julilili42/papers huggingface dataset:
Facilitating frontal-occipital communication via closed-loop EEG -TMS enhances visual perception
2022-12-05

Accumulating evidence has shown that frontal regions exert top-down control over the visual system to successfully prioritize processing of visual information. The communication-through-coherence theory (Fries, 2005) suggests that effective communication between anatomically distinct brain regions depends on the extent to which their oscillatory activity is synchronized. Indeed, it was shown that synchronization of alpha oscillations mediates frontal-occipital communication during attention allocation. However, how these distant regions communicate to determine visual performance had not been causally tested. Therefore, the goal of the current study was to causally test whether enhancing frontal-occipital synchronization of alpha oscillations would facilitate visual performance. To actively enhance frontal-occipital synchronization, we deployed a novel technique that combines electroencephalography (EEG) and non-invasive transcranial magnetic stimulation (TMS), (Zrenner et al., 2018). In a closed-loop procedure, TMS was delivered over the right frontal eye field (FEF) according to the phase of occipital alpha oscillations, measured in real time with scalp EEG. To evaluate the effect of stimulation, subjects underwent a classical visual detection-attention task, known to require the engagement of frontal and occipital regions, before and after the closed-loop procedure. In the task, subjects were required to detect a peripheral low contrast target that appeared after the onset of either a valid or neutral cue. Participants in a control condition completed the same task, without a closed-loop stimulation procedure. Preliminary results show that frontal-occipital closed-loop EEG-TMS enhanced visual sensitivity in the neutral condition relative to the control condition. Consistently, closed-loop stimulation over the right FEF induced greater right occipital alpha power suppression during the neutral cue condition. Furthermore, the magnitude of visual improvements was correlated with the accuracy of the occipital alpha phase estimation used to initiate the closed-loop stimulations. These results point to a causal relation between real-time modulation of frontal-occipital communication and enhanced visual perception.
Sensory tuning in neuronal movement commands: neurophysiological evidence
2022-12-05

Movement control is critical for successful interaction with our environment. However, movement does not occur in complete isolation of sensation, and this is particularly true of eye movements. Here, the superior colliculus (SC) plays a fundamental role, issuing saccade motor commands in the form of strong peri-movement bursts that are very widely believed to specify both saccade metrics (direction and amplitude) and kinematics (speed). However, most models of saccade control by the SC rely on observations with small light spots as saccade targets. Instead, we asked two monkeys to “look” at images, akin to natural behavior. We tested gratings of different contrasts, spatial frequencies, and orientations, and also animate and inanimate object images. Despite matched saccade properties across trials within a given image manipulation, SC neurons’ motor bursts were strongly different for different images. Such sensory tuning in the SC neuronal movement commands could even be sharper than that in passive visual responses: the difference in movement burst strength between the most and least preferred image features (for the same saccade vector) was larger than that in visual bursts, consistent with known pre-saccadic perceptual enhancement. Most intriguingly, even purely motor neurons exhibited strong sensory tuning in their saccade-related bursts. Since SC motor bursts are relayed virtually unchanged to the cortex (Sommer & Wurtz, 2004), one implication of our results is that the visual system is primed not only about the sizes and directions of upcoming saccades, as is traditionally believed, but also about the movement targets’ visual sensory properties. Consistent with this, in a companion study (VSS 2022), we additionally found that saccade-target visual features significantly modulate peri-saccadic perception. Our results provide novel insights about the functional role of SC motor commands, and they motivate extending theoretical accounts of corollary discharge beyond just spatial movement-related reference frames.
Exploring the effects of spontaneous body movements on activity in the macaque visual cortex
2022-12-05

Previous work in mice reported neuronal modulations in visual cortex by movements. Beyond the sizeable effects of locomotion, such modulations were associated with task-unrelated spontaneous body movements, challenging the view that the activity of neurons in early sensory cortices is driven predominantly by sensory input of a single modality. These modulations were not limited to stimulus-evoked responses but also observed for spontaneous activity, suggesting that the population activity in early sensory cortices spans multiple dimensions defined by ongoing behavioral states. To examine the possibility of modulation by body movements in non-human primates, we recorded extracellularly from neuronal populations in V1, V2 and V3/V3A (n=188, 92, 191 units, respectively) in three macaque monkeys, seated in primate chairs, while their body movements were monitored with multiple cameras. The animals maintained central fixation while visual stimuli (random dots, random lines, sinusoidal luminance gratings) or a blank screen were presented. One animal additionally performed a visual task that allowed us to manipulate spatial attention directed to the neuronal receptive fields. The definition of motion periods was based on the average of the absolute pixel-wise difference between successive video frames. For each unit, the modulation by movement was quantified with a movement index (MI): the difference in the stimulus-conditioned mean response in the presence and absence of body movements divided by their sum. MI averaged across units was modest, ranging -0.080 – 0.080 (mean = -0.004) across all areas and subjects but statistically significant for some areas (V1, V2 for one, V3/V3A for two animals, p<0.05, t-test). Conversely, the response modulation by attention measured with an index equivalent to MI was greater by an order of magnitude and increased monotonically from V1 to V3/V3A. These results, which contrast with those in mice, may reflect the varying degrees to which visual cortex specialized during evolution.
Prioritization of mixtures of neurotoxic chemicals for biomonitoring using high-throughput toxicokinetics and mixture toxicity modeling
2022-12-06

Modern society continues to pollute the environment with larger quantities of chemicals that have also become more structurally and functionally diverse. Risk assessment of chemicals can hardly keep up with the sheer numbers that lead to complex mixtures of increasing chemical diversity including new chemicals, substitution products on top of still abundant legacy compounds. Fortunately, over the last years computational tools have helped us to identify and prioritize chemicals of concern. These include toxicokinetic models to predict exposure to chemicals as well as new approach methodologies such as in-vitro bioassays to address toxicodynamic effects. Combined, they allow for a prediction of mixtures and their respective effects and help overcome the lack of data we face for many chemicals. In this study we propose a high-throughput approach using experimental and predicted exposure, toxicokinetic and toxicodynamic data to simulate mixtures, to which a virtual population is exposed to and predict their mixture effects. The general workflow is adaptable for any type of toxicity, but we demonstrated its applicability with a case study on neurotoxicity. If no experimental data for neurotoxicity were available, we used baseline toxicity predictions as a surrogate. Baseline toxicity is the minimal toxicity any chemical has and might underestimate the true contribution to the mixture effect but many neurotoxicants are not by orders of magnitude more potent than baseline toxicity. Therefore, including baseline-toxic effects in mixture simulations yields a more realistic picture than excluding them in mixture simulations. This workflow did not only correctly identify and prioritize known chemicals of concern like benzothiazoles, organochlorine pesticides and plasticizers but we were also able to identify new potential neurotoxicants that we recommend to include in future biomonitoring studies and if found in humans, to also include in neurotoxicity screening.
Horizontal Transfer of Bacteriocin Biosynthesis Genes Requires Metabolic Adaptation To Improve Compound Production and Cellular Fitness
2022-12-06

Human microbiomes are critically associated with human health and disease. Importantly, pathogenic bacteria can hide in human-associated communities and can cause disease when the composition of the community becomes unbalanced.
Automation of Measurements for Personalized Medical Appliances by Means of CAD Software—Application in Robin Sequence Orthodontic Appliances
2022-12-06

Measuring the dimensions of personalized devices can provide relevant information for the production of future such devices used in various medical specialties. Difficulties with standardizing such measurement and obtaining high accuracy, alongside cost-intensive measuring methodologies, has dampened interest in this practice. This study presents a methodology for automatized measurements of personalized medical appliances of variable shape, in this case an orthodontic appliance known as Tübingen Palatal Plate (TPP). Parameters such as length, width and angle could help to standardize and improve its future use. A semi-automatic and custom-made program, based on Rhinoceros 7 and Grasshopper, was developed to measure the device (via an extraoral scanner digital file). The program has a user interface that allows the import of the desired part, where the user is able to select the necessary landmarks. From there, the program is able to process the digital file, calculate the necessary dimensions automatically and directly export all measurements into a document for further processing. In this way, a solution for reducing the time for measuring multiple dimensions and parts while reducing human error can be achieved.
Associations of Betatrophin/ANGPTL8 with Septic Dyslipidemia in Human Peritonitis: An Explorative Analysis
2022-12-06

Sepsis is defined by life-threatening organ dysfunction mediated by the host’s response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p &lt; 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p &lt; 0.05).
Performance of the Deep Neural Network Ciloctunet, Integrated with Open-Source Software for Ciliary Muscle Segmentation in Anterior Segment OCT Images, Is on Par with Experienced Examiners
2022-12-06

Anterior segment optical coherence tomography (AS-OCT), being non-invasive and well-tolerated, is the method of choice for an in vivo investigation of ciliary muscle morphology and function. The analysis requires the segmentation of the ciliary muscle, which is, when performed manually, both time-consuming and prone to examiner bias. Here, we present a convolutional neural network trained for the automatic segmentation of the ciliary muscle in AS-OCT images. Ciloctunet is based on the Freiburg U-net and was trained and validated using 1244 manually segmented OCT images from two previous studies. An accuracy of 97.5% for the validation dataset was achieved. Ciloctunet’s performance was evaluated by replicating the findings of a third study with 180 images as the test data. The replication demonstrated that Ciloctunet performed on par with two experienced examiners. The intersection-over-union index (0.84) of the ciliary muscle thickness profiles between Ciloctunet and an experienced examiner was the same as between the two examiners. The mean absolute error between the ciliary muscle thickness profiles of Ciloctunet and the two examiners (35.16 μm and 45.86 μm) was comparable to the one between the examiners (34.99 μm). A statistically significant effect of the segmentation type on the derived biometric parameters was found for the ciliary muscle area but not for the selective thickness reading (“perpendicular axis”). Both the inter-rater and the intra-rater reliability of Ciloctunet were good to excellent. Ciloctunet avoids time-consuming manual segmentation, thus enabling the analysis of large numbers of images of ample study cohorts while avoiding possible examiner biases. Ciloctunet is available as open-source.
Urinary Metabolic Profiling in Volunteers Undergoing Malaria Challenge in Gabon
2022-12-06

The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-naïve Europeans, who were all challenged with direct venous inoculation of live P. falciparum sporozoïtes (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas.
MAP-MUSIC2VEC: A SIMPLE AND EFFECTIVE BASELINE FOR SELF-SUPERVISED MUSIC AUDIO REPRESENTATION LEARNING
2022-12-06

&lt;p&gt;The deep learning community has witnessed an exponentially growing interest in self-supervised learning (SSL). However, it still remains unexplored how to build a framework for learning useful representations of raw music waveforms in a self-supervised manner. In this work, we design Music2Vec, a framework exploring different SSL algorithmic components and tricks for music audio recordings. Our model achieves comparable results to the state-of-the-art (SOTA) music SSL model Jukebox, despite being significantly smaller with less than 2% of parameters of the latter. The model will be released on Huggingface.(https://huggingface.co/m-a-p/music2vec-v1)&lt;/p&gt; &lt;p&gt;&nbsp;&lt;/p&gt; &lt;p&gt;The paper has been published at ISMIR LBD 2022. We only used&nbsp;1k/130k hours of data to train the ISMIR LBD demo and will further scale up to get&nbsp;better performance.&lt;/p&gt;
Immune cell targeted Fumaric Esters support a role of GPR109A as a 2 primary target of Monomethyl Fumarate in vivo
2022-12-06

Abstract Dimethyl fumarate (DMF) is approved as a treatment for multiple sclerosis (MS), however, its mode of action remains unclear. One hypothesis proposes that Michael addition to thiols by DMF, notably gluta- thione is immunomodulatory. The alternative proposes that monomethyl fumarate (MMF), the hydrolysis product of DMF, is a ligand to the fatty acid receptor GPR109A found in the lysosomes of immune cells. We prepared esters of MMF and macrolides derived from azithromycin, which were tropic to immune cells by virtue of lysosomal trapping. We tested the effects of these substances in an assay of response to LPS in freshly isolated human peripheral blood mononuclear cells (PBMCs). In this system, we observed that the 4’’ ester of MMF (compound 2 and 3) reduced levels of IL-1β, IL-12 and TNFα significantly at a concentration of 1 μM, while DMF required about 25 μM for the same effect. The 2’ esters of MMF (compound 1 and 2) were, like MMF itself, inactive in vitro. The 4’’ ester formed glutathione conjugates rapidly while the 2’ conjugates did not react with thiols but did hydrolyze slowly to release MMF in these cells. We then tested the sub-stances in vivo using the imiquimod/isostearate model of psoriasis where the 2’ ester was the most active at 0.06 to 0.12 mg/kg (approximately 0.1 μmol/kg), improving skin score, body weight and cytokine levels (TNFα, IL-17A, IL-17F, IL-6, IL-1β, NLRP3 and IL-23A). In contrast, the thiol reactive 4’’ ester was less active than the 2’ ester while DMF was ca. 300-fold less active. The thiol reactive 4’’ ester was not easily recovered from either plasma or organs while the 2’ ester exhibited conventional uptake and elimination. The 2’ ester also reduced levels of IL-6 in acute MSU induced inflammation. These data suggest that mechanisms that are relevant in vivo center on the release of MMF. Given that GPR109A is localized to the lysosome, and that lysosomal trapping increases 2’ ester activity by &gt;300 fold, these data suggest that GPR109A may be the main target in vivo. In contrast, the effects associated with GSH conjugation in vitro are unlikely to be as effective in vivo due the much lower dose in use which cannot titrate the more concentrated thiols. These data support the case for GPR109A modulation in autoimmune diseases.
Gravitational Waves from Extreme-Mass-Ratio Systems in Astrophysical Environments
2022-12-07

We establish a generic, fully relativistic formalism to study gravitational-wave emission by extreme-mass-ratio systems in spherically symmetric, nonvacuum black hole spacetimes. The potential applications to astrophysical setups range from black holes accreting baryonic matter to those within axionic clouds and dark matter environments, allowing one to assess the impact of the galactic potential, of accretion, gravitational drag, and halo feedback on the generation and propagation of gravitational waves. We apply our methods to a black hole within a halo of matter. We find fluid modes imparted to the gravitational-wave signal (a clear evidence of the black hole fundamental mode instability) and the tantalizing possibility to infer galactic properties from gravitational-wave measurements by sensitive, low-frequency detectors.
What is conservation paleobiology? Tracking 20 years of research and development
2022-12-07

Conservation paleobiology has coalesced over the last two decades since its formal coining, united by the goal of applying geohistorical records to inform the conservation, management, and restoration of biodiversity and ecosystem services. Yet, the field is still attempting to form an identity distinct from its academic roots. Here, we ask a deceptively simple question: What is conservation paleobiology? To track its development as a field, we synthesize complementary perspectives from a survey of the scientific community that is familiar with conservation paleobiology and a systematic literature review of publications that use the term. We present an overview of conservation paleobiology’s research scope and compare survey participants’ perceptions of what it is and what it should be as a field. We find that conservation paleobiologists use a variety of geohistorical data in their work, although research is typified by near-time records of marine molluscs and terrestrial mammals collected over local to regional spatial scales. Our results also confirm the field’s broad disciplinary basis: survey participants indicated that conservation paleobiology can incorporate information from a wide range of disciplines spanning conservation biology, ecology, historical ecology, paleontology, and archaeology. Finally, we show that conservation paleobiologists have yet to reach a consensus on how applied the field should be in practice. The survey revealed that many participants thought the field should be more applied but that most do not currently engage with conservation practice. Reflecting on how conservation paleobiology has developed over the last two decades, we discuss opportunities to promote community cohesion, strengthen collaborations within conservation science, and align training priorities with the field’s identity as it continues to crystallize.
Acute, periprocedural and longterm antithrombotic therapy in older adults
2022-12-07

Abstract The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.