julilili42/papers huggingface dataset:
Weaving into the mediascape: an institutional ethnography of NGO Media Activism in South Africa
2019-07-01

Media Monitoring Africa (hereafter MMA), is a Johannesburg-based non-governmental organization (NGO) with the goals to increase media quality, refocus media ethics, foster media diversity, and advance media democracy. Via an institutional ethnography, conducted during six weeks of fieldwork, I take up MMA’s particular case to investigate how the NGO has become understood as “part” of the South African mediascape, rather than an auxiliary agent. Through participant observation of the NGO’s daily routines, in-depth interviews with MMA members and local media professionals, as well as textual analysis of organizational documents, I found that MMA has managed to weave into the organizational fabric of the South African mediascape. The ethnographic data reveals that MMA is commonly perceived as a necessary element of the South African mediascape—a status that moves beyond the often strictly interventionist role of activist NGOs. I argue that MMA has achieved this unique social position in the mediascape through four central organizational-activist practices: 1. consistent intervention on the same sets of issues; 2. activist innovation around the mode of their intervention(s); 3. multilateral activism (political economy, media policy, media content); and 4. successful curation of relationships with media stakeholders.
Characterization of Biostable Atomic Layer Deposited (ALD) Multilayer Passivation Coatings for Active Implants
2019-07-01

The next generation of flexible, electrically active implants, such as brain implants or retina chips require a flexible, biostable as well as biocompatible passivation, ensuring a degradation-free usage for long time periods on the order of several years. Until today, these passivations are prepared mostly by polyimides or parylene, both of which are water vapor permeable to a certain degree. To remedy this deficiency, Atomic Layer Deposited (ALD) thin films are characterized regarding their electrical passivating features under conditions of accelerated aging, such as elevated temperatures in a liquid environment. The initial electrical passivation by various ALD deposited multilayers, combining alternating thin Al<sub>2</sub>O<sub>3</sub> and TiO<sub>2</sub> layers is the goal of this research as well as the stability of these layers under induced degradation. Such layers, in combination with a parylene passivation, would ensure a water vapor impermeable and biocompatible coating.
Fault Diagnosis Approach for Pedelec Drive Units Based on Support Vector Machines
2019-07-01

In the field of electric drives, current fault detection approaches are already able to recognize a device fault and locate its root. Nevertheless, such methods require the integration of additional sensors that give a clear state of the equipment's health, as well as enough computing resources that allow the processing of the large amount of data generated by these sensors. In contrast to these approaches, we present a method with which it is possible to identify faults in systems with limited computing performance and storage space, such as pedelecs, without requiring the integration of additional sensors or memory units. The core of this method is finding the operating conditions under which the fault identification is clearer, and the set of features that provide the most relevant information for the fault diagnosis. This approach implements a Support Vector Machine (SVM) for the identification of the features that enlarges the distance between the classes (fault types). An SVM classifier is then trained with the resultant feature-set. To validate the presented framework, the signals of 5 pedelec Drive Units (DUs) without faults and 10 faulty DUs were gathered, during normal trips. The results of the experimental study show that the proposed approach achieves a great accuracy and due to the low size of the generated classifier, it can be deployed in a device with limited available storage, allowing real-time accurate classification.
Finite Element Breast Simulation for Sonography Image Registration
2019-07-01

In case of female breast cancer, a breast conserving excision is often necessary. For this purpose, information from multiple medical imaging techniques have to be combined. Sonography imaging is essential for dense breast tissue and the only medical imaging technique available during surgery. During sonography of the outer breast quadrants the woman is usually in contralateral posterior oblique position, being in supine orientation while holding her ipsilateral arm over the head. Thus, these images cannot be directly registered with MRI or mammography images because these imaging technologies are performed in other patient positions with hands on the side of the body. Thus, we present a novel Finite Element approach how to enable a sonography image registration by showing the first time how to transfer the supine position with the arm straight on side into a supine position with the ipsilateral arm over the head which can be used to include information from MRI or mammography images. This approach is shown and validated with 3D scanner breast surface data as proof of concept. When comparing the simulation result with a 3D surface scan in supine orientation with the arm over the head, a mean surface distance error of 1.57 mm is achieved.
Should every patient with muscle-invasive bladder cancer receive neoadjuvant chemotherapy?
2019-07-01

The use of cisplatin-based neoadjuvant chemotherapy (NAC) for all patients with muscle-invasive bladder cancer (MIBC) is recommended by current guidelines (1,2). However, the study of Bhindi et al . suggest, that patients not responding to NAC show an inferior survival than a comparable control group (3). Furthermore, only 20–38% of the patients exposed towards NAC show a histopathological response (4). Taking these aspects and the known chemotherapy-related toxicity into consideration leads both, providers and patients, to the question whether the potential benefits of NAC outweigh its disadvantages.
Abstract 4377: Liver X receptor mediated lipotoxicity represents a treatment option for liver cancer
2019-07-01

Abstract 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.
P1.35: Spectrum of major abdominal surgical procedures within a pediatric intestinal rehabilitation (IR) program
2019-07-01

Background: Surgery plays a key role for the intestinal rehabilitation (IR) of children with short bowel syndrome or chronical intestinal failure. Whereas single procedures – especially for intestinal lengthening - are regularly being evaluated and described, the whole spectrum of surgical procedures within large IR programs in children is often difficult to assess. Our aim was to analyse the complete spectrum of major abdominal surgical procedures in a pediatric IR program. Methods: We retrospectively analysed patients’ data from our pediatric IR program with special focus on all patients undergoing major abdominal surgery. Patients characteristics as well as surgical data were evaluated. Results: The study period ranged from 2013 until 2018. During that period 184 patients were treated within our IR program. Of these children, 58 (31,5%) underwent major abdominal surgery. There were 35 male and 23 female patients. Diagnoses were anatomical short bowel syndrome (gastroschisis, atresia, volvulus on others) in 40 patients, hypoperistaltic conditions (aganglionosis, hypoganglionosis, MMIHS) in 17 patients and malabsorption (Microvillus Inclusion Disease) in one patient. Ten children originated from our own area, whereas 48 children were referred to us from different national or international regions. Mean number of operations prior to referral to us in those patients coming from other sites was 2.6 (0–7). In the 58 patients, 107 operations were performed (median 1.5, range 1–6). One operation was performed in 29 children, 19 children underwent 2 operations, 6 children underwent 3 operations, 2 children received 4 operations and 2 children underwent 6 operations. The types of surgical procedures were mostly reconstructive (n=100), while lengthening procedures were performed on 7 occasions (6.5%). Mean operating time was 145.2 minutes (range 31–1356). One child died in the early postoperative phase because of SIRS and two children died independently from the surgical procedure because of the central line sepsis. Conclusion: The spectrum of surgical procedures in a pediatric IR program displays a wide variety of indications; reconstructive procedures are predominant. The procedures are complex and time consuming and require a comprehensive management including preoperative workup and indication, intraoperative surgical and anaesthesiological care as well as postoperative intensive care treatment.
P4‐689: INACTIVATION OF PATHOGENIC Aβ SEEDS AT PRE‐AMYLOID DISEASE STAGES
2019-07-01

Failed clinical trials for Alzheimer's disease (AD) suggest that Aβ aggregation must be targeted at very early disease stages to be effective. Furthermore, the deposition of amyloid per se, as assessed microscopically or via PET imaging, is likely to be a relatively late manifestation of the pathogenic process. It is not known when the initial, pre-amyloid Aβ seeds begin to form, propagate, and spread through the brain, nor has the structure of the initial Aβ seeds been defined. We tested a variety of well-described and clinically-tested antibodies for their in vivo recognition of pre-amyloid seeds in Aβ-precursor protein(APP)-transgenic mice. In parallel, we used immunoprecipitation of size-fractionated, native, brain-derived Aβ assemblies and established antibody recognition profiles to allow prediction of Aβ seed recognition. We identified at least one antibody (the murine version of aducanumab) that administered for only 5 consecutive days at pre-deposition stage, achieved long-lasting (50%) prevention of Aβ deposition and associated pathologies in APP-transgenic mice 6 months later. These findings demonstrate the presence of pathogenic Aβ seeds well before amyloid formation becomes detectable. Lowering such bioactive, pre-amyloid seeds maybe an effective paradigm for AD prevention.
P2‐359: 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.
IC‐P‐094: CROSS‐SECTIONAL AND LONGITUDINAL 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).
P1‐407: RELATIONSHIP BETWEEN GLOBAL CONNECTIVITY, AMYLOID AND TAU IN DIFFERENT STAGES DURING THE DEVELOPMENT OF ALZHEIMER'S DISEASE AS DEMONSTRATED IN THE DZNE DELCODE COHORT
2019-07-01

Recent multicenter studies provide rich insights in restingstate alterations, while different scanning protocols between sites sometimes lower interpretability (Teipel et al., 2017a, 2017b). Global brain connectivity (GBC) is a local restingstate measure with good clinical applicability (Cole et al. 2012). As little is known about changes in GBC during the development of Alzheimer's disease (AD) and its relationship to amyloid or tau, this question was assessed using data from the first release of the DZNE - Longitudinal Cognitive Impairment and Dementia Study (DELCODE) making use of standardized MR-protocols including healthy elderly subjects (HC), patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and AD. Data was taken from the second-release (n=698) of the DELCODE study. All subjects, which successfully completed both, an eyes-closed restingstate scan - as part of a general scanning protocol - and a lumbar puncture, were included in our analysis. Preprocessing of the restingstate fMRI data was carried out using DPARSF (Yan et al., 2016) and SPM12. GBC was calculated on whole brain level using Matlab 2012a and compared between groups. Cerebrospinal fluid was analyzed for Aß40, Aß42, p-tau and t-tau. Simple regression analysis was used to compare GBC with subjects' Aß40/Aß42-ratio and tau-levels. We found a main effect of diagnosis on GBC in the hippocampus and precuneus, with a gradual decrease of GBC in those regions over the diagnostic stages towards the development of AD. A direct correlation was found between the Aß40/Aß42-ratio and GBC in the precuneus as well as between ptau-levels and GBC in the hippocampus. We identified gradual changes in global brain connectivity between the different stages over the development of AD, correlating with amyloid and tau levels. Complementing previous studies (Teipel et al., 2017a,b), those results might be useful to define early markers of disease progression, that might serve as biomarkers on longitudinal level. References: Cole et al. (2012), The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 32(26), 8988–8999. Teipel et al. (2017), Frontiers in Aging Neuroscience, 8. Teipel et al. (2017), NeuroImage: Clinical, 14, 183–194. Yan et al. (2016), Neuroinformatics, 14(3), 339–351.
P1‐447: DIAGNOSTIC VALUE OF DIGITAL CLOCK DRAWING TEST IN COMPARISON WITH CERAD NEUROPSYCHOLOGICAL BATTERY TOTAL SCORE FOR DISCRIMINATION OF PATIENTS IN THE EARLY COURSE OF ALZHEIMER'S DISEASE FROM HEALTHY INDIVIDUALS
2019-07-01

Currently available diagnostic tools to detect mild cognitive impairment (MCI) or dementia are time-consuming, invasive or expensive and thus not suitable for wide application as screening instruments. Digital Clock Drawing Test (dCDT) was performed in 138 patients with amnestic MCI (aMCI), 106 patients with mild Alzheimer's dementia (mAD) and in 137 healthy controls (HCs) and was compared with the diagnostic value of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery total score. dCDT variables provided a slightly higher diagnostic accuracy of 81.5 % for discrimination of aMCI from HCs than using CERAD total score (accuracy 77.5 %). In aMCI patients with normal conventional Clock Drawing Test (cCDT) scores, both dCDT (accuracy 78.0 %) and CERAD total scores (accuracy 76.0 %) were equally accurate in discriminating against HCs. Finally, in differentiating patients with mAD from healthy individuals, accuracy of both dCDT (93.0 %) and CERAD total scores (92.3 %) was comparably high. dCDT is a fast, simple and suitable screening tool to identify early cognitive changes. Its performance is comparably well as the time-consuming established psychometric measure CERAD test battery.
IC‐P‐028: PATTERNS OF INCREASED AND DECREASED PRECUNEUS FUNCTIONAL CONNECTIVITY IN SCD DEPENDING ON AMYLOID STATUS
2019-07-01

The precuneus/posterior cingulate (PCC) is a hub region of the default-mode network (DMN) and a prominent target of amyloid-beta (Aß) deposition in MCI and AD causing subsequent disruptions of DMN functional connectivity (FC). In subjective cognitive decline (SCD), amyloid load effects on posterior DMN FC are less well known. We aimed to compare precuneus FC in SCD with and without amyloid deposition and to disentangle the contributions of regional & global Aß load. We included age and sex-matched 24 SCDAß+ and 22 SCDAß- individuals from the DELCODE-PET sub-cohort (Tab. 1), based on qualitative ratings of [18F]florbetaben (NeuraceqTM) PET scans by two experienced readers. Global and regional amyloid burden was quantified by standard uptake value ratios (SUVR) using cerebellar cortex as reference region. Resting-state fMRI data were acquired at 3T, and preprocessed and analyzed with DPARSFA. Seed-based FC maps were generated between the time series of a bilateral precuneus seed region and each voxel of the whole brain, respectively. Voxelwise FC group differences in two-sample t-tests were considered significant at p < 0.005 voxel-level and p < 0.05 FWE cluster-level. For clusters showing significant group differences, follow-up analyses explored correlations between their mean FC values and (i) regional PCC amyloid load and (ii) global amyloid load. Precuneus FC was significantly increased with occipital and lingual/cerebellar regions, and significantly decreased with left superior/middle frontal and left inferior parietal / angular regions in SCDAß+ as compared to SCDAß (Tab.2, Fig.1). In the SCDAß+ group only, precuneus-occipital mean FC showed a significant positive correlation with PCC amyloid load (r=0.42, p=0.04) (Fig.2).