Miracle-dz/UniFAR-FTUs huggingface dataset:
Neoplastic characteristics of the DNA found in the plasma of cancer patients.

About one third of patients with various malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in normal controls. Using the test established by one of us (M.B.), which is based on decreased strand stability of cancer cell DNA, we have found that several plasma DNA originate from cancer cells.
Loss of chromosome Y in blood, but not in brain, of suicide completers

Men have a higher rate of completed suicide than women, which suggests that sex chromosome abnormalities may be related to the pathophysiology of suicide. Recent studies have found an aberrant loss of chromosome Y (LOY) in various diseases; however, no study has investigated whether there is an association between LOY and suicide. The purpose of this study was to determine whether LOY occurs in men who completed suicide. Our study consisted of 286 male Japanese subjects comprised of 140 suicide completers without severe physical illness (130 post-mortem samples of peripheral blood and 10 brains) and 146 age-matched control subjects (130 peripheral blood samples from healthy individuals and 16 post-mortem brains). LOY was measured as the chromosome Y/chromosome X ratio of the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX). Regression analyses showed that LOY in the blood of suicide completers was significantly more frequent than that found in controls (odds ratio = 3.50, 95% confidence interval = 1.21–10.10), but not in the dorsolateral prefrontal cortex (DLPFC) region of brain. Normal age-dependent LOY in blood was found in healthy controls (r = -0.353, p < 0.001), which was not seen in suicide completers (r = -0.119, p = 0.177). DLPFC tissue had age-dependent LOY (B = -0.002, p = 0.015), which was independent of phenotype. To our knowledge, this is the first study demonstrating that LOY in blood is associated with suicide completion. In addition, our findings are the first to also indicate that age-dependent LOY may occur not only in blood, but also in specific brain regions.
Nanocomposites of EVA/polystyrene nanoparticles/montmorillonite

Nanocomposites of ethylene vinyl acetate (EVA) copolymer, polystyrene (PS) nanoparticles, and montmorillonite (MMT) were prepared by latex compounding. The nanolatex of PS was synthesized by differential microemulsion polymerization and then blended with EVA at EVA/PS dry weight ratios of 90/10, 80/20, and 70/30, before mixing with MMT at 1, 3, or 5 parts per hundred rubbers. The latex composite mixtures were cast on a glass mold and compressed into thin sheets. The nanocomposites were characterized for their structures, mechanical properties, and thermal behaviors. The tensile strength, Young’s modulus, storage modulus, and thermal stability were all improved with the incorporation of MMT, although the extent of such depended upon and varied with the EVA/PS ratio of the nanocomposite.
Non-enhanced versus low-dose contrast-enhanced renal magnetic resonance angiography at 7 T: a feasibility study

Background Considering the currently reported association between a repetitive application and cumulative dosage of Gadolinium (Gd)-based contrast agents and Gd-deposition in brain tissue as well as the risk for the advent of nephrogenic systemic fibrosis (NSF), techniques allowing for a dose reduction become an important key aspect aside from non-enhanced magnetic resonance angiography (MRA) techniques. Thus, this study was focused on the reduction and/or complete omission of contrast agent for renal MRA at 7T. Purpose To evaluate the performance of time-of-flight MRA versus low-dose contrast-enhanced (CE) renal MRA at 7T. Material and Methods Ten healthy volunteers were examined on a 7T MR system comprising a TOF MRA and three-dimensional (3D) fast low angle shot spoiled gradient-echo sequence (FLASH) MRA after administration of one-quarter of clinical dose of gadobutrol. Qualitative image analysis was performed including overall image quality, artery delineation and presence of artifacts. Contrast ratio (CR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the renal arteries were calculated. Results TOF MRA and low-CE MRA achieved comparable overall ratings, with slightly superior delineation of the main renal arteries in TOF MRA (TOF = 3.10 ± 0.75, low-CE = 2.95 ± 0.75). Segmental branches outside and inside the parenchyma were delineated significantly better on TOF MRA. Quantitative analysis demonstrated the superiority of TOF MRA, yielding higher scores for CR, SNR, and CNR. Conclusion The initial results of our study demonstrate the feasibility and comparable diagnostic performance of TOF and low-dose CE renal MRA at 7T.
Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

CONTEXT In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. OBJECTIVE To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. DESIGN A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. SETTING Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. PARTICIPANTS A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects MAIN OUTCOME MEASURES Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. RESULTS Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. CONCLUSIONS Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.
Should Sponsors and DSMBs Share Interim Results Across Trials?

Increasing numbers of multinational clinical trials have generated new ethical obligations of research sponsors and their DSMBs. Although sponsors and DSMBs clearly have ethical obligations to protect subjects in their trials, future patients, and the integrity of their trial, the obligations they have to protect subjects in other trials have been overlooked. When interim results from clinical trials can significantly affect the conduct of other trials and the welfare of the subjects in those trials, sponsors and DSMBs may have obligations to disclose results to the relevant parties. We propose that sponsors and DSMBs routinely work together in advance to develop a plan for disclosing relevant information in cases where it is necessary to protect the welfare of subjects in other trials. Channels of communication between sponsors, DSMBs, IRBs, and others involved in similar and concurrent trials will better protect both research participants and the integrity of the research enterprise.
Electrical functionality of inkjet-printed silver nanoparticle conductive tracks on nanostructured paper compared with those on plastic substrates

In this study, we use nanostructured paper made from cellulose nanofibres (CNFs) as a flexible printable material for inkjet-printing of silver nanoparticle (AgNP) ink. The nanostructured paper is prepared by sheet casting of 10–40 nm wide mechanically fibrillated aqueous CNFs in suspension. The resulting nanostructured paper, in the form of densely packed laminar layers, has low surface roughness (40 ± 2.3 nm) and a nanoporous network structure. This unique surface feature helps the ink vehicles to permeate through the nanopores and also aids absorption along the fibril direction parallel to the surface while retaining the silver nanoparticles on the surface to compete with the initial spreading and final evaporation processes. As a result, well-defined inkjet-printed AgNP conductive tracks (∼400 μm wide) on nanostructured paper show lower electrical resistance (1.57 ± 0.09 Ω cm−1) than those on commonly used plastics, including polyimide (PI, 2.07 ± 0.17 Ω cm−1) and poly(ethylene naphthalate) (PEN, 2.10 ± 0.16 Ω cm−1), at a moderate curing temperature of 150 °C for 1 h. The inkjet-printed conductive tracks on nanostructured paper also show better electrical performance during and after folding than those printed on plastic substrates, such as PI, and exhibit stable electrical properties throughout a test period of 1000 h in a moisture resistance test (85 °C and 85% relative humidity). The better overall electrical performance compared with that of tracks on plastic substrates highlights the potential of genuinely nanostructured paper as a printing substrate for flexible printed electronics.
On the design of multi-dimensional irregular repeat-accumulate lattice codes

We propose and design the lattice codes with finite lattice constellations based on multi-dimensional (more than two dimensions) lattice partitions. The codes are constructed from non-binary irregular repeat-accumulate (IRA) codes. Most notably, we propose a novel encoding structure to ensure that the decoder's messages exhibit permutation-invariance and symmetry properties. With these two properties, the densities of the messages in our iterative decoder can be well modeled by Gaussian distributions described by a single parameter. Under the Gaussian approximation, extrinsic information transfer charts for our multi-dimensional IRA lattice codes are developed and used for analysing the convergence behaviour and optimising the decoding threshold. Simulation results show that our proposed lattice codes outperform the previously designed lattice codes with two-dimensional lattice partitions.
Multivalency effects of hemagglutinin component of type B botulinum neurotoxin complex on epithelial barrier disruption

Hemagglutinin (HA) is one of the components of botulinum neurotoxin (BoNT) complexes and it promotes the absorption of BoNT through the intestinal epithelium by at least two specific mechanisms: cell surface attachment by carbohydrate binding, and epithelial barrier disruption by E‐cadherin binding. It is known that HA forms a three‐arm structure, in which each of three protomers has three carbohydrate‐binding sites and one E‐cadherin‐binding site. A three‐arm form of HA is considered to bind to these ligands simultaneously. In the present study, we investigated how the multivalency effect of HA influences its barrier‐disrupting activity. We prepared type B full‐length HA (three‐arm form) and mini‐HA, which is a deletion mutant lacking the trimer‐forming domain. Size‐exclusion chromatography analysis showed that mini‐HA exists as dimers (two‐arm form) and monomers (one‐arm form), which are then separated. We examined the multivalency effect of HA on the barrier‐disrupting activity, the E‐cadherin‐binding activity, and the attachment activity to the basolateral cell surface. Our results showed that HA initially attaches to the basal surface of Caco‐2 cells by carbohydrate binding and then moves to the lateral cell surface, where the HA acts to disrupt the epithelial barrier. Our results showed that the multivalency effect of HA enhances the barrier‐disrupting activity in Caco‐2 cells. We found that basal cell surface attachment and binding ability to immobilized E‐cadherin were enhanced by the multivalency effect of HA. These results suggest that at least these two factors induced by the multivalency effect of HA cause the enhancement of the barrier‐disrupting activity.
Preparation and Characterization of Biodegradable β-TCP-Based Composite Microspheres as Bone Tissue Engineering Scaffolds

Since a small globular particle was first used as support for three-dimensional (3D) growth of anchorage-dependent cells in suspended cultures, a variety of microspheres as tissue engineering scaffolds have been developed. In this paper, β-TCP and chitosan were selected as the components of microspheres due to their biodegradability and osteogenic properties. The biodegradable β-TCP/chitosan composite microspheres were prepared by a solid-in-water-in-oil (s/w/o) emulsion cross-linking method in this paper. The size distribution, surface morphology, and microstructure of the microspheres were evaluated. Scanning electron microscopy revealed that the size of the microspheres with good spherical morphology was distributed in the range of 50~200μm. In vitro immersion experiments were carried out to evaluate the degradability of the microspheres, and the results demonstrated that the chitosan/β-TCP composite microspheres were potential materials as tissue engineering scaffolds for bone repair.
Toxicity assessment of technetium-labeled human beta-defensin-3 in CD 1 mice

Objective: Human beta-defensin-3 (HBD-3) is an antimicrobial peptide which is up-regulated during 99m in ammation. Based on the previously demonstrated capacity of technetium-99m ( Tc) labelled HBD-3 of distinguishing infection from in ammation in rats, we have decided to collect information on the potential toxicity of the tracer in view of its possible use for imaging in humans. Materials and Methods: 99m Recombinant HBD-3 underwent labeling with Tc. The CD1 mice were selected as standard rodent species. Ten mice, 5 male and 5 female, were subjected to physical examination and housed in a dedicated room in 5 per cage. After 9 days pre-test period, all mice were weighted for dose adjustment and received 99m intravenously 6mcg/mouse of Tc-HBD-3. Mortality was recorded daily, while body weight was registered once a week. Clinical observation of animals was performed daily for sickness symptoms due to 99m the drug treatment. At day 19 a second dose of 6mcg/mouse Tc-HBD-3, was administered. Twenty-four hours after the second dose (day 20) the animals were euthanized. A piece of liver, kidneys, heart and lungs was collected for histopathological analysis. Results: Our results showed that the labelled-HBD-3 dose did not induce signi cant toxicity in mice. Of course these parameters were not su cient to authorize use in humans. This non-toxic dose of HBD-3 when translated from animals to humans resulted in an equivalent dose of approximately 25 times higher than that needed for imaging. Conclusion: Our non toxicity data of 99m using Tc-beta-defensin-3 in mice o er a further indication in favour of the clinical use of this radiopharmaceutical in all cases where discrimination between infection and in ammation is needed. Hell J Nucl Med 2015; 18(3): 233-237 Epub ahead of print: 18 November 2015 Published online: 5 December 2015
Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy.

BACKGROUND We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. METHODS DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach. RESULTS Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) < 0.05]. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight. CONCLUSIONS We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome.
Clinical significance of central corneal thickness in the management of glaucoma.

OBJECTIVE To evaluate the effect of central corneal thickness determination on the clinical management of patients with glaucoma and glaucoma suspect. METHODS A cross-sectional retrospective study was performed on 188 consecutive patients. Mean ultrasound pachymetry measurements of central corneal thickness and corresponding Goldmann applanation tonometry measurements were obtained. Intraocular pressures (IOPs) were corrected using linear and mathematical (Orssengo-Pye) algorithms. Measurement-significant outcomes were defined as an IOP adjustment of 1.5 mm Hg or greater and outcomes-significant results as an IOP adjustment of 3.0 mm Hg or greater. Changes in therapy such as the use of eyedrops and addition or cancellation of laser therapy or surgery were then noted for those individuals with measurement- or outcomes-significant changes. RESULTS Using the linear correction scale, 105 (55.9%) of 188 patients had at least a measurement-significant adjustment in their IOP measurements: 67 (35.6%) had adjustments between 1.5 and 3.0 mm Hg, while 38 (20.2%) had an outcomes-significant IOP adjustment (> or =3.0 mm Hg). Among the 188 patients, 16 (8.5%) had a change in eyedrop therapy, 4 (2.1%) had a change regarding laser therapy, and 6 (3.2%) had a change in the decision regarding glaucoma surgery. Using the exponential correction (Orssengo-Pye) scale, similar percentages were obtained. CONCLUSION Pachymetry-measured central corneal thickness has a significant effect on the clinical management of patients with glaucoma and glaucoma suspect.
Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat.

In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.
Morphological characterization of Langmuir–Blodgett films from polyaniline and a ruthenium complex (Rupy): influence of the relative concentration of Rupy

We report on the use of dynamic scale theory and fractal analyses in a study of the growth stages of Langmuir–Blodgett (LB) films of polyaniline and a neutral biphosphinic ruthenium complex, namely mer-[RuCl3 (dppb)(py)] (dppb = 1,4-bis(diphenylphosphine)buthane, py = pyridine), Rupy. The LB films were deposited onto indium-tin-oxide substrates and characterized with atomic force microscopy. From the granular morphology exhibited by the films one could infer growth processes inside and outside the grains. Growth outside was found to follow the Kardar–Parisi–Zhang model, with fractal dimensions of about 2.7. As one would expect, inside the grains the morphology is close to a Euclidian surface with fractal dimension of about 2.