Planet Neuroscience

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Deficits in or Preservation of Basic Number Processing in Parkinson's Disease? A Registered Report

Parkinson patients with mild cognitive impairment do not only show established motor (e.g., tremor and rigor) and nonmotor (e.g., depression and global cognitive impairment) symptoms. They also show deficits in some basic numerical functions: (non-) symbolic magnitude comparison and number line estimation In contrast, auditory and written transcoding skills were preserved.

ABSTRACT

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health care system. Until now, diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests mechanisms of both primary and secondary dyscalculia. The current study systematically investigated basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consisted of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients were stratified into patients with normal cognition (PD-NC) or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing was assessed using transcoding, number line estimation, and (non-) symbolic number magnitude comparison tasks. Discriminant analysis was employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants were subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Results indicate a profile of preserved (verbal representation) and impaired (magnitude representation, place × value activation) function in PD-MCI, hinting at basal ganglia dysfunction affecting numerical cognition in PD. Numerical deficits could not be explained by domain-general cognitive impairments, so that future research needs to incorporate domain-specific tasks of sufficient difficulty.

in Journal of Neuroscience Research on 2024-11-16 08:04:23 UTC.

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Issue Information ‐ Editorial Board

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Dissecting the Hippocampal Regulation of Approach‐Avoidance Conflict: Integrative Perspectives From Optogenetics, Stress Response, and Epigenetics

ABSTRACT

Psychiatric disorders are multifactorial conditions without clear biomarkers, influenced by genetic, environmental, and developmental factors. Understanding these disorders requires identifying specific endophenotypes that help break down their complexity. Here, we undertake an in-depth analysis of one such endophenotype, namely imbalanced approach-avoidance conflict (AAC), reviewing its significant dependency on the hippocampus. Imbalanced AAC is a transdiagnostic endophenotype, being a feature of many psychiatric conditions in humans. However, it is predominantly examined in preclinical research through paradigms that subject rodents to conflict-laden scenarios. This review offers an original perspective by discussing the AAC through three distinct lights: optogenetic modulation of the AAC, which updates our understanding of the hippocampal contribution to behavioral inhibition; the impact of environmental stress, which exacerbates conflict and strengthens the stress-psychopathology axis; and inherent epigenetic aspects, which uncover crucial molecular underpinnings of environmental (mal) adaptation. By integrating these perspectives, in this review we aim to underline a cross-species causal nexus between heightened hippocampal activity and avoidance behavior. In addition, we suggest a rationale to explore epigenetic pharmacology as a potential strategy to tackle AAC-related psychopathology. This review assumes greater significance when viewed through the lens of advancing AAC-centric diagnostics in human subjects. Unlike traditional questionnaires, which struggle to accurately measure individual differences in AAC-related dimensions, new approaches using virtual reality and computer games show promise in better focusing the magnitude of AAC contribution to psychopathology.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Egr1 Expression Is Correlated With Synaptic Activity but Not Intrinsic Membrane Properties in Mouse Adult‐Born Dentate Granule Cells

ABSTRACT

The discovery of adult-born granule cells (aDGCs) in the dentate gyrus of the hippocampus has raised questions regarding how they develop, incorporate into the hippocampal circuitry, and contribute to learning and memory. Here, we used patch-clamp electrophysiology to investigate the intrinsic and synaptic excitability of mouse aDGCs as they matured, enabled by using a tamoxifen-induced genetic label to birth date the aDGCs at different animal ages. Importantly, we also undertook immunofluorescence studies of the expression of the immediate early gene Egr1 and compared these findings with the electrophysiology data in the same animals. We examined two groups of animals, with aDGC birthdating when the mice were 2 months and at 7–9 months of age. In both groups, cells 4 weeks old had lower thresholds for current-evoked action potentials than older cells but fired fewer spikes during long current pulses and responded more poorly to synaptic activation. aDGCs born in both 2 and 7–9-month-old mice matured in their intrinsic excitability and synaptic properties from 4–12 weeks postgenesis, but this occurred more slowly for the older age animals. Interestingly, this pattern of intrinsic excitability changes did not correlate with the pattern of Egr1 expression. Instead, the development of Egr1 expression was correlated with the frequency of spontaneous excitatory postsynaptic currents. These results suggest that in order for aDGCs to fully participate in hippocampal circuitry, as indicated by Egr1 expression, they must have developed enough synaptic input, in spite of the greater input resistance and reduced firing threshold that characterizes young aDGCs.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Distinct Ventral Hippocampus Network Properties in Dissociated Cultures

ABSTRACT

Extensive research has been focused in the past century on structural, physiological, and molecular attributes of the hippocampus. This interest was created by the unique involvement of the hippocampus in cognitive and affective functions of the brain. Functional analysis revealed that the hippocampus has divergent properties along its axial dimension to the extent that the dorsal sector (dorsal hippocampus, DH) has different connections with the rest of the brain than those of the ventral sector (VH). Still, longitudinal pathways connect the DH with the VH and dampen the functional differences between the sectors. To be able to identify the intrinsic functional difference between the DH and VH, we produced dissociated monolayer cultures from prenatal DH and VH and examined their properties at 10–20 days after plating by imaging the spontaneous activity of the network using Fluo-2 AM, a calcium indicator. Surprisingly, while DH and VH sectors produced dissociated cultures with similar morphological attributes, VH cultures were more active spontaneously than DH cultures. Furthermore, when stimulated to produce action potentials, VH neurons triggered network bursts in postsynaptic neurons more often than DH cultures. Finally, in both DH and VH cultures, electrical stimulation of single cells produced network bursts in response to a burst of action potentials rather than to single spikes. These experiments indicate that even in dissociated cultures, neurons of the VH are more excitable and sensitive to electrical stimulation than DH; hence, they are more likely to generate network bursts and epileptic seizures, as suggested for in vivo brains.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Comparable Theta Phase Coding Dynamics Along the Transverse Axis of CA1

ABSTRACT

Topographical projection patterns from the entorhinal cortex to area CA1 of the hippocampus have led to a hypothesis that proximal CA1 (pCA1, closer to CA2) is spatially more selective than distal CA1 (dCA1, closer to the subiculum). While earlier studies have shown evidence supporting this hypothesis, we recently showed that this difference does not hold true under all experimental conditions. In a complex environment with distinct local texture cues on a circular track and global visual cues, pCA1 and dCA1 display comparable spatial selectivity. Correlated with the spatial selectivity differences, the earlier studies also showed differences in theta phase coding dynamics between pCA1 and dCA1 neurons. Here we show that there are no differences in theta phase coding dynamics between neurons in these two regions under the experimental conditions where pCA1 and dCA1 neurons are equally spatially selective. These findings challenge the established notion of dCA1 being inherently less spatially selective and theta modulated than pCA1 and suggest further experiments to understand theta-mediated activation of the CA1 sub-networks to represent space.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Flexible Behavioral Adjustment to Frustrative Nonreward in Anticipatory Behavior, but Not in Consummatory Behavior, Requires the Dorsal Hippocampus

ABSTRACT

The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3–5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Adult Neurogenesis and the Initiation of Social Aggression in Male Mice

ABSTRACT

The hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult-born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals. However, mice with suppressed neurogenesis displayed decreased offensive and defensive aggression in a resident-intruder paradigm, and less resistance in a social dominance test, relative to neurogenesis-intact controls, when paired with weight and strain-matched (CD-1) mice. During aggression tests, TK mice were frequently attacked by the CD-1 intruder mice, which never occurred with WTs, and normal CD-1 male mice investigated TK mice less than controls when corralled in the social investigation test. Importantly, TK mice showed normal aggression toward prey (crickets) and smaller, nonaggressive (olfactory bulbectomized) C57BL/6J intruders, suggesting that mice lacking adult neurogenesis do not avoid aggressive social interactions if they are much larger than their opponent and will clearly win. Taken together, our findings show that adult hippocampal neurogenesis plays an important role in the instigation of intermale aggression, possibly by weighting a cost–benefit analysis against confrontation in cases where the outcome of the fight is not clear.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Supramammillary Theta Oscillations in Water Maze Learning

ABSTRACT

The supramammillary nucleus (SuM) in the hypothalamus, in conjunction with the hippocampus (HPC), has been implicated through theta oscillations in various brain functions ranging from locomotion to learning and memory. While the indispensable role of the SuM in HPC theta generation in anesthetized animals is well-characterized, the SuM is not always necessary for HPC theta in awake animals. This raises questions on the precise behavioral relevance of SuM theta activity and its interaction with HPC theta activity. We used simultaneously recorded SuM and HPC local field potentials (LFPs) in a one-day water maze (WM) learning paradigm in rats (n = 8), to show that theta activities recorded from the SuM itself were not positively correlated with locomotor (swimming) speed nor acceleration, but the individual relationship between acceleration and SuM theta frequency is correlated with WM learning rates. In contrast, we found that SuM-HPC theta phase coherence is strongly correlated with swimming speed and acceleration, but these do not relate to WM learning. SuM-HPC-directed coherence analysis demonstrated no swimming kinetics nor learning rate associations, but revealed that periods of high SuM-HPC theta phase coherence are driven by the SuM at relatively low (~6.2 Hz) frequencies. Additionally, we demonstrate that the SuM and the HPC also engage in non-random, non-coherent phase coupling modes where either structure preferentially displays a ± 2 Hz difference with the other. Our data indicate SuM theta LFPs do not appear to be related to either speed coding or spatial learning in swimming rats and display non-random out-of-phase theta frequency coupling with the HPC.

in Hippocampus on 2024-11-16 04:40:25 UTC.

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Hypercapnia impacts neural drive and timing of diaphragm neuromotor control

in Journal of Neurophysiology on 2024-11-16 02:23:01 UTC.

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Q&A with Ping Gao

in Cell Reports: Current Issue on 2024-11-16 00:00:00 UTC.

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PrP turnover in vivo and the time to effect of prion disease therapeutics

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Impact of adolescent high-fat diet and psychosocial stress on neuroendocrine stress responses and binge eating behavior in adult male Lewis rats

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Chemogenetic Breakdown of the Dentate Gate Causes Seizures and Spatial Memory Deficits

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Heat Acclimation in Mice Requires Preoptic BDNF Neurons and Postsynaptic Potentiation

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Type I interferon signaling enhances kainic acid-induced seizure severity

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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WMH-DualTasker: A Dual-Task Deep Learning Model with Self-supervised Consistency for Automated Segmentation and Visual Rating of White matter Hyperintensities - a Multicentre study

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Sortilin C-terminal fragment deposition depicts tangle-related nonamyloid neuritic plaque growth in Alzheimers disease

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Attention-dependent attribute comparisons underlie multi-attribute decision-making in orbitofrontal cortex

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Functional Connectivity Alterations in Cocaine Use Disorder: Insights from the Triple Network Model and the Addictions Neuroclinical Assessment Framework

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Morphological brain alterations and morphological brain network disorganizations in heroin and methamphetamine abstinent patients

in bioRxiv: Neuroscience on 2024-11-16 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1150: Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus

Brain Sciences, Vol. 14, Pages 1150: Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus

Brain Sciences doi: 10.3390/brainsci14111150

Authors: Yi-Tse Hsiao Ching-Yuan Chang Ting-Yen Lee Wan-Ting Liao Wen-Sung Lai Fang-Chia Chang

Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. Methods: We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Results: Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Conclusions: Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions.

in Brain Sciences on 2024-11-16 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1149: Sensitivity of Spiking Neural Networks Due to Input Perturbation

Brain Sciences, Vol. 14, Pages 1149: Sensitivity of Spiking Neural Networks Due to Input Perturbation

Brain Sciences doi: 10.3390/brainsci14111149

Authors: Haoran Zhu Xiaoqin Zeng Yang Zou Jinfeng Zhou

Background. To investigate the behavior of spiking neural networks (SNNs), the sensitivity of input perturbation serves as an effective metric for assessing the influence on the network output. However, existing methods fall short in evaluating the sensitivity of SNNs featuring biologically plausible leaky integrate-and-fire (LIF) neurons due to the intricate neuronal dynamics during the feedforward process. Methods. This paper first defines the sensitivity of a temporal-coded spiking neuron (SN) as the deviation between the perturbed and unperturbed output under a given input perturbation with respect to overall inputs. Then, the sensitivity algorithm of an entire SNN is derived iteratively from the sensitivity of each individual neuron. Instead of using the actual firing time, the desired firing time is employed to derive a more precise analytical expression of the sensitivity. Moreover, the expectation of the membrane potential difference is utilized to quantify the magnitude of the input deviation. Results/Conclusions. The theoretical results achieved with the proposed algorithm are in reasonable agreement with the simulation results obtained with extensive input data. The sensitivity also varies monotonically with changes in other parameters, except for the number of time steps, providing valuable insights for choosing appropriate values to construct the network. Nevertheless, the sensitivity exhibits a piecewise decreasing tendency with respect to the number of time steps, with the length and starting point of each piece contingent upon the specific parameter values of the neuron.

in Brain Sciences on 2024-11-16 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1148: Visual Cortical Function Changes After Perceptual Learning with Dichoptic Attention Tasks in Adults with Amblyopia: A Case Study Evaluated Using fMRI

Brain Sciences, Vol. 14, Pages 1148: Visual Cortical Function Changes After Perceptual Learning with Dichoptic Attention Tasks in Adults with Amblyopia: A Case Study Evaluated Using fMRI

Brain Sciences doi: 10.3390/brainsci14111148

Authors: Chuan Hou Zhangziyi Zhou Ismet Joan Uner Spero C. Nicholas

Background: Amblyopia is a neurodevelopmental disorder of vision, commonly caused by strabismus or anisometropia during early childhood. While studies demonstrated that perceptual learning improves visual acuity and stereopsis in adults with amblyopia, accompanying changes in visual cortical function remain unclear. Methods: We measured functional magnetic resonance imaging (fMRI) responses before and after perceptual learning in seven adults with amblyopia. Our learning tasks involved dichoptic high-attention-demand tasks that avoided V1 function-related tasks and required high-level cortical functions (e.g., intraparietal sulcus) to train the amblyopic eye. Results: Perceptual learning induced low-level visual cortical function changes, which were strongly associated with the etiology of amblyopia and visual function improvements. Anisometropic amblyopes showed functional improvements across all regions of interest (ROIs: V1, V2, V3, V3A, and hV4), along with improvements in visual acuity and stereoacuity. In contrast, strabismic amblyopes showed robust improvements in visual cortical functions only in individuals who experienced significant gains in visual acuity and stereoacuity. Notably, improvements in V1 functions were significantly correlated with the magnitude of visual acuity and stereoacuity improvements when combining both anisometropic and strabismic amblyopes. Conclusions: Our findings provide evidence that learning occurs in both high-level and low-level cortical processes. Our study suggests that early intervention to correct eye alignment (e.g., strabismus surgery) is critical for restoring both visual and cortical functions in strabismic amblyopia.

in Brain Sciences on 2024-11-16 00:00:00 UTC.

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A new look at TFPI inhibition of factor X activation

by Fabian Santiago, Amandeep Kaur, Shannon Bride, Dougald Monroe, Karin Leiderman, Suzanne Sindi

in PLoS Computational Biology on 2024-11-15 14:00:00 UTC.

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Social learning is triggered by environmental cues in immigrant birds

by Rachel A. Harrison

in PLoS Biology on 2024-11-15 14:00:00 UTC.

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MosAIC: An annotated collection of mosquito-associated bacteria with high-quality genome assemblies

by Aidan Foo, Laura E. Brettell, Holly L. Nichols, 2022 UW-Madison Capstone in Microbiology Students , Miguel Medina Muñoz, Jessica A. Lysne, Vishaal Dhokiya, Ananya F. Hoque, Doug E. Brackney, Eric P. Caragata, Michael L. Hutchinson, Marcelo Jacobs-Lorena, David J. Lampe, Edwige Martin, Claire Valiente Moro, Michael Povelones, Sarah M. Short, Blaire Steven, Jiannong Xu, Timothy D. Paustian, Michelle R. Rondon, Grant L. Hughes, Kerri L. Coon, Eva Heinz

in PLoS Biology on 2024-11-15 14:00:00 UTC.

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The impact of Perspective-Taking on weight stigma among Chinese University students: The mediating role of Common ingroup identity [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-15 10:24:37 UTC.

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Financial inclusion and stability in Ethiopia using bank-level data: A two-step system GMM estimation [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-15 10:21:26 UTC.

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Performance of Forensic Age Estimation by Aspartic Acid Racemization and DNA Methylation: A Systematic Review [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-15 10:18:56 UTC.

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“Unmasking the Uncommon”: A case series of multi-drug resistant Elizabethkingia meningoseptica causing late-onset sepsis and meningitis in preterm neonates [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-15 10:16:51 UTC.

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A glutamine metabolic switch supports erythropoiesis

in Science on 2024-11-15 08:00:00 UTC.

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SPL13 controls a root apical meristem phase change by triggering oriented cell divisions

in Science on 2024-11-15 08:00:00 UTC.

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Sequence modeling and design from molecular to genome scale with Evo

in Science on 2024-11-15 08:00:00 UTC.

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Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1

in Science on 2024-11-15 08:00:00 UTC.

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Chemical genetic approaches to dissect microbiota mechanisms in health and disease

in Science on 2024-11-15 08:00:00 UTC.

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Gibbs states and Brownian models for coexisting haze and cloud droplets

in Science Advances on 2024-11-15 08:00:00 UTC.

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Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing

in Science Advances on 2024-11-15 08:00:00 UTC.

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Generative adversarial networks accurately reconstruct pan-cancer histology from pathologic, genomic, and radiographic latent features

in Science Advances on 2024-11-15 08:00:00 UTC.

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Decoding the interplay between m6A modification and stress granule stability by live-cell imaging

in Science Advances on 2024-11-15 08:00:00 UTC.

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Landscape burning facilitated Aboriginal migration into Lutruwita/Tasmania 41,600 years ago

in Science Advances on 2024-11-15 08:00:00 UTC.

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Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome

in Science Advances on 2024-11-15 08:00:00 UTC.

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Gas-phase preparation of silylacetylene (SiH3CCH) through a counterintuitive ethynyl radical (C2H) insertion

in Science Advances on 2024-11-15 08:00:00 UTC.

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B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor

in Science Advances on 2024-11-15 08:00:00 UTC.

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Projected increase in the frequency of extremely active Atlantic hurricane seasons

in Science Advances on 2024-11-15 08:00:00 UTC.

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The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy

in Science Advances on 2024-11-15 08:00:00 UTC.

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Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria

in Science Advances on 2024-11-15 08:00:00 UTC.

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Archaeal type six secretion system mediates contact-dependent antagonism

in Science Advances on 2024-11-15 08:00:00 UTC.

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Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission

in Science Advances on 2024-11-15 08:00:00 UTC.

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Dynamical control of nanoscale electron density in atomically thin n-type semiconductors via nano-electric pulse generator

in Science Advances on 2024-11-15 08:00:00 UTC.

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Gene-environment interactions in the influence of maternal education on adolescent neurodevelopment using ABCD study

in Science Advances on 2024-11-15 08:00:00 UTC.

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H2S-Prdx4 axis mitigates Golgi stress to bolster tumor-reactive T cell immunotherapeutic response

in Science Advances on 2024-11-15 08:00:00 UTC.

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Robust generation of intrinsic C points with magneto-optical bound states in the continuum

in Science Advances on 2024-11-15 08:00:00 UTC.

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Same rule, different genes: Blimp1 is a pair-rule gene in the milkweed bug Oncopeltus fasciatus

in Science Advances on 2024-11-15 08:00:00 UTC.

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CO2 capture, geological storage, and mineralization using biobased biodegradable chelating agents and seawater

in Science Advances on 2024-11-15 08:00:00 UTC.

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Mechano-gradients drive morphogen-noise correction to ensure robust patterning

in Science Advances on 2024-11-15 08:00:00 UTC.

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Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy

in Science Advances on 2024-11-15 08:00:00 UTC.

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Issue Information

in Journal of Comparative Neurology on 2024-11-15 07:42:57 UTC.

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Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID‐HS

Objective

Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE.

Methods

We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls.

Results

HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions.

Interpretation

Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024

in Annals of Neurology on 2024-11-15 06:14:52 UTC.

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Q&A with Ilaria Elia

in Cell Reports: Current Issue on 2024-11-15 00:00:00 UTC.

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Integration of overlapping sequences emerges with consolidation through medial prefrontal cortex neural ensembles and hippocampal–cortical connectivity

in eLife on 2024-11-15 00:00:00 UTC.

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Targeting resident astrocytes attenuates neuropathic pain after spinal cord injury

in eLife on 2024-11-15 00:00:00 UTC.

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Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility

in eLife on 2024-11-15 00:00:00 UTC.

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A hierarchical multiscale model of forward and backward alpha-band traveling waves in the visual system

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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High-resolution imaging atlas reveals context-dependent role of pancreatic sympathetic innervation in diabetic mice

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Attentional failures after sleep deprivation represent moments of cerebrospinal fluid flow

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Variable Cerebral Blood Flow Responsiveness to Acute Hypoxic Hypoxia

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Single MAPT knock-in mouse models of frontotemporal dementia for sharing with the neurodegenerative research community

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Regional Brain Entropy, Brain Network and Structural-Functional Coupling in Human Brain

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Filling-in of the Blindspot is Multisensory

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Regenerative potential of human enteric glia in a preclinical model of acute brain injury

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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On Levodopa interactions with brain disease proteins at the nanoscale

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Putative Role of Norrin in Neuroretinal Differentiation Revealed by bulk and scRNA Sequencing of Human Retinal Organoids

in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.

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Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach

in Cerebral Cortex on 2024-11-15 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1147: The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson’s Disease: Preliminary In Vivo Data

Brain Sciences, Vol. 14, Pages 1147: The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson’s Disease: Preliminary In Vivo Data

Brain Sciences doi: 10.3390/brainsci14111147

Authors: Luca Magistrelli Elena Contaldi Annalisa Visciglia Giovanni Deusebio Marco Pane Angela Amoruso

Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson’s disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-α, IFN-γ, IL-6, and TGF-β) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 ± 4.08 vs. 12.74 ± 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 ± 21.41 vs. 30.11 ± 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 ± 4.14 vs. 1.89 ± 2.54, p = 0.021). A reduction of IFN-γ levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-β. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs.

in Brain Sciences on 2024-11-15 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1145: New Pharmacological Insight into Etanercept and Pregabalin in Allodynia and Nociception: Behavioral Studies in a Murine Neuropathic Pain Model

Brain Sciences, Vol. 14, Pages 1145: New Pharmacological Insight into Etanercept and Pregabalin in Allodynia and Nociception: Behavioral Studies in a Murine Neuropathic Pain Model

Brain Sciences doi: 10.3390/brainsci14111145

Authors: Loulwah Alothman Emad Alhadlaq Asma Alhussain Alwaleed Alabdulkarim Youssef Sari Shakir D. AlSharari

Background/Objectives: Neuropathic pain is challenging to treat, often resistant to current therapies, and associated with significant side effects. Pregabalin, an anticonvulsant that modulates calcium channels, is effective but can impair mental and motor functions, especially in older patients. To improve patient outcomes, reducing the doses of pregabalin and combining it with other drugs targeting different neuropathic pain mechanisms may be beneficial. TNF-α blockers such as etanercept have shown potential in addressing neuropathic pain by affecting sodium channels, synaptic transmission, and neuroinflammation. This study evaluates the efficacy and safety of combining low doses of etanercept and pregabalin in allodynia and nociceptive tests. Materials and Methods: Male C57/BL6 mice underwent chronic constriction injury (CCI) of the sciatic nerve to induce neuropathic pain. They were divided into seven groups: sham control, CCI control, low and high doses of pregabalin, low and high doses of etanercept, and a combination of low doses of both drugs. Behavioral tests, including von Frey, hot-plate, and rotarod tests, were used to assess pain responses and motor activity. Results: The results indicated that a high dose of pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia but impaired motor function. Conversely, low doses of etanercept alone had no significant effect. However, the combination of low doses of etanercept (20 mg/kg) and pregabalin (5 mg/kg) effectively alleviated pain without compromising locomotor activity. Conclusions: These results suggest a novel therapeutic strategy for neuropathic pain, enhancing analgesic efficacy while minimizing adverse effects.

in Brain Sciences on 2024-11-15 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1146: High Expression of GABAA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma

Brain Sciences, Vol. 14, Pages 1146: High Expression of GABAA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma

Brain Sciences doi: 10.3390/brainsci14111146

Authors: Jander M. Monteiro Matheus Dalmolin Marcelo A. C. Fernandes Jaqueline I. R. Ramos Carmen A. P. M. Ribas Fernando I. Tabushi Rafael Roesler Gustavo R. Isolan

Background/Objectives: Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABAA) receptor, which is a ligand-gated ion channel. GABAA receptor activation via GABA binding allows for an intracellular influx of Cl− ions, thus inducing cellular hyperpolarization. Each GABAA receptor consists of a combination of five subunits, and several subunits have been proposed as biomarkers and therapeutic targets in cancer. Here, we show the expression of genes encoding β subunits of the GABAA receptor, namely GABRB1, GABRB2, and GABRB3, across the four different molecular subgroups of medulloblastoma (MB), which is the most common malignant pediatric brain tumor. We also show the associations of GABAA receptor β subunits with MB patients’ overall survival (OS). Methods: The expression of genes encoding GABAA receptor β subunits was analyzed using a previously described dataset comprising 763 MB tumor samples. Patients were classified into high- and low-gene-expression groups, and the Kaplan–Meier estimate was used to examine the relationship between gene expression levels and patient OS. Results: High GABRB1 expression was associated with better OS within each of the four molecular subgroups. The GABRB2 gene showed higher transcript levels in Group 3 MB compared to all other subgroups, and high expression was associated with better prognosis in Group 3 tumors. GABRB3 expression was significantly higher in Group 3 and Group 4 MB, and high expression of GABRB3 genes was associated with longer OS in the sonic hedgehog (SHH) subgroup. The high expression of GABRB1, GABRB2, and GABRB3 is associated with longer patient OS in a subgroup-specific manner. Conclusions: These results indicate a role for GABAA receptors containing β subunits in influencing MB progression.

in Brain Sciences on 2024-11-15 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1144: The Role of Cognitive Reserve in Post-Stroke Rehabilitation Outcomes: A Systematic Review

Brain Sciences, Vol. 14, Pages 1144: The Role of Cognitive Reserve in Post-Stroke Rehabilitation Outcomes: A Systematic Review

Brain Sciences doi: 10.3390/brainsci14111144

Authors: Debora Bertoni Stefania Bruni Donatella Saviola Antonio De Tanti Cosimo Costantino

Background/Objectives: Stroke remains a major cause of disability and death, with survivors facing significant physical, cognitive, and emotional challenges. Rehabilitation is crucial for recovery, but outcomes can vary widely. Cognitive reserve (CR) has emerged as a factor influencing these outcomes. This systematic review evaluates the role of CR in post-stroke rehabilitation, examining whether higher CR is associated with better outcomes. Methods: A systematic search of PubMed, Google Scholar, Scopus, and Cochrane Library databases was conducted for studies published between 2004 and 2024. Studies examining social-behavior CR proxies (e.g., education, bilingualism) and their impact on post-stroke outcomes were included. Data were analyzed using descriptive statistics. The study quality was assessed using the Methodological Index for NOn-Randomized Studies (MINORS) scale. Results: Among 3851 articles screened, 27 met the inclusion criteria. Higher education levels, bilingualism, and engagement in cognitively stimulating activities were associated with better cognitive outcomes and functional recovery. Lower socioeconomic status (SES) correlated with poorer outcomes. Early rehabilitation and dynamic CR proxies showed stronger associations with cognitive recovery than static ones. Conclusions: CR may predict post-stroke rehabilitation outcomes, with education, bilingualism, and active engagement in cognitive activities showing potential benefits. Future research should explore CR’s role alongside factors like lesion location and severity in enhancing recovery.

in Brain Sciences on 2024-11-15 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review

Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review

Brain Sciences doi: 10.3390/brainsci14111143

Authors: Francesco Signorelli Omar Ktari Ludovico Agostini Giorgio Ducoli Fabio Zeoli Massimiliano Visocchi

Background: Spontaneous intracranial hypotension (SIH) is a rare and frequently misdiagnosed disorder characterized by a low volume of cerebrospinal fluid (CSF) caused by the leakage of CSF through the spinal dural membrane. Patients with Marfan Syndrome (MS) and other connective tissue disorders are at an increased risk for dural ectasia, which may predispose them to spontaneous CSF leaks due to the structural weakness of their dural membranes. The management of SIH in MS patients is debated. Conservative measures, an epidural blood patch (EBP), and surgical treatments are the options generally provided. Methods: Herein, we report on the case of a 52-year-old female affected by MS, genetically confirmed, with a two-month history of sudden-onset, “thunderclap” headache, worsened in an upright position and horizontal diplopia. A Computed Tomography (CT) scan of the brain showed a bilateral chronic subdural hematoma, slit ventricles, and a caudal descent of the brainstem without overt tonsillar herniation. The Magnetic Resonance Imaging (MRI) scan of the whole spine revealed dural ectasia in the lumbosacral area and presacral perineural cyst without extradural CSF collection. The case was successfully managed with bed rest and high-dose corticosteroid therapy. Then, we discuss the pertinent literature, consisting of 25 papers dealing with the treatment of SIH in patients affected by MS. Results: The literature review yielded 25 papers dealing with SIH management in patients with MS, including 28 patients overall; 21 patients underwent EBP, of whom 7 patients had multiple procedures. Overall, in 23 cases (82%), the symptoms improved. In three cases, the patients were managed conservatively with bed rest. In three of these cases, there was an improvement. In one case, the surgical fenestration of two lumbar intradural spinal meningeal cysts was performed and the patient improved after the procedure. Our patient underwent 15 days of steroid therapy (dexamethasone iv 12 mg/day for 7 days, then reduced to 4 mg/day) and intravenous hydration (Ringer lactate 1500 mL/day). In ten days, the symptoms disappeared. At the 6-month follow-up, the patient was in good clinical condition, and a CT scan showed an almost complete regression of the bilateral subdural hematoma. Conclusions: The management of SIH in MS patients is still challenging. Patients with connective tissue disorders such as MS are at an increased risk for SIH. Few studies have assessed the management of these patients and different strategies. Our case and the available literature provide further data for this type of case.

in Brain Sciences on 2024-11-15 00:00:00 UTC.

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Assessment of Pelargonium graveolens flower essential oil: Antimicrobial, antioxidant, enzyme inhibition and in vivo topical analgesic and anti-inflammatory efficacy as treatment for atopic dermatitis [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-14 17:57:35 UTC.

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Clust&See3.0 : clustering, module exploration and annotation [version 2; peer review: 1 approved, 2 approved with reservations]

in F1000Research on 2024-11-14 17:43:17 UTC.

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Evaluation of the fintech era on the performance of Moroccan banks: analysis through non-performing loans [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-14 17:40:03 UTC.

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Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Nontarget Retrieval during Visual Working Memory

Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, pNT). In Experiment 2 (N = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported "remembered" in nontarget responses) or informed guessing trials (participants self-reported "forgotten" in nontarget responses). We replicated the main findings in Experiment 1 and observed greater tDCS effects of PPC on RT in informed guessing trials while there are comparable effects on pNT in these two types of trials. In Experiment 3 (N = 28), we then examined whether the tDCS effects over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provided direct causal evidence supporting the specific involvement of PPC in feature binding during VWM retrieval, from both aspects of speed and response preference, expanding our understanding of the neural basis of feature binding in VWM.

in eNeuro on 2024-11-14 17:30:23 UTC.

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Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood

Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)–exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Furthermore, the firing rate of putative pyramidal neurons in mPFC and hippocampus was increased, while that of putative inhibitory neurons was decreased during both adolescence and adulthood. In conclusion, PV loss in mPFC and hippocampus of MAM-exposed mice may contribute to the impaired inhibitory function leading to the attenuation of inhibition in the brain both in vitro and in vivo.

in eNeuro on 2024-11-14 17:30:23 UTC.

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Erratum: White et al., "Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision-Making"

in eNeuro on 2024-11-14 17:30:23 UTC.

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Erratum: Lakhani et al., "Homeostatic Regulation of Spike Rate within Bursts in Two Distinct Preparations"

in eNeuro on 2024-11-14 17:30:23 UTC.

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Health care workers hospitalized for COVID-19 in Liberia: who were they, and what were their outcomes? [version 2; peer review: 1 approved, 1 approved with reservations]

in F1000Research on 2024-11-14 16:59:59 UTC.

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The quality of life in Thai senior table tennis players [version 3; peer review: 1 approved with reservations, 1 not approved]

in F1000Research on 2024-11-14 15:21:20 UTC.

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The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review [version 2; peer review: 1 approved with reservations]

in F1000Research on 2024-11-14 15:17:25 UTC.

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Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study [version 2; peer review: 2 approved with reservations]

in F1000Research on 2024-11-14 15:15:00 UTC.

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Knowledge and attitudes of health care professionals regarding birth preparedness of women in labour at selected Hospitals in KwaZulu-Natal, South Africa: A qualitative study [version 2; peer review: awaiting peer review]

in F1000Research on 2024-11-14 15:13:17 UTC.

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Digital and Financial Literacy for Uplifting Women and Achieving Sustainable Development Goals [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-14 15:11:00 UTC.

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Teaching Self-efficacy and Teaching Methods in the Aquatic Environment [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-14 15:09:27 UTC.

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Annals of Neurology: Volume 96, Number 6, December 2024

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Issue Information

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS

Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report “Living with ALS,” recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035–1039

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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MEK Pathway Inhibitor‐Mediated Response in BRAF V600‐Mutant Melanoma with Brain Parenchymal and Leptomeningeal Metastases

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Miyazaki Syndrome as a Complication of Shunt Drainage

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Neuro‐Image of a Ring‐Liked Sign in Serpentine Aneurysm

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Syrinx beyond Cord: Syringocephalia Extending to Corona Radiata

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Slowly Expanding Lesions Differentiate Pediatric Multiple Sclerosis from Myelin Oligodendrocyte Glycoprotein Antibody Disease

Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.3 and 9.4 years, respectively) recruited to the Canadian Pediatric Demyelinating Disease Study with: (1) ≥3 research scans 12 months apart; and (2) ≥1 T2-lesions on the earliest scan. A total of 70 SELs from 16 POMS participants and 1 SEL in the MOGAD group were detected. SELs are an early feature of POMS and essentially not a feature of MOGAD. ANN NEUROL 2024;96:1086–1091

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Polygenic Landscape of Cryptogenic New‐Onset Refractory Status Epilepticus: A Comprehensive Whole‐Genome Sequencing Study

Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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RAN Translation of C9orf72‐Related Dipeptide Repeat Proteins in Zebrafish Recapitulates Hallmarks of Amyotrophic Lateral Sclerosis and Identifies Hypothermia as a Therapeutic Strategy

Objective

Hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A large body of evidence implicates dipeptide repeats (DPRs) proteins as one of the main drivers of neuronal injury in cell and animal models.

Methods

A pure repeat-associated non-AUG (RAN) translation zebrafish model of C9orf72-ALS/FTD was generated. Embryonic and adult transgenic zebrafish lysates were investigated for the presence of RAN-translated DPR species and adult-onset motor deficits. Using C9orf72 cell models as well as embryonic C9orf72-ALS/FTD zebrafish, hypothermic-therapeutic temperature management (TTM) was explored as a potential therapeutic option for C9orf72-ALS/FTD.

Results

Here, we describe a pure RAN translation zebrafish model of C9orf72-ALS/FTD that exhibits significant RAN-translated DPR pathology and progressive motor decline. We further demonstrate that hypothermic-TTM results in a profound reduction in DPR species in C9orf72-ALS/FTD cell models as well as embryonic C9orf72-ALS/FTD zebrafish.

Interpretation

The transgenic model detailed in this paper provides a medium throughput in vivo research tool to further investigate the role of RAN-translation in C9orf72-ALS/FTD and further understand the mechanisms that underpin neuroprotective strategies. Hypothermic-TTM presents a viable therapeutic avenue to explore in the context of C9orf72-ALS/FTD. ANN NEUROL 2024;96:1058–1069

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Population‐Based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

Objective

Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations.

Methods

We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders.

Results

Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels.

Interpretation

Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024;96:1040–1057

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy

Objective

Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo-electroencephalography (SEEG) -informed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT).

Methods

A retrospective review of consecutive cases from a single high-volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.

Results

Thirty-nine patients underwent SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow-up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p < 0.001).

Interpretation

PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024;96:1174–1184

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B)

Objectives

Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.

Methods

We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B.

Results

In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine.

Interpretation

Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024;96:1092–1103

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Higher Validity, Lower Radiation: A New Ictal Single‐Photon Emission Computed Tomography Framework

Objective

To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted.

Methods

We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories.

Results

Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases.

Interpretation

We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024;96:1160–1173

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Single‐Nucleus RNA Sequencing Unravels Early Mechanisms of Human Becker Muscular Dystrophy

Objective

The transcriptional heterogeneity at a single-nucleus level in human Becker muscular dystrophy (BMD) dystrophic muscle has not been explored. Here, we aimed to understand the transcriptional heterogeneity associated with myonuclei, as well as other mononucleated cell types that underly BMD pathogenesis by performing single-nucleus RNA sequencing.

Methods

We profiled single-nucleus transcriptional profiles of skeletal muscle samples from 7 BMD patients and 3 normal controls.

Results

A total of 17,216 nuclei (12,879 from BMD patients and 4,337 from controls) were classified into 13 known cell types, including 9 myogenic lineages and 4 non-myogenic lineages, and 1 unclassified nuclear type according to their cell identities. Among them, type IIx myonuclei were the first to degenerate in response to dystrophin reduction. Differential expression analysis revealed that the fibro-adipogenic progenitors (FAPs) population had the largest transcriptional changes among all cell types. Sub-clustering analysis identified a significantly compositional increase in the activated FAPs (aFAPs) subpopulation in BMD muscles. Pseudotime analysis, regulon inference, and deconvolution analysis of bulk RNA-sequencing data derived from 29 BMD patients revealed that the aFAPs subpopulation, a distinctive and previously unrecognized mononuclear subtype, was profibrogenic and expanded in BMD patients. Muscle quantitative real-time polymerase chain reaction and immunofluorescence analysis confirmed that the mRNA and protein levels of the aFAPs markers including LUM, DCN, and COL1A1 in BMD patients were significantly higher than those in controls, respectively.

Interpretation

Our results provide insights into the transcriptional diversity of human BMD muscle at a single-nucleus resolution and new potential targets for anti-fibrosis therapies in BMD. ANN NEUROL 2024;96:1070–1085

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease

Objective

Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes.

Methods

Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells.

Results

We identified biallelic GUK1 pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T-lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. GUK1 encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands’ fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies.

Interpretation

Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T-lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024;96:1209–1224

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Fetal Intraparenchymal Hemorrhage Imaging Patterns, Etiology, and Outcomes: A Single Center Cohort Study

Objective

This study examines associations among fetal brain magnetic resonance imaging (MRI) injury patterns, etiologies, and outcomes in fetal intraparenchymal hemorrhage (IPH).

Methods

This is a retrospective, single-center cohort study of IPH diagnosed on fetal MRI (1996–2022). IPH and associated abnormalities were categorized by 2 pediatric neuroradiologists; electronic medical records were reviewed by 2 pediatric neurologists to classify etiology and outcomes including cerebral palsy, epilepsy, developmental delay, and death.

Results

Forty-four fetuses with IPH were identified (34 singleton and 10 twin gestations) with MRI at median 24 weeks gestation (interquartile range [IQR] = 22–28 weeks). IPH was commonly supratentorial (84%) and focal (50%) or focal with diffuse injury (43%) and was often associated with germinal matrix hemorrhage (GMH; 75%) and/or intraventricular hemorrhage (IVH; 52%). An etiology was identified in 75%, including twin-twin transfusion syndrome (TTTS, n = 10), COL4A1/2 variants (n = 8), or other fetal/maternal conditions (n = 15). COL4A1/2 variants were associated with focal IPH and the presence of hemorrhagic porencephaly, and intrauterine transfusion was associated with infratentorial hemorrhage. Twenty-two fetuses were liveborn, and 18 pregnancies were terminated. Among those with follow-up ≥ 12 months (median = 7 years), 12 of 13 had cerebral palsy, 6 of 13 had developmental delay, and 5 of 13 had epilepsy.

Interpretation

An etiology for fetal IPH with or without GMH-IVH is identified in most cases in our cohort and is commonly TTTS, COL4A1/2 variants, or other maternal/fetal comorbidities. Pattern of fetal IPH on MRI is associated with etiology. Cerebral palsy and neurodevelopmental impairment were common in liveborn infants. Genetic studies should be considered in cases of fetal IPH without an otherwise apparent cause. ANN NEUROL 2024;96:1137–1147

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Comparison of Perfusion Imaging Definitions of the No‐Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?

The no-reflow phenomenon is a potential contributor to poor outcome despite successful thrombectomy. There are multiple proposed imaging-based definitions of no-reflow leading to wide variations in reported prevalence. We investigated the agreement between existing imaging definitions and compared the characteristics and outcomes of patients identified as having no-reflow.

Methods

We performed an external validation of 4 existing published definitions of no-reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c-3) angiographic reperfusion who underwent 24-hour perfusion imaging from 2 international randomized controlled trials (EXTEND-IA TNK part-1 and 2) and a multicenter prospective observational study. Receiver-operating-characteristic and Bayesian-information-criterion (BIC) analyses were performed with the outcome variable being dependent-or-dead at 90-days (modified Rankin Score [mRS] ≥3).

Results

Of 131 patients analyzed, the prevalence of no-reflow significantly varied between definitions (0.8–22.1%; p < 0.001). There was poor agreement between definitions (kappa 5/6 comparisons <0.212). Among patients with no-reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (p = 0.006), cerebral blood volume (CBV) (p < 0.001), and mean-transit-time (MTT) (p = 0.005). No-reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of >15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = −8.105) and demonstrated an association between no-reflow and clinical outcome among patients with eTICI3 reperfusion.

Conclusions

Existing imaging definitions of no-reflow varied significantly in prevalence and post-treatment perfusion imaging profile, potentially explaining the variable prevalence of no-reflow reported in literature. The definition of >15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024;96:1104–1114

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Interferon Stimulated Gene Expression Is a Biomarker for Primary Mitochondrial Disease

Objective

Mitochondria are implicated in regulation of the innate immune response. We hypothesized that abnormalities in interferon signaling may contribute to pathophysiology in patients with primary mitochondrial disease (PMD).

Methods

Expression of interferon stimulated genes (ISGs) was measured by real-time polymerase chain reaction (PCR) in whole blood samples from a cohort of patients with PMD.

Results

Upregulated ISG expression was observed in a high proportion (41/55, 75%) of patients with PMD on at least 1 occasion, most frequently IFI27 upregulation, seen in 50% of the samples. Some patients had extremely high IFI27 levels, similar to those seen in patients with primary interferonopathies. A statistically significant correlation was observed between elevated IFI27 gene expression and PMD, but not between IFI27 and secondary mitochondrial dysfunction, suggesting that ISG upregulation is a biomarker of PMD. In some patients with PMD, ISG abnormalities persisted on repeat measurement over several years, indicative of ongoing chronic inflammation. Subgroup analyses suggested common ISG signatures in patients with similar mitochondrial disease mechanisms and positive correlations with disease severity among patients with identical genetic diagnoses.

Interpretation

Dysregulated interferon signaling is frequently seen in patients with PMD suggesting that interferon dysregulation is a contributor to pathophysiology. This may indicate a role for repurposing of immunomodulatory therapies for the treatment of PMDs by targeting interferon signaling. ANN NEUROL 2024;96:1185–1200

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Prevalence and Distribution of Intracranial Vessel Occlusion on Angiography and Its Association with Functional Outcome in Patients with Atrial Fibrillation Presenting with Ischemic Stroke

Objectives

To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke.

Methods

Multicenter cohort study enrolling consecutive patients with AF with imaging-confirmed ischemic stroke who underwent CT- or MR-angiography on admission (2014–2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3–6) at 90 days.

Results

The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71–2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40–2.80; DOAC, aOR: 2.35, 95% CI: 1.83–3.03; none, aOR: 1.76, 95% CI: 1.49–2.09).

Interpretation

Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024;96:1115–1123

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40‐Year Follow‐Up Study Highlighting Female Vulnerability

Objective

Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear.

Methods

Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect.

Results

High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men.

Interpretation

High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124–1134

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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Pro‐Ictal EEG Scheduling Improves the Yield of Epilepsy Monitoring: Validating the Use of Multiday Seizure Cycles to Optimize Video‐EEG Timing

Objective

A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. In this study, we introduce and validate “pro-ictal EEG scheduling”, a method to schedule vEEG monitoring to coincide with periods of increased seizure likelihood as a low-risk approach to enhance the diagnostic yield.

Methods

A database of long-term ambulatory vEEG monitoring sessions (n = 5,038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events) to generate cycle-based estimates of seizure risk. In adults, vEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (n = 305) and compared to remaining studies (baseline: n = 3,586). Test of proportions and risk-ratios (RR) were applied to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure, and diary event) during monitoring. The impact of clinical and demographic factors (age, sex, epilepsy-type, and medication) was also explored.

Results

During vEEG monitoring, the high-risk group was significantly more likely to have an abnormal vEEG report (190/305:62% vs 1,790/3,586:50% [%change = 12%], RR = 1.25, 95% confidence interval [CI] = [1.137–1.370], p < 0.001), present with a confirmed seizure (56/305:18% vs 424/3,586:11% [%change = 7%], RR = 1.63, 95% CI = [1.265–2.101], p < 0.001) and report an event (153/305:50% vs 1,267/3,586:35% (%change = 15%), RR = 1.420, 95% CI = [1.259:1.602], p < 0.001). Similar effects were observed across clinical and demographic features.

Interpretation

This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management. ANN NEUROL 2024;96:1148–1159

in Annals of Neurology on 2024-11-14 14:07:31 UTC.

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GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies

by Lin Lin, Rachel L. Spreng, Kelly E. Seaton, S. Moses Dennison, Lindsay C. Dahora, Daniel J. Schuster, Sheetal Sawant, Peter B. Gilbert, Youyi Fong, Neville Kisalu, Andrew J. Pollard, Georgia D. Tomaras, Jia Li

in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.

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Human-like dissociations between confidence and accuracy in convolutional neural networks

by Medha Shekhar, Dobromir Rahnev

in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.

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AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis

by Michael Alexander Ramirez Sierra, Thomas R. Sokolowski

in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.

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Decrease in decision noise from adolescence into adulthood mediates an increase in more sophisticated choice behaviors and performance gain

by Vanessa Scholz, Maria Waltmann, Nadine Herzog, Annette Horstmann, Lorenz Deserno

in PLoS Biology on 2024-11-14 14:00:00 UTC.

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Immigrant birds learn from socially observed differences in payoffs when their environment changes

by Michael Chimento, Gustavo Alarcón-Nieto, Lucy M. Aplin

in PLoS Biology on 2024-11-14 14:00:00 UTC.

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Sex‐Specific Vulnerabilities to Subclinical Vascular Brain Injury in Early Late‐Life: The Framingham Heart Study

Objective

Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well-established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex-specific prevention guidelines. We aimed to establish the extent to which sex moderates associations between vascular risk factors and magnetic resonance imaging (MRI) measures of subclinical brain injury in stroke-free older adults.

Methods

We leveraged cross-sectional data from 1,579 stroke- and dementia-free Framingham Heart Study Offspring participants at exam 8 (age 65.7 ± 8.8 years, 53% women). Vascular risks were assessed using components of the Framingham Stroke Risk Profile (FSRP) and diastolic blood pressure (DBP). White matter hyperintensity volume (WMH), total cerebral brain volume (TBV), and covert brain infarcts were quantified using MRI. We examined whether vascular risk factors were associated with MRI measures across the combined cohort, and then determined whether sex modified these associations.

Results

Higher FSRP and specifically systolic blood pressure (SBP) were associated with greater WMH. These associations were stronger in women and remained after adjusting for menopause age and hormone therapy use. By contrast, diabetes and lower DBP were associated with smaller TBV primarily in men. The DBP-atrophy relationship was only observed in men with declining DBP or prior hypertension.

Interpretation

Our findings highlight differential vulnerability to the impact of vascular risk factors on white matter health in women and global atrophy in men, supporting the development of sex-specific guidelines to better preserve vascular brain health in aging. ANN NEUROL 2024

in Annals of Neurology on 2024-11-14 10:14:09 UTC.

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Distinct Constructs Underlie Patient‐Reported and Performance‐Rated Outcomes after Stroke

Objective

Patient-reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance-rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self-awareness (i.e., parietal regions and the salience/ventral-attention network) may also impair self-report outcomes. This study examined the relationship between PROMs and performance-based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance-based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self-perception.

Methods

We longitudinally assessed 54 stroke survivors using patient-reported and performance-rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel-lesion-symptom-mapping, region-of-interest-based analysis, and voxel-lesion-network-mapping investigated the relationship between classes of outcomes and stroke-related injury.

Results

Performance-based and patient-reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient-reported, but not performance-rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient-reported outcomes; greater corticospinal tract injury related to worse performance-rated outcomes. Lesions with greater functional connectivity to the salience/ventral-attention network were associated with worse patient-reported outcomes (r = −0.35, p = 0.009).

Interpretation

Our findings reveal important differences between performance-rated and patient-reported outcomes, each with specific associated factors and anatomy post-stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2024

in Annals of Neurology on 2024-11-14 09:56:32 UTC.

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The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-14 09:48:09 UTC.

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The metaphors of artificial intelligence

in Science on 2024-11-14 08:00:00 UTC.

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A voyage to victory

in Science on 2024-11-14 06:59:04 UTC.

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Tomorrow’s trees

in Science on 2024-11-14 06:59:04 UTC.

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Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy

in Science on 2024-11-14 06:59:04 UTC.

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High-temperature carbon dioxide capture in a porous material with terminal zinc hydride sites

in Science on 2024-11-14 06:59:04 UTC.

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Synchronous recognition of amines in oxidative carbonylation toward unsymmetrical ureas

in Science on 2024-11-14 06:59:04 UTC.

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Glaciation of liquid clouds, snowfall, and reduced cloud cover at industrial aerosol hot spots

in Science on 2024-11-14 06:59:04 UTC.

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Diverse and larger tree islands promote native tree diversity in oil palm landscapes

in Science on 2024-11-14 06:59:04 UTC.

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Ribozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophies

in Science on 2024-11-14 06:59:04 UTC.

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A mechanical qubit

in Science on 2024-11-14 06:59:04 UTC.

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Subambient daytime radiative cooling of vertical surfaces

in Science on 2024-11-14 06:59:04 UTC.

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Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states

in Science on 2024-11-14 06:59:04 UTC.

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Truly listening

in Science on 2024-11-14 06:59:04 UTC.

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In Other Journals

in Science on 2024-11-14 06:59:04 UTC.

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The journey to a mechanical qubit

in Science on 2024-11-14 06:59:04 UTC.

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Learning the language of DNA

in Science on 2024-11-14 06:59:04 UTC.

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Heat up to catch carbon

in Science on 2024-11-14 06:59:04 UTC.

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The disciplinary matrix of holobiont biology

in Science on 2024-11-14 06:59:04 UTC.

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End illegal sand mining in China

in Science on 2024-11-14 06:59:04 UTC.

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Plastics treaty: Address building materials

in Science on 2024-11-14 06:59:04 UTC.

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Argentina’s unsustainable policies

in Science on 2024-11-14 06:59:04 UTC.

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News at a glance

in Science on 2024-11-14 06:59:04 UTC.

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Research advocates see ‘no good news for science’

in Science on 2024-11-14 06:59:04 UTC.

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Trump won. Is NIH in for a major shake-up?

in Science on 2024-11-14 06:59:04 UTC.

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‘America first’ could affect health worldwide

in Science on 2024-11-14 06:59:04 UTC.

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Famed flipping ship gets second shot at research

in Science on 2024-11-14 06:59:04 UTC.

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Preprint on Alzheimer’s drug deaths ignites author dispute

in Science on 2024-11-14 06:59:04 UTC.

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Russia postpones three scientific ‘megaprojects’

in Science on 2024-11-14 06:59:04 UTC.

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The counterattack

in Science on 2024-11-14 06:59:04 UTC.

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Science is neither red nor blue

in Science on 2024-11-14 06:59:04 UTC.

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Advancing alternative methods to reduce animal testing

in Science on 2024-11-14 06:59:04 UTC.

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Gatekeepers of the brain: Identifying hidden mechanisms of type A GABA receptor signaling and assembly

in Science on 2024-11-14 06:59:04 UTC.

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Digging below the surface: Hidden risks for ground-nesting bees

in Science on 2024-11-14 06:59:04 UTC.

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How to build a human: Piecing together the body’s cellular puzzle

in Science on 2024-11-14 06:59:04 UTC.

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To target, to escape, perchance to cure: Borrowing a page from cancer’s playbook, scientists learn to evade their own therapies

in Science on 2024-11-14 06:59:04 UTC.

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In Science Journals

in Science on 2024-11-14 06:59:04 UTC.

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Input-specific properties of excitatory synapses on oxytocin receptor-expressing neurons in the lateral septum

in Journal of Neurophysiology on 2024-11-14 05:30:15 UTC.

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Harvey's Story

Harvey enjoying a good discussion at a lab party in 1996 (photo provided by Harald Luksch).

ABSTRACT

Harvey Jules Karten passed away on July 15, 2024. With his passing, the world lost a remarkable and energetic man who had made major contributions to neuroscience, in particular, resetting our understanding of the evolution of the forebrain and the evolution of intelligence. He left behind a legion of loyal colleagues with whom he had collaborated and shared ideas, students he had inspired and trained, and non-neuroscientist friends he had made in the passionate pursuit of his hobbies—sailing, skiing, and hiking.

in Journal of Comparative Neurology on 2024-11-14 04:44:24 UTC.

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Altered control of breathing in a rat model of allergic lower airway inflammation

in Journal of Neurophysiology on 2024-11-14 03:52:07 UTC.

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Palytoxin evokes reversible spreading depolarization in the locust CNS

in Journal of Neurophysiology on 2024-11-14 03:52:06 UTC.

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Clinical efficacy of low-intensity pulsed ultrasound in Parkinson’s disease with cognitive impairment

in Journal of Neurophysiology on 2024-11-14 03:52:05 UTC.

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Examining motor evidence for the pause-then-cancel model of action-stopping: insights from motor system physiology

in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC.

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Rat movements reflect internal decision dynamics in an evidence accumulation task

in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC.

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Bayesian inference in arm posture perception

in Journal of Neurophysiology on 2024-11-14 03:52:03 UTC.

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Impact of sleep deprivation on aperiodic activity: a resting-state EEG study

in Journal of Neurophysiology on 2024-11-14 03:52:02 UTC.

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Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond

in Trends in Neurosciences: In press on 2024-11-14 00:00:00 UTC.

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Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells

in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC.

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ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma

in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC.

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Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling

in Cell Reports: In press on 2024-11-14 00:00:00 UTC.

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Structure of scavenger receptor SCARF1 and its interaction with lipoproteins

in eLife on 2024-11-14 00:00:00 UTC.

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An antimicrobial drug recommender system using MALDI-TOF MS and dual-branch neural networks

in eLife on 2024-11-14 00:00:00 UTC.

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The epigenetic trajectory of type 1 regulatory T cells

in eLife on 2024-11-14 00:00:00 UTC.

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Isobaric crosslinking mass spectrometry technology for studying conformational and structural changes in proteins and complexes

in eLife on 2024-11-14 00:00:00 UTC.

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Proteomic and functional comparison between human induced and embryonic stem cells

in eLife on 2024-11-14 00:00:00 UTC.

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Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses

in eLife on 2024-11-14 00:00:00 UTC.

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Chemokine expression profile of an innate granuloma

in eLife on 2024-11-14 00:00:00 UTC.

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Predictive models for secondary epilepsy in patients with acute ischemic stroke within one year

in eLife on 2024-11-14 00:00:00 UTC.

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Feature similarity: a sensitive method to capture the functional interaction of brain regions and networks to support flexible behavior

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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SEX-RELATED GENE EXPRESSION IN THE POSTERODORSAL MEDIAL AMYGDALA OF CYCLING FEMALE RATS ALONG WITH PROLACTIN MODULATION OF LORDOSIS BEHAVIOR

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Multimodal investigation of the neurocognitive deficits underlying dyslexia in adulthood

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Comparative analysis of spike-sorters in large-scale brainstem recordings

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Brain functional network connectivity interpolation characterizes neuropsychiatric continuum and heterogeneity

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Older is Order: Entropy reduction in cortical spontaneous activity marks healthy aging

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Modeling Complex Animal Behavior with Latent State Inverse Reinforcement Learning

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Interactions established by isoform-specific TrkB-T1 sequences govern inflammatory response and neurotoxicity in stroke

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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A Unified Approach for Identifying PET-based Neuronal Activation and Molecular Connectivity with the functional PET toolbox

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain

in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.

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Neural representations of phonological information in bilingual language production

in Cerebral Cortex on 2024-11-14 00:00:00 UTC.

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Local and interareal alpha and low-beta band oscillation dynamics underlie the bilateral field advantage in visual working memory

in Cerebral Cortex on 2024-11-14 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials

Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials

Brain Sciences doi: 10.3390/brainsci14111142

Authors: Stephanie J. Powell Srishti Nayak Cyrille L. Magne

Background/Objectives: The Implicit Prosody Hypothesis (IPH) posits that individuals generate internal prosodic representations during silent reading, mirroring those produced in spoken language. While converging behavioral evidence supports the IPH, the underlying neurocognitive mechanisms remain largely unknown. Therefore, this study investigated the neurophysiological markers of sensitivity to speech rhythm cues during silent word reading. Methods: EEGs were recorded while participants silently read four-word sequences, each composed of either trochaic words (stressed on the first syllable) or iambic words (stressed on the second syllable). Each sequence was followed by a target word that was either metrically congruent or incongruent with the preceding rhythmic pattern. To investigate the effects of metrical expectancy and lexical stress type, we examined single-trial event-related potentials (ERPs) and time&amp;ndash;frequency representations (TFRs) time-locked to target words. Results: The results showed significant differences based on the stress pattern expectancy and type. Specifically, words that carried unexpected stress elicited larger ERP negativities between 240 and 628 ms after the word onset. Furthermore, different frequency bands were sensitive to distinct aspects of the rhythmic structure in language. Alpha activity tracked the rhythmic expectations, and theta and beta activities were sensitive to both the expected rhythms and specific locations of the stressed syllables. Conclusions: The findings clarify neurocognitive mechanisms of phonological and lexical mental representations during silent reading using a conservative data-driven approach. Similarity with neural response patterns previously reported for spoken language contexts suggests shared neural networks for implicit and explicit speech rhythm processing, further supporting the IPH and emphasizing the centrality of prosody in reading.

in Brain Sciences on 2024-11-14 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis

Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis

Brain Sciences doi: 10.3390/brainsci14111141

Authors: Alin Ciubotaru Daniel Alexa Cristina Grosu Lilia Böckels Ioana Păvăleanu Alexandra Maștaleru Maria Magdalena Leon Roxana Covali Emanuel Matei Roman Cătălina Elena Bistriceanu Cristina Mihaela Ghiciuc Doina Azoicăi Emilian Bogdan Ignat

Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can progress to SPMS (secondary progressive multiple sclerosis). Our study aimed to validate the criteria proposed by a working group of the Romanian Society of Neurology versus the criteria proposed by a group of experts from Spain, Karolinska, and Croatia concerning the progression from RRMS to SPMS. Methods: This was done by gathering epidemiological data (age, gender) and by applying clinical tests such as the 9HPT (9-hole peg test), 25FWT (25-foot walk test), and EDSS (expanded disability status scale) tests and the SDMT test (symbol digit modalities test). The present research is a cohort study that included a number of 120 patients diagnosed with MS according to the McDonald Diagnostic Criteria 2017. The study was carried out between January 2023 and April 2024, including patients hospitalized in the Neurology Clinic of the Clinical Rehabilitation Hospital from Iasi, Romania. The data were collected at baseline (T0) and at a 12-month interval (T1). Results: The statistical analysis was conducted using Kaiser&amp;ndash;Meyer&amp;ndash;Olkin analysis, which indicated a value of 0.683, thus validating the clinical tests used. The correlation matrix and the linear regression for all the tests showed highly significant statistical results. Furthermore, the ROC curve analysis of the criteria suggested by the working group of the Romanian Society of Neurology demonstrated that the EDSS, 9HPT, and 25FWT are highly sensitive in diagnosing SPMS, an opinion that is shared with the Spanish experts, but not with the Karolinska expert panel. Using the criteria given by the Croatian expert group in the ROC curve analysis showed that only the EDSS was strongly significant for the progression to the SPMS phase. Conclusions: In conclusion, all clinical methods used demonstrated that they are valid and can contribute to identifying patients with an increased risk of progression. The model proposed by the Romanian Society of Neurology working group is similar to other countries&amp;rsquo; expert opinions and can be used to detect the risk of disease progression and establish a more tailored therapeutic management of SPMS.

in Brain Sciences on 2024-11-14 00:00:00 UTC.

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Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents—The Mediating Role of Maladaptive Perfectionism

Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents&mdash;The Mediating Role of Maladaptive Perfectionism

Brain Sciences doi: 10.3390/brainsci14111140

Authors: Magdalena Chęć Sylwia Michałowska Alicja Gnych-Pietrzak Albina Rybarska Klaudia Strochalska

Background: Adolescence is an important point in the emotional development of young people. It is a time when young people are characterised by a high degree of emotional instability and seek effective ways to regulate their emotions. One of the frequent methods they use to cope with emotional tension is self-injurious behaviour. Methods: In the context of the rising incidence of self-harm among adolescents, this study aims to understand the association of temperament with the experience of tension and self-injurious behaviour along with the mediating role of perfectionism among 366 adolescents aged 15 to 20 years (Mage = 17.98, SD = 1.302, 52.7% female). Participants completed questionnaires on temperament traits, level of perfectionism, and experience of tension and self-injurious behaviour. Results: The results show that traits such as perfectionism, sensory sensitivity and emotional reactivity increase the risk of self-injurious behaviour. Maladaptive perfectionism partially mediates the relationship between these traits and the tendency to experience emotional tension. A temperament profile with a protective role was also identified. Conclusions: The results of the study highlight the importance of innate traits as well as environmental and cognitive influences, and may contribute to a better understanding of the mechanisms leading to self-injurious behaviour and strategies aimed at its prevention.

in Brain Sciences on 2024-11-14 00:00:00 UTC.

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Analysis of Circulating Plasma MicroRNA Profile in Low-Grade and High-Grade Glioma – A Cross-Sectional Study [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-13 18:17:12 UTC.

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Climate Change and Veterinary Medicine: A Call to Action for a Healthier Planet [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-13 18:10:34 UTC.

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De-ethnicizing Ethiopian higher education leadership: the quest for merit-based governance [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-13 18:05:17 UTC.

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Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol [version 1; peer review: awaiting peer review]

in F1000Research on 2024-11-13 17:39:17 UTC.

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Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [version 2; peer review: 1 approved with reservations]

in F1000Research on 2024-11-13 17:31:58 UTC.