranol and oakmoss, but not by atranol. Chloroatranol was found to be more cytotoxic than atranol against keratinocytes.ConclusionsAtranol and chloroatranol can elicit both sensitization and challenge reactions, but the mixture of allergens in oakmoss absolute is more potent than atranol and chloroatranol alone.
Exotic birds show lags in population growth
Authors: Aagaard Kevin , Lockwood Julie 
Published: January 2014

AbstractAimA key aspect of the ecology and management of biological invasions is the prevalence and duration of lag phases in population growth. Here, we explore the occurrence of lag phases in exotic bird populations using theAudubonChristmasBirdCount database.LocationHawaiianIsland archipelago.MethodsWe expand on the use of piecewise model fitting techniques to detect lags in exotic bird populations onHawaii. We searched for explanations as to the occurrence of these lags using five possible mechanisms (body size, niche breadth, propagule pressure, length of record and lag phase growth rate).ResultsWe found evidence of lag phases for 14 of 17 species we evaluated (range: 10–38 years, mean using observed data = 16 ± 12), and we discovered very rapid growth to maximum abundance following the end of the lag phase (mean using observed data = 8 ± 6 years). We found no evidence for any association between the possible mechanisms influencing the occurrence and duration of the lag phases.Main conclusionsOur results are the first to rigorously quantify lags in exotic animal populations; most existing evidence comes from plants. We show that lags are as common in birds as in plants, although we provide preliminary evidence that the duration of lags in birds is shorter than in plants. We highlight the need for continued efforts to elucidate lag phase occurrence and duration in biological invasions, and we demonstrate the expanded utility of piecewise model fitting approaches to quantify these lags using count data.
Approaching low liver iron burden in chelated patients with non‐transfusion‐dependent thalassemia: the safety profile of deferasirox
Authors: Taher Ali T. , Porter John B. , Viprakasit Vip , Kattamis Antonis , Chuncharunee Suporn , Sutcharitchan Pranee , Siritanaratkul Noppadol , Origa Raffaella , Karakas Zeynep , Habr Dany , Zhu Zewen , Cappellini M. Domenica 
Published: January 2014

AbstractObjectivePatients with non‐transfusion‐dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over‐chelation emerges as patients reach low, near‐normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3.MethodsTHALASSA was a randomized, double‐blind, placebo‐controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1‐yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end‐of‐core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2).ResultsMean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure‐adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment.ConclusionsThe deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over‐chelation.
Role of a histamine 4 receptor as an anti‐inflammatory target in carrageenan‐induced pleurisy in mice
Authors: Ahmad Sheikh Fayaz , Zoheir Khairy M. A. , Abdel‐Hamied Hala E. , Alrashidi Ibrahim , Attia Sabry M. , Bakheet Saleh A. , Ashour Abdelkader E. , Abd‐Allah Adel R. A. 
Published: January 2014

SummaryThe histamine 4 receptor (H4R) is expressed primarily on cells involved in inflammation and immune responses. Despite much research into inflammatory diseases, no drugs with favourable safety profiles are yet available for their treatment. The aim of the present study was to determine the potential anti‐inflammatory effect of 4‐methylhistamine (4‐MeH) or JNJ77777120 (JNJ) and to explore the role of H4R in a mouse model of carrageenan (Cg) ‐induced pleurisy. A single dose of 4‐MeH or JNJ (30 mg/kg) was administered intraperitoneally 1 hr before Cg administration. The results illustrate that both the numbers of CD4+, CD25+, CD4+ CD25+, GITR+, GITR+ IL‐17A+‐expressing T cells and the levels of T helper type 1 (Th1)/Th17 cytokines were markedly increased in both the Cg‐treated and 4‐MeH‐treated groups, whereas the cytokines produced by Th2 cells were significantly decreased in the same groups. However, JNJ treatment significantly decreased both the number of T‐cell subsets and GITR+, GITR+ IL‐17A+‐expressing T cells, and the production of Th1/Th17 cytokines. Further, JNJ up‐regulated the expression of the Th2 cytokines. RT‐PCR analysis revealed an increased expression of interleukin‐1β, tumour necrosis factor‐α, monocyte chemoattractant protein‐1 and intercellular adhesion molecule‐1 in the Cg‐treated and 4‐MeH‐treated groups, which was reduced by treatment with JNJ in lung tissues. Moreover, histological examinations revealed anti‐inflammatory effects of JNJ, whereas 4‐MeH worsened Cg‐induced inflammation. In conclusion, the results of the present work clearly indicate that JNJ possesses important anti‐inflammatory properties that are increased in 4‐MeH‐treated mice, suggesting that H4R are involved in pleurisy and that JNJ has an anti‐inflammatory effect in associated disease conditions.
Pericellular oxygen monitoring with integrated sensor chips for reproducible cell culture experiments
Authors: Kieninger J. , Aravindalochanan K. , Sandvik J. A. , Pettersen E. O. , Urban G. A. 
Published: January 2014

AbstractObjectivesHere we present an application, in two tumour cell lines, based on the Sensing Cell Culture Flask system as a cell culture monitoring tool for pericellular oxygen sensing.Materials and methodsT‐47D (human breast cancer) and T98G (human brain cancer) cells were cultured either in atmospheric air or in a glove‐box set at 4% oxygen, in both cases with 5% CO2 in the gas phase. Pericellular oxygen tension was measured with the help of an integrated sensor chip comprising oxygen sensor arrays.ResultsObtained results illustrate variation of pericellular oxygen tension in attached cells covered by stagnant medium. Independent of incubation conditions, low pericellular oxygen concentration levels, usually associated with hypoxia, were found in dense cell cultures.ConclusionsRespiration alone brought pericellular oxygen concentration down to levels which could activate hypoxia‐sensing regulatory processes in cultures believed to be aerobic. Cells in culture believed to experience conditions of mild hypoxia may, in reality, experience severe hypoxia. This would lead to incorrect assumptions and suggests that pericellular oxygen concentration readings are of great importance to obtain reproducible results when dealing with hypoxic and normoxic (aerobic) incubation conditions. The Sensing Cell Culture Flask system allows continuous monitoring of pericellular oxygen concentration with outstanding long‐term stability and no need for recalibration during cell culture experiments. The sensor is integrated into the flask bottom, thus in direct contact with attached cells. No additional equipment needs to be inserted into the flask during culturing. Transparency of the electrochemical sensor chip allows optical inspection of cells attached on top of the sensor.
Assessment and Treatment of Challenging Behaviour for Individuals with Intellectual Disability: A Research Review
Authors: Lloyd Blair P. , Kennedy Craig H. 
Published: January 2014

BackgroundChallenging behaviour is frequently associated with the presence of intellectual disability. If not effectively treated, chronic challenging behaviour can negatively impact a variety of quality of life outcomes for individuals with intellectual disability.Methods and ResultsWe review the current status of research relating to the assessment and treatment of challenging behaviour for people with intellectual disability. We briefly review the history of interventions for challenging behaviour that led to the development of function‐based approaches widely in use today. We then discuss the various operant functions of challenging behaviour, functional behaviour assessment technologies and reinforcement‐based interventions.ConclusionsWe conclude with a discussion of future directions that include models of prevention, ecological validity of assessment procedures and the widespread use of comprehensive behavioural support programmes.
Dissection of additive genetic variability for quantitative traits in chickens using SNP markers
Authors: Abdollahi‐Arpanahi R. , Pakdel A. , Nejati‐Javaremi A. , Moradi Shahrbabak M. , Morota G. , Valente B.D. , Kranis A. , Rosa G.J.M. , Gianola D. 
Published: January 2014

SummaryThe aim of this study was to separate marked additive genetic variability for three quantitative traits in chickens into components associated with classes of minor allele frequency (MAF), individual chromosomes and marker density using the genomewide complex trait analysis (GCTA) approach. Data were from 1351 chickens measured for body weight (BW), ultrasound of breast muscle (BM) and hen house egg production (HHP), each bird with 354 364 SNP genotypes. Estimates of variance components show that SNPs on commercially available genotyping chips marked a large amount of genetic variability for all three traits. The estimated proportion of total variation tagged by all autosomal SNPs was 0.30 (SE 0.04) for BW, 0.33 (SE 0.04) for BM, and 0.19 (SE 0.05) for HHP. We found that a substantial proportion of this variation was explained by low frequency variants (MAF <0.20) for BW and BM, and variants with MAF 0.10–0.30 for HHP. The marked genetic variance explained by each chromosome was linearly related to its length (R2 = 0.60) for BW and BM. However, for HHP, there was no linear relationship between estimates of variance and length of the chromosome (R2 = 0.01). Our results suggest that the contribution of SNPs to marked additive genetic variability is dependent on the allele frequency spectrum. For the sample of birds analysed, it was found that increasing marker density beyond 100K SNPs did not capture additional additive genetic variance.
Engineering of pre‐vascularized urethral patch with muscle flaps and hypoxia‐activated hUCMSCs improves its therapeutic outcome
Authors: Sun Dongchong , Yang Yong , Wei Zhitao , Xu Yong , Zhang Xu , Hong Baofa 
Published: January 2014

AbstractTissue engineering has brought new hopes for urethral reconstruction. However, the absence of pre‐vascularization and the subsequent degradation of materials often lead to the failure of in vivo application. In this study, with the assistance of hypoxia‐activated human umbilical cord mesenchymal stem cells (hUCMSCs), pedicled muscle flaps were used as materials and pre‐incubated in ventral penile subcutaneous cavity of rabbit for 3 weeks to prepare a pre‐vascularized urethral construct. We found that small vessels and muscle fibres were scattered in the construct after 3 weeks' pre‐incubation. The construct presented a fibrous reticular structure, which was similar to that of the corpus spongiosum under microscope examination. The produced constructs were then used as a patch graft for reconstruction of the defective rabbit urethra (experimental group), natural muscular patch was used as control (control group). Twelve weeks after the reconstructive surgery, urethrography and urethroscope inspections showed wide calibres of the reconstructed urethra in the experimental group. Histopathological studies revealed that fibrous connective tissues and abundant muscle fibres constituted the main body of the patch‐grafted urethra. In contrast, in the control group, only adipose tissue was found in the stenosis‐reconstructed urethra, replacing the originally grafted muscular tissue. To our knowledge, this is the first report that successfully constructed a pre‐vascularized urethral construct by using hypoxia‐activated hUCMSC and pedicled muscle flaps. More importantly, the pre‐vascularized construct showed a good performance in urethral reconstruction when applied in vivo. The study provided a novel strategy for tissue engineering of pre‐vascularized urethral construct for the defective urethra, representing a further advancement in urethral reconstruction.
Skin‐Tissue‐sparing Excision with Electrosurgical Peeling (STEEP): a surgical treatment option for severe hidradenitis suppurativa Hurley stage II/III
Authors: Blok J.L. , Spoo J.R. , Leeman F.W.J. , Jonkman M.F. , Horváth B. 
Published: January 2014

AbstractBackgroundSurgery is the only curative treatment for removal of the persistent sinus tracts in the skin that are characteristic of severe hidradenitis suppurativa (HS). Complete resection of the affected tissue by wide excision is currently regarded as the preferred surgical technique in these cases. However, relatively large amounts of healthy tissue are removed with this method and suitable skin‐tissue‐saving techniques aiming at creating less‐extensive surgical defects are therefore needed in severe HS.MethodWe describe a skin‐tissue‐saving surgical technique for HS Hurley stage II–III disease: the Skin‐Tissue‐sparing Excision with Electrosurgical Peeling (STEEP) procedure.DiscussionIn contrast to wide excisions that generally reach into the deep subcutaneous fat, the fat is maximally spared with the STEEP procedure by performing successive tangential excisions of lesional tissue until the epithelialized bottom of the sinus tracts has been reached. From here, secondary intention healing can occur. In addition, fibrotic tissue is completely removed in the same manner as this also serves as a source of recurrence. This tissue‐sparing technique results in low recurrence rates, high patient satisfaction with relatively short healing times and favourable cosmetic outcomes without contractures.