julilili42/papers huggingface dataset:
Brain network dysfunction associated with blood neurofilament light chain in autosomal dominant Alzheimer disease
2020-12-01

Abstract Background Alzheimer disease is characterized by accrual of amyloid‐b and tau, cortical thinning, and disruptions in brain connectivity. Recent reports suggest neurofilament light chain (NfL), a measure of brain damage and atrophy, is measurable in the blood and is predictive of presymptomatic cognitive decline in individuals with autosomal dominant Alzheimer Disease. We sought to investigate the relationship between serum blood estimates of NfL and functional brain connectivity. We hypothesized that increasing NfL levels would be associated with increasing disruption of within and between network connectivity. Method We performed neuroimaging and blood serum NfL assessments in a longitudinal sample of 78 mutation non‐carriers (NC) and 112 mutation carriers (MC) age 20‐65 enrolled in the Dominantly Inherited Alzheimer Network. Serum blood samples were collected and assayed in duplicate for NfL. Resting state‐functional MRI (rs‐fMRI) data were acquired on 3T Siemens scanners. For each subject, five minutes of low‐motion rs‐fMRI data were included (scrubbing with FD &lt;0.2 mm). Functional connectivity (FC) was estimated using zero‐lag Pearson correlations calculated between 246 regions of interest (Figure 1A). NfL values were compared between mutation carriers and non‐carriers using non‐parametric Mann‐Whitney U tests (Figure 1B). We examined associations between FC and NfL using a Network Level Analysis (NLA) approach. Briefly, NLA uses non‐parametric test statistics and permutation testing to determine FC networks associated with NfL scores (Figure 1A). Result NfL was correlated with a wide‐range of within and between‐network connectivity in MC but not NC subjects (Figure 2A). The five strongest associations with NfL were within the DMN, cingulo opercular (CO) and dorsal attention (DAN) networks. Specifically, greater levels of NfL were associated with reduced magnitude of within‐ and between‐network connectivity (Figure 2D&amp;E). Conclusion Only in the MC group was NfL correlated with deterioration of the DMN and reduced connectivity between the DMN and other brain systems. Reduced connectivity between DMN and CO and DAN with increasing atrophy may be associated with executive and cognitive decline following full progression to Alzheimer’s disease. The present study suggests that indirect measurement of cell death and brain atrophy with serum NfL corresponds to reduced functional connectivity in presymptomatic Alzheimer’s disease.
Debating Post-Critical Pedagogy: A Conversation in Letters
2020-12-01

This contribution discusses objections to and concerns with the concept of post-critical pedagogy in general and Wortmann’s introduction to the topic in issue 9 of On Education (Wortmann, 2020) in particular. In the first section, Selma Haupt identifies three main issues as missing in post-critical pedagogy: first, the lack of a concrete notion of what counts as critical pedagogy, second the lack of criteria for what is good in education, and third the lack of connection to established research traditions within education. In the second section, Kai Wortmann responds to these issues, and in the third section, Selma Haupt reflects on her reading of post-critical thinking. While objections remain, she attempts to capture what post-critical pedagogy may mean.
Impurities in Drug Vials Intended for Intravitreal Medication
2020-12-01

Sterility is an important prerequisite for minimizing the risk of severe vision loss due to endophthalmitis after intravitreal injections. We describe three cases series of incidents where an unclear contamination of the drug solution or syringe caused the injection process to stop and continue with a new preparation. During a period of 12 months with 30,502 intravitreal injections at a tertiary center, wherein 7,076 were of the drug Aflibercept drawn up from a glass vial, three cases of the critical incident reporting system relating to intravitreal injections were identified: (1) After a typical contact with the filter cannula, the glass of an Aflibercept vial was no longer intact. (2) In the course of another injection, there was a clear deposition of debris on the outer edge of the syringe when removing the attached filter cannula. (3) After inserting the syringe into the rubber top of the vial, a whitish particle of unclear origin was identified within the drug solution. Later, this contamination/particle was identified as part of the greyish rubber that was punched out with the cannula, according to the analyses of the material sent in and the manufacturer’s investigations. Thus, even in busy clinics, visual inspection of the injection solution and materials used for impurities, preferably before and after pulling them out of a vial, must be an essential part of the injection process. Even when using ready-to-use prefilled syringes (PFS), vigilance must be kept high, knowing the risk of potential contamination.
Performance for proton anisotropic flow measurement of the CBM experiment at FAIR
2020-12-01

Abstract The Compressed Baryonic Matter experiment (CBM) performance for proton anisotropic flow measurements is studied with Monte-Carlo simulations using collisions of gold ions at lab momentum of 12 A GeV/ c employing DCM-QGSM-SMM heavy-ion event generator. Realistic procedures are used for centrality estimation with the number of registered tracks and particle identification with information from Time-Of-Flight detector. Variation of directed flow estimates depending on various combinations of PSD modules is used to evaluate possible systematic biases due to collision symmetry plane estimation.
Dynamical quark mass generation in QCD3 within the Hamiltonian approach in Coulomb gauge
2020-12-01

Abstract We investigate the equal-time (static) quark propagator in Coulomb gauge within the Hamiltonian approach to QCD in d = 2 spatial dimensions. Although the underlying Clifford algebra is very different from its counterpart in d = 3, the gap equation for the dynamical mass function has the same form. The additional vector kernel which was introduced in d = 3 to cancel the linear divergence of the gap equation and to preserve multiplicative renormalizability of the quark propagator makes the gap equation free of divergences also in d = 2.
Analysis of copy number variation in a Turkish dementia cohort
2020-12-01

Abstract Background Copy number variations (CNVs) arise from copied or deleted regions of the genome. These regions vary in size and may span genes known to play a role in human disease. For example, duplications and triplications of SNCA have been shown to cause forms of Parkinson’s disease, while extra copies of APP are associated with early onset Alzheimer’s disease (AD). We have previously studied a Turkish dementia cohort for variants in known disease‐causing genes for both AD and frontotemporal dementia (FTD) and have also reported variants in the new AD‐associated genes TREM2 and NOTCH3 . The goal of the current study was to perform a systematic analysis of CNVs in order to further characterize the genetic causes of dementia in this Turkish dementia cohort. Method Ninety‐nine Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD or FTD, were whole‐genome genotyped using Illumina HumanOmniExpress chips. We used GenomeStudio cnvPartition v3.2.1 plug‐in (Illumina, Inc) to analyze the data. Result We did not identify any CNVs segregating with disease in any of the four dementia families present in the studied cohort. We also did not observe any CNVs across our entire data set overlapping genes which have been previously associated with neurodegenerative diseases. We identified 9 distinct CNVs overlapping regions previously reported to have potential disease‐associated gene dosage alterations in patients with dementia phenotypes using PennCNV‐1.0.5; these were confirmed by manually checking CNVs on GenomeStudio. We observed potential disease‐associated CNVs in single individuals overlapping LOC286367 , ABCA1 , NIPSNAP3A , NIPSNAP3B , OR13C2 , OR13C5 , OR13C8 , OR13C9 , OR13D1 , CNTN6 , NIPA1 , CYFIP1 , GALNTL6 , NLGN1 , XPO1 , SNORA70B , USP34 , and HLA‐G . Additionally, two identical heterozygous duplications spanning MICA were identified in two AD patients; CNVs spanning this gene have been previously reported in four AD patients and no controls. Conclusion In this study, we integrated whole‐genome genotyping results from a Turkish cohort with previously reported findings and data publicly available to add further evidence to the role of specific CNVs in the pathogenesis of dementia.
“For me democracy is …” meanings of democracy from a phenomenological perspective
2020-12-01

Abstract Meanings of democracy are far more complex than results of standardized survey research imply. They are diverse and intertwined with other individual concepts and subjective experiences. In terms of phenomenological adequacy, they are important first order constructions that can be used for building second order typologies and explanations for political action. Survey-based quantitative research has clear limits in terms of gathering such first order constructions, even if one wants to integrate them. Drawing from a phenomenological perspective of methodology and experience from 389 qualitative interviews conducted in the state of Baden-Württemberg, Germany, we argue that research on meanings of democracy might rather use open, qualitative assessments and consider four methodological aspects. First, we need to have a theoretical and methodological basis for analyzing “everyday philosophies” and root our concepts in these first order constructions. Phenomenology and the concept of lifeworld offer such a guideline. Second, we should not oversimplify analysis. People differ greatly in how they define democracy, and this should be reflected in research. Third, we advocate a qualitative multi-dimensional analysis that separates democracy, politics and actual use of democracy. This can be used to develop a typology of individual, but collectively shared, political lifeworlds. Finally, we argue that insights from this kind of research could be used to compliment standard survey instruments and contribute to developing and frequently testing a comprehensive instrument to assess the meanings of democracy in a more holistic way and to control our scientific second-order constructions of democracy.
MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT
2020-12-01

Abstract OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71). RESULTS Patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) (n=42) had 93% 5-year PFS, 100% 5-year OS and 93% 5-year CSI-free survival. Patients with CMB/LCA (n=45) had 37% 5y-PFS, 62% 5y-OS and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in CMB/LCA patients. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH_INF subgroup. Group 3 patients (5y-PFS 36% [n=14]) relapsed more frequently than SHH_INF (5y-PFS 93% [n=28]) or Group 4 patients (5y-PFS 83% [n=6], p&amp;lt;0.001). SHH_INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I 73% vs. iSHH-II 83%, p=0.25, n=99). Mean IQ was 90 (radiotherapy-free survivors) vs. 74 (patients that received CSI) [p=0.012]. CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH-subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in non-WNT/non-SHH CMB/LCA patients was not improved by local radiotherapy. Survival was more favorable in patients with Group 4 than in patients with Group 3 medulloblastoma.
Cross‐modal associations between traditional and emerging CSF biomarkers and grey matter network disruption in autosomal dominant Alzheimer disease
2020-12-01

Abstract Background The grey matter covariance network of the brain, extracted from structural MR, becomes disrupted in neurodegenerative disorders such as Alzheimer disease (AD). While these disruptions ‐ as indicated by lower small‐world values ‐ relate to cognitive performance and can predict subsequent cognitive decline, the precise biological underpinnings of these network changes are unknown. Besides amyloid and tau, cerebrospinal fluid (CSF) biomarker levels can reflect synaptic damage, axonal degeneration and inflammatory processes. Here, we investigate whether CSF biomarker levels, reflecting a range of pathophysiological processes, are associated with grey matter network disruption in autosomal dominant AD (ADAD). Method From the Dominantly Inherited Alzheimer Network (DIAN) Observational study, we included all participants with both T1‐weighted MRI and CSF collection at the same visit. We extracted individual‐level structural grey matter covariance networks [1], and calculated the small world coefficient summary statistic. CSF biomarkers included: Aβ 42/40 ratio (amyloid aggregation), pTau181 (hyperphosphorylation), tTau and VILIP‐1 (neuronal injury and death), SNAP‐25 and neurogranin (synaptic damage), NfL (axonal injury), YKL‐40 and soluble TREM2 (neuro‐inflammation). We fitted univariate linear regression models with CSF markers as predictor and small world coefficient as outcome. To discern whether cross‐modal relationships were specific for AD, we assessed the interaction effects of mutation status. Result Across the whole group (219 mutation carriers/136 non‐carriers, 39±11 [mean±SD] years old, Table 1), CSF biomarker abnormality was associated with lower small‐world values, indicating disrupted network integrity (p&lt;0.001), and with the highest effect size for NfL (β±SE= ‐0.72±0.05). Examining interactions with mutation status (p&lt;0.05), we found that effects were driven by mutation carriers for pTau181 (β±SE= ‐0.58±0.05), tTau (β±SE= ‐0.55±0.06), SNAP‐25 (β±SE= ‐0.37±0.07), neurogranin (β±SE= ‐0.35±0.07), NfL (β±SE= ‐0.76±0.06)), and YKL‐40 (β±SE= ‐0.61±0.06, Figure 1), and to a smaller degree also present in non‐carriers for NfL (β±SE= ‐0.44±0.014) and YKL‐40 (β±SE= ‐0.32±0.08). Conclusion Grey matter network changes on MRI may involve multiple pathological processes. The strong relationship with NfL suggests that axonal loss contributes to disrupted grey matter networks as observed in AD. Studying cross‐modal relationships between MRI and CSF biomarkers can inform our understanding of underlying mechanisms of cognitive impairment due to neurodegeneration in AD. Grant: P50AG005681. Ref1:Tijms,2012 Cerebral Cortex.
Edward Roberts, Flodoard of Rheims and the Writing of History in the Tenth Century. (Cambridge Studies in Medieval Life and Thought, Vol. 113.) Cambridge, Cambridge University Press 2019
2020-12-01

Article Edward Roberts, Flodoard of Rheims and the Writing of History in the Tenth Century. (Cambridge Studies in Medieval Life and Thought, Vol. 113.) Cambridge, Cambridge University Press 2019 was published on December 1, 2020 in the journal Historische Zeitschrift (volume 311, issue 3).
Medin amyloid forms age‐associated aggregates in the brain vasculature and may contribute to cerebral β‐amyloidosis
2020-12-01

Abstract Background The most common human amyloid is probably medin (AMed), which deposits in the aorta of nearly everyone above 50 years of age. Previous studies reported that medin amyloid may co‐aggregate and seed serum amyloid A. Because of this finding and its exceedingly high prevalence in the aging population, we studied whether medin aggregates form in the brain during aging and may interact with other age‐associated amyloids such as Aβ. Method In order to study the pathobiology of medin amyloid and its contribution to vascular and parenchymal amyloidosis, we first investigated the occurrence of medin in wildtype mice. Additionally, we used APP transgenic mouse lines and human tissue for immuno‐histochemical and immunoprecipitation experiments to study a potential protein‐protein interaction with Aβ. Result We find that medin deposits are prevalent in the human brain vasculature and seem to increase both with age and Aβ pathology. Moreover, co‐immunoprecipitation experiments indicate an interaction of Aβ and medin. Strikingly, we also observe that, similar to the human situation, amyloid‐like deposits of medin are formed in the aorta as well as in the brain vasculature of aging wildtype mice. Further experiments in APP transgenic mice showed that medin does not only co‐localize with Aβ Plaques and CAA, but may also promote cerebral β‐amyloidosis in mouse models of Alzheimer’s pathology. Conclusion Our findings suggest that age‐associated medin deposition occurs both in the mouse and human brain, where it may promote cerebral β‐amyloidosis.
Lifestyle differences modulate the effects of cognitive reserve on functional connectivity
2020-12-01

Abstract Background Cognitive reserve (CR) refers to the individual differences in cognition relative to brain aging or neurodegenerative changes. Recently, various studies tried to quantify a marker that represents CR. Among others, the residual approach suggested being relatively reliable as it has been studied not only with cross‐sectional but also with longitudinal observations. However, it is unknown if brain connectivity changes in the resting‐state are related to reserve factors e.g. lifestyle factors. Method In the present study we defined a CR Marker based on residuals calculated through a multimodal (multi‐linear) regression model adapted from a recent study using pathological changes of AD such as atrophy, demographic and genetic information as predictors. The data of 546 participants including healthy controls, participants with subjective cognitive decline, 62 patients with MCI, and 64 patients with AD from the German multicentric DELCODE cohort was assessed. To examine neural substrates of defined CR marker, we constructed a weighted undirected partial correlation matrix in the GraphVar toolbox and analyzed graph theoretical metrics in global topography with various network thresholds. Permutation‐based FDR‐correction has been used in statistical analyses with graph measures. Then we examined the possible associations between CR and lifestyle factors specifically the Lifetime Experiences Questionnaire(LEQ). Result CR was positively correlated (r=0.247, p=0.012) with higher scores in LEQ which includes leisure, educational and physical activities across the lifespan. We demonstrated that LEQ interacts with CR in functional connectivity changes, we used a multivariate regression model, in which LEQ was binarized using median values of total normalized scores. At the global level, interaction between CR and binarized LEQ score has been found with clustering coefficient (p=0.02), transitivity (p=0.017), but not with global efficiency(p=0.45). Moreover, component of LEQ scores corresponding to young adulthood, mid‐life, and late‐life didn’t interact with CR. However, LEQ of late‐life showed interaction at marginal level(uncorrected p=0.03). Conclusion Overall, CR and lifestyle differences appear to be reflected by changes in brain connectivity with increased global information processing capacity in participants exhibit higher CR. These findings foster understanding of early AD and will be useful to help identify individuals with vulnerability or resistance to AD pathology.
MBCL-11. TIME TO RADIOTHERAPY IMPACTS SURVIVAL IN PEDIATRIC AND ADOLESCENT NON-METASTATIC MEDULLOBLASTOMA TREATED BY UPFRONT RADIOTHERAPY – A REPORT FROM THE HIT 2000 TRIAL
2020-12-01

Abstract PURPOSE To evaluate prognostic factors and impact of participation in a randomized trial in non-metastatic medulloblastoma. METHODS AND PATIENTS 382 patients with non-metastatic medulloblastoma aged 4–21 years with primary neurosurgical resections between 2001 and 2011 were enrolled into the HIT 2000 trial and centrally reviewed. Between 2001 and 2006, 176 of these patients participated in the randomized trial HIT-SIOP PNET 4. Three different radiotherapy protocols were applied. Molecular subgroup was available for 157 patients. RESULTS Median follow-up was 6.35 [0.09–13.86] years. The 5-year progression-free (PFS) and overall survival (OS) rates were 80.3 % ± 2.1 % and 86.5 % ± 1.8 %, respectively. On univariate analysis, there was no difference in PFS and OS according to radiotherapy protocols or in patients who participated in the HIT-SIOP PNET 4 trial or not, while histology, molecular subgroup and postoperative residual tumor influenced PFS significantly. Time interval between surgery and irradiation (≤48 days vs. ≥49 days) failed the significance level (p=0.052). On multivariate analyses, molecular subgroup (WNT activated vs. Group3 HR 5.49; p=0.014) and time interval between surgery and irradiation (HR 2.2; p=0.018) were confirmed as independent risk factors. CONCLUSION Using a centralized review system, multiprofessional and multiinstitutional collaboration as established for pediatric brain tumor patients in Germany, and risk-stratified therapy, outcome for non-metastatic medulloblastoma treated within HIT-SIOP PNET4 could be maintained outside the randomized trial. Prolonged time to radiotherapy negatively influenced survival.
Seismological evidence for the earliest global subduction network at 2 Ga ago
2020-12-01

The earliest evidence for subduction, which could have been localized, does not signify when plate tectonics became a global phenomenon. To test the antiquity of global subduction, we investigated Paleoproterozoic time, for which seismic evidence is available from multiple continents. We used a new high-density seismic array in North China to image the crustal structure that exhibits a dipping Moho bearing close resemblance to that of the modern Himalaya. The relict collisional zone is Paleoproterozoic in age and implies subduction operating at least as early as ~2 billion years (Ga) ago. Seismic evidence of subduction from six continents at this age is interpreted as the oldest evidence of global plate tectonics. The sutures identified can be linked in a plate network that resulted in the assembly of Nuna, likely Earth's first supercontinent. Global subduction by ~2 Ga ago can explain why secular planetary cooling was not appreciable until Proterozoic time.