bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of baseline lung function and bronchodilator response in 4-year-old children
Authors: Dom Sandra , Weyler Joost J. , Droste Jos H.J. , Hagendorens Margo M. , Dierckx Elke , Bridts Chris H. , De Backer Wilfried , Oostveen Ellie 
Published: June 2014

The prolonged period required for maturation of the respiratory system makes it vulnerable to environmental exposure. This study aimed to investigate the association between early-life factors and lung function in preschool children.Children aged 4 years, who were included in a prospective birth cohort, underwent lung function testing at baseline (n=535) and after bronchodilation (n=498) by forced oscillations. Information on symptoms and exposures was collected through half-yearly questionnaires. Allergen-specific serum IgE was quantified at 1 and 4 years.Multiple linear regression analysis showed that the baseline respiratory resistance and reactance area were larger in the children with previous wheeze, those with early-onset sensitisation to inhalant allergens and those who were smaller. Furthermore, children with previous lower respiratory tract infections exhibited higher baseline resistance values. The baseline resistance was the only independent determinant of the bronchodilator-induced change in resistance, whereas current height and baseline reactance area were independently associated with the change in reactance area.In conclusion, previous lower respiratory tract infections, the timing of previous wheeze, inhalant sensitisation and current height independently influence the baseline lung function of 4-year-old children, whereas baseline lung function is the principal determinant of the bronchodilator response.
Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life
Authors: Kellberger Jessica , Peters-Weist Astrid S. , Heinrich Sabine , Pfeiffer Susanne , Vogelberg Christian , Roller Diana , Genuneit Jon , Weinmayr Gudrun , von Mutius Erika , Heumann Christian , Nowak Dennis , Radon Katja 
Published: June 2014

Although work-related asthma and allergies are a huge burden for society, investigation of occupational exposures in early work life using an unexposed reference group is rare. Thus, the present analyses aimed to assess the potential impact of occupational exposure and other risk factors on the prevalence of work-related sensitisation and incidence of allergic rhinitis/asthma using a population-based approach and taking into account an unexposed reference group.In SOLAR (Study on Occupational Allergy Risks) II, German participants of ISAAC (International Study of Asthma and Allergies in Childhood) phase II were followed from childhood (9–11 years) until early adulthood (19–24 years). Data on 1570 participants were available to fit predictive models.Occupational exposure was not statistically significantly associated with disease prevalence/incidence. Sensitisation in childhood, parental asthma, environmental tobacco smoke exposure during puberty, sex and study location were statistically significant predictors of outcome.Our results indicate that occupational exposure is of little relevance for work-related sensitisation prevalence and allergic rhinitis/asthma incidence in early work life, while other risk factors can be used to improve career guidance for adolescents. Further research on the role of a potential healthy hire effect and the impact of longer exposure duration is needed.
The effect of 3% and 6% hypertonic saline in viral bronchiolitis: a randomised controlled trial
Authors: Teunissen Jasmijn , Hochs Anne H.J. , Vaessen-Verberne Anja , Boehmer Annemie L.M. , Smeets Carien C.J.M. , Brackel Hein , van Gent René , Wesseling Judith , Logtens-Stevens Danielle , de Moor Ronald , Rosias Philippe P.R. , Potgieter Steph , Faber Marianne R. , Hendriks Han J.E. , Janssen-Heijnen Maryska L.G. , Loza Bettina F. 
Published: June 2014

Bronchiolitis is a common disorder in young children that often results in hospitalisation. Except for a possible effect of nebulised hypertonic saline (sodium chloride), no evidence-based therapy is available. This study investigated the efficacy of nebulised 3% and 6% hypertonic saline compared with 0.9% hypertonic saline in children hospitalised with viral bronchiolitis.In this multicentre, double-blind, randomised, controlled trial, children hospitalised with acute viral bronchiolitis were randomised to receive either nebulised 3%, 6% hypertonic saline or 0.9% normal saline during their entire hospital stay. Salbutamol was added to counteract possible bronchial constriction. The primary endpoint was the length of hospital stay. Secondary outcomes were need for supplemental oxygen and tube feeding.From the 292 children included in the study (median age 3.4 months), 247 completed the study. The median length of hospital stay did not differ between the groups: 69 h (interquartile range 57), 70 h (IQR 69) and 53 h (IQR 52), for 3% (n=84) and 6% (n=83) hypertonic saline and 0.9% (n=80) normal saline, respectively, (p=0.29). The need for supplemental oxygen or tube feeding did not differ significantly. Adverse effects were similar in the three groups.Nebulisation with hypertonic saline (3% or 6% sodium chloride) although safe, did not reduce the length of stay in hospital, duration of supplemental oxygen or tube feeding in children hospitalised with moderate-to-severe viral bronchiolitis.
MORT: a powerful foundational library for computational biology and CADD
Authors: Zhang Qian , Zhang Wei , Li Youyong , Wang Junmei , Zhang Jian , Hou Tingjun 
Published: June 2014

Abstract

Background
A foundational library called MORT (Molecular Objects and Relevant Templates) for the development of new software packages and tools employed in computational biology and computer-aided drug design (CADD) is described here.

Results
MORT contains several advantages compared with the other libraries. Firstly, MORT written in C++ natively supports the paradigm of object-oriented design, and thus it can be understood and extended easily. Secondly, MORT employs the relational model to represent a molecule, and it is more convenient and flexible than the traditional hierarchical model employed by many other libraries. Thirdly, a lot of functions have been included in this library, and a molecule can be manipulated easily at different levels. For example, it can parse a variety of popular molecular formats (MOL/SDF, MOL2, PDB/ENT, SMILES/SMARTS, etc.), create the topology and coordinate files for the simulations supported by AMBER, calculate the energy of a specific molecule based on the AMBER force fields, etc.

Conclusions
We believe that MORT can be used as a foundational library for programmers to develop new programs and applications for computational biology and CADD. Source code of MORT is available at http://cadd.suda.edu.cn/MORT/index.htm.
The future of antibiotics
Authors: Spellberg Brad 
Published: June 2014

AbstractAntibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed.
Treatment for infections with carbapenem-resistant Enterobacteriaceae: what options do we still have?
Authors: Yamamoto Michele , Pop-Vicas Aurora E 
Published: June 2014

AbstractThe global spread of carbapenem-resistant Enterobacteriaceae (CRE) is increasingly becoming a major challenge in clinical and public health settings. To date, the treatment for serious CRE infections remains difficult. The intelligent use of antimicrobials and effective infection control strategies is crucial to prevent further CRE spread. Early consultation with experts in the treatment of infections with multidrug-resistant organisms is valuable in patient management. This brief review will focus on the current, yet limited, treatment options for CRE infections.
Tight glycemic control in the ICU - is the earth flat?
Authors: Steil Garry M , Agus Michael SD 
Published: June 2014

AbstractTight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today.
A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival
Authors: Anjum Shahzia , Fourkala Evangelia-Ourania , Zikan Michal , Wong Andrew , Gentry-Maharaj Aleksandra , Jones Allison , Hardy Rebecca , Cibula David , Kuh Diana , Jacobs Ian J , Teschendorff Andrew E , Menon Usha , Widschwendter Martin 
Published: June 2014

Abstract
Background
BRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer.

Methods
In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (1) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (2) the UKCTOCS trial (119 oestrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls).

Results
We found that our blood-based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a receiver operating characteristics (ROC) area under the curve (AUC) of 0.65 (95% CI 0.51 to 0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50 to 0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1-mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51 to 0.83; P = 0.02). We also found that the 1,074 CpGs which are hypermethylated in BRCA1 mutation carriers are significantly enriched for stem cell polycomb group target genes (P <10-20).

Conclusions
A DNAme signature derived from BRCA1 carriers is able to predict breast cancer risk and death years in advance of diagnosis. Future studies may need to focus on DNAme profiles in epithelial cells in order to reach the AUC thresholds required of preventative measures or early detection strategies.
Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites
Authors: Firouzi Sanaz , López Yosvany , Suzuki Yutaka , Nakai Kenta , Sugano Sumio , Yamochi Tadanori , Watanabe Toshiki 
Published: June 2014

AbstractTransformation and clonal proliferation of T-cells infected with human T-cell leukemia virus type-I (HTLV-1) cause adult T-cell leukemia. We took advantage of next-generation sequencing technology to develop and internally validate a new methodology for isolating integration sites and estimating the number of cells in each HTLV-1-infected clone (clone size). Initial analysis was performed with DNA samples from infected individuals. We then used appropriate controls with known integration sites and clonality status to confirm the accuracy of our system, which indeed had the least errors among the currently available techniques. Results suggest potential clinical and biological applications of the new method.
Split luciferase complementation assay to detect regulated protein-protein interactions in rice protoplasts in a large-scale format
Authors: Fujikawa Yukichi , Nakanishi Takahiro , Kawakami Hiroko , Yamasaki Kanako , Sato Masa H , Tsuji Hiroyuki , Matsuoka Makoto , Kato Naohiro 
Published: June 2014

AbstractBackgroundThe rice interactome, in which a network of protein-protein interactions has been elucidated in rice, is a useful resource to identify functional modules of rice signal transduction pathways. Protein-protein interactions occur in cells in two ways, constitutive and regulative. While a yeast-based high-throughput method has been widely used to identify the constitutive interactions, a method to detect the regulated interactions is rarely developed for a large-scale analysis.ResultsA split luciferase complementation assay was applied to detect the regulated interactions in rice. A transformation method of rice protoplasts in a 96-well plate was first established for a large-scale analysis. In addition, an antibody that specifically recognizes a carboxyl-terminal fragment ofRenillaluciferase was newly developed. A pair of antibodies that recognize amino- and carboxyl- terminal fragments ofRenillaluciferase, respectively, was then used to monitor quality and quantity of interacting recombinant-proteins accumulated in the cells. For a proof-of-concept, the method was applied to detect the gibberellin-dependent interaction between GIBBERELLIN INSENSITIVE DWARF1 and SLENDER RICE 1.ConclusionsA method to detect regulated protein-protein interactions was developed towards establishment of the rice interactome.
Renin modulates HIV replication in T cells
Authors: Chandel Nirupama , Ayasolla Kamesh , Lan Xiqian , Rai Partab , Mikulak Joanna , Husain Mohammad , Malhotra Ashwani , McGowan Joseph , Singhal Pravin C 
Published: June 2014

AbstractHIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-κB activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved Gag polyproteins (protease substrate) to p24. Furthermore, aliskiren, a renin inhibitor, reduced renin- and Hpr-induced cleavage of Agt and Gag polyproteins. These findings indicate that renin contributes to HIV replication in TCs via the (P)RR-PLZF signaling cascade and through cleavage of the Gag polyproteins.
Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling
Authors: Burghardt Sven , Claass Benjamin , Erhardt Annette , Karimi Khalil , Tiegs Gisa 
Published: June 2014

AbstractThe liver plays a pivotal role in maintaining immunological tolerance, although the exact molecular mechanism is still largely unknown. The induction of systemic tolerance by liver resident APCs has been attributed to peripheral deletion and to the induction of Tregs. HCs, the parenchymal cells in the liver, could function as nonprofessional APCs and interact and establish cell–cell contact with T lymphocytes. We hypothesized that HCs from healthy or regenerated livers may contribute to induction of functional Tregs. Here, we show that murine HCs induced Foxp3+ Tregs within CD4+ T cells in vitro, which increased in the presence of TGF-β. Interestingly, a further Foxp3+ Treg expansion was observed if HCs were isolated from regenerated livers. Additionally, the induction of Foxp3+ Tregs was associated with the Notch signaling pathway, as the ability of HCs to enhance Foxp3 was abolished by γ-secretase inhibition. Furthermore, HC-iTregs showed ability to suppress the proliferative response of CD4+ T cells to anti-CD3 stimulation in vitro. Thus, HCs may play a pivotal role in the induction of tolerance via Notch-mediated conversion of CD4+ T cells into Foxp3+ Tregs upon TCR stimulation.
Word use in first-person accounts of schizophrenia
Authors: Fineberg S. K. , Deutsch-Link S. , Ichinose M. , McGuinness T. , Bessette A. J. , Chung C. K. , Corlett P. R. 
Published: June 2014

BackgroundLanguage use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights.AimsTo test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia.MethodWord counting software was applied to first-person accounts of schizophrenia and mood disorder.ResultsMore third-person plural pronouns (‘they’) and fewer first-person singular pronouns (‘I’) were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts.ConclusionsDifferences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.
Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder
Authors: Korgaonkar Mayuresh S. , Williams Leanne M. , Song Yun Ju , Usherwood Tim , Grieve Stuart M. 
Published: June 2014

BackgroundFunctional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder (MDD) and responsiveness to antidepressants. Diffusion tensor imaging (DTI) enables characterisation of white matter tracts that relate to these regions.AimsTo examine whether DTI measures of anterior cingulate and limbic white matter are useful prognostic biomarkers for MDD.MethodOf the 102 MDD out-patients from the International Study to Predict Optimized Treatment for Depression (iSPOT-D) who provided baseline magnetic resonance imaging (MRI) data, 74 completed an 8-week course of antidepressant medication (randomised to escitalopram, sertraline or extended-release venlafaxine) and were included in the present analyses. Thirty-four matched controls also provided DTI data. Fractional anisotropy was measured for five anterior cingulate–limbic white matter tracts: cingulum cingulate and hippocampus bundle, fornix, stria terminalis and uncinate fasciculus. (Trial registered at ClinicalTrials.gov: NCT00693849.)ResultsA cross-validated logistic regression model demonstrated that altered connectivity for the cingulum part of the cingulate and stria terminalis tracts significantly predicted remission independent of demographic and clinical measures with 62% accuracy. Prediction improved to 74% when age was added to this model.ConclusionsAnterior cingulate–limbic white matter is a useful predictor of antidepressant treatment outcome in MDD.
Recovery From SIADH-Associated Osteoporosis: A Case Report
Authors: Sejling Anne-Sophie , Thorsteinsson Anne-Luise , Pedersen-Bjergaard Ulrik , Eiken Pia 
Published: June 2014

Abstract

Introduction:
Recent studies show an association between hyponatremia and osteoporosis. We have previously reported a case of severe male osteoporosis due to chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we provide a follow-up on this case after cure of the condition that further supports the causal relationship.

The Case:
A 38-year-old man had been diagnosed with severe osteoporosis most likely due to chronic SIADH. The SIADH was believed to be idiopathic. A magnetic resonance imaging scan, however, revealed a tumor in the sinus, and biopsies showed an esthesioneuroblastoma, immunohistochemically positive for antidiuretic hormone (ADH). After the tumor was removed, ADH and sodium levels normalized. A dual-energy x-ray absorptiometry scan performed 7 months after the patient's last surgery showed a significant spontaneous improvement in bone mineral density in the lumbar vertebrae.

Conclusion:
This case provides evidence for a causal relationship between SIADH and chronic hyponatremia and impaired bone metabolism that can lead to severe secondary osteoporosis. The effect on bone metabolism is at least partially reversible.
Unexpected [3 + 2] Cycloaddition of Diphenyldienamine with C60 via Single Electron Transfer and Hydrogen Shift of the Radical Cation Intermediate
Authors: Ikuma Naohiko , Yamamoto Hiroyuki , Kokubo Ken , Oshima Takumi 
Published: June 2014

Abstract
Novel single electron transfer (SET) reaction of dienamine with C60 is presented. The generated dienamine radical cation underwent a 1,6-hydrogen shift followed by a radical–ion coupling with a C60 radical anion to give pyrrolidinofullerene. The radical process was proven by spin-trapping experiments as well as DFT calculations.