bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical test concerning bone mass apposition under electrical and mechanical stimulus
Authors: Garzón-Alvarado Diego A , Ramírez-Martínez Angélica M , Cardozo de Martínez Carmen Alicia 
Published: May 2012

Abstract
This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is altered under electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects.
Clinical guidelines contribute to the health inequities experienced by individuals with intellectual disabilities
Authors: Mizen Lindsay AM , Macfie Marjorie L , Findlay Linda , Cooper Sally-Ann , Melville Craig A 
Published: May 2012

Abstract

Background
Clinical practice guidelines are developed to improve the quality of healthcare. However, clinical guidelines may contribute to health inequities experienced by disadvantaged groups. This study uses an equity lens developed by the International Clinical Epidemiology Network (INCLEN) to examine how well clinical guidelines address inequities experienced by individuals with intellectual disabilities.

Methods
Nine health problems relevant to the health inequities experienced by persons with intellectual disabilities were selected. Clinical guidelines on these disorders were identified from across the world. The INCLEN equity lens was used as the basis for a purpose-designed, semistructured data collection tool. Two raters independently examined each guideline and completed the data collection tool. The data extracted by each rater were discussed at a research group consensus conference and agreement was reached on a final equity lens rating for each guideline.

Results
Thirty-six guidelines were identified, one of which (2.8%) explicitly excluded persons with intellectual disabilities. Of the remaining 35, six (17.1%) met the first criterion of the equity lens, identifying persons with intellectual disabilities at high risk for the specific health problem. Eight guidelines (22.9%) contained any content on intellectual disabilities. Six guidelines addressed the fourth equity lens criterion, by giving specific consideration to the barriers to implementation of the guideline in disadvantaged populations. There were no guidelines that addressed the second, third, and fifth equity lens criteria.

Conclusions
The equity lens is a useful tool to systematically examine whether clinical guidelines address the health needs and inequities experienced by disadvantaged groups. Clinical guidelines are likely to further widen the health inequities experienced by persons with intellectual disabilities, and other disadvantaged groups, by being preferentially advantageous to the general population. There is a need to systematically incorporate methods to consider disadvantaged population groups into the processes used to develop clinical guidelines.
Synthesis of naringin 6"-ricinoleate using immobilized lipase
Authors: Almeida Verônica M , Branco Carla RC , Assis Sandra A , Vieira Ivo JC , Braz-Filho Raimundo , Branco Alexsandro 
Published: May 2012

Abstract

Background
Naringin is an important flavanone with several biological activities, including antioxidant action. However, this compound shows low solubility in lipophilic preparations, such as is used in the cosmetic and food industries. One way to solve this problem is to add fatty acids to the flavonoid sugar unit using immobilized lipase. However, there is limited research regarding hydroxylation of unsaturated fatty acids as an answer to the low solubility challenge. In this work, we describe the reaction of naringin with castor oil containing ricinoleic acid, castor oil's major fatty acid component, using immobilized lipase from Candida antarctica. Analysis of the 1H and 13 C NMR (1D and 2D) spectra and literature comparison were used to characterise the obtained acyl derivative.

Results
After allowing the reaction to continue for 120 hours (in acetone media, 50°C), the major product obtained was naringin 6″-ricinoleate. In this reaction, either castor oil or pure ricinoleic acid was used as the acylating agent, providing a 33% or 24% yield, respectively. The chemical structure of naringin 6″-ricinoleate was determined using NMR analysis, including bidimensional (2D) experiments.

Conclusion
Using immobilized lipase from C. antarctica, the best conversion reaction was observed using castor oil containing ricinoleic acid as the acylating agent rather than an isolated fatty acid.

Graphical abstract
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A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy
Authors: Hallett Robin M , Pond Gregory , Hassell John A 
Published: May 2012

AbstractBackgroundThe efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available.MethodsWe used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents.ResultsHere, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol.ConclusionsImportantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.
Low pressure hyperbaric oxygen therapy and SPECT brain imaging in the treatment of blast-induced chronic traumatic brain injury (post-concussion syndrome) and post traumatic stress disorder: a case report
Authors: Harch Paul G , Fogarty Paul G , Staab Paul K , Van Meter Keith 
Published: May 2012

Abstract
A 25-year-old male military veteran presented with diagnoses of post concussion syndrome and post traumatic stress disorder three years after loss of consciousness from an explosion in combat. The patient underwent single photon emission computed tomography brain blood flow imaging before and after a block of thirty-nine 1.5 atmospheres absolute hyperbaric oxygen treatments. The patient experienced a permanent marked improvement in his post-concussive symptoms, physical exam findings, and brain blood flow. In addition, he experienced a complete resolution of post-traumatic stress disorder symptoms. After treatment he became and has remained employed for eight consecutive months. This case suggests a novel treatment for the combined diagnoses of blast-induced post-concussion syndrome and post-traumatic stress disorder.
Unusual histological presentation in neurofibromas: Two case reports
Authors: Joshi Deepti , Gangane Nitin , Kishore Sanjeev , Vagha Sunita 
Published: May 2012

Abstract
Various histological variants of neurofibroma have been described. The objective of this paper is to discuss the unusual histological findings seen in two cases of neurofibromas associated with neurofibromatosis type 1 Both cases presented with multiple subcutaneous nodules. Surgical excision of the largest nodule was done in both the cases. Histological examination of case no.1 revealed a benign tumor of the peripheral nerve sheath, of neurofibroma type with presence of mucus producing glands. The epithelial component was benign in this case. The second case showed presence of rosettes in between areas of typical neurofibroma.
Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report
Authors: Mashitani Tsuyoshi , Yoshiji Hitoshi , Yamazaki Masaharu , Ikenaka Yasuhide , Noguchi Ryuichi , Ishikawa Masatoshi , Kawaratani Hideto , Matsuo Norihide , Uemura Masahito , Yamao Junichi , Fujimoto Masao , Mitoro Akira , Toyohara Masahisa , Yoshida Motoyuki , Sawai Masayoshi , Morioka Chie , Tsujimoto Tatsuhiro , Kitade Mitsuteru , Kaji Kosuke , Aihara Yosuke , Fukui Hiroshi 
Published: May 2012

Abstract

Background
Although several recent reports have shown that hepatocellular carcinoma (HCC) developed in patients with chronic hepatitis C (CH-C) even after having a sustained virological response (SVR) to interferon (IFN) therapy, it is not common for HCC to develop more than 10 years after SVR.

Case presentation
A 73-year-old Japanese man with CH-C who achieved SVR to IFN therapy 13 years ago was admitted into our hospital because of huge multiple liver tumors along with marked elevation of the tumor markers. Several diagnostic modalities strongly suggested HCC, and we performed histopathological examination. After confirming the diagnosis as well-differentiated HCC, we successfully treated these tumors with intensive combination therapies.

Conclusion
Our report highlights the need for careful follow-up for more than 10 years even if the patients with CH-C achieve SVR to IFN therapy.
Differences in adhesion and protrusion properties correlate with differences in migration speed under EGF stimulation
Authors: Hou Yue , Hedberg Sarah , Schneider Ian C 
Published: May 2012

Abstract

Background
Cell migration plays an essential role in many biological processes, such as cancer metastasis, wound healing and immune response. Cell migration is mediated through protrusion and focal adhesion (FA) assembly, maturation and disassembly. Epidermal growth factor (EGF) is known to enhance migration rate in many cell types; however it is not known how FA maturation, FA dynamics and protrusion dynamics are regulated during EGF-induced migration. Here we use total internal reflection fluorescence (TIRF) microscopy and image analysis to quantify FA properties and protrusion dynamics under different doses of EGF stimulation.

Results
EGF was found to broaden the distribution of cell migration rates, generating more fast and slow cells. Furthermore, groups based on EGF stimulation condition or cell migration speed were marked by characteristic signatures. When data was binned based on EGF stimulation conditions, FA intensity and FA number per cell showed the largest difference among stimulation groups. FA intensity decreased with increasing EGF concentration and FA number per cell was highest under intermediate stimulation conditions. No difference in protrusion behavior was observed. However, when data was binned based on cell migration speed, FA intensity and not FA number per cell showed the largest difference among groups. FA intensity was lower for fast migrating cells. Additionally, waves of protrusion tended to correlate with fast migrating cells.

Conclusions
Only a portion of the FA properties and protrusion dynamics that correlate with migration speed, correlate with EGF stimulation condition. Those that do not correlate with EGF stimulation condition constitute the most sensitive output for identifying why cells respond differently to EGF. The idea that EGF can both increase and decrease the migration speed of individual cells in a population has particular relevance to cancer metastasis where the microenvironment can select subpopulations based on some adhesion and protrusion characteristics, leading to a more invasive phenotype as would be seen if all cells responded like an “average” cell.
p53tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis
Authors: Yamanishi Yuji , Boyle David L , Green Douglas R , Keystone Edward C , Connor Alison , Zollman Susan , Firestein Gary S 
Published: May 2012

AbstractAbnormalities in the p53 tumor suppressor gene have been detected in rheumatoid arthritis (RA) and could contribute to the pathogenesis of chronic disease. To determine whether synoviocytes from invasive synovium in RA have an increased number of mutations compared with non-erosion synoviocytes, p53 cDNA subclones from fibroblast-like synoviocytes (FLS) derived from erosion and non-erosion sites of the same synovium were examined in patients requiring total joint replacement. Ten erosion FLS lines and nine non-erosion FLS lines were established from nine patients with RA. Exons 5–10 from 209 p53 subclones were sequenced (114 from erosion FLS, 95 from non-erosion FLS). Sixty percent of RA FLS cell lines and 8.6% of the p53 subclones isolated from FLS contained p53 mutations. No significant differences were observed between the erosion and non-erosion FLS with regard to the frequency or type of p53 mutation. The majority of the mutations were missense transition mutations, which are characteristic of oxidative damage. In addition, paired intact RA synovium and cultured FLS from the same joints were evaluated for p53 mutations. Matched synovium and cultured synoviocytes contained p53 mutations, although there was no overlap in the specific mutations identified in the paired samples. Clusters of p53 mutations in subclones were detected in some FLS, including one in codon 249, which is a well-recognized 'hot spot' associated with cancer. Our data are consistent with the hypothesis that p53 mutations are randomly induced by genotoxic exposure in small numbers of RA synoviocytes localized to erosion and non-erosion regions of RA synovium. The determining factor for invasiveness might be proximity to bone or cartilage rather than the presence of a p53 mutation.
NOS2polymorphisms associated with the susceptibility to pulmonary arterial hypertension with systemic sclerosis: contribution to the transcriptional activity
Authors: Kawaguchi Yasushi , Tochimoto Akiko , Hara Masako , Kawamoto Manabu , Sugiura Tomoko , Katsumata Yasuhiro , Okada Jun , Kondo Hirobumi , Okubo Mitsuo , Kamatani Naoyuki 
Published: May 2012

AbstractSystemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. One of several complications of SSc, pulmonary arterial hypertension (PAH) can be refractory to treatment, both novel and established. In the present study we investigated the ratio of circulating nitric oxide to endothelin-1 in patients with both SSc and PAH, and determined whether polymorphisms in NOS2 (the nitric oxide synthase 2 gene) are associated with susceptibility to PAH. Endothelin-1 in plasma and nitric oxide metabolites (nitrate and nitrite) in serum were measured. The nitric oxide/endothelin-1 ratio was significantly lower in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. We confirmed the presence of two single nucleotide polymorphisms at positions -1,026 and -277 and a pentanucleotide repeat (CCTTT) at -2.5 kilobases. There were significant differences in single nucleotide polymorphisms between patients with SSc who had PAH and those who did not, and between patients with both SSc and PAH and healthy control individuals. The CCTTT repeat was significantly shorter in patients with both SSc and PAH than in patients with SSc only or in healthy control individuals. Transcriptional activity were analyzed using the luciferase reporter assay. The transcriptional activity of NOS2 was much greater in fibroblasts transfected by a vector with a long allele of the CCTTT repeat than in those transfected by a vector with a short allele. Polymorphisms in the NOS2 gene are associated with transcriptional activity of the NOS2 gene and with susceptibility to SSc-related PAH.
Type IX collagen deficiency enhances the binding of cartilage-specific antibodies and arthritis severity
Authors: Carlsen Stefan , Nandakumar Kutty Selva , Holmdahl Rikard 
Published: May 2012

AbstractJoint cartilage is attacked in both autoimmune inflammatory and osteoarthritic processes. Type IX collagen (CIX) is a protein of importance for cartilage integrity and stability. In this study we have backcrossed a transgenic disruption of the col9a1 gene, which leads to an absence of CIX, into two different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient mice developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice had more pronounced enthesopathic arthritis, the so-called stress-induced arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of collagen-induced arthritis, and CIX deficiency in both strains led to the development of a more severe arthritis than in the controls. Induction of arthritis with monoclonal antibodies against type II collagen (CII) led to an earlier arthritis in the paws that also involved the knee joints. The antibodies used, which were specific for the J1 and the C1I epitopes of CII, initiate their arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound to cartilage better in CIX-deficient mice than in wild-type animals, demonstrating that the lack of CIX in cartilage leads to an increased accessibility of structures for antibody binding and thus making the joints more vulnerable to inflammatory attack. These findings accentuate the importance of cartilage stability; cartilage disrupted as a result of genetic disorders could be more accessible and vulnerable to an autoimmune attack by pathogenic antibodies.
Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment
Authors: Simon Teresa A , Askling Johan , Lacaille Diane , Franklin Jarrod , Wolfe Frederick , Covucci Allison , Suissa Samy , Hochberg Marc C ,   the Abatacept Epidemiology Study Group
Published: May 2012

Abstract
Introduction
Patients with rheumatoid arthritis (RA) have an increased risk of infection and this risk appears to be higher with anti-TNF (tumor necrosis factor) agents. We pooled data from the cumulative abatacept RA clinical development program, both double-blind and open-label periods, to estimate the incidence rates (IRs) of infections requiring hospitalization including pneumonia and opportunistic infections, in comparison with RA patients treated with non-biologic disease-modifying antirheumatic drugs (DMARDs) from several reference cohorts.

Methods
Infections reported in seven abatacept clinical trials of RA patients (double-blind and open-label periods) were tabulated. Comparisons were made between the observed IRs in abatacept-treated patients and those in over 133,000 patients exposed to non-biologic DMARDs in six reference RA cohorts. Age- and sex-adjusted IRs of infections requiring hospitalization, including pneumonia (most frequent hospital infection), were used to estimate the expected IRs with abatacept by the method of indirect adjustment. Standardized incidence ratios (SIR) and 95% CI were calculated comparing incidence in the cumulative abatacept experience with incidence in each RA cohort.

Results
A total of 1,955 (double-blind period) and 4,134 (double-blind + open-label periods with a cumulative exposure of 8,392 person-years) abatacept-treated RA patients were analyzed. Observed IRs for infections requiring hospitalization during the double-blind period were 3.05 per 100-patient years for abatacept-treated patients and 2.15 per 100 patient years for placebo. In the cumulative population, observed IR for infections requiring hospitalization was 2.72 per 100-patient years. Rates for abatacept were similar to expected IRs based on other RA non-biologic DMARD cohorts.

Conclusions
IRs of infections requiring hospitalization and pneumonia in abatacept trials are consistent with expected IRs based on reference RA DMARD cohorts. RA patients are at higher risk of infection compared with the general population, making the RA DMARD cohorts an appropriate reference group. The safety of abatacept, including incidence of infections requiring hospitalization, will continue to be monitored in a post-marketing surveillance program.
A1298C polymorphism in the MTHFRgene predisposes to cardiovascular risk in rheumatoid arthritis
Authors: Palomino-Morales Rogelio , Gonzalez-Juanatey Carlos , Vazquez-Rodriguez Tomas R , Rodriguez Luis , Miranda-Filloy Jose A , Fernandez-Gutierrez Benjamin , Llorca Javier , Martin Javier , Gonzalez-Gay Miguel A 
Published: May 2012

Abstract
Introduction
We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA.

Methods
Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo and Hospital San Carlos, Madrid, were studied. Patients and controls (n = 865) were genotyped using predesigned TaqMan SNP genotyping assays.

Results
No significant differences in allele or genotype frequencies for the MTHFR gene polymorphisms between RA patients and controls were found. Also, no association between the MTHFR 677 C>T polymorphism and CV events or endothelial dysfunction was observed. However, the MTHFR 1298 allele C frequency was increased in patients with CV events after 5 years (38.7% versus 30.3%; odds ratio = 1.45; 95% confidence interval = 1.00 to 2.10; P = 0.04) and 10 years (42.2% versus 31.0%; odds ratio = 1.62; 95% confidence interval = 1.08 to 2.43; P = 0.01) follow up. Moreover, patients carrying the MTHFR 1298 AC and CC genotypes had a significantly decreased flow-mediated endothelium-dependent vasodilatation (4.3 ± 3.9%) compared with those carrying the MTHFR 1298 AA genotype (6.5 ± 4.4%) (P = 0.005).

Conclusions
Our results show that the MTHFR 1298 A>C gene polymorphism confers an increased risk for subclinical atherosclerosis and CV events in patients with RA.