Miracle-dz/UniFAR-FTUs huggingface dataset:
Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent MR imaging with conventional, DTI, and DSC perfusion imaging. Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas from tumefactive demyelinating lesions. DTI metrics (p:q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas. The highest specificity was found for ADC, the anisotropic component of the diffusion tensor, and relative CBV. The authors conclude that DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. BACKGROUND AND PURPOSE: Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics (p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. MATERIALS AND METHODS: Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. RESULTS: Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas (P = .049) from tumefactive demyelinating lesions. DTI metrics (p:q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas (P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. CONCLUSIONS: DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI metrics and DSC perfusion markedly improved diagnostic accuracy.
The Virgin Mary and Religious Conflict in Victorian Britain

The Virgin Mary was a powerful and evocative figure around whom the competing religious parties of Victorian Britain arrayed their forces. She was at the forefront of controversy whenever Scottish and English Protestants clashed with Irish Catholics, and whenever evangelicals attempted to purge the Church of England of ritualism. Roman Catholic leaders placed the cult of the Virgin at the centre of their campaign to evangelise Britain after 1840. This article analyses the development of Marian Catholicism in Victorian Britain, and considers Anglo-Catholic and Protestant responses to the growth of the Marian cult.
Association of VDR BsmI gene polymorphism, bone turnover markers and bone mineral density in severe postmenopausal osteoporosis

Currently there is no clear answer whether specific vitamin D receptor gene genotype is associated with lower bone mineral density and higher fracture risk. The aim of this study was to analyze the associations of vitamin D receptor gene BsmI polymorphisms with bone turnover markers and bone mineral density in postmenopausal women with severe osteoporosis. Patients and methods. Vitamin D, parathyroid hormone (PTH), bone turnover markers were measured by electrochemical luminescence immunoassay, polymorphism of VDR gene (BsmI) was determined using polymerase chain reaction (PCR) analysis. Bone mineral density was measured by the dual-energy X-ray absorptiometry (iDXA, GE Lunar). Differences between groups were determined using ANOVA test. Subgroup corelation analysis was also conducted. Results. In total, 73 postmenopausal women were included in this study - 28 patients with severe postmenopausal osteoporosis and 45 control persons. It was not found the significant difference of VDR BsmI genotypes between patients and controls. There were no statistically significant correlations between lumbar spine and total hip BMD and biochemical bone markers in bb or Bb genotypes either in women with severe osteoporosis or in control women. In patients with severe postmenopausal osteoporosis, the lumbar spine BMD was significantly higher in the BB genotype bearers as compared to the bb and Bb genotype bearers. In patients with severe osteoporosis bearing VDR BsmI bb genotype, the vitamin D concentration was negatively related to PTH and positively related to femoral neck BMD; PINP was positively related to sCTX-I. Conclusions. The findings of this study suggest that VDR BsmI gene polymorphism has weak non-significant association with BMD level and severe postmenopausal osteoporosis and needs to be further analyzed. In patients with severe postmenopausal osteoporosis, the lumbar spine BMD was significantly higher in the BB genotype bearers as compared to the bb and Bb genotype bearers.
Translational Shift of HSP90 as a Novel Therapeutic Target from Cancer to Neurodegenerative Disorders: An Emerging Trend in the Cure of Alzheimer's and Parkinson's Diseases.

BACKGROUND Despite having extensive research, the apparent pathogenic mechanism of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDs) have not yet fully understood. The Heat Shock Protein 90 (HSP90), a ubiquitous molecular chaperone, found to have an important role in averting protein misfolding and aggregation through inhibition of apoptotic activity in neuro-inflammatory diseases. Various researchers have confirmed its role in maintaining aberrant neuronal protein's functional stability to a great capacity. It is also involved in regulating the activity of the heat shock factor-1 (HSF-1), a vital regulator of the heat shock response mechanism that cells employ to protect themselves against stress conditions. This quality makes the HSP90 an ideal candidate for novel inhibitory target for therapeutic modality in NDs. METHODS An extensive literature search was conducted for relevant studies on PubMed, ScienceDirect, Springer- Link etc. The articles were carefully read in their entirety to determine whether they contained information on the topic of interest. Additionally, the reference sections of these articles were searched manually to get more relevant and eligible studies. RESULTS We have taken an attempt to reveal how HSP90 play important roles with key neuronal proteins involved in supporting the AD and PD pathology. We have further on structure-function relationship of HSP90 to understand its efficacy as a new target in AD and PD by utilizing new generation of HSP90 inhibitors such as geldanamycin and its derivatives, 17-AAG, 17-DMAG, IPI-504, radicicol and its derivatives. HSP90 inhibition leads to suppress atypical neuronal activity by assisting in improving protein aggregation and its related toxicity. Further, the formation of neuronal aggregates is also influenced by HSP90 inhibitors and provides protection from toxicity of protein through HSF-1 activation and HSP70 induction in AD. CONCLUSION HSP90 inhibition has emerged as a potential target in treating diverse array of diseases especially NDs. In spite of a large amount of research in this direction, the clear cut molecular mechanisms of HSPs associated with neuroprotection are still poorly elucidated and hence more focus is needed toward HSPs and its inhibitory mechanism. The development of HSP90 inhibitors that induce heat-shock response without cytotoxicity for treatment of NDs are still in its early stage. A panel of novel designed research and clinical trial studies are greatly needed to establish the therapeutic reliability and efficacy of HSPs in order to provide best cure for NDs.
IgG‐Fc‐mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation

Summary: The Fr region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions often of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter‐CH2‐CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x‐ray crystal structures for Fc and Fc‐ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is “disordered”, suggesting “internal mobility”. We propose a model in which such “internal mobility” results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.
A Wearable Multichannel Tactile Display of Voice Fundamental Frequency

This paper describes a wearable sensory aid that provides the deaf with factually encoded information about intonation. Fundamental frequency is represented as both place and rate of vibration in a linear array of solenoids. Pitch extraction is accomplished through low-pass filtering and peak detection. A microcomputer is used to measure pitch period, which in turn determines which of the solenoids is actuated. By comparing consecutive periods, the system discriminates against random, noiserelated inputs. The device is switchable between 1-, 8-, and 16- channel operation. The electronics package is contained in a case that may be worn on a belt. The solenoid array is worn on the forearm. The system is powered by five, rechargeable lithium cells and runs for at least 6 hours between charges. Proposed developments include the incorporation of digital pitch extraction methods and the option to use the spatial output dimension to encode speech parameters other than fundamental frequency.
PERSONALITY FACTORS IN OBESITY AND CHRONIC PAIN Original Article

2overweight and obese (BMI ? 25 kg/m ). The patients completed questionnaires to identify pain severity, anxiety, optimism, pessimism, gelotophobia and life satisfaction. Pain severity and days per week with pain were similar in the weight groups. Gelotophobia is defined as the pathological fear to appear as an object of ridicule to social partners. Gelotophobia at its extreme involves a more or less pronounced paranoid tendency, a marked sensitivity to offence, and social withdrawal. Gelotophobia was related to increasing weight, and increased BMI was associated with more days per week with reduced activity. Anxiety scores also correlated to the weight category, with an average Spielberger Anxiety Inventory score of 31.62 ± 5.25 in normal, and of 43.78 ± 11.04 in overweight and obese patients. Optimism and pessimism are general expectancies for the occurrence of positive or negative events in the future or an explanatory style, attributing positive or negative events to internal, stable, and global causes. Optimism was also reduced in relation to weight. Weight is associated with anxiety, gelotophobia and reduced life satisfaction in chronic pain patients. This study found that pessimism may positively or negatively influence efforts to increase healthpromoting behaviors. Calculation of the BMI should become a routine part of the screening evaluation for chronic pain patients, with an additional screening for personality and psychologic distress in patients with elevated BMIs.
Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer.

PURPOSE Pazopanib and lapatinib are tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit or epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/neu), respectively. In cervical cancer, EGFR and HER2/neu overexpression and high microvascular density correlate with survival. PATIENTS AND METHODS Patients with measurable stage IVB persistent/recurrent cervical carcinoma not amenable to curative therapy and at least one prior regimen in the metastatic setting were randomly assigned in a ratio of 1:1:1 to pazopanib at 800 mg once daily, lapatinib at 1,500 mg once daily, or lapatinib plus pazopanib combination therapy (lapatinib at 1,000 mg plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 800 mg once daily). Therapy continued until progression or withdrawal because of adverse events (AEs). Primary end point was progression-free survival (PFS), and secondary end points were overall survival (OS), response rate (RR), and safety. The futility boundary was crossed at the planned interim analysis for combination therapy compared with lapatinib therapy, and the combination was discontinued. RESULTS Of 230 patients enrolled, 152 were randomly assigned to the monotherapy arms: pazopanib (n = 74) or lapatinib (n = 78). Most patients (62%) had recurrent cancer. Pazopanib improved PFS (hazard ratio [HR], 0.66; 90% CI, 0.48 to 0.91; P = .013) and OS (HR, 0.67; 90% CI, 0.46 to 0.99; P = .045). Median OS was 50.7 weeks and 39.1 weeks and RRs were 9% and 5% for pazopanib and lapatinib, respectively. The only grade 3 AE > 10% was diarrhea (11% pazopanib and 13% lapatinib). Grade 4 AEs were 9% (lapatinib) and 12% (pazopanib). CONCLUSION This study confirms the activity of antiangiogenesis agents in advanced and recurrent cervical cancer and demonstrates the benefit of pazopanib based on the prolonged PFS and favorable toxicity profile.
Co-Evolution of Meta-Modeling Syntax and Informal Semantics in Domain-Specific Modeling Environments — A Case Study of AUTOSAR

One domain-specific modeling environment is centered around a domain-specific meta-model which defines syntax (modeling elements, e.g., classes) for the domain models. However, in order for the system designers to be able to construct meaningful models, semantics of the domain-specific meta-model needs to be described as well. This semantics is often provided in a form of informal natural language specifications that contain a set of design requirements, each describing the intended use of one or more modeling elements. Intuitively, introduction of new concepts into the modeling environment is expected to require changes in both meta-modeling syntax and informal semantics in such a way that their co-evolution is highly correlated. In order to test this hypothesis, we analyzed the relation between added classes, attributes, and connectors, as meta-modeling syntax, and modified/added design requirements, as meta-modeling semantics, in a case study of the AUTOSAR meta-modeling environment. We found that new AUTOSAR concepts usually require both new modeling elements and new design requirements, but surprisingly adding more elements is not always followed by more requirements. This finding is also validated by the moderately strong correlation between the evolution of these two AUTOSAR meta-modeling artifacts (Spearman's rho 0,63 and Kendall's tau 0,49). For system designers, this means that both meta-modeling syntax and informal semantics is important to be considered in the analysis of domain-specific meta-model evolution, but it may not be enough for understanding the use of all modeling elements. For designers responsible for the maintenance of domain-specific meta-models, this means that more effort shall be put into describing the semantics of all introduced modeling elements.
Design and characterization of a power transfer inductive link for wireless sensor network nodes

This paper describes a design of a power transfer inductive link for charging batteries of wireless sensor network nodes. The application physical constraints imposes a maximum size for the coils and demands a design methodology to maximize output power delivered to the load and energy transmission efficiency. This paper presents a complete methodology for designing the coils of wireless power transfer systems applied to rechargeable batteries of wireless sensor network nodes. The design of an inductive link is presented as a case study, in which two planar coils are built in order to validate the proposed method. Moreover, a complete wireless power transfer system is developed for the proposal, including coils, primary power source, capacitor network compensation, and secondary power management, with rectification, filtering, regulation, and battery charge control. The experimental results for working distances between the coils from 1 mm to 10 mm are reported as well as the frequency response of the entire system.
Prognostic factors in adult patients with acute leukemia at first relapse

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction‐responders was significantly prolonged in comparison to the reinduction‐nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction‐responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction‐responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.
Vitamin E consumption and the risk of coronary heart disease in men.

BACKGROUND The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. METHODS In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. RESULTS After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. CONCLUSIONS These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.
Edugraph: Software to Teach Computer Graphics Concepts

Computational processing capacity allows the development of sophisticated interactive animation with different kinds of media resources. Computer games are examples of multimedia software with entertainment and high sophistication characteristics. Such technology allied with cognitive concepts can be used to implement educational software. This poster describes the implementation of a software to teach computer graphics concepts based on entertainment and cognitive criteria.
Degradation of HMG-CoA Reductase in Vitro

We have recently shown that the endoplasmic reticulum (ER) membrane protein, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is cleaved in isolated membrane fractions enriched for endoplasmic reticulum. Importantly, the cleavage rate is accelerated when the membranes are prepared from cells that have been pretreated with mevalonate or sterols, physiological regulators of the degradation process in vivo (McGee, T. P., Cheng, H. H., Kumagai, H., Omura, S., and Simoni, R. D. (1996)J. Biol. Chem. 271, 25630–25638). In the current study, we further characterize this in vitro cleavage of HMG-CoA reductase. E64, a specific inhibitor of cysteine-proteases, inhibits HMG-CoA reductase cleavage in vitro. In contrast, lactacystin, an inhibitor of the proteasome, inhibits HMG-CoA reductase degradation in vivo but does not inhibit the in vitro cleavage. Purified ER fractions contain lactacystin-sensitive and E64-insensitive proteasome activity as measured by succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin hydrolysis. We removed the proteasome from purified ER fractions by solubilization with heptylthioglucoside and observed that the detergent extracted, proteasome-depleted membrane fractions retain regulated cleavage of HMG-CoA reductase. This indicates that ER-associated proteasome is not involved in degradation of HMG-CoA reductase in vitro. In order to determine the site(s) of proteolysis of HMG-CoA reductasein vitro, four antisera were prepared against peptide sequences representing various domains of HMG-CoA reductase and used for detection of proteolytic intermediates. The sizes and antibody reactivity of the intermediates suggest that HMG-CoA reductase is cleaved in the in vitro degradation system near the span 8 membrane region, which links the N-terminal membrane domain to the C-terminal catalytic domain of the protein. We conclude that HMG-CoA reductase can be cleaved in the membrane-span 8 region by a cysteine protease(s) tightly associated with ER membranes.