bluuebunny/crossref_metadata_2025_split huggingface dataset:
amplisas: a web server for multilocus genotyping using next‐generation amplicon sequencing data
Authors: Sebastian Alvaro , Herdegen Magdalena , Migalska Magdalena , Radwan Jacek 
Published: August 2015

AbstractNext‐generation sequencing (NGS) technologies are revolutionizing the fields of biology and medicine as powerful tools for amplicon sequencing (AS). Using combinations of primers and barcodes, it is possible to sequence targeted genomic regions with deep coverage for hundreds, even thousands, of individuals in a single experiment. This is extremely valuable for the genotyping of gene families in which locus‐specific primers are often difficult to design, such as the major histocompatibility complex (MHC). The utility of AS is, however, limited by the high intrinsic sequencing error rates of NGS technologies and other sources of error such as polymerase amplification or chimera formation. Correcting these errors requires extensive bioinformatic post‐processing of NGS data. Amplicon Sequence Assignment (amplisas) is a tool that performs analysis of AS results in a simple and efficient way, while offering customization options for advanced users. amplisas is designed as a three‐step pipeline consisting of (i) read demultiplexing, (ii) unique sequence clustering and (iii) erroneous sequence filtering. Allele sequences and frequencies are retrieved in excel spreadsheet format, making them easy to interpret. amplisas performance has been successfully benchmarked against previously published genotyped MHC data sets obtained with various NGS technologies.
IgG4‐related disease
Authors: Kubo Kanae , Yamamoto Kazuhiko 
Published: August 2015

AbstractImmunoglobulin G4‐related disease (IgG4‐RD) is a regional or systemic fibro‐inflammatory disease of unknown etiology. It presents a distinctive histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4‐positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or tumefactive lesions. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel thyroiditis, interstitial nephritis and retroperitoneal fibrosis. Glucocorticoid therapy can resolve the clinical and pathological abnormalities and impaired organ function. IgG4‐RD was recognized internationally in 2011, and new evidence has accumulated regarding its pathogenesis, clinical features and treatment. In this review, we outline our present understanding of IgG4‐RD.
Functional significance of subjective response to alcohol across levels of alcohol exposure
Authors: Bujarski Spencer , Hutchison Kent E. , Prause Nicole , Ray Lara A. 
Published: August 2015

AbstractPre‐clinical neurobiological models of addiction etiology including both the allostatic model and incentive sensitization theory suggest that alcohol consumption among alcohol‐dependent (AD) individuals will be dissociated from hedonic reward as positive reinforcement mechanisms wane in later stage dependence. The aims of this study are to test this claim in humans by examining the relationship between dimensions of subjective responses to alcohol (SR) and alcohol craving across levels of alcohol exposure. Non‐treatment‐seeking drinkers (n = 205) completed an i.v. alcohol challenge (final target breath alcohol concentration = 0.06 g/dl) and reported on SR and craving. Participants were classified as light‐to‐moderate drinkers (LMD), heavy drinkers (HD) or AD. Analyses examined group differences in SR and craving response magnitude, as well as concurrent and predictive associations between SR domains and craving. At baseline, LMD and AD reported greater stimulation than HD, which carried over post‐alcohol administration. However, stimulation was dose‐dependently associated with alcohol craving in HD only. Furthermore, lagged models found that stimulation preceded craving among HD only, whereas this hypothesized pattern of results was not observed for craving preceding stimulation. Sedation was also positively associated with craving, yet no group differences were observed. In agreement with the prediction of diminished positive reinforcement in alcohol dependence, this study showed that stimulation/hedonic reward from alcohol did not precede craving in AD, whereas stimulation was dose‐dependently associated with and preceded craving among non‐dependent HD.
The impact of CYP3A5*3 polymorphism on sirolimus pharmacokinetics: insights from predictions with a physiologically‐based pharmacokinetic model
Authors: Emoto Chie , Fukuda Tsuyoshi , Venkatasubramanian Raja , Vinks Alexander A. 
Published: August 2015

AimsSirolimus is an mTOR inhibitor metabolized by CYP3A4 and CYP3A5. Reported effects of CYP3A5 polymorphisms on sirolimus pharmacokinetics (PK) have shown unexplained discrepancies across studies. We quantitatively assessed the effect of CYP3A5*3 status on sirolimus PK by in vitro assessment and simulation using a physiologically‐based PK (PBPK) model. In addition, we explored designs for an adequately powered pharmacogenetic association study.MethodIn vitro metabolism studies were conducted to confirm individual CYP contribution to sirolimus metabolism. PK profiles were simulated in CYP3A5 expressers and non‐expressers with a PBPK model. The pre‐dose concentration predictions were used as the outcome parameter to estimate the required sample size for a pharmacogenetic association study.ResultsSirolimus metabolism was inhibited by over 90% by ketoconazole, a CYP3A specific inhibitor. The PBPK model developed based on CLint of recombinant CYP3A4, CYP3A5 and CYP2C8 predicted a small CYP3A5*3 effect on simulated sirolimus PK profiles. A subsequent power analysis based on these findings indicated that at least 80 subjects in an enrichment design, 40 CYP3A5 expressers and 40 non‐expressers, would be required to detect a significant difference in the predicted trough concentrations at 1 month of therapy (P < 0.05, 80% power).ConclusionsThis study suggests that CYP3A5 contribution to sirolimus metabolism is much smaller than that of CYP3A4. Observed discrepancies across studies could be explained as the result of inadequate sample size. PBPK model simulations allowed mechanism‐based evaluation of the effects of CYP3A5 genotype on sirolimus PK and provided preliminary data for the design of a future prospective study.
Quaternion Julia Set Shape Optimization
Authors: Kim Theodore 
Published: August 2015

AbstractWe present the first 3D algorithm capable of answering the question: what would a Mandelbrot‐like set in the shape of a bunny look like? More concretely, can we find an iterated quaternion rational map whose potential field contains an isocontour with a desired shape? We show that it is possible to answer this question by casting it as a shape optimization that discovers novel, highly complex shapes. The problem can be written as an energy minimization, the optimization can be made practical by using an efficient method for gradient evaluation, and convergence can be accelerated by using a variety of multi‐resolution strategies. The resulting shapes are not invariant under common operations such as translation, and instead undergo intricate, non‐linear transformations.
Personality, attrition and weight loss in treatment seeking women with obesity
Authors: Dalle Grave R. , Calugi S. , Compare A. , El Ghoch M. , Petroni M. L. , Colombari S. , Minniti A. , Marchesini G. 
Published: August 2015

SummaryStudies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre‐treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m−2) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12‐month observation period, 32.3% of cases were lost to follow‐up. After adjustment for demographic confounders and the severity of eating disorders, noTCIpersonality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss ≥10% (odds ratio, 0.983; 95% confidence interval, 0.975–0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight.
Synchronous mantle cell lymph node lymphoma and pulmonary adenocarcinoma: a case report with literature review
Authors: Braham Emna , Zarrouk Mourad , Mlika Mouna , Kilani Tarek , El Mezni Faouzi 
Published: August 2015

AbstractBackground and AimsCoexistence of mantle cell lymphoma and lung adenocarcinoma is extremely rare. The aim of this study is to present the first case of incidental discovery of primary lung adenocarcinoma associated to lymph node mantle cell lymphoma.MethodsA 45 year‐old man, admitted for inguinal mass appeared since three months. Physical examination showed a 1 cm axillary and 3 cm inguinal adenopathies which were hard and fixed. A biopsy of inguinal mass revealed mantle cell lymphoma. Assessment of disease extension found a right superior lobe tumor with mediastinal lymphadenopathies. Fibreoptic bronchoscopy was normal. A fine needle biopsy of lung tumor was performed to determinate the nature of the pulmonary lesion. Histopathological findings were consistent with primary poor differentiated pulmonary adenocarcinoma with TTF‐1 expression. A first mediastinoscopy was realized to verify mediastinal lymphadenopathies; frozen section showed a mantle cell lymphoma. A right lobectomy was then performed confirming the diagnosis of lung adenocarcinoma.Then, the patient was treated for the mantle cell lymphoma by 6 cures of alternating RCHOP and RDHAP (dexamethasone, high‐dose Ara‐Cytarabine and cisplatin) regimens followed by autologous stem cell transplantation.ResultsThe patient died because of treatment complications 3 years after diagnosis.ConclusionProgresses are necessary to understand the pathogenesis of of synchronous occurrence of both diseases.
A RCT of telehealth for COPD patient's quality of life: the whole system demonstrator evaluation
Authors: Rixon Lorna , Hirani Shashivadan P. , Cartwright Martin , Beynon Michelle , Doll Helen , Steventon Adam , Henderson Catherine , Newman Stanton P. 
Published: August 2015

AbstractIntroduction/ObjectivesDespite some concerns that the introduction of telehealth (TH) may lead to reductions in quality of life (QoL), lower mood and increased anxiety in response to using assistive technologies to reduce health care utilisation and manage long term conditions, this research focuses on the extent to which providing people with tools to monitor their condition can improve QoL.MethodsThe Chronic Obstructive Pulmonary Disease (COPD) cohort of the Whole Systems Demonstrator Trial is a pragmatic General Practitioner (GP) clustered randomised controlled trial (RCT) evaluating TH in the UK from three regions in England. All patients at a participating GP practice were deemed eligible for inclusion in the study if they were diagnosed with COPD.Results447 participants completed baseline and either a short (4 months) or long term (12 months) follow‐up. There was a trend of improved QoL and mood in the TH group at longer‐term follow‐up, but not short term follow‐up. Emotional functioning (g = 0.280 95%CI, 0.051–0.510) and mastery reached (g = 2.979 95%CI, 0–0.46) significance at P < 0.05 (all Hedges g <0.3).ConclusionsTH showed minimal benefit to QoL in COPD patients who were not preselected to be at increased risk of acute exacerbations. Benefits were more likely in disease specific measures at longer term follow‐up. TH is a complex intervention and should be embedded in a service that is evidenced based. Outcome measures must be sensitive enough to detect changes in the target population for the specific intervention.
Elucidation of the structure of retroviral proteases: a reminiscence
Authors: Jaskolski Mariusz , Miller Maria , Mohana Rao J. K. , Gustchina Alla , Wlodawer Alexander 
Published: August 2015

Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV‐1, published just over 25 years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure‐assisted drug design effort that offered new hope for controlling the then‐escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined.
Eutrophication effects on greenhouse gas fluxes from shallow‐lake mesocosms override those of climate warming
Authors: Davidson Thomas A. , Audet Joachim , Svenning Jens‐Christian , Lauridsen Torben L. , Søndergaard Martin , Landkildehus Frank , Larsen Søren E. , Jeppesen Erik 
Published: August 2015

AbstractFresh waters make a disproportionately large contribution to greenhouse gas (GHG) emissions, with shallow lakes being particular hot spots. Given their global prevalence, how GHG fluxes from shallow lakes are altered by climate change may have profound implications for the global carbon cycle. Empirical evidence for the temperature dependence of the processes controlling GHG production in natural systems is largely based on the correlation between seasonal temperature variation and seasonal change in GHG fluxes. However, ecosystem‐level GHG fluxes could be influenced by factors, which while varying seasonally with temperature are actually either indirectly related (e.g. primary producer biomass) or largely unrelated to temperature, for instance nutrient loading. Here, we present results from the longest running shallow‐lake mesocosm experiment which demonstrate that nutrient concentrations override temperature as a control of both the total and individual GHG flux. Furthermore, testing for temperature treatment effects at low and high nutrient levels separately showed only one, rather weak, positive effect of temperature (CH4 flux at high nutrients). In contrast, at low nutrients, the CO2 efflux was lower in the elevated temperature treatments, with no significant effect on CH4 or N2O fluxes. Further analysis identified possible indirect effects of temperature treatment. For example, at low nutrient levels, increased macrophyte abundance was associated with significantly reduced fluxes of both CH4 and CO2 for both total annual flux and monthly observation data. As macrophyte abundance was positively related to temperature treatment, this suggests the possibility of indirect temperature effects, via macrophyte abundance, on CH4 and CO2 flux. These findings indicate that fluxes of GHGs from shallow lakes may be controlled more by factors indirectly related to temperature, in this case nutrient concentration and the abundance of primary producers. Thus, at ecosystem scale, response to climate change may not follow predictions based on the temperature dependence of metabolic processes.
Morpho‐anatomical traits of root and non‐enzymatic antioxidant system of leaf tissue contribute to waterlogging tolerance in Brachiaria grasses
Authors: Jiménez Juan de la Cruz , Cardoso Juan Andrés , Dominguez Moralba , Fischer Gerhard , Rao Idupulapati 
Published: August 2015

AbstractSoil waterlogging is a major abiotic stress that affects the growth and yield of forage grasses in the tropics. Brachiaria forage grasses are widely planted in the tropics to sustain livestock production. An outdoor study was conducted using plastic cylinders under drained and waterlogged soil conditions in order to identify root and shoot traits associated with waterlogging tolerance in Brachiaria ruziziensis (waterlogging sensitive) and Brachiaria humidicola (waterlogging tolerant). For that reason, dry mass, leaf chlorophyll content, photosynthetic efficiency, root morpho‐anatomical traits (aerenchyma, stele proportion, suberin deposition) and total non‐enzymatic antioxidant activity in leaf tissue were determined. Under waterlogging, reductions of shoot biomass, chlorophyll loss, impairment of photosynthetic efficiency and diminution of antioxidant system were found in B. ruziziensis but not in B. humidicola. In B. humidicola an increase of the antioxidant system in response to waterlogging was found. Under waterlogging, both grasses showed an increase in root aerenchyma, reduction of root stele proportion and shorter roots than plants grown under drained conditions. We conclude that a combination of greater aerenchyma formation, smaller stele proportions, increased suberin deposition in the outer part of the root and an escalation of the non‐enzymatic antioxidant system acts to enhance root aeration and prevent the deleterious effect of reactive oxygen species in plants of B. humidicola subjected to waterlogged conditions.
Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners
Authors: Bennett A. L. , Buckton S. , Lawrance I. , Leong R. W. , Moore G. , Andrews J. M. 
Published: August 2015

AbstractBackgroundCurrent models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management.AimsThis study aimed to produce and evaluate evidence‐based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision‐making.MethodsThree tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014.ResultsThree quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC.ConclusionEvidence‐based outpatient clinical management tools for UC can be developed. The concept and end‐product have been well received by all stakeholder groups. These tools should support non‐specialist clinicians to optimise UC management and empower patients by facilitating them to safely self‐manage and identify when medical support is needed.
Disability and Domination: Lessons from Republican Political Philosophy
Authors: O'Shea Tom 
Published: August 2015

AbstractThe republican ideal of non‐domination identifies the capacity for arbitrary interference as a fundamental threat to liberty that can generate fearful uncertainty and servility in those dominated. I argue that republican accounts of domination can provide a powerful analysis of the nature of legal and institutional power that is encountered by people with mental disorders or cognitive disabilities. In doing so, I demonstrate that non‐domination is an ideal which is pertinent, distinctive, and desirable in thinking through psychological disability. Finally, I evaluate republican strategies for contesting domination, focusing on the limits of contestatory democracy, and proposing a participatory alternative which better addresses problems of political agency in the mentally disordered and cognitively disabled.
Better to Exploit than to Neglect? International Clinical Research and the Non‐Worseness Claim
Authors: Malmqvist Erik 
Published: August 2015

AbstractClinical research is increasingly ‘offshored’ to developing countries, a practice that has generated considerable controversy. It has recently been argued that the prevailing ethical norms governing such research are deeply puzzling. On the one hand, sponsors are not required to offshore trials, even when participants in developing countries would benefit considerably from these trials. On the other hand, if sponsors do offshore, they are required not to exploit participants, even when the latter would benefit from and consent to exploitation. How, it is asked, can it be worse to exploit the global poor than to neglect them when exploitation is voluntary and makes them better off? The present article seeks to respond to this challenge. I argue that mutually beneficial and voluntary exploitation can be worse than neglect when — as is typically true of exploitative international research — it takes advantage of unjust background conditions. This is because, in such cases, exploitation overlaps with another, less familiar wrong: complicity in injustice. Recognising complicity as a distinct wrong should make us judge exchanges arising from background injustice more harshly than we typically do, in research and elsewhere.
Minimally invasive non‐surgical approach for the treatment of periodontal intrabony defects: a retrospective analysis
Authors: Nibali Luigi , Pometti Daniela , Chen Tzu‐Ting , Tu Yu‐Kang 
Published: August 2015

AbstractAimThe aim of this retrospective analysis was to assess healing of intrabony defects treated with minimally invasive non‐surgical therapy (MINST).MethodsA retrospective analysis was carried out in 35 consecutive intrabony defects treated by MINST (without any adjuncts) in 23 non‐smoking patients. All defects had a radiographic intrabony component > 3 mm and had clinical and radiographic data available at baseline and 12 after treatment. Pre‐ and post‐treatment radiographs were analysed and bone levels were compared by multilevel linear regression adjusted by latent variable method.ResultsFollowing MINST, the average PPD and CAL reduction in the intra‐bony defects were 3.12 mm and 2.78 mm respectively (p < 0.001). The average radiographic intrabony vertical defect depth was reduced by 2.93 mm (from 6.74 mm to 3.81 mm) (p < 0.001), whereas the average defect angle changed from and 28.5° at baseline to 44.4° at re‐evaluation (p < 0.001). Smaller initial defect angles and deeper initial defect depths were associated with greater defect depth reduction. Greater initial defect angles were associated with less defect angle change.ConclusionsThis paper shows considerable clinical and radiographic improvements after MINST, therefore bringing evidence to support its efficacy for the treatment of intrabony defects in non‐smokers.