Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin A Decreases Cytotoxicity of Oxidized Low-Density Lipoprotein in Patients with Atherosclerosis

ABSTRACT Background: Oxidized low-density lipoprotein (ox-LDL) is implicated in initiation and progression of atherosclerosis. Previously, we found that ox-LDL increases vulnerability of peripheral blood mononuclear cells (PBMCs) in atherosclerotic patients compared to controls. Vitamin A induces proliferation of PBMCs. The aim of this study was to determine the effect of vitamin A supplementation on PBMC survival against LDL and different doses of ox-LDL. Method: In this double-blind placebo-controlled trial, we recruited 35 atherosclerotic patients and 38 healthy controls and randomly allocated them into placebo and vitamin A groups, which received either placebo or 25,000 IU/day of vitamin A for 3 months. PBMCs were isolated, cultured, and stimulated by 1 µg/mL LDL as well as 1 µg/mL and 50 µg/mL ox-LDL. The stimulation indexes (SIs) of PBMCs were calculated to identify cell viability. Additionally, the circulating ox-LDL levels were measured by ELISA. Results: Viability of PBMCs stimulated by 50 µg/mL ox-LDL significantly increased following vitamin A supplementation in patients (p < 0.01). The levels of circulating ox-LDL were not changed by vitamin A treatment. Ox-LDL levels were strongly and positively correlated to SI of PBMCs stimulated by 1 µg/mL LDL and1 µg/mL ox-LDL in all groups. Conclusion: Vitamin A decreases cytotoxicity of high-dose ox-LDL and improves PBMC viability. The protective effect of vitamin A is not mediated by an antioxidative mechanism, but may instead have been due to intracellular protection of the apoptotic machinery or induction of proliferation of the cells. Higher levels of ox-LDL increase PBMC irritability in all participants.
Reverse Sample Genome Probing, a New Technique for Identification of Bacteria in Environmental Samples by DNA Hybridization, and Its Application to the Identification of Sulfate-Reducing Bacteria in Oil Field Samples

A novel method for the identification of bacteria in environmental samples by DNA hybridization is presented. It is based on the fact that, even within a genus, the genomes of different bacteria may have little overall sequence homology. This allows the use of the labeled genomic DNA of a given bacterium (referred to as a “standard”) to probe for its presence and that of bacteria with highly homologous genomes in total DNA obtained from an environmental sample. Alternatively, total DNA extracted from the sample can be labeled and used to probe filters on which denatured chromosomal DNA from relevant bacterial standards has been spotted. The latter technique is referred to as reverse sample genome probing, since it is the reverse of the usual practice of deriving probes from reference bacteria for analyzing a DNA sample. Reverse sample genome probing allows identification of bacteria in a sample in a single step once a master filter with suitable standards has been developed. Application of reverse sample genome probing to the identification of sulfate-reducing bacteria in 31 samples obtained primarily from oil fields in the province of Alberta has indicated that there are at least 20 genotypically different sulfate-reducing bacteria in these samples.
Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

BACKGROUND Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. AIM To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. DESIGN Cluster-randomized controlled trial. METHODS We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. RESULTS Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. CONCLUSIONS Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.
Identification of Candidate Genes at Quantitative Trait Loci on Chicken Chromosome Z Using Orthologous Comparison of Chicken, Mouse, and Human Genomes

This study was undertaken to identify novel candidate genes at quantitative trait loci (QTL) on chicken chromosome Z (GGAZ) by comparing orthologous regions of chicken, human and mouse genomes. Primer sequences from marker flanking QTL positions (https://acedb.asg.wur.nl/) were obtained from www.iastate. edu/chickmap and blasted against the chicken genome (www.ensembl.org) using BLASTN. The best matches were those with the highest score, lowest E-values and highest percent identity. Orthologous regions in mice and humans, together with genes located on or around those loci were identified using the Ensembl website. Forty-six chicken genes, 91 mouse genes and 60 human genes associated with QTL on GGAZ were identified in the current study. Among the most promising candidate genes for egg production and egg shell quality are annexin A1 (ANXA1), osteoclast stimulating factor (OSF), thrombospondin-4 (THBS4), programmed cell death proteins (PDCD), follistatin (FST), growth hormone receptor (GHR), interferon (IFN) alpha and beta. The chicken IFN alpha and beta were located on GGAZ around position 13,000,000 bp on the draft chicken sequence map. The neuronal nicotinic acetylcholine receptor (nAChR) is located at a QTL region for abdominal fat (GGAZ 25483091 bp). Nicotine is an agonist at the nAChRs and has been shown to decrease lipolysis and triglyceride uptake, thereby reducing net storage in adipose tissue. Therefore, the nAchRs could be used as therapeutic targets for regulating feed intake and obesity. This study has identified 197 putative candidate genes in probable QTL regions of chicken chromosome Z.
Antigenic heterogeneity of lipopolysaccharides from Campylobacter jejuni and Campylobacter fetus

The lipopolysaccharide (LPS) structure of Campylobacter spp. can be visualized with polyacrylamide gel electrophoresis by examining proteinase K-treated whole cell lysates. Polyacrylamide gel electrophoresis LPS profiles of C. jejuni strains are rough type with low concentrations of low-molecular-weight polysaccharide side chains, serum-resistant C. fetus strains have smooth-type LPS, and serum-sensitive C. fetus strains have rough-type LPS. We electroblotted the proteinase K-treated whole cell lysates of 17 C. jejuni and 9 C. fetus strains from polyacrylamide gel electrophoresis to nitrocellulose paper to examine antigenicity to immune rabbit sera. There was virtually no antigenic cross-reactivity of C. jejuni and C. fetus LPS. Among C. jejuni strains, core LPS structures were cross-reactive, but the O-polysaccharide side chains were best recognized by homologous antisera. Antisera to several serum-resistant C. fetus strains recognized only the polysaccharide side-chain regions of serum-resistant strains and no part of the LPS from the sensitive strain. Antiserum raised against a serum-sensitive C. fetus strain but not homologous antisera recognized the core region of the LPS of the serum-resistant C. fetus strains. These findings suggest that core LPS antigens are widely shared within C. fetus subsp. fetus strains but that in the serum-resistant strains this core region is not surface exposed and therefore not immunogenic to rabbits infected with whole cells.
Intratumoral Heterogeneity of HER-2/neu in Invasive Mammary Carcinomas Using Fluorescence In-Situ Hybridization and Tissue Microarray

Fluorescence in-situ hybridization is increasingly being used to determine HER-2/neu status in patients with breast carcinoma. The possibility that intratumoral heterogeneity of HER-2/neu gene amplification may potentially contribute to inaccurate assessment of HER-2/neu status was investigated in routine cases of invasive mammary carcinomas. From 169 representative formalin-fixed, paraffin-embedded blocks of invasive duct mammary carcinomas with grade 3 architecture, 48 cases were analyzed by fluorescence in-situ hybridization and 59 analyses were performed. Intratumoral heterogeneity for HER-2/neu gene amplification was demonstrated in only 5 (16%) of 31 cases where morphologically similar areas of a single tumor were analyzed. We conclude from this study that intratumoral heterogeneity of HER-2/neu gene amplification is a demonstrable but relatively uncommon occurrence. For invasive mammary carcinomas, the accurate assessment of HER-2/neu status by fluorescence in-situ hybridization analysis is not significantly confounded by intratumoral heterogeneity of HER-2/neu gene amplification in individual tumors.
Evolutionary history of a complex adaptation: Tetrodotoxin resistance in salamanders

Understanding the processes that generate novel adaptive phenotypes is central to evolutionary biology. We used comparative analyses to reveal the history of tetrodotoxin (TTX) resistance in TTX‐bearing salamanders. Resistance to TTX is a critical component of the ability to use TTX defensively but the origin of the TTX‐bearing phenotype is unclear. Skeletal muscle of TTX‐bearing salamanders (modern newts, family: Salamandridae) is unaffected by TTX at doses far in excess of those that block action potentials in muscle and nerve of other vertebrates. Skeletal muscle of non‐TTX‐bearing salamandrids is also resistant to TTX but at lower levels. Skeletal muscle TTX resistance in the Salamandridae results from the expression of TTX‐resistant variants of the voltage‐gated sodium channel NaV 1.4 (SCN4a). We identified four substitutions in the coding region of salSCN4a that are likely responsible for the TTX resistance measured in TTX‐bearing salamanders and variation at one of these sites likely explains variation in TTX resistance among other lineages. Our results suggest that exaptation has played a role in the evolution of the TTX‐bearing phenotype and provide empirical evidence that complex physiological adaptations can arise through the accumulation of beneficial mutations in the coding region of conserved proteins.
Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System1

ABSTRACT Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP−/−) exhibit a gestational hypertensive phenotype. In the current study, female ANP+/+ and ANP−/− mice were mated with ANP+/+ males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP+/+ and ANP−/− dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT1a genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.
Relating RFID implementation critical success factors to organizational strategy types: An empirical study

Radio frequency identification (RFID) is one of the most anticipated technologies in the manufacturing industry. It gives benefits like real-time asset tracking, increase in product visibility, and reduction in product theft and inventory level, which gives a competitive advantage to the organization. In order to reap the full benefits from RFID implementation, it is required to successfully implement the RFID system. There are a number of factors which are critically important for a successful implementation of a RFID project. This study establishes a framework for the relationship between RFID implementation critical success factors (ICSFs) and organizational strategy types and empirically tests the relationship between RFID ICSFs and organizational strategy types. The results show that ICSFs which are out of organizational control have an almost similar influence on all the organizational strategy types, but the impact of other ICSFs depends on organizational strategy types. We have found out that majority of RFID ICSFs have more impact on innovators and prospectors than defenders. 80% of our hypotheses that constitute the theoretical framework are supported by the empirical data collected from the organizations which have implemented RFID.
Down syndrome, drug metabolism and chromosome 21

It has been recognized that chromosomal abnormalities in childhood leukemia, are linked to both leukemogenesis and segregate patients into prognostic treatment groups. This is best exemplified in cases of children with Down syndrome (DS), who have significantly higher risks of developing leukemia compared to non‐DS children and distinctive treatment outcomes, particularly in cases of acute myeloid leukemia (AML). The high event‐free survival (EFS) rates of DS AML patients and in particular, patients with megakaryocytic leukemia (AMkL), at least in part reflects an increased sensitivity to cytosine arabinoside (ara‐C) secondary to increased expression of the chromosome 21‐localized gene, cystathionine‐β‐synthase, and potentially global mechanisms which increase the susceptibility of cells to undergo apoptosis. Somatic mutations of the X‐linked transcription factor gene, GATA1, have been detected uniformly and exclusively in DS AMkL cases, which may lead to altered expression of GATA1 target genes and alter the metabolism of drugs including ara‐C. Hyperdiploid acute lymphoblastic leukemia (ALL) cells with extra copies of chromosome 21, generate higher levels of the active methotrexate (MTX) metabolite, MTX polyglutamates. This is on account of increased intracellular transport of MTX via the reduced folate carrier (RFC) whose gene is localized to chromosome 21 and may also account for the increased MTX‐associated toxicity of DS ALL patients. Microarray technology should lead to the identification of additional gene targets linked to the treatment response of specific cytogenetic leukemia subgroups. © 2004 Wiley‐Liss, Inc.
Measuring Creativity for Innovation Management

Identifying the extent and nature of the creativity of new products is a key for innovation management. The revised Creative Solution Diagnosis Scale (CSDS) is a 27-item scale based on a theoretical model of functional creativity, consisting of five main criteria: Relevance & Effectiveness, Problematization, Propulsion, Elegance and Genesis. The CSDS offers potential for differentiated assessments of product creativity as part of the larger process of innovation. Non-expert judges rated a series of mousetrap designs using a 30-item version of the CSDS. Confirmatory factor analysis revealed a simple structure that corresponded closely to the a priori theoretical model of functional creativity. The untrained judges were able to use the scale with a high degree of reliability and internal consistency. The scale offers a tool for managing innovation, especially for stimulating creativity and diagnosing the creativity of products.
The Combining Sites of Anti-lipid A Antibodies Reveal a Widely Utilized Motif Specific for Negatively Charged Groups*

Lipopolysaccharide dispersed in the blood by Gram-negative bacteria can be a potent inducer of septic shock. One research focus has been based on antibody sequestration of lipid A (the endotoxic principle of LPS); however, none have been successfully developed into a clinical treatment. Comparison of a panel of anti-lipid A antibodies reveals highly specific antibodies produced through distinct germ line precursors. The structures of antigen-binding fragments for two homologous mAbs specific for lipid A, S55-3 and S55-5, have been determined both in complex with lipid A disaccharide backbone and unliganded. These high resolution structures reveal a conserved positively charged pocket formed within the complementarity determining region H2 loops that binds the terminal phosphates of lipid A. Significantly, this motif occurs in unrelated antibodies where it mediates binding to negatively charged moieties through a range of epitopes, including phosphorylated peptides used in diagnostics and therapeutics. S55-3 and S55-5 have combining sites distinct from anti-lipid A antibodies previously described (as a result of their separate germ line origin), which are nevertheless complementary both in shape and charge to the antigen. S55-3 and S55-5 display similar avidity toward lipid A despite possessing a number of different amino acid residues in their combining sites. Binding of lipid A occurs independent of the acyl chains, although the GlcN-O6 attachment point for the core oligosaccharide is buried in the combining site, which explains their inability to recognize LPS. Despite their lack of therapeutic potential, the observed motif may have significant immunological implications as a tool for engineering recombinant antibodies.
Left ventricular hypertrophy: reduction of blood pressure already in the normal range further regresses left ventricular mass

Objective: Left ventricular hypertrophy (LVH) confers high cardiovascular risk. Regression of LVH reduces risk. Patients with blood pressure in the normal range and LVH are common. We investigated whether further reduction in blood pressure would further regress LVH. Methods: 51 subjects with blood pressure in the normal range and echocardiographic left ventricular hypertrophy were randomly assigned to active treatment (antihypertensive medication) or placebo in a ratio of 2:1. The aim was to maintain office systolic blood pressure at 10 mm Hg less than baseline in the active arm and at baseline level in the placebo arm. Cardiac magnetic resonance imaging was used to measure change in left ventricular mass index over 12 months. Results: 35 subjects completed the study (active 23: placebo 12). Average mean baseline office systolic blood pressure was 122 (SD 9) mm Hg in the active group and 124 (9) mm Hg in the placebo group (p = 0.646). The mean baseline left ventricular mass index was 65.88 (11.87) g/m2 in the active group and 59.16 (11.13) g/m2 in the placebo group (p = 0.114). The mean difference between baseline and end of study office systolic blood pressure was −9.33 (8.56) mm Hg in the active group and −0.08 (9.27) mm Hg in the placebo group (p = 0.007). The mean change in left ventricular mass index was −4.68 (7.31) g/m2 in the active group and +1.97 (6.68) g/m2 in the placebo group (p = 0.014). Conclusions: Reduction in office systolic blood pressure, already in the normal range, of approximately 9 mm Hg, leads to a reduction in left ventricular mass. Further work is required to see if this also leads to a reduction in cardiovascular events. Trial registration number: ISRCTN48331653.
Cholangioscopic findings in bile duct tumors.

BACKGROUND Cholangioscopy has been used in the treatment of bile duct stones and the diagnosis of various bile duct tumors. However, the cholangioscopic characteristics of the various types of bile duct tumors have not been clearly described. We analyzed the results of cholangioscopic examinations and classified the findings according to tumor histology. METHODS Cholangioscopic findings from 111 patients with benign or malignant bile duct tumors were reviewed. The mucosal changes, the presence of neovascularization, and the patterns of luminal narrowing were analyzed and compared with the histologic diagnosis. RESULTS Bile duct adenocarcinoma can be classified into 3 different types according to the cholangioscopic findings: nodular, papillary, and infiltrative. Bile duct adenoma, hepatocellular carcinoma and other types of bile duct cancer such as mucin-hypersecreting cholangiocarcinoma, biliary cystadenocarcinoma, and squamous cell carcinoma also presented unique cholangioscopic characteristics. CONCLUSIONS Bile duct tumors exhibit characteristic cholangioscopic findings and cholangioscopy seems to be useful for differential diagnosis.
Developmental Regulation of Nitric Oxide Synthase Expression in Rat Skeletal Bone

Nitric oxide (NO) has been implicated in bone growth and remodeling by studies showing that inhibition of NO‐synthase (NOS) activity retards normal gain in bone mineral density both during skeletal development and after sexual maturity. In the present study, we aimed to assess the level of expression and cellular localization of the three NOS isoforms during skeletal bone development from neonatal to sexual maturity in female Wistar rats. Reverse transcription polymerase chain reaction (RT‐PCR) was used to analyze the presence of NOS1 (neuronal), NOS2 (inducible), and NOS3 (endothelial) transcripts in femoral bone from neonatal, 4‐, 8‐, and 12‐week‐old rats. RT‐PCR amplified NOS1, NOS2, and NOS3 transcripts of 472‐, 807‐, and 289‐bp, respectively. There were no detectable differences in the levels of NOS1 mRNA between the groups; however, NOS2 mRNA was more abundant in the neonatal group compared with 4‐, 8‐, and 12‐week groups. Expression of NOS1 protein could not be detected in bones by either Western blotting or immunocytochemistry in any of the age groups investigated. Western blots for NOS2 revealed expression in the neonatal group only and it was not detected in any of the older age groups. Immunostaining for NOS2 was also most evident in the neonatal group and was localized specifically to trabecular osteoblasts and osteoclasts. In all age groups studied, NOS3 mRNA and protein were found in bone‐resorbing osteoclasts, cuboidal active osteoblasts, and osteocytes. Semiquantitative RT‐PCR provided evidence of down‐regulation of NOS3 transcripts during the skeletal development. This was confirmed using in situ hybridization, which showed higher expression in neonatal and 4‐week groups than in other groups. Western blots and counting the ratio of trabecular osteoblasts that were NOS3 immunoreactive showed parallel down‐regulation of NOS3 protein during skeletal development. Taken together, these data show that there is regulation of NOS2 and in particular NOS3 expression during skeletal development and this may be significant to trabecular bone growth and remodeling.