bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between anti-U1 ribonucleoprotein antibodies and inflammatory mediators in cerebrospinal fluid of patients with neuropsychiatric systemic lupus erythematosus
Authors: Yokoyama T , Fujii T , Kondo-Ishikawa S , Yamakawa N , Nakano M , Yukawa N , Yoshifuji H , Ohmura K , Mimori T 
Published: February 2014

Objective We investigated possible associations between neurotoxic inflammatory mediators (IMs) and anti-U1RNP antibodies (Abs) in cerebrospinal fluid (CSF) of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Serum and CSF anti-U1RNP Abs were detected using an RNA-immunoprecipitation assay and CSF anti-U1RNP Ab levels were measured by ELISA. IFN-α, MCP-1 and IL-8 levels in CSF were determined by quantitative multiplex cytokine analysis. IM levels were compared among anti-U1RNP-positive and anti-U1RNP-negative NPSLE as well as other rheumatic disease controls (controls). Results Anti-U1RNP Abs were detected in serum (58%) and in CSF (18%) of 82 NPSLE patients. CSF MCP-1 levels were higher in NPSLE than in controls. CSF IFN-α level was higher in CSF anti-U1RNP Ab-positive than in -negative patients or controls. When limited to serum anti-U1RNP Ab-positive patients, however, levels of all three IMs in CSF were higher in CSF anti-U1RNP Ab-positive than in -negative patients. Anti-U1RNP Ab levels in CSF correlated with CSF MCP-1, but not IFN-α and IL-8 levels. Conclusions CSF anti-U1RNP Ab positivity is associated with increased level of CSF IFN-α. MCP-1 levels correlated with CSF anti-U1RNP Ab levels, whereas the increased CSF MCP-1 was not specific to CSF anti-U1RNP Ab-positive NPSLE.
Improving medication safety in UK care homes: challenges and current perspective
Authors: Fahrni Mathumalar Loganathan , Franklin Bryony Dean , Rawaf Salman , Majeed Azeem 
Published: February 2014

Summary In the UK, there are policy and regulatory concerns regarding the governance of care homes and healthcare provision within these homes. From a public health perspective, these issues can pose significant challenges to the provision of safe and quality medication use services to care home residents. The objective of this paper is to highlight an important and neglected issue for the growing population of institutionalized older adults. We reviewed relevant literature for the years 2000 to present and identified recent efforts undertaken to improve medication safety standards in UK care homes. We consider the limitations and reasons for the National Health Service’s restricted role and lack of leadership in providing medical services for this institutionalized population. The efforts taken by the Department of Health and other healthcare authorities targeting medication safety in care homes are also highlighted. In order to improve the quality of healthcare, specifically in areas related to medication safety and quality use of medicines, interventions need to be taken by the national government and similarly by local authorities and NHS commissioners.
Gelatin tannate ameliorates acute colitis in mice by reinforcing mucus layer and modulating gut microbiota composition: Emerging role for ‘gut barrier protectors’ in IBD?
Authors: Scaldaferri Franco , Lopetuso Loris Riccardo , Petito Valentina , Cufino Valerio , Bilotta Mirna , Arena Vincenzo , Stigliano Egidio , Maulucci Giuseppe , Papi Massimiliano , Emiliana Caristo Maria , Poscia Andrea , Franceschi Francesco , Delogu Giovanni , Sanguinetti Maurizio , Spirito Marco De , Sgambato Alessandro , Gasbarrini Antonio 
Published: February 2014

BackgroundGelatin tannate, a gelatin powder containing tannic acids, is commonly employed as an intestinal astringent. Neither information nor animal model exist to confirm its efficacy or unravel mechanisms of action.ObjectiveTo evaluate the action of gelatin tannate in murine dextran sodium sulphate (DSS)‐induced acute colitis.MethodsMice were exposed to DSS and received gelatin tannate by gavage. At sacrifice, colon histological degree of inflammation was assessed. Stool samples were cultured for microbiological analysis. Colon samples were analysed by two‐photon confocal microscopy and atomic force microscopy. Elisa was performed on murine serum to assess lipopolysaccharide and peptidoglycan levels.ResultsGelatin tannate treatment reduced disease activity, bodyweight loss, and preserved colonic length. It produced a decrease in the amount of enterobacteria and enterococci. At confocal microscopy, intestinal samples from healthy and treated mice displayed similar structure in mucus layer thickness and composition; samples from placebo group had no mucus layer or a thinner stratus. Atomic force microscopy confirmed these findings. Treated mice showed lower blood LPS levels vs. control.ConclusionsGelatin tannate decreased the severity of colitis. Acting as a gut barrier enhancer, it re‐establishes gut homeostasis by recovering intestinal permeability and mucus layer integrity in gut mucosa and by modulating microbiota composition.
Cryotherapy in prostate cancer
Authors: Phillips Jason M , Catarinicchia Salvatore , Krughoff Kevin , Barqawi Al B 
Published: February 2014

Review objectives: Cryotherapy use has increased due to technological advances. A review of the literature was performed to evaluate the efficacy and outcomes of whole gland, salvage and targeted focal cryotherapy in the management of prostate cancer. Review findings: Cryotherapy use has increased significantly over the last 10 years with a trend towards focal ablation. Whole gland cryotherapy, salvage cryotherapy and focal cryotherapy biochemical recurrence rates appear to be comparable to other treatment modalities for low risk disease, however biochemical failure remains difficult to compare across studies due to a lack of consensus regarding appropriate end points for evaluation of cryotherapy. Short-term focal cryotherapy outcomes are encouraging. Side effect profiles for cryotherapy have significantly improved with fourth generation systems while salvage cryotherapy continues to carry a slightly higher risk of incontinence than primary whole gland cryotherapy. The incidence of erectile dysfunction after focal cryotherapy is dramatically lower than that for whole gland ablation. Conclusions: Cryotherapy continues to have an active role in the primary and salvage treatment of prostate cancer. Targeted focal cryotherapy is a promising treatment with minimal morbidity. Further long-term data is needed to support targeted therapy in addition to direct comparison with other treatment modalities.
STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense
Authors: Zhang Hong , Clemens Regina A. , Liu Fengchun , Hu Yongmei , Baba Yoshihiro , Theodore Pierre , Kurosaki Tomohiro , Lowell Clifford A. 
Published: February 2014

Key PointsSTIM1-mediated calcium entry is critical for neutrophil superoxide release via activation of calcium-sensitive PKCα and PKCβ. STIM1 deficiency results in profound susceptibility to bacterial infection, but also protection in hepatic ischemia/reperfusion injury.
Loss of imprinting at the 14q32 domain is associated with microRNA overexpression in acute promyelocytic leukemia
Authors: Manodoro Floriana , Marzec Jacek , Chaplin Tracy , Miraki-Moud Farideh , Moravcsik Eva , Jovanovic Jelena V. , Wang Jun , Iqbal Sameena , Taussig David , Grimwade David , Gribben John G. , Young Bryan D. , Debernardi Silvana 
Published: February 2014

Key Points
Loss of imprinting occurs at the 14q32 domain in APL. DNA methylation at the CTCF binding sites correlates with the overexpression of 14q32 miRNAs.
A network-assisted co-clustering algorithm to discover cancer subtypes based on gene expression
Authors: Liu Yiyi , Gu Quanquan , Hou Jack P , Han Jiawei , Ma Jian 
Published: February 2014

Abstract

Background
Cancer subtype information is critically important for understanding tumor heterogeneity. Existing methods to identify cancer subtypes have primarily focused on utilizing generic clustering algorithms (such as hierarchical clustering) to identify subtypes based on gene expression data. The network-level interaction among genes, which is key to understanding the molecular perturbations in cancer, has been rarely considered during the clustering process. The motivation of our work is to develop a method that effectively incorporates molecular interaction networks into the clustering process to improve cancer subtype identification.

Results
We have developed a new clustering algorithm for cancer subtype identification, called “network-assisted co-clustering for the identification of cancer subtypes” (NCIS). NCIS combines gene network information to simultaneously group samples and genes into biologically meaningful clusters. Prior to clustering, we assign weights to genes based on their impact in the network. Then a new weighted co-clustering algorithm based on a semi-nonnegative matrix tri-factorization is applied. We evaluated the effectiveness of NCIS on simulated datasets as well as large-scale Breast Cancer and Glioblastoma Multiforme patient samples from The Cancer Genome Atlas (TCGA) project. NCIS was shown to better separate the patient samples into clinically distinct subtypes and achieve higher accuracy on the simulated datasets to tolerate noise, as compared to consensus hierarchical clustering.

Conclusions
The weighted co-clustering approach in NCIS provides a unique solution to incorporate gene network information into the clustering process. Our tool will be useful to comprehensively identify cancer subtypes that would otherwise be obscured by cancer heterogeneity, using high-throughput and high-dimensional gene expression data.
Statistical analysis of differential gene expression relative to a fold change threshold on NanoString data of mouse odorant receptor genes
Authors: Vaes Evelien , Khan Mona , Mombaerts Peter 
Published: February 2014

AbstractBackgroundA challenge in gene expression studies is the reliable identification of differentially expressed genes. In many high-throughput studies, genes are accepted as differentially expressed only if they satisfy simultaneously a p value criterion and a fold change criterion. A statistical method, TREAT, has been developed for microarray data to assess formally if fold changes are significantly higher than a predefined threshold. We have recently applied the NanoString digital platform to study expression of mouse odorant receptor genes, which form with 1,200 members the largest gene family in the mouse genome. Our objectives are, on these data, to decrease false discoveries when formally assessing the genes relative to a fold change threshold, and to provide a guided selection in the choice of this threshold.ResultsStatistical tests have been developed for microarray data to identify genes that are differentially expressed relative to a fold change threshold. Here we report that another approach, which we refer to as tTREAT, is more appropriate for our NanoString data, where false discoveries lead to costly and time-consuming follow-up experiments. Methods that we refer to as tTREAT2 and the running fold change model improve the performance of the statistical tests by protecting or selecting the fold change threshold more objectively. We show the benefits on simulated and real data.ConclusionsGene-wise statistical analyses of gene expression data, for which the significance relative to a fold change threshold is important, give reproducible and reliable results on NanoString data of mouse odorant receptor genes. Because it can be difficult to set in advance a fold change threshold that is meaningful for the available data, we developed methods that enable a better choice (thus reducing false discoveries and/or missed genes) or avoid this choice altogether. This set of tools may be useful for the analysis of other types of gene expression data.
Confirmation of warfarin resistance of naturally occurring VKORC1 variants by coexpression with coagulation factor IX and in silico protein modelling
Authors: Müller Elisabeth , Keller Alexander , Fregin Andreas , Müller Clemens R , Rost Simone 
Published: February 2014

AbstractBackgroundVKORC1 has been identified some years ago as the gene encoding vitamin K epoxide reductase (VKOR) – the target protein for coumarin derivates like warfarin or phenprocoumon. Resistance against warfarin and other coumarin-type anticoagulants has been frequently reported over the last 50 years in rodents due to problems in pest control as well as in thrombophilic patients showing variable response to anticoagulant treatment. Many different mutations have already been detected in the VKORC1 gene leading to warfarin resistance in rats, mice and in humans. Since the conventionalin vitrodithiothreitol (DTT)-driven VKOR enzymatic assay often did not reflect thein vivostatus concerning warfarin resistance, we recently developed a cell culture-based method for coexpression of VKORC1 with coagulation factor IX and subsequent measurement of secreted FIX in order to test warfarin inhibition in wild-type and mutated VKORC1.ResultsIn the present study, we coexpressed wild-type factor IX with 12 different VKORC1 variants which were previously detected in warfarin resistant rats and mice. The results show that amino acid substitutions in VKORC1 maintain VKOR activity and are associated with warfarin resistance. When we projectedin silicothe amino acid substitutions onto the published three-dimensional model of the bacterial VKOR enzyme, the predicted effects matched well the catalytic mechanism proposed for the bacterial enzyme.ConclusionsThe established cell-based system for coexpression of VKORC1 and factor IX uses FIX activity as an indicator of carboxylation efficiency. This system reflects the warfarin resistance status of VKORC1 mutations from anticoagulant resistant rodents more closely than the traditional DTT-driven enzyme assay. All mutations studied were also predicted to be involved in the reaction mechanism.
Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry
Authors: Han Dohyun , Moon Sungyoon , Kim Yikwon , Min Hophil , Kim Youngsoo 
Published: February 2014

Abstract

Background
Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited.

Results
To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses.

Conclusions
Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases.
The Vibrio cholerae diguanylate cyclase VCA0965 has an AGDEF active site and synthesizes cyclic di-GMP
Authors: Hunter Jessica L , Severin Geoffrey B , Koestler Benjamin J , Waters Christopher M 
Published: February 2014

Abstract

Background
Diguanylate cyclases (DGCs) regulate biofilm formation and motility in bacteria by synthesizing the second messenger cyclic di-GMP (c-di-GMP) in response to environmental stimuli. DGC enzymatic activity is believed to be dependent on the presence of a GG(D/E)EF active site motif, however approximately 25% of known DGCs contain a degenerate active site. The Vibrio cholerae protein VCA0965 contains an AGDEF active site and is presumed to be an inactive DGC.

Results
Ectopic expression of VCA0965 in V. cholerae causes a 3-fold reduction in flagellar-based motility. Additionally, an RXXD allosteric inhibition mutant of VCA0965 strongly inhibited motility and stimulated biofilm formation. This activity was lost when the active site of VCA0965 was mutated to AGDAF, suggesting that VCA0965 synthesizes c-di-GMP. In support of this, ectopic expression of VCA0965 and VCA0965 containing a mutation in its RXXD motif significantly increased the intracellular c-di-GMP levels in V. cholerae and Escherichia coli. Furthermore, we found that purified VCA0965 was able to synthesize c-di-GMP in vitro. Systematic mutation of the first amino acid in the AGDEF motif of VCA0965 revealed that glycine, methionine, and histidine also produced an active DGC capable of inhibiting motility and increasing the intracellular concentration of c-di-GMP in V. cholerae.

Conclusions
Based on these results, we conclude that VCA0965 is capable of c-di-GMP synthesis and that the first amino acid of the GG(D/E)EF motif is more tolerant of substitutions than currently appreciated.
A case of granulomatosis with polyangiitis complicated by cyclophosphamide toxicity and opportunistic infections: choosing between Scylla and Charybdis
Authors: Ernst Elena , Girndt Matthias , Pliquett Rainer U 
Published: February 2014

Abstract

Background
We report a case of progressive Granulomatosis with Polyangiitis (Wegener’s Granulomatosis) with life-threatening complications of both the underlying disease and induction immunosuppressive therapy. Here, for the first time, cyclophosphamide toxicity and severe opportunistic infections including pneumocystis jirovecii- pneumonia were found in one case in a close temporal relationship.

Case presentation
A 34-year-old male patient of Caucasian ethnicity presented with acute renal failure necessitating hemodialysis treatment due to Granulomatosis with Polyangiitis (Wegener’s Granulomatosis). Kidney disease progressed to end-stage renal disease shortly after first diagnosis. After the 2nd bolus of cyclophosphamide shortly, induction immunosuppression (glucocorticoid/cyclophosphamide) was interrupted for repeat infections and resumed 5 years later. By that time, the lungs developed large pulmonary cavernae most likely due to smoldering granuloma indicative for the failed goal of disease remission. Therefore, induction immunosuppression was resumed. Following two monthly boli of cyclophosphamide, the patient developed pericardial effusion and, consecutively, atrioventricular blockade most likely due to cyclophosphamide. After recovery, the patient was discharged without cotrimoxacole. 10 weeks after the last cyclophosphamide bolus and 6 weeks after cessation of cotrimoxacole, the patient was readmitted to the intensive-care unit with Pneumocystis jirovecii pneumonia, and died 6 months later or 74 months after first diagnosis of Granulomatosis with Polyangiitis.

Conclusions
This case illustrates both the need for adequate immunosuppressive therapy to reach disease remission and the limitations thereof in terms of complications including cardiotoxicity of cyclophosphamide and Pneumocystis jirovecii pneumonia. In line with current recommendations, the present case strongly encourages pneumocystis jirovecii- pneumonia chemoprophylaxis for at least 6 months following induction therapy in Granulomatosis with Polyangiitis.
The return-to-work process of individuals sick-listed because of whiplash-associated disorder: a three-year follow-up study in a Danish cohort of long-term sickness absentees
Authors: Biering-Sørensen Sarah , Møller Anne , Stoltenberg Christian DG , Holm Jonas W , Skov Peder G 
Published: February 2014

Abstract

Background
The chronic course of whiplash-associated disorder (WAD) has implications for both the individual and society. It has been shown that up to 50% of patients have not yet returned to work six months after a whiplash injury. We wanted to study the return-to-work (RTW) process in individuals sick-listed for more than eight weeks in six Danish municipalities. RTW in individuals sick-listed due to WAD was compared to that in those sick-listed for other musculoskeletal disorders (MSD).

Methods
Information about long-term sick-listed individuals in six Danish municipalities was retrieved from an existing database. Data on public transfer income were collected and the RTW process was followed on a weekly basis. Multivariate logistic regression analysis of RTW was done four times during the first three years after the start of sick-listing.

Results
One hundred and four individuals were sick-listed due to WAD and 3,204 individuals were sick-listed due to other MSDs. After 6 months, the RTW was significantly lower in the WAD group. OR for RTW in the WAD group was 0.29 (0.18–0.49) compared to the MSD group. The RTW process for both groups stabilised after two years of follow-up; 44% returned to work in the WAD group as compared to 58% in the MSD group.

Conclusion
Sick-listed individuals with whiplash-associated disorder are less likely to return to work than individuals who are sick-listed because of other musculoskeletal disorders. In both groups, RTW stabilised after two years of follow-up.