Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis D: Clinical Features and Therapy

Surveys in the 1980s showed that the hepatitis D virus (HDV) is endemic worldwide, though with prevalences and patterns of infection varying in different areas. Medical scrutiny confirmed that chronic hepatitis D usually runs a severe and progressive course, the prototype patient having HBsAg in blood, elevated ALT, a liver biopsy exhibiting aggressive hepatitis and markers of HDV (but no marker of HBV replication in serum). Although the circulation of HDV has declined significantly following the control of HBV achieved over the last 20 years, depriving HDV of the HBV network necessary to propagate its infection, there is still a consistent reservoir of the virus in Europe, sustained by two different pools of HDV-infected patients: the residual ageing domestic pool that survived the brunt of the hepatitis D epidemic in the 1970s and 1980s and the population of young patients with recent HDV infections migrating to Europe. Therapy of hepatitis D remains an unsolved business. The therapy available today is not different from the limited interferon treatment attempted more than 20 years ago. The problem is formidable as HDV has no enzymatic protein to be targeted by conventional antiviral therapy. A potential target of therapy is offered by the process of hepatitis D virion assembly.
Multiscale Geometric Methods for Estimating Intrinsic Dimension

We present a novel approach for estimating the intrinsic dimension of certain point clouds: we assume that the points are sampled from a manifold M of dimension k, with k << D, and corrupted by D-dimensional noise. When M is linear, one may analyze this situation by PCA: with no noise one would obtain a rank k matrix, and noise may be treated as a perturbation of the covariance matrix. WhenM is a nonlinear manifold, global PCA may dramatically overestimate the intrinsic dimension. We discuss a multiscale version of PCA and how one can extract estimators for the intrinsic dimension that are highly robust to noise, and we derive some of their finite-sample-size properties. Keywords— Dimension estimation, multiscale analysis, geometric measure theory, point cloud data
Olomoucine II, but Not Purvalanol A, Is Transported by Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1)

Purine cyclin-dependent kinase inhibitors have been recognized as promising candidates for the treatment of various cancers; nevertheless, data regarding interaction of these substances with drug efflux transporters is still lacking. Recently, we have demonstrated inhibition of breast cancer resistance protein (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able to synergistically potentiate the antiproliferative effect of mitoxantrone, an ABCG2 substrate. In this follow up study, we investigated whether olomoucine II and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine II will be affected by both ABCB1 and ABCG2 transport proteins, which might potentially result in limited accumulation of the compound in tumor tissues or lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically favoring this drug in the potential treatment of efflux transporter-based multidrug resistant tumors. In addition, we observed intensive sulfatation of olomoucine II in MDCKII cell lines with subsequent active efflux of the metabolite out of the cells. Therefore, care should be taken when performing pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates are used; the generated sulfated conjugate may largely contaminate pharmacokinetic analysis and result in misleading interpretation. With regard to chemical structures of olomoucine II and purvalanol A, our data emphasize that even drugs with remarkable structure similarity may show different pharmacokinetic behavior such as interactions with ABC transporters or biotransformation enzymes.
Hepatocyte transplantation in rats with decompensated cirrhosis

Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver‐based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL4 ) and animals were studied only when evidence of liver failure did not improve when CCL4 was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2‐G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P < .01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P < .01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P < .01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.
Load transfer across cracks and joints in concrete slabs on grade

This research has investigated the behaviour of joints and cracks under single and multiple cycles of load. This provides an increased understanding of concrete slab on grade performance, enabling more effective design and monitoring procedures. Examination of the geometry of cracks and joints within concrete slabs on grade has demonstrated that the commonly assumed parallel formation is erroneous. Measurements using embedded strain gauges, coring and surface profile levelling have uncovered that a high percentage of joints will contain larger crack widths at the surface than at the base, caused by differential shrinkage. The opening itself is relatively linear; however, the top 50mm of the slab is prone to a higher gradient of movement due to the increased drying effect towards the surface. A series of deflection tests using a Falling Weight Deflectometer and Prima dynamic plate enabled slab response under load to be evaluated. Four sites were examined in total and correlations found between: load transfer, load step, edge cantilever and crack geometry. This produced valuable information regarding the influence of load transfer and crack width on the overall slab behaviour. Foundation voiding and crack face free slip was also shown to influence deflection magnitude. A small-scale test facility was developed for the assessment of deterioration in various 'V' shaped and parallel crack widths under high cycle loading. The data demonstrated that joint/crack failure contains four distinct phases of deterioration, each of which is controlled by a different mechanism. 'V' shaped cracks produced a much greater load transfer than that of a parallel crack with the incorporation of A142 mesh and steel fibres reducing differential displacement. Load magnitude and aggregate size were also shown to have significant effects. The value of reinforcement was found to assist with serviceability requirements, keeping displacement within acceptable levels and preventing the onset of serious degradation A finite element model was developed to enable the load transfer mechanism results from the laboratory test to be used in the assessment of full slab response. Simulations of field testing produced a series of lower bounds in respect to deflections and the associated response calculations. Theoretical behaviour of a typical slab was assessed with subbase support, joint stiffness, slab thickness and the incorporation of a subbase, found to be highly influential in reducing slab deflections. The three main sections of work comprising site data collection, laboratory testing and Finite Element modelling have been used together to provide a much greater understanding of the influence of cracks and joints. This has included the deterioration of cracks over time and an examination of how this and other site-based factors affect overall slab behaviour.
Mutation and cloning of eryG, the structural gene for erythromycin O-methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli

A mutant strain derived by chemical mutagenesis of Saccharopolyspora erythraea (formerly known as Streptomyces erythreus) was isolated that accumulated erythromycin C and, to a lesser extent, its precursor, erythromycin D, with little or no production of erythromycin A or erythromycin B (the 3"-O-methylation products of erythromycin C and D, respectively). This mutant lacked detectable erythromycin O-methyltransferase activity with erythromycin C, erythromycin D, or the analogs 2-norerythromycin C and 2-norerythromycin D as substrates. A 4.5-kilobase DNA fragment from S. erythraea originating approximately 5 kilobases from the erythromycin resistance gene ermE was identified that regenerated the parental phenotype and restored erythromycin O-methyltransferase activity when transformed into the erythromycin O-methyltransferase-negative mutant. Erythromycin O-methyltransferase activity was detected when the 4.5-kilobase fragment was fused to the lacZ promoter and introduced into Escherichia coli. The activity was dependent on the orientation of the DNA relative to lacZ. We have designated this genotype eryG in agreement with Weber et al. (J.M. Weber, B. Schoner, and R. Losick, Gene 75:235-241, 1989). It thus appears that a single enzyme catalyzes all of the 3"-O-methylation reactions of the erythromycin biosynthetic pathway in S. erythraea and that eryG codes for the structural gene of this enzyme.
Randomized, Double-blind, Placebo-controlled Phase III Trial of Duloxetine Monotherapy in Japanese Patients With Chronic Low Back Pain

Study Design. A 14-week, randomized, double-blind, multicenter, placebo-controlled study of Japanese patients with chronic low back pain (CLBP) who were randomized to either duloxetine 60 mg once daily or placebo. Objective. This study aimed to assess the efficacy and safety of duloxetine monotherapy in Japanese patients with CLBP. Summary of Background Data. In Japan, duloxetine is approved for the treatment of depression, diabetic neuropathic pain, and pain associated with fibromyalgia; however, no clinical study of duloxetine has been conducted for CLBP. Methods. The primary efficacy measure was the change in the Brief Pain Inventory (BPI) average pain score from baseline to Week 14. Secondary efficacy measures included BPI pain (worst pain, least pain, pain right now), Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and Roland-Morris Disability Questionnaire, among other measures, and safety and tolerability. Results. In total, 458 patients were randomized to receive either duloxetine (n = 232) or placebo (n = 226). The BPI average pain score improved significantly in the duloxetine group compared with that in the placebo group at Week 14 [−2.43 ± 0.11 vs. −1.96 ± 0.11, respectively; between-group difference (95% confidence interval), − 0.46 [−0.77 to−0.16]; P = 0.0026]. The duloxetine group showed significant improvement in many secondary measures compared with the placebo group, including BPI pain (least pain, pain right now) (between-group difference: −1.69 ± 0.10, P = 0.0009; −2.42 ± 0.12, P P = 0.0230, respectively), Patient's Global Impression of Improvement (2.46 ± 0.07, P = 0.0026), Clinical Global Impressions of Severity (−1.46 ± 0.06, P = 0.0019), and Roland-Morris Disability Questionnaire (−3.86 ± 0.22, P = 0.0439). Adverse events occurring at a significantly higher incidence in the duloxetine group were somnolence, constipation, nausea, dizziness, and dry mouth, most of which were mild or moderate in severity and were resolved or improved. Conclusion. Duloxetine 60 mg was effective and well tolerated in Japanese CLBP patients. Level of Evidence: 2
Polymeric Chitosan‐based Vesicles for Drug Delivery

A simple carbohydrate polymer glycol chitosan (degree of polymerization 800 approx.) has been investigated for its ability to form polymeric vesicle drug carriers. The attachment of hydrophobic groups to glycol chitosan should yield an amphiphilic polymer capable of self‐assembly into vesicles. Chitosan is used because the membrane‐penetration enhancement of chitosan polymers offers the possibility of fabricating a drug delivery system suitable for the oral and intranasal administration of gut‐labile molecules.
Response to ‘Comments on “Combining spatial transition probabilities for stochastic simulation of categorical fields” with communications on some issues related to Markov chain geostatistics’

Li and Zhang (2012b, Comments on ‘Combining spatial transition probabilities for stochastic simulation of categorical fields’ with communications on some issues related to Markov chain geostatics) raised a series of comments on our recent paper (Cao, G., Kyriakidis, P.C., and Goodchild, M.F., 2011. Combining spatial transition probabilities for stochastic simulation of categorical fields. International Journal of Geographical Information Science, 25 (11), 1773–1791), which include a notation error in the model equation provided for the Markov chain random field (MCRF) or spatial Markov chain model (SMC), originally proposed by Li (2007b, Markov chain random fields for estimation of categorical variables. Mathematical Geology, 39 (3), 321–335), and followed by Allard et al. (2011, An efficient maximum entropy approach for categorical variable prediction. European Journal of Soil Science, 62, 381–393) about the misinterpretation of MCRF (or SMC) as a simplified form of the Bayesian maximum entropy (BME)-based approach, the so-called Markovian-type categorical prediction (MCP) (Allard, D., D'Or, D., and Froideveaux, R., 2009. Estimating and simulating spatial categorical data using an efficient maximum entropy approach. Avignon: Unite Biostatisque et Processus Spatiaux Institute National de la Recherche Agronomique. Technical Report No. 37; Allard, D., D'Or, D., and Froideveaux, R., 2011. An efficient maximum entropy approach for categorical variable prediction. European Journal of Soil Science, 62, 381–393). Li and Zhang (2012b, Comments on ‘Combining spatial transition probabilities for stochastic simulation of categorial fields’ with communication on some issues related to Markov chain geostatistics. International Journal of Geographical Information Science) also raised concerns regarding several statements Cao et al. (2011, Combining spatial transition probabilities for stochastic simulation of categorical fields. International Journal of Geographical Information Science, 25 (11), 1773–1791) had made, which mainly include connections between permanence of ratios and conditional independence, connections between MCRF and Bayesian networks and transiograms as spatial continuity measures. In this response, all of the comments and concerns will be addressed, while also communicating with Li and other colleagues on general topics in Markov chain geostatistics.
Dislocation bowing and passing in persistent slip bands

In response to a recent paper by Mughrabi and Pschenitzka (Phil. Mag. 85 3029 (2005). ), an estimate is given of the saturation stress in cyclic plasticity, assuming only the bowing of screw dislocations and the simultaneous passing of them at a critical separation determined by their cross-section for mutual annihilation by cross-slip. Although, as Mughrabi and Pschenitzka show, the simple addition of the two stresses is a poor approximation, if the bowing stress is made equal to the passing stress, the equations governing the saturation stress and the associated average plastic strain in a persistent slip band are scarcely altered from earlier work (Phil. Mag. 84 2501 (2004). ). A comparison between theory and experiment shows good quantitative agreement. Finally, an estimate is made of the alternating internal stress in a band, and reasons suggested for why it does not contribute to the saturation stress.
Imbalance between Th17 and Treg Cells May Play an Important Role in the Development of Chronic Unpredictable Mild Stress-Induced Depression in Mice

Background: Recent data suggest that major depression is potentially associated with dysregulated cytokine production. However, the roles of T helper (Th) cells and their subsets in the development of depression still remain to be determined. The present study assessed changes in Th cell subsets and cytokines during the development of depression in a mouse model. Methods: Chronic unpredictable mild stress (CUMS) was used to simulate depression behavior in mice. The open field test, sucrose preference, and ingestion were used as evaluative indicators of depressive behavior. During the CUMS protocol, on days 3, 7, 14, and 21, we assessed behavioral changes, cytokine levels in serum or stimulated (CD3/CD28) cell culture medium, and mRNA expression (ELISA, RT-PCR), regulatory T (Treg) and Th17 subsets in spleen (ex vivo, flow cytometry, RT-PCR), and CD3/rIL-23-stimulated Th17 cell proliferation (MTT assay). Results: The results showed that in the depression model mice, IL-4 mRNA expression and serum levels increased on day 7, while no detectable change was observed in IFN-γ. Notably, a reduced proportion of Th17 cells with decreased proliferation capacity was observed at later stages, in parallel with a decline in serum IL-23 levels. In contrast, an increased Treg cell proportion and increased Foxp3 mRNA expression were observed in the mid-stages. Correlation analysis showed that the proportion of Tregs was correlated negatively with sucrose preference, while the proliferation of Th17 cells was notably correlated positively with sucrose preference. Also, an increased TGF-β level was detected in serum and was believed to be a key factor responsible for the imbalance between Th17 and Treg cells. Furthermore, the sucrose preference in TGF-β type I receptor blockade mice increased considerably, compared with CUMS mice. Conclusion: These results indicate that in CUMS-induced depression, behavioral changes may closely correlate with the imbalance between Th17 and Treg cell subsets, and TGF-β may be a key regulatory cytokine.
Newcastle University E-prints Citation for Item: Publisher's Copyright Statement: Effects of Aversive Odour Presentation on Inhibitory Control in the Stroop Colour-word Interference Task

Effects of aversive odour presentation on inhibitory control in the Stroop colour-word interference task. Always use the definitive version when citing. The full-text may be used and/or reproduced and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not for profit purposes provided that: • A full bibliographic reference is made to the original source • A link is made to the metadata record in Newcastle E-prints • The full text is not changed in any way. The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Abstract Background: Due to the unique neural projections of the olfactory system, odours have the ability to directly influence affective processes. Furthermore, it has been shown that emotional states can influence various non-emotional cognitive tasks, such as memory and planning. However, the link between emotional and cognitive processes is still not fully understood. The present study used the olfactory pathway to induce a negative emotional state in humans to investigate its effect on inhibitory control performance in a standard, single-trial manual Stroop colour-word interference task. An unpleasant (H 2 S) and an emotionally neutral (Eugenol) odorant were presented in two separate experimental runs, both in blocks alternating with ambient air, to 25 healthy volunteers, while they performed the cognitive task.
Increased Aortic Pulse Wave Velocity Is Associated With Silent Cerebral Small-Vessel Disease in Hypertensive Patients

Aortic stiffness predicts an excess risk of stroke, supposedly via cerebral small-vessel disease. White matter hyperintensities, silent lacunar infarcts, and brain microbleeds, manifestations of cerebral small-vessel disease on neuroimaging, may precede overt cerebrovascular disease. Therefore, we assessed whether aortic stiffness is also related to such lesions. In 167 hypertensive patients (85 men) without a history of cardiovascular or cerebrovascular disease, a mean age of 51.8±13.1 years, and untreated office blood pressure levels of 169±25/104±12 mm Hg, we determined aortic pulse wave velocity and office and ambulatory 24-hour pulse pressure (off medication), as well as the volume of white matter hyperintensities and the presence of lacunar infarcts and microbleeds using brain MRI. Linear and logistic regression analyses were performed to assess the relationships between the arterial stiffness measures and brain lesions. Aortic stiffness and pulse pressure were significantly related to each of the brain lesions in univariate analyses (P<0.05). Multivariate analyses, adjusted for age, sex, brain volume, mean arterial pressure, and heart rate, showed that a higher pulse wave velocity was significantly associated with a greater volume of white matter hyperintensities (unstandardized regression coefficient: 0.041; 95% CI: 0.005 to 0.078; P<0.05) and the presence of lacunar infarcts (odds ratio [per SD increase in pulse wave velocity]: 1.78; 95% CI: 1.06 to 2.99; P<0.05) but not with microbleeds. The models for pulse pressure failed to reach statistical significance in multivariate analyses. In conclusion, aortic stiffness is independently associated with manifestations of cerebral small-vessel disease in hypertensive patients, linking systemic large- to cerebral small-artery disease.
Acute Flaccid paralysis in adults: Our experience

Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. Materials and Methods: One hundred and thirty-three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. Results: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. Conclusion: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study.