julilili42/papers huggingface dataset:
O3‐12‐01: ASSOCIATION BETWEEN SERUM NEUROFILAMENT LIGHT AND ESTABLISHED WHITE MATTER NEUROIMAGING MARKERS IN AUTOSOMAL DOMINANT ALZHEIMER DISEASE
2019-07-01

White matter (WM) alterations are a common feature of Alzheimer Disease (AD), typically detected in vivo with diffusion tensor imaging (DTI). Blood-based neurofilament light (NfL) is an emerging biomarker for monitoring neurodegeneration. While NfL is thought to reflect damage to myelinated axons, minimal work has directly examined this association. The objective of this study was to examine the cross-sectional and longitudinal relationship between WM neuroimaging markers and serum NfL levels. Individuals enrolled in the Dominantly Inherited Alzheimer Network (DIAN; 117 mutation carriers (MC) and 84 non-carriers (NC)) completed a blood draw and MRI. SIMOA technology was used to measure NfL in serum. WM integrity measures examined included fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. Using tract-based spatial statistics we compared the association between NfL and WM metrics in MC and NC, adjusting for baseline age and sex. To examine tract-specific associations, atlas-based fiber tract values for WM measures were extracted and used as regions of interest (ROI) in a series of linear mixed effect models (LME). A subset (N=42) of MC had longitudinal NfL and MRI data (mean follow-up 2.1 yrs; range:1.0−4.4 yrs). LMEs were performed to examine the longitudinal association between the rate of change in serum NfL and change in fractional anisotropy and mean diffusivity in the posterior corpus callosum (PCC). There was a significant interaction between mutation status and NfL on WM metrics. Specifically, in MC, elevated NfL was positively associated with mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy throughout the brain (Figure 1). There were no relationships between NfL and WM metrics in NC. This same pattern was repeated in the ROI analyses (Figure 2). Rate of change in NfL was associated with rate of change in fractional anisotropy and mean diffusivity in the PCC (p=7.35e-05 and p=7.58e-04, for fractional anisotropy and mean diffusivity, respectively; Figure 3).
YBa2Cu3O7 and Nb NanoSQUIDs for the Investigation of Magnetization Reversal of Individual Magnetic Nanoparticles
2019-07-01

We report on the fabrication, performance and application of sensitive YBa2Cu3O7 (YBCO) and Nb nanoSQUIDs to magnetization reversal measurements of individual magnetic nanoparticles. The YBCO SQUIDs are based on grain boundary Josephson junctions and are patterned in a single layer of epitaxially grown YBCO films by Ga focused ion beam milling. The Nb SQUIDs contain sandwich-type Josephson junctions with normal conducting HfTi barriers; they are fabricated with a multilayer technology that includes patterning by e-beam lithography and a combination of milling techniques and chemical-mechanical polishing. Due to the small inductance of the SQUID loops, ultralow white flux noise at 4.2 K can be achieved, which yields spin sensitivities of down to a few Bohr magnetons per unit bandwidth for a magnetic nanoparticle placed at 10 nm distance to the SQUID loop.
P4‐310: ALTERATIONS OF INTRINSIC CONNECTIVITY IN POSTERIOR DEFAULT MODE NETWORK ACROSS AT RISK STAGES OF ALZHEIMER'S DEMENTIA
2019-07-01

Altered intrinsic connectivity within the default mode network (DMN) has been frequently observed in patients with Alzheimer's disease (AD) as well as in its at risk stages such as mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Recent studies showed that DMN can be further segregated into several sub-networks. It is unclear whether the intrinsic connectivity within these sub-networks is altered in individuals with AD, MCI and SCD. T1 images and resting state fMRI images of 301 subjects (28 AD, 48 MCI, 98 SCD, and 127 healthy controls) were obtained from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia (DELCODE) Study (mean age ± S.D. = 70.5 ± 5.7 years). Preprocessing of the functional MRI images was performed using SPM12 with standardized procedures including DARTEL normalization. The functional data were then decomposed into 75 independent components (ICs) using the GIFT toolbox. Meaningful ICs including sub-networks of DMN were selected via spatial correlation using an online template (Allen et al., 2011). Differences in functional connectivity strength of all ICs among the four groups were calculated using one-way ANOVA implemented in SPM12. Twenty-three meaningful ICs including three sub-networks of DMN emerged via spatial correlation. Significant gradient changes (HC > SCD > MCI > AD) in the functional connectivity were found in bilateral precuneus (pFWE=0.012) and posterior cingulate cortex (PCC) (pFWE=0.002) within the posterior DMN.
Correction to: Engineering Tissues from Induced Pluripotent Stem Cells by Loskill P and Huebsch N. Tissue Eng Part A 2019;25(9–10):707–710. DOI: 10.1089/ten.tea.2019.0118
2019-07-01

In the May 2019 issue of Tissue Engineering: Part A (vol. 25, no. 9-10; 707-710) the article entitled "Engineering Tissues from Induced Pluripotent Stem Cells" by Loskill and Huebsch requires correction.
Abstract 4377: Liver X receptor mediated lipotoxicity represents a treatment option for liver cancer
2019-07-01

Solid tumors evolve significant changes in metabolic pathways during development by virtue of their specific biosynthetic demands, their particular microenvironment and the potential occurrence of toxic metabolites such as reactive oxygen species. However, the development of cancer treatment approaches that are based on the inhibition of biosynthetic routes is impaired due to the high plasticity of metabolic networks, e.g. resulting in activation of compensatory pathways or in an increased exchange of metabolites between cancer cells and the tumor environment. Therefore, such therapies could not be translated into efficient clinical applications so far.Here we show that an enhanced lipogenesis, triggered by a pharmacological activation of the Liver X receptor (LXR), represents a new therapeutic strategy for the treatment of liver carcinoma (HCC). A combination of LXR mediated fatty acid synthesis and concomitant Raf suppression results in oxidative stress, induction of a critical ER stress response and subsequently in apoptosis of different murine and human liver cancer cells. Our mechanistic studies identified Raf as an important regulator of lipid metabolism in liver cancer. We found that Raf-1 directly interacts with Stearoyl-CoA desaturase-1 (Scd1), the central enzyme for the conversion of saturated into mono-unsaturated fatty acids and thereby maintains Scd1 protein stability in HCC cells. Thus, inhibition of Raf by Sorafenib diminished Scd1 protein abundance leading to toxic accumulation of saturated fatty acids and metabolic stress in cancer cells under sustained lipogenesis. Treatment studies in autochthonous liver cancer mouse models and xenograft models of human HCC revealed that a combinatorial therapy, consisting of the LXR agonist T0901317 and Sorafenib is highly potent to suppress liver cancer development and to extend the survival of tumor bearing animals. Such a therapy was efficient against hepatic neoplasia with different metabolic phenotypes and well tolerated by mice, even by animals that already suffer from a fatty liver disease.Taken together, we here propose a pharmacologically induced accumulation of toxic metabolites in cancer cells as a new strategy for efficient metabolic targeting of therapy refractory solid tumors.Citation Format: Ramona Rudalska, Jule Harbig, Marteinn Snaebjoernsson, Lyudmyla Taranets, Florian Heinzmann, Stefan Zwirner, Wei Ciu Hu, Thales Kronenberger, Tae-Won Kang, Antti Poso, Stefan Laufer, Mathias Rosenfeldt, Nisar P. Malek, Bernd Pichler, Nikita Popov, Almut Schulze, Lars Zender, Daniel Dauch. Liver X receptor mediated lipotoxicity represents a treatment option for liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4377.
IC‐P‐016: CORTICAL AMYLOID BURDEN CORRELATES WITH ATROPHY OF THE POSTERIOR PART OF THE NUCLEUS BASALIS MEYNERT IN AMYLOID‐POSITIVE SCD
2019-07-01

One of the earliest brain regions affected during the development of Alzheimer's disease (AD) is the cholinergic basal forebrain (BF). Especially the posterior part of the Nucleus basalis Meynert (Ch4p) seems to be affected already during subclinical stages of AD, leading to early cholinergic depletion. In subjects with subjective cognitive decline (SCD) as an at-risk population for AD significant volume decreases were reported. However, the relation between Ch4p volume loss and markers of AD pathology in SCD is still largely unknown. This study investigated how cortical amyloid status relates to potential BF volume loss in SCD, specifically whether there are any signs for Ch4p degeneration in amyloid-positive (SCDAß+) compared with amyloid-negative (SCDAß-) individuals. From the PET sub-cohort of DELCODE (Jessen et al., 2018), 25 SCDAß+ and 25 SCDAß- age- and sex-matched individuals were included (Tab. 1). Amyloid status was based on qualitative ratings of [18F]florbetaben (NeuraceqTM) PET scans by two experienced readers. Global cortical amyloid burden was quantified by standard uptake value ratios relative to a cerebellar cortex reference region (SUVRglobal). For each participant, 3D-T1weighed MRI data were acquired. Cholinergic forebrain volumes were extracted based on the procedure described by Kilimann et al. (2014). We specifically tested group differences in Ch4p volume between SCDAß+ and SCDAß- and conducted a correlation analysis between Ch4p volume and SUVRglobal. The other BF subnuclei were also examined exploratively. In this cohort, we found no significant volume differences of the Ch4p between SCDAß+ and SCDAß- subgroups (Tab. 2). However, correlation analyses revealed that the Ch4p volume was significantly negatively correlated with the global amyloid SUVR for the SCDAß+ group only (Fig. 1). The difference between the correlation coefficients for SCDAß+ and SCDAß- subgroups was statistically significant. Explorative analyses for the other BF nuclei did not reveal any significant results.
Chagas Disease: From Discovery to a Worldwide Health Problem
2019-07-02

Carlos Chagas discovered American trypanosomiasis, also named Chagas disease (CD) in his honor, just over a century ago. He described the clinical aspects of the disease, characterized by its etiological agent (<i>Trypanosoma cruzi</i>) and identified its insect vector. Initially, CD occurred only in Latin America and was considered a silent and poorly visible disease. More recently, CD became a neglected worldwide disease with a high morbimortality rate and substantial social impact, emerging as a significant public health threat. In this context, it is crucial to better understand better the epidemiological scenarios of CD and its transmission dynamics, involving people infected and at risk of infection, diversity of the parasite, vector species, and <i>T. cruzi</i> reservoirs. Although efforts have been made by endemic and non-endemic countries to control, treat, and interrupt disease transmission, the cure or complete eradication of CD are still topics of great concern and require global attention. Considering the current scenario of CD, also affecting non-endemic places such as Canada, USA, Europe, Australia, and Japan, in this review we aim to describe the spread of CD cases worldwide since its discovery until it has become a global public health concern.
Kidney Injury after Intravenous versus Intra-arterial Contrast Agent in Patients Suspected of Having Coronary Artery Disease: A Randomized Trial
2019-07-02

Background In the absence of randomized studies, it has been controversial whether the likelihood of acute kidney injury (AKI) differs between intravenous and intra-arterial contrast agent administration. Purpose To compare intravenous versus intra-arterial contrast agent administration in relationship to AKI and analyze the association between AKI and chronic kidney disease (defined as at least mildly decreased estimated glomerular filtration rates [eGFRs]). Materials and Methods This was a prospective study (<i>ClinicalTrials.gov</i>: NCT00844220) that involved randomizing participants with atypical chest pain and suspected coronary artery disease (CAD) between February 2009 and August 2015 to undergo coronary CT angiography with intravenous contrast agent administration or cardiac catheterization angiography with intra-arterial contrast agent administration. This prespecified secondary analysis compared AKI (serum creatinine increase of ≥ 25% or 0.5 mg/dL after 18-24 or 46-50 hours) determined by blinded investigators using absolute differences and relative risks, including two-sided 95% confidence intervals (CIs). Results A total of 320 participants (163 [50.9%] women; mean age, 60 years ± 11) were included. Baseline eGFR did not differ between the CT angiography group (84.3 mL/min/1.73 m<sup>2</sup> ± 17.2) and the catheterization group (87.1 mL/min/1.73 m<sup>2</sup> ± 16.7) (<i>P</i> = .14). AKI occurred in nine of 161 participants in the CT angiography group (5.6%; 95% CI: 3%, 10%) and in 21 of 159 participants in the catheterization group (13.2%; 95% CI: 9%,19%) (relative risk, 2.4; 95% CI: 1.1, 5.0; <i>P</i> = .02). Also in the subgroup of participants without obstructive CAD, in those not requiring coronary interventions, AKI was more common in the catheterization group (11.9%; 95% CI: 8%, 19%) than in the CT angiography group (4.3% [95% CI: 2%, 9%]; difference, 7.7% [95% CI: 1.3%, 14.1%]; relative risk, 2.8 [95% CI: 1.1, 7.0]; <i>P</i> = .02). Obstructive CAD (odds ratio [OR]: 2.7 [95% CI: 1.1, 6.6]; <i>P</i> = .02), femoral catheter access (OR: 2.5 [95% CI: 1.1, 5.6]; <i>P</i> = .04), and cine ventriculography were associated with AKI (OR: 2.3 [95% CI: 1.0, 4.9]; <i>P</i> = .03). In multivariable analysis, the presence of postcontrast AKI was associated with chronic kidney disease (hazard ratio: 12.4 [95% CI: 4.5, 34.6]; <i>P</i> < .01). Conclusion Acute kidney injury was more common after cardiac catheterization than after CT angiography in this prospective randomized study of patients suspected of having coronary artery disease. © RSNA, 2019 <i>Online supplemental material is available for this article.</i> See also the editorial by Einstein and Newhouse in this issue.
Mass Transfer Limitation during Slow Anaerobic Biodegradation of 2-Methylnaphthalene
2019-07-02

While they are theoretically conceptualized to restrict biodegradation of organic contaminants, bioavailability limitations are challenging to observe directly. Here we explore the onset of mass transfer limitations during slow biodegradation of the polycyclic aromatic hydrocarbon 2-methylnaphthalene (2-MN) by the anaerobic, sulfate-reducing strain NaphS2. Carbon and hydrogen compound specific isotope fractionation was pronounced at high aqueous 2-MN concentrations (60 μM) (ε<sub>carbon</sub> = -2.1 ± 0.1‰/ε<sub>hydrogen</sub> = -40 ± 7‰) in the absence of an oil phase but became significantly smaller (ε<sub>carbon</sub> = -0.9 ± 0.3‰/ε<sub>hydrogen</sub> = -6 ± 3‰) or nondetectable when low aqueous concentrations (4 μM versus 0.5 μM) were in equilibrium with 80 or 10 mM 2-MN in hexadecane, respectively. This masking of isotope fractionation directly evidenced mass transfer limitations at (sub)micromolar substrate concentrations. Remarkably, oil-water mass transfer coefficients were 60-90 times greater in biotic experiments than in the absence of bacteria (<i>k</i><sup>org</sup>-<sub>aq</sub>2-MN = 0.01 ± 0.003 cm h<sup>-1</sup>). The ability of isotope fractionation to identify mass transfer limitations may help study how microorganisms adapt and navigate at the brink of bioavailability at low concentrations. For field surveys our results imply that, at trace concentrations, the absence of isotope fractionation does not necessarily indicate the absence of biodegradation.
On the decay of the pair correlation function and the line of vanishing excess isothermal compressibility in simple fluids
2019-07-02

We revisit the competition between attractive and repulsive interparticle forces in simple fluids and how this governs and connects the macroscopic phase behavior and structural properties, as manifested in pair correlation functions. We focus on the asymptotic decay of the total correlation function h(r) which is, in turn, controlled by the form of the pair direct correlation function c(r). The decay of rh(r) to zero can be exponential (monotonic) if attraction dominates repulsion and exponentially damped oscillatory otherwise. The Fisher-Widom (FW) line separates the phase diagram into two regions characterized by the two different types of asymptotic decays. We show that there is a new and physically intuitive thermodynamic criterion which approximates well the actual FW line. This new criterion defines a line where the isothermal compressibility takes its ideal gas value χT=χTid. We test our hypothesis by considering four commonly used models for simple fluids. In all cases, the new criterion yields a line in the phase diagram that is close to the actual FW line for the thermodynamic state points that are most relevant. We also investigate (Widom) lines of maximal correlation length, emphasizing the importance of distinguishing between the true and Ornstein-Zernike correlation lengths.
Suicide gene‑armed measles vaccine virus for the treatment of AML
2019-07-02

Virotherapy comprises a novel therapeutic approach to selectively eliminate cancer cells. Preclinical, as well as clinical data have demonstrated the efficacy of tumor‐selective (oncolytic) viruses in hematological malignancies. In this study, we infected AML cell lines and primary AML cells from patients with measles vaccine virus either expressing GFP or armed with super cytosine deaminase, which converts the prodrug, 5‐fluorocytosine, into the chemotherapeutic compound, 5‐fluorouracil. Target cell density of the measles entry receptor, CD46, infection rates of targeted leukemic cells, tumor cell viability, and apoptotic rates were determined. We found that measles vaccine virus infected the leukemic blasts and profoundly diminished the number and viability of leukemic cells via the induction of apoptosis. The conversion of 5‐fluorocytosine to 5‐fluorouracil exerted a potent additive tumoricidal effect. This was also observed in cases when leukemic cells displayed only moderate susceptibility to the oncolytic virus and hence direct oncolysis. Taken together, in this study, we provide a first characterization of the combinatorial use of measles vaccine virus and 5‐fluorouracil for treatment of AML. Our approach to site‐specifically produce the active drug and combine this agent with the direct lytic effect of virotherapy may overcome present limitations and constitutes a feasible method with which to introduce 5‐fluorouracil in the treatment of AML.
Educational and occupational aspirations at the end of secondary school: The importance of regional labour-market conditions
2019-07-02

The transition from general schooling to vocational training or to the labour market marks a crucial threshold in the life course of young adults. It has been well documented that successful school-to-work transitions are influenced by (regional) labour-market conditions. However, what has been rather neglected is that before actual transitions take place, adolescents need to make plans and evaluate their wishes and choices against the background of existing constraints. (Regional) labour-market conditions are a part of such constraints. This paper complements previous research by focusing on the impact of the regional labour market on students’ educational and occupational aspirations before school-to-work transitions take place. Regionalised administrative data on unemployment is linked with survey data from the Starting Cohort 4 of the German National Educational Panel Study (NEPS-SC4). Results indicate that a relatively higher level of regional unemployment is associated with aspirations for higher-status occupations. Their status aspiration push students towards continuing general school to obtain higher general qualifications. The effects vary with the attended secondary school track and with parents’ educational aspirations for their children.
Two photon ophthalmoscopy reveals a new oddity of S cones
2019-07-02

Two-photon excited fluorescence (TPEF) ophthalmoscopy provides novel images of retinal structure and function, such as the first images of single ganglion cells and tracking intermediate stages of the visual cycle in the primate eye. TPEF uses femtosecond infrared pulses to image fluorophores such as retinol and NADH that cannot be observed with conventional fluorescence in the living eye because their excitation spectra lie in the ultraviolet, outside the eye’s spectral transmittance. Before TPEF can be used in humans, improved safety standards for the ultrashort pulses used in TPEF must be established. We have previously established conditions using a two-photon adaptive optics scanning light ophthalmoscope in the living macaque eye that do not produce detectable signs of damage. At light levels that were 40 times higher (retinal radiant exposures of 856 J/cm2), however, permanent selective S cone damage was observed without corresponding effects in the other receptor classes. Immediately after the exposure, S cones emitted about 2.6 times less TPEF and showed an altered TPEF time course. Several weeks after the initial exposure, the S cone outer segments had disappeared. Rods migrated in the peripheral retina and cones near the fovea to fill gaps vacated by S cones. The susceptibility of S cones to damage by ultrashort pulses is surprising because the infrared light used in TPEF is expected to be far more strongly absorbed in the other receptor classes than the S cones, adding to the long list of ways S cones differ from their M and L cone neighbors.
Activity and rotation of the X-ray emittingKeplerstars
2019-07-03

The relation between magnetic activity and rotation in late-type stars provides fundamental information on stellar dynamos and angular momentum evolution. Rotation-activity studies found in the literature suffer from inhomogeneity in the measurement of activity indexes and rotation periods. We overcome this limitation with a study of the X-ray emitting, late-type main-sequence stars observed by XMM-Newton and Kepler . We measured rotation periods from photometric variability in Kepler light curves. As activity indicators, we adopted the X-ray luminosity, the number frequency of white-light flares, the amplitude of the rotational photometric modulation, and the standard deviation in the Kepler light curves. The search for X-ray flares in the light curves provided by the EXTraS (Exploring the X-ray Transient and variable Sky) FP-7 project allows us to identify simultaneous X-ray and white-light flares. A careful selection of the X-ray sources in the Kepler field yields 102 main-sequence stars with spectral types from A to M. We find rotation periods for 74 X-ray emitting main-sequence stars, 20 of which do not have period reported in the previous literature. In the X-ray activity-rotation relation, we see evidence for the traditional distinction of a saturated and a correlated part, the latter presenting a continuous decrease in activity towards slower rotators. For the optical activity indicators the transition is abrupt and located at a period of ~10 d but it can be probed only marginally with this sample, which is biased towards fast rotators due to the X-ray selection. We observe seven bona-fide X-ray flares with evidence for a white-light counterpart in simultaneous Kepler data. We derive an X-ray flare frequency of ~0.15 d −1 , consistent with the optical flare frequency obtained from the much longer Kepler time-series.