bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis
Authors: Morales Crystal , Rachidi Saleh , Hong Feng , Sun Shaoli , Ouyang Xinshou , Wallace Caroline , Zhang Yongliang , Garret-Mayer Elizabeth , Wu Jennifer , Liu Bei , Li Zihai 
Published: December 2013

Abstract
Macrophages are important drivers in the development of inflammation-associated colon cancers, but the mechanistic underpinnings for their contributions are not fully understood. Furthermore, Toll-like receptors have been implicated in colon cancer, but their relevant cellular sites of action are obscure. In this study, we show that the endoplasmic reticulum chaperone gp96 is essential in tumor-associated macrophages (TAM) to license their contributions to inflammatory colon tumorigenesis. Mice where gp96 was genetically deleted in a macrophage-specific manner exhibited reduced colitis and inflammation-associated colon tumorigenesis. Attenuation of colon cancer in these mice correlated strikingly with reduced mutation rates of β-catenin, increased efficiency of the DNA repair machinery, and reduced expression of proinflammatory cytokines, including interleukin (IL)-17 and IL-23 in the tumor microenvironment. The genotoxic nature of TAM-associated inflammation was evident by increased expression of genes in the DNA repair pathway. Our work deepens understanding of how TAM promote oncogenesis by altering the molecular oncogenic program within epithelial cells, and it identifies gp96 as a lynchpin chaperone needed in TAM to license their function and impact on expression of critical inflammatory cytokines in colon tumorigenesis. Cancer Res; 74(2); 446–59. ©2013 AACR.
Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells
Authors: Weide Benjamin , Martens Alexander , Zelba Henning , Stutz Christina , Derhovanessian Evelyna , Di Giacomo Anna Maria , Maio Michele , Sucker Antje , Schilling Bastian , Schadendorf Dirk , Büttner Petra , Garbe Claus , Pawelec Graham 
Published: December 2013

AbstractPurpose: To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared with functional tumor antigen–specific T cells in patients with melanoma with distant metastasis.Experimental Design: The percentage of CD14+CD11b+HLA-DR−/low MDSCs, CD4+CD25+FoxP3+ Tregs, and the presence of NY-ESO-1- or Melan-A–specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan–Meier and log-rank tests. Multivariate analyses were performed using Cox regression models.Results: NY-ESO-1–specific T cells, the M-category, and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1–specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of &gt;11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months versus 8 months for others (P &lt; 0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma antigen–specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs.Conclusions: Circulating CD14+CD11b+HLA-DR−/low MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen–specific T cells in patients with advanced melanoma. Our findings provide a rationale to investigate MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches. Clin Cancer Res; 20(6); 1601–9. ©2013 AACR.
Personalized Therapy for Acute Myeloid Leukemia
Authors: Hourigan Christopher S. , Karp Judith E. 
Published: December 2013

Abstract
Summary: Patient-specific ex vivo drug sensitivity and resistance screening can identify rational drug candidates for the testing of personalized targeted therapy. An iterative approach of genomic and drug susceptibility characterization at sequential time points during clinical trials of targeted therapy in acute myeloid leukemia may be useful both for characterizing mechanisms of resistance and clonal evolution and also for identification of novel therapeutic targets and drug combinations. Cancer Discov; 3(12); 1336–8. ©2013 AACR.
See related article by Pemovska et al., p. 1416
Outcomes of Combined Furlow Palatoplasty and Sphincter Pharyngoplasty for Velopharyngeal Insufficiency
Authors: Bohm Lauren A. , Padgitt Noëlle , Tibesar Robert J. , Lander Timothy A. , Sidman James D. 
Published: December 2013

ObjectiveTo compare surgical outcomes between pharyngeal flap, sphincter pharyngoplasty, and combined Furlow palatoplasty and sphincter pharyngoplasty in the management of pediatric velopharyngeal insufficiency.Study DesignCase series with chart review.SettingTertiary care pediatric hospital.Subjects and MethodsAfter exclusion of children with velocardiofacial syndrome, 96 patients who underwent surgical intervention between 2008 and 2012 were identified. Surgical interventions were categorized as pharyngeal flap, sphincter pharyngoplasty, and combined Furlow palatoplasty and sphincter pharyngoplasty. Main outcome measures included perceptual speech analyses, complications, and surgical revision rates.ResultsOf the 96 reviewed patients, 38 (39.6%) underwent pharyngeal flap, 20 (20.8%) sphincter pharyngoplasty, and 38 (39.6%) combined Furlow palatoplasty and sphincter pharyngoplasty. Choice of surgical intervention was based on patient characteristics, observed palatal length, and formal speech assessments. There were no differences in patient demographics or preoperative perceptual speech analysis scores among the 3 surgical groups. The mean speech improvement was significantly greater in both the pharyngeal flap (P =. 031) and combined procedure (P =. 013) compared with sphincter pharyngoplasty alone, but no differences were observed between the pharyngeal flap and combined procedure (P =. 797). There were no differences in complications among the 3 surgical interventions (P =. 220). The combined procedure required significantly less surgical revisions than the pharyngeal flap (P =. 019).ConclusionCombined Furlow palatoplasty and sphincter pharyngoplasty is an effective procedure for the management of pediatric velopharyngeal insufficiency and may result in superior speech outcomes and lower revision rates than sphincter pharyngoplasty and pharyngeal flap, respectively.
Fluorescence Visualization Screening for EBV‐LMP1‐Targeted DNAzymes
Authors: You Xi , Yang Yu Cheng , Ke Xia , Hong Su Ling , Hu Guo Hua 
Published: December 2013

ObjectivesTo develop a novel screening method for DNAzymes targeting the LMP1 carboxy region.Study DesignTo design a method to screen special DNAzymes toward the Epstein‐Barr virus (EBV)–associated carcinoma before clinic use.SettingKey Laboratory of the Ministry of Education–Molecular Biology of Infectious Diseases in Chongqing Medical University.Subjects and MethodsFour novel 10‐23 DNAzymes (DZ509, DZ1037, DZ893, and DZ827) targeting the EBV‐LMP1 gene were designed and evaluated by detecting enhanced green fluorescence protein (EGFP) expression of LMP1 mRNA and the protein in the nasopharyngeal carcinoma (NPC) cell line CNE2 transfected with the pEGFP‐C1‐LMP1c vector. The screened specific DNAzymes were then transfected into NPC cell lines C666‐1 while a mutant oligonucleotide mutDZ509 and an antisense oligonucleotide ASODN509 were designed as positive and negative controls. Cell proliferation, cell apoptosis, LMP1 mRNA, and the protein were assessed using 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay, Annexin V‐fluorescence isothiocyanate (FITC), reverse transcription polymerase chain reaction (RT‐PCR), and Western blots.ResultsThe inhibition rates of fluorescence expression of the DNAzymes DZ509, DZ1037, DZ893, and DZ827 were 91.25%, 65.84%, 49.02%, and 44.56%, respectively. The results were in accordance with the inhibition effects of mRNA and protein expression. The screened DZ509 could effectively knock down endogenous LMP1 expression in C666‐1 cells, inhibit cell proliferation, and induce cell apoptosis compared with mutDZ509 and ASODN509.ConclusionLMP1 could present a potential target for DNAzymes toward the EBV‐associated carcinoma, and the EGFP expression vector could be a visible method for screening special DNAzymes before clinic use.
How to measure pain in neurological conditions? A systematic review of psychometric properties and clinical utility of measurement tools
Authors: Tyson Sarah F , Brown Philip 
Published: December 2013

Objective: To systematically review the psychometric properties and clinical utility of measures of pain in neurological conditions. Data sources: Electronic databases (AMED, CINAHL, MEDLINE, PEDro and Web of Knowledge) were searched from their inception to February 2013. Review methods: Studies investigating any measurement tool to assess pain in central nervous system conditions were systematically identified. Data about their psychometric properties and clinical utility were extracted and analysed independently. The strength of the psychometric properties and clinical utility were assessed. Results: A total of 13 articles met the selection criteria, which assessed 11 measurement tools; eight pain rating scales; one Neuropathic Pain Scale; and two measures of pain interference with every-day life. Most of the pain rating scales were specifically for hemiplegic shoulder pain. None had been sufficiently developed to recommend for use in clinical practice or research. Evaluation of reliability and the ability to detect change were particularly sparse. Reliability depended on the type of tools used. Patients with right hemisphere damage favoured verbal/written responses, while people with left hemisphere damage preferred and reported more effectively using visual/numeric responses. Validity between measures of pain intensity was moderate, while validity with mood or quality of life was weak to moderate. Conclusion: None of the selected measures of pain have been fully developed or evaluated to demonstrate that they provide accurate, relevant reproducible information.
Frameworks for change in healthcare organisations: A formative evaluation of the NHS Change Model
Authors: Martin Graham P , Sutton Elizabeth , Willars Janet , Dixon-Woods Mary 
Published: December 2013

Background Organisational change in complex healthcare systems is a multifaceted process. The English National Health Service recently introduced a ‘Change Model’ that seeks to offer an evidence-based framework for guiding change. We report findings from a formative evaluation of the NHS Change Model and make recommendations for those developing the Model and its users. Methods The evaluation involved 28 interviews with managers and clinicians making use of the Change Model in relation to a variety of projects. Interviews were fully transcribed and were analysed using an approach based on the Framework method. Findings Participants saw the Change Model as valuable and practically useful. Fidelity to core principles of the Model was variable: participants often altered the Model, especially when using it to orchestrate the work of others. In challenging organisational contexts, the Change Model was sometimes used to delegitimise opposition rather than identify shared purpose among different interest groups. Conclusions Those guiding change may benefit from frameworks, guidance and toolkits to structure and inform their planning and activities. Participants’ experiences suggested the Change Model has much potential. Further work on its design and on supporting materials may optimise the approach, but its utility rests in particular on organisational cultures that support faithful application.
Can Admission Neutrophil to Lymphocyte Ratio Predict Infarct-Related Artery Patency in ST-Segment Elevation Myocardial Infarction
Authors: Doğan Mehmet , Akyel Ahmet , Bilgin Murat , Erat Mehmet , Çimen Tolga , Sunman Hamza , Efe Tolga Han , Açıkel Sadık , Yeter Ekrem 
Published: December 2013

Objectives: In this study, we aimed to investigate the relationship between neutrophil to lymphocyte ratio (NLR) and infarct-related artery (IRA) patency in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 349 patients with STEMI were recruited to this retrospective study. Baseline characteristics were reviewed. Patency of IRA was evaluated by thrombolysis in myocardial infarction flow grade. Results: Of all patients, 293 patients formed the occluded IRA group and 56 patients formed the patent IRA group. The NLR was significantly higher in occluded IRA group (4.4 ± 4.1 vs 1.9 ± 1.1, P < .001). Glucose levels were also higher in occluded IRA group (171.3 ± 78.0 vs 144.7 ± 49.7, P = .022). Regression analysis demonstrated admission NLR and plasma glucose levels as independent predictors of IRA patency. Conclusion: In this study, we found that admission NLR and glucose levels were higher in patients with occluded IRA than in patients with STEMI. We also found that NLR and glucose levels were independent predictors of IRA patency. Because hemogram is a cheap, fast, and widely available test, it can be used in daily practice as a predictor of IRA patency.
Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset
Authors: Collongues N , Marignier R , Jacob A , Leite MI , Siva A , Paul F , Zephir H , Akman-Demir G , Elsone L , Jarius S , Papeix C , Mutch K , Saip S , Wildemann B , Kitley J , Karabudak R , Aktas O , Kuscu D , Altintas A , Palace J , Confavreux C , De Seze J 
Published: December 2013

Background: Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab). Objective: To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death. Methods: We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model. Results: We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate. Conclusion: LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.
Intrathecal Leptin Inhibits Expression of the P2X2/3 Receptors and Alleviates Neuropathic Pain Induced by Chronic Constriction Sciatic Nerve Injury
Authors: Li Xin , Kang Lumei , Li Guilin , Zeng Huihong , Zhang Lei , Ling Xiang , Dong Hui , Liang Shangdong , Chen Hongping 
Published: December 2013

Background Leptin, an adipocytokine produced mainly by white adipose tissue, has a broad role in the regulation of neuronal functions. Accumulating evidence has revealed that leptin plays an important role in influencing neuropathic pain, shown recently by the finding that chronic administration of leptin induced thermal hyperalgesia and mechanical allodynia in naïve rats. Chronic constriction sciatic nerve injury (CCI) is a well characterized model used for studying neuropathic pain. The present study was designed to investigate whether leptin plays a role in neuropathic pain in rats induced by CCI by examining particular pain behaviors. Results After sciatic nerve injury in rats, endogenous levels of leptin and leptin receptor (OB-Rb) were increased in a time dependent manner within the ipsilateral dorsal root ganglion (DRG). Intrathecal administration of leptin once daily for 6 days, beginning 7 days after CCI, alleviated neuropathic pain and decreased the expression of IL-6, TNFα, and the P2X2 and P2X3 receptors. Attenuation of endogenous OB-Rb in the DRG by intrathecal administration of OB-Rb antisense oligonucleotides did not change thermal hyperalgesia or mechanical allodynia induced by CCI. Conclusions Our findings suggest that exogenous leptin can alleviate the chronic neuropathic pain caused by CCI. The leptin effect may be mediated by attenuated expression of IL-6, TNFα, and the P2X2 and P2X3 receptors in the DRG of CCI rats.
Childhood cancers: what is a possible role of infectious agents?
Authors: Alibek Kenneth , Mussabekova Assel , Kakpenova Ainur , Duisembekova Assem , Baiken Yeldar , Aituov Bauyrzhan , Karatayeva Nargis , Zhussupbekova Samal 
Published: December 2013

AbstractThe etiology of childhood cancers has been studied for more than 40 years. However, most if not all cancers occurring in children are attributed to unknown causes. This review is focused on the role of infections in cancer development and progression in children. The main infectious agents include human herpesviruses, polyoma viruses, and human papilloma viruses. It is known that infections can lead to carcinogenesis through various mechanisms, and most likely act in addition to genetic and environmental factors. Given the importance of the infectious etiology of childhood cancers, clinical implications and possible prevention strategies are discussed.
A novel CLDN16 mutation in a large family with familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
Authors: Deeb Asma , Abood Salima Atia , Simon Job , Dastoor Hormazdiar , Pearce Simon HS , Sayer John A 
Published: December 2013

Abstract

Background
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is a rare tubulopathy leading to renal calcification and progressive renal failure.

Case presentation
We report a consanguineous Arab family (of Qatari origin) with 7 affected siblings with variable phenotypes including hypomagnesaemia, hypercalciuria, nephrocalcinosis and renal stones. Presenting features included haematuria and recurrent urinary tract infections. As the biochemical and clinical phenotypes of this family resembled familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, we performed genetic investigation in order to provide a precise molecular diagnosis. We screened all coding regions of the CLDN16 gene and identified a novel mutation (c.G647A, p.R216H) which was found homozygously in the six severely affected cases, who manifested significant nephrocalcinosis, often nephrolithiasis and sometimes reduced GFR. Parents were both heterozygous for the mutation and, together with children carrying the mutation in its heterozygous state, exhibited mild or no biochemical phenotypes.

Conclusion
Mutations in CLDN16 underlie familial hypomagnesaemia with hypercalciuria and nephrocalcinosis but remain a rare cause of nephrocalcinosis and nephrolithiasis. Management includes reduction of hypercalciuria with thiazide diuretics, correction of serum magnesium and close monitoring of renal function given the significant risk of end stage renal failure with this inherited form of nephrocalcinosis.
Comparative preclinical pharmacokinetics study of 3,3′-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon?
Authors: Paltsev Mikhail , Kiselev Vsevolod , Muyzhnek Ekaterina , Drukh Vadim , Kuznetsov Igor , Pchelintseva Olga 
Published: December 2013

Abstract

Background
3,3′-Diindolylmethane (DIM) is known as an agent of natural origin that provides protection against different cancers due to the broad spectrum of its biological activities in vivo. However, this substance has a very poor biodistribution and absorption in animal tissues. This preclinical trial was conducted to evaluate the pharmacokinetics and bioavailability of various DIM formulations in animal model.

Materials and methods
The pharmacokinetic parameters of one crystalline DIM formulation and one liquid DIM formulation (oil solution) compared to non-formulated crystalline DIM (control) were tested in 200 rats. The formulations were orally administered to animals by gavage at doses of 200 mg/kg per DIM (crystalline DIM formulation and non-formulated crystalline DIM) and 0.1 mg/kg per DIM (DIM in oil solution). DIM plasma elimination was measured using HPLC method; after that, the area under the curve (AUC), relative bioavailability, and absolute bioavailability were estimated for two formulations in relation to non-formulated crystalline DIM.

Results and conclusion
The highest bioavailability was achieved by administering liquid DIM (oil solution), containing cod liver oil and polysorbate. The level of DIM in rat blood plasma was about fivefold higher, though the 2,000-fold lower dose was administered compared to crystalline DIM forms. The novel pharmacological DIM substance with high bioavailability may be considered as a promising targeted antitumor chemopreventive agent. It could be used to prevent breast and ovarian cancer development in patients with heterozygous inherited and sporadic BRCA1 gene mutations. Further preclinical and clinical trials are needed to prove this concept.
Wonderful resolutions and categorical crepant resolutions of singularities
Authors: Abuaf Roland 
Published: December 2013

Abstract

Let X be an algebraic variety with Gorenstein singularities. We define the
notion of a wonderful resolution of singularities of X by analogy
with the theory of wonderful compactifications of semi-simple linear algebraic
groups. We prove that if X has rational singularities and has a wonderful
resolution of singularities, then X admits a categorical crepant resolution of
singularities. As an immediate corollary, we get that all determinantal
varieties defined by the minors of a generic square/symmetric/skew-symmetric
matrix admit categorical crepant resolution of singularities.
Accounting Informs Investors and Earnings Management is Rife: Two Questionable Beliefs
Authors: Ball Ray 
Published: December 2013

SYNOPSIS
This short essay addresses the inordinate amount of attention given in the literature to two seemingly widely-held but questionable beliefs: that a major role of financial reporting is providing new information for equity investors, and that “earnings management” is rampant. In this essay, I discuss these beliefs, indicate why I consider them “most incorrect,” and offer conjectures on why they have not been corrected.