julilili42/papers huggingface dataset:
Machine learning-based classification of Alzheimer’s disease and its at-risk states using personality traits, anxiety, and depression
2022-11-30

Abstract Background Alzheimer’s disease (AD) is often preceded by stages of cognitive impairment, namely subjective cognitive decline (SCD) and mild cognitive impairment (MCI). While cerebrospinal fluid (CSF) biomarkers are established predictors of AD, other non-invasive candidate predictors include personality traits, anxiety, and depression, among others. These predictors offer non-invasive assessment and exhibit changes during AD development and preclinical stages. Methods In a cross-sectional design, we comparatively evaluated the predictive value of personality traits (Big Five), geriatric anxiety and depression scores, resting-state functional magnetic resonance imaging activity of the default mode network, apoliprotein E (ApoE) genotype, and CSF biomarkers (tTau, pTau181, Aβ42/40 ratio) in a multi-class support vector machine classification. Participants included 189 healthy controls (HC), 338 individuals with SCD, 132 with amnestic MCI, and 74 with mild AD from the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Results Mean predictive accuracy across all participant groups was highest when utilizing a combination of personality, depression, and anxiety scores. HC were best predicted by a feature set comprised of depression and anxiety scores and participants with AD were best predicted by a feature set containing CSF biomarkers. Classification of participants with SCD or aMCI was near chance level for all assessed feature sets. Conclusion Our results demonstrate predictive value of personality trait and state scores for AD. Importantly, CSF biomarkers, personality, depression, anxiety, and ApoE genotype show complementary value for classification of AD and its at-risk stages. Key Points - Multi-class support vector machine classification was used to compare the predictive value of well-established and non-invasive, easy-to-assess candidate variables for classifying participants with healthy cognition, subjective cognitive decline, amnestic mild cognitive impairment, and mild Alzheimer’s disease. - Personality traits, geriatric anxiety and depression scores, resting-state functional magnetic resonance imaging activity of the default mode network, ApoE genotype, and CSF biomarkers were comparatively evaluated. - A combination of personality, anxiety, and depression scores provided the highest predictive accuracy, comparable to CSF biomarkers, indicating complementary value. - Established and candidate predictors had limited success in classifying SCD and aMCI, underscoring the heterogeneity of these cognitive states and emphasizing the need for standardizing terminology and diagnostic criteria.
The Emergence of Habitual Ochre Use in Africa and its Significance for The Development of Ritual Behavior During The Middle Stone Age
2022-12-01

Abstract Over the last two decades, red ochre has played a pivotal role in discussions about the cognitive and cultural evolution of early modern humans during the African Middle Stone Age. Given the importance of ochre for the scholarly debate about the emergence of ‘behavioral modernity’, the lack of long-term spatio-temporal analyses spanning large geographical areas represents a significant gap in knowledge. Here we take a continent-wide approach, rather than focusing on specific sites, regions or technocomplexes. We report the most comprehensive meta-analysis of ochre use to date, spanning Africa between 500 and 40 thousand years ago, to examine data from more than a hundred archaeological sites. Using methods based on time averaging, we identified three distinct phases of ochre use: the initial phase occurred from 500,000 to 330,000; the emergent phase from 330,000 to 160,000; and the habitual phase from 160,000 to 40,000 years ago. The number of sites with ochre increased with each subsequent phase. More importantly, the ratio of sites with ochre compared to those with only stone artifacts also followed this trend, indicating the increasing intensity of ochre use during the Middle Stone Age. While the geographical distribution expanded with time, the absolute number of ochre finds grew significantly as well, underlining the intensification of ochre use. We determine that ochre use established itself as a habitual cultural practice in southern, eastern and northern Africa starting about 160,000 years ago, when a third of archaeological sites contain ochre. We argue that this pattern is a likely material manifestation of intensifying ritual activity in early populations of Homo sapiens . Such ritual behavior may have facilitated the demographic expansion of early modern humans, first within and eventually beyond the African continent. We discuss the implications of our findings on two models of ritual evolution, the Female Cosmetic Coalitions Hypothesis and the Ecological Stress Hypothesis, as well as a model about the emergence of complex cultural capacities, the Eight-Grade Model for the Evolution and Expansion of Cultural Capacities .
The X-Ray Polarimetry View of the Accreting Pulsar Cen X-3
2022-12-01

Abstract The first X-ray pulsar, Cen X-3, was discovered 50 yr ago. Radiation from such objects is expected to be highly polarized due to birefringence of plasma and vacuum associated with propagation of photons in the presence of the strong magnetic field. Here we present results of the observations of Cen X-3 performed with the Imaging X-ray Polarimetry Explorer. The source exhibited significant flux variability and was observed in two states different by a factor of ∼20 in flux. In the low-luminosity state, no significant polarization was found in either pulse phase-averaged (with a 3 σ upper limit of 12%) or phase-resolved (the 3 σ upper limits are 20%–30%) data. In the bright state, the polarization degree of 5.8% ± 0.3% and polarization angle of 49.°6 ± 1.°5 with a significance of about 20 σ were measured from the spectropolarimetric analysis of the phase-averaged data. The phase-resolved analysis showed a significant anticorrelation between the flux and the polarization degree, as well as strong variations of the polarization angle. The fit with the rotating vector model indicates a position angle of the pulsar spin axis of about 49° and a magnetic obliquity of 17°. The detected relatively low polarization can be explained if the upper layers of the neutron star surface are overheated by the accreted matter and the conversion of the polarization modes occurs within the transition region between the upper hot layer and a cooler underlying atmosphere. A fraction of polarization signal can also be produced by reflection of radiation from the neutron star surface and the accretion curtain.
Holocene ice-stream shutdown and drainage basin reconfiguration in northeast Greenland
2022-12-01

Abstract Reliable knowledge of ice discharge dynamics for the Greenland ice sheet via its ice streams is essential if we are to understand its stability under future climate scenarios. Currently active ice streams in Greenland have been well mapped using remote-sensing data while past ice-stream paths in what are now deglaciated regions can be reconstructed from the landforms they left behind. However, little is known about possible former and now defunct ice streams in areas still covered by ice. Here we use radio-echo sounding data to decipher the regional ice-flow history of the northeastern Greenland ice sheet on the basis of its internal stratigraphy. By creating a three-dimensional reconstruction of time-equivalent horizons, we map folds deep below the surface that we then attribute to the deformation caused by now-extinct ice streams. We propose that locally this ancient ice-flow regime was much more focused and reached much farther inland than today’s and was deactivated when the main drainage system was reconfigured and relocated southwards. The insight that major ice streams in Greenland might start, shift or abruptly disappear will affect future approaches to understanding and modelling the response of Earth’s ice sheets to global warming.
Cenozoic Proxy Constraints on Earth System Sensitivity to Greenhouse Gases
2022-12-01

Abstract The long‐term extent of the Earth system response to anthropogenic interference remains uncertain. However, the geologic record offers insights into this problem as Earth has previously cycled between warm and cold intervals during the Phanerozoic. We present an updated compilation of surface temperature proxies for several key time intervals to reconstruct global temperature changes during the Cenozoic. Our data synthesis indicates that Earth’s surface slowly cooled by ca. 9°C during the early Paleogene to late Neogene and that continent‐scale ice sheets developed after global temperature dropped to less than 10°C above preindustrial conditions. Slow cooling contrasts with the steep decrease in combined radiative forcing from past CO 2 concentrations, solar luminosity, and ocean area, which was close to preindustrial levels even as Earth remained in a much warmer state. From this, we infer that the Earth system was less sensitive to greenhouse gas forcing for most of the Cenozoic and that sensitivity must have increased by at least a factor of 2 during the Plio‐Pleistocene. Our results imply that slow feedbacks will raise global surface temperatures by more than 3°C in the coming millennia, even if anthropogenic forcing is stabilized at the present‐day value (2 W/m 2 ), and that their impact will diminish with further warming.
T cells of colorectal cancer patients’ stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells
2022-12-01

Background Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc). Methods Colorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients’ Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay. Results 100 tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. The neoantigens originated from single nucleotide substitutions in the genes IQGAP1, CTNNB1, and TRIT1 . Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment. Conclusion These results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
Simulation-based inference of differentiation trajectories from RNA velocity fields
2022-12-01

We report Cytopath, a method for trajectory inference that takes advantage of transcriptional activity information from the RNA velocity of single cells to perform trajectory inference. Cytopath performs this task by defining a Markov chain model, simulating an ensemble of possible differentiation trajectories, and constructing a consensus trajectory. We show that Cytopath can recapitulate the topological and molecular characteristics of the differentiation process under study. In our analysis, we include differentiation trajectories with varying bifurcated, circular, convergent, and mixed topologies studied in single-snapshot as well as time-series single-cell RNA sequencing experiments. We demonstrate the capability to reconstruct differentiation trajectories, assess the association of RNA velocity-based pseudotime with actually elapsed process time, and identify drawbacks in current state-of-the art trajectory inference approaches.
A chromatic feature detector in the retina signals visual context changes
2022-12-01

The retina transforms patterns of light into visual feature representations supporting behaviour. These representations are distributed across various types of retinal ganglion cells (RGCs), whose spatial and temporal tuning properties have been extensively studied in many model organisms, including the mouse. However, it has been difficult to link the potentially nonlinear retinal transformations of natural visual inputs to specific ethological purposes. Here, we discover a novel selectivity to chromatic contrast in an RGC type that allows the detection of transitions of the horizon across a retinal region. We trained a convolutional neural network (CNN) model on large-scale functional recordings of RGC responses to natural mouse movies, and then used this model to search in silico for stimuli that maximally excite distinct types of RGCs. This procedure predicted centre colour-opponency in transient Suppressed-by-Contrast RGCs (tSbC), a cell type whose function is being debated. We confirmed experimentally that these cells indeed responded very selectively to Green-OFF, UV-ON contrasts, which we found to be characteristic of transitions from ground to sky in the visual scene, as might be elicited by head- or eye-movements across the horizon. Because tSbCs reliably detected these transitions, we suggest a role for this RGC type in providing contextual information (i.e. sky or ground) necessary for the selection of appropriate behavioural responses to other stimuli, such as looming objects. Our work showcases how a combination of experiments with natural stimuli and computational modelling allows discovering novel types of stimulus selectivity and identifying their potential ethological relevance.
Assessing aerosol induced errors in Monte Carlo based air-shower reconstruction for atmospheric Cherenkov detectors
2022-12-01

Abstract Aerosol levels influence the wavelength dependent transmission properties of the atmosphere. Variations in aerosol levels therefore affect the amount of Cherenkov light from air-showers that can reach an atmospheric Cherenkov detector. As the amount of detected Cherenkov light is directly related to a primary shower particle’s energy, deviations between actual and assumed atmospheric transmission properties yield errors in reconstructed particle energies as well as energy axes of instrument response functions. In this work, a scheme is presented to assess this influence and potentially reduce related errors in the air-shower reconstruction. The proposed scheme relies on estimations or measurements of the aerosol optical depth and atmospheric density profile which are then used in radiative transfer simulations to generate atmospheric transmission profiles. As the scheme furthermore uses detector specific quantum efficiencies and generalised shower evolution models, it does not rely on detailed Monte Carlo simulations for the different atmospheric conditions but only on the transmission profile which the initial shower reconstruction algorithm is based on. The approach is derived and presented on the example of the H.E.S.S. experiment which employs imaging atmospheric Cherenkov telescopes in the Khomas Highland of Namibia to detect gamma rays in the GeV to TeV energy range.
Dose-escalated radiotherapy with simultaneous integrated boost for bone metastases in selected patients with assumed favourable prognosis
2022-12-01

Abstract Background Stereotactic body radiotherapy (SBRT) concepts for dose escalation are increasingly used for bone metastases in patients with oligometastatic or oligoprogressive disease. For metastases that are not suitable for SBRT-regimens, a treatment with 30/40 Gy with simultaneous integrated boost (SIB) in 10 fractions represents a possible regimen. The aim of this study was to investigate the feasibility of this concept and the acute and subacute toxicities. Patients and methods Clinical records for dose-escalated radiotherapy of all consecutive patients treated with this regimen were evaluated retrospectively (24 patients with 28 target volumes for oncologic outcomes and 25 patients with 29 target volumes for treatment feasibility and dose parameters analysis). Analysis of radiotherapy plans included size of target volumes and dosimetric parameter for target volumes and organs at risk (OAR). Acute and subacute toxicities were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V4.0. Results The most common localization was the spine (71.4%). The most common histology was prostate cancer (45.8%). Oligometastatic or oligoprogressive disease was the indication for dose-escalated radiotherapy in 19/24 patients (79.2%). Treatment was feasible with all patients completing radiotherapy. Acute toxicity grade 1 was documented in 36.0% of the patients. During follow up, one patient underwent surgery due to bone instability. The 1-year local control and patient-related progression-free survival (PFS) were 90.0 ± 6.7% and 33.3 ± 11.6%, respectively. Conclusions Dose-escalated hypofractionated radiotherapy with simultaneous integrated boost for bone metastases resulted in good local control with limited acute toxicities. Only one patient required surgical intervention. The regimen represents an alternative to SBRT in selected patients.
Search for exotic physics in double-β decays with GERDA Phase II
2022-12-01

Abstract A search for Beyond the Standard Model double- β decay modes of 76 Ge has been performed with data collected during the Phase II of the GERmanium Detector Array ( Gerda ) experiment, located at the Laboratori Nazionali del Gran Sasso of INFN (Italy). Improved limits on the decays involving Majorons have been obtained, compared to previous experiments with 76 Ge, with half-life values on the order of 10 23 yr. For the first time with 76 Ge, limits on Lorentz invariance violation effects in double- β decay have been obtained. The isotropic coefficient å of (3) , which embeds Lorentz violation in double- β decay, has been constrained at the order of 10 -6 GeV. We also set the first experimental limits on the search for light exotic fermions in double- β decay, including sterile neutrinos.
A Comparative Study on Heterogeneity of Clay Rocks Using Pore‐Scale Diffusion Simulations and Experiments
2022-12-01

Abstract Accurate modeling and simulation of radionuclide migration in clay rocks such as the Opalinus Clay (OPA) play a key role in the safety assessment of deep geological repositories for nuclear wastes. At the continuum scale, the representative elementary volume (REV) is a fundamental constraint to quantify the effective diffusivity, which is a key parameter in reactive transport (RT) models. Therefore, an accurate estimation of the REV is essential for a meaningful continuum‐scale RT simulation in heterogeneous clay rocks. This study presents a comprehensive analysis of the heterogeneities of porosity and effective diffusivity in clay rocks by using the classical sampling theory and pore‐scale simulations. First, in this study, the two‐dimensional representative elementary area is correlated with the REV for porosity via a characteristic length. Next, it is shown that the REV for diffusivity is larger than the REV for porosity. Moreover, these two REVs can be correlated using Archie's law. In such a way, the REV for diffusivity can be determined by the developed correlations through analyzing two‐dimensional microstructures, thus significantly reducing the computational cost. Finally, the applicability of our approach for clay rocks is validated by experimental data on the diffusion of tritiated water in the heterogeneous sandy facies of OPA. From both the experimental data and the modeling prediction, the REV for diffusivity in the sandy facies of OPA is in the order of cubic centimeters. This study provides critical insights into the diffusion in heterogeneous clay rocks toward an enhanced predictability of radionuclide migration.
Effects of tablet‐based drawing and paper‐based methods on medical students' learning of gross anatomy
2022-12-01

Abstract The way medical students learn anatomy is constantly evolving. Nowadays, technologies such as tablets support established learning methods like drawing. In this study, the effect of drawing on a tablet on medical students' anatomy learning was investigated compared to drawing or summarizing on paper. The quality of drawings or summaries was assessed as a measure of the quality of strategy implementation. Learning outcome was measured with an anatomy test, both immediately afterward and after 4–6 weeks to assess its sustainability. There were no significant group differences in learning outcome at both measurement points. For all groups, there was a significant medium strength correlation between the quality of the drawings or summaries and the learning outcome ( p &lt; 0.05). Further analysis revealed that the quality of strategy implementation moderated outcomes in the delayed test: When poorly implemented, drawing on a tablet ( M = 48.81) was associated with lower learning outcome than drawing on paper ( M = 58.95); The latter ( M = 58.89) was related to higher learning outcome than writing summaries ( M = 45.59). In case of high‐quality strategy implementation, drawing on a tablet ( M = 60.98) outperformed drawing on paper ( M = 52.67), which in turn was outperformed by writing summaries ( M = 62.62). To conclude, drawing on a tablet serves as a viable alternative to paper‐based methods for learning anatomy if students can make adequate use of this strategy. Future research needs to identify how to support student drawing, for instance, by offering scaffolds with adaptive feedback to enhance learning.
35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma
2022-12-01

Aldesleukin (IL-2), at high doses in repeat cycles, is approved as monotherapy for patients (pts) with metastatic melanoma. Its limited efficacy is mediated through endogenous T cell activation, which also contributes to considerable toxicity (Rosenberg NEJM 1988). Lifileucel, a one-time investigational TIL cell therapy, showed a 31% IRC-assessed objective response rate (ORR) in 153 pts with advanced melanoma who progressed after immune checkpoint inhibitors and targeted therapy (if BRAF mutation positive) in the phase 2 C-144-01 trial (Sarnaik SITC 2022) using abbreviated high-dose IL-2 (≤6 doses) with 79% lower potential maximum cumulative exposure than monotherapy.