bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis
Authors: Graves MC , Benton M , Lea RA , Boyle M , Tajouri L , Macartney-Coxson D , Scott RJ , Lechner-Scott J 
Published: December 2013

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk of developing MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation are recognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure and inherited genetic systems. Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing–remitting MS and 28 healthy controls using Illumina 450K methylation arrays. Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. After prioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of a major effect CpG island in DRB1 in MS cases ( pFDR < 3 × 10−3). In addition, we found 55 non-HLA CpGs that exhibited differential methylation, many of which localise to genes previously linked to MS. Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.
Completing the cycle: The use of audit to develop a mental health service in times of austerity
Authors: Shah Nisha , Donaldson Lucinda , Giridhar Ramya 
Published: December 2013

Background A published audit demonstrated that a pilot psychiatric clinic failed to capture predicted numbers of women with severe and enduring mental illness. Methods On the basis of recommendations from this audit, along with those from the Royal College of Psychiatrists and NICE guidelines, a more comprehensive psychiatric service was developed to meet this demand and therefore manage risk more effectively. Results Over the course of a year, the new service attracted a higher rate of referrals of pregnant women with severe and enduring mental illness. The majority referral source continued to be midwifery-led. Conclusions Audit is a useful tool for evaluating and informing service development and helped us identify further improvements needed to deliver an effective mental health service.
Pregnancy outcomes in a patient with Sjögren's disease with renal involvement
Authors: Joshi Abhishek , O'Donoghue Keelin , Mahmood Uzma , Banerjee Debasish , Banerjee Anita 
Published: December 2013

Background: Maternal and fetal outcome in pregnancy with renal failure is unpredictable, where each condition can adversely affect the other. We present a case of steroid sensitive Sjögren's nephritis worsened by pregnancy, demonstrated over the course of multiple pregnancies and investigated the aetiology. Case: A 28-year-old nullipara with a diagnosis of primary Sjögren's syndrome presented with a deterioration of renal function. A diagnosis of secondary tubulo-interstitial nephritis was made on renal biopsy. Her first pregnancy ended in the second trimester with a decision to deliver a female infant at 27 weeks due to worsening maternal renal function. Renal function improved immediately. A second pregnancy ended in a first trimester miscarriage. The third and fourth pregnancies delivered male infants at 35 and 34 weeks, with worsening renal function in each pregnancy, reaching end stage. Repeat biopsy showed extensive glomerulosclerosis and male cells were identified. Conclusions: This case of Sjögren's syndrome with renal disease demonstrated the increased risk of fetal and maternal adverse pregnancy outcomes. Renal function worsened in each pregnancy and progressed to end-stage renal disease. Fetal microchimerism offers an interesting mechanism for our patient's renal failure and its apparent relationship to her pregnancies.
Managing difficult emergency catheterization: what do urologists want?
Authors: Jones Abeyna LC , Armitage James N , Srirangam Shalom J 
Published: December 2013

Objectives: Acute urinary retention (AUR) is a common urological emergency; however, when approaching a difficult catheterization, this is an evidence-free zone. Our objective is to investigate current practice with the intent to reach a workable consensus for the management of patients in AUR who cannot be easily catheterized urethrally. Subjects: We performed a hypothetical scenario-based, multideanery survey with urology consultants and ST3+ trainees. Participants were asked how they would manage three patients who prove difficult to catheterize using standard methods: benign prostatic obstruction (BPO), urethral stricture, and meatal stenosis. Results: Of respondents, 38% ( n=23) indicated that a 16F curved-tip silicone catheter would be their first choice in managing a patient with BPO, followed by a suprapubic catheter (SPC) (20%, n=12) if this failed. SPC would be the first-line option for patients with a urethral stricture for 67% ( n=40) consultants, and for those with meatal stenosis, 60% would use a meatal dilator followed by SPC (22%, n=13) if this failed. Conclusion: Although there are general trends in preference towards managing a patient who is difficult to catheterize with AUR, there still remains considerable variation in practice due to lack of evidence in this area. We would recommend further multicentre data determining guidelines for best practice.
SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage
Authors: Clifford Ruth , Louis Tania , Robbe Pauline , Ackroyd Sam , Burns Adam , Timbs Adele T. , Wright Colopy Glen , Dreau Helene , Sigaux Francois , Judde Jean Gabriel , Rotger Margalida , Telenti Amalio , Lin Yea-Lih , Pasero Philippe , Maelfait Jonathan , Titsias Michalis , Cohen Dena R. , Henderson Shirley J. , Ross Mark T. , Bentley David , Hillmen Peter , Pettitt Andrew , Rehwinkel Jan , Knight Samantha J. L. , Taylor Jenny C. , Crow Yanick J. , Benkirane Monsef , Schuh Anna 
Published: December 2013

Key Points
Acquired pathogenic mutations in SAMHD1 are found in up to 11% of relapsed/refractory patients with CLL. SAMHD1 is mobilized to sites of DNA damage.
Differences in content and organisational aspects of pulmonary rehabilitation programmes
Authors: Spruit Martijn A. , Pitta Fabio , Garvey Chris , ZuWallack Richard L. , Roberts C. Michael , Collins Eileen G. , Goldstein Roger , McNamara Renae , Surpas Pascale , Atsuyoshi Kawagoshi , López-Campos José-Luis , Vogiatzis Ioannis , Williams Johanna E.A. , Lareau Suzanne , Brooks Dina , Troosters Thierry , Singh Sally J. , Hartl Sylvia , Clini Enrico M. , Wouters Emiel F.M. 
Published: December 2013

The aim was to study the overall content and organisational aspects of pulmonary rehabilitation programmes from a global perspective in order to get an initial appraisal on the degree of heterogeneity worldwide.A 12-question survey on content and organisational aspects was completed by representatives of pulmonary rehabilitation programmes that had previously participated in the European Respiratory Society (ERS) COPD Audit. Moreover, all ERS members affiliated with the ERS Rehabilitation and Chronic Care and/or Physiotherapists Scientific Groups, all members of the American Association of Cardiovascular and Pulmonary Rehabilitation, and all American Thoracic Society Pulmonary Rehabilitation Assembly members were asked to complete the surveyviamultiple e-mailings.The survey has been completed by representatives of 430 centres from 40 countries. The findings demonstrate large differences among pulmonary rehabilitation programmes across continents for all aspects that were surveyed, including the setting, the case mix of individuals with a chronic respiratory disease, composition of the pulmonary rehabilitation team, completion rates, methods of referral and types of reimbursement.The current findings stress the importance of future development of processes and performance metrics to monitor pulmonary rehabilitation programmes, to be able to start international benchmarking, and to provide recommendations for international standards based on evidence and best practice.
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Authors: Chung Kian Fan , Wenzel Sally E. , Brozek Jan L. , Bush Andrew , Castro Mario , Sterk Peter J. , Adcock Ian M. , Bateman Eric D. , Bel Elisabeth H. , Bleecker Eugene R. , Boulet Louis-Philippe , Brightling Christopher , Chanez Pascal , Dahlen Sven-Erik , Djukanovic Ratko , Frey Urs , Gaga Mina , Gibson Peter , Hamid Qutayba , Jarjour Nizar N. , Mauad Thais , Sorkness Ronald L. , Teague W. Gerald 
Published: December 2013

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
A deep insight into the sialotranscriptome of the mosquito, Psorophora albipes
Authors: Chagas Andrezza C , Calvo Eric , Rios-Velásquez Claudia M , Pessoa Felipe AC , Medeiros Jansen F , Ribeiro José MC 
Published: December 2013

Abstract

Background

Psorophora mosquitoes are exclusively found in the Americas and have been associated with transmission of encephalitis and West Nile fever viruses, among other arboviruses. Mosquito salivary glands represent the final route of differentiation and transmission of many parasites. They also secrete molecules with powerful pharmacologic actions that modulate host hemostasis, inflammation, and immune response. Here, we employed next generation sequencing and proteome approaches to investigate for the first time the salivary composition of a mosquito member of the Psorophora genus. We additionally discuss the evolutionary position of this mosquito genus into the Culicidae family by comparing the identity of its secreted salivary compounds to other mosquito salivary proteins identified so far.

Results
Illumina sequencing resulted in 13,535,229 sequence reads, which were assembled into 3,247 contigs. All families were classified according to their in silico-predicted function/ activity. Annotation of these sequences allowed classification of their products into 83 salivary protein families, twenty (24.39%) of which were confirmed by our subsequent proteome analysis. Two protein families were deorphanized from Aedes and one from Ochlerotatus, while four protein families were described as novel to Psorophora genus because they had no match with any other known mosquito salivary sequence. Several protein families described as exclusive to Culicines were present in Psorophora mosquitoes, while we did not identify any member of the protein families already known as unique to Anophelines. Also, the Psorophora salivary proteins had better identity to homologs in Aedes (69.23%), followed by Ochlerotatus (8.15%), Culex (6.52%), and Anopheles (4.66%), respectively.

Conclusions
This is the first sialome (from the Greek sialo = saliva) catalog of salivary proteins from a Psorophora mosquito, which may be useful for better understanding the lifecycle of this mosquito and the role of its salivary secretion in arboviral transmission.
Analysis of mass spectrometry data from the secretome of an explant model of articular cartilage exposed to pro-inflammatory and anti-inflammatory stimuli using machine learning
Authors: Swan Anna L , Hillier Kirsty L , Smith Julia R , Allaway David , Liddell Susan , Bacardit Jaume , Mobasheri Ali 
Published: December 2013

Abstract

Background
Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions.

Methods
This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified.

Results
BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein.

Conclusions
Using this protocol, combining an in vitro model of OA with bioinformatics analysis, a number of relevant extracellular matrix proteins were identified, thereby supporting the application of these bioinformatics tools for analysis of proteomic data from in vitro models of cartilage degradation.
Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry
Authors: Vermeer Marloes , Kievit Wietske , Kuper Hillechiena H , Braakman-Jansen Louise MA , Bernelot Moens Hein J , Zijlstra Theo R , den Broeder Alfons A , van Riel Piet LCM , Fransen Jaap , van de Laar Mart AFJ 
Published: December 2013

Abstract

Background
Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA).

Methods
We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up.

Results
Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years.

Conclusions
We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.
Cytotoxicity, mode of action and antibacterial activities of selected Saudi Arabian medicinal plants
Authors: Kuete Victor , Wiench Benjamin , Alsaid Mansour S , Alyahya Muhammad A , Fankam Aimé G , Shahat Abdelaaty A , Efferth Thomas 
Published: December 2013

Abstract

Background
The flora of Saudi Arabia is one of the richest biodiversity areas in the Arabian Peninsula and comprises very important genetic resources of crop and medicinal plants. The present study was designed to investigate the cytotoxicity and the antibacterial activities of the organic extracts from twenty six Saudi Arabian medicinal plants. The study was also extended to the investigation of the effects of the extracts from the four best plants, Ononis serrata (SY160), Haplophyllum tuberculatum (SY177), Pulicaria crispa (SY179), and Achillea beiberstenii (SY-200) on cell cycle distribution, apoptosis, caspases activities and mitochondrial function in leukemia CCRF-CEM cell line.

Methods
A resazurin assay was used to assess the cytotoxicity of the extracts on a panel of human cancer cell lines whilst the microbroth dilution was used to determine the minimal inhibitory concentration (MIC) of the samples against twelve bacterial strains belonging to four species, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Results
The best activity on leukemia cell lines were recorded with SY177 (IC50 of 9.94 μg/mL) and SY179 (IC50 of 1.81 μg/mL) against CCRF-CEM as well as Ach-b (IC50 of 9.30 μg/mL) and SY160 (IC50 of 5.06 μg/mL) against HL60 cells. The extracts from SY177 and SY179 were also toxic against the seven solid cancer cell lines studied with the highest IC50 values of 31.64 μg/mL (SY177 against Hep-G2 cells). SY177 and Ach-b induced cell cycle arrest in G0/G1 and S phases whilst SY160 and SY179 induced arrest in G0/G1 phase. All the four plant extracts induced apoptosis in CCRF-CEM cells with the alteration of the mitochondrial membrane potential. In the antibacterial assays, only Ach-b displayed moderate antibacterial activities against E. coli and E. aerogenes ATCC strains (MIC of 256 μg/mL), AG100ATeT and K. pneumoniae ATCC strains (MIC of 128 μg/mL).

Conclusions
Finally, the results of the present investigation provided supportive data for the possible use of some Saudi Arabian plants investigated herein, and mostly Haplophyllum tuberculatum, Pulicaria crispa, Ononis serrata and Achillea beiberstenii in the control of cancer diseases.
Id4 dependent acetylation restores mutant-p53 transcriptional activity
Authors: Knowell Ashley E , Patel Divya , Morton Derrick J , Sharma Pankaj , Glymph Shanora , Chaudhary Jaideep 
Published: December 2013

Abstract

Background
The mechanisms that can restore biological activity of mutant p53 are an area of high interest given that mutant p53 expression is observed in one third of prostate cancer. Here we demonstrate that Id4, an HLH transcriptional regulator and a tumor suppressor, can restore the mutant p53 transcriptional activity in prostate cancer cells.

Methods
Id4 was over-expressed in prostate cancer cell line DU145 harboring mutant p53 (P223L and V274F) and silenced in LNCaP cells with wild type p53. The cells were used to quantitate apoptosis, p53 localization, p53 DNA binding and transcriptional activity. Immuno-precipitation/-blot studies were performed to demonstrate interactions between Id4, p53 and CBP/p300 and acetylation of specific lysine residues within p53.

Results
Ectopic expression of Id4 in DU145 cells resulted in increased apoptosis and expression of BAX, PUMA and p21, the transcriptional targets of p53. Mutant p53 gained DNA binding and transcriptional activity in the presence of Id4 in DU145 cells. Conversely, loss of Id4 in LNCaP cells abrogated wild type p53 DNA binding and transactivation potential. Gain of Id4 resulted in increased acetylation of mutant p53 whereas loss of Id4 lead to decreased acetylation in DU145 and LNCaP cells respectively. Id4 dependent acetylation of p53 was in part due to a physical interaction between Id4, p53 and acetyl-transferase CBP/p300.

Conclusions
Taken together, our results suggest that Id4 regulates the activity of wild type and mutant p53. Id4 promoted the assembly of a macromolecular complex involving CBP/P300 that resulted in acetylation of p53 at K373, a critical post-translational modification required for its biological activity.
Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer
Authors: Li Laisheng , Luo Jinmei , Wang Bo , Wang Dong , Xie Xinhua , Yuan Linjing , Guo Jiaoli , Xi Shaoyan , Gao Jie , Lin Xiaoti , Kong Yanan , Xu Xiangdong , Tang Hailing , Xie Xiaoming , Liu Min 
Published: December 2013

Abstract

Background
MicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.

Methods
The expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.

Results
We found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.

Conclusions
Our study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.