Miracle-dz/UniFAR-FTUs huggingface dataset:
Change from conventional haemodiafiltration to on-line haemodiafiltration.

BACKGROUND On-line haemodiafiltration (HDF) is a technique which combines diffusion with elevated convection and uses pyrogen-free dialysate as a replacement fluid. The purpose of this study was to evaluate the difference between conventional HDF (1-3 l/h) and on-line HDF (6-12 l/h). METHODS The study included 37 patients, 25 males and 12 females. The mean age was 56.5 +/- 13 years and duration of dialysis was 62.7 +/- 49 months. Three patients dropped out for transplantation, three patients died and three failed to complete the study period. Initially all patients were on conventional HDF with high-flux membranes over the preceding 34 +/- 32 months. Treatment was performed with blood flow (QB) 402 +/- 41 ml/min, dialysis time (Td) 187 min, dialysate flow (QD) 654 +/- 126 ml/min and replacement fluid (Qi) 4.0 +/- 2 l/session. Patients were changed to on-line HDF with the same filtre and dialysis time, QD 679 +/- 38 ml/min (NS), QB 434 +/- 68 ml/min (P < 0.05) and post-dilutional replacement fluid 22.5 +/- 4.3 l/session (P < 0.001). We compared conventional HDF with on-line HDF over a period of 1 year. Dialysis adequacy was monitored according to standard clinical and biochemical criteria. Kinetic analysis of urea and beta2-micro-globulin (beta2m) was performed monthly. RESULTS Tolerance was excellent and no pyrogenic reactions were observed. Pre-dialysis sodium increased 2 mEq/l during on-line HDF. Plasma potassium, pre- and post-dialysis bicarbonate, uric acid, phosphate, calcium, iPTH, albumin, total proteins, cholesterol and triglycerides remained stable. The mean plasma beta2m reduction ratio increased from 56.1 +/- 8.7% in conventional HDF to 71.1 +/- 9.1% in on-line HDF (P < 0.001). The pre-dialysis plasma beta2m decreased from 27.4 +/- 8.1 to 24.2 +/- 6.5 mg/l (P < 0.01). Mean Kt/V (Daugirdas 2nd generation) was 1.35 +/- 0.21 in conventional HDF compared with 1.56 +/- 0.29 in on-line HDF (P < 0.01), Kt/Vr (Kt/V taking into consideration post-dialysis urea rebound) 1.12 +/- 0.17 vs 1.26 +/- 0.20 (P < 0.01), BUN time average concentration (TAC) 44.4 +/- 9 vs 40.6 +/- 10 mg/dl (P < 0.05) and protein catabolic rate (PCR) 1.13 +/- 0.22 vs 1.13 +/- 0.24 g/kg (NS). There was a significant increase in haemoglobin (10.66 +/- 1.1 vs 11.4 +/- 1.5) and haematocrit (32.2 +/- 2.9 vs 34.0 +/- 4.4%), P < 0.05, during the on-line HDF period, which allowed a decrease in the erythropoietin doses (3861 +/- 2446 vs 3232 +/- 2492 UI/week), (P < 0.05). Better blood pressure control (MAP 103.8 +/- 15 vs 97.8 +/- 11 mmHg, P < 0.01) and a lower percentage of patients requiring antihypertensive drugs were also observed. CONCLUSION The change from conventional HDF to on-line HDF results in increased convective removal and fluid replacement (18 l/session). During on-line HDF treatment, dialysis dose was increased for both small and large molecules with a decrease in uraemic toxicity level (TAC). On-line HDF provided a better correction of anaemia with lower dosages of erythropoietin. Finally, blood pressure was easily controlled.
TGF-β signalling and immunity in prostate tumourigenesis

Importance of the field: The TGF-β's are pleiotropic cytokines that regulate multiple cellular functions. Their role in the prostate is important for normal prostate development and also in prostate tumourigenesis. Areas covered in this review: The interactions TGF-β-mediated signalling has with maintaining prostate health, as well as its role in prostate tumourigenesis and prostate tumour immune evasion, with emphasis on how a breakdown in these interactions may influence disease progression. What the reader will gain: That TGF-β influences normal prostate growth and differentiation by regulating the balance between epithelial cell proliferation and apoptosis, and involving the androgen receptor pathway. That TGF-β protects and maintains prostate stem cells and a review of the contrasting role TGF-β has in prostate tumourigenesis and tumour development, where TGF-β acts as a tumour suppressor and then switches roles to become a tumour promoter, and creates a local immunosuppressive niche leading to systemic tumour tolerance. Take home message: TGF-β signalling in prostate cancer is a valid target for the treatment of this disease; however any therapeutic regimen will require an understanding of all aspects of the TGF-β-signalling nexus, otherwise by the very pleiotrophic nature of TGF-β, limited clinical benefits may result.
Analysis of the In Vitro Transcriptional Response of Human Pharyngeal Epithelial Cells to Adherent Streptococcus pneumoniae: Evidence for a Distinct Response to Encapsulated Strains

ABSTRACT Infection of the human host by Streptococcus pneumoniae begins with colonization of the nasopharynx, which is mediated by the adherence of bacteria to the respiratory epithelium. Several studies have indicated an important role for the pneumococcal capsule in this process. Here, we used microarrays to characterize the in vitro transcriptional response of human pharyngeal epithelial Detroit 562 cells to the adherence of serotype 2 encapsulated strain D39, serotype 19F encapsulated strain G54, serotype 4 encapsulated strain TIGR4, and their nonencapsulated derivatives (Δcps). In total, 322 genes were found to be upregulated in response to adherent pneumococci. Twenty-two genes were commonly induced, including those encoding several cytokines (e.g., interleukin 1β [IL-1β] and IL-6), chemokines (e.g., IL-8 and CXCL1/2), and transcriptional regulators (e.g., FOS), consistent with an innate immune response mediated by Toll-like receptor signaling. Interestingly, 85% of genes were induced specifically by one or more encapsulated strains, suggestive of a capsule-dependent response. Importantly, purified capsular polysaccharides alone had no effect. Over a third of these loci encoded products predicted to be involved in transcriptional regulation and signal transduction, in particular mitogen-activated protein kinase signaling pathways. Real-time PCR of a subset of 10 genes confirmed the microarray data and showed a time-dependent upregulation of, especially, innate immunity genes. The downregulation of epithelial genes was most pronounced upon adherence of D39Δcps, as 68% of the 161 genes identified were repressed only by this nonencapsulated strain. In conclusion, we identified a subset of host genes specifically induced by encapsulated strains during in vitro adherence and have demonstrated the complexity of interactions occurring during the initial stages of pneumococcal infection.
The A3 adenosine receptor as a new target for cancer therapy and chemoprotection.

Adenosine, a purine nucleoside, acts as a regulatory molecule, by binding to specific G-protein-coupled A(1), A(2A), A(2B), and A(3) cell surface receptors. We have recently demonstrated that adenosine induces a differential effect on tumor and normal cells. While inhibiting in vitro tumor cell growth, it stimulates bone marrow cell proliferation. This dual activity was mediated through the A3 adenosine receptor. This study showed that a synthetic agonist to the A3 adenosine receptor, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-uronamide (Cl-IB-MECA), at nanomolar concentrations, inhibited tumor cell growth through a cytostatic pathway, i.e., induced an increase number of cells in the G0/G1 phase of the cell cycle and decreased the telomeric signal. Interestingly, Cl-IB-MECA stimulates murine bone marrow cell proliferation through the induction of granulocyte-colony-stimulating factor. Oral administration of Cl-IB-MECA to melanoma-bearing mice suppressed the development of melanoma lung metastases (60.8 +/- 6.5% inhibition). In combination with cyclophosphamide, a synergistic anti-tumor effect was achieved (78.5 +/- 9.1% inhibition). Furthermore, Cl-IB-MECA prevented the cyclophosphamide-induced myelotoxic effects by increasing the number of white blood cells and the percentage of neutrophils, demonstrating its efficacy as a chemoprotective agent. We conclude that A3 adenosine receptor agonist, Cl-IB-MECA, exhibits systemic anticancer and chemoprotective effects.
A systematic review of the effectiveness of interventions using the Common Sense Self-Regulatory Model to improve adherence behaviours

This systematic review assessed the effectiveness of the Common Sense Self-Regulatory Model in the design of interventions to improve adherence behaviours. Of nine eligible studies, six reported improvements in adherence behaviours and three showed moderate to large effects on return to work and lifestyle recommendations. Four studies stated how Common Sense Self-Regulatory Model constructs were addressed in the intervention and five measured illness perceptions as outcomes. Evidence was found for targeting cure/control perceptions in studies aimed at improving adherence behaviours. Future studies need to measure illness perceptions pre- and post-intervention to enable mediational analyses to assess the effect of Common Sense Self-Regulatory Model interventions on improving health outcomes.
Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death Published, JLR Papers in Press, April 27, 2006.

Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological disorder caused by the pathogenomic accumulation of psychosine (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside β-galactosidase. This study underscores the mechanism of action of psychosine in the regulation of oligodendrocyte cell death via the generation of lysophosphatidylcholine (LPC) and arachidonic acid (AA) by the activation of secretory phospholipase A2 (sPLA2). There was a significant increase in the level of LPC, indicating a phospholipase A2 (PLA2)-dependent pathobiology, in the brains of Krabbe disease patients and those of twitcher mice, an animal model of Krabbe disease. In vitro studies of the treatment of primary oligodendrocytes and the oligodendrocyte MO3.13 cell line with psychosine also showed the generation of LPC and the release of AA in a dose- and time-dependent manner, indicating psychosine-induced activation of PLA2. Studies with various pharmacological inhibitors of cytosolic phospholipase A2 and sPLA2 and psychosine-mediated induction of sPLA2 enzymatic activity in media supernatant suggest that psychosine-induced release of AA and generation of LPC is mainly contributed by sPLA2. An inhibitor of sPLA2, 7,7-dimethyl eicosadienoic acid, completely attenuated the psychosine-mediated accumulation of LPC levels, release of AA, and generation of reactive oxygen species, and blocked oligodendroyte cell death, as evident from cell survival, DNA fragmentation, and caspase 3 activity assays. This study documents for the first time that psychosine-induced cell death is mediated via the sPLA2 signaling pathway and that inhibitors of sPLA2 may hold a therapeutic potential for protection against oligodendrocyte cell death and resulting demyelination in Krabbe disease.
High-Performance Concrete in Fire-Exposed Reinforced Concrete Sections

In this research, the ultimate behavior of 3 different reinforced concrete square sections subjected to an eccentric axial force is investigated with reference to typical high-performance concrete (HPC) and to several fire durations. In addition, to the M-N envelopes of the undamaged sections, those at high temperatures and after cooling are worked out. Comparisons are made with normal-strength concrete (NSC) sections having the same size or ultimate capacity, as well as with HPC sections characterized by different bar arrangements or protected by cementitious lining, and a few performance indicators are introduced to describe the marked reduction of the failure envelopes. The main findings are given and discussed. HPC sections are more temperature-sensitive than NSC sections, but not to the extent expected.
Placental HtrA3 is regulated by oxygen tension and serum levels are altered during early pregnancy in women destined to develop preeclampsia.

CONTEXT The pathogenic origin of preeclampsia is defective placental development (placentation) and function. Preeclampsia is not diagnosed until later in pregnancy, and reliable early detection is highly desirable. HtrA3 is a recently cloned gene with high expression during placentation in the mouse, rhesus monkey, and human. OBJECTIVE The present study examined the placental production and the serum profile of HtrA3 across gestation in women, the potential molecular mechanisms regulating HtrA3 production, and the association between maternal HtrA3 serum levels and preeclampsia. METHODS Immunohistochemistry determined HtrA3 expression pattern and cellular localization in first-, second-, and third-trimester placenta. The maternal serum HtrA3 levels were analyzed by Western blotting. The regulation of placental HtrA3 production and the secretion by oxygen tension was investigated in first-trimester placental explants and trophoblast cells. RESULTS Placental HtrA3 protein was maximally produced in the first trimester and then dramatically down-regulated, especially in the syncytiotrophoblast. HtrA3 was secreted into the maternal circulation with a serum profile reflecting placental production. Oxygen tension regulated HtrA3; low oxygen enhanced, whereas the transition from low to high oxygen decreased, HtrA3 protein production in syncytiotrophoblast. Maternal serum HtrA3 levels at approximately 13-14 wk of gestation were significantly higher in women who subsequently developed preeclampsia. It appeared that HtrA3 down-regulation was delayed in preeclamptic pregnancies. CONCLUSIONS HtrA3 protein production is closely associated with changing in oxygen tension in the placenta. The decline in HtrA3 at the end of first trimester may reflect the placental low to high oxygen switch. Abnormally high levels of serum HtrA3 at approximately 13-14 wk of gestation is associated with preeclampsia.
On the refinement of carbide precipitates by cryotreatment in AISI D2 steel

Refinement of carbide particles by cryotreatment is often proposed as a major factor for the improvement of wear resistance in tool steels. However, this proposition is not substantiated by experimental evidence. This has been examined in this report by (i) detailed micro-structural analyses of the nature, volume fraction, size, population density and distribution of carbide particles, (ii) XRD and EDX micro-analysis on the bulk samples and electrochemically extracted carbides, and (iii) measurement of hardness and wear rate of a series of differently cryotreated AISI D2 steel. The results conclusively establish that (i) cryotreatment, in comparison to conventional treatment, induces precipitation of finer carbides with higher volume fraction and more uniform distribution, and (ii) population density and the size of secondary carbide particles significantly increases with holding time up to a critical duration at 77 K in cryotreatment. The latter observation indicates the pioneering direction towards optimization of cryotreatment design for techno-economic benefit.
Human Herpesvirus 8 Envelope Glycoprotein K8.1A Interaction with the Target Cells Involves Heparan Sulfate

ABSTRACT Human herpesvirus-8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus K8.1 gene encodes for two immunogenic glycoproteins, gpK8.1A and gpK8.1B, originating from spliced messages. The 228-amino-acid (aa) gpK8.1A is the predominant form associated with the virion envelope, consisting of a 167-aa region identical to gpK8.1B and a 61-aa unique region (L. Zhu, V. Puri, and B. Chandran, Virology 262:237–249, 1999). HHV-8 has a broad in vivo and in vitro cellular tropism, and our studies showed that this may be in part due to HHV-8's interaction with the ubiquitous host cell surface molecule, heparan sulfate (HS). Since HHV-8 K8.1 gene is positionally colinear to the Epstein-Barr virus (EBV) gene encoding the gp350/gp220 protein involved in EBV binding to the target cells, gpK8.1A's ability to interact with the target cells was examined. The gpK8.1A without the transmembrane and carboxyl domains (ΔTMgpK8.1A) was expressed in a baculovirus system and purified. Radiolabeled purified ΔTMgpK8.1A protein bound to the target cells, which was blocked by unlabeled ΔTMgpK8.1A. Unlabeled ΔTMgpK8.1A blocked the binding of [3H]thymidine-labeled purified HHV-8 to the target cells. Binding of radiolabeled ΔTMgpK8.1A to the target cells was inhibited in a dose-dependent manner by soluble heparin, a glycosaminoglycan (GAG) closely related to HS, but not by other GAGs such as chondroitin sulfate A and C, N-acetyl heparin and de-N-sulfated heparin. Cell surface absorbed ΔTMgpK8.1A was displaced by soluble heparin. Radiolabeled ΔTMgpK8.1A also bound to HS expressing Chinese hamster ovary (CHO-K1) cells, and binding to mutant CHO cell lines deficient in HS was significantly reduced. The ΔTMgpK8.1A specifically bound to heparin-agarose beads, which was inhibited by HS and heparin, but not by other GAGs. Virion envelope-associated gpK8.1A was specifically precipitated by heparin-agarose beads. These findings suggest that gpK8.1A interaction with target cells involves cell surface HS-like moieties, and HHV-8 interaction with HS could be in part mediated by virion envelope-associated gpK8.1A.
Ultrahigh enhancement in absolute and relative rotation sensing using fast and slow light

We describe a resonator-based optical gyroscope whose sensitivity for measuring absolute rotation is enhanced via use of the anomalous dispersion characteristic of superluminal light propagation. The enhancement is given by the inverse of the group index, saturating to a bound determined by the group velocity dispersion. We also show how the offsetting effect of the concomitant broadening of the resonator linewidth may be circumvented by using an active cavity. For realistic conditions, the enhancement factor is as high as 10{sup 6}. We also show how normal dispersion used for slow light can enhance relative rotation sensing in a specially designed Sagnac interferometer, with the enhancement given by the slowing factor.
Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study

Abstract Objective To evaluate the effect of dietary folate intake on the relation between alcohol consumption and breast cancer risk. Design Prospective cohort study. Setting Melbourne, Australia. Participants 17 447 Anglo-Australian women resident in Melbourne, aged 40-69 years at recruitment in 1990-4, and followed up until 31 December 2003. Main outcome measure Invasive breast cancers diagnosed during follow-up and ascertained through the Victorian cancer registry. Results 537 invasive breast cancers were diagnosed. Compared with lifetime abstainers, the hazard ratio for breast cancer in women who consumed an average of 40 g or more of alcohol daily at baseline was 1.41 (95% confidence interval 0.90 to 2.23). No direct association was found between dietary folate intake and risk of breast cancer, but a high folate intake mitigated the excess risk associated with alcohol. The estimated hazard ratio of an alcohol consumption of 40 g/day or more was 2.00 (1.14 to 3.49) for women with intakes of 200 μg/day of folate and 0.77 (0.33 to 1.80) for 400 μg/day of folate (P = 0.04 for interaction between alcohol and folate). Conclusions An adequate dietary intake of folate might protect against the increased risk of breast cancer associated with alcohol consumption.
Approach for investigating crowdfunding campaigns with platform data: case indiegogo

Crowdfunding via the internet is a relatively new phenomenon in research and gaining momentum currently. While taking a data-driven approach into investigating the properties and dynamics of crowdfunding campaigns would allow the use of computational social science in investigations on crowdfunding, existing data-driven research on crowdfunding remains very limited. This is particularly true on the level of individual funder data. In this study, we contribute to the empirical body of knowledge on crowdfunding by introducing Indiegogo as a data source and, more specifically, the development and implementation of a crawler and scraper for accessing Indiegogo campaign data, and sharing this openly for other researchers. Due to the extremely dynamic and rapidly increasing amount of crowdfunding data in terms of the number of crowdfunding campaigns and the available investment and individual investor data, we believe our approach is useful for supporting public and open data-driven research, instead of providing merely a static data set.
Serum midkine levels are increased in patients with various types of carcinomas

The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n= 135) was 0.154 ± 0.076 (mean ± SD) ng ml–1with an apparent cut-off value as 0.5 ng ml–1. Serum MK level was significantly elevated in the cancer patients (n= 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml–1. All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application. © 2000 Cancer Research Campaign
Late Conversion of Kidney Transplant Recipients from Ciclosporin to Tacrolimus Improves Graft Function: Results from a Randomized Controlled Trial

Background Tacrolimus (TAC) to ciclosporin A (CSA) conversion studies in stable kidney transplant recipients have reported varying effects on graft function. Here we study graft function (eGFR) trajectories using linear mixed models, which provide effect estimates on both slope and baseline level of GFR and offer increased statistical power. Methods Secondary analysis of a randomized controlled trial of CSA treated kidney transplant recipients with stable graft function assigned to receive 0.1 mg/kg/day TAC (target 5–8 ng/ml) or to continue CSA based immunosuppression (target 70–150 ng/ml) at a 2:1 ratio. Renal graft function was estimated via the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) formulas. Results Forty-five patients continued CSA and 96 patients were converted to TAC with a median follow up of 24 months. Baseline demographics (except for recipient age) including native kidney disease, transplant characteristics, kidney graft function, medication use and comorbid conditions did not differ between groups. In respect to long-term renal graft function, linear mixed models showed significantly improved eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p<0.001) in the TAC versus CSA group over 24 months of follow up. Estimated eGFRCKD-EPI group differences between TAC and CSA were −3.49 (p = 0.019) at 3 months, −5.50 (p<0.001) at 12 months, and −4.48 ml/min/1.73m2 (p = 0.003) at 24 months of follow up. Baseline eGFR was a significant predictor of eGFR trajectories (eGFRMDRD: p<0.001, eGFRCKD-EPI: p<0.001). Significant effects for randomization group were evident despite short-term trough levels in the supratherapeutic range (27% (n = 26) of TAC patients at week one). Median TAC trough levels were within target range at week 4 after conversion. Conclusion Conversion of CSA treated kidney transplant recipients with stable graft function to TAC (target 5–8 ng/ml) showed significantly improved long-term eGFR trajectories when compared to CSA maintenance (target 70–150 ng/ml). Trial Registration ClinicalTrials.gov NCT00182559 EudraCT identifier: 2004-004209-98