bluuebunny/crossref_metadata_2025 huggingface dataset:
Fortuitous discovery of a microfilaria of the genus Loa loa during a routine blood smear at the Hematology Laboratory of the Mohamed V Military Instruction Hospital in Rabat: A case report
Authors: Labrigui Mohammed , Layat Hamza , Bouikhif Manal , Ziad Fatima , Khalil Zimi , Jerroundi Zineb , Zahid Hafid , Ouzzif Zohra
Published: August 2024

Loiasis is a neglected nematode infestation that is endemic in the rainforests of western and central Africa. The disease is transmitted to man by tabanid flies of the genus Chrysops, and is frequently associated with significant and persistent hyper eosinophilia.
We present a case involving a 28-year-old Cameroonian soldier who underwent a blood examination. The findings revealed hyper eosinophilia with a count of 1500/µl, and no indications of anemia or thrombocytopenia. Analysis of a blood smear, using MGG (May-Grünwald-Giemsa) staining, identified small worms that are indicative of microfilariae of the genus Loa loa.
This case of Loa loa, identified in the hematology laboratory, is one of the rare diagnoses in Morocco. Therefore, biologists need to remain vigilant and carry out a thorough analysis of the blood count and blood smear.
Recurrent connections facilitate occluded object recognition by explaining-away
Authors: Kang Byungwoo , Midler Benjamin , Chen Feng , Druckmann Shaul
Published: August 2024

Despite the ubiquity of recurrent connections in the brain, their role in visual processing is less understood than that of feedforward connections. Occluded object recognition, an ethologically critical cognitive capacity, is thought to rely on recurrent processing of visual information, but it remains unclear whether and how recurrent processing improves recognition of occluded objects. Using convolutional models of the visual system, we demonstrate how a novel form of computation arises in recurrent–but not feedforward–networks that leverages information about the occluder to “explain-away” the occlusion. This occurs without any constraint placed on the computation and was found in both abstract networks used to sweep across architectures and a network explicitly constructed to model the primate visual system. Following these computational results, we performed a behavioral experiment to study explaining-away in humans, finding evidence consistent with explaining-away. Finally, to demonstrate a specific mechanism for explaining-away, we next developed an experimentally inspired recurrent model that was able to recover fine-grained features of occluded stimuli by explaining-away. Recurrent connections’ capability to explain away may extend to more general cases where undoing context-dependent changes in representations could benefit perception.
Use of a truffle dog provides insight into the ecology and abundant occurrence ofGenea(Pyronemataceae) in western Oregon, U.S.A
Authors: Dawson Hilary Rose , Dawson Heather A.
Published: August 2024

Hypogeous fungi (“truffles”) are challenging to study because they produce underground sporocarps that may not be found during traditional fungal surveys. Commercially valuable truffles are located using scent-detection dogs trained on truffles. However, the dogs are not necessarily limited to commercial truffle species when trained on other truffle taxa of interest. For example,Genea(Pyronemataceae, Ascomycota) is a genus of common but difficult to find truffles that develops small and often soil-colored hypogeous ascomata (truffles).. We used a truffle dog trained to locateGeneatruffles in the southern Willamette Valley and associated mountains in western Oregon, U.S.A, recording when the sporocarps were present at a wide range of elevations (113 to 1879 m). We foundGeneawas present in half of our surveys, and noted that it rarely fruited in areas that had experienced wildfire. This study demonstrates the value of using truffle dogs in documenting truffle diversity, particularly those that are difficult to locate visually, and provides further evidence for the abundance ofGenea.
Augmenting complex and dynamic performance through mindfulness-based cognitive training: an investigation of on-task EEG dynamics.
Authors: Dziego Chloe Anna , Bornkessel-Schlesewsky Ina , Immink Maarten A , Cross Zachariah Reuben , Schlesewsky Matthias
Published: August 2024

Mindfulness-based cognitive training exhibits great propensity for improving cognitive performance across a range of contexts. However, the neurophysiological basis of these cognitive enhancements has remained relatively unclear. Previous studies have widely examined EEG during mindfulness practice - or made comparisons with long-term meditators and controls - but have failed to capture how EEG dynamics in subsequent cognitive testing scenarios might be altered as a function of mindfulness-based interventions. The current study therefore aimed to assess a variety of EEG dynamics (oscillatory, aperiodic, and event-related) during engagement in a dynamic and complex cognitive task, following a mindfulness-based cognitive training regime. Participants (n = 40, age range = 18 - 38) attended the lab on two separate occasions (pre- and post- a web-based one-week mindfulness intervention), where EEG was recorded during engagement in the Target Motion Analyst (TMA) task. Previous analysis of the same participants demonstrated that greater adherence to the mindfulness-based cognitive training was associated with improved performance on the TMA task (Dziego, Bornkessel-Schlesewsky, Schlesewsky et al., 2024). Here, we capitalise on these previous findings to assess whether adherence is paralleled by measurable differences in on-task EEG dynamics. Linear mixed-effects modelling demonstrated that, while main effects were observed across session, adherence to cognitive training was not directly associated with alpha power, theta power or 1/f parameters. Challenges also arose when computing event-related potentials (ERPs), illustrating the difficulties of using this technique in more complex testing environments. While these results are challenging to place within the context of previous EEG studies on meditation and cognitive performance, our findings highlight the complexities in understanding the cognitive benefits of mindfulness-based training interventions through EEG dynamics observed during subsequent cognitive testing.
The Body Mirroring Thought: The Relationship Between Thought Transitions and Fluctuations in Autonomic Nervous Activity Mediated by Interoception
Authors: Sakuragi Mai , Shinagawa Kazushi , Terasawa Yuri , Umeda Satoshi
Published: August 2024

Our thought states change unconsciously. This study verified that the transference of thought states varies with fluctuations in autonomic nervous activity, and that this effect is modulated by interoceptive accuracy. The participants completed the heartbeat counting task (HCT) and vigilance task (VT). We assessed the participants' interoceptive accuracy based on their performance on the HCT. The VT is a simple attention task, and during this task, we asked the participants to report the content and contemplation of their thoughts. Consequently, participants with accurate interoception were more likely to remain in a highly contemplative thought state when sympathetic activity was activated. In contrast, the dominance of parasympathetic activity facilitated transitions to different thought states or experiences of less contemplative thought states in them. The results suggest that even subtle changes in bodily responses at rest can affect thought transitions in people with accurate interoception.
A plasma proteomic signature links secretome of senescent monocytes to aging- and obesity-related clinical outcomes in humans
Authors: Olinger Bradley , Banarjee Reema , Dey Amit , Tsitsipatis Dimitrios , Tanaka Toshiko , Ram Anjana , Nyunt Thedoe , Daya Gulzar , Peng Zhongsheng , Cui Linna , Candia Julián , Simonsick Eleanor M. , Gorospe Myriam , Walker Keenan A. , Ferrucci Luigi , Basisty Nathan
Published: August 2024

Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence associated with diverse clinical traits in humans to facilitate future non-invasive assessment of individual senescence burden and efficacy testing of novel senotherapeutics. Using a novel nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in monocytes and examined these proteins in plasma samples (N = 1060) from the Baltimore Longitudinal Study of Aging (BLSA). Machine learning models trained on monocyte SASP associated with several age-related phenotypes in a test cohort, including body fat composition, blood lipids, inflammation, and mobility-related traits, among others. Notably, a subset of SASP-based predictions, including a ‘high impact’ SASP panel that predicts age- and obesity-related clinical traits, were validated in InCHIANTI, an independent aging cohort. These results demonstrate the clinical relevance of the circulating SASP and identify relevant biomarkers of senescence that could inform future clinical studies.
Durability of SARS-CoV-2 IgG Antibodies: Insights from a Longitudinal Study, Puerto Rico
Authors: Madewell Zachary J. , Graff Nathan , Lopez Velma K. , Rodriguez Dania M. , Wong Joshua M. , Maniatis Panagiotis , Medina Freddy A. , Muñoz Jorge L. , Briggs-Hagen Melissa , Adams Laura E. , Rivera-Amill Vanessa , Paz-Bailey Gabriela , Major Chelsea G.
Published: August 2024

Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020–August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.
Relating Standardized Automated Perimetry Performed with Stimulus Sizes III and V in Eyes With Field Loss due to Glaucoma and NAION
Authors: Szanto David , Wall Michael , Chong Luke X , Kupersmith Mark
Published: August 2024

Objective: Standard automated perimetry (SAP) visual field (VF) results are more repeatable using Goldmann stimulus size V (stimV) in eyes with moderate/severe deficits due to glaucoma. There are few reports relating VFs using stimulus size V and III, typically used in the clinic for glaucoma, and none for non-arteritic anterior ischemic optic neuropathy (NAION). We hypothesized that we could compare and relate the VFs with both stimuli for glaucoma and NAION. Methods: We utilized 1992 same-day pairs of stimIII and stimV SAP VFs using the 24-2 strategy for eyes with glaucoma or NAION. We explored the optimal threshold to censor the raw sensitivities, prior to calculating age-standardized total deviations (TD). We determined the mean and standard deviation of the differences among all TD pairs. We computed a line of best fit to determine closeness to the line of unity. Results: The ideal censoring conversion threshold was 21 dB for stimIII and 24 dB for stimV. The difference between stimV and stimIII censored (0.0 +/- 1.9 dB) and uncensored (0.4 +/- 2.6 dB) TD pairings strongly correlate with each other (r2 = 0.70, p < 0.001). The line of best fit from these pairings has a slope of 0.92, which is similar to that of the line of unity (m = 1). Conclusion: Censoring plus age correction is a valid method of comparison between stimIII and stimV SAP VFs with moderate to severe VF loss due to optic nerve disorders. Translational Relevance: StimIII and stimV TDs are interchangeable in clinical practice.
Telehealth Utilization and Patient Experiences: The Role of Social Determinants of Health Among Individuals with Hypertension and Diabetes
Authors: Chen Haoxin , Simmons Will , Hashish Malak Abu , Ye Jiancheng
Published: August 2024

Objective

To evaluate the utilization patterns, effectiveness, and patient satisfaction of telehealth services among individuals with hypertension and/or diabetes, and to investigate the influence of social determinants of health (SDOH) on telehealth access and utilization in this population.

Methods

We conducted a cross-sectional analysis using data from the 2022 Health Information National Trends Survey (HINTS 6) by the National Cancer Institute. The study sample included 3,009 respondents with self-reported diabetes, hypertension, or both conditions. Telehealth usage was assessed through 14 survey questions, and participant characteristics were analyzed using sociodemographic, baseline health, and SDOH data.

Results

Of the 6,252 HINTS 6 survey respondents, 3,009 met the inclusion criteria. Significant sociodemographic differences were observed across the diabetes and/or hypertension groups. No significant differences were found in telehealth usage among the groups, with 43.9% of respondents utilizing telehealth in the past year. Common reasons for telehealth use included provider recommendation, convenience, and infection avoidance. Social determinants of health, such as food insecurity and transportation issues, were more prevalent among individuals with both conditions, though no significant differences in telehealth experiences were noted across groups.

Conclusion

Telehealth shows potential for managing chronic conditions like hypertension and diabetes, demonstrating substantial adoption and universal accessibility. However, disparities influenced by SDOH highlight the need for targeted interventions to ensure equitable access. Addressing privacy concerns, leveraging healthcare providers’ recommendations, and tackling SDOH barriers are crucial for fostering wider telehealth adoption and improving outcomes. Future research should focus on the long-term impacts of telehealth and further investigate SDOH factors to develop tailored interventions that enhance engagement and equitable access across diverse patient populations.
Unraveling the Neural Landscape of Mental Disorders using Double Functional Independent Primitives (dFIPs)
Authors: Soleimani Najme , Iraji Armin , Pearlson Godfrey , Preda Adrian , Calhoun Vince D.
Published: August 2024

Mental illnesses extract a high personal and societal cost, and thus explorations of the links between mental illness and functional connectivity in the brain are critical. Investigating major mental illnesses, believed to arise from disruptions in sophisticated neural connections, allows us to comprehend how these neural network disruptions may be linked to altered cognition, emotional regulation, and social interactions. Although neuroimaging has opened new avenues to explore neural alterations linked to mental illnesses, the field still requires precise and sensitive methodologies to inspect these neural substrates of various psychological disorders. In this study, we employ a hierarchical methodology to derive double functionally independent primitives (dFIPs) from resting state functional magnetic resonance neuroimaging data (rs-fMRI). These dFIPs encapsulate canonical overlapping patterns of functional network connectivity (FNC) within the brain. Our investigation focuses on the examination of how combinations of these dFIPs relate to different mental disorder diagnoses. The central aim is to unravel the complex patterns of FNC that correspond to the diverse manifestations of mental illnesses. To achieve this objective, we used a large brain imaging dataset from multiple sites, comprising 5805 total individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and controls. The key revelations of our study unveil distinct patterns associated with each mental disorder through the combination of dFIPs. Notably, certain individual dFIPs exhibit disorder-specific characteristics, while others demonstrate commonalities across disorders. This approach offers a novel, data-driven synthesis of intricate neuroimaging data, thereby illuminating the functional changes intertwined with various mental illnesses. Our results show distinct signatures associated with psychiatric disorders, revealing unique connectivity patterns such as heightened cerebellar connectivity in SCZ and sensory domain hyperconnectivity in ASD, both contrasted with reduced cerebellar-subcortical connectivity. Utilizing the dFIP concept, we pinpoint specific functional connections that differentiate healthy controls from individuals with mental illness, underscoring its utility in identifying neurobiological markers. In summary, our findings delineate how dFIPs serve as unique fingerprints for different mental disorders.
Intra-subgenome regulation induces unbalanced expression and function among bread wheat homoeologs
Authors: Wang Xiaoming , Liu Yuxiu , Zhao Peng , Hou Wenyang , Cheng Mingzhu , Shi Xue , Simmonds James , Borrill Philippa , Ji Wanquan , Xu Shengbao
Published: August 2024

The differential expression of homoeologous genes confers expression plasticity and facilitates the adaptation and domestication of major polyploid crops. However, how this homoeolog expression bias (HEB) is regulated remains elusive. Here, transcriptome analysis of 406 wheat (Triticum aestivum; AABBDD) accessions revealed great variation in HEB among accessions. We identified 14,727 QTLs regulating HEB (hebQTLs), indicating that HEB is genetically regulated and can be predicted using genotyping data. The hebQTLs only regulate the expression of homoeologs in the same subgenome and downregulate their expression to result in HEB, suggesting that intra-subgenomic rather than inter-subgenomic interactions induce HEB. Furthermore, non-hebQTL-regulated homoeologs have stronger biological functions, are under higher selection pressure and exhibit lower genetic diversity than hebQTL-regulated homoeologs and compensate for the downregulated expressions of hebQTL-regulated homoeologs. Our findings reveal how homoeolog expression is coordinated at the genetic level and provide an avenue for leveraging HEB to improve polyploid crops.
An Evolutionary Statistics Toolkit for Simplified Sequence Analysis on Web with Client-Side Processing
Authors: Karagöl Alper , Karagöl Taner
Published: August 2024

We present the Evolutionary Statistics Toolkit, a user-friendly web-based platform designed for specialized analysis of genetic sequences, which integrates multiple evolutionary statistics. The toolkit focuses on a selection of specialized tools, including Tajima’s D calculator with Site Frequency Spectrum (SFS), Shannon’s Entropy (H), alignment re-formatting, HGSV to FASTA conversion, pair-wise frequency analysis, FASTA to SEQRES, RNA 2D structure alignment, Kyte-Doolittle hydrophilicity plot tool and kurtosis coefficient calculator. Tajima’s D is calculated using the reference formula: D = (π - θW) / sqrt(VD), where π corresponds to the average number of differences, θWis Watterson’s estimator of θ, and VDis the variance of π - θW. Shannon’s Entropy is defined as H = -∑ pi* log2(pi), where piis the probability of occurrence of each unique character (nucleotide or amino acid) in the sequence. The toolkit facilitates streamlined workflows for early researchers in evolutionary biology, genomics, and related fields. With comparing with existing codes, we propose it also emerges as an educational interactive website for beginners in evolutionary statistics. The source code for each tool in the toolkit is available through GitHub links provided on the website. This open-source approach allows users to inspect the code, suggest improvements, or further adapt the tools for their specific usage and research needs. This article describes the functionalities, and validation of each tool within the platform, along with comparison with accessible existing statistical utilities. The toolkit is freely accessible on:https://www.alperkaragol.com/toolkit
Primed responses to damage signals mediate mycorrhiza-induced resistance in tomato plants
Authors: Minchev Zhivko , Garcia Juan M. , Pozo Estefania , Pozo Maria J. , Gamir Jordi
Published: August 2024

Arbuscular mycorrhizal fungi establish mutualistic associations with the roots of most vascular plants, enhancing plant immunity and activating mycorrhiza-induced resistance (MIR). In this study, we hypothesised that differential recognition of endogenous damage signals contributes to MIR in tomato plants. To test the hypothesis, we compared responses in mycorrhizal and non-mycorrhizal tomato plants after applying the cell-wall derived damage signal oligogalacturonides (OGs). We analysed the proteomic and metabolomic profiles, and the expression of marker genes related to plant defense, and the effects on plant resistance to the necrotrophic pathogenBotrytis cinerea. Our results show that mycorrhizal plants are more sensitive to these damage signals, as they respond to lower doses and exhibit stronger responses at the protein and metabolic level compared to non-mycorrhizal plants. Mycorrhizal plants showed primed accumulation of defense proteins, receptor kinases, flavonoids, and activation of the jasmonic acid and ethylene signaling pathways in response to OGs. Expression levels of the wall-associated kinase 1 (slWAK1) gene, coding for an OG receptor kinase in tomato, are elevated in mycorrhizal plants, and MIR againstB. cinereais abolished in awak1mutant. Together, these results provide the first indication that self-damage recognition is essential to induce MIR againstB. cinerea.

Highlight

Mycorrhizal tomato plants exhibit enhanced sensitivity to damage signals, leading to primed defense responses and induced resistance to fungal pathogens.
Sensory population activity reveals confidence computations in the primate visual system
Authors: Boundy-Singer Zoe M. , Ziemba Corey M. , Goris Robbe L. T.
Published: August 2024

Perception is fallible1–3. Humans know this4–6, and so do some non-human animals like macaque monkeys7–14. When monkeys report more confidence in a perceptual decision, that decision is more likely to be correct. It is not known how neural circuits in the primate brain assess the quality of perceptual decisions. Here, we test two hypotheses. First, that decision confidence is related to the structure of population activity in sensory cortex. And second, that this relation differs from the one between sensory activity and decision content. We trained macaque monkeys to judge the orientation of ambiguous stimuli and additionally report their confidence in these judgments. We recorded population activity in the primary visual cortex and used decoders to expose the relationship between this activity and the choice-confidence reports. Our analysis validated both hypotheses and suggests that perceptual decisions arise from a neural computation downstream of visual cortex that estimates the most likely interpretation of a sensory response, while decision confidence instead reflects a computation that evaluates whether this sensory response will produce a reliable decision. Our work establishes a direct link between neural population activity in sensory cortex and the metacognitive ability to introspect about the quality of perceptual decisions.
Modeling impairment of ionic regulation with extended Adaptive Exponential integrate-and-fire models
Authors: Depannemaecker Damien , Tesler Federico , Desroches Mathieu , Jirsa Viktor , Destexhe Alain
Published: August 2024

To model the dynamics of neuron membrane excitability many models can be considered, from the most biophysically detailed to the highest level of phenomenological description. Recent works at the single neuron level have shown the importance of taking into account the evolution of slow variables such as ionic concentration. A reduction of such a model to models of the integrate-and-fire family is interesting to then go to large network models. In this paper, we introduce a way to consider the impairment of ionic regulation by adding a third, slow, variable to the adaptive Exponential integrate-and-fire model (AdEx). We then implement and simulate a network including this model. We find that this network was able to generate normal and epileptic discharges. This model should be useful for the design of network simulations of normal and pathological states.
Single-cell differential expression analysis between conditions within nested settings
Authors: Hafner Leon , Sturm Gregor , List Markus
Published: August 2024

Differential expression analysis provides insights into fundamental biological processes and with the advent of single-cell transcriptomics, gene expression can now be studied at the level of individual cells. Many analyses treat cells as samples and assume statistical independence. As cells are pseudoreplicates, this assumption does not hold, leading to reduced robustness, reproducibility, and an inflated type 1 error rate.

In this study, we investigate various methods for differential expression analysis on single-cell data, conduct extensive benchmarking and give recommendations for method choice. The tested methods include DESeq2, MAST, DREAM, scVI, the Permutation Test and distinct. We additionally adapt Hierarchical Bootstrapping to differential expression analysis on single-cell data and include it in our benchmark.

We found that differential expression analysis methods designed specifically for single-cell data do not offer performance advantages over conventional pseudobulk methods such as DESeq2 when applied to individual data sets. In addition, they mostly require significantly longer run times. For atlas-level analysis, permutation-based methods excel in performance but show poor runtime, suggesting to use DREAM as a compromise between quality and runtime. Overall, our study offers the community a valuable benchmark of methods across diverse scenarios and offers guidelines on method selection.
Machine learning enables high-throughput, low-replicate screening for novel anti-seizure targets and compounds using combined movement and calcium fluorescence in larval zebrafish
Authors: McGraw Christopher Michael , Poduri Annapurna
Published: August 2024

Abstract

Identifying new, more efficacious anti-seizure medications (ASMs) is challenging, partly due to limitations in animal-based assays. Zebrafish (Danio rerio) can serve as a model of chemical and genetic seizures, but methods for detecting seizure-like activity in zebrafish, though powerful, have been hampered by low sensitivity (locomotor/behavioral assays) or low-throughput (tectal electrophysiology or calcium fluorescence microscopy). To address these issues, we developed a novel approach to assay seizure-like activity using combined locomotor and calcium fluorescence features, measured simultaneously from unrestrained larval zebrafish using a 96-well fluorescent plate reader. Using custom software to track fish movement and changes in fluorescence (deltaF/F0) from high-speed time-series (12.6Hz), we trained logistic classifiers using elastic net regression to distinguish seizure-like activity from non-seizure related changes based on event-specific and subject-specific features in response to the GABAAR antagonist, pentylenetetrazole (PTZ). We demonstrate that a classifier trained on combined movement and fluorescence data achieves high accuracy (“PTZ M+F”; area-under-curve receiver-operator characteristic (AUC-ROC): 0.98; F1 score: 0.912) and out-performs classifiers trained on movement (“PTZ M”; AUC-ROC: 0.9, F1: 0.9) or fluorescence features alone (“PTZ F”; AUC-ROC 0.96; F1: 0.87). The rate of classified seizure-like events increases as a dose-response to PTZ (serial dose escalation, 0, 2.5mM, 15mM) and is strongly suppressed by ASM treatment (valproic acid, VPA; tiagabine, TGB). At high-dose PTZ, we show that VPA reduces seizure-like activity defined by either “PTZ M+F” or “PTZ M” classifiers. Meanwhile, TGB selectively reduces events defined by the “PTZ M+F” classifier, paralleling previous reports that TGB reduces electrographic but not locomotor seizures and highlighting the potential for our approach to combine features of previously orthogonal assays. Using ASM benchmark data, we employ bootstrap simulation to calculate the expected statistical power of our method as a function of sample size. We demonstrate that anti-seizure responses (robust strictly standardized mean difference, RSSMD, versus control) with magnitudes similar to those associated with VPA or TGB can be reliably detected (true positive rate (TPR) > 90%) with as few as N=4 biological replicates per group, while maintaining a 5% false positive rate. In a prospective test screen with 3-6 replicates per group and on-plate controls, the anti-seizure effect of 4 out of 5 tested ASMs (CBZ, LEV, LZP, TGB) was detected. In summary, we demonstrate a simple high-throughput approach to whole organism anti-seizure phenotyping combining two previously reported metrics to facilitate screens for novel anti-seizure interventions in zebrafish.
Brain magnetic resonance imaging software to support dementia diagnosis in routine clinical practice: a barrier to adoption study in the National Health Service (NHS) England
Authors: Griffanti Ludovica , Serres Florence , Cini Laura , Walsh Jessica , Hanayik Taylor , Pervaiz Usama , Smith Stephen , Johansen-Berg Heidi , Rose James , Bajre Mamta
Published: August 2024

With the rise in numbers of people living with dementia and new disease modifying therapies entering the market, there is increasing need for brain magnetic resonance imaging (MRI) for diagnosis and safety monitoring. The number of scans that need reporting is expected to rapidly grow. Clinical radiology reports are currently largely qualitative and variable in structure and content. By contrast, research software typically uses automated methods to extract quantitative metrics from brain scans.

To better understand the unmet clinical need for brain reporting software for dementia we conducted a barrier to adoption study using the Lean Assessment Process (LAP)methodology. We first assessed the role of brain imaging in the diagnostic pathway for people with suspected dementia in the NHS in England. We then explored the views of (neuro)radiologists, neurologists and psychiatrists on the potential benefits and level of acceptance of software to support brain MRI analysis, using the FMRIB software library (FSL) as a technology exemplar.

The main perceived utilities of the proposed software were: increased diagnostic confidence; support for delivery of disease modifying therapies; and the possibility to compare individual results with population norms. In addition to assessment of global atrophy, hippocampal atrophy and white matter hyperintensities, additional user requirements included assessment of microbleeds, segmentation of multiple brain structures, clear information about the control population used for reference, and possibility to compare multiple scans. The main barriers to adoption related to the limited availability of 3T MRI scanners in the UK, integration into the clinical workflow, and the need to demonstrate cost-effectiveness. These findings will guide future technical development, clinical validation, and health economic evaluation.
The breath volatilome is shaped by the gut microbiota
Authors: Hernandez-Leyva Ariel J. , Berna Amalia Z. , Liu Yang , Rosen Anne L. , Lint Michael A. , Whiteside Samantha A. , Jaeger Natalia , McDonough Ryan T. , Joardar Nikhilesh , Santiago-Borges Jesús , Tomera Christopher P. , Luo Wentai , Odom John Audrey R. , Kau Andrew L.
Published: August 2024

The gut microbiota is widely implicated in host health and disease, inspiring translational efforts to implement our growing body of knowledge in clinical settings. However, the need to characterize gut microbiota by its genomic content limits the feasibility of rapid, point-of-care diagnostics. The microbiota produces a diverse array of xenobiotic metabolites that disseminate into tissues, including volatile organic compounds (VOCs) that may be excreted in breath. We hypothesize that breath contains gut microbe-derived VOCs that inform the composition and metabolic state of the microbiota. To explore this idea, we compared the breath volatilome and fecal gut microbiomes of 27 healthy children and found that breath VOC composition is correlated with gut microbiomes. To experimentally interrogate this finding, we devised a method for capturing exhaled breath from gnotobiotic mice. Breath volatiles are then profiled by gas-chromatography mass-spectrometry (GC-MS). Using this novel methodology, we found that the murine breath profile is markedly shaped by the composition of the gut microbiota. We also find that VOCs produced by gut microbes in pure culture can be identifiedin vivoin the breath of mice monocolonized with the same bacteria. Altogether, our studies identify microbe-derived VOCs excreted in breath and support a mechanism by which gut bacterial metabolism directly contributes to the mammalian breath VOC profiles.
Social and environmental predictors of gut microbiome age in wild baboons
Authors: Dasari Mauna R. , Roche Kimberly E. , Jansen David , Anderson Jordan , Alberts Susan C. , Tung Jenny , Gilbert Jack A. , Blekhman Ran , Mukherjee Sayan , Archie Elizabeth A.
Published: August 2024

Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting “microbiome clock” predicts host chronological age. Deviations from the clock’s predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual’s “microbiome age” does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.
Tissue and Extracellular Matrix Remodeling of the Subchondral Bone during Osteoarthritis of Knee Joints as revealed by Spatial Mass Spectrometry Imaging
Authors: Schurman Charles A. , Bons Joanna , Woo Jonathon J. , Yee Cristal , Tao Nannan , Alliston Tamara , Angel Peggi , Schilling Birgit
Published: August 2024

Osteoarthritis (OA) is a degenerative condition of the skeletal extracellular matrix (ECM) marked by the loss of articular cartilage and changes to subchondral bone homeostasis. Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease. Mass Spectrometry Imaging (MSI) enables molecular spatial mapping of the proteomic landscape of tissues. Histologic sections of human tibial plateaus from knees of human OA patients and cadaveric controls were treated with collagenase III to target ECM proteins prior to MS Imaging of bone and cartilage proteins using a timsTOF fleX mass spectrometer. Spatial MSI data of the knee were processed and automatically segmented identifying distinct areas of knee joint damage. ECM peptide markers were compared between i) the medial halves of OA patient joints and the medial side of non-OA (cadaveric) joints, and ii) between the same medial OA tissues and their corresponding, less OA impacted, lateral joint halves. Distinct peptide signatures distinguished OA medial tissues from the cadaveric medial and OA lateral tissues (AUROC >0.85). Overall, 31 peptide candidates from ECM proteins, including Collagen alpha-1(I), Collagen alpha-1(III), and surprisingly, Collagen alpha-1(VI) and Collagen alpha-3(VI), exhibited significantly elevated abundance in diseased tissues. Highly specific hydroxyproline-containing collagen peptides, mainly from collagen type I, dominated OA subchondral bone directly under regions of lost cartilage. The identification of specific protein markers for subchondral bone remodeling in OA advances our molecular understanding of disease progression in OA and provides potential new biomarkers for OA detection and disease grading.
The grasshopper genome reveals long-term gene content conservation of the X Chromosome and temporal variation in X Chromosome evolution
Authors: Li Xinghua , Mank Judith E. , Ban Liping
Published: August 2024

We present the first chromosome-level genome assembly of the grasshopper,Locusta migratoria, one of the largest insect genomes. We use coverage differences between females (XX) and males (X0) to identify the X Chromosome gene content, and find that the X Chromosome shows both complete dosage compensation in somatic tissues and an underrepresentation of testis-expressed genes. X-linked gene content fromL. migratoriais highly conserved across seven insect orders, namely Orthoptera, Odonata, Phasmatodea, Hemiptera, Neuroptera, Coleoptera, and Diptera, and the 800 Mb grasshopper X Chromosome is homologous to the fly ancestral X Chromosome despite 400 million years of divergence, suggesting either repeated origin of sex chromosomes with highly similar gene content, or long-term conservation of the X Chromosome. We use this broad conservation of the X Chromosome to test for temporal dynamics to Fast-X evolution, and find evidence of a recent burst evolution for new X-linked genes in contrast to slow evolution of X-conserved genes.
Generalized analytical description of relativistic strong-field ionization
Authors: Klaiber Michael , Hatsagortsyan Karen Z. , Keitel Christoph H.
Published: August 2024

A relativistic analytical theory of strong-field ionization applicable across the regimes of deep tunneling up to over-the-barrier ionization (OTBI) is developed, accounting also for the bound-state polarization and the Stark shift beyond perturbation theory. The latter improvement with respect to the state-of-the-art quasiclassical theory of Perelomov-Popov-Terent'ev (PPT) for strong-field ionization is essential to describe analytically the ionization in the OTBI regime and to resolve the order-of-magnitude discrepancy of the ionization yield in the relativistic regime with respect to PPT theory that has remained unexplained since the numerical result using the Klein-Gordon equation of Hafizi []. The predictions of the present relativistic model, in deviation to PPT theory, are shown to be observable using ultrashort laser pulses of relativistic intensities.

Published by the American Physical Society
2024
Circular motion of noncollinear spin textures in Corbino disks: Dynamics of Néel- versus Bloch-type skyrmions and skyrmioniums
Authors: de Assis Ismael Ribeiro , Mertig Ingrid , Göbel Börge
Published: August 2024

Magnetic skyrmions are nanoscale magnetic whirls that can be driven by currents via spin torques. They are promising candidates for spintronic devices such as the racetrack memory, where a motion along the uniform current is typically desired. However, for spin torque nano-oscillators in Corbino disks, the goal is to achieve a circular motion, perpendicular to the radially applied current. As we show, based on analytical calculations and micromagnetic simulations, Bloch skyrmions engage in a circular motion with frequencies in the MHz range when driven by spin-orbit torques. In contrast, Néel skyrmions get stuck at the edges of the disk. Our analysis reveals that the antagonistic dynamics between Bloch- and Néel-type magnetic textures arise from their helicity. Furthermore, we find that skyrmioniums, which are topologically trivial variations of skyrmions, move even faster and allow an increase in the current density without being pushed toward the edges of the disk. When driven by spin-transfer torques instead, Bloch and Néel skyrmions no longer exhibit different dynamics. Instead, they move along a circular trajectory due to the skyrmion Hall effect caused by their topological charge. Consequently, the topologically trivial skyrmioniums inevitably become trapped at the disk edge in this scenario. To provide a comprehensive understanding, our paper also examines currents applied tangentially, further enriching our insights into skyrmion dynamics and appropriate current injection methods for skyrmion-based devices.

Published by the American Physical Society
2024
Self-consistent theory of cosmic ray penetration into molecular clouds: Relativistic case
Authors: Chernyshov D. O. , Ivlev A. V. , Kiselev A. M.
Published: August 2024

We study penetration of interstellar cosmic rays (CRs) into molecular clouds surrounded by nonuniform diffuse envelopes. The present work generalizes our earlier model of CR self-modulation [Ivlev ; Dogiel ], in which the value for the envelope’s gas density where CRs excite MHD waves was treated as a free parameter. Now, we investigate the case where the density monotonically increases toward the center. Assuming that CRs are relativistic, we obtain a universal analytical solution which does not depend on the particular shape of gas distribution in the envelope, and self-consistently derive boundaries of the diffusion zone formed within the envelope, where CRs are scattered at the self-excited waves. The values of the gas density at the boundaries are found to be substantially smaller than those assumed in the earlier model, which leads to a significantly stronger modulation of penetrating CRs. We compute the impact of CR self-modulation on the gamma-ray emission and show that the results of our theoretical model are in excellent agreement with recent observations of nearby giant molecular clouds by Yang [].

Published by the American Physical Society
2024
Rigorous Holographic Bound on AdS Scale Separation
Authors: Perlmutter Eric
Published: August 2024

We give an elementary proof of the following property of unitary, interacting four-dimensional N=2 superconformal field theories: At large central charge c, there exist at least c single-trace, scalar superconformal primary operators with dimensions Δ≲c (suppressing multiplicative logarithmic corrections). This follows from a stronger, more refined bound on the spectral density in terms of the asymptotic growth rate of the central charge. The proof employs known results on the structure of Coulomb branch operators. Interpreted holographically, this bounds the possible degree of scale separation in semiclassical AdS5 half-maximal supergravity. In particular, the bulk must contain an infinite tower of charged scalar states of energies parametrically below the large black hole threshold EBH∼c. We address the extreme case of AdS5 pure supergravity, ruling it out as the asymptotic limit of certain sequences in theory space, though the general question remains open.

Published by the American Physical Society
2024
Non-Fermi-liquid behavior consistent with a preasymptotic disorder-tuned ferromagnetic quantum critical point in the heavy fermion system
CeTi1−xVxGe3
Authors: Lin R.-Z. , Jin H. , Klavins P. , Chen W.-T. , Chang Y.-Y. , Chung C.-H. , Taufour V. , Huang C.-L.
Published: August 2024

An investigation of the thermodynamic and electrical transport properties of the isoelectronic chemical substitution series CeTi1−xVxGe3 (CTVG) single crystals is reported. As x increases, the ferromagnetic (FM) transition temperature is suppressed, reaching absolute zero at the critical concentration x=0.4, where a non-Fermi-liquid low-temperature specific heat and electrical resistivity, as well as the hyperscaling of specific heat and magnetization, are found. Our study suggests the presence of an FM quantum critical point (QCP) in CTVG. The obtained critical exponents indicate that CTVG falls in the preasymptotic region of the disorder-tuned FM QCP predicted by the Belitz-Kirkpatrick-Vojta theory.

Published by the American Physical Society
2024
Charge separation at liquid interfaces
Authors: Majee Arghya , Weber Christoph A. , Jülicher Frank
Published: August 2024

We present a theory for phase-separated liquid coacervates with salt, taking into account spatial heterogeneities and interfacial profiles. We find that charged layers of alternating sign can form around the interface while the bulk phases remain approximately charge neutral. We show that the salt concentration regulates the number of layers and the amplitude of the layer's charge density and electrostatic potential. Such charged layers can either repel or attract single-charged molecules diffusing across the interface. Our theory could be relevant for artificial systems and biomolecular condensates in cells. Our work suggests that interfaces of biomolecular condensates could mediate charge-specific transport similar to membrane-bound compartments.

Published by the American Physical Society
2024
Development and performance simulations of a soft X-ray and XUV split-and-delay unit at beamlines FL23/24 at FLASH2 for time-resolved two-color pump–probe experiments
Authors: Dreimann Matthias , Wahlert Frank , Roling Sebastian , Treusch Rolf , Plönjes Elke , Zacharias Helmut
Published: August 2024

The split-and-delay unit (SDU) at FLASH2 will be upgraded to enable the simultaneous operation of two temporally, spatially and spectrally separated probe beams when the free-electron laser undulators are operated in a two-color scheme. By means of suitable thin filters and an optical grating beam path a wide range of combinations of photon energies in the spectral range from 150 eV to 780 eV can be chosen. In this paper, simulations of the spectral transmission and performance parameters of the filter technique are discussed, along with a monochromator with dispersion compensation presently under construction.