julilili42/papers huggingface dataset:
BRAIN-MAGNET: A novel functional genomics atlas coupled with convolutional neural networks facilitates clinical interpretation of disease relevant variants in non-coding regulatory elements
2024-04-16

Abstract Genome-wide assessment of genetic variation is becoming routine in human genetics, but functional interpretation of non-coding variants both in common and rare diseases remains extremely challenging. Here, we employed the massively parallel reporter assay ChIP- STARR-seq to functionally annotate the activity of &gt;145 thousand non-coding regulatory elements (NCREs) in human neural stem cells, modelling early brain development. Highly active NCREs show increased sequence constraint and harbour de novo variants in individuals affected by neurodevelopmental disorders. They are enriched for transcription factor (TF) motifs including YY1 and p53 family members and for primate-specific transposable elements, providing insights on gene regulatory mechanisms in NSCs. Examining episomal NCRE activity of the same sequences in human embryonic stem cells identified cell type differential activity and primed NCREs, accompanied by a rewiring of the epigenome landscape. Leveraging the experimentally measured NCRE activity and nucleotide composition of the assessed sequences, we built BRAIN-MAGNET, a functionally validated convolutional neural network that predicts NCRE activity based on DNA sequence composition and identifies functionally relevant nucleotides required for NCRE function. The application of BRAIN-MAGNET allows fine-mapping of GWAS loci identified for common neurological traits and prioritizing of possible disease-causing rare non-coding variants in currently genetically unexplained individuals with neurogenetic disorders, including those from the Genomics England 100,000 Genomes project, identifying novel enhanceropathies. We foresee that this NCRE atlas and BRAIN-MAGNET will help reduce missing heritability in human genetics by limiting the search space for functionally relevant non-coding genetic variation.
Magnetar QPOs and Neutron Star Crust Elasticity
2024-04-16

The crust region is a tiny fraction of neutron stars, but it has a variety of physical properties and plays an important role in astronomical observations. One of the properties characterizing the crust is the elasticity. In this review, with the approach of asteroseismology, we systematically examine neutron star oscillations excited by crust elasticity, adopting the Cowling approximation. In particular, by identifying the quasi-periodic oscillations observed in magnetar flares with the torsional oscillations, we make a constraint on the nuclear saturation parameters. In addition, we also discuss how the shear and interface modes depend on the neutron star properties. Once one detects an additional signal associated with neutron star oscillations, one can get a more severe constraint on the saturation parameters and/or neutron star properties, which must be a qualitatively different constraint obtained from terrestrial experiments, and help us to complementarily understand astrophysics and nuclear physics.
The Middle Paleolithic of the Côte Chalonnaise: Chronology, Technology and Palethnological Elements
2024-04-16

This article examines the technological and general appearance of Middle Paleolithic assemblages from a number of sites in the Côte Chalonnaise, Burgundy, France. Emanating from several assemblage characteristics observed within the stratified material from Grotte de la Verpillière II, ongoing research could demonstrate congruent technological patterns in the assemblages of a number of surrounding sites. Major common features are the presence of Keilmesser, with and without tranchet blow, and consistent production strategies, predominantly based on the Levallois concept. Thus, this paper gives initial indications for a conjunct site cluster in the region. Initial dating results suggest a chronological context in the Late Middle Paleolithic. Furthermore, the spatial allocation of the sites and their respective industries allow us to forward a preliminary hypothesis concerning functional inter-site organization. In addition, recently conducted fieldwork and subsequent analysis provide evidence for intra-site spatiality, which completes the micro-regional overview of the Late Middle Paleolithic in the interplay between technology, chronology and spatiality.
Using the Technological Feature of Tranchet Blow on Keilmesser as a Connecting Element Between Similar Middle Paleolithic Assemblages from the Côte Chalonnaise (Saône-et-Loire, France)
2024-04-16

This article examines lithic artifacts which, because of a particular modification, may be considered a shared feature of late Middle Paleolithic assemblages from the Saône-et-Loire Department in eastern France. There, the modification of the cutting edges referred to as tranchet blow was first described in detail in the 1970s using the lithic material from Grotte de la Verpillière I, which was excavated in 1868. However, research carried out in recent years has shown that this tranchet blow modification on Keilmesser is not confined to this site; in fact, it also occurs at several surrounding sites. Thus, the tranchet blow modification can be seen as a specific regional phenomenon. Research on Keilmesser and the tranchet blow modification brings us face to face with the problem of terminology. It is not the linguistic barrier that is important here, but rather the use of different terms and very different spellings in the literature. This makes the search for further assemblages featuring this phenomenon considerably more difficult. In this context, a technological and terminological rethink is called for. In previous studies, the similarity between burin blow and tranchet blow modification was highlighted. It has recently been more often assumed that the technological prerequisites of these two reduction variants can be regarded as similar but nevertheless different. This article addresses these technological concerns in a general overview and proposes a coherent standardized terminology using the more neutral term “Keilmesser” with the addition of the qualifier “with tranchet blow.” Furthermore, regional research on Keilmesser, and related tranchet blow modification, is described and the initial results of recent studies on the suggested technological clustering of Middle Paleolithic behavior in Saône-et-Loire are presented.
Handaxes: New Perspectives from the Mâconnais and Beaujolais
2024-04-16

This paper presents a preliminary analysis of the open-air site of Charbonnières in the Mâconnais region of France. The collection of Georges Lamercerie, now housed within the Department of Early Prehsitory and Quaternary Ecology, University of Tübingen, was used as the basis for this study. The material was previously included in a BA thesis and, in this paper, is compared to assemblages that include handaxes from the adjacent region of Beaujolais.
The Châtelperronian Lithic Industries of Eastern France: Germolles and Châtelperron
2024-04-16

In this paper we discuss two Châtelperronian sites in eastern France: Grotte de la Verpillière I, the easternmost known Châtelperronian site as of today, and the eponymous site of Grotte des Fées in Châtelperron. While the Châtelperronian of the Grotte des Fées has been at the center of many discussions over the past decade, the Châtelperronian assemblage from Grotte de la Verpillière I has not received much attention; there is a prevailing opinion that the number of Châtelperronian artifacts and the stratigraphic integrity of the latter site are insufficient at best. We revised this view of Grotte de la Verpillière I in an earlier paper by presenting the results of our analyses of the Châtelperronian artifacts from past excavations and from our own recent work (Floss et al. 2016). Here, we will provide an overview of the Châtelperronian lithics of eastern France, with a special focus on the technological aspects of the assemblages by comparing them to our analyses of the lithic material from Grotte des Fées in Châtelperron.
Middle Paleolithic Sites atop the Scoria Cones of the East Eifel Volcanic Field of the Central Rhine Valley
2024-04-16

While controversial from the point of view of its impact on the landscape, the large-scale mining of lava from the scoria cones of the East Eifel led to the discovery of many Middle Paleolithic find horizons within the volcanic craters atop these elevated positions. This paper summarizes the important finds from sites including Plaidter Hummerich, Schweinskopf, Tönchesberg and Wannen and discusses their chronostratigraphic and cultural stratigraphic context. Archaeologists based at the museum and research institute of Monrepos overlooking the Neuwied Basin excavated most of these sites during the 1980s as part of a major research project exploring the geology and prehistory of the East Eifel. Subse-quently little field work has been conducted on the Middle Paleolithic in the region. The find horizons date to the penultimate and last glaciations and document a wealth of often ephemeral occupations in the craters of the scoria cones. In the case of Wannen, researchers discovered cranial remains of a Neanderthal associated with lithic artifacts in a loess from the penultimate glaciation. The lithic assemblages recovered from the volcanic craters document a high level of technological variability and the use of diverse local and non-local raw materials. While patterns of subsistence varied from site to site, Neanderthals often hunted equids, cervids and bovids in or near the scoria cones. Archaic hominins were likely drawn to the top of these small volcanic mountains to exploit the view they commanded over the landscape and perhaps to use the water that at times collected in these settings. Such water sources may also have attracted game to the top of the scoria cones. While these settings contain numerous Middle Paleolithic find horizons, Upper Paleolithic finds are extremely rare. We hypothesize that the many scoria cones of the Eifel that have not been subjected to large-scale mining also contain similar Middle Paleolithic find horizons, making this prominent feature of the landscape an important part of the Middle Paleolithic settlement dynamics of the region.
Middle Paleolithic Open-Air Sites of the Swabian Jura
2024-04-16

For several decades, Paleolithic research in the Swabian Jura has mainly focused on the numerous cave sites situated in the Ach and Lone valleys. These sites, such as Vogelherd, Hohle Fels, Geißenklösterle or Hohlenstein-Stadel, are famous for producing evidence for the world’s oldest figurative art and musical instruments, dating to the Aurignacian, and have also yielded important Middle and Upper Paleolithic assemblages. In recent years, the work group directed by H. Floss has begun to intensify research efforts regarding Paleolithic open-air sites in the Swabian Jura and adjacent areas. With the discovery of the Aurignacian open-air site of Königsbach-Stein near Pforzheim as a starting point, ongoing systematic surveys led to the discovery of the site of Börslingen-Eisenberg in 2009. The site is situated directly on an outcrop of Jurassic chert and has yielded c. 300 Middle Paleolithic artifacts, including Keilmesser, other bifacial elements and a strong Levallois component, as well as some Upper Paleolithic pieces. The local raw material was used in nearby cave sites, e.g., Bockstein (Middle Paleolithic context) and Vogelherd (Upper Paleolithic context).
The Fauna from the Middle Paleolithic: Settlement, Dietary Patterns and Technology in the Swabian Jura
2024-04-16

With 150 years of research on the Paleolithic of the Swabian Jura, the region offers one of the richest records of Neanderthal occupation. The faunal remains from the caves of the Ach and Lone valleys provide an important source of data from Central Europe. Sites in the Lauchert and Brenz valleys further augment the picture. The frequency of burned bone remains demonstrates inter-site variability in Neanderthal occupation and some sites show carnivore and cave bear activities, which spatially overlapped with that of hominins. The studies demonstrate that Bockstein was the most frequently visited site during the Middle Paleolithic (MP). Horse often dominates the faunal assemblages with additional exploitation of reindeer and bovids. The role of mammoth and woolly rhinoceros in MP subsistence is hotly debated, remaining an open-ended question, but megafauna were occasionally exploited albeit at a lower frequency than during the Aurignacian. In addition, retouchers were a common osseous tool type during the MP in the Swabian Jura. These data compliment the MP record of the Rhine region and help us better understand the adaptation of Neanderthals in Central Europe.
Metacognitive biases in anxious-depression and compulsivity extend across perception and memory
2024-04-16

Metacognitive biases are characteristic of common mental health disorders like depression and obsessive-compulsive disorder (OCD). However, recent transdiagnostic approaches consistently contradict traditional clinical studies, with overconfidence in perception among highly compulsive individuals versus underconfident memory in OCD patients. To reconcile these differences, we investigated whether these metacognitive divergences arise due to cognitive domain-specific effects, comorbid overshadowing effects, and/or different manifestations at disparate levels of a metacognitive hierarchy. Using a transdiagnostic individual differences approach (N=327), we quantified metacognitive patterns across memory and perception. Across cognitive domains, we found that underconfidence was linked to anxious-depression and overconfidence was linked to compulsivity. These associations varied across the confidence hierarchy, with anxious-depression being predominantly explained by global low self-esteem, whereas compulsivity exhibited more specific alterations at lower metacognitive levels. Our results support a domain-general alteration of metacognition in psychopathology, with differential contributions from distinct levels of a metacognitive hierarchy, akin to an overshadowing effect.
Comment on egusphere-2024-545
2024-04-16

<strong class="journal-contentHeaderColor">Abstract.</strong> Paleoclimatological field reconstructions are valuable for understanding hydroclimatic variability. While being similarly impactful on societies as temperature variability, hydroclimatic variability has still remained less in focus. However, reconstructing globally complete fields of climate variables lacks adequate proxy data from tropical regions like South America, limiting our understanding of past hydroclimatic changes in these areas. This study addresses this gap using low resolution climate archives, including speleothems, previously omitted from reconstructions. Speleothems record climate variations on decadal to centennial time scales and provide a rich dataset for the otherwise proxy data scarce region of tropical South America. By employing a multi-time scale Paleoclimate Data Assimilation approach, we synthesize climate proxy records and climate model simulations, capable of simulating water isotopologues in the atmosphere, to reconstruct 2000 years of South American climate. This includes surface air temperature, precipitation amount, drought index, isotopic composition of precipitation amount, and the intensity of the South American Summer Monsoon. The reconstruction reveals anomalous climate periods: a wetter and colder phase during the Little Ice Age (1500&ndash;1850 CE) and a drier, warmer period corresponding to the early Medieval Climate Anomaly (600&ndash;900 CE). However, these patterns are not uniform across the continent, with exceptions in northeastern Brazil and the Southern Cone, indicating regional variability. The anomalies are more pronounced than in previous reconstructions, but align with local proxy record studies, thus highlighting the importance of including speleothem proxies. The multi-timescale approach is essential for reconstructing multi-decadal and centennial climate variability. Despite methodological uncertainties regarding climate model biases and proxy record interpretations, this study marks a crucial first step in incorporating speleothems into climate field reconstructions, potentially enhancing insights into past hydroclimatic variability and hydroclimate projections.
The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients—a multicenter real-world analysis
2024-04-17

SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.
Retrieval-Based Diagnostic Decision Support: Mixed Methods Study
2024-04-17

Background Diagnostic errors pose significant health risks and contribute to patient mortality. With the growing accessibility of electronic health records, machine learning models offer a promising avenue for enhancing diagnosis quality. Current research has primarily focused on a limited set of diseases with ample training data, neglecting diagnostic scenarios with limited data availability. Objective This study aims to develop an information retrieval (IR)–based framework that accommodates data sparsity to facilitate broader diagnostic decision support. Methods We introduced an IR-based diagnostic decision support framework called CliniqIR. It uses clinical text records, the Unified Medical Language System Metathesaurus, and 33 million PubMed abstracts to classify a broad spectrum of diagnoses independent of training data availability. CliniqIR is designed to be compatible with any IR framework. Therefore, we implemented it using both dense and sparse retrieval approaches. We compared CliniqIR’s performance to that of pretrained clinical transformer models such as Clinical Bidirectional Encoder Representations from Transformers (ClinicalBERT) in supervised and zero-shot settings. Subsequently, we combined the strength of supervised fine-tuned ClinicalBERT and CliniqIR to build an ensemble framework that delivers state-of-the-art diagnostic predictions. Results On a complex diagnosis data set (DC3) without any training data, CliniqIR models returned the correct diagnosis within their top 3 predictions. On the Medical Information Mart for Intensive Care III data set, CliniqIR models surpassed ClinicalBERT in predicting diagnoses with &lt;5 training samples by an average difference in mean reciprocal rank of 0.10. In a zero-shot setting where models received no disease-specific training, CliniqIR still outperformed the pretrained transformer models with a greater mean reciprocal rank of at least 0.10. Furthermore, in most conditions, our ensemble framework surpassed the performance of its individual components, demonstrating its enhanced ability to make precise diagnostic predictions. Conclusions Our experiments highlight the importance of IR in leveraging unstructured knowledge resources to identify infrequently encountered diagnoses. In addition, our ensemble framework benefits from combining the complementary strengths of the supervised and retrieval-based models to diagnose a broad spectrum of diseases.
Arabidopsis WALL-ASSOCIATED KINASES are not required for oligogalacturonide-induced signaling and immunity
2024-04-17

Abstract Carbohydrate-based cell wall signaling impacts plant growth, development, and stress responses; however, how cell wall signals are perceived and transduced remains poorly understood. Several cell wall breakdown products have been described as typical damage-associated molecular patterns (DAMPs) that activate plant immunity, including pectin-derived oligogalacturonides (OGs). Receptor kinases (RKs) of the WALL-ASSOCIATED KINASE (WAK) family have been shown to bind pectin and OGs, and were previously proposed as OG receptors. However, unambiguous genetic evidence for the role of WAKs in OG responses is lacking. Here, we investigated the role of Arabidopsis WAKs in OG perception using a novel deletion mutant of the clustered WAK family. Using a combination of immune assays for early and late pattern-triggered immunity (PTI), we show that WAKs are dispensable for OG-induced signaling and immunity, indicating that they are not bona fide OG receptors.
First evidence for human occupation of a lava tube in Arabia: The archaeology of Umm Jirsan Cave and its surroundings, northern Saudi Arabia
2024-04-17

Recent advances in interdisciplinary archaeological research in Arabia have focused on the evolution and historical development of regional human populations as well as the diverse patterns of cultural change, migration, and adaptations to environmental fluctuations. Obtaining a comprehensive understanding of cultural developments such as the emergence and lifeways of Neolithic groups has been hindered by the limited preservation of stratified archaeological assemblages and organic remains, a common challenge in arid environments. Underground settings like caves and lava tubes, which are prevalent in Arabia but which have seen limited scientific exploration, offer promising opportunities for addressing these issues. Here, we report on an archaeological excavation and a related survey at and around Umm Jirsan lava tube in the Harrat Khaybar, north-western Saudi Arabia. Our results reveal repeated phases of human occupation of the site ranging from at least the Neolithic through to the Chalcolithic/Bronze Age. Pastoralist use of the lava tube and surrounding landscape is attested in rock art and faunal records, suggesting that Umm Jirsan was situated along a pastoral route linking key oases. Isotopic data indicates that herbivores primarily grazed on wild grasses and shrubs rather than being provided with fodder, while humans had a diet consistently high in protein but with increasing consumption of C 3 plants through-time, perhaps related to the emergence of oasis agriculture. While underground and naturally sheltered localities are globally prominent in archaeology and Quaternary science, our work represents the first such combined records for Saudi Arabia and highlight the potential for interdisciplinary studies in caves and lava tubes.
Drivers and Limits of the Geoeconomic Turn in EU Infrastructure Policy
2024-04-17

In recent years, the EU has increasingly applied state-interventionist practices to initiate and implement infrastructure policy projects. This stands in stark contrast to a phase of liberalization of infrastructure networks and services accompanying European integration and fiscal consolidation and infrastructure decay during the euro crisis. This article argues that the new state interventionism is strongly driven by the changing global constellation of a “new triad competition” where the EU is increasingly competing over infrastructures with the US and China. As a consequence, EU infrastructure policy undergoes a geoeconomic turn that aims to control transnational value chains and related political-economic spaces. Drawing on concepts of critical geography and international political economy, the article outlines the core features of this geoeconomic design logic of infrastructures and contrasts it with complementary or competing ones. The article substantiates these arguments by analyzing EU decision-making on two cases of high-tech infrastructure in the fields of communication and energy: the federated data infrastructure Gaia-X and the Hydrogen Strategy. Both cases provide evidence for the geoeconomic turn in EU infrastructure policy. Yet, the analysis also highlights that the turn is at times supported but also hampered by a capitalist logic that is reflected in the positioning of European and non-European businesses, as well as the EU’s reliance on private action. Furthermore, it illustrates that an ecological and a social-integrative design logic to key infrastructures are largely subordinated. The conclusions reflect on the discrepancy between the EU’s geoeconomic agenda and its less far-reaching implementation.