julilili42/papers huggingface dataset:
IMMU-28. THE INTRA-TUMORAL SPATIAL HETEROGENEITY OF T CELL ANTIGENS IN GLIOBLASTOMA: AN INTEGRATED MULTI-OMICS APPROACH
2022-11-01

Abstract This study investigates the intratumoral heterogeneity of T cell antigen presentation in 15 newly diagnosed glioblastoma patients. Our multi-omics approach includes mass spectrometry-based immunopeptidome analysis, next-generation sequencing (whole-exome and RNA sequencing), and imaging mass cytometry performed on biopsies deriving from the necrotic core (NEC), the gadolinium contrast-enhancing region (T1), and the peritumoral infiltrating zone (INF, 5-ALA positive). A total of 24493 unique HLA class I and 17394 unique HLA class II peptides were identified. Comparative profiling of peptides from our study and a benign tissue database (in-house; n = 429 donors combined with HLA ligand atlas (https://hla-ligand-atlas.org)) revealed that 20% of HLA class I ligands are glioblastoma exclusive. Of these ligands, 21%, 21%, and 15% were exclusively presented in the INF, T1, or NEC zone, respectively. Here, we focused on the INF-specific antigens as this zone is likely to remain after tumor resection and gives rise to glioblastoma recurrence. Interestingly, two INF-specific HLA ligands showed a frequency presentation of 45% in our patient cohort. One ligand originated from BAALC (Brain and acute leukemia cytoplasmic protein) and one from NCAN (Neurocan core protein), which are both known to be glioblastoma-associated proteins. Immunogenicity of pre-selected candidate antigens was assessed with autologous expanded T cells and revealed a set of novel promising targets for immunotherapy. Integrated RNA/DNA sequencing also enabled the identification of neoepitopes deriving from tumor- and region-specific mutations. Furthermore, imaging mass cytometry contributed to investigating the immune compartment of the tumor microenvironment in high dimensionality and spatial resolution. In conclusion, our approach characterized the intra-tumoral regional heterogeneity of both infiltrating immune cells and tumor antigens. This multi-omics spatial atlas of the immune landscape can be used for the informed design of immunotherapy strategies against glioblastoma.
DISP-11. GENDER DISPARITY REGARDING WORK-LIFE BALANCE SATISFACTION AMONG GERMAN NEURO-ONCOLOGISTS: A YOUNGNOA SURVEY
2022-11-01

Abstract PURPOSE Satisfaction with work-life balance (WLB) is an essential factor for persistent motivation of early career researchers. However, WLB satisfaction in the neuro-oncological landscape is not well characterized. We present the results of an interdisciplinary survey focusing on WLB satisfaction among neuro-oncologists in Germany. METHODS The questionnaire was sent to 351 physicians, all of whom were members of the Neuro-oncology Working Group “Neuroonkologische Arbeitsgemeinschaft” (NOA) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG). The participants were asked for personal information, individual motivations, scientific interests, activities, individual workload, and job satisfaction. The questionnaire was accessible from 18 March 2021 to 1 April 2021. RESULTS Ninety-six physicians (36 female, 60 male) participated in this survey. Age, gender and relationship status were significantly different between participants who were satisfied and those not satisfied with their WLB. Female participants were less likely to be satisfied with their WLB than male participants (25% vs 75%, p = 0.005). In a logistic regression model, the finding that female participants were less likely to be satisfied with their WLB than male participants remained statistically significant (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.21–0.84, p = 0.023) after accounting for possible confounding variables such as age (OR 1.06; 95% CI 1.01–1.11, p = 0.025), childlessness (children available vs not available, OR 0.40; 95% CI 0.10–1.35, p = 0.156), and relationship status (unmarried vs single, OR 2.49; 95% CI 0.50–13.98, p = 0.275; married vs single, OR 6.18; 95% CI 1.29–35.46, p = 0.029). CONCLUSIONS This survey demonstrates that WLB satisfaction is significantly decreased among female neuro-oncologists in Germany. It highlights the importance of programs such as “Diversity in Neurooncology” (DivINe), founded by the NOA and aiming to address gender disparities.
Mobile-based, emotion-sensitive video diaries and ambulatory third-party assessments as indicators of mood states in bipolar disorder
2022-11-01

This article investigates the clinical value of a newly developed, mobile-based emotion recognition approach and ambulatory third-party assessments with respect to the recognition of symptom severity in bipolar disorder. We present three case studies with patients with bipolar disorder, examining either the emotion recognition approach (case 1 and 2) or the third-party assessments (case 3). Correlative analyses or Granger causality tests were conducted in order to evaluate the statistical association between the assessed parameters and clinically evaluated or self-assessed bipolar symptoms. As for case 1 and 2, manic symptoms are associated with changes of usage-related behavioral aspects of the system. Especially with case 2, there are multiple mood-dependent changes in the verbally or facially expressed emotions. Granger causality further indicates the predictive value of facially expressed happiness and behavioral patterns regarding occurring manic symptoms of this patient. As for case 3, third-party assessments are highly correlated with self-assessed symptoms. The exploratory and case-based approach comes with the limitations of small data sets, an increased risk of alpha inflation, or the limited generalizability of the results. Furthermore, missing values limit the implications of case 1 and 3. The findings indicate that bipolar symptoms are related to complex changes on the behavioral and emotional levels captured by the recognition approach. The results further support the high individuality of symptom ramifications that should be considered by future systems. More research is needed to confirm these findings and to examine the value of third-party assessments.
Wie ist die Welt zu erklären, wenn sie einer Erklärung bedarf?
2022-11-01

Abstract The essay explores in four steps the question of whether the world needs an explanation and how it is to be explained in the case of its need for explanation. The first step argues that the principle of sufficient reason is valid and may be applied to the world as a whole. The three following steps examine different possibilities of explaining the world. It is shown that neither an immanent nor an axiogenetic explanation is possible, but that only an ontotheological explanation has a chance of success.
Masāne kī horī: Singing life in the cremation ground
2022-11-01

Named after the Hindu spring festival of Holī, horī songs generally portray the frolicsome play of the day with the throwing of coloured powders by Kṛṣṇa as the main protagonist pranking Rādhā and the gopī-s in Braj. The horī analysed in the present paper shows idiosyncrasies unveiling religious, theological, and ritual significance, besides offering precious insights into a ‘living tradition’: the celebration of Holī in the city of Banaras, at the cremation ground in Maṇikarṇikā ghāṭ where śaiva devotees enact and ‘actualise’ the horī. The song depicts Śiva playing Holī in the cremation ground with his retinue of ghostly creatures that are his favourite companions along with Aghorī-s. In place of colours, Śiva tosses the ashes from funeral pyres. In his divine dance and drumming, Mahādev uses the poisonous snakes adorning him as water-guns to squirt venom instead of gulāl. The atypical choice of Śiva in one of his fearful manifestations as the subject of a horī is discussed through references to philosophical and theological interpretations and specific symbolism. The apparent contradiction of the celebration of a lively festival in the setting of the cremation ground, resolved in the divine character of Śiva, is illustrated and contextualised starting from textual analysis.
Artificial Intelligence–Driven Ultra-Fast Superresolution MRI
2022-11-02

Abstract Magnetic resonance imaging (MRI) is the keystone of modern musculoskeletal imaging; however, long pulse sequence acquisition times may restrict patient tolerability and access. Advances in MRI scanners, coil technology, and innovative pulse sequence acceleration methods enable 4-fold turbo spin echo pulse sequence acceleration in clinical practice; however, at this speed, conventional image reconstruction approaches the signal-to-noise limits of temporal, spatial, and contrast resolution. Novel deep learning image reconstruction methods can minimize signal-to-noise interdependencies to better advantage than conventional image reconstruction, leading to unparalleled gains in image speed and quality when combined with parallel imaging and simultaneous multislice acquisition. The enormous potential of deep learning–based image reconstruction promises to facilitate the 10-fold acceleration of the turbo spin echo pulse sequence, equating to a total acquisition time of 2–3 minutes for entire MRI examinations of joints without sacrificing spatial resolution or image quality. Current investigations aim for a better understanding of stability and failure modes of image reconstruction networks, validation of network reconstruction performance with external data sets, determination of diagnostic performances with independent reference standards, establishing generalizability to other centers, scanners, field strengths, coils, and anatomy, and building publicly available benchmark data sets to compare methods and foster innovation and collaboration between the clinical and image processing community. In this article, we review basic concepts of deep learning–based acquisition and image reconstruction techniques for accelerating and improving the quality of musculoskeletal MRI, commercially available and developing deep learning–based MRI solutions, superresolution, denoising, generative adversarial networks, and combined strategies for deep learning–driven ultra-fast superresolution musculoskeletal MRI. This article aims to equip radiologists and imaging scientists with the necessary practical knowledge and enthusiasm to meet this exciting new era of musculoskeletal MRI.
Recursive sequence generation in crows
2022-11-02

Recursion, the process of embedding structures within similar structures, is often considered a foundation of symbolic competence and a uniquely human capability. To understand its evolution, we can study the recursive aptitudes of nonhuman animals. We adopted the behavioral protocol of a recent study demonstrating that humans and nonhuman primates grasp recursion. We presented sequences of bracket pair stimuli (e.g., [ ] and { }) to crows who were instructed to peck at training lists. They were then tested on their ability to transfer center-embedded structure to never-before-seen pairings of brackets. We reveal that crows have recursive capacities; they perform on par with children and even outperform macaques. The crows continued to produce recursive sequences after extending to longer and thus deeper embeddings. These results demonstrate that recursive capabilities are not limited to the primate genealogy and may have occurred separately from or before human symbolic competence in different animal taxa.
Shear wave elastography characterizes passive and active mechanical properties of biceps brachii muscle in vivo
2022-11-02

Mechanical characterization of individual muscles in their in vivo environment is not well studied. Shear wave elastography (SWE) as a non-invasive technique was shown to be promising in quantifying the local mechanical properties of skeletal muscles. This study aimed to investigate the mechanics of the biceps brachii muscle (BB) derived from SWE in relation to elbow joint position and contraction intensity during isometric contraction. 14 healthy, young subjects participated in the study and five different joint positions (60°-180° elbow angle) were investigated. Shear elastic modulus and surface electromyography (sEMG) of the BB and elbow torque were measured simultaneously, both in passive (i.e., resting) and active states during slow, sub-maximal isometric ramp contractions up to 25%, 50%, and 75% of the maximum voluntary contraction. At passive state, the shear elastic modulus of the BB increased with increasing elbow angle (p < 0.001). Maximum elbow flexion torque was produced at 60° and it decreased with increasing elbow angle (p = 0.001). During sub-maximal contractions, both elbow angle (p < 0.001) and contraction intensity (p < 0.001) had significant effects on the shear elastic modulus but only contraction intensity (p < 0.001) affected sEMG amplitude of the BB. Although torque was decreased at extended elbow positions (150°, 180°), higher active shear elastic modulus of BB muscle was found compared to flexed positions (60°, 90°). Linear regression of the BB sEMG amplitude over elbow torque showed good agreement for all joint positions (R<sup>2</sup> between 0.69 and 0.89) while the linear agreement between shear elastic modulus of BB and elbow torque differed between flexed (R<sup>2</sup> = 0.70 at 60° and R<sup>2</sup> = 0.79 at 90°) and extended positions (with the lowest R<sup>2</sup> = 0.57 at 150°). We conclude that using SWE, we can detect length-dependent mechanical changes of BB both in passive and active states. More importantly, SWE can be used to characterize active muscle properties in vivo. The present findings have critical importance for developing muscle stiffness as a measure of individual muscle force to validate muscle models and using SWE in clinical diagnostics.
Parental environmental effects are common and strong, but unpredictable, in Arabidopsis thaliana
2022-11-02

Summary The phenotypes of plants can be influenced by the environmental conditions experienced by their parents. However, there is still much uncertainty about how common and how predictable such parental environmental effects really are. We carried out a comprehensive experimental test for parental effects, subjecting plants of multiple Arabidopsis thaliana genotypes to 24 different biotic or abiotic stresses, or combinations thereof, and comparing their offspring phenotypes in a common environment. The majority of environmental stresses caused significant parental effects, with −35% to +38% changes in offspring fitness. The expression of parental effects was strongly genotype‐dependent, and multiple environmental stresses often acted nonadditively when combined. The direction and magnitude of parental effects were unrelated to the direct effects on the parents: Some environmental stresses did not affect the parents but caused substantial effects on offspring, while for others, the situation was reversed. Our study demonstrates that parental environmental effects are common and often strong in A. thaliana , but they are genotype‐dependent, act nonadditively, and are difficult to predict. We should thus be cautious with generalizing from simple studies with single plant genotypes and/or only few individual environmental stresses. A thorough and general understanding of parental effects requires large multifactorial experiments.
Machine learning-based event generator for electron-proton scattering
2022-11-02

We present a new machine learning-based Monte Carlo event generator using generative adversarial networks (GANs) that can be trained with calibrated detector simulations to construct a vertex-level event generator free of theoretical assumptions about femtometer scale physics. Our framework includes a GAN-based detector folding as a fast-surrogate model that mimics detector simulators. The framework is tested and validated on simulated inclusive deep-inelastic scattering data along with existing parametrizations for detector simulation, with uncertainty quantification based on a statistical bootstrapping technique. Our results provide for the first time a realistic proof of concept to mitigate theory bias in inferring vertex-level event distributions needed to reconstruct physical observables.
Luminescence chronology of fluvial and aeolian deposits from the Emirate of Sharjah, UAE
2022-11-02

Abstract Quaternary environments on the Arabian Peninsula shifted between pronounced arid conditions and phases of increased rainfall, which had a profound impact on Earth surface processes. However, while aeolian sediment dynamics are reasonably well understood, there is a lack of knowledge with regard to variability in the fluvial systems. Presented here are the findings from several locations within wadi drainage systems to the west of the Hajar Mountains (United Arab Emirates). The performance of optically stimulated luminescence dating using a customized standardized growth curve approach is investigated, showing that this approach allows reliable determination of ages by reducing the machine time required. Three main periods of fluvial activity occurred at 160–135, 43–34, and ca. 20 ka. Additional ages fall into the latest Pleistocene and Late Holocene. None of the ages coincides with major wet periods in SE Arabia that have been identified in stalagmites and by the deposition of lake sediments. It is shown that fluvial activity was partly contemporaneous (within the given time resolution) with phases of aeolian deposition and was almost continuous, but likely sporadic, during the Middle to Late Pleistocene. This highlights the need for regionally defined paleoenvironmental records to fully understand the response of dryland systems to long-term climatic change.
Mugharet el'Aliya: Affinities of an enigmatic north African Aterian maxillary fragment
2022-11-02

Abstract Objectives This study uses a virtual framework to examine the left maxillary fragment of the juvenile fossil from Mugharet el'Aliya, Morocco, found in association with an Aterian lithic industry. Previously, this fossil had been ascribed to modern humans or the Neanderthal lineage based on its “archaic”/“Neanderthal‐like” features and apparent large size. Here, we conducted a novel 3D shape comparative analysis of the maxillary fragment to clarify its taxonomic affinities with regard to its size and ontogeny. Materials and Methods Eighty Computed Tomography and surface scans representing ontogenetic samples of Homo sapiens and Homo neanderthalensis were used to capture species‐specific differences. The toolkit of geometric morphometrics in combination with surface registration and an elastic iterative closest point algorithm were used to create a dataset of meshes with an identical number of corresponding vertices for the maxillae. Multivariate statistics were applied to Procrustes superimposed coordinates derived from the vertices of this dataset. Results Our analysis showed affinities of the Mugharet el'Aliya individual with our H. sapiens sample, especially with a subadult individual from Qafzeh. No size‐independent affinities with Neanderthals of comparable dental age could be identified. Discussion Our results add to the evidence connecting fossils from western Asia, especially Qafzeh and Skhul, and the North African Aterian. Furthermore, Mugharet el'Aliya adds to our knowledge of the ontogenetic development of adult morphology that is frequently used to characterize hominin groups, for example, Neanderthals and modern humans.
In vitro effects of eslicarbazepine (S‐licarbazepine) as a potential precision therapy on SCN8A variants causing neuropsychiatric disorders
2022-11-02

Background and Purpose Variants in SCN8A , the Na V 1.6 channel's coding gene, are characterized by a variety of symptoms, including intractable epileptic seizures, psychomotor delay, progressive cognitive decline, autistic features, ataxia or dystonia. Standard anticonvulsant treatment has a limited impact on the course of disease. Experimental Approach We investigated the therapeutic potential of eslicarbazepine (S‐licarbazepine; S‐lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain‐of‐function (G1475R and M1760I) and one variant with biophysical gain‐of‐function but neuronal loss‐of‐function (A1622D) in neuroblastoma cells and in murine primary hippocampal neuron cultures. These three variants cover the broad spectrum of Na V 1.6‐associated disease and are linked to representative phenotypes of mild to moderate epilepsy (G1475R), developmental and epileptic encephalopathy (M1760I) and intellectual disability without epilepsy (A1622D). Key Results Similar to known effects on Na V 1.6 wildtype channels, S‐lic predominantly enhances slow inactivation on all tested variants, irrespective of their particular biophysical mechanisms. Beyond that, S‐lic exhibits variant‐specific effects including a partial reversal of pathologically slowed fast inactivation dynamics (A1622D and M1760I) and a trend to reduce enhanced persistent Na + current by A1622D variant channels. Furthermore, our data in primary transfected neurons reveal that not only variant‐associated hyperexcitability (M1760I and G1475R) but also hypoexcitability (A1622D) can be modulated by S‐lic. Conclusions and Implications S‐lic has not only substance‐specific effects but also variant‐specific effects. Personalized treatment regimens optimized to achieve such variant‐specific pharmacological modulation may help to reduce adverse side effects and improve the overall therapeutic outcome of SCN8A ‐related disease.