Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative effectiveness and adverse effects of interferon alpha-2b plus ribavirin therapy in hepatitis 'C' for 26 weeks.

BACKGROUND Hepatitis C is major emerging challenge for pathologists and treating physicians all over the world. Already 10 million Pakistani population has become anti-HCV positive. It is not only affecting hepatobiliary system but with passage of time research is revealing that Hepatitis C is going to involve almost every organ of the body. With timely diagnosis and treatment, millions of patients can be saved from morbidity and mortality. The nation has to sacrifice initial economic allocations to avoid later millions of mortalities and greater economic losses on affected patients and to support their families. The objective of this study was to evaluate effectiveness of combine therapy of Hepatitis C in local population of Pakistan. METHODS This case series study was done at CMH Okara, Kohat, Abbottabad, and PAF Hospital, Shorkot from August 2000 to August 2009. All 1,000 patients from 10 to 60 years of age, confirmed anti-HCV Positive by ELISA and PCR Positive for HCV RNA, were subjected to Interferon alpha-2b and Ribavirin therapy for similar period of time. Response and adverse affects were observed by clinical examination, blood complete picture including platelet count and ALT fortnightly. PCR for HCV RNA and ultrasound abdomen (hepatobilliary system) was done quarterly during treatment and 6 monthly for 2 years after treatment to review the sustained response and relapse. RESULTS Over all cure rate after 2 years was 855 (85.5%) excluding the 50 (5%) of initial resistant to one year treatment and 95 (9.5%) re-treated relapse cases. One hundred and forty-five (14.5%) patients were found to be resistant to treatment. CONCLUSION Hepatitis C must be treated timely after proper diagnosis. Interferon and Ribavirin combination have shown high 'cure' rate in Hepatitis C. In spite of high cure rate of 85.5% with timely and proper treatment, low socio-economic status is a major problem for poor individuals to get treatment. Preventive aspect must be strictly followed and implemented.
An ID-Based Mutual Authentication and Key Exchange Protocol for Low-Power Mobile Devices

The identity (ID)-based public-key system using bilinear pairings defined on elliptic curves offers a flexible approach to simplify the certificate management. In 2006, the IEEE P1363.3 committee has defined the ID-based public-key system with bilinear pairings as one of public-key cryptography standards. In this, an authenticated key agreement (AKA) protocol is one important issue that provides mutual authentication and key exchange between two parties. Owing to the fast growth of mobile networks, the computational cost on the client side with low-power computing devices is a critical factor in designing an AKA protocol suited for mobile networks. In this paper, we present an efficient and secure ID-based mutual authentication and key exchange protocol using bilinear pairings. Performance analysis and experimental data are given to demonstrate that our proposed protocol is well suited for a client–server environment with low-power mobile devices. In comparison with the recently proposed ID-based protocols, our protocol has the best performance on the client side.
Relationship between low-density lipoprotein subclasses and asymptomatic atherosclerosis in subjects from the atherosclerosis risk in communities (ARIC) Study

Low-density lipoprotein (LDL) particle size has been associated with coronary heart disease, but an association between LDL size and preclinical atherosclerosis is less well established. Using gradient gel electrophoresis, large (A), intermediate (I) and small (B) LDL size subclasses were determined in 198 cases with asymptomatic carotid artery atherosclerosis (determined by B-mode ultrasonography) and 318 controls from the Atherosclerosis Risk in Communities (ARIC) Study. In Caucasians, a smaller LDL size was more prevalent in men and associated with a higher body mass index, hypertension prevalence, and plasma total- and LDL-cholesterol and triglycerides, but lower HDL-cholesterol. In African-Americans, a smaller LDL size was associated with higher triglycerides and lower HDL-cholesterol and hypertension prevalence. In Caucasians, Subclass B prevalence was 29.1% among cases and 14.8% among controls. The odds ratio (95% confidence interval) for Subclass B rather than Subclass A in Caucasian cases was 2.94 (1.67–5.17); the association remained significant after controlling for age, body mass index, smoking, and either plasma triglycerides or HDL-cholesterol. In African-Americans, however, there was no significant association between LDL subclass and case status. A predominance of smaller LDL particles is associated with asymptomatic carotid artery atherosclerosis in Caucasians, through mechanisms that remain to be elucidated.
Antibody‐Functionalized Magnetic Polymersomes: In vivo Targeting and Imaging of Bone Metastases using High Resolution MRI

Multifunctional polymersomes loaded with maghemite nanoparticles and grafted with an antibody, directed against human endothelial receptor 2, are developed as novel MRI contrast agents for bone metastasis imaging. Upon administration in mice bearing bone tumor grown from human breast cancer cells, MR images show targeting and enhanced retention of antibody-labeled polymersomes at the tumor site.
In vivo formation and persistence of DNA and protein adducts in mouse and rat skin exposed to (+/-)benzo[a]pyrene-4,5-oxide.

The objective of the present study was to compare DNA and protein adduct formation of benzo[a]pyrene-4,5-oxide (BPO) in vivo and to determine the persistence of the adducts in both mouse and rat epidermis. (+/-)BPO at a dose of 100 nmol/mouse and 200 nmol/rat was topically applied to male Swiss mice and Wistar rats. Three hours after application, there was 3-fold less binding of BPO to mouse epidermal DNA than to rat epidermal DNA; inversely, the amount of BPO bound to mouse skin protein was 3.6 times higher than in rat skin protein. One and three weeks after application of BPO, persistence of 17-20% of the initial amount of BPO-DNA adducts and 2-4% of initial amount of BPO bound to protein was detected in both mouse and rat skin epidermis. H.p.l.c. analysis of the enzymatic hydrolysates of DNA from mouse and rat epidermis 3 h after application of BPO showed five distinct products: one early-eluting, two BPO-deoxyguanosine (dGuo) (ratio 1.5:1) and two BPO-deoxyadenosine (dAdo) adducts (ratio 2:1). The ratio of the total modified dGuo to the total modified dAdo was 2:1. The amount of total BPO-dGuo and BPO-dAdo adducts was 3.5 times greater in rat than in mouse epidermis. Persistence of the major BPO-dAdo adduct was observed in mouse and rat epidermal DNA, and 1 and 3 weeks after topical application of BPO there was a 6-fold greater amount of the persisting BPO-dAdo adduct in rat skin epidermis than in mouse skin epidermis (4.1 and 0.66 pmol/mg DNA, respectively). Minor amounts of the BPO-dGuo were found to persist in rat skin epidermis DNA.
Relative efficacy of 32P and 89Sr in palliation in skeletal metastases.

UNLABELLED 32p and 89Sr have been shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. Clinically significant pancytopenia has not been reported in doses up to 12 mCi (444 MBq) of either radionuclide. To date, no reports comparing the relative efficacy and toxicity of the two radionuclides in comparable patient populations have been available. Although a cure has not been reported, both treatments have achieved substantial pain relief. However, several studies have used semiquantitative measures such as "slight," "fair," "partial" and "dramatic" responses, which lend themselves to subjective bias. This report examines the responses to treatment with 32P or 89Sr by attempting a quantification of pain relief and quality of life using the patients as their own controls and compares toxicity in terms of hematological parameters. METHODS Thirty-one patients with skeletal metastases were treated for pain relief with either 32P (16 patients) or 89Sr (15 patients). Inclusion criteria were pain from bone scan-positive sites above a subjective score of 5 of 10 despite analgesic therapy with narcotic or non-narcotic medication, limitation of movement related to the performance of routine daily activity and a predicted life expectancy of at least 4 mo. The patients had not had chemotherapy or radiotherapy during the previous 6 wk and had normal serum creatinine, white cell and platelet counts. 32P was given orally as a 12 mCi dose, and 89Sr was given intravenously as a 4 mCi (148 MBq) dose. The patients were monitored for 4 mo. RESULTS Complete absence of pain was seen in 7 of 16 patients who were given 32P and in 7 of 15 patients who were given 89Sr. Pain scores fell by at least 50% of the pretreatment score in 14 of 16 patients who were given 32P and 14 of 15 patients who were given 89Sr. Mean duration of pain relief was 9.6 wk with 32P and 10 wk with 89Sr. Analgesic scores fell along with the drop in pain scores. A fall in total white cell, absolute granulocyte and platelet counts occurred in all patients. Subnormal values of white cells and platelets were seen in 5 and 7 patients, respectively, with 32P, and in 0 and 4 patients, respectively, after 89Sr therapy. The decrease in platelet count (but not absolute granulocyte count) was statistically significant when 32P patients were compared with 89Sr patients. However, in no instance did the fall in blood counts require treatment. Absolute granulocyte counts did not fall below 1000 in any patient. There was no significant difference between the two treatments in terms of either efficacy or toxicity. CONCLUSION No justification has been found in this study for the recommendation of 89Sr over the considerably less expensive oral 32P for the palliation of skeletal pain from metastases of advanced cancer.
The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: novel insights from genetically altered mice

We tested the hypothesis that chronic changes in intracellular Ca2+ (Ca2+i) can result in changes in ion channel expression; this represents a novel mechanism of crosstalk between changes in Ca2+ cycling proteins and the cardiac action potential (AP) profile. We used a transgenic mouse with cardiac‐specific overexpression of sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoform 1a (SERCA1a OE) with a significant alteration of SERCA protein levels without cardiac hypertrophy or failure. Here, we report significant changes in the expression of a transient outward K+ current (Ito,f), a slowly inactivating K+ current (IK,slow) and the steady state current (ISS) in the transgenic mice with resultant prolongation in cardiac action potential duration (APD) compared with the wild‐type littermates. In addition, there was a significant prolongation of the QT interval on surface electrocardiograms in SERCA1a OE mice. The electrophysiological changes, which correlated with changes in Ca2+i, were further corroborated by measuring the levels of ion channel protein expression. To recapitulate the in vivo experiments, the effects of changes in Ca2+i on ion channel expression were further tested in cultured adult and neonatal mouse cardiac myocytes. We conclude that a primary defect in Ca2+ handling proteins without cardiac hypertrophy or failure may produce profound changes in K+ channel expression and activity as well as cardiac AP.
Underweight: another risk factor for cardiovascular disease?

Abstract Obesity is a well-established risk factor for cardiovascular disease (CVD), but the underweight population of body mass index (BMI) below 18.5 kg/m2 has not been an object of concern. The objective of this study is to investigate whether underweight could be an independent risk factor for CVD in a population-based cross-sectional study. Cross-sectional data of 2013 Behavioral Risk Factor Surveillance System (BRFSS) database encompassing 491,773 US adult subjects were used to assess risk for CVD. Primary outcomes were the incidence and relative risks (RRs) of CVD including stroke, heart attack/myocardial infarction, or coronary artery disease according to BMI category. All analyses used weighted sampling probabilities of data source. The underweight population had a 19.7% greater risk of CVD than did the normal-weight, and the overweight and obese population had a 50% and 96% increased risk, respectively. When adjusted with covariates, the relative risk for CVD elevated in underweight population (adjusted RR 1.34 [95% confidence interval (CI) 1.335–1.348]). Conversely, the adjusted relative risk was significantly attenuated in the obese group (adjusted RR 1.149 [95% CI 1.147–1.151]) and it was even insignificant in the overweight group (adjusted RR 1.00 [95% CI 1.000–1.003]). In subanalysis for each CVD category, being underweight among BMI status was the strongest independent risk factor for stroke (adjusted RR 1.441 [95% CI 1.431–1.450]), heart attack/ myocardial infarction (MI) (adjusted RR 1.23 [95% CI 1.217–1.233]), and angina/coronary artery disease (adjusted RR 1.20 [95% CI 1.189–1.206]). Especially among the population below 40-year old, relative risk estimates remained increased in the underweight population; persons who were underweight had a 2.3-fold greater adjusted relative risk of CVD as compared with those with normal weight when we stratified with age. Underweight below BMI 18.5 kg/m2 may be another risk factor for CVD, and CVD risk of the overweight and obese population largely depended on other comorbidities accompanied by obesity.
Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule

Abstract The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.
Catalytic Mechanism of 2-Hydroxybiphenyl 3-Monooxygenase, a Flavoprotein from Pseudomonas azelaica HBP1*

2-Hydroxybiphenyl 3-monooxygenase (EC1.14.13.44) from Pseudomonas azelaica HBP1 is an FAD-dependent aromatic hydroxylase that catalyzes the conversion of 2-hydroxybiphenyl to 2,3-dihydroxybiphenyl in the presence of NADH and oxygen. The catalytic mechanism of this three-substrate reaction was investigated at 7 °C by stopped-flow absorption spectroscopy. Various individual steps associated with catalysis were readily observed at pH 7.5, the optimum pH for enzyme turnover. Anaerobic reduction of the free enzyme by NADH is a biphasic process, most likely reflecting the presence of two distinct enzyme forms. Binding of 2-hydroxybiphenyl stimulated the rate of enzyme reduction by NADH by 2 orders of magnitude. The anaerobic reduction of the enzyme-substrate complex involved the formation of a transient charge-transfer complex between the reduced flavin and NAD+. A similar transient intermediate was formed when the enzyme was complexed with the substrate analog 2-sec-butylphenol or with the non-substrate effector 2,3-dihydroxybiphenyl. Excess NAD+ strongly stabilized the charge-transfer complexes but did not give rise to the appearance of any intermediate during the reduction of uncomplexed enzyme. Free reduced 2-hydroxybiphenyl 3-monooxygenase reacted rapidly with oxygen to form oxidized enzyme with no appearance of intermediates during this reaction. In the presence of 2-hydroxybiphenyl, two consecutive spectral intermediates were observed which were assigned to the flavin C(4a)-hydroperoxide and the flavin C(4a)-hydroxide, respectively. No oxygenated flavin intermediates were observed when the enzyme was in complex with 2,3-dihydroxybiphenyl. Monovalent anions retarded the dehydration of the flavin C(4a)-hydroxide without stabilization of additional intermediates. The kinetic data for 2-hydroxybiphenyl 3-monooxygenase are consistent with a ternary complex mechanism in which the aromatic substrate has strict control in both the reductive and oxidative half-reaction in a way that reactions leading to substrate hydroxylation are favored over those leading to the futile formation of hydrogen peroxide. NAD+ release from the reduced enzyme-substrate complex is the slowest step in catalysis.
Expression of HGF, Its Receptor c-met, c-myc, and Albumin in Cirrhotic and Neoplastic Human Liver Tissue

Hepatocellular carcinoma (HCC) is a common type of cancer, with approximately 260,000 new cases each year, and liver cirrhosis is generally considered a major predisposing factor for HCC. However, specific changes of gene expression in liver cirrhosis and HCC remain obscure. The expression of genes for hepatocyte growth factor (HGF), its receptor c-met proto-oncogene, c-myc proto-oncogene, and albumin was analyzed. Gene expression was studied by PCR in seven normal human livers, nine cases of hepatitis C cirrhosis, 12 cases of alcoholic cirrhosis, two cases of liver adenoma, and 12 cases of HCC. HGF and c-met protein were revealed by immunofluorescent staining. HGF mRNA was not expressed in normal livers but was detected in adenomas, in 80% of HCC, and in some cirrhoses. Paraffin-embedded and fresh-frozen tissue samples yielded similar results. Immunohistochemical data correlated with PCR results regarding the overexpression of the HGF/c-met system in HCC. Albumin gene expression was decreased in HCC vs normal livers, consistent with altered function of tumor hepatocytes. The elevated expression of the HGF/c-met system in HCC may play a role in tumor development and/or progression. Tissue localization studies of HGF and its receptor c-met protein support the existence of both autocrine and paracrine mechanisms of action of HGF in HCC vs only a paracrine mechanism in normal liver.
Interdependence between technical web accessibility and usability: its influence on web quality models

Quality assurance is one of the most significant issues web engineering has to deal with. It is crucial to define adequate quality models in order to determine the most significant properties for quality evaluation of websites. Usability should be one of those properties as it bears on efficiency, effectiveness and user satisfaction. Moreover, it has been demonstrated to be a key property for users in recent European Commission's benchmark studies on quality and usage of public e-services. Web accessibility is also a significant property that websites have to fulfil in order to ensure equal access for all people in the Information Society. Therefore, both accessibility and usability should be included in such quality models. This paper presents an empirical study carried out with the aim of analysing the relationship between these two properties. The results show that the provision of technical web accessibility does not intrinsically guarantee web usability. Actually, other non-accessibility metrics such as the number of images, links and words of the web home page were better predictors of the users' effectiveness, efficiency and satisfaction.
Genome flux in tomato cell clones cultured in vitro in different physiological equilibria. II. A RAPD analysis of variability.

An analysis of the effect of changing physiological conditions on genome evolution in tomato cell populations has been carried out on long-term in vitro cultured clones grown on different auxin-cytokinin equilibria or selected for low-high competence for active defense against Fusarium oxysporum f.sp. lycopersici. RAPD analysis, confirmed through pattern rehybridization, was used as a random tool to measure the genetic variability. Through the use of a modified ANOVA, variation was shown to depend on both the initial genotype and the physiological conditions. Pattern correlation analysis through a mutual information algorithm suggested the fixation of RAPD patterns specific to physiological equilibria. The results are discussed in view of the possible relevance for evolution at hierarchical levels higher than cell populations. Key words : tomato clones, somaclonal variation, RAPD, coadaptation.
Defocus cue and saliency preserving video compression

Abstract. There are monocular depth cues present in images or videos that aid in depth perception in two-dimensional images or videos. Our objective is to preserve the defocus depth cue present in the videos along with the salient regions during compression application. A method is provided for opportunistic bit allocation during the video compression using visual saliency information comprising both the image features, such as color and contrast, and the defocus-based depth cue. The method is divided into two steps: saliency computation followed by compression. A nonlinear method is used to combine pure and defocus saliency maps to form the final saliency map. Then quantization values are assigned on the basis of these saliency values over a frame. The experimental results show that the proposed scheme yields good results over standard H.264 compression as well as pure and defocus saliency methods.
Bacteriophage T4 late promoters: mapping 5′ ends of T4 gene 23 mRNAs.

More than thirty 5′ ends of RNA molecules which transverse the bacteriophage T4 late gene, gene 23, have been mapped by nuclease protection and reverse transcription, to a 1.7 kilobase pair (kbp) region upstream of gene 23. Most of these 5′ ends arise from RNA processing and degradation. Two sites at which RNA synthesis is initiated have been identified by guanylylation of diphosphate‐ or triphosphate‐terminated RNA with vaccinia virion “capping” enzyme and are situated approximately 0.1 and 0.9 kbp upstream of gene 23. At least one other promoter lies more than 1.7 kbp upstream of gene 23, that is, outside of the mapped region.
In vivo assessment of vascular endothelial growth factor‐induced angiogenesis

To determine whether vascular endothelial growth factor (VEGF)‐induced tumor microvascularity is detectable by in vivo NMR imaging, an experimental study was conducted in nude mice. Human breast cancer cells (MCF‐7) and MCF‐7 cells stably transfected with the cDNA for the VEGF165 isoform (MV165) were grown in nude mice and models were characterized by RT‐PCR, Western blotting, ELISA, immunohistochemistry and NMR imaging using a novel synthetic protected graft copolymer (PGC) as a vascular probe. MV165 tumors showed a 1.6‐fold higher microvascular density by histology. Both tumors showed identical MR signal intensities on non‐contrast and Gd‐DTPA enhanced images. PGC enhanced MR imaging of tumoral vascular volume fraction (VVF), however, revealed significant differences between the 2 tumor types (MV165: 8.9 ± 2.1; MCF‐7: 1.7 ± 0.5; p < 0.003), as expected from histology. VVF changes were more heterogeneous in the MV165 model both among tumors as well as within tumors as determined 3‐dimensionally at submillimeter resolutions. Our results have potential applications for non‐invasive assessment of angiogenesis by in vivo imaging and for clinical monitoring during angiogenic therapies. Int. J. Cancer 83:798–802, 1999. © 1999 Wiley‐Liss, Inc.