Miracle-dz/UniFAR-FTUs huggingface dataset:
[Relationship between genetic polymorphism of tumor necrosis factor-alpha and susceptibility to intrauterine HBV infection].

OBJECTIVE To study the possible relationship between tumor necrosis factor (TNF)-alpha-238G/A gene polymorphism and the susceptibility to intrauterine HBV infection. METHODS Two hundred and fifty-six children, including 130 infants born to HBsAg positive mothers were divided into two groups: forty-five children with intrauterine HBV infection (group I) and 85 children without intrauterine HBV infection (group II), with a control group of 126. TNF-alpha-238G/A gene polymorphism was examined in all 256 children, by means of real-time quantitative fluorescent PCR. RESULTS A significant difference of TNF-alpha-238A allele frequency was found between group I and group II (x2=6.797, P=0.009), and between group I and the controls group (x2=0.047, P=0.002), but there was no significant difference between group II and the control groups (x2=0.047, p=0.828). CONCLUSION This study found that genetic polymorphism of tumor necrosis factor-a was associated with intrauterine HBV infection
The Mpc Comes of Age

As the MPC's tenth anniversary approaches, Rachel Lomax, Deputy Governor for monetary policy, considers what was special about the 1997 policy framework, and how age and success have changed it. In her view, the key characteristic of the current approach to monetary policy is 'constrained discretion'  the combination of a strong commitment to low inflation with considerable flexibility to respond to shocks. While the so-called Great Stability of the past decade has bestowed on the MPC 'the great gift of credibility', it has had both helpful and unhelpful legacies. On one hand, the credibility of the framework has helped to contain inflation, in the face of large shocks. On the other, the public may have acquired unrealistic expectations about what monetary policy can achieve. She concludes that the policy framework can only offer flexibility as long as it remains credible. But that credibility needs to reflect reality.
Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND & AIMS Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.
Transplanted astrocytes internalize deposited β‐amyloid peptides in a transgenic mouse model of Alzheimer's disease

Alzheimer's disease (AD) is one of the most devastating neurodegenerative disorders. The neuropathological hallmarks include extracellular senile plaques consisting of deposited β‐amyloid (Aβ) peptides and intraneuronal neurofibrillary tangles. Neuroinflammation and activation of astrocytes are also well‐established features of AD neuropathology; however, the relationships between astrocytes and Aβ deposition remain unclear. Previous studies have shown that adult mouse astrocytes internalize and degrade Aβ deposits in brain sections prepared from human amyloid precursor protein (APP) transgenic mice. In the present study, we demonstrate that cultured adult, but not neonatal mouse astrocytes, respond morphologically and degrade Aβ deposits present in human AD brain. We also transplanted astrocytes isolated from enhanced green fluorescent protein expressing adult and neonatal mice into the hippocampi of human Aβ plaque‐bearing transgenic APPSwe+PS1dE9 (APdE9) mice and their wild‐type littermates and followed the migration and localization of these astrocytes by confocal microscopy upto 7 days after transplantation. Posttransplantation the astrocytes localized as aggregates or thin strings of many cells within the hippocampi of APdE9 and wild‐type mice and showed limited migration from the injection site. Interestingly, most of the transplanted astrocytes were found near Aβ deposits in the hippocampi of APdE9 mice. In contrast to findings in ex vivo degradation assay, confocal microscopy revealed that both adult and neonatal transplanted astrocytes internalized human Aβ immunoreactive material in vivo. These results support the role of astrocytes as active Aβ clearing cells in the CNS that may have important implications for future development of therapeutic strategies for AD. © 2007 Wiley‐Liss, Inc.
Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder.

OBJECTIVE Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. METHOD Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. RESULTS Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. CONCLUSIONS These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.
SCN1A duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis

Objective: We aimed to determine the type, frequency, and size of microchromosomal copy number variations (CNVs) affecting the neuronal sodium channel α 1 subunit gene (SCN1A) in Dravet syndrome (DS), other epileptic encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+).
Preventive Effects of Escherichia coli Strain Nissle 1917 on Acute and Chronic Intestinal Inflammation in Two Different Murine Models of Colitis

ABSTRACT Escherichia coli strain Nissle 1917 (EcN) is as effective in maintaining remission in ulcerative colitis as is treatment with mesalazine. This study aims to evaluate murine models of acute and chronic intestinal inflammation to study the antiinflammatory effect of EcN in vivo. Acute colitis was induced in mice with 2% dextran-sodium sulfate (DSS) in drinking water. EcN was administered from day −2 to day +7. Chronic colitis was induced by transfer of CD4+ CD62L+ T lymphocytes from BALB/c mice in SCID mice. EcN was administered three times/week from week 1 to week 8 after cell transfer. Mesenteric lymph node (MLN) cytokine secretion (of gamma interferon [IFN-γ], interleukin 5 [IL-5], IL-6, and IL-10) was measured by enzyme-linked immunosorbent assay. Histologic sections of the colon were analyzed by using a score system ranging from 0 to 4. Intestinal contents and homogenized MLN were cultured, and the number of E. coli-like colonies was determined. EcN was identified by repetitive extragenic palindromic (REP) PCR. EcN administration to DSS-treated mice reduced the secretion of proinflammatory cytokines (IFN-γ, 32,477 ± 6,377 versus 9,734 ± 1,717 [P = 0.004]; IL-6, 231 ± 35 versus 121 ± 17 [P = 0.02]) but had no effect on the mucosal inflammation. In the chronic experimental colitis of the transfer model, EcN ameliorated the intestinal inflammation (histology score, 2.7 ± 0.2 versus 1.9 ± 0.3 [P = 0.02]) and reduced the secretion of proinflammatory cytokines. Translocation of EcN and resident E. coli into MLN was observed in the chronic colitis model but not in healthy controls. Administration of EcN ameliorated acute and chronic experimental colitis by modifying proinflammatory cytokine secretion but had no influence on the acute DSS-induced colitis. In this model, preexisting colitis was necessary for translocation of EcN and resident E. coli into MLN.
Nonlinear Min-Max Model Predictive Control based on Volterra models. Application to a pilot plant

This paper presents a new Nonlinear Min-Max Model Predictive Control strategy based on Volterra models. This control strategy is computationally efficient as the exact worst case cost can be computed in polynomial time. The reduced complexity of the proposed strategy allows its use in real time applications with typical prediction and control horizons. The controller has been implemented to control the temperature of a chemical reaction in the reactor of a pilot plant. A non-autoregressive second order Volterra series model has been identified from experimental data and used as a prediction model. The controller behavior is illustrated by experimental results.
Thriving in an increasingly digital ecosystem

The business world is rapidly digitizing, breaking down industry barriers and creating new opportunities while destroying long-successful business models. Given the amount of turmoil digital disruption is causing, authors Peter Weill and Stephanie L. Woerner of the MIT Center for Information Systems Research say its time for companies to evaluate these threats and opportunities and create new business options for the more-connected future of digital ecosystems. In recent research, board members at large companies estimated that 32% of their companys revenue would be under threat from digital disruption in the next five years; 60% of board members felt their boards should spend significantly more time on this issue next year. Despite the threats from companies including Uber, Airbnb and Amazon, increasing digitization offers opportunities for companies to leverage strong customer relationships and increase cross-selling, the authors argue. The authors offer a framework, supported by examples, for helping managers think about their competitive environments. The combination of moving from value chains to ecosystems and increasing consumer knowledge, the authors write, provides business leaders with four distinct business models, each with associated capabilities and relationships. Companies can choose to operate as (1) suppliers, (2) omnichannel businesses, (3) modular producers or (4) ecosystem drivers. The authors found that businesses focused narrowly on value chains were at a disadvantage compared with those that thought more broadly about their business ecosystems. Companies that had 50% or more of their revenues from digital ecosystems and understood their end customers better than their average competitor saw 32% higher revenue growth and 27% higher profit margins than their industry averages. As they prepare for growing digital disruption, companies have two major decisions to make. First, they need to decide the extent to which they want to control the value chain or become part of a more complex ecosystem. Second, they need to decide how much they want to invest in knowing their end customers. Companies with ecosystem drivers as their dominant business model had the highest margins and growth of all the four options in the companies the authors studied
Transfection of molecularly cloned Friend murine leukemia virus DNA yields a highly leukemogenic helper-independent type C virus

Unintegrated viral DNA was isolated via the Hirt procedure from mouse fibroblasts newly infected with Friend murine leukemia virus (F-MuLV) clone 201, a biologically cloned helper virus isolated from stocks of F-MuLV complex. A physical map of the unintegrated in vivo linear viral DNA was generated for several restriction endonucleases. The supercoiled viral DNA was digested with EcoRI, which cleaved the viral DNA at a unique site. The linearized viral DNA was then inserted into lambda gtWES.lambda B at the EcoRI site and cloned in an approved EK2 host. Eight independent lambda-mouse recombinants were identified as containing F-MuLV DNA inserts by hybridization with F-MuLV 32P-labeled complementary DNA. One of the F-MuLV DNA inserts was 9.1 kilobases (kb) and had the same restriction enzyme sites as the unintegrated linear F-MuLV DNA. Six inserts were 8.5 kb; each lacked a single copy of the terminally redundant sequences of the unintegrated linear viral DNA. One insert was 8.2 kb and contained a 0.9-kb deletion. After digestion with EcoRI, one recombinant DNA preparation containing an 8.5-kb insert was infectious for NIH 3T3 cells. Undigested recombinant DNA was not infectious. The infectivity of the EcoRI-digested DNA followed multihit kinetics, indicating that more than one molecule was required to register as an infectious unit. The virus isolated from this transfection (F-MuLV-57) was NB-ecotropic, helper-independent, and formed XC plaques. Inoculation of this virus into newborn NIH Swiss mice induced leukemia and splenomegaly in greater than 90% of animals within 3 to 4 weeks. The gross and microscopic abnormalities induced by F-MuLV clone 57 were identical to those seen with the original parent stocks of F-MuLV clone 201. These results indicate that this helper-independent F-MuLV can induce a rapid nonthymic leukemia in the absence of the spleen focus-forming virus.
Expression in COS-1 cells of Epstein-Barr virus nuclear antigen from a complete gene and a deleted gene

In a previous study the BamHI-K fragment of Epstein-Barr virus DNA was shown to induce a nuclear antigen, Epstein-Barr virus nuclear antigen (EBNA), when cotransfected with the herpes simplex virus thymidine kinase gene into mouse LTK- cells. We have now inserted the BamHI-K fragment and a BamHI/HindIII subfragment, I1f , into shuttle vectors containing the origin of replication of simian virus 40. These plasmids have been introduced into COS-1, which are monkey kidney cells transformed by an origin-defective simian virus 40 genome. This expression system permitted rapid characterization of antigens, mRNAs, and proteins related to EBNA. The same-sized EBNA protein (approximately 78,000) was made after transfection with BamHI-K (5.2 kilobase pairs [kbp]) or the I1f subfragment (2.9 kbp). A deletion of about 600 bp occurred when the I1f fragment was propagated on the pSV2 plasmid in Escherichia coli. The deleted fragment gave rise to a smaller protein (approximately 52,000). These data provide evidence that EBNA is encoded by the 2.9-kbp I1f and is not an induced cellular protein. Nuclear antigen and polypeptide expression occurred equally well when the Epstein-Barr virus DNA was cloned on PSV2 -gpt or pSVOd . The latter plasmid lacks sequences allowing for efficient early gene transcription as well as splicing and polyadenylation signals which are present in pSV2 . Preliminary mapping of the EBNA gene transcripts demonstrated that two mRNAs (2.9 and 2.4 kilobases [kb]) are homologous to the I1f fragment. Taken together, the data suggest that the 2.9-kbp I1f fragment contains the structural gene for EBNA synthesis. COS-1 cells will thus provide a valuable system in which to analyze functional domains of the EBNA gene.
Integrating service development with evaluation in telehealthcare: an ethnographic study

Abstract Objectives To identify issues that facilitate the successful integration of evaluation and development of telehealthcare services. Design Ethnographic study using various qualitative research techniques to obtain data from several sources, including in-depth semistructured interviews, project steering group meetings, and public telehealthcare meetings. Setting Seven telehealthcare evaluation projects (four randomised controlled trials and three pragmatic service evaluations) in the United Kingdom, studied over two years. Projects spanned a range of specialties—dermatology, psychiatry, respiratory medicine, cardiology, and oncology. Participants Clinicians, managers, technical experts, and researchers involved in the projects. Results and discussion Key problems in successfully integrating evaluation and service development in telehealthcare are, firstly, defining existing clinical practices (and anticipating changes) in ways that permit measurement; secondly, managing additional workload and conflicting responsibilities brought about by combining clinical and research responsibilities (including managing risk); and, thirdly, understanding various perspectives on effectiveness and the limitations of evaluation results beyond the context of the research study. Conclusions Combined implementation and evaluation of telehealthcare systems is complex, and is often underestimated. The distinction between quantitative outcomes and the workability of the system is important for producing evaluative knowledge that is of practical value. More pragmatic approaches to evaluation, that permit both quantitative and qualitative methods, are required to improve the quality of such research and its relevance for service provision in the NHS.
Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis

Resminostat, a novel class I, IIb, and IV histone deacetylase inhibitor, was studied in advanced hepatocellular carcinoma (HCC) patients after relapse to sorafenib (SHELTER study). In this phase I/II clinical trial, combination of sorafenib and resminostat was safe and showed early signs of efficacy. However, the molecular mechanisms behind this synergism have not been explored yet. In this work, we aimed to analyze whether resminostat regulates epithelial-mesenchymal and stemness phenotype as a mechanism of sensitization to sorafenib. Three HCC cell lines with differences in their epithelial/mesenchymal characteristics were treated with resminostat and sorafenib alone, or in combination. Resminostat prevented growth and induced cell death in the HCC cells, in a time and dose dependent manner. A collaborative effect between resminostat and sorafenib was detected in the mesenchymal HCC cells, which were insensitive to sorafenib-induced apoptosis. Expression of mesenchymal-related genes was decreased in resminostat-treated HCC cells, concomitant with an increase in epithelial-related gene expression, organized tight junctions and reduced invasive growth. Moreover, resminostat down-regulated CD44 expression, coincident with decreased capacity to form colonies at low cell density. Conclusion: Resminostat shifts mesenchymal cells towards a more epithelial phenotype, lower invasive and stemness properties, which may contribute to the sensitization to sorafenib-induced apoptosis.
Oxidative stress: potential of distinct peroxide determination systems

Abstract When reactive oxygen species attack biological structures, peroxides, which are short-lived oxidative intermediates, are generated. We evaluated the potential of two different, commercially available peroxide activity assays (Pox-Act and d-ROMS) to see whether the results were associated with the clinical condition of subjects who were participating in a routine health care program. Furthermore, we determined the total antioxidant status (TAS) and the titer of autoantibodies against oxidized low-density lipoprotein (oLAb) to verify the hydroperoxide measurements. Subjects with medical conditions (hereafter referred to as patients) had significantly increased serum peroxide levels compared to healthy subjects. The d-ROMS kit indicated that 86% of subjects had an increased level of total peroxides. Although the assays had a significant correlation (p < 0.001), 34% of the subjects had an increased total peroxide concentration in the Pox-Act assay that was clearly associated with clinical symptoms. Furthermore, the sensitivity of the Pox-Act assay was 35 times higher than that of the d-ROMS kit. In subjects with medical conditions, there was a trend toward a decreased TAS and a slightly increased oLAb titer in comparison to healthy subjects, but this was not statistically significant. The Pox-Act assay seems to be a valuable tool for the determination of total peroxides, while the results from the d-ROMS kit should be considered with caution.
One-Year Clinical Outcome of Dental Implants Placed in Patients With Type 2 Diabetes Mellitus: A Case Series

Purpose:Diabetes mellitus is a prevalent medical disorder. It is often accompanied with systemic adverse sequelae, such as wound healing alterations, which may affect osseointegration of dental implants. The use of dental implants in patients with diabetes mellitus remains controversial because altered bone healing around implants has been reported. The purpose of this study was to present 1-year clinical outcomes of 23 implants placed in 10 patients with well-, or moderately well, controlled type 2 diabetes mellitus. Materials:All implants were uneventfully placed in the mandible or maxilla. Three different types of definitive implant-supported prostheses, cement- or screw-retained fixed dental prostheses, and overdentures were delivered to the patients. Results:At 1-year follow-up recall, no implants were lost, and 0.3 ± 0.2 mm marginal bone loss was noted. No periapical radiolucencies, no bleeding on probing, or pathologic probing depth were recorded at these recalls. Conclusion:This clinical report supports the use of dental implants in patients with well-, or moderately well, controlled type 2 diabetes mellitus as a dental treatment modality. No evidence of diminished clinical success or significant complication related to implant treatment was found for this patient population.