julilili42/papers huggingface dataset:
Unveiling Movement Intention after Stroke: Integrating EEG and EMG for Motor Rehabilitation
2024-02-27

Abstract Detecting attempted movements of a paralyzed limb is a key step for neural interfaces for motor rehabilitation and restoration after a stroke. In this paper, we present a systematic evaluation of electroencephalographic (EEG) and electromyographic (EMG) activity to decode when stroke patients with severe upper-limb paralysis attempt to move their affected arm. EEG and EMG recordings of 35 chronic stroke patients were analyzed. We trained classifiers to discriminate between rest and movement attempt states relying on brain, muscle, or both types of features combined. Our results reveal that: i) EEG and residual EMG features provide complementary information to detect attempted movements, obtaining significantly higher decoding accuracy when both sources of activity are combined; ii) EMG-based, but not EEG-based, decoding accuracy correlates with the degrees of impairment of the patient; and iii) the percentage of patients that achieve decoding accuracy above the chance level strongly depends on the type of features considered, and can be as low as 50% of them if only ipsilesional EEG is used. These results offer new perspectives to develop improved neurotechnologies that establish a more accurate contingent link between the central and peripheral nervous system after a stroke, leveraging Hebbian learning and facilitating functional plasticity and recovery.
PalVol v1: a proxy-based semi-stochastic ensemble reconstruction of volcanic stratospheric sulfur injection for the last glacial cycle (140 000–50 BP)
2024-02-27

Abstract. Perturbations in stratospheric aerosol due to explosive volcanic eruptions are a primary contributor to natural climate variability. Observations of stratospheric aerosol are available for the past decades, and information from ice cores has been used to derive estimates of stratospheric sulfur injections and aerosol optical depth over the Holocene (approximately 10 000 BP to present) and into the last glacial period, extending back to 60 000 BP. Tephra records of past volcanism, compared to ice cores, are less complete but extend much further into the past. To support model studies of the potential impacts of explosive volcanism on climate variability across timescales, we present here an ensemble reconstruction of volcanic stratospheric sulfur injection (VSSI) over the last 140 000 years that is based primarily on terrestrial and marine tephra records. VSSI values are computed as a simple function of eruption magnitude based on VSSI estimates from ice cores and satellite observations for identified eruptions. To correct for the incompleteness of the tephra record, we include stochastically generated synthetic eruptions assuming a constant background eruption frequency from the ice core Holocene record. While the reconstruction often differs from ice core estimates for specific eruptions due to uncertainties in the data used and reconstruction method, it shows good agreement with an ice-core-based VSSI reconstruction in terms of millennial-scale cumulative VSSI variations over the Holocene. The PalVol reconstruction provides a new basis to test the contributions of forced vs. unforced natural variability to the spectrum of climate and the mechanisms leading to abrupt transitions in the palaeoclimate record with low- to high-complexity climate models. The PalVol volcanic forcing reconstruction is available at https://doi.org/10.26050/WDCC/PalVolv1 (Toohey and Schindlbeck-Belo, 2023).
Perpetrators from Treblinka: interdisciplinary investigations of seven single graves with “Trawniki Men”
2024-02-27

Abstract At the Treblinka extermination and forced labor camp only a few SS soldiers and around a hundred watchmen kept guard over thousands of prisoners. Despite their lower rank in the Nazi hierarchy than SS soldiers, watchmen were vital to implementing “Operation Reinhard” in the field. Prisoners in Nazi camps were terrified by their brutality and ruthlessness. The guards were intermediaries between the camp’s inmates and the commanding crew, so in cases of a prisoners’ riot, they were the first target. The historical records mention several incidents where the watchmen died at the hands of the captives. However, little is known regarding how the dead bodies of the guards were treated nor what the funeral customs looked like in the camps. In 2019, a row of individual burials was discovered at the former Treblinka extermination and forced labor camp. Seven of those graves were explored to identify the people buried in such an unusual manner and to find out what had caused their deaths. A thorough multidisciplinary study, combining the forensic disciplines of archaeology, anthropology, medicine, and genetics provided the answer. Considering archaeological findings, it can be deduced that the graves belong to the Treblinka guards. The analysis conducted by an anthropologist indicates that the assessed biological profile aligns with the antemortem data of the Treblinka watchmen. Moreover, a study examining perimortem trauma has unveiled that out of the seven men studied, at least two met a violent demise. These findings are crucial in narrowing down the identification process. The results of our study contribute to a general understanding of the funerary customs prevalent in concentration camps worldwide. Prior to this work, there had never been any analysis or publication of the characteristics of watchmen graves at Nazi camps, making our results unique.
Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymBx Establish Their Chemoselectivity
2024-02-27

Abstract Cyclodipeptides (CDPs) build an important class of secondary metabolites with a plethora of pharmacological impact such as antibiotic, cytotoxic, antifungal properties or even as anti‐Alzheimer drug candidates. The core structure of 2,5‐diketopiperazines, a subclass of CDPs, is composed of two ‘head‐to‐tail’ connected α‐amino acids. Their chemical diversity is broadened by tailoring enzymes as members of their biosynthetic gene clusters, such as CDP‐dimerizing P450s. Recently, a new class of P450 enzymes, termed GymB x , was identified in the biosynthetic pathway of guatyromycines. These enzymes catalyse both an intramolecular C−C bond formation within cyclo ‐ l ‐Tyr‐ l ‐Tyr (cYY) and a nucleobase transfer reaction, which is unique for CDP‐modifying P450 enzymes. In this study, we report the structures of two members, GymB 1 and GymB 5 , in their unbound states, as well as GymB 5 in complex with hypoxanthine and cYY. Structural data of the ternary complex shed light into CDP binding and nucleobase transfer reaction, identified key residues for substrate recognition and modified the enzymatic bifunctionality. By mutagenesis we successfully established a GymB5 variant that strictly switched the chemoselectivity of the reaction towards an intermolecular coupling enzyme. This data set a solid basis for future protein engineering of P450 enzymes to synthesize new CDP‐nucleobase adducts.
Nietzsches Hermeneutik der Einsamkeit. Transformationen im Labyrinth der Wahrheit
2024-02-27

Abstract Nietzsche’s Hermeneutics of Loneliness. Transformations in the Labyrinth of Truth. This article delves into Nietzsche’s intricate exploration of solitude and its multifaceted manifestations in Thus Spoke Zarathustra . By distinguishing between various instances of solitude experienced by Zarathustra, including his initial journey, recurring returns, and dreamt solitude, the study unveils the creative nature of his solitude. Unlike the ascetic pursuit of transcendent truth, Nietzsche reevaluates solitude, highlighting its eternal ambiguity and challenging the notion of a fixed self or ultimate truth attainable through isolation. The hermeneutics of solitude in Nietzsche’s philosophy illustrates how perspectives and self-interpretation intertwine, shaping one’s experience within the labyrinth of truth. The article further examines the intimate relationship between solitude and perspective, emphasizing that genuine solitude emerges only through communication. Through a comprehensive analysis of shame as a mirror-motif of solitude, this study underscores the inherent connection among these concepts, rooted in the dynamics of human communication and self-revelation. It concludes that one’s position toward truth is fundamentally linked to one’s role as an interpreter and something interpreted, offering insights into the complexities of human existence and self-understanding.
Digital Gait Measures Capture 1‐Year Progression in Early‐Stage Spinocerebellar Ataxia Type 2
2024-02-28

Abstract Background With disease‐modifying drugs in reach for cerebellar ataxias, fine‐grained digital health measures are highly warranted to complement clinical and patient‐reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. Objective Our aim is to unravel gait measures sensitive to longitudinal change in the—particularly trial‐relevant—early stage of spinocerebellar ataxia type 2 (SCA2). Methods We performed a multicenter longitudinal study with combined cross‐sectional and 1‐year interval longitudinal analysis in early‐stage SCA2 participants (n = 23, including nine pre‐ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2‐minute walk, with analyses focused on gait measures of spatio‐temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). Results We found significant changes for gait measures between baseline and 1‐year follow‐up with large effect sizes (lateral step deviation P = 0.0001, effect size r prb = 0.78), whereas the SARA score showed no change ( P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test–retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1‐year change. Conclusions Gait measures assessed by wearable sensors can capture natural progression in early‐stage SCA2 within just 1 year—in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Novel Secreted Effectors Conserved Among Smut Fungi Contribute to the Virulence ofUstilago maydis
2024-02-28

Fungal pathogens deploy a set of molecules (proteins, specialized metabolites, and sRNAs), so-called effectors, to aid the infection process. In comparison to other plant pathogens, smut fungi have small genomes and secretomes of 20 Mb and around 500 proteins, respectively. Previous comparative genomic studies have shown that many secreted effector proteins without known domains, i.e., novel, are conserved only in the Ustilaginaceae family. By analyzing the secretomes of 11 species within Ustilaginaceae, we identified 53 core homologous groups commonly present in this lineage. By collecting existing mutants and generating additional ones, we gathered 44 Ustilago maydis strains lacking single core effectors as well as 9 strains containing multiple deletions of core effector gene families. Pathogenicity assays revealed that 20 of these 53 mutant strains were affected in virulence. Among the 33 mutants that had no obvious phenotypic changes, 13 carried additional, sequence-divergent, structurally similar paralogs. We report a virulence contribution of seven previously uncharacterized single core effectors and of one effector family. Our results help to prioritize effectors for understanding U. maydis virulence and provide genetic resources for further characterization. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia
2024-02-28

Neonatal hypoxia-ischemia (HI) is a major cause of perinatal death and long-term disabilities worldwide. Post-ischemic neuroinflammation plays a pivotal role in HI pathophysiology. In the present study, we investigated the temporal dynamics of microglia (CX3CR1<sup>GFP/+</sup>) and infiltrating macrophages (CCR2<sup>RFP/+</sup>) in the hippocampi of mice subjected to HI at postnatal day 9. Using inflammatory pathway and transcription factor (TF) analyses, we identified a distinct post-ischemic response in CCR2<sup>RFP/+</sup> cells characterized by differential gene expression in sensome, homeostatic, matrisome, lipid metabolic, and inflammatory molecular signatures. Three days after injury, transcriptomic signatures of CX3CR1<sup>GFP/+</sup> and CCR2<sup>RFP/+</sup> cells isolated from hippocampi showed a partial convergence. Interestingly, microglia-specific genes in CX3CR1<sup>GFP/+</sup> cells showed a sexual dimorphism, where expression returned to control levels in males but not in females during the experimental time frame. These results highlight the importance of further investigations on metabolic rewiring to pave the way for future interventions in asphyxiated neonates.
Dormancy of cutaneous melanoma
2024-02-28

Abstract Many cancer-related deaths including melanoma result from metastases that develop months or years after the initial cancer therapy. Even the most effective drugs and immune therapies rarely eradicate all tumor cells. Instead, they strongly reduce cancer burden, permitting dormant cancer cells to persist in niches, where they establish a cellular homeostasis with their host without causing clinical symptoms. Dormant cancers respond poorly to most drugs and therapies since they do not proliferate and hide in niches. It therefore remains a major challenge to develop novel therapies for dormant cancers. In this review we focus on the mechanisms regulating the initiation of cutaneous melanoma dormancy as well as those which are involved in reawakening of dormant cutaneous melanoma cells. In recent years the role of neutrophils and niche components in reawakening of melanoma cells came into focus and indicate possible future therapeutic applications. Sophisticated in vitro and in vivo melanoma dormancy models are needed to make progress in this field and are discussed.
The lithic assemblages from the Palaeolithic survey research in the Megalopolis Basin, Greece
2024-02-28

An intensive, target-oriented surface survey conducted in the Megalopolis basin during 2012-2013 led to the discovery of several Palaeolithic sites and findspots with lithics and faunal remains, including Marathousa-1, a Lower Palaeolithic open-air elephant-butchering site, dated to ca. 400-500 ka BP. This study presents the results from the techno-typological analysis of 413 lithic artefacts collected as surface or stratified finds during the survey research. The aim of the work is to evaluate the diachronic occupation of the area in relation to the lithic technologies used, the typology of the artefacts, and the raw materials exploited. It was possible to provide a chrono-cultural attribution of 167 artefacts, ranging from the Lower Palaeolithic to the Holocene, with a significant component of the collection attributed to the Middle Palaeolithic. Several diagnostic retouched tools allow us to infer that the open-air sites were occupied comparatively more intensively during the Middle Palaeolithic period. We also provide a detailed account of the lithic assemblage from Kavia cave, a previously unstudied site identified during the survey. The high frequency of artefacts pertaining to the Upper Palaeolithic in Kavia is in line with previously identified settlement and mobility patterns of the Peloponnese, where the occupation of caves becomes more intensive from the Upper Palaeolithic onward, as attested at the sites of Klissoura, Kephalari, and Franchthi. The Upper Palaeolithic component from Kavia Cave adds new data to a meagre sample of known sites from this period. The results from the typological and technological analysis of the lithic assemblages collected during the survey in Megalopolis support the conclusions of the basin's long-term and ongoing research, indicating a relatively continuous hominin presence during the Pleistocene.
A Mechanistic Model and Experiments on Bedrock Incision and Channelization by Rockfall
2024-02-28

Abstract Rockfall and rock avalanches are common in steep terrain on Earth and potentially on other planetary bodies such as the Moon and Mars. Since impacting rocks can damage exposed bedrock as they roll and bounce downhill, rockfall might be an important erosive agent in steep landscapes, even in the absence of water. We developed a new theory for rockfall‐driven bedrock abrasion using the ballistic trajectories of rocks transported under gravity. We calibrated this theory using laboratory experiments of rockfall over an inclined bedrock simulant. Both the experiments and the model demonstrate that bedrock hillslopes can be abraded by dry rockfall, even at gradients below the angle of repose, depending on the bedrock roughness. Feedback between abrasion and topographic steering of rockfall can produce channel‐like forms, such as bedrock chutes, in the absence of water. Particle size has a dominant influence on abrasion rates and runout distances, while the hillslope angle has a comparatively minor influence. Rockfall transport is sensitive to bedrock roughness; terrain with high friction angles can trap rocks creating patches of rock cover that affect subsequent rockfall pathways. Our results suggest that dry rockfall can play an important role in eroding and channelizing steep, rocky terrain on Earth and other planets, such as crater degradation on the Moon and Mars.
Higher conversion rate to knee arthroplasty in female patients following medial open‐wedge high tibial osteotomy
2024-02-28

Abstract Purpose Most studies about medial open‐wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long‐term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. Methods The data of three cohorts with long‐term outcomes were analysed ( n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow‐up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender‐specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan–Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. Results Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower ( p = 0.0010). The 5‐ and 10‐year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow‐up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p &lt; 0.0001). Females had significantly lower preoperative and postoperative IKDC ( p = 0.0438; p = 0.0035) and Lysholm scores ( p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. Conclusions Females had higher conversion rates to TKA and lower knee function at the last follow‐up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. Level of Evidence Level II.
Decoding Motor Excitability in TMS using EEG-Features: An Exploratory Machine Learning Approach
2024-02-28

Abstract Background With the burgeoning interest in personalized treatments for brain network disorders, closed-loop transcranial magnetic stimulation (TMS) represents a promising frontier. Relying on the real-time adjustment of stimulation parameters based on brain signal decoding, the success of this approach depends on the identification of precise biomarkers for timing the stimulation optimally. Objective We aimed to develop and validate a supervised machine learning framework for the individualized prediction of motor excitability states, leveraging a broad spectrum of sensor and source space EEG features. Methods Our approach integrates multi-scale EEG feature extraction and selection within a nested cross-validation scheme, tested on a cohort of 20 healthy participants. We assessed the framework’s performance across different classifiers, feature sets, and experimental protocols to ensure robustness and generalizability. Results Personalized classifiers demonstrated a statistically significant mean predictive accuracy of 72 ± 11%. Consistent performance across various testing conditions highlighted the sufficiency of sensor-derived features for accurate excitability state predictions. Subtype analysis revealed distinct clusters linked to specific brain regions and oscillatory features as well as the need for a more extensive feature set for effective biomarker identification than conventionally considered. Conclusions Our machine learning framework effectively identifies predictive biomarkers for motor excitability, holding potential to enhance the efficacy of personalized closed-loop TMS interventions. While the clinical applicability of our findings remains to be validated, the consistent performance across diverse testing conditions and the efficacy of sensor-only features suggest promising avenues for clinical research and wider applications in brain signal classification.
Unveiling pathogenic and non-pathogenic FGF14 repeat expansions: identification, sequence, and secondary structure
2024-02-28

<title>Abstract</title> Repeat expansions in <italic>FGF14</italic>cause autosomal dominant late-onset cerebellar ataxia (SCA27B), with pathogenic thresholds estimated between 250 and 300 AAG repeats. However, the complete sequences of pathogenic and non-pathogenic alleles remain largely unknown. Here, we identify <italic>FGF14</italic> repeat expansions as the most commonly missed cause of cerebellar ataxia using a combination of short-read genome sequencing, long-range PCR and nanopore sequencing. We compare <italic>FGF14</italic> alleles in 154 patients with ataxia and 802 controls and report an enrichment of pure <italic>FGF14</italic> expansions above 180-220 repeats in patients. Conversely, AAGGAG and interrupted alleles are more frequent in controls. Distinct 5'-flanking regions correlate with repeat stability. SCA27B patients have a characteristic phenotype, including frequent episodic ataxia and downbeat nystagmus, similar to those with a novel nonsense variant (SCA27A). Interestingly, pathogenic and non-pathogenic repeats form different secondary structures. Our results emphasize the importance of sequencing both the repeat expansion and its flanking region for accurate clinical interpretation.