Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of metaphase HR‐CGH and targeted chromosomal microarray analyses to genomic characterization of 116 patients with mental retardation and dysmorphic features

Recent advances in molecular cytogenetics enable identification of small chromosomal aberrations that are undetectable by routine chromosome banding in 5–20% of patients with mental retardation/developmental delay (MR/DD) and dysmorphism. The aim of this study was to compare the clinical usefulness of two molecular cytogenetic techniques, metaphase high‐resolution comparative genomic hybridization (HR‐CGH) and targeted array CGH, also known as Chromosomal Microarray Analysis (CMA). A total of 116 patients with unexplained mild to severe MR and other features suggestive of a chromosomal abnormality with apparently normal or balanced karyotypes were analyzed using HR‐CGH (43 patients) and/or CMA (91 patients). Metaphase HR‐CGH detected seven interstitial deletions (16.3%). Rare deletions of chromosomes 16 (16p11.2p12.1) and 8 (8q21.11q21.2) were identified. Targeted CMA revealed copy‐number changes in 19 of 91 patients (20.8%), among which 11 (11.8%) were clinically relevant, 6 (6.5%) were interpreted as polymorphic variants and 2 (2.1%) were of uncertain significance. The changes varied in size from 0.5 to 12.9 Mb. In summary, our results show that metaphase HR‐CGH and array CGH techniques have become important components in cytogenetic diagnostics, particularly for detecting cryptic constitutional chromosome imbalances in patients with MR, in whom the underlying genetic defect is unknown. Additionally, application of both methods together increased the detection rates of genomic imbalances in the tested groups. © 2008 Wiley‐Liss, Inc.
Problem-Based Learning in Wind Energy Using Virtual and Real Setups

The use of wind energy is now an established fact, and many educational institutions are introducing this topic into their engineering studies. Problem-based learning (PBL), as a student-centered instructional approach, has contributed to important developments in engineering education over the last few years. This paper presents the experience of a problem-based learning approach within the context of teaching wind energy conversion systems for electricity generation at an Electrical and Electronic Master's degree level. Students were given the problem of finding the response of a wind turbine to a grid fault. Groups of three students worked on a cooperative learning project for 15 weeks, with the instructor providing resource assistance and information at all stages of the work. Two tools were designed to help the students: a virtual wind turbine simulator and a real wind turbine setup. Both experimental tools are described, and the results obtained by the students are discussed. The results show that the students valued both tools and were able to address problems at a high cognitive level.
Gene expression silencing with ‘specific’ small interfering RNA goes beyond specificity – a study of key parameters to take into account in the onset of small interfering RNA off‐target effects

RNA‐mediated gene silencing (RNA interference) is a powerful way to knock down gene expression and has revolutionized the fields of cellular and molecular biology. Indeed, the transfection of cultured cells with small interfering RNAs (siRNAs) is currently considered to be the best and easiest approach to loss‐of‐function experiments. However, several recent studies underscore the off‐target and potential cytotoxic effects of siRNAs, which can lead to the silencing of unintended mRNAs. In this study, we used a low‐density microarray to assess gene expression modifications in response to five different siRNAs in various cell types and transfection conditions. We found major differences in off‐target signature according to: (a) siRNA sequence; (b) cell type; (c) duration of transfection; and (d) post‐transfection time before analysis. These results contribute to a better understanding of important parameters that could impact on siRNA side effects in knockdown experiments.
Multiple spells of in-patient treatment in a calendar year.

Starting on January 1, 1962, the Oxford Record Linkage Study (ORLS) set out to collect data about every birth, discharge from hospital, and death of persons giving an address in Oxford County Borough, Oxfordshire (except Henley), and the part of Berkshire which adjoins Oxford City, an area which on June 30, 1962, was estimated to have a population of 325,000. The material used in this analysis consists of the 22,525 completed in-patient spells which occurred in the calendar year 1962. An in-patient spell was defined as a period of in-patient treatment in a single hospital which was completed (i.e. by discharge home, death, transfer to another hospital, etc.) during the calendar year 1962. It follows that a proportion of the spells dealt with commenced before January 1, 1962, but these are offset by the absence from the series of spells commencing in 1962 which had not been completed by December 31, 1962. This definition is identical to that used in the Hospital In-patient Inquiry (1959 et seq.) and is synonymous with the term "discharge" used in that publication. The collection of data, which has been described elsewhere (Acheson, 1964; Acheson and Evans, 1964), was limited to the 29 National Health Service (NHS) hospitals within the boundaries of the area. Day cases, private and staff cases, and cases discharged from the maternity hospitals and from the local convalescent hospital are excluded from this analysis. The degree of ascertainment was checked against the number of in-patient soells notified to the Ministry of Health on Form SH3 and, when allowance was made for the exclusions, was found to amount to 94-3 per cent, of these notifications. The number of persons living in the area who were dis charged from NHS hospitals outside the area in 1962 is not known exactly, but was probably about 5 per cent. * Method
Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term ‘diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions.
Music causes deterioration of source memory: Evidence from normal ageing

Previous research has shown that music exposure can impair a wide variety of cognitive and behavioural performance. We investigated whether this is the case for source memory. Forty-one younger adults and 35 healthy elderly were required to retain the location in which pictures of coloured objects were displayed. On a subsequent recognition test they were required to decide whether the objects were displayed in the same location as before or not. Encoding took place (a) in silence, (b) while listening to street noise, or (c) while listening to Vivaldi's “Four Seasons”. Recognition always took place during silence. A significant reduction in source memory was observed following music exposure, a reduction that was more pronounced for older adults than for younger adults. This pattern was significantly correlated with performance on an executive binding task. The exposure to music appeared to interfere with binding in working memory, worsening source recall.
High gene copy number of epidermal growth factor receptor by fluorescence in situ hybridization is frequent in head and neck squamous cell carcinomas and associates with worse recurrence-free survival.

5502 Background: Epidermal growth factor receptor (EGFR) is expressed in 90-95% of head and neck squamous cell carcinoma (HNSCC). High EGFR gene copy number and activating mutations correlate with response and survival in lung cancer upon the treatment with EGFR tyrosine kinase inhibitors, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors and provide a rationale for combination therapy. METHODS Tumor samples were obtained from 47 patients and analyzed for increased EGFR copy numbers by fluorescence in situ hybridization (FISH) (Vysis/Abbot) (N = 47), by immunohistochemistry (IHC) using antibodies against EGFR, phospho-EGFR (Tyr1173) and phospho-AKT (Ser473) (N = 31), for activating mutations in EGFR exons 18, 19 and 21 (N = 29), and for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip (N = 18). Results from these assessments were tested for associations with patient characteristics and clinical endpoints. Univariate analysis was performed to test for differences in recurrence-free survival (RFS) and overall survival. RESULTS Twenty-six (63%) of 41 samples with FISH result demonstrated EGFR high polysomy and/or gene amplification (FISH+). The FISH(+) group did not differ from the FISH(-) group with regard to age, sex, race, tumor grade and site, disease stage, total EGFR, phospho-EGFR, or phospho-AKT, although the total EGFR protein score was close to significance (p = 0.10, Chi2-test for trend). The FISH(+) were associated with worse RFS, although this association did not reach significance (p = 0.057, Wilcoxon test). No activating EGFR point mutations were found. Using the FISH results as a supervising parameter, microarray data was interrogated and expression of genes involved in wnt signalling, cell motility, G-protein regulation and epithelial-mesenchymal transition pathways were found to be enhanced in the FISH(+) group (FDR <25%). CONCLUSIONS High gene copy number of EGFR by FISH is frequent in HNSCC and may be a poor prognosticator. This data suggests that FISH(+) may be a marker of clinical benefit upon EGFR inhibition in HNSCC and further investigation is indicated. [Table: see text].
Epiprofin Regulates Enamel Formation and Tooth Morphogenesis by Controlling Epithelial‐Mesenchymal Interactions During Tooth Development

The synchronization of cell proliferation and cytodifferentiation between dental epithelial and mesenchymal cells is required for the morphogenesis of teeth with the correct functional shapes and optimum sizes. Epiprofin (Epfn), a transcription factor belonging to the Sp family, regulates dental epithelial cell proliferation and is essential for ameloblast and odontoblast differentiation. Epfn deficiency results in the lack of enamel and ironically the formation of extra teeth. We investigated the mechanism underlying the functions of Epfn in tooth development through the creation of transgenic mice expressing Epfn under the control of an epithelial cell‐specific K5 promoter (K5‐Epfn). We found that these K5‐Epfn mice developed abnormally shaped incisors and molars and formed fewer molars in the mandible. Remarkably, ameloblasts differentiated ectopically and enamel was formed on the lingual side of the K5‐Epfn incisors. By contrast, ameloblasts and enamel were found only on the labial side in wild‐type mice, as Follistatin (Fst) expressed in the lingual side inhibits BMP4 signaling necessary for ameloblast differentiation. We showed that Epfn transfection into the dental epithelial cell line SF2 abrogated the inhibitory activity of Fst and promoted ameloblast differentiation of SF2 cells. We found that Epfn induced FGF9 in dental epithelial cells and this dental epithelial cell‐derived FGF9 promoted dental mesenchymal cell proliferation via the FGF receptor 1c (FGFR1c). Taken together, these results suggest that Epfn preserves the balance between cell proliferation and cytodifferentiation in dental epithelial and mesenchymal cells during normal tooth development and morphogenesis. © 2016 American Society for Bone and Mineral Research.
Evaluation of Current Biological Exposure Index for Occupational N, N-dimethylformamide Exposure From Synthetic Leather Workers

The aim of this study was (1) to investigate the correlation between external exposure to N, N-dimethylformamide (DMF) and urinary excretion of DMF and N-methylformamide; (2) to assess whether the correspondence between the current occupational exposure limit setting and recommended urinary biological exposure index is substantial; and (3) to evaluate whether coexposure to toluene, methyl ethyl ketone, and ethyl acetate has an effect on urinary excretion of DMF and N-methylformamide (NMF). Urinary DMF and NMF were significantly correlated (P < 0.01) with one another and also significantly correlated with airborne DMF (P < 0.01) over the range of 1.55 to 152.8 mg/m3. Urinary DMF can be considered a complementary marker for short-term exposure. Urinary concentration of NMF and DMF, corresponding to the 8-hour exposure to airborne DMF at 30 mg/m3, was estimated to 38.4 mg/L or 39.4 mg/g creatinine for NMF and to 0.92 mg/L or 0.96 mg/g creatinine for DMF.
Effects of thermal change and third-body media particle on wear behaviour of dental restorative composite materials

ABSTRACT The aim of this work was to examine the effect of thermal change cycle and the third-body media particle on the wear behavior of four different composite materials. All specimens were kept in distilled water for 1 week and determined Vicker’s hardness and surface roughness values before contact-free wear tests. Then contact-free wear test procedures were performed using a dual-axis chewing simulation. The mean volume loss of all specimens after the contact-free wear tests was determined with use non-contact 3D profilometer. In this study tested all composite materials showed significantly more volume loss when occurred thermal load than constant 37 °C irrespective of third-body media particle after contact-free chewing tests. It can be suggested in this work that the larger monomer and harder surface glass structure contained in the composite material causes more volume loss when occurred thermal change loading wear mechanism.
Large Scale-Free Network Organization is Likely Key for Biofilm Phase Transition

Non-linear Kuramoto model has been used to study synchronized or sync behavior in numerous fields, however, its application in biology is scare. Here, I introduce the basic model and provide examples where large scale small-world or scale-free networks are crucial for spontaneous sync even for low coupling strength. This information was next checked for relevance in living systems where it is now well-known that biological networks are scale-free. Our recent transcriptome-wide data analysis of Saccharomyces cerevisiae biofilm showed that low to middle expressed genes are key for scale invariance in biology. Together, the current data indicate that biological network connectivity structure with low coupling strength, or expression levels, is sufficient for sync behavior. For biofilm regulation, it may, therefore, be necessary to investigate large scale low expression genes rather than small scale high expression genes.
Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of either sodium borocaptate or boronophenylalanine with or without blood-brain barrier disruption.

The purpose of the present study was to determine whether the efficacy of boron neutron capture therapy could be enhanced by means of intracarotid (i.c.) injection of sodium borocaptate (BSH) or boronophenylalanine (BPA) with or without blood-brain barrier disruption (BBB-D). For biodistribution studies, F98 glioma-bearing rats were injected i.v. or i.c. with either BSH (30 mg of boron/kg of body weight) or BPA (24 mg of boron/kg of body weight) with or without mannitol-induced, hyperosmotic BBB-D and killed 2.5 h later. The highest tumor boron concentrations for BSH and BPA were attained following i.c. injection with BBB-D (48.6 and 94.0 microg/g, respectively) compared to i.c. (30.8 and 42.7 microg/g) and i.v. injection (12.9 and 20.8 microg). Using the same doses of BSH and BPA, therapy experiments were initiated 14 days after intracerebral implantation of F98 glioma cells. Animals were irradiated 2.5 h after i.v. or i.c. administration of the capture agent with or without BBB-D using a collimated beam of thermal neutrons at the Brookhaven Medical Research Reactor. The median survival times of rats given BSH or BPA i.c. were 52 and 69 days, respectively, for rats with BBB-D; 39 and 48 days for rats without BBB-D; 33 and 37 days for i.v. injected rats; 29 days for irradiated controls; and 24 days for untreated controls. i.c. injection of either BSH or BPA resulted in highly significant enhancement (P = 0.01 and P = 0.0002, respectively) of survival times compared to i.v. injection, and this was further augmented by BBB-D (P = 0.02 and P = 0.04, respectively) compared to i.c. injection. Normal brain tissue tolerance studies were carried out with non-tumor-bearing rats, which were treated in the same way as tumor-bearing animals. One year after irradiation, the brains of these animals showed only minimal radiation-induced changes in the choroid plexus, but no differences were discernible between irradiated controls and those that had BBB-D followed by i.c. injection of either BSH or BPA. Our data clearly show that the route of administration, as well as BBB-D, can enhance the uptake of BSH and BPA, and, subsequently, the efficacy of boron neutron capture therapy.
Magnetic Resonance-guided Laser-induced Thermotherapy in Patients With Oligonodular Hepatocellular Carcinoma: Long-term Results Over a 15-year Period

Goals: To prospectively evaluate the therapeutic potential of magnetic resonance (MR)-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. Study: A total of 113 patients with 175 intrahepatic lesions were treated with MR-guided LITT. The Nd-YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. Survival data were calculated using the Kaplan-Meier method. Results: All patients tolerated the procedure well under local anesthesia. The total procedure time was 90 minutes. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization of the extension of laser-induced changes and their relationship to the neighboring anatomy. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application; larger lesions were treated with a dual, triple, and quadruple simultaneous application. In 98% of the patients we achieved a complete necrosis of the tumor and up to 5 mm of safety margin. The mean survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 4.9 years (95% confidence interval, 3.6, 5.1). The median survival rate for all patients, with calculation started on the date of diagnosis of the HCC nodules treated with LITT, was 3.5 years (95% confidence interval, 2.7, 4.2). One-year survival was 95%; 2-year survival 72%, 3-year survival 54%; and 5-year survival 30%. Conclusions: In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure.
500 HIPPOCAMPUS DYSFUNCTION MAY EXPLAIN SYMPTOMS OF FIBROMYALGIA SYNDROME

In fibromyalgia (FM) a combination of symptoms frequently exists, including impaired cognition, memory changes, widespread pain, and disrupted sleep rhythm, with no sufficient explanations for these bizarre symptoms. Many theories have been developed and it is still not clear whether FM is a chronic stress syndrome caused by many factors, including society or just a part of the spectrum of chronic pain. FM is the second most common rheumatic disorder behind osteoarthritis and, though still widely a puzzling syndrome, is now considered to be a central nervous system disorder, which is responsible for amplified and intensive pain. Over the years, three main ideas of hippocampal function have dominated the literature: Response inhibition, episodic memory, and spatial cognition. Given that the hippocampus plays integral roles in memory, cognition, and sleep regulations the later functions may be influenced by prolonged stress know to exist in FM syndrome. Moreover the hippocampus is an integral component of the limbic system, and as such may contribute to the negative affect and avoidance motivation experienced during pain experience and chronic stress. The aim of the current review is to focus on the physiological roles of the hippocampus and its relation to symptoms production in FM syndrome.
Computational prediction and characterisation of ubiquitously expressed new splice variant of Prkaca gene in mouse

Prkaca gene of mouse encodes for a cAMP dependent protein kinase catalytic alpha subunit. PKA occurs naturally as a 4‐membered structure having two regulatory (R) and two catalytic (C) subunits each encoded by separate gene. Alternatively spliced two transcript variants are known for the Prkaca gene, which encode for two isoforms of PKA C‐subunits, namely Cα1 and Cα2. These isoforms arise as a result of alternative splicing of the first coding exon with the internal exons. We have identified a new transcript variant using combinatorial approach of bioinformatics and molecular biology techniques involving RT‐PCR, semi‐nested PCR and sequencing. The new transcript variant encoding Cα3 isoform has N‐terminus that differs from Cα1 and Cα2 isoforms. Cα3 isoform also arise as a result of alternative splicing of first coding exon with the internal exon. Newly identified transcript is expressed ubiquitously in different tissues examined.