bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large diaphragmatic hernia subject to successful reconstruction – case report
Authors: Kurek Józef , Gierek Marcin , Ochała Gabriela , Majewski Jakub 
Published: August 2015

AbstractThe study presented a case of a large left-sided diaphragmatic hernia treated by means of successful phrenic reconstruction. The above-mentioned are very challenging considering general surgery, although reluctantly supplied in General Surgery Departments
Anab initioand density functional theory study on neutral pterin radicals
Authors: Reibnegger Gilbert 
Published: August 2015

AbstractThe electronic structures of the five radicals resulting from homolytic elimination of one of the hydrogen atoms from the most stable tautomeric form of neutral pterin were investigated in gas phase as well as in aqueous solution. Molecular wave functions obtained by density functional theory were analysed by quantum theory of atoms in molecules and electron localisation functions (ELF). Spin densities of the radicals as well as electrostatic potential functions were analysed. Radicals resulting from elimination of N-bonded hydrogen atoms are more stable in comparison with radicals obtained after abstraction of C-bonded hydrogen atoms. N-centred radicals show strong delocalisation of spin density over both heteroaromatic rings; in C-centred radicals delocalisation does not occur. ELF analyses showed that in N-derived radicals particularly the lone electron pair at N2′ is strongly involved into the bicyclic heteroaromatic π-electron system. Thereby, bonding geometry at N2′ in these radicals changes from pyramidal to planar. Transition from gas phase to solution phase (water) generally leads to increased polarity of the structures. Pterin-derived free radicals have been implicated in several biologically important reactions; so this investigation provides first insights into the detailed electronic structures of such molecular systems.
The role of nitric oxide in chronic rhinosinusitis
Authors: Vlad Diana , Trombitas Veronica , Capusan Mircea , Albu Silviu 
Published: August 2015

Abstract
Chronic rhinosinusitis is a very common medical condition that affects nasal and paranasal sinuses mucosa in both adults and children. Its pathology, however, still remains unclear and researchers focus more and more on the role of nitric oxide (NO), a free radical produced in normal conditions by the paranasal sinuses epithelium in healthy patients, in the development of this disease. NO’s role in the upper airway disease is not completely known, but it appears to act like a first-line host defence agent, maintaining the sinuses sterile due to its antiviral and bacteriostatic properties and by increasing mucociliary clearance. NO levels in the exhaled air of patients with CRS are lower than in healthy patients. One explanation for this might be the sinus obstruction that occurs in CRS because subjects with complete sinus opacification have the lowest levels. Furthermore, NO levels decrease after CRS treatments, suggesting that its measurement might help in monitoring the patient’s response to therapy. In this review, we discuss the NO synthesis in the respiratory tract, its involvement in airway pathology, its role in the pathogenesis of CRS and the current clinical uses for NO in CRS and several other airway diseases.
Revisiting the statistical specification of near-multicollinearity in the logistic regression model
Authors: Atems Bebonchu , Bergtold Jason 
Published: August 2015

Abstract
This paper revisits the statistical specification of near-multicollinearity in the logistic regression model. We argue that the ceteris paribus clause, which assumes that the maximum likelihood estimator of β remains constant as the correlation (ρ) between the regressors increases, invoked under the traditional account of near-multicollinearity is rather misleading. We derive the parameters of the logistic regression model and show that they are functions of ρ, indicating that the ceteris paribus clause is unattainable. Monte Carlo simulations confirm these findings and further show that: coefficient estimates and related statistics fluctuate in a non-symmetric, non-monotonic way as |ρ|→1; that the impact of near-multicollinearity is centered on the estimates of β; and that the impact on substantive inferences does not necessarily follow what the traditional account implies.
A Tool Set for the Genome-Wide Analysis ofNeurospora crassaby RT-PCR
Authors: Hurley Jennifer M , Dasgupta Arko , Andrews Peter , Crowell Alexander M , Ringelberg Carol , Loros Jennifer J , Dunlap Jay C 
Published: August 2015

AbstractNeurospora crassa is an important model organism for filamentous fungi as well as for circadian biology and photobiology. Although the community-accumulated tool set for the molecular analysis of Neurospora is extensive, two components are missing: (1) dependable reference genes whose level of expression are relatively constant across light/dark cycles and as a function of time of day and (2) a catalog of primers specifically designed for real-time PCR (RT-PCR). To address the first of these we have identified genes that are optimal for use as reference genes in RT-PCR across a wide range of expression levels; the mRNA/transcripts from these genes have potential for use as reference noncycling transcripts outside of Neurospora. In addition, we have generated a genome-wide set of RT-PCR primers, thereby streamlining the analysis of gene expression. In validation studies these primers successfully identified target mRNAs arising from 70% (34 of 49) of all tested genes and from all (28) of the moderately to highly expressed tested genes.
GC-Content of Synonymous Codons Profoundly Influences Amino Acid Usage
Authors: Li Jing , Zhou Jun , Wu Ying , Yang Sihai , Tian Dacheng 
Published: August 2015

Abstract
Amino acids typically are encoded by multiple synonymous codons that are not used with the same frequency. Codon usage bias has drawn considerable attention, and several explanations have been offered, including variation in GC-content between species. Focusing on a simple parameter—combined GC proportion of all the synonymous codons for a particular amino acid, termed GCsyn—we try to deepen our understanding of the relationship between GC-content and amino acid/codon usage in more details. We analyzed 65 widely distributed representative species and found a close association between GCsyn, GC-content, and amino acids usage. The overall usages of the four amino acids with the greatest GCsyn and the five amino acids with the lowest GCsyn both vary with the regional GC-content, whereas the usage of the remaining 11 amino acids with intermediate GCsyn is less variable. More interesting, we discovered that codon usage frequencies are nearly constant in regions with similar GC-content. We further quantified the effects of regional GC-content variation (low to high) on amino acid usage and found that GC-content determines the usage variation of amino acids, especially those with extremely high GCsyn, which accounts for 76.7% of the changed GC-content for those regions. Our results suggest that GCsyn correlates with GC-content and has impact on codon/amino acid usage. These findings suggest a novel approach to understanding the role of codon and amino acid usage in shaping genomic architecture and evolutionary patterns of organisms.
Conservation of Regional Variation in Sex-Specific Sex Chromosome Regulation
Authors: Wright Alison E , Zimmer Fabian , Harrison Peter W , Mank Judith E 
Published: August 2015

AbstractRegional variation in sex-specific gene regulation has been observed across sex chromosomes in a range of animals and is often a function of sex chromosome age. The avian Z chromosome exhibits substantial regional variation in sex-specific regulation, where older regions show elevated levels of male-biased expression. Distinct sex-specific regulation also has been observed across the male hypermethylated (MHM) region, which has been suggested to be a region of nascent dosage compensation. Intriguingly, MHM region regulatory features have not been observed in distantly related avian species despite the hypothesis that it is situated within the oldest region of the avian Z chromosome and is therefore orthologous across most birds. This situation contrasts with the conservation of other aspects of regional variation in gene expression observed on the avian sex chromosomes but could be the result of sampling bias. We sampled taxa across the Galloanserae, an avian clade spanning 90 million years, to test whether regional variation in sex-specific gene regulation across the Z chromosome is conserved. We show that the MHM region is conserved across a large portion of the avian phylogeny, together with other sex-specific regulatory features of the avian Z chromosome. Our results from multiple lines of evidence suggest that the sex-specific expression pattern of the MHM region is not consistent with nascent dosage compensation.
In Vivo Transcriptional Activation Using CRISPR/Cas9 in Drosophila
Authors: Lin Shuailiang , Ewen-Campen Ben , Ni Xiaochun , Housden Benjamin E , Perrimon Norbert 
Published: August 2015

Abstract
A number of approaches for Cas9-mediated transcriptional activation have recently been developed, allowing target genes to be overexpressed from their endogenous genomic loci. However, these approaches have thus far been limited to cell culture, and this technique has not been demonstrated in vivo in any animal. The technique involving the fewest separate components, and therefore the most amenable to in vivo applications, is the dCas9-VPR system, where a nuclease-dead Cas9 is fused to a highly active chimeric activator domain. In this study, we characterize the dCas9-VPR system in Drosophila cells and in vivo. We show that this system can be used in cell culture to upregulate a range of target genes, singly and in multiplex, and that a single guide RNA upstream of the transcription start site can activate high levels of target transcription. We observe marked heterogeneity in guide RNA efficacy for any given gene, and we confirm that transcription is inhibited by guide RNAs binding downstream of the transcription start site. To demonstrate one application of this technique in cells, we used dCas9-VPR to identify target genes for Twist and Snail, two highly conserved transcription factors that cooperate during Drosophila mesoderm development. In addition, we simultaneously activated both Twist and Snail to identify synergistic responses to this physiologically relevant combination. Finally, we show that dCas9-VPR can activate target genes and cause dominant phenotypes in vivo, providing the first demonstration of dCas9 activation in a multicellular animal. Transcriptional activation using dCas9-VPR thus offers a simple and broadly applicable technique for a variety of overexpression studies.
Cuidados al final de la vida: una oportunidad para fortalecer el patrón emancipatorio de enfermería
Authors: Lopera Betancur Martha Adiela 
Published: August 2015

<p class="MsoNormal"><span><span style="font-size: 10pt; line-height: 115%; font-family: Arial, sans-serif; background-position: initial initial; background-repeat: initial initial;">El objetivo es analizar parte de la situación que viven los pacientes con enfermedad en fase terminal en el marco del sistema de salud colombiano y el papel de las enfermeras.<br />La ley 100 de 1993 trajo cambios, uno de los cuales está relacionado con el cuidado a los enfermos terminales, el otro, con el papel de las enfermeras. Este artículo explora los conceptos de los cuidados paliativos y qué ha pasado en Colombia con este mecanismo legal y con el rol de la enfermera.</span></span></p><p class="MsoNormal"><span><span style="font-size: 10pt; line-height: 115%; font-family: Arial, sans-serif; background-position: initial initial; background-repeat: initial initial;">Conclusión: Las enfermeras pueden ser claves al aplicar el patrón de conocimiento emancipatorio, en el cuidado en la adversidad, la abogacía y el empoderamiento de los derechos<br />de los pacientes, así como en la definición de políticas.</span></span></p><div> </div>
The Burden of Care for Children with Unilateral Cleft Lip: A Systematic Review of Revision Surgery
Authors: Sitzman Thomas J. , Coyne Sarah M. , Britto Maria T. 
Published: August 2015

Objective To identify the average rate of revision surgery following cleft lip repair. Design PubMed, CINAHL, and SCOPUS were searched from database inception through March 2013 using the search terms cleft lip and surgery. Two investigators independently screened all abstracts and determined eligibility from review of full manuscripts using prespecified inclusion and exclusion criteria. Strengths and limitation of the studies were assessed, followed by qualitative synthesis. The I2 test of homogeneity was performed to determine if meta-analysis was appropriate. Results The search identified 3034 articles. Of those, 45 met the inclusion criteria. Studies were primarily case series and retrospective cohort studies, with only one randomized controlled trial. One-third of studies (n = 15) did not describe how the study sample was selected. Follow-up duration was not reported in one-fourth of studies (n = 11). Nasolabial aesthetics were reported in 44% of studies (n = 20). The incidence of revision surgery ranged from 0% to 100%. Meta-analysis was precluded because of study heterogeneity (I2 = 97%). Conclusions The average incidence of cleft lip revision surgery cannot be estimated from the published literature, due to significant heterogeneity among existing reports and limited study quality. To provide valid information about the burden of care for unilateral cleft lip, a population-based or multicenter longitudinal cohort study is necessary; this study should measure the number of surgical procedures and the patient's aesthetic outcomes.
Ultrasound Evaluation of Primary Alveolar Grafting in Cleft Lip/Palate Treatment: Development of a Novel Sonographic Grading System
Authors: Chang Daniel K. , Kanack Melissa , Pretorius Dolores , Calvert Stephanie , Patino-Ochoa Cesar , Gosman Amanda 
Published: August 2015

Objective To explore ultrasonographic evaluation of primary alveolar repair in cleft lip/palate patients and develop a grading system to assess outcomes of graft success. Design Sixteen patients with an average age of 2 years 1 month had sonograms performed at various points in their treatment to determine the feasibility of ultrasound in visualizing alveolar bone defects and changes over time postgrafting. A total of 23 sonograms were performed: 21 at an average of 12 months postoperatively and 2 at an average of 1 month preoperatively. Main Outcome Measures A 10-point grading system was developed assessing three categories: locations of lateral bone bridging across the cleft, quantification of residual defects with air or fluid channels, and locations of calcification. Three operators graded 10 sonograms to assess interobserver reliability, and the scores were also validated against dental radiographs in patients old enough for radiographic imaging. Results Linear weighted kappa statistics revealed substantial interobserver agreement for total scores, with an average kappa value of .708. In limited patients with radiographs, a total score of 9/10 correlated with a Chelsea score of 6.5/8 and category A. Conclusions Sonographic evaluation, coupled with this novel grading system, shows potential for early assessment of outcomes of graft success when evaluating new techniques of primary alveolar grafting.
Orthotic Management of Deformational Plagiocephaly: Consensus Clinical Standards of Care
Authors: Lin Robert S. , Stevens Phillip M. , Wininger Michael , Castiglione Charles L. 
Published: August 2015

Objective To establish consensus on definitive, actionable standards for the management of deformational plagiocephaly. Design Three-stage Delphi Survey process based on best practice statements obtained through literature review. Setting Electronic survey delivery. Participants Review panel of 10 multidisciplinary subject matter experts (SMEs); survey panel of 30 cranial orthotists. Results Fifty-four best practice statements were accepted in four categories: diagnosis, presentation and severity, initiating treatment, and management principles. Conclusions Clinical practice can be guided en route to robust evidence as to the efficacy of various plagiocephaly management strategies, in pursuit of definitive standards.
Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer
Authors: Guarneri Valentina , Dieci Maria Vittoria , Frassoldati Antonio , Maiorana Antonino , Ficarra Guido , Bettelli Stefania , Tagliafico Enrico , Bicciato Silvio , Generali Daniele Giulio , Cagossi Katia , Bisagni Giancarlo , Sarti Samanta , Musolino Antonino , Ellis Catherine , Crescenzo Rocco , Conte PierFranco 
Published: August 2015

Abstract

Background.
The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers.

Materials and Methods.
Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses.

Results.
A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR.

Conclusion.
PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib.

Implications for Practice:
HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more and more new anti-HER2 treatments are becoming available. There is a need to identify markers of sensitivity to different treatments to move in the direction of treatment personalization. This study identified PIK3CA mutations as a potential predictive marker of resistance to dual anti-HER2 treatment that should be further studied in breast cancer.
Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma
Authors: Goyal Lipika , Govindan Aparna , Sheth Rahul A. , Nardi Valentina , Blaszkowsky Lawrence S. , Faris Jason E. , Clark Jeffrey W. , Ryan David P. , Kwak Eunice L. , Allen Jill N. , Murphy Janet E. , Saha Supriya K. , Hong Theodore S. , Wo Jennifer Y. , Ferrone Cristina R. , Tanabe Kenneth K. , Chong Dawn Q. , Deshpande Vikram , Borger Darrell R. , Iafrate A. John , Bardeesy Nabeel , Zheng Hui , Zhu Andrew X. 
Published: August 2015

Abstract

Background.
Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC.

Methods.
Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging.

Results.
Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status.

Conclusion.
The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation.

Implications for Practice:
Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with unresectable or metastatic disease, and the current study is the first to focus on the prognosis and clinical phenotype of this population and reports on the largest cohort of patients with advanced IDH mutant ICC to date. The finding that the IDH mutation lacks prognostic significance in advanced ICC is preliminary and needs to be confirmed prospectively in a larger study.
Rethinking Progress. On the Origin of the Modern Sustainability Discourse, 1970–2000
Authors: Seefried Elke 
Published: August 2015

Rethinking Progress. On the Origin of the Modern Sustainability Discourse, 1970-2000 Sustainability has become a key concept in the national and international policy discourse, and nonetheless it has not been clearly defined. This article argues that it is precisely the vagueness of the concept that has made it so attractive for politics. Focusing on the international politics arena and the West German case, the article shows that dominating political notions of development and progress were partly reconceptualised in order to incorporate long-term ecological and social issues around 1970. Against this backdrop, from the late 1980s onwards, «sustainable development» and «sustainability» became political concepts for the future which, explicitly vague, appeared to balance economic, ecological and social goals in both short-term and long-term perspectives. The notions of sustainable development and sustainability oscillated between crisis perceptions, steady-state thinking and a new semantics of modernisation from the 1970s to 2000. In this light, it is argued that there is no «end of confidence» but rather that understandings of progress have been reconfigured.