julilili42/papers huggingface dataset:
Automated real‐time EEG sleep spindle detection for brain‐state‐dependent brain stimulation
2022-09-21

Summary Sleep spindles are a hallmark electroencephalographic feature of non‐rapid eye movement sleep, and are believed to be instrumental for sleep‐dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real‐time with sensory or non‐invasive brain‐stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real‐time is highly challenging due to their spontaneous and transient nature. Here, we present the real‐time spindle detector, a robust multi‐channel electroencephalographic signal‐processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase‐specific manner. We validated the real‐time spindle detection method by streaming pre‐recorded sleep electroencephalographic datasets to a real‐time computer system running a Simulink® Real‐TimeTM implementation of the algorithm. Sleep spindles were detected with high levels of Sensitivity (~83%), Precision (~78%) and a convincing F1‐Score (~81%) in reference to state‐of‐the‐art offline algorithms (which reached similar or lower levels when compared with each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude and symmetry, and showed the typical time–frequency characteristics as well as a centroparietal topography. Spindles were detected close to their centre and reliably at the predefined target phase. The real‐time spindle detection algorithm therefore empowers researchers to target spindles during human sleep, and apply the stimulation method and experimental paradigm of their choice.
The Immune Contexture of Liposarcoma and Its Clinical Implications
2022-09-21

Liposarcomas (LPS) are the most frequent malignancies in the soft tissue sarcoma family and consist of five distinctive histological subtypes, termed well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. They display variations in genetic alterations, clinical behavior, and prognostic course. While accumulating evidence implicates a crucial role of the tumor immune contexture in shaping the response to anticancer treatments, the immunological landscape of LPS is highly variable across different subtypes. Thus, DDLPS is characterized by a higher abundance of infiltrating T cells, yet the opposite was reported for MLPS. Interestingly, a recent study indicated that the frequency of pre-existing T cells in soft tissue sarcomas has a predictive value for immune checkpoint inhibitor (CPI) therapy. Additionally, B cells and tertiary lymphoid structures were identified as potential biomarkers for the clinical outcome of LPS patients and response to CPI therapy. Furthermore, it was demonstrated that macrophages, predominantly of M2 polarization, are frequently associated with poor prognosis. An improved understanding of the complex LPS immune contexture enables the design and refinement of novel immunotherapeutic approaches. Here, we summarize recent studies focusing on the clinicopathological, genetic, and immunological determinants of LPS.
Cortical mechanisms of movement recovery after freezing in Parkinson's disease
2022-09-21

Involuntary interruptions of upper limb movements, referred to as “upper limb freezing” (ULF) belong to the most disabling symptoms of Parkinson's disease (PD). Our study aimed to explore the cortical neuronal mechanisms underlying the reinstation of regular movement after a freezing episode and to control them by voluntary stops. We hypothesized that this movement recovery after a freeze would be accompanied by a decrease of beta power (13-30 Hz) over the primary sensorimotor cortex (electrode “C3”). We recorded a 62-channel surface EEG in 14 PD patients during a repetitive finger tapping task. After performing time-frequency analysis of the EEG data we segmented it to i) regular finger taps, ii) ULF episodes, and iii) voluntary movement stops (VS). We analysed cortical activity during each movement modality and later focused on the last 500 ms of ULF and VS and the first half of the following regular tap. At the beginning of regular finger taps we found decreased alpha power (6-12 Hz) over C3 (P = 0.01). During ULF, there was no significant activity modulation in the alpha and beta frequency bands, whereas beta power increased over C3 during VS (P = 0.0038). When tapping was reinstated after a freeze, we found that 100 ms before movement onset beta power decreased first present over C3, followed by fronto-central electrodes and then reaching the ipsilateral right fronto-temporal electrodes when reinstating regular tapping (P = 0.0256). Initiating movement after a VS showed a different pattern with a decrease of parieto-occipital beta activity 200 ms prior to the first tap (P = 0.044). Our findings suggest that PD freezers make use of different cortical pathways when re-initiating movement after ULF or VS. This includes either fronto-central or parieto-occipital pathways. These findings may help to customize novel neuromodulation strategies to counteract freezing behaviour.
Diagnostics in Waldenström’s Macroglobulinemia: a consensus statement of the European Consortium for Waldenström’s Macroglobulinemia
2022-09-21

Abstract The diagnosis of Waldenström’s macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström’s Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
LRRK2-G2019S Synergizes With Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation That Precede Nigrostriatal Degeneration
2022-09-21

Abstract Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). The incomplete penetrance of LRRK2 mutations suggest that additional hits are required for disease onset. We hypothesized that chronic low-grade inflammation interacts with LRRK2 G2019S, the most frequent PD-associated mutation, to activate peripheral and central immune reactions and drive age-dependent neurodegeneration. We exposed wild-type and LRRK2 G2019S mice to a low chronic dose of lipopolysaccharide and performed a longitudinal analysis of central and peripheral immune reactions and neurodegeneration. Low-dose inflammation triggered nigrostriatal degeneration, peripheral monocyte infiltration, and astro-/microgliosis. LRRK2 G2019S mice showed an early dysregulation of peripheral cytokines as well as increased CD4+ T-cell infiltration and α-synuclein aggregation in the colon. Peripheral immune activation and colonic α-synuclein aggregation preceded brain inflammation and degeneration. Our study suggests an early role of the peripheral immune system and the gut in LRRK2 PD and provides a novel model to study early therapeutic immune targets and biomarkers.
Mastery-approach goals: A large-scale cross-cultural analysis of antecedents and consequences.
2022-09-22

Mastery-approach (MAP) goals, focusing on developing competence and acquiring task mastery, are posited to be the most optimal, beneficial type of achievement goal for academic and life outcomes. Although there is meta-analytic evidence supporting this finding, such evidence does not allow us to conclude that the extant MAP goal findings generalize across cultures. Meta-analyses have often suffered from overrepresentation of Western, educated, industrialized, rich, and democratic (WEIRD) samples; reliance on bivariate correlations; and lack the ability to directly control individual-level background variables. To address these limitations, this study used nationally representative data from 77 countries/regions (<i>N</i> = 595,444 adolescents) to examine the relations of MAP goals to four antecedents (workmastery, competitiveness, fear of failure, fixed mindset) and 16 consequences (task-specific motivational, achievement-related, and well-being outcomes), and tested the cross-cultural generalizability of these relations. Results showed that MAP goals were: (a) grounded primarily in positive but not negative achievement motives/beliefs; (b) most strongly predictive of well-being outcomes, followed by adaptive motivation; (c) positively but consistently weakly associated with achievement-related outcomes, particularly for academic performance (β = .069); (d) negatively and weakly associated with maladaptive outcomes; and (e) uniquely predictive of various consequences, controlling for the antecedents and covariates. Further, the MAP goal predictions were generalizable across countries/regions for 13 of 16 consequences. While directions of effect sizes were slightly mixed for academic performance, perceived reading, and PISA test difficulty, the effect sizes were consistently small for most countries/regions. This generalizability points to quite strong cross-cultural support for the observed patterns. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
CORK1, A LRR-Malectin Receptor Kinase, Is Required for Cellooligomer-Induced Responses in Arabidopsis thaliana
2022-09-22

Cell wall integrity (CWI) maintenance is central for plant cells. Mechanical and chemical distortions, pH changes, and breakdown products of cell wall polysaccharides activate plasma membrane-localized receptors and induce appropriate downstream responses. Microbial interactions alter or destroy the structure of the plant cell wall, connecting CWI maintenance to immune responses. Cellulose is the major polysaccharide in the primary and secondary cell wall. Its breakdown generates short-chain cellooligomers that induce Ca2+-dependent CWI responses. We show that these responses require the malectin domain-containing CELLOOLIGOMER-RECEPTOR KINASE 1 (CORK1) in Arabidopsis and are preferentially activated by cellotriose (CT). CORK1 is required for cellooligomer-induced cytoplasmic Ca2+ elevation, reactive oxygen species (ROS) production, mitogen-associated protein kinase (MAPK) activation, cellulose synthase phosphorylation, and the regulation of CWI-related genes, including those involved in biosynthesis of cell wall material, secondary metabolites and tryptophan. Phosphoproteome analyses identified early targets involved in signaling, cellulose synthesis, the endoplasmic reticulum/Golgi secretory pathway, cell wall repair and immune responses. Two conserved phenylalanine residues in the malectin domain are crucial for CORK1 function. We propose that CORK1 is required for CWI and immune responses activated by cellulose breakdown products.
Dendritic axon origin enables information gating by perisomatic inhibition in pyramidal neurons
2022-09-22

Information processing in neuronal networks involves the recruitment of selected neurons into coordinated spatiotemporal activity patterns. This sparse activation results from widespread synaptic inhibition in conjunction with neuron-specific synaptic excitation. We report the selective recruitment of hippocampal pyramidal cells into patterned network activity. During ripple oscillations in awake mice, spiking is much more likely in cells in which the axon originates from a basal dendrite rather than from the soma. High-resolution recordings in vitro and computer modeling indicate that these spikes are elicited by synaptic input to the axon-carrying dendrite and thus escape perisomatic inhibition. Pyramidal cells with somatic axon origin can be activated during ripple oscillations by blocking their somatic inhibition. The recruitment of neurons into active ensembles is thus determined by axonal morphological features.
Three perspectives on the prediction of chemical effects in ecosystems
2022-09-22

Abstract The increasing production, use and emission of synthetic chemicals into the environment represents a major driver of global change. The large number of synthetic chemicals, limited knowledge on exposure patterns and effects in organisms and their interaction with other global change drivers hamper the prediction of effects in ecosystems. However, recent advances in biomolecular and computational methods are promising to improve our capacity for prediction. We delineate three idealised perspectives for the prediction of chemical effects: the suborganismal, organismal and ecological perspective, which are currently largely separated. Each of the outlined perspectives includes essential and complementary theories and tools for prediction but captures only part of the phenomenon of chemical effects. Links between the perspectives may foster predictive modelling of chemical effects in ecosystems and extrapolation between species. A major challenge for the linkage is the lack of data sets simultaneously covering different levels of biological organisation (here referred to as biological levels) as well as varying temporal and spatial scales. Synthesising the three perspectives, some central aspects and associated types of data seem particularly necessary to improve prediction. First, suborganism‐ and organism‐level responses to chemicals need to be recorded and tested for relationships with chemical groups and organism traits. Second, metrics that are measurable at many biological levels, such as energy, need to be scrutinised for their potential to integrate across levels. Third, experimental data on the simultaneous response over multiple biological levels and spatiotemporal scales are required. These could be collected in nested and interconnected micro‐ and mesocosm experiments. Lastly, prioritisation of processes involved in the prediction framework needs to find a balance between simplification and capturing the essential complexity of a system. For example, in some cases, eco‐evolutionary dynamics and interactions may need stronger consideration. Prediction needs to move from a static to a real‐world eco‐evolutionary view.
Molecular Epidemiology of HIV-1 in Eastern Europe and Russia
2022-09-22

The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.
MR Imaging and Clinical Characteristics of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters
2022-09-22

This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.
What do complexity measures measure? Correlating and validating corpus-based measures of morphological complexity
2022-09-22

Abstract We present an analysis of eight measures used for quantifying morphological complexity of natural languages. The measures we study are corpus-based measures of morphological complexity with varying requirements for corpus annotation. We present similarities and differences between these measures visually and through correlation analyses, as well as their relation to the relevant typological variables. Our analysis focuses on whether these ‘measures’ are measures of the same underlying variable, or whether they measure more than one dimension of morphological complexity. Principal component analysis indicates that the first principal component explains 92.62 percent of the variation in eight measures, indicating a strong linear dependence between the complexity measures studied.
To start or to discontinue the pill – changes in progestogens reflected by resting-state connectivity and positive mood
2022-09-22

Abstract Oral contraceptive (OC) intake has been associated with alterations in functional brain architecture and socio-affective processes. However, most previous studies have been limited by cross-sectional designs and/or did not account for synthetic sex hormone concentrations. The aim of this longitudinal study was to determine the effects of starting vs discontinuing OCs on socio-affective functions such as mood and emotion cognition, and to identify their possible neuroendocrinological substrates. To this end, 88 young healthy women performed the behavioral and fMRI measures twice, three to eight months apart: 26 natural cycling women twice during menstruation, 26 OC users twice during OC intake, 25 OC discontinuers and 11 OC starters before and after discontinuation or start, respectively. In addition to mean-based analyses, we used intersubject representational similarity analyses to determine relationships between interindividual variability in within-subject changes of hormone profiles, including concentrations of endogenous and synthetic hormones, region-specific resting state functional connectivity (parcelwise RSFC) and socio-affective measures. Across the whole sample, interindividual patterns of changes in RSFC of fronto-parietal regions, parts of the left hippocampus and the right cerebellum reflected change patterns of progestogen levels. For the right superior orbitofrontal gyrus (OFG), a trinity of idiosyncratic patterns was found in changes of progestogens, RSFC and positive mood. Active OC intake was associated with higher self-reported depressive symptoms in OC discontinuers (and starters). Emotion recognition performance was not associated with changes in hormone profiles or RSFC. Overall, progestogens rather than estrogens appear to be associated with functional brain architecture of the frontal and subcortical/cerebellar regions and positive mood. The right superior OFG represents a possible neural substrate for progestogen-induced changes in positive mood. This study indicates the importance of a multidimensional, longitudinal approach when being interested in effects of hormonal contraception on women’s brain and behavior.
Transmitter and receiver of the low frequency horseshoe bat Rhinolophus paradoxolophus are functionally matched for fluttering target detection
2022-09-22

Abstract Flutter-detecting foragers require specific adaptations of the transmitter and the receiver of their echolocation systems to detect and evaluate flutter information in the echoes of potential prey. These adaptations include Doppler shift compensation (DSC), which keeps the echo frequency from targets ahead constant at a reference frequency (f ref ), and an auditory fovea in the cochlea, which results in foveal areas in the hearing system with many sharply tuned neurons with best frequencies near f ref . So far, this functional match has been verified only for a very few key species, but is postulated for all flutter-detecting foragers. In this study we determined both, the transmitter and receiver properties within individuals of the Bourret’s horseshoe bat ( Rhinolophus paradoxolophus ), an allometric outlier in the rhinolophid family. Here we show that the transmitter and receiver are functionally matched in a similar way as postulated for all flutter-detecting foragers. The performance of DSC, measured as the ability to keep the echo frequency constant at f ref , had a precision similar to that found in other flutter-detecting foragers, and the audiogram showed the characteristic course with a minimum at f ref . Furthermore, we show for a rhinolophid bat a variation over time of the coupled resting frequency and f ref . Finally, we discuss the tight match between transmitter and receiver properties, which is guaranteed by the link between the foveal areas of the receiver and the audio–vocal control system for DSC.
Computational modelling in health and disease: highlights of the 6th annual SysMod meeting
2022-09-22

Abstract Summary The Community of Special Interest (COSI) in Computational Modelling of Biological Systems (SysMod) brings together interdisciplinary scientists interested in combining data-driven computational modelling, multi-scale mechanistic frameworks, large-scale -omics data and bioinformatics. SysMod’s main activity is an annual meeting at the Intelligent Systems for Molecular Biology (ISMB) conference, a meeting for computer scientists, biologists, mathematicians, engineers and computational and systems biologists. The 2021 SysMod meeting was conducted virtually due to the ongoing COVID-19 pandemic (coronavirus disease 2019). During the 2-day meeting, the development of computational tools, approaches and predictive models was discussed, along with their application to biological systems, emphasizing disease mechanisms. This report summarizes the meeting. Availability and implementation All resources and further information are freely accessible at https://sysmod.info.
Improved localization of language areas using single voxel signal analysis of unprocessed fMRI data
2022-09-22

Activated brain regions can be visualized and localized with the use of fMRI (functional magnetic imaging). This is based on changes in the blood flow in activated regions, or more precisely on the hemodynamic response function (HRF) and the Blood-Oxygen-Level-Dependent (BOLD) effect. This study used a task-based fMRI examination with language paradigms in order to stimulate the language areas. The measured fMRI data are frequently altered by different preprocessing steps for the analysis and the display of activations. These changes can lead to discrepancies between the displayed and the truly measured location of the activations. Simple t -maps were created with unprocessed fMRI data, to provide a more realistic representation of the language areas. HRF-dependent single-voxel fMRI signal analysis was performed to improve the analyzability of these activation maps.