julilili42/papers huggingface dataset:
A Cognitive Reserve Network That Moderates the Relationship Between Alzheimer’s Disease Pathology and Cognition
2022-12-01

Abstract Background The new consensus definition of cognitive reserve (CR) provides a framework to study individual differences in cognitive functioning relative to aging and disease. CR denotes a property of the brain that allows for better than expected cognitive performance given the degree of age‐related brain changes or disease. More specifically, individual differences in patterns of brain activity during fMRI tasks might explain the differential susceptibility to pathological burden. Method According to the consensus definitions, we sought to identify and quantify CR from fMRI novelty‐contrast maps in a large multi‐centric sample (DELCODE) consisting of 215 participants with SCD, 79 with MCI, 30 with AD dementia, 56 AD relatives and 156 cognitively normal controls (CN). CSF amyloid‐42/40 ratio, CSF p‐tau and hippocampal volume (ATN) were reduced to a single number, representing a (Alzheimer’s) disease progression (DP) score. To identify a CR network, voxel‐wise linear regression models determined where functional task‐activation moderates the relationship between DP and cognition. Finally, task‐related activity within the CR network was extracted to obtain individual fMRI‐based CR scores. Result The DP score showed a strong negative quadratic association with baseline memory scores. CR voxels, in which higher or lower activation were associated with better cognition, weakening the effect of DP, were mainly located within the novelty network. They included lateral‐occipital and superior‐parietal regions, lingual and fusiform gyrus, cuneus and small parts of cingulate. While there was no association between the CR score and cognition in CNs, higher CR scores in MCI and AD patients were related to higher PACC5 scores. Conclusion We established a DP score that collapses the ATN measures into a single number, while retaining its deleterious effect on an individual’s memory score. Furthermore, a newly identified task‐dependent CR network could be used to establish a CR score, which was related to higher PACC5 scores in MCI and AD patients, suggesting a functional compensation mechanism at later stages of AD that is not yet present in CN. Thus, targeted alteration of brain activity might be a promising route to modify cognitive trajectories in MCI and AD patients. Further, detailed examination of individuals with high CR might reveal additional disease‐modifying factors.
EP115/#640 Are all stage IA p53abn endometrial cancers the same? Seeking clarity in the management of stage IA p53abn and/or non-endometrioid endometrial cancers without myometrial invasion
2022-12-01

<h3>Objectives</h3> Optimal management of stage IA p53abn and/or high-grade non-endometrioid endometrial cancer(EC) without myometrial invasion is unclear, classified as intermediate risk in new 2020 ESGO-ESTRO-ESP guidelines. Current practice varies from surgery alone to adjuvant vault brachytherapy (VB)±chemotherapy. Our aim was to assess the risk of disease recurrence within three subcategories of stage IA ECs without myoinvasion compared to IA with myoinvasion(&lt;50%). <h3>Methods</h3> Stage IA p53abn and high-grade non-endometrioid ECs of other molecular subtypes were identified from a retrospective EC cohort (2005–2016). Cases were segregated into IA with no myoinvasion, including i) tumor restricted to a polyp, ii) tumor confined to the endometrium, and iii) no residual tumor, vs. stage IA with myoinvasion(&lt;50%), with treatment and outcomes assessed. <h3>Results</h3> 169 stage IA p53abn and 49 stage IA non-endometrioid ECs of other molecular subtypes were identified (7 POLEmut, 24 MMRd and 18 NSMP). Table 1 shows the subcategories, adjuvant treatment, and disease recurrences. 12 patients(15%) with stage IA no myoinvasion recurred; 1 had received chemotherapy, 3 VB, 1 EBRT, 7 no adjuvant therapy. 35 patients with disease confined to the endometrium had received no adjuvant therapy with 6 (17.1%) recurrences (2 additional recurrences with VB). Stage IA patients not receiving chemotherapy had a ~17% recurrence rate, whether with myoinvasion (17.1%) or without (16.7%). <h3>Conclusions</h3> Rates of recurrence were the same in patients with stage IA p53abn and/or non-endometrioid EC regardless of myoinvasion. Optimal treatment for the diverse spectrum of stage IA p53abn disease remains a challenge but these recurrence rates should prompt consideration of adjuvant therapy.
EP222/#606 Acid ceramidase (ASAH1) expression is associated with improved overall survival in patients with high-grade serous ovarian cancer from the ICON-7 trial
2022-12-01

<h3>Objectives</h3> Despite recent progress in the treatment of epithelial ovarian cancer the cure of this disease remains a challenge. Therefore new treatment options along with new prognostic and predictive makers are urgently needed. The enzyme acid ceramidase (AC) plays a central role in the sphingolipid network which is involved in tumorigenesis and progression. Furthermore AC directed therapies are currently under development. We investigated the expression of AC and its prognostic impact on ovarian cancers. <h3>Methods</h3> Patients of the AGO-cohort of the ICON-7 trial were analysed. In this randomized trial patients with advanced EOC received carboplatin+paclitaxel vs. carboplatin+paclitaxel+bevacizumab. Tissue micro arrays (TMAs) were constructed for performing immunohistochemical analysis of AC. The results were correlated with clinico-pathological characteristics and survival data. <h3>Results</h3> Kaplan-Meier analysis (n=351) revealed that high levels of AC were associated with improved progression-free survival (PFS; 24.12 months [95% confidence interval (CI): 19.36 – 28.86] vs. 16.69 months [95% CI: 14.91 – 18.71], p &lt; 0.0001) and overall-survival (OS; 66.83 months [95%CI: –] vs. 44.12 months [95%CI: 37.37 – 50.87], p &lt; 0.0001). Subsequently, the prognostic value of AC expression together with clinical factors (i.e. FIGO stage, grading, histological subtype, bevacizumab medication and residual tumour burden after surgery) was further confirmed in multivariate Cox regression analysis in n= 426 patients (PFS: hazard ratio (HR) = 0.69 [95% CI: 0.550 – 0.877], p = 0.002; OS: HR = 0.67 [95%CI: 0.504 – 0.881], p = 0.004). <h3>Conclusions</h3> Our data identify high levels of AC expression as a strong favorable prognostic marker in ovarian cancer patients.
On adiabatic theory for extended fermionic lattice systems
2022-12-01

We review recent results on adiabatic theory for ground states of extended gapped fermionic lattice systems under several different assumptions. More precisely, we present generalized super-adiabatic theorems for extended but finite and infinite systems, assuming either a uniform gap or a gap in the bulk above the unperturbed ground state. The goal of this Review is to provide an overview of these adiabatic theorems and briefly outline the main ideas and techniques required in their proofs.
Sustainable Exploitation of Bio-Engineered Microorganisms for the Discovery and Development of Novel Biosurfactants and Siderophores with Industrial Applications
2022-12-01

SECRETed project aims to exploit the potential of Systems and Synthetic Biology toolboxes and their application within aquatic biotechnology to develop novel hybrid compounds for the agrochemical, pharmaceutical, cosmetic and chemistry sectors. Biosynthetic pathways of marine and extremophilic microorganisms will be reverse engineered to infer the individual roles of their constituent genes, which will be further combined for the production of non-natural biosurfactants and siderophores with tailor-made properties. Biosurfactants are compounds with surface-active nature tendency to adsorb at interfaces, while siderophores have the ability to chelate and transport Fe3+ ions. An iterative procedure following the Design-Build-Test-Learn methodological steps ([Fig. 1]) will be used to produce new microbial strains that support the selected genetic elements and satisfy sustainable industrial processing solutions for the production of biosurfactants and siderophores. The amphiphilic nature of biosurfactants and marine siderophores provides an exciting opportunity to develop methods of biosynthesis that would enable the exchange of their hydrophobic and hydrophilic chemical parts enabling the development of new-to-nature compounds.
Relativity and normativity as a challenge of subject- matter teaching and learning
2022-12-01

Abstract In a plural and democratic society teaching challenges not only arise from the conditionality and perspectivity of knowledge, convictions and value systems, but also from a postfactual thinking. Questions of how to deal with one’s own subject-specific norms are sometimes pushed into the background in academic subject didactics. The article shows the potential of interdisciplinary comparison by using the example of classroom communication norms within different disciplines with strong subject cultures. An exchange regarding relativity and normativity could profile the subject-specificity of knowledge and knowledge communication as a necessary orientation against simplification and disambiguation for teachers and students in an uncertain world.
The institutionalisation of childhood and the institutionalisation of education. Reconsidering a not so simple relationship
2022-12-01

In social sciences, the notion of institutionalisation of childhood is well established as a concept for theorizing childhood and analysing the social position of children in modern societies. Among scholars, there is broad agreement that the institutionalisation of education, especially scholarisation, makes up a major part of the institutionalisation of childhood. Assuming that both processes of institutionalisation are entangled, this paper will, nonetheless, argue, that they should not be confused with each other. Otherwise, it would not possible to study how these processes are related and interfere. In a first step, it will be illustrated in how far the institutionalisation of childhood can systematically and analytically be distinguished from the notion of the institutionalisation of education. In a second step, the relationship of both processes will be further clarified by referring to empirical findings and data of two research projects. Besides the interference, the two examples demonstrate as well the different theoretical conclusions which both perspectives suggest.
Induction of significant neutralizing antibodies against SARS-CoV-2 by a highly attenuated pangolin coronavirus variant with a 104nt deletion at the 3'-UTR
2022-12-01

SARS-CoV-2 related coronaviruses (SARS-CoV-2r) from Guangdong and Guangxi pangolins have been implicated in the emergence of SARS-CoV-2 and future pandemics. We previously reported the culture of a SARS-CoV-2r GX_P2V from Guangxi pangolins. Here we report the GX_P2V isolate rapidly adapted to Vero cells by acquiring two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104-nucleotide deletion in the hypervariable region (HVR) of the 3′-terminus untranslated region (3′-UTR). We further report the characterization of the GX_P2V variant (renamed GX_P2V(short_3UTR)) in <i>in vitro</i> and <i>in vivo</i> infection models. In cultured Vero, BGM and Calu-3 cells, GX_P2V(short_3UTR) had similar robust replication kinetics, and consistently produced minimum cell damage. GX_P2V(short_3UTR) infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection in pulmonary, not extrapulmonary, tissues. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V(short_3UTR) is highly attenuated in <i>in vitro</i> and <i>in vivo</i> infection models. Attenuation of the variant is likely partially due to the 104-nt deletion in the HVR in the 3′-UTR. This study furthers our understanding of pangolin coronaviruses pathogenesis and provides novel insights for the design of live attenuated vaccines against SARS-CoV-2.
Miro1 R272Q disrupts mitochondrial calcium handling and neurotransmitter uptake in dopaminergic neurons
2022-12-02

The Rho GTPase Miro1, located at the mitochondrial outer membrane is known to properly distribute mitochondria to synapses, aid calcium buffering and initiate PINK1-Parkin mediated mitophagy. Several heterozygous RHOT1 /Miro1 variants were identified in sporadic Parkinson’s disease patients. Miro1 R272Q is located within a calcium binding domain, but the functional outcome of this point mutation and its contribution to the development of disease are unclear. To address this, we introduced a heterozygous RHOT1 /Miro1 R272Q point mutation in healthy induced pluripotent stem cells. In dopaminergic neurons, Miro1 R272Q does not affect Miro1 protein levels, CCCP-induced mitophagy, nor mitochondrial movement yet causes the fragmentation of mitochondria with reduction of cristae and ATP5A. Inhibition of the mitochondrial calcium uniporter phenocopied Miro1 R272Q cytosolic calcium response to Thapsigargin in active neurons, a similar effect was observed during the calcium buffering phase in Miro1 knockdown neuroblastoma cells. Altered mitochondrial calcium regulation is associated with reduced mitochondrial respiration and reduced catecholamine neurotransmitter uptake. Synaptic changes are not coupled to dopamine distribution or dopamine transporters but are linked to Miro1 R272Q-related calcium handling via the mitochondria concomitant with defective dopamine regulation at the mitochondrial surface by monoamine oxidase. We conclude that the Miro1 R272Q heterozygous point mutation dampens mitochondrial-calcium regulation and mitochondrial capacity via events at the outer membrane that are sufficient to disrupt dopaminergic function.
Knapping force as a function of stone heat treatment
2022-12-02

We propose a quantitative framework for understanding the knapping force requirements imposed by different raw materials in their unheated and heat-treated states. Our model interprets stone tool knapping as being the result of cracks formed during the first impact with a hammer stone, followed by continued stressing of these cracks that eventually leads to flake detachment. We combine bending strength, indentation fracture resistance and “Griffith” crack lengths of flint and silcrete to obtain functions identifying critical forces for flaking without or after heat treatment. We argue that these forces are a key factor for understanding the “knappability” of different raw materials, because only forces with 100N or less can be used for very precise strike control. Our model explains for the first time why experimental knappers frequently observe that flint (a stronger material, which, in our case, has a strength above 100 MPa) is easier to knap than silcretes (which is relatively weaker with strength values at or below 60 MPa). Our findings allow for understanding the differences between heat-treated and untreated flint and silcrete in terms of knapping quality, and they allow to compare the qualities of different raw materials.
Deep‐time invention and hydrodynamic convergences through amniote flipper evolution
2022-12-02

Abstract The diapsid plesiosaurs were pelagic and inhabited the oceans from the Triassic to the Cretaceous. A key evolutionary character of plesiosaurs is the four wing‐like flippers. While it is mostly accepted that plesiosaurs were underwater fliers like marine turtles, penguins, and maybe whales, other swimming styles have been suggested in the past. These are rowing and a combination of rowing and underwater flight (e.g., pig‐nosed turtle, sea lion). Underwater fliers use lift in contrast to rowers that employ drag. For efficiently profiting of lift during underwater flying, it is necessary that plesiosaurs twisted their flippers by muscular activity. To research the evolution of flipper twisting in plesiosaurs and functionally analogous taxa, including turtles, we used anatomical network analysis (AnNA) and reassessed distal flipper muscle functions. We coded bone‐to‐bone and additionally muscle‐to‐bone contacts in N × N matrices for foreflippers of the plesiosaur, the loggerhead sea turtle, the pig‐nosed turtle, the African penguin, the California sea lion, and the humpback whale based on literature data. In “R,” “igraph” was run by using a walktrap algorithm to obtain morphofunctional modules. AnNA revealed that muscle‐to‐bone contacts are needed to detect contributions of modules to flipper motions, whereas only‐bone matrices are not informative for that. Furthermore, the plesiosaur, the marine turtles, the seal, and the penguin flipper twisting mechanisms, but the penguin cannot actively twist the flipper trailing edge. Finally, the foreflipper of the pig‐nosed turtle and of the whale is not actively twisted during swimming.
A Feasibility Study for Immediate Histological Assessment of Various Skin Biopsies Using Ex Vivo Confocal Laser Scanning Microscopy
2022-12-02

Background: Digitally stained ex vivo confocal laser scanning microscopy (CLSM) scans are a possible alternative to formalin-fixed and paraffin-embedded (FFPE) and hematoxylin-eosin (H&amp;E) stained slides. This study explores the diagnostic accuracy of digitally-stained CLSM scans in comparison to H&amp;E-stained slides in various dermatologic diseases in a real-life setting. Methods: Samples of patients out of one selected dermatologic office were primarily scanned via CLSM; a diagnosis was made afterwards using FFPE- and H&amp;E-stained slides by two experienced dermatopathologists. Primary outcomes were sensitivity and specificity of diagnosis in digitally stained CLSM scans in three separate diagnostic groups. Results: CLSM evaluation of epithelial tumors (n = 132) demonstrated a sensitivity of 64.3%/83.9% and a specificity of 84.2%/71.1%. Diagnosis of melanocytic tumors (n = 86) showed a sensitivity of 19.1%/85.1% and a specificity of 96.3%/66.7%. In the diagnosis of other tumors/cysts and inflammatory dermatoses (n = 42), a sensitivity of 96.4%/96.8% and a specificity of 57.1%/45.5% was reached. Conclusions: This study shows the possibilities and limitations of a broad use of CLSM. Because of a partly low diagnostic accuracy, such an application does not seem to be recommendable at present for every indication.
Longitudinal morphological changes of the aorta and the endograft position before and after distal stent graft-induced new entry in aortic dissections
2022-12-02

Abstract OBJECTIVES The aim of this study was to assess the endograft position and aortic geometry changes after thoracic endovascular aortic repair (TEVAR) and frozen elephant trunk (FET) in distal stent-induced new entry (dSINE) patients. METHODS In this retrospective cohort study, the baseline demographic and the follow-up data were extracted from the hospital records, and computed tomography scans of dSINE patients after TEVAR or FET between 2011 and 2021 were analysed regarding endograft oversizing, length and migration, taper ratio, aortic diameter at the endograft end, aortic elongation (thoracic inner and outer curvature), wedge apposition angle and tortuosity angle in the distal landing zone. RESULTS dSINE was found in 22/213 (10%) of TEVAR and 10/31 (32%) of FET patients. The total follow-up time was 45 (27; 59) months. TEVAR was mainly performed with Relay NBS endograft (77%) and FET with Evita open prosthesis (80%). Paraplegia and stroke rates were 3%. dSINE occurred 17 (7; 35) months post-TEVAR and was instantly treated in 18 patients (56%) or followed up for 21 (11; 34) months (n = 14). Migration [+5 mm (1; 11; P &amp;lt; 0.001)], birdbeak angle [+9° (0; 27; P = 0.039)] and aortic diameter +5 mm (1; 11; P &amp;lt; 0.001) increased after dSINE, whereas aortic elongation increased already before [+12 mm (0; 27; P = 0.015)] and peaked after dSINE [+30 mm (9; 38; P &amp;lt; 0.001)]. The aortic elongation was more pronounced in the outer aortic curvature before and after dSINE (before: P = 0.039, after: P = 0.024). Postoperative wedge apposition [17° (12; 20)] increased before dSINE [21° (16; 35; P &amp;lt; 0.001)] and peaked thereafter [31° (21; 40; P &amp;lt; 0.001)]. CONCLUSIONS Aortic elongation may influence the endograft position and provoke TEVAR failure in the distal and proximal landing zones.
Soy lecithin: A beneficial substance for adjusting the ADC in aqueous solutions to the values of biological tissues
2022-12-02

Purpose To test soy lecithin as a substance added to water for the construction of MRI phantoms with tissue‐like diffusion coefficients. The performance of soy lecithin was assessed for the useable range of adjustable ADC values, the degree of non‐Gaussian diffusion, simultaneous effects on relaxation times, and spectral signal properties. Methods Aqueous soy lecithin solutions of different concentrations (0%, 0.5%, 1%, 2%, 3% ..., 10%) and soy lecithin–agar gels were prepared and examined on a 3 Tesla clinical scanner at 18.5° ± 0.5°C. Echoplanar sequences ( b values: 0–1000/3000 s/mm 2 ) were applied for ADC measurements. Quantitative relaxometry and MRS were performed for assessment of T 1 , T 2 , and detectable spectral components. Results The presence of soy lecithin significantly restricts the diffusion of water molecules and mimics the nearly Gaussian nature of diffusion observed in tissue (for b values &lt;1000 s/mm 2 ). ADC values ranged from 2.02 × 10 −3 mm 2 /s to 0.48 × 10 −3 mm 2 /s and cover the entire physiological range reported on biological tissue. Measured T 1 /T 2 values of pure lecithin solutions varied from 2685/2013 to 668/133 ms with increasing concentration. No characteristic signals of soy lecithin were observed in the MR spectrum. The addition of agar to the soy lecithin solutions allowed T 2 values to be well adjusted to typical values found in parenchymal tissue without affecting the soy lecithin–controlled ADC value. Conclusion Soy lecithin is a promising substance for the construction of diffusion phantoms with tissue‐like ADC values. It provides several advantages over previously proposed substances, in particular a wide range of adjustable ADC values, the lack of additional 1 H‐signals, and the possibility to adjust ADC and T 2 values (by adding agar) almost independently of each other.
Generating and authoring high-variability exercises from authentic texts
2022-12-02

Integrating adaptivity into Task-Based Language Teaching requires exercises that transmit a specific content but whose complexity is adjusted to the learner’s level. Thus, exercises of varying complexity based on the same text are needed. Revising generated exercise variants is time consuming and redundant where the same underlying linguistic annotations can be used for exercise generation. We present a fully implemented approach to generate generalized exercise specifications as an interim step before turning them into concrete exercises, as well as an interface for efficient reviewing of the specifications.