julilili42/papers huggingface dataset:
[P3–437]: LATENT‐FACTOR STRUCTURE OF THE DELCODE STUDY NEUROPSYCHOLOGICAL TEST BATTERY
2017-07-01

A major aim of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) is to improve characterization of subjective cognitive decline (SCD) as an at risk condition for preclinical Alzheimer's disease (AD). In order to characterize early cognitive changes in DELCODE, an extensive neuropsychological test battery (DELCODE-NP) was applied in the study. Here we report on a first confirmatory factor analysis (CFA) of this battery. We analysed data of 141 healthy controls (HC), 126 SCD, 65 amnestic MCI, 40 mild AD dementia, and 22 first degree relatives of AD dementia patients. This sample (n=394) is a preliminary subset of the whole baseline sample (planned N=1000, end of recruitment: Dec. 2017). The DELCODE-NP consists of tests representing the following five cognitive domains: (1) Learning & Memory (MEM; e.g. ADAScog Wordlist, Logical Memory), (2) Executive Functions & Speed (EXEC; e.g. Trail-Making, Symbol-Digit-Modalities), (3) Language (LANG; e.g. Verbal Fluency, Confrontation Naming), (4) Working Memory (WM; e.g. Digit Span forward/backward), (5) Visuospatial Functions (VIS; e.g. Clock-drawing, Constructional praxis). We used CFA methods to confirm a latent 5-factor structure comprising these (inter-correlated) domains within the complete sample. To test whether these cognitive domains are sensitive to early, preclinical AD related deficits, we compared composite z-score performance in AD-biomarker positive vs. negative cognitively normal participants (i.e. HC+SCD) for each cognitive domain. The CFA revealed a very good fit of the proposed five-factor structure in the preliminary baseline sample (RMSEA=0.053, 90% C.I.: 0.045–0.061, CFI=0.954, SRMR=0.046). In addition, cognitively normal participants with abnormal CSF-Aβ42/40 and/or CSF-Aβ42/tau values showed significantly lower (age-adjusted) performance in MEM and EXEC (Cohen's d= 0.4–0.5, p<0.05; Figure 1). No significant differences were found for LANG, WM and VIS. The results yield a first psychometric basis for using the proposed 5-factor structure in DELCODE. The structure matches well with those of the ADNI (Park et al. 2012) and WRAP (Dowling et al. 2010) cohort, thus yielding excellent comparability to these studies, and seems to capture subtle cognitive deficits in domains known to be affected earliest in AD. “Learning and Memory” performance in Cognitively Normal Participants (Healthy Controls and Subjective Cognitive Decline) according to their CSF biomarker status. “Executive Functions & Speed” performance in Cognitively Normal Participants (Healthy Controls and Subjective Cognitive Decline) according to their CSF biomarker status.
Chondrification and Character Identification in the Skull Exemplified for the Basicranial Anatomy of Early Squamate Embryos.
2017-07-01

The neurocranium of vertebrates is mainly derived from early cartilaginous anlagen, the so-called chondrocranium, the base of the future skull. Two initial bar-shaped and paired chondrifications flank the notochord, the rostral trabecles and the caudal parachordals. In most reptiles, there is an additional component, the transverse acrochordal, which is placed between trabecles and parachordals. All these elements compose the base of the future chondrocranium. There are several drastically different hypotheses concerning the development and interrelationship of these elements. We reexamined the basicranial development in four squamates and found that all species show very similar conditions of early chondrocranial development. The anterior part of the notochord is not embedded into the basal plate as it was previously reported. It remains free. The medial edges of the parachordals form the lateral walls of the basicranial fenestra. Only the posterior portions of the parachordals fuse and form the basal plate. The space in-between the parachordals is filled with a thin layer of cells, which never chondrify. The anterior tips of the parachordals later fuse with the posterior edge of the acrochordal, which ultimately delimitates, as crista sellaris, the basicranial fenestra anteriorly. We consider the observed processes a common development at least in lizards and review a variety of methodological approaches and differences in data interpretation as reasons for the anatomical differences reported in the literature. Moreover, based on our data we argue that the acrochordal is of mesodermal origin, which coincides with results of fate map experimental studies.
Improved CT-detection of acute bowel ischemia using frequency selective non-linear image blending
2017-07-01

Background Computed tomography (CT) as a fast and reliable diagnostic technique is the imaging modality of choice for acute bowel ischemia. However, diagnostic is often difficult mainly due to low attenuation differences between ischemic and perfused segments. Purpose To compare the diagnostic efficacy of a new post-processing tool based on frequency selective non-linear blending with that of conventional linear contrast-enhanced CT (CECT) image blending for the detection of bowel ischemia. Material and Methods Twenty-seven consecutive patients (19 women; mean age = 73.7 years, age range = 50–94 years) with acute bowel ischemia were scanned using multidetector CT (120 kV; 100–200 mAs). Pre-contrast and portal venous scans (65–70 s delay) were acquired. All patients underwent surgery for acute bowel ischemia and intraoperative diagnosis as well as histologic evaluation of explanted bowel segments was considered “gold standard.” First, two radiologists read the conventional CECT images in which linear blending was adapted for optimal contrast, and second (three weeks later) the frequency selective non-linear blending (F-NLB) image. Attenuation values were compared, both in the involved and non-involved bowel segments creating ratios between unenhanced and CECT. Results The mean attenuation difference between ischemic and non-ischemic wall in the portal venous scan was 69.54 HU (reader 2 = 69.01 HU) higher for F-NLB compared with conventional CECT. Also, the attenuation ratio between contrast-enhanced and pre-contrast CT data for the non-ischemic walls showed significantly higher values for the F-NLB image (CECT: reader 1 = 2.11 (reader 2 = 3.36), F-NLB: reader 1 = 4.46 (reader 2 = 4.98)]. Sensitivity in detecting ischemic areas increased significantly for both readers using F-NLB (CECT: reader 1/2 = 53%/65% versus F-NLB: reader 1/2 = 62%/75%). Conclusion Frequency selective non-linear blending improves detection of bowel ischemia compared with conventional CECT by increasing attenuation differences between ischemic and perfused segments.
Evaluation of filtering techniques to extract movement intention information from low-frequency EEG activity
2017-07-01

Low-frequency electroencephalographic (EEG) activity provides relevant information for decoding movement commands in healthy subjects and paralyzed patients. Brainmachine interfaces (BMI) exploiting these signals have been developed to provide closed-loop feedback and induce neuroplasticity. Several offline and online studies have already demonstrated that discriminable information related to movement can be decoded from low-frequency EEG activity. However, there is still not a well-established procedure to guarantee that this activity is optimally filtered from the background noise. This work compares different configurations of non-causal (i.e., offline) and causal (i.e., online) filters to classify movement-related cortical potentials (MRCP) with six healthy subjects during reaching movements. Our results reveal important differences in MRCP decoding accuracy dependent on the selected frequency band for both offline and online approaches. In summary, this paper underlines the importance of optimally choosing filter parameters, since their variable response has an impact on the classification of low EEG frequencies for BMI.
Hypergroup structures arising from certain dual objects of a hypergroup
2017-07-01

In the present paper hypergroup structures are investigated on distinguished dual objects related to a given hypergroup , especially to a semi-direct product hypergroup defined by an action of a locally compact group on a commutative hypergroup . Typical dual objects are the sets of equivalence classes of irreducible representations of , of infinite-dimensional irreducible representations of type I hypergroups , and of quasi-equivalence classes of type factor representations of non-type I hypergroups . The method of proof relies on the notion of a character of a representation of .
Abstract 159: Pharmacological characterization of the selective, orally bioavailable, potent dual PI3K/mTORC1/2 inhibitor PQR530
2017-07-01

Abstract Introduction: The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a fundamental role in many cellular processes like growth, survival, proliferation, differentiation and motility. In cancers several mutations have been identified that lead to constitutive activation of PI3K. PQR530 is a novel, ATP site directed inhibitor of all PI3K isoforms and the mammalian target of rapamycin (mTOR) complexes C1/2 that is currently in pre-clinical development. PQR530 potently binds to its targets, inhibits cell proliferation and shows excellent selectivity versus related and unrelated kinases [1]. Results: PQR530 inhibits PI3K signaling in stimulated MCF7 cells as detected by PathScan analysis. Excellent tolerability has been found for PQR530 during GLP toxicological testing in rats and dogs. Increase in insulin and blood glucose, a treatable class effect of PI3K inhibitors, has been observed after PQR530 administration to mice. Investigation of mutagenicity and hERG binding resulted in a clean profile. PQR530 exhibited dose-proportional pharmacokinetics (PK) in male C57BL/6J mice. A maximum concentration (Cmax) in plasma and brain was reached after 30 minutes (7.8 μg/ml and 112.6 μg/ml, respectively) indicating that efficacious concentrations were reached in both tissues. The calculated half-life (t1/2) for plasma and brain was approximately 5 hours. PQR530 potently inhibited PI3K signaling in vivo for several hours after administration of a single oral dose of 50 mg/kg. Tumor growth was significantly decreased in SUDHL-6 lymphoma, RIVA lymphoma and OVCAR-3 ovarian cancer mouse xenografts using daily, oral administration. Conclusion: PQR530 is a potent, ATP competitive pan-PI3K and mTORC1/2 inhibitor. The physico-chemical properties of PQR530 result in good oral bioavailability and excellent brain penetration. PQR530 is well tolerated and efficiently inhibits tumor growth in xenograft models. Preclinical data allow for further development of the compound. [1] Rageot D, et al., Discovery and biological evaluation of PQR530, a highly potent dual pan-PI3K/mTORC1/2 inhibitor, abstract submitted for AACR Annual Meeting 2017, April 1-5, Washington, D. C., USA. Citation Format: Petra Hillmann, Denise Rageot, Florent Beaufils, Anna Melone, Alexander Sele, Robert A. Ettlin, Jürgen Mestan, Vladimir Cmiljanovic, Marc Lang, Elisabeth Singer, Carolin Walter, Hoa HP Nguyen, Paul Hebeisen, Matthias P. Wymann, Doriano Fabbro. Pharmacological characterization of the selective, orally bioavailable, potent dual PI3K/mTORC1/2 inhibitor PQR530 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 159. doi:10.1158/1538-7445.AM2017-159
[P3–218]: TAU PLASMA LEVELS IN SUBJECTIVE COGNITIVE DECLINE: RESULTS FROM THE DELCODE STUDY
2017-07-01

Previous studies have demonstrated increased Tau plasma levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD. Recently, the BioFINDER (Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably) study failed to demonstrate increased Tau plasma levels in the pre-MCI stage of subjective cognitive decline (SCD). In the present study we measured Tau plasma levels in 111 SCD patients and 134 age- and gender-matched cognitively healthy controls participating at the DZNE (German Center for Neurodegenerative Diseases) longitudinal study on cognition and dementia (DELCODE). Tau plasma levels were measured using ultra-sensitive, single-molecule array (Simoa) technology. Using a general linear model, we found no significant different Tau plasma levels in SCD patients (3.4 pg/ml) compared with healthy controls (3.6 pg/ml) after controlling for age, gender, and education (p=0.139). In addition, Tau plasma levels did not correlate with Aβ42 (r=0.102; p=0.506), tTau (r=-0.168; p=0.270), and pTau181 (r=-0.161; p=0.289) cerebrospinal fluid (CSF) levels in a subgroup of 45 SCD patients with available CSF. Plasma Tau is not increased in clinically diagnosed SCD patients. In addition, the lack of correlation between Tau in plasma and CSF in the examined SCD cohort indicates that Tau may derive from different sources in both biofluids.
Rationality, time and normativity: On Hedden’s time-slice rationality
2017-07-01

In his stimulating recent book Reasons without Persons, Brian Hedden develops a novel theory of rationality that he calls Time-Slice Rationality (TSR). One of the main theses of TSR is that all rational requirements are synchronic. We argue here first that this thesis is not well-motivated. We also demonstrate that Hedden is in fact committed to an even stronger claim about the rationality of an agent at a time. Finally, we provide some arguments against the conception of rationality that results from this stronger claim.
[IC‐P‐080]: USEFULNESS AND STABILITY OF MULTICENTER DIFFUSION TENSOR IMAGING AS AN EARLY MARKER FOR SUBJECTIVE COGNITIVE DECLINE AND AMNESTIC MILD COGNITIVE IMPAIRMENT: FIRST RESULTS FROM THE PROSPECTIVE DZNE DELCODE STUDY
2017-07-01

Diffusion tensor imaging (DTI) is a useful diagnostic marker for differentiating patients with mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD) from cognitively normal controls, as reported in various monocentric studies. Few monocentric studies performed DTI in individuals with subjective cognitive decline (SCD), who may be at risk of future AD. Compared to normal controls, most of these studies showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD). However, multicenter studies using retrospective data reported a high vulnerability of DTI indices to nuisance variance, introduced by differences in acquisition parameters and study procedures. In the present study, we examined the stability of DTI in a large prospective multicenter cohort using identical scanning protocols and high-level standardized procedures. Furthermore, we assessed the usefulness of multicenter DTI to differentiate between individuals with SCD, MCI patients, AD patients and normal controls. N = 198 subjects from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study were included in the analysis. We calculated the FA and MD indices for the baseline DTI data that was acquired across seven sites and analyzed them using tract-based spatial statistics (TBSS) and voxel-based analysis. For the latter approach, we applied partial volume correction to reduce the effect of cerebrospinal fluid contamination on grey matter MD estimates. Results will be presented at the conference. We expect to find reduced inter-site variability compared to a multicenter DTI study without harmonized acquisition parameters (European DTI study on Dementia; EDSD). Comparing the diagnostic groups, we expect to find decreased FA and increased MD indices in SCD subjects compared to normal controls, as well as in MCI and AD patients compared to SCD subjects and normal controls. The results from this study will contribute to the evaluation of DTI as a diagnostic marker at prodromal and at-risk stages of AD.
Abstract LB-017: HSP110 sustains aberrant NFkB signaling in activated B-cell diffuse large B-cell lymphoma through MyD88 stabilization
2017-07-01

Abstract Diffuse large B cell lymphoma (DLBCL) is an aggressive lymphoproliferative disorder of B lymphocytes accounting for 30 % of adult Non Hodgkin Lymphoma (NHL). Among DLBCL, Activated B Cell - DLBCL (ABC-DLBCL) is the most aggressive form and has a poor prognosis. Heat-shock proteins (HSPs) are molecular chaperons highly expressed in cancer cells and implicated in resistance to radio- and chemotherapy. Therefore, HSPs are envisioned as therapeutic targets in many cancers. Among the different HSPs, HSP110 has been recently identified as a pro-survival factor in germinal center-derived DLBCL (GC-DLBCL), through stabilization of the GC-DLBCL oncogene Bcl-6. Here, we have explored if HSP110 could also be involved in the survival of the most aggressive form of DLBCL. We observed a high HSP110 expression in all ABC-DLBCL patient samples, compared to normal reactive lymph nodes by using IHC staining of ABC-DLBCL tumor sections and transcriptional analysis of ABC-DLBCL patient tumors. Furthermore, shRNA silencing of HSP110 decreases the survival of several ABC-DLBCL cell lines, and downregulates the expression of pro-survival factors such as BcL2 and BcL-XL. SiRNA silencing of HSP110 abrogates NF-kB signaling, which is the major oncogenic pathway in ABC-DLBCL cell lines. In accord with these results, over-expression of HSP110 in DLBCL and non-DLBCL cell lines increases NF-kB signaling, indicating a tight interplay between HSP110 and the NF-kB pathway. Using immune-precipitation and DuolinkTM assays, we identified an in vitro and in cellulo interaction between HSP110 and Myd88, a critical protein of the NF-kB pathway that bears an activated mutation in many ABC-DLBC patients and that is responsible for lymphoma aggressiveness. Finally, we demonstrate that HSP110 stabilizes the wild type as well as the mutated form of Myd88, therefore facilitating the chronic NF-kB pathway activation in those cells. In conclusion, we identified HSP110 as a regulator of NF-kB signaling through MyD88 stabilization in ABC-DLBCL. This finding highlights HSP110 as a new potential therapeutic target in DLBCL. Citation Format: Christophe Boudesco, Sebastien Causse, Arlette Hammann, Els Verhoeyen, Laurent Martin, Thierry Fest, Oliver Wolz, Alexander Weber, Carmen Garrido, Gaetan Jego. HSP110 sustains aberrant NFkB signaling in activated B-cell diffuse large B-cell lymphoma through MyD88 stabilization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-017. doi:10.1158/1538-7445.AM2017-LB-017
Abstract 1224: Combination of rapamycin and crizotinib induces partial remission of pleural mesothelioma in a patient-derived xenograft model
2017-07-01

Abstract Introduction: Malignant pleural mesothelioma (MPM) is a neoplasm with inferior prognosis and notorious chemotherapeutic resistance. New treatment approaches may be based on specific inhibitors against kinases that are overexpressed in MPM, such as mTOR and MET. Here we examined the tyrosine kinase ALK as a potential therapeutic target and the combinatorial efficacy of the ALK/MET inhibitor crizotinib and the mTOR inhibitor rapamycin. Methods: We investigated the ALK status and the expression of mTOR and MET in 145 primary MPM and 8 murine patient-derived xenograft models. ALK overexpression, rearrangement and mutation were studied by qRT-PCR, FISH, immunohistochemistry and sequence analysis. Expression of mTOR and MET was analyzed by qRT-PCR and immunohistochemistry. The combined anti-tumor effect of crizotinib and rapamycin was evaluated in a patient derived xenograft model. Effects of single drug vs. combination treatment on proliferation, apoptosis and autophagy were assessed using Ki-67 immunohistochemistry, TUNEL assay and LC3B immunofluorescence, respectively. Results: Overexpression of ALK transcripts was detected in 25 (19.5%) of 128 interpretable primary MPM and two xenograft tumors and was neither associated with ALK rearrangement nor with mutation of the kinase domain. ALK protein was expressed in 8.3% MPM and the two xenograft tumors expressing ALK transcript. mTOR protein expression was detected in 28.7% MPM, co-expressed with ALK and/or MET in 17.8% MPM. Applied to a patient derived MPM xenograft model that co-expressed ALK, MET and mTOR, crizotinib alone did not exert anti-tumor growth activity, but enhanced the anti-tumor effect of rapamycin: Rapamycin was effective in 3 of 5 tumors (pathological partial remission in 1, stable tumor in 2 cases). Combination treatment was active in all 5 tumors (partial remission in 4, stable tumor in 1 case). Simultaneous treatment with rapamycin and crizotinib, however, significantly suppressed tumor proliferation compared to rapamycin-single treatment. Autophagy was induced by both single drug treatments and distinctly enhanced by combination treatment, while apoptosis was not promoted. Conclusion: Dual combinatory treatment of rapamycin and crizotinib is more effective than rapamycin as single agent in suppressing MPM tumor growth and therefore merits further investigation. Citation Format: Dina Mönch, Sabine Bode-Erdmann, Jörg Kalla, Jörn Sträter, Carsten Schwänen, Roger-Fei Falkenstern-Ge, Martin Kimmich, Martin Kohlhäufl, Godehard Friedel, German Ott, Claudia Kalla. Combination of rapamycin and crizotinib induces partial remission of pleural mesothelioma in a patient-derived xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1224. doi:10.1158/1538-7445.AM2017-1224