julilili42/papers huggingface dataset:
Spatial neuronal synchronization and the waveform of oscillations: Implications for EEG and MEG
2019-05-14

Neuronal oscillations are ubiquitous in the human brain and are implicated in virtually all brain functions. Although they can be described by a prominent peak in the power spectrum, their waveform is not necessarily sinusoidal and shows rather complex morphology. Both frequency and temporal descriptions of such non-sinusoidal neuronal oscillations can be utilized. However, in non-invasive EEG/MEG recordings the waveform of oscillations often takes a sinusoidal shape which in turn leads to a rather oversimplified view on oscillatory processes. In this study, we show in simulations how spatial synchronization can mask non-sinusoidal features of the underlying rhythmic neuronal processes. Consequently, the degree of non-sinusoidality can serve as a measure of spatial synchronization. To confirm this empirically, we show that a mixture of EEG components is indeed associated with more sinusoidal oscillations compared to the waveform of oscillations in each constituent component. Using simulations, we also show that the spatial mixing of the non-sinusoidal neuronal signals strongly affects the amplitude ratio of the spectral harmonics constituting the waveform. Finally, our simulations show how spatial mixing can affect the strength and even the direction of the amplitude coupling between constituent neuronal harmonics at different frequencies. Validating these simulations, we also demonstrate these effects in real EEG recordings. Our findings have far reaching implications for the neurophysiological interpretation of spectral profiles, cross-frequency interactions, as well as for the unequivocal determination of oscillatory phase.
XSPEC model for testing the Kerr black hole hypothesis using the continuum-fitting method
2019-05-14

We present NKBB, an XSPEC model for the thermal spectrum of thin accretion\\ndisks in parametric black hole spacetimes. We employ the Novikov-Thorne model\\nfor the description of the accretion disk and the formalism of the transfer\\nfunction proposed by Cunningham for storing all the relativistic effects of the\\nspacetime metric. The current version of the model assumes the Johannsen\\nmetric, but it can be easily extended to any stationary, axisymmetric, and\\nasymptotically-flat spacetime without pathological properties. The model can be\\nused within the XSPEC package to test the Kerr nature of astrophysical black\\nholes with the continuum-fitting method.\\n
Derivatize, Racemize, and Analyze—an Easy and Simple Procedure for Chiral Amino Acid Standard Preparation for Enantioselective Metabolomics
2019-05-14

A simple, controllable, and reproducible stereoisomerization (racemization and epimerization) protocol for the preparation of scalemic α-amino acid mixtures from stereoisomerically pure standards was developed. Simply derivatize your amino acids with a racemization tag that incorporates a urea bond on the N-terminus of the target amino acid and incubate at elevated temperatures up to 95 °C for defined time periods until the targeted d-amino acid levels are obtained. The racemization tags investigated were 6-aminoquinolyl- N-hydroxysuccinimidyl carbamate (AQC), aminophenyl- N-hydroxysuccinimidyl carbamate (AC), and 3-aminopyridyl- N-hydroxysuccinimidyl carbamate (APC). Employing this method, it was possible to create a ready-to-use, tailor-made chiral uniformly <sup>13</sup>C and <sup>15</sup>N labeled [U -<sup>13</sup>C<sup>15</sup>N]-amino acid standard with the desired d-amino acid percentage within minutes or hours without sample cleanup. A racemization time of 30 min at 95 °C will lead to a d-amino acid level of 1-5%, while 6 h at 95 °C provides 15-30% d-amino acids. Racemization occurs due to imine formation at the chiral carbon atom bound to the urea-linking group without decomposition of labile amino acids such as Asn, Gln, Trp, Cit, and theanine. For amino acids possessing two chiral centers such as dl-Ile or dl-Thr, only the epimerization of isomers with different stereochemistry at the second chiral center will produce all four possible isobaric enantiomers. All measurements were performed on the zwitterionic Chiralpak ZWIX(+) column using a dual hydro-organic flow gradient combined with HPLC-ESI-QTOF-MS analysis. This new racemization method solves the problem of (enantioselective) matrix effects and inaccurate results in LC-MS based enantioselective metabolomics and warrants full MS-compatibility.
Dual vs. Single Tasking During Circular Walking: What Better Reflects Progression in Parkinson's Disease?
2019-05-14

<b>Background and Aim:</b> Reliable, valid and sensitive measures of dual-task-associated impairments in patients with Parkinson's disease (PD) may reveal progressive deficits unnoticed under single-task walking. The aim of this study was to quantitatively identify markers of progressive gait deficits in idiopathic PD while walking over a circular trajectory condition in single-task walking and in different dual-task conditions: (1) circular walking while checking boxes on a paper sheet as fast as possible and (2) circular walking while performing subtraction of 7 as fast as possible. In addition, we aimed to study the added value of dual-tasking assessment over single (circular) walking task assessment in the study of PD progression. <b>Methods:</b> The assessments were performed every 6 months over a (up to) 5 years period for 22 patients in early-stage PD, 27 patients in middle-stage PD and 25 healthy controls (HC). Longitudinal changes of 27 gait features extracted from accelerometry were compared between PD groups and HCs using generalized estimating equations analysis, accounting for gait speed, age, and levodopa medication state confounders when required. In addition, dual-task-interference with gait and cognitive performance was assessed, as well as their combination. <b>Results:</b> The results support the validity and robustness of some of the gait features already identified in our previous work as progression markers of the disease in single-task circular walking. However, fewer gait features from dual-task than from single-task assessments were identified as markers of progression in PD. Moreover, we did not clearly identify progressive worsening of dual-task-interference in patients with PD, although some group differences between early and middle stages of PD vs. the control group were observed for dual-task interference with the gait task and with the concurrent tasks. <b>Conclusions:</b> Overall, the results showed that dual-tasking did not have added value in the study of PD progression from circular gait assessments. Our analyses suggest that, while single-task walking might be sensitive enough, dual-tasking may introduce additional (error) variance to the data and may represent complex composite measures of cognitive and motor performance.
Machine learning to detect Alzheimer’s disease from circulating non-coding RNAs
2019-05-14

Abstract Background To develop therapeutics for Alzheimer’s disease, early detection of patients awakes new hope. Circulating small non-coding RNAs are among the prominent candidates for a blood-based diagnosis, requiring however growing cohort sizes. Methods We determined abundance levels of 21 known circulating microRNAs in 465 individuals encompassing Alzheimer’s patients and controls recruited in US and Germany. We computed models to assess the relation between microRNA-expression and phenotypes, gender, age and disease severity (Mini-Mental State Examination MMSE). Results 20 of 21 miRNAs were consistently dys-regulated in the US and Germany. 18 were significantly correlated to neurodegeneration (adjusted p&lt;0.05) with highest significance for miR-532-5p (adjusted p=4.8×10 −30 ). Ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted p=0.0002). Machine learning models reached an AUC value of 87.6% in differentiating AD patients from controls. Conclusions Our data provide strong evidence for the relevance of circulating non-coding RNAs to detect Alzheimer’s from a blood sample.
Open doors by fair means: Study protocol for a 3-year prospective controlled study with a quasi-experimental design towards an open Ward policy in acute care units
2019-05-14

BACKGROUND: Acute psychiatric wards in Germany are often locked due to the assumption that opening could endanger patients and society. On the contrary, some findings suggest that aversive events such as absconding and attempted suicides do not occur more often on wards with an open-door policy. However, these data are probably biased with regard to differing patient populations on open and locked wards. To our best knowledge, the present study is the first prospective controlled study with a quasi-experimental design dealing with this issue. METHODS: This study investigates whether indicators of an open-door policy, as measured by a priori determined outcomes, can be improved by a defined complex intervention on two intervention wards in two psychiatric hospitals, compared to two control wards with otherwise very similar conditions. Both hospitals contain two wards identical in structure and patient admittance policies, so that a similar study protocol can be followed with similar patient populations. Both hospitals have a defined catchment area and receive voluntary and involuntary admissions. In a baseline phase, wards will be opened facultatively (i.e., if it seems possible to staff). In the following intervention period, one ward per hospital will establish an enhanced open-door policy by applying additional strategic and personnel support. As a control group, the control ward will continue to be opened facultatively. After one year, control wards will be opened according to the open-door policy as well. Interventions will include the continuous identification of patients at risk as well as the development of individual care concepts and additional staffing. For this purpose, nursing and medical staff will be methodically supported on an ongoing basis by study staff. Outcomes variables will be the percentage of door opening on each ward between 8 a.m. and 8 p.m., the percentage of all treatment days with the door opened and the number of involuntary treatment days with open doors. Data on frequencies of aggressive incidents, absconding, police searches, and seclusion or restraint will be used as control variables. Additional costs will be calculated. DISCUSSION: Treating mentally ill patients on locked wards is a highly relevant and critically discussed topic. In particular, it is controversially discussed whether changes in door policy can be established without increasing risks to patients and others. This study aims to gain robust data on this issue, going beyond beliefs and questionable retrospective observational studies. TRIAL REGISTRATION: Our trial “Open Doors By Fair Means” is retrospectively registered with DRKS (DRKS00015154) on Sept. 10th 2018 and displayed on the public web site. It is searchable via its Meta-registry (http://apps.who.int/trialsearch/).
Fast enzymatic synthesis of n.c.a. 6‐[18F]fluorodopamine (FDA) from n.c.a. 6‐[18F]FDOPA and the fate of 6‐FDOPA and 6‐FDA in neuroblastoma and Caki‐1 cells after their uptake
2019-05-14

The catecholamine analogue [ 123 I] m IBG has been used for scintigraphic imaging of neuroblastoma since 1984. It is taken up by the noradrenaline transporter (NAT), which is present in most neuroblastoma cells. An alternative imaging method could be PET with 6‐[ 18 F]fluorodopamine, which is also taken up by NAT, but—in contrast to m IBG—also by dopamine transporter (DAT), present in neuroblastoma cells (NAT &gt; DAT). An enzymatic method was established allowing a rapid, quantitative transformation of FDOPA to FDA by DOPA decarboxylase within 25 minutes. This strategy was applied to [ 18 F]FDOPA, which was produced via nucleophilic synthesis (RCY 15%, 10 GBq, 50 GBq/μmol) and subsequently converted to [ 18 F]FDA (RCY 35%‐50%, n = 5). Uptake and metabolism of FDOPA and FDA were analyzed in human Kelly and SK‐N‐SH neuroblastoma cell lines and in human Caki‐1 kidney cells that can take up catecholamines and m IBG via an organic cation transporter (OCT). FDOPA and FDA were taken up by all three cells, but FDOPA could only be converted to FDA in neuroblastoma cells. As today, [ 18 F]FDOPA is well available in high yields, efficient enzymatic conversion to [ 18 F]FDA to be used for NAT/DAT PET imaging in neuroendocrine tumors is an attractive, alternative synthesis route.
Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy
2019-05-15

Abstract RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination ( p &lt; 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants ( p &lt; 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls ( p &lt; 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48–0.76]) and avidity to C-terminus (0.07 [0.05–0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.
Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity
2019-05-15

Since the realization that immature myeloid cells are powerful modulators of the immune response, many studies on “myeloid-derived suppressor cells” (MDSCs) have documented their ability to promote tumor progression in melanoma and other cancers. Whether MDSCs are induced solely pathologically in tumorigenesis, or whether they also represent physiological immune control mechanisms, is not well-understood, but is particularly important in the light of ongoing attempts to block their activities in order to enhance anti-tumor immunity. Here, we briefly review studies which explore (1) how best to identify MDSCs in the context of cancer and how this compares to other conditions in humans; (2) what the suppressive mechanisms of MDSCs are and how to target them pharmacologically; (3) whether levels of MDSCs with various phenotypes are informative for clinical outcome not only in cancer but also other diseases, and (4) whether MDSCs are only found under pathological conditions or whether they also represent a physiological regulatory mechanism for the feedback control of immunity. Studies unequivocally document that MDSCs strongly influence cancer outcomes, but are less informative regarding their relevance to infection, autoimmunity, transplantation and aging, especially in humans. So far, the results of clinical interventions to reverse their negative effects in cancer have been disappointing; thus, developing differential approaches to modulate MSDCs in cancer and other diseases without unduly comprising any normal physiological function requires further exploration.
Lepton-Jet Correlations in Deep Inelastic Scattering at the Electron-Ion Collider
2019-05-15

We propose the lepton-jet correlation in deep inelastic scattering as a unique tool for the tomography of nucleons and nuclei at the electron-ion collider (EIC). The azimuthal angular correlation between the final state lepton and jet depends on the transverse momentum dependent quark distributions. We take the example of single transverse spin asymmetries to show the sensitivity to the quark Sivers function. When the correlation is studied in lepton-nucleus collisions, transverse momentum broadening effects can be used to explore cold nuclear matter effects. These features make lepton-jet correlations an important new hard probe at the EIC.
Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment
2019-05-15

Although cardiovascular disease (CVD) is the leading cause of morbimortality worldwide, promising new drug candidates are lacking. We compared the arterial high-resolution proteome of patients with advanced versus early-stage CVD to predict, from a library of small bioactive molecules, drug candidates able to reverse this disease signature. Of the approximately 4000 identified proteins, 100 proteins were upregulated and 52 were downregulated in advanced-stage CVD. Arachidonyl trifluoromethyl ketone (AACOCF3), a cytosolic phospholipase A2 (cPLA2) inhibitor was predicted as the top drug able to reverse the advanced-stage CVD signature. Vascular cPLA2 expression was increased in patients with advanced-stage CVD. Treatment with AACOCF3 significantly reduced vascular calcification in a cholecalciferol-overload mouse model and inhibited osteoinductive signaling in vivo and in vitro in human aortic smooth muscle cells. In conclusion, using a systems biology approach, we have identified a potentially new compound that prevented typical vascular calcification in CVD in vivo. Apart from the clear effect of this approach in CVD, such strategy should also be able to generate novel drug candidates in other complex diseases.
Chimpanzee extractive foraging with excavating tools: Experimental modeling of the origins of human technology
2019-05-15

It is hypothesized that tool-assisted excavation of plant underground storage organs (USOs) played an adaptive role in hominin evolution and was also once considered a uniquely human behavior. Recent data indicate that savanna chimpanzees also use tools to excavate edible USOs. However, those chimpanzees remain largely unhabituated and we lack direct observations of this behavior in the wild. To fill this gap in our knowledge of hominoid USO extractive foraging, we conducted tool-mediated excavation experiments with captive chimpanzees naïve to this behavior. We presented the chimpanzees with the opportunity to use tools in order to excavate artificially-placed underground foods in their naturally forested outdoor enclosure. No guidance or demonstration was given to the chimpanzees at any time. The chimpanzees used tools spontaneously in order to excavate the underground foods. They exhibited six different tool use behaviors in the context of excavation: probe, perforate, dig, pound, enlarge and shovel. However, they still excavated manually more often than they did with tools. Chimpanzees were selective in their choice of tools that we provided, preferring longer tools for excavation. They also obtained their own tools mainly from naturally occurring vegetation and transported them to the excavation site. They reused some tools throughout the study. Our new data provide a direction for the study of variables relevant to modeling USO extractive foraging by early hominins.
Uterine Fibroids - Current Trends and Strategies.
2019-05-15

Fibroids are the most common benign tumors in women of childbearing age and can be found in almost 80-90% of all women by age 50 years. They can cause pain, excessive menstrual bleeding or infertility. The development of fibroids increases with age. Since the age of women in industrial countries who are trying to conceive is generally increasing, there has been a growing demand for minimally invasive and uterine-sparing surgical treatment of fibroids. Whereas the main focus of previous surgical techniques for the treatment of fibroids was enucleation of the tumour with subsequent closure of the uterine incision, modern devices developed over the past decade can destroy fibroids by using ultrasound or radio-frequency without incising the uterine wall. Thus, there is no uterine scar, which would impart a risk of rupture during labour or pregnancy. This article provides an overview of the latest techniques and devices used for uterine-sparing surgical treatment of fibroids. While laparoscopic myomectomy is still the gold standard, novel laparoscopic and transcervical radiofrequency ablation techniques use low-voltage and alternating current to induce heat in the uterine tissue, which triggers necrosis in fibroids. This enables the removal of multiple fibroids without the need for large incisions in the uterine wall. In addition, we address the benefits and potential risks, as well as the impact on fertility and pregnancy, of the different surgical approaches used for the treatment of uterine fibroids.
Assessing the spatial scale of context effects: The example of neighbourhoods’ educational composition and its relevance for individual aspirations
2019-05-15

The neighbourhood environment has repeatedly proven to be a relevant context for central aspects of individuals' lives, such as educational attainment. The conventional approach of measuring neighbourhood characteristics within disjunct geographical units fixed at a particular scale is less suitable for representing the characteristics of individual action spaces in everyday activities and for detecting scale-dependent relationships. We, therefore, adapted an ego-centred context approach by aggregating contextual characteristics within (approximately) circular areas around individual respondents' places of residence (ego-hoods). We also used an analytical framework that considers the quality of hierarchical context effects. This allowed us to derive conclusions about the spatial reference of micro-level mechanisms from the scale of context effects observed as a macro-micro relationship. We linked contextual indicators to individual-level data from the German Socio-Economic Panel. Comparing ego-hoods of different ranges, we confirmed the expectation of distance decay in the relevance of neighbours for individual educational aspirations.
Academic majors of social studies teachers and student achievement in the U.S.
2019-05-15

The education of social studies teachers has been understudied at a large scale, relative to other subject areas. This study estimated whether the undergraduate and/or graduate majors of social studies teachers are associated with student achievement in civics, U.S. history, and geography. Broad categorizations of social studies-related majors were not associated with student achievement. However, a graduate major in political science for students' teachers was positively and significantly associated with student achievement in civics, and an undergraduate major in geography/geography education was negatively associated with student achievement in civics and U.S. history. Implications for policy and research are discussed.