bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes
Authors: Fonda Stephanie J. , Graham Claudia , Munakata Julie , Powers Julia M. , Price David , Vigersky Robert A. 
Published: February 2016

Background: This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients’ behavior. Method: The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base-case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM “refresher” after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. Results: Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a “refresher” were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. Conclusions: RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness.
Penetrating retro-orbital foreign body – large glass shards: A maxillofacial surgery case report
Authors: Blackhall Kristian K , Laraway David C 
Published: February 2016

Objectives: This case report looks at a 53-year-old patient who had suffered a penetrating foreign body injury to the retro-orbital space and the surgical approach taken to remove the large glass fragments found and to correct the damage caused. Having fallen while holding a drinking glass, this patient suffered multiple laceration injuries to the maxillofacial region upon the glass shattering in contact with the face. However, unbeknownst to the patient, several glass fragments became embedded in the retro-orbital space, and this was only detected on presentation 2 days post-injury with unusual symptoms of sharp, sudden pain elicited on extreme gaze as well as ocular motility restriction. Methods: This embedded foreign body required a creative surgical approach to remove it involving gaining access to the retro-orbital space via a superior approach and cautiously following the path the glass shards took upon entry, all the way to the posterior aspect of superior rectus. Intra-operative radiographic guidance was required due to the restriction of operating within this space and particularly when removing glass fragments distal to superior rectus. Results and Conclusion: The patient recovered well and experienced an immediate improvement in ocular motility with a return to relative normality over the next few months.
Benign cementoblastoma (true cementoma) in a cat
Authors: Villamizar-Martinez Lenin A , Reiter Alexander M , Sánchez Melissa D , Soltero-Rivera Maria M 
Published: February 2016

Case summary A 10-year-old castrated male domestic shorthair cat was presented for assessment of a gingival mass surrounding the left maxillary third and fourth premolar teeth. The mass was surgically removed by means of a marginal rim excision, and the tissue was submitted for histological assessment. It was identified as a benign cementoblastoma (true cementoma). There was proliferation of mineralized eosinophilic material with multiple irregularly placed lacunae and reversal lines, reminiscent of cementum. The cat recovered uneventfully from the anesthesia, and there was no evidence of tumor recurrence 6 months after surgery. Relevance and novel information Cementoblastomas (true cementomas) in domestic animals are rare, with just a few reports in ruminants, monogastric herbivores and rodents. Cementoblastoma is considered a benign tumor that arises from the tooth root. The slow, expansive and constant growth that characterizes these masses may be accompanied by signs of oral discomfort and dysphagia. This case report is intended to increase knowledge regarding this tumor in cats and also highlights the importance of complete excision of the neoplasm. To our knowledge, there are no previous reports in the literature of cementoblastoma in the cat.
sciReptor: analysis of single-cell level immunoglobulin repertoires
Authors: Imkeller Katharina , Arndt Peter F. , Wardemann Hedda , Busse Christian E. 
Published: February 2016

Abstract
Background
The sequencing of immunoglobulin (Ig) transcripts from single B cells yields essential information about Ig heavy:light chain pairing, which is lost in conventional bulk sequencing experiments. The previously limited throughput of single-cell approaches has recently been overcome by the introduction of multiple next-generation sequencing (NGS)-based platforms. Furthermore, single-cell techniques allow the assignment of additional data types (e.g. cell surface marker expression), which are crucial for biological interpretation. However, the currently available computational tools are not designed to handle single-cell data and do not provide integral solutions for linking of sequence data to other biological data.

Results
Here we introduce sciReptor, a flexible toolkit for the processing and analysis of antigen receptor repertoire sequencing data at single-cell level. The software combines bioinformatics tools for immunoglobulin sequence annotation with a relational database, where raw data and analysis results are stored and linked. sciReptor supports attribution of additional data categories such as cell surface marker expression or immunological metadata. Furthermore, it comprises a quality control module as well as basic repertoire visualization tools.

Conclusion
sciReptor is a flexible framework for standardized sequence analysis of antigen receptor repertoires on single-cell level. The relational database allows easy data sharing and downstream analyses as well as immediate comparisons between different data sets.
RETRACTED ARTICLE: Transcriptional repression of SOCS3 mediated by IL-6/STAT3 signaling via DNMT1 promotes pancreatic cancer growth and metastasis
Authors: Huang Li , Hu Bin , Ni Jianbo , Wu Jianghong , Jiang Weiliang , Chen Congying , Yang Lijuan , Zeng Yue , Wan Rong , Hu Guoyong , Wang Xingpeng 
Published: February 2016

Abstract
Background
Previous studies have investigated the sustained aberrantly activated Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for pancreatic cancer growth and metastasis. Suppressor of cytokine signaling 3 (SOCS3), as a key negative feedback regulator of this signaling pathway, is usually down-regulated in various cancers. In the present study, we aim at exploring the biological function and the underlying molecular regulation mechanisms of SOCS3 in pancreatic cancer.

Methods
The expression of SOCS3 and other genes in pancreatic cancer was examined by Quantitative real-time PCR, western blotting and immunohistochemical staining. The interaction between pSTAT3 and DNA Methyltransferase 1 (DNMT1) was investigated by co-immunoprecipitation assay. Luciferase reporter assay was used to investigate the transcriptional regulation of pSTAT3 and DNMT1 on the SOCS3 gene. The effects of SOCS3 on the biological behavior of pancreatic cancer cells were assessed both in vitro and vivo. Furthermore, we performed a comprehensive analysis of the expression of SOCS3 in a pancreatic cancer tissue microarray (TMA) and correlated our findings with pathological parameters and outcomes of the patients.

Results
We showed that SOCS3 expression was decreased in phosphorylated STAT3 (pSTAT3)-positive tumors and was negatively correlated with pSTAT3 in pancreatic cancer cells. We also found that IL-6/STAT3 promoted SOCS3 promoter hypermethylation by increasing DNMT1 activity; silencing DNMT1 or 5-aza-2-deoxycytidine (5-AZA) treatment could reverse the down-regulation of SOCS3 mediated by IL-6. Using co-immunoprecipitation and luciferase reporter assays, we found that STAT3 recruited DNMT1 to the promoter region of SOCS3 and inhibited its transcriptional activity. Overexpression of SOCS3 significantly inhibited cell proliferation, which may be due to the increase in G1-S phase arrest; overexpression of SOCS3 also inhibited cell migration and invasion as well as tumorigenicity in nude mice. Pancreatic cancer tissue microarray analysis showed that high SOCS3 expression was a good prognostic factor and negatively correlated with tumor volume and metastasis.

Conclusion
We demonstrated that activated IL-6/STAT3 signaling could induce SOCS3 methylation via DNMT1, which led to pancreatic cancer growth and metastasis. These data also provided a mechanistic link between sustained aberrantly activated IL-6/STAT3 signaling and SOCS3 down-regulation in pancreatic cancer. Thus, inhibitors of STAT3 or DNMT1 may become novel strategies for treating pancreatic cancer.
Outcomes of Saudi Arabian Patients With Nasopharyngeal Cancer Treated With Primarily Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiotherapy
Authors: Al-Wassia Rolina , Abusanad Atlal , Awad Nesreen , Marzouki Hani , Alkhayyat Shadi , Al-Khatib Talal , Constantinescu Camelia 
Published: February 2016

Purpose Nasopharyngeal cancer (NPC) is the most common head and neck cancer in Saudi Arabia. This study reports the locoregional disease control and survival outcomes in patients with NPC treated in King Abdulaziz University Hospital. Methods Patients treated for NPC between June 2007 and October 2014 were retrospectively reviewed. Demographic information, clinicopathologic variables, and chemotherapy data were collected and analyzed. Cumulative survival and disease control rates were calculated by Kaplan-Meier product-limit actuarial method. Results Thirty-nine patients with NPC were reviewed. Thirty-five (90%) patients received definitive radiotherapy (RT) and four (10%) had palliative RT. Mean prescribed dose for definitive RT was 68 Gy (range, 60 to 70.2 Gy), delivered with mean doses per fraction of 1.9 Gy (range, 1.8 to 2.1 Gy). After a median follow-up of 15 months (range, 1 to 84 months), 22 (63%) patients who underwent definitive RT were disease free and 13 (37%) were still with disease. During this period, seven (18%) patients died of the disease; five (13%) of them received definitive RT. After 2 years’ follow-up, the actuarial estimate rates were: 85.7% for local control, 91.4% for nodal control, and 85.7% for distant control. Conclusion Our study showed a disease with clinical behavior similar to what has been observed in East and Southeast Asia. Further it explored the neoadjuvant chemotherapy approach in treating NPC with results that are comparable to literature. However, little is known about the molecular pathogenesis of this disease in this region, and further research integrating clinical and molecular biomarkers is required.
Pulmonary Nodules in Patients With Nonpulmonary Cancer: Not Always Metastases
Authors: Caparica Rafael , Mak Milena Perez , Rocha Claudio Henrique , Velho Pedro Henrique Isaacsson , Viana Publio , Moura Mauricio R.L. , Menezes Marcos Roberto , Amato Marcelo B.P. , Feher Olavo 
Published: February 2016

Introduction The differential diagnosis of pulmonary nodules (PNs) includes metastases, lung cancers, infectious diseases, and scar tissue, among others. Because data regarding whether and when to perform a PN biopsy in patients with cancer are scarce, clinicians tend to assume that PNs are metastatic disease based solely on imaging. The current study evaluated the findings of PN biopsies in a population of patients with cancer and sought to determine the variables that correlated with higher odds of metastatic disease. Patients and Methods We conducted a retrospective, single-institution study that included consecutive patients with nonpulmonary solid malignancies who underwent PN biopsy from January 2011 to December 2013. Imaging and clinical variables were analyzed by logistic regression to determine the correlation between such variables and the odds of metastatic disease. Patients with previously known metastatic disease or primary hematologic malignancies were excluded. Results Two hundred twenty-eight patients were included in the study. Metastatic disease was found in 146 patients (64%), 60 patients (26.3%) were diagnosed with a second primary lung tumor, and 22 patients (9.6%) had no cancer on biopsy. On multivariate analysis, the presence of multiple PNs (> 5 mm) and cavitation/necrosis were the only variables associated with higher odds (P < .05) of metastatic disease. We registered six (2.6%) procedure complications demanding active interventions, and no procedure-related death occurred. Conclusion Multiple PNs (> 5 mm) and cavitation were the two characteristics associated with the highest chances of metastatic disease. Our findings demonstrate that PNs should not be assumed to be metastases without performing a biopsy. This assumption may lead to high rates of misdiagnosis. Tissue sampling is fundamental for accurately diagnosing patients with cancer.
From Grief to Leisure: “Lycidas” In the Eighteenth Century
Authors: Brady Andrea 
Published: February 2016

AbstractMilton’s elegy for Edward King was widely admired and imitated in the eighteenth century. These imitations tend to celebrate the poem as an ornamental, musical work while suppressing its politics. By contrast, Samuel Johnson recognized that the poem’s prosody and its generic heterogeneity were intrinsically related to its political critique. His objections to “Lycidas” also reflected his view that pastoral depicted an idealized life of rural leisure to distract and entertain city men. This ancient association between pastoral and leisure may have informed eighteenth-century readers’ delight in the poem’s “ease and variety,” but it is also a fundamental misreading of the ethics of labor set out in the poem. In its enactment of the spiritual and writerly work of the shepherd, in Milton’s revisions, and in its monodic form, “Lycidas” offers readers a choice between sensual dalliance and arduous song. Monody was both a collective song, performed during work to relieve its strains, and an individual utterance. This form reasserts the labor idealized by pastoral as a spiritual necessity. The eighteenth-century reception of “Lycidas” reveals how the revolutionary potential of lyric was converted to entertainment, a moment whose legacies may be perceived in some contemporary theories of lyric.
Comparative analysis of fertility signals and sex-specific cuticular chemical profiles of Odontomachus trap-jaw ants
Authors: Smith Adrian A. , Millar Jocelyn G. , Suarez Andrew V. 
Published: February 2016

ABSTRACT
The lipid mixture that coats the insect cuticle contains a number of chemical signals. Mate choice in solitary insects is mediated by sexually dimorphic cuticular chemistry, whereas in eusocial insects, these profiles provide information through which colony members are identified and the fertility status of individuals is assessed. Profiles of queens and workers have been described for a number of eusocial species, but there have been few comparisons of fertility signals among closely related species. Additionally, sexual dimorphism in cuticular lipid profiles has only been reported in two species of ants. This study describes the cuticular chemical profiles of queens, workers and males of three species of Odontomachus trap-jaw ants: O. ruginodis, O. relictus and O. haematodus. These are compared with fertility signals and sexually dimorphic profiles already described from O. brunneus. We report that fertility signals are not conserved within this genus: chemical compounds that distinguish queens from workers vary in number and type among the species. Furthermore, the compounds that were most abundant in cuticular extracts of O. ruginodis queens relative to workers were novel 2,5-dialkyltetrahydrofurans. Bioassays of extracts of O. ruginodis queens indicate that the dialkyltetrahydrofuran and hydrocarbon fractions of the profile are likely to work synergistically in eliciting behavioral responses from workers. In contrast, cuticular lipids that distinguish males from females are more conserved across species, with isomeric and relative abundance variations comprising the main differences among species. Our results provide new insights into how these contact chemical signals may have arisen and evolved within eusocial insects.
Meeting the sexual health needs of looked after children
Authors: Stacey Sarah 
Published: February 2016

This paper looks at knowledge and use of contraception in looked after children (LAC) and how they access sexual health services. Despite LAC being classed as high risk for teenage pregnancy, few studies have been dedicated to identifying what LAC know about contraception and sexual health services. This project collects data from 28 14–17-year-old LAC in one county in the East of England using semi-structured interviews. The findings indicate that sex education was poor and knowledge of local sexual health services limited. Sixty four percent were sexually active but only 39% of those consistently used contraception. There was also some confusion about contraception use generally. The implication is that this group of young people's needs are not being met by sex education in schools or by the traditional mode of sexual health service delivery. A change is needed in how this group of young people's sexual health needs are met.
General practice nurse education: Attitudes to training
Authors: Beardmore Gill 
Published: February 2016

Aim: To investigate how attitudes to general practice nurse (GPN) education might affect the future of the GPN workforce. Background: In the past, GPN education has lacked co-ordination and structure and has frequently been neglected owing to a variety of constraints and pressures ( Atkin and Lunt, 1995 ; Crossman, 2008 ). While there is widespread recognition that this must change, little is known about the effects this might have on the workforce. This study focuses on this important issue. In particular it investigates the possible effects of introducing a degree programme for new GPNs in the east Midlands. Methods: A qualitative approach was selected and the methods used to collect data were in depth interviews and thematic analysis. Eight experienced GPNs, who worked in a variety of general practice settings across the East Midlands, were interviewed. Each experienced GPN worked in the same practice as a student who was enrolled on the east Midlands degree programme. Results: Overwhelmingly, participants revealed a positive approach to the East Midlands programme. There was little evidence of experienced nurses feeling personally threatened by their more junior colleagues even though they recognised that novice nurses were being offered a more structured and academic base to their education. The data did reveal some specific attitudes to GPN education, in particular to competence and to approach to change. Conclusions: The financing of GPN education and the lack of a national qualification in general practice nursing are revealed as longstanding, unresolved issues. Solutions to these and other issues need to be found if GPN education is to develop in the future. The recommendations made may provide an opportunity for considering a way forward.
Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement
Authors: Wendling A. , Mar D. , Wischmeier N. , Anderson D. , McIff T. 
Published: February 2016

ObjectivesThe objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength.MethodsThree batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priori t-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group.ResultsThe delayed technique showed a significant increase in elution on day one compared with the standard mix technique (p < 0.001). The transition point from Phase I to Phase II occurred on day ten. LFUS treatments significantly increased elution amounts for all groups above control. Delayed technique resulted in significantly higher elution amounts for the five-minute- (p = 0.004) and 45-minute- (p < 0.001) duration groups compared with standard technique. Additionally, the correlations between LFUS duration and total elution amount for both mix techniques were significant (p = 0.03). Both antibiotic-impregnated groups exhibited a significant decrease in offset yield stress compared with the control group (p < 0.001), however, their lower 95% confidence intervals were all above the 70 MPa limit defined by International Standards Organization (ISO) 5833-2 reference standard for acrylic bone cement.ConclusionThe combination of a delayed mix technique with LFUS treatments provides a reasonable means for increasing both short- and long-term antibiotic elution without affecting mechanical strength. Cite this article: Dr. T. McIff. Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement. Bone Joint Res 2016;5:26–32. doi: 10.1302/2046-3758.52.2000412
Systematic Evaluation of Sanger Validation of Next-Generation Sequencing Variants
Authors: Beck Tyler F , Mullikin James C ,   the NISC Comparative Sequencing Program, Biesecker Leslie G 
Published: February 2016

Abstract

BACKGROUND
Next-generation sequencing (NGS) data are used for both clinical care and clinical research. DNA sequence variants identified using NGS are often returned to patients/participants as part of clinical or research protocols. The current standard of care is to validate NGS variants using Sanger sequencing, which is costly and time-consuming.

METHODS
We performed a large-scale, systematic evaluation of Sanger-based validation of NGS variants using data from the ClinSeq® project. We first used NGS data from 19 genes in 5 participants, comparing them to high-throughput Sanger sequencing results on the same samples, and found no discrepancies among 234 NGS variants. We then compared NGS variants in 5 genes from 684 participants against data from Sanger sequencing.

RESULTS
Of over 5800 NGS-derived variants, 19 were not validated by Sanger data. Using newly designed sequencing primers, Sanger sequencing confirmed 17 of the NGS variants, and the remaining 2 variants had low quality scores from exome sequencing. Overall, we measured a validation rate of 99.965% for NGS variants using Sanger sequencing, which was higher than many existing medical tests that do not necessitate orthogonal validation.

CONCLUSIONS
A single round of Sanger sequencing is more likely to incorrectly refute a true-positive variant from NGS than to correctly identify a false-positive variant from NGS. Validation of NGS-derived variants using Sanger sequencing has limited utility, and best practice standards should not include routine orthogonal Sanger validation of NGS variants.