bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG denoising during transcutaneous auricular vagus nerve stimulation across simulated, phantom and human data
Authors: Woller Joshua P. , Menrath David , Gharabaghi Alireza 
Published: May 2024

AbstractObjectiveThe acquisition of electroencephalogram (EEG) data during neurostimulation, particularly concurrent transcutaneous electrical stimulation of the auricular vagus nerve, introduces unique challenges for data preprocessing and analysis due to the presence of significant stimulation artifacts. This study evaluates various denoising techniques to address these challenges effectively.MethodsA variety of denoising techniques were investigated, including interpolation methods, spectral filtering, and spatial filtering techniques. The techniques evaluated included low-pass and notch filtering, spectrum interpolation, average artifact subtraction, the Zapline algorithm, and advanced methods such as independent component analysis (ICA), signal-space projection (SSP), and generalized eigendecomposition with stimulation artifact source separation (GED/SASS). The efficacy of these algorithms was evaluated across three distinct datasets: simulated data, data from a gelatin phantom model, and real human subject data.ResultsOur findings indicate that GED (SASS) and SSP significantly outperformed other methods in reducing artifacts while preserving the integrity of the EEG signal. ICA and Zapline were effective too, but came with important limitations. These methods demonstrated robustness across different data types and conditions, providing effective artifact mitigation with minimal disruption to other essential signal components.ConclusionThis comprehensive analysis demonstrates the efficacy of advanced spatial filtering techniques in the preprocessing of EEG data during auricular vagus nerve stimulation. These methods offer promising avenues for enhancing the quality and reliability of neurostimulation-associated EEG data, facilitating a deeper understanding and wider applications in clinical and research settings.
The development of aperiodic and periodic resting-state power between early childhood and adulthood: new insights from optically pumped magnetometers
Authors: Vandewouw Marlee M. , Sato Julie , Safar Kristina , Rhodes Natalie , Taylor Margot J. 
Published: May 2024

AbstractNeurophysiological signals, comprised of both periodic (e.g., oscillatory) and aperiodic (e.g., non-oscillatory) activity, undergo complex developmental changes between childhood and adulthood. With much of the existing literature primarily focused on the periodic features of brain function, our understanding of aperiodic signals is still in its infancy. Here, we are the first to examine age-related changes in periodic (peak frequency and power) and aperiodic (slope and offset) activity using optically pumped magnetometers (OPMs), a new, wearable magnetoencephalography (MEG) technology that is particularly well-suited for studying development. We examined age-related changes in these spectral features in a sample (N=65) of toddlers (1-3 years), children (4-5 years), young adults (20-26 years), and adults (27-38 years). Consistent with the extant literature, we found significant age-related decreases in the aperiodic slope and offset, and changes in peak frequency and power that were frequency-specific; we are the first to show that the effect sizes of these changes also varied across brain regions. This work not only adds to the growing body of work highlighting the advantages of using OPMs, especially for studying development, but also contributes novel information regarding the variation of neurophysiological changes with age across the brain.
Race/ethnicity and socioeconomic status affect the assessment of lipoprotein(a) levels in clinical practice
Authors: Pavlyha Marianna , Li Yihao , Crook Sarah , Anderson Brett R. , Reyes-Soffer Gissette 
Published: May 2024

AbstractBackground and ObjectiveHigh Lp(a) levels are a risk factor for ASCVD, however Lp(a) ordering in clinical practice is low. This study examines how race/ethnicity and socioeconomic status influence Lp(a) ordering.MethodsThis is a single center, retrospective study (2/1/2020-6/30/2023) using electronic medical records of adults with at least one ICD-10 diagnosis of ASCVD or resistant hyperlipidemia (LDL-C >160 mg/dL on statin therapy). We evaluated Lp(a) level differences among racial/ethnic groups and sexes. We also assessed associations between diagnosis type, diagnosis number, age at diagnosis, race, socioeconomic score (based on zip codes), public health coverage and presence of Lp(a) orders.Results4% of our cohort (N=56,833) had an Lp(a) order (17.3% Hispanic, 8.7% non-Hispanic Black, 47.5% non-Hispanic White and, 27% Asian/others). Non-Hispanic Black and Hispanic patients had lower rates of Lp(a) orders (0.17%, 0.28%, respectively) when compared to non-Hispanic White patients (2.35%), p<0.001, however, their median Lp(a) levels were higher. Individuals belonging to deprived socioeconomic groups or on Medicaid, were less likely to have an Lp(a) order (RR=0.39, p<0.001 and RR=0.40, p<0.001 respectively). Certain diagnoses (carotid stenosis, family history of ASCVD and FH) and multiple diagnoses (>2) resulted in more Lp(a) orders compared to those with only one diagnosis (p<0.001).ConclusionsLp(a) ordering is low in patients with ASCVD. Non-Hispanic Black and Hispanic patients at risk are less likely to have an Lp(a) order. Individuals residing in socioeconomically deprived neighborhoods and on Medicaid are also less like have Lp(a) order. Lp(a) orders depend on the type and number of patients’ diagnoses.
Effect of developmental and adult diet composition on reproductive aging inDrosophila melanogaster
Authors: Ruchitha B G , Kumar Devashish , Chandrakanth Mohankumar , Farooq Itibaw , Kumar Nishant , Sura Chand , Chetan S. , Tung Sudipta 
Published: May 2024

ABSTRACTDiet significantly affects reproductive outcomes across species, yet the precise effects of macronutrient compositions beyond caloric intake on reproductive aging are understudied. Existing literature presents conflicting views on the fertility impacts of nutrient-rich versus nutrient-poor developmental diets, underscoring a notable research gap. This study addresses these gaps by examining effects of isocaloric diets with varied protein-to-carbohydrate ratios during both developmental and adult stages on reproductive aging of a large, outbred Drosophila melanogaster population (n = ∼2100). Our results clearly demonstrate an age-dependent dietary impact on reproductive output, initially dominated by the developmental diet, then by a combination of developmental and adult diets in early to mid-life, and ultimately by the adult diet in later life. Importantly, we found that the effects of developmental and adult diets on reproductive output are independent, with no significant interaction. Further investigations into the mechanisms revealed that the effect of developmental diet on fecundity is regulated via ovarioles formation and vitellogenesis; while, the effect of adult diet on fecundity is mostly regulated only via vitellogenesis. These insights resolve disputes in the literature about dietary impacts on fertility and offer valuable perspectives for optimizing fertility strategies in improving public health and conservation efforts in this changing world.HighlightsEffect of developmental and adult diet composition on reproduction is age-dependentDevelopmental diet affects early-life; adult diet late-life; and both affect mid-lifeBut the effect of developmental and adult diets do not interact with each otherDevelopmental diet regulates reproduction via ovarioles formation and vitellogenesisWhereas, adult diet regulates reproduction via differential vitellogenesis across age
BlueRecording: A pipeline for the efficient calculation of extracellular recordings in large-scale neural circuit models
Authors: Tharayil Joseph , Blanco Alonso Jorge , Farcito Silvia , Lloyd Bryn , Romani Armando , Boci Elvis , Cassara Antonino , Schürmann Felix , Neufeld Esra , Kuster Niels , Reimann Michael 
Published: May 2024

AbstractAs the size and complexity of network simulations accessible to computational neuroscience grows, new avenues open for research into extracellularly recorded electric signals. Biophysically detailed simulations permit the identification of the biological origins of the different components of recorded signals, the evaluation of signal sensitivity to different anatomical, physiological, and geometric factors, and selection of recording parameters to maximize the signal information content. Simultaneously, virtual extracellular signals produced by these networks may become important metrics for neuro-simulation validation. To enable efficient calculation of extracellular signals from large neural network simulations, we have developedBlueRecording, a pipeline consisting of standalone Python code, along with extensions to the Neurodamus simulation control application, the CoreNEURON computation engine, and the SONATA data format, to permit online calculation of such signals. In particular, we implement a general form of the reciprocity theorem, which is capable of handling non-dipolar current sources, such as may be found in long axons and recordings close to the current source, as well as complex tissue anatomy, dielectric heterogeneity, and electrode geometries. To our knowledge, this is the first application of this generalized (i.e., non-dipolar) reciprocity-based approach to simulate EEG recordings. We use these tools to calculate extracellular signals from anin silicomodel of the rat somatosensory cortex and hippocampus and to study signal contribution differences between regions and cell types.
Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network
Authors: Toure Mohammed A. , Motoyama Keisuke , Xiang Yichen , Urgiles Julie , Kabinger Florian , Koglin Ann-Sophie , Iyer Ramya S. , Gagnon Kaitlyn , Kumar Amruth , Ojeda Samuel , Harrison Drew A. , Rees Matthew G. , Roth Jennifer A. , Ott Christopher J. , Schiavoni Richard , Whittaker Charles A. , Levine Stuart S. , White Forest M. , Calo Eliezer , Richters Andre , Koehler Angela N. 
Published: May 2024

SummaryCyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs. As a result, numerous drug development campaigns to inhibit CDK9 kinase activity have been pursued. More recently, targeted degradation has emerged as an attractive approach. However, comprehensive evaluation of degradation versus inhibition is still critically needed to assess the biological contexts in which degradation might offer superior therapeutic benefits. We validated that CDK9 inhibition triggers a compensatory mechanism that dampens its effect on MYC expression and found that this feedback mechanism was absent when the kinase is degraded. Importantly, CDK9 degradation is more effective than its inhibition for disrupting MYC transcriptional regulatory circuitry likely through the abrogation of both enzymatic and scaffolding functions of CDK9.Highlights–KI-CDK9d-32 is a highly potent and selective CDK9 degrader.–KI-CDK9d-32 leads to rapid downregulation of MYC protein and mRNA transcripts levels.–KI-CDK9d-32 represses canonical MYC pathways and leads to a destabilization of nucleolar homeostasis.–Multidrug resistance ABCB1 gene emerged as the strongest resistance marker for the CDK9 PROTAC degrader.
PIEZO acts in an intestinal valve to regulate swallowing inC. elegans
Authors: Park Yeon-Ji , Yeon Jihye , Cho Jihye , Kim Do-Young , Bai Xiaofei , Oh Yuna , Kim Jimin , Nam HoJin , Hwang Hyeonjeong , Heo Woojung , Kim Jinmahn , Jun Seoyoung , Lee Kyungeun , Kang KyeongJin , Kim Kyuhyung 
Published: May 2024

ABSTRACTSensations of the internal state of the body play crucial roles in regulating the physiological processes and maintaining homeostasis of an organism. However, our understanding of how internal signals are sensed, processed, and integrated to generate appropriate biological responses remains limited. Here, we show that theC. elegansPIEZO channel, encoded bypezo-1, regulates food movement in the intestine by detecting food accumulation in the anterior part of the intestinal lumen, thereby triggering rhythmical movement of the pharynx, referred to as the pharyngeal plunge.pezo-1deletion mutants exhibit defects in the pharyngeal plunge, which is rescued by PEZO-1 or mouse PIEZO1 expression, but not by PIEZO2, in a single isolated non-neuronal tissue of the digestive tract, the pharyngeal-intestinal valve. Genetic ablation or optogenetic activation of this valve inhibits or induces the pharyngeal plunge, respectively. Moreover, pressure built in the anterior lumen of the intestine results in apezo-1-dependent pharyngeal plunge, which is driven by head muscle contraction. These findings illustrate how interoceptive processes in a digestive organ regulate swallowing through the PIEZO channel, providing insights into how interoception coordinates ingestive processes in higher animals, including humans.
Proteins associated withCryptococcusspp. extracellular polysaccharides are implicated in virulence, capsule integrity, and biofilm formation
Authors: Stempinski Piotr R. , Jacobs Ella , Lopes Livia Liporagi , Rodrigues Dos Santos Junior Samuel , Rojas Kevin , Wear Maggie P. , Casadevall Arturo 
Published: May 2024

AbstractCryptococcus neoformansandCryptococcus gattiiare pathogenic fungi comprising species complexes that are the etiological agents of cryptococcosis. Both fungal species complexes possess a variety of virulence factors that include a polysaccharide capsule, melanin production, enzymes, and the release of polysaccharides. In this study, we characterized the proteins associated with cryptococcal polysaccharides and analyzed their function by studying mutants deficient in their expression. Mass spectrometry analysis of exopolysaccharide fractions revealed 62 proteins, many of which were previously uncharacterized. Analysis of capsule size, structure, and integrity in protein-deficient mutants allowed us to identify four proteins, which we namedExtracellular PolysaccharideRelated proteins (Exa1-4), and whose absence affected proper capsule assembly and EPS release. In summary, cryptococcal exopolysaccharide is associated with proteins that are implicated in virulence, capsular integrity, and biofilm formation. Our results associated new phenotypes for four previously unknown genes and show that the filtered polysaccharide preparations are a rich source of proteins that can inform capsular assembly, virulence, and immunological studies.
Neural correlates of embodied and vibratory mechanisms associated with vocal emotion production
Authors: Selosse Garance , Grandjean Didier , Ceravolo Leonardo 
Published: May 2024

AbstractDespite a large body of literature on the psychological and brain mechanisms of vocal emotion perception, less is known on expression and production mechanisms, especially the vibrations originating in the vocal cords and their role in emotional voice production. In the present study, we aimed to fill this gap. Participants had to produce angry, happy and neutral emotional vocalizations in different production conditions (‘normal’, ‘whisper’, ‘articulate’). An accelerometer recorded the vibrations on the throat, close to the vocal folds. Results showed effects of the Emotion factor with activations in the bilateral temporal voice areas, the inferior frontal gyri as well as motor and supplementary motor areas. The Production factor and its interaction with Emotion revealed significant effects in motor, somatosensory cortices, insula and inferior frontal cortex. Exploratory analysis of the brain correlates of emotional vocal tract vibrations specific to ‘normal’ voice production showed significant correlations with brain regions involved in interoceptive processing (insula, inferior frontal cortex, cerebellum). Our results highlight the crucial role of vibro-tactile body resonances in vocal emotion production that might play an important role for the interoceptive phenomena involved in the representation of our own emotions such as in emergent feelings related to emotional vocal production.
Task-irrelevant stimuli reliably boost phasic pupil-linked arousal but do not affect decision formation
Authors: Hebisch J. , Ghassemieh A.-C. , Zhecheva E. , Brouwer M. , van Gaal S. , Schwabe L. , Donner T.H. , de Gee J.W. 
Published: May 2024

AbstractThe arousal systems of the brainstem, specifically the locus coeruleus-noradrenaline system, respond “phasically” during decisions. These central arousal transients are accompanied by dilations of the pupil. Mechanistic attempts to understand the impact of phasic arousal on cognition would benefit from the ability to experimentally manipulate arousal in a temporally precise manner. Here, we evaluated a non-invasive candidate approach for such a manipulation in humans: presenting task-irrelevant auditory stimuli at different latencies during the execution of a challenging task. Task-irrelevant auditory stimuli drive responses of brainstem nuclei involved in the control of pupil size. But it is unknown whether such sound-evoked responses mimic the central arousal transients evoked during cognitive computations. A large body of evidence has implicated central arousal transients in a bias reduction during challenging perceptual decisions. We thus used challenging visual decisions as a testbed, combining them with task-irrelevant sounds of varying onset latency or duration. Across three experiments, the sounds consistently elicited well-controlled pupil responses that superimposed onto task-evoked responses. While we replicated a negative correlation between task-evoked pupil responses and bias established in previous work, the task-irrelevant sounds had no behavioral effect. This dissociation suggests that cognitive task engagement and task-irrelevant sounds may recruit distinct neural systems contributing to the control of pupil size.
Stress-induced dysfunction of neurovascular astrocytes contributes to sex-specific behavioral deficits
Authors: Bollinger Justin L. , Johnsamuel Shobha , Vollmer Lauren L. , Kuhn Alexander M. , Wohleb Eric S. 
Published: May 2024

AbstractAstrocytes form an integral component of the neurovascular unit, ensheathing brain blood vessels with projections high in aquaporin-4 (AQP4) expression. These AQP4-rich projections facilitate interaction between the vascular endothelium, astrocytes, and neurons, and help stabilize vascular morphology. Studies using preclinical models of psychological stress and post-mortem tissue from patients with major depressive disorder (MDD) have reported reductions in AQP4, loss of astrocytic structures, and vascular impairment in the prefrontal cortex (PFC). Though compelling, the role of AQP4 in mediating stress-induced alterations in blood vessel function and behavior remains unclear. Here, we address this, alongside potential sex differences in chronic unpredictable stress (CUS) effects on astrocyte phenotype, blood-brain barrier integrity, and behavior. CUS led to pronounced shifts in stress-coping behavior and working memory deficits in male –but not female– mice. Following behavioral testing, astrocytes from the frontal cortex were isolated for gene expression analyses. We found that CUS increased various transcripts associated with blood vessel maintenance in astrocytes from males, but either had no effect on-or decreased-these genes in females. Furthermore, CUS caused a reduction in vascular-localized AQP4 and elevated extravasation of a small molecule fluorescent reporter (Dextran) in the PFC in males but not females. Studies showed that knockdown of AQP4 in the PFC in males is sufficient to disrupt astrocyte phenotype and increase behavioral susceptibility to a sub-chronic stressor. Collectively, these findings provide initial evidence that sex-specific alterations in astrocyte phenotype and neurovascular integrity in the PFC contribute to behavioral and cognitive consequences following chronic stress.
Slow Oscillations Modulate Functional Brain Changes Supporting Working Memory
Authors: Zhang Jing , Chen Pin-Chun , Mednick Sara C. , Tambini Arielle 
Published: May 2024

AbstractWorking memory (WM), the temporary mental storage and manipulation of information, is a skill that can improve with training. Sleep, and specifically slow oscillations (SOs), has been linked with WM improvement, yet it is unknown how processing during SOs modulates WM function across sleep. The current study examines how WM-related neural processing changes with sleep, and how these changes are related to activity during SOs. To do so, participants performed a WM task during fMRI before and after sleep, and the first 2.5 hrs of sleep was monitored by simultaneous EEG-fMRI. Reliable overnight changes in WM-related activity patterns were found, with reduced recruitment of the dorsal precuneus after compared to before sleep. Moreover, greater neural activation during SOs was associated with reduced overnight recruitment during WM across multiple levels of analysis. Our findings highlight the important role of SOs, elucidating how SOs may support changes in WM function across sleep.
Stress hyperglycemia exacerbates inflammatory brain injury after stroke
Authors: Won Seok Joon , Zhang Yiguan , Butler Nicholas J. , Kim Kyungsoo , Mocanu Ebony , Nzoutchoum Olive Tambou , Lakkaraju Ramya , Davis Jacqueline , Ghosh Soumitra , Swanson Raymond A. 
Published: May 2024

ABSTRACTPost-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47phox-/-mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.