bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swirl sign in intracerebral haemorrhage: definition, prevalence, reliability and prognostic value
Authors: Selariu Eufrozina , Zia Elisabet , Brizzi Marco , Abul-Kasim Kasim 
Published: September 2012

Abstract

Background
Swirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density. The aims of this study were to describe swirl sign in ICH, study its prevalence, study the reliability of the subjective evaluation on computed tomography (CT), and to explore its prognostic value.

Methods
CTs of 203 patients with ICH were retrospectively evaluated for the presence of swirl sign. Association between swirl sign and different clinical and radiological variables was studied.

Results
Inter- and intraobserver agreement with regard to the occurrence of swirl sign was substantial (К 0.80) and almost perfect (К 0.87), respectively. Swirl sign was found in 30% of the study population. 61% of patients with swirl sign were dead at one month compared with 21% of those with no swirl sign (p < 0.001). Only 19% of patients with swirl sign exhibited favorable outcome at three months compared with 53% of those with no swirl sign (p < 0.001). Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 ± 50 ml (median 42 ml) compared with 15 ± 25 ml (median 6) in patients whose CT did not show swirl sign (p < 0.001). Swirl sign was independent predictor of death at one month (p = 0.03; adjusted odds ratio 2.6, 95% CI 1.1 – 6), and functional outcome at three months (p = 0.045; adjusted odds ratio 2.6, 95% CI 1.02 – 6.5).

Conclusions
As swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.
Targeting of CD34+CD38-cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia
Authors: Jawad Mays , Yu Ning , Seedhouse Claire , Tandon Karuna , Russell Nigel H , Pallis Monica 
Published: September 2012

Abstract

Background
The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.

Methods
Chemosensitivity in phenotypically defined subsets from 34 primary AML samples was measured by flow cytometry following 48 hr in vitro treatment with gemtuzumab ozogamicin (GO, Mylotarg) and the farnesyltransferase inhibitor tipifarnib/zarnestra. The DNA damage response was measured using flow cytometry, immunofluorescence and immunohistochemistry.

Results
Using a previously validated in vitro minimal residual disease model, we now show that the combination of GO (10 ng/ml) and tipifarnib (5 μM) targets the CD34+CD38- subset resulting in 65% median cell loss compared to 28% and 13% CD34+CD38- cell loss in GO-treated and tipifarnib-treated cells, respectively. Using phosphokinome profiling and immunofluorescence in the TF-1a cell line, we demonstrate that the drug combination is characterised by the activation of a DNA damage response (induction of γH2A.X and thr68 phosphorylation of chk2). Higher induction of γH2AX was found in CD34+CD38- than in CD34+CD38+ patient cells. In a model system, we show that dormancy impairs damage resolution, allowing accumulation of γH2AX foci.

Conclusions
The chemosensitivity of the CD34+CD38- subset, combined with enhanced damage indicators, suggest that this subset is primed to favour programmed cell death as opposed to repairing damage. This interaction between tipifarnib and GO suggests a potential role in the treatment of AML.
Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study
Authors: Johnson Shanthi , Sathyaseelan Manoranjitham , Charles Helen , Jeyaseelan Visalakshi , Jacob Kuruthukulangara Sebastian 
Published: September 2012

Abstract

Background
The sole focus of models of insight on bio-medical perspectives to the complete exclusion of local, non-medical and cultural constructs mandates review. This study attempted to investigate the impact of insight, psychopathology, explanatory models of illness on outcome of first episode schizophrenia.

Method
Patients diagnosed to have DSM IV schizophrenia (n = 131) were assessed prospectively for insight, psychopathology, explanatory models of illness at baseline, 6, 12 and 60 months using standard instruments. Multiple linear and logistic regression and generalized estimating equations (GEE) were employed to assess predictors of outcome.

Results
We could follow up 95 (72.5%) patients. Sixty-five of these patients (68.4%) achieved remission. There was a negative relationship between psychosis rating and insight scores. Urban residence, fluctuating course of the initial illness, and improvement in global functioning at 6 months and lower psychosis rating at 12 months were significantly related to remission at 5 years. Insight scores, number of non-medical explanatory models and individual explanatory models held during the later course of the illness were significantly associated with outcome. Analysis of longitudinal data using GEE showed that women, rural residence, insight scores and number of non-medical explanatory models of illness held were significantly associated with BPRS scores during the study period.

Conclusions
Insight, the disease model and the number of non-medical model positively correlated with improvement in psychosis arguing for a complex interaction between the culture, context and illness variables. These finding argue that insight and explanatory models are secondary to psychopathology, course and outcome of the illness. The awareness of mental illness is a narrative act in which people make personal sense of the many challenges they face. The course and outcome of the illness, cultural context, acceptable cultural explanations and the prevalent social stigma interact to produce a complex and multifaceted understanding of the issues. This complexity calls for a nuanced framing of insight.
Observation of strain effect on the suspended graphene by polarized Raman spectroscopy
Authors: Huang Cheng-Wen , Lin Bing-Jie , Lin Hsing-Ying , Huang Chen-Han , Shih Fu-Yu , Wang Wei-Hua , Liu Chih-Yi , Chui Hsiang-Chen 
Published: September 2012

Abstract
We report the strain effect of suspended graphene prepared by micromechanical method. Under a fixed measurement orientation of scattered light, the position of the 2D peaks changes with incident polarization directions. This phenomenon is explained by a proposed mode in which the peak is effectively contributed by an unstrained and two uniaxial-strained sub-areas. The two axes are tensile strain. Compared to the unstrained sub-mode frequency of 2,672 cm−1, the tension causes a red shift. The 2D peak variation originates in that the three effective sub-modes correlate with the light polarization through different relations. We develop a method to quantitatively analyze the positions, intensities, and polarization dependences of the three sub-peaks. The analysis reflects the local strain, which changes with detected area of the graphene film. The measurement can be extended to detect the strain distribution of the film and, thus, is a promising technology on graphene characterization.
Some new common fixed point results through generalized altering distances on partial metric spaces
Authors: Ahmad Abd Ghafur Bin , Fadail Zaid Mohammed , Nashine Hemant Kumar , Kadelburg Zoran , Radenović Stojan 
Published: September 2012

Abstract
We establish common fixed point results for two pairs of weakly compatible mappings on a partial metric space, satisfying a weak contractive condition involving generalized control functions. The presented theorems extend and unify various known fixed point results. Examples are given to show that our results are proper extensions of the known ones.

MSC:47H10, 54H25, 54H10.
Prostaglandin Metabolite Induces Inhibition of TRPA1 and Channel-Dependent Nociception
Authors: Weng Yingqi , Batista-Schepman Patricia A , Barabas Marie E , Harris Eli Q , Dinsmore Thomas B , Kossyreva Elena A , Foshage Audra M , Wang Michelle H , Schwab Matthew J , Wang Victoria M , Stucky Cheryl L , Story Gina M 
Published: September 2012

Background: The Transient Receptor Potential (TRP) ion channel TRPA1 is a key player in pain pathways. Irritant chemicals activate ion channel TRPA1 via covalent modification of N-terminal cysteines. We and others have shown that 15-Deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) similarly activates TRPA1 and causes channel-dependent nociception. Paradoxically, 15d-PGJ2 can also be anti-nociceptive in several pain models. Here we hypothesized that activation and subsequent desensitization of TRPA1 in dorsal root ganglion (DRG) neurons underlies the anti-nociceptive property of 15d-PGJ2. To investigate this, we utilized a battery of behavioral assays and intracellular Ca2+ imaging in DRG neurons to test if pre-treatment with 15d-PGJ2 inhibited TRPA1 to subsequent stimulation. Results: Intraplantar pre-injection of 15d-PGJ2, in contrast to mustard oil (AITC), attenuated acute nocifensive responses to subsequent injections of 15d-PGJ2 and AITC, but not capsaicin (CAP). Intraplantar 15d-PGJ2—administered after the induction of inflammation—reduced mechanical hypersensitivity in the Complete Freund's Adjuvant (CFA) model for up to 2 h post-injection. The 15d-PGJ2-mediated reduction in mechanical hypersensitivity is dependent on TRPA1, as this effect was absent in TRPA1 knockout mice. Ca2+ imaging studies of DRG neurons demonstrated that 15d-PGJ2 pre-exposure reduced the magnitude and number of neuronal responses to AITC, but not CAP. AITC responses were not reduced when neurons were pre-exposed to 15d-PGJ2 combined with HC-030031 (TRPA1 antagonist), demonstrating that inhibitory effects of 15d-PGJ2 depend on TRPA1 activation. Single daily doses of 15d-PGJ2, administered during the course of 4 days in the CFA model, effectively reversed mechanical hypersensitivity without apparent tolerance or toxicity. Conclusions: Taken together, our data support the hypothesis that 15d-PGJ2 induces activation followed by persistent inhibition of TRPA1 channels in DRG sensory neurons in vitro and in vivo. Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics.
A single-institution study of stereotactic body radiotherapy for patients with unresectable visceral pulmonary or hepatic oligometastases
Authors: Fumagalli Ingrid , Bibault Jean-Emmanuel , Dewas Sylvain , Kramar Andrew , Mirabel Xavier , Prevost Bernard , Lacornerie Thomas , Jerraya Hajer , Lartigau Eric 
Published: September 2012

Abstract

Purpose
The purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy.

Methods and materials
Between July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity.

Results
A total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23–84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7–110 mm) for liver and 12.5 mm (range, 5–63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55–81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18–37%) and 10% (95% CI: 4–20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1–9.5 months). Observed toxicities included grade 1–3 acute toxicities. One grade 3 and no grade 4 toxicity were reported.

Conclusion
High-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy.

Summary
Stereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients’ life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.
Enhanced DPPH radical scavenging activity and DNA protection effect of litchi pericarp extract by Aspergillus awamoribioconversion
Authors: Lin Sen , Yang Bao , Chen Feng , Jiang Guoxiang , Li Qing , Duan Xuewu , Jiang Yueming 
Published: September 2012

Abstract

Background
Litchi (Litchi chinensis Sonn.) pericarp is a major byproduct which contains a significant amount of polyphenol. This study was designed to biotransformation litchi pericarp extract (LPE) by Aspergillus awamori to produce more bioactive compounds with stronger antioxidant activities.

Results
The study exhibited that the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities significantly (p < 0.05) increased from 15.53% to 18.23% in the water-extracted fraction and from 25.41% to 36.82% in the ethyl acetate-extracted fraction. Application of DNA cleavage assay further demonstrated the enhanced protection effect of the fermented phenolics on DNA damage. It is also noted that the water-extracted fraction of the fermented LPE possessed a much stronger capacity than the ethyl acetate-extracted fraction to prevent from damage of supercoiled DNA. Interestingly, it was found that some new compounds such as catechin and quercetin appeared after of A. awamori fermentation of LPE, which could account for the enhanced antioxidant activity.

Conclusion
The DPPH radical scavenging activity and DNA protection effect of LPE were increased by Aspergillus awamori bioconversion while some compounds responsible for the enhanced antioxidant activity were identified. This study provided an effective way of utilizing fruit pericarp as a readily accessible source of the natural antioxidants in food industry and, thus, extended the application area such as fruit by-products.
Predicting the difficulty of pure, strict, epistatic models: metrics for simulated model selection
Authors: Urbanowicz Ryan J , Kiralis Jeff , Fisher Jonathan M , Moore Jason H 
Published: September 2012

Abstract

Background
Algorithms designed to detect complex genetic disease associations are initially evaluated using simulated datasets. Typical evaluations vary constraints that influence the correct detection of underlying models (i.e. number of loci, heritability, and minor allele frequency). Such studies neglect to account for model architecture (i.e. the unique specification and arrangement of penetrance values comprising the genetic model), which alone can influence the detectability of a model. In order to design a simulation study which efficiently takes architecture into account, a reliable metric is needed for model selection.

Results
We evaluate three metrics as predictors of relative model detection difficulty derived from previous works: (1) Penetrance table variance (PTV), (2) customized odds ratio (COR), and (3) our own Ease of Detection Measure (EDM), calculated from the penetrance values and respective genotype frequencies of each simulated genetic model. We evaluate the reliability of these metrics across three very different data search algorithms, each with the capacity to detect epistatic interactions. We find that a model’s EDM and COR are each stronger predictors of model detection success than heritability.

Conclusions
This study formally identifies and evaluates metrics which quantify model detection difficulty. We utilize these metrics to intelligently select models from a population of potential architectures. This allows for an improved simulation study design which accounts for differences in detection difficulty attributed to model architecture. We implement the calculation and utilization of EDM and COR into GAMETES, an algorithm which rapidly and precisely generates pure, strict, n-locus epistatic models.
Interactions of the CpxA sensor kinase and cognate CpxR response regulator from Yersinia pseudotuberculosis
Authors: Thanikkal Edvin J , Mangu Jagadish C K , Francis Matthew S 
Published: September 2012

Abstract

Background
The CpxA sensor kinase-CpxR response regulator two-component regulatory system is a sentinel of bacterial envelope integrity. Integrating diverse signals, it can alter the expression of a wide array of components that serve to shield the envelope from damage and to promote bacterial survival. In bacterial pathogens such as Yersinia pseudotuberculosis, this also extends to pathogenesis. CpxR is thought to dimerize upon phosphorylation by the sensor kinase CpxA. This phosphorylation enables CpxR binding to specific DNA sequences where it acts on gene transcription. As Cpx pathway activation is dependent on protein-protein interactions, we performed an interaction analysis of CpxR and CpxA from Y. pseudotuberculosis.

Results
CpxR full-length and truncated versions that either contained or lacked a putative internal linker were all assessed for their ability to homodimerize and interact with CpxA. Using an adenylate cyclase-based bacterial two hybrid approach, full-length CpxR readily engaged with CpxA. The CpxR N-terminus could also homodimerize with itself and with a full-length CpxR. A second homodimerization assay based upon the λcI repressor also demonstrated that the CpxR C-terminus could homodimerize. While the linker was not specifically required, it enhanced CpxR homodimerization. Mutagenesis of cpxR identified the aspartate at residue 51, putative N-terminal coiled-coil and C-terminal winged-helix-turn-helix domains as mediators of CpxR homodimerization. Scrutiny of CpxA full-length and truncated versions revealed that dimerization involved the N-terminus and an internal dimerization and histidine phosphotransfer domain.

Conclusions
This interaction analysis mapped regions of CpxR and CpxA that were responsible for interactions with self or with each other. When combined with other physiological and biochemical tests both hybrid-based assays can be useful in dissecting molecular contacts that may underpin Cpx pathway activation and repression.
Distinct mechanisms of axonal globule formation in mice expressing human wild type α-synuclein or dementia with Lewy bodies-linked P123H ß-synuclein
Authors: Sekigawa Akio , Fujita Masayo , Sekiyama Kazunari , Takamatsu Yoshiki , Hatano Taku , Rockenstein Edward , La Spada Albert R , Masliah Eliezer , Hashimoto Makoto 
Published: September 2012

Abstract

Background
Axonopathy is critical in the early pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Axonal swellings such as globules and spheroids are a distinct feature of axonopathy and our recent study showed that transgenic (tg) mice expressing DLB-linked P123H β-synuclein (P123H βS) were characterized by P123H βS-immunoreactive axonal swellings (P123H βS-globules). Therefore, the objectives of this study were to evaluate α-synuclein (αS)-immunoreactive axonal swellings (αS-globules) in the brains of tg mice expressing human wild-type αS and to compare them with the globules in P123H βS tg mice.

Results
In αS tg mice, αS-globules were formed in an age-dependent manner in various brain regions, including the thalamus and basal ganglia. These globules were composed of autophagosome-like membranous structures and were reminiscent of P123H βS-globules in P123H βS tg mice. In the αS-globules, frequent clustering and deformation of mitochondria were observed. These changes were associated with oxidative stress, based on staining of nitrated αS and 4-hydroxy-2-nonenal (4-HNE). In accord with the absence of mitochondria in the P123H βS-globules, staining of nitrated αS and 4-HNE in these globules was weaker than that for αS-globules. Leucine-rich repeat kinase 2 (LRRK2), the PARK8 of familial PD, was detected exclusively in αS-globules, suggesting a specific role of this molecule in these globules.

Conclusions
Lysosomal pathology was similarly observed for both αS- and P123H βS-globules, while oxidative stress was associated with the αS-globules, and to a lesser extent with the P123H βS-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for αS-globules. Collectively, both αS- and P123H βS-globules were formed through similar but distinct pathogenic mechanisms. Our findings suggest that synuclein family members might contribute to diverse axonal pathologies.
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Authors: Morgan Xochitl C , Tickle Timothy L , Sokol Harry , Gevers Dirk , Devaney Kathryn L , Ward Doyle V , Reyes Joshua A , Shah Samir A , LeLeiko Neal , Snapper Scott B , Bousvaros Athos , Korzenik Joshua , Sands Bruce E , Xavier Ramnik J , Huttenhower Curtis 
Published: September 2012

Abstract
Background
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status.

Results
Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways.

Conclusions
This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.