bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motor somatotopy impacts imagery strategy success in human intracortical brain-computer interfaces
Authors: Kunigk N.G. , Schone H.R. , Gontier C. , Hockeimer W. , Tortolani A.F. , Hatsopoulos N.G. , Downey J.E. , Chase S.M. , Boninger M.L. , Dekleva B.D. , Collinger J.L. 
Published: August 2024

AbstractThe notion of a somatotopically organized motor cortex, with movements of different body parts being controlled by spatially distinct areas of cortex, is well known. However, recent studies have challenged this notion and suggested a more distributed representation of movement control. This shift in perspective has significant implications, particularly when considering the implantation location of electrode arrays for intracortical brain-computer interfaces (iBCIs). We sought to evaluate whether the location of neural recordings from the precentral gyrus, and thus the underlying somatotopy, has any impact on the imagery strategies that can enable successful iBCI control. Three individuals with a spinal cord injury were enrolled in an ongoing clinical trial of an iBCI. Participants had two intracortical microelectrode arrays implanted in the arm and/or hand areas of the precentral gyrus based on presurgical functional imaging. Neural data were recorded while participants attempted to perform movements of the hand, wrist, elbow, and shoulder. We found that electrode arrays that were located more medially recorded significantly more activity during attempted proximal arm movements (elbow, shoulder) than did lateral arrays, which captured more activity related to attempted distal arm movements (hand, wrist). We also evaluated the relative contribution from the two arrays implanted in each participant to decoding accuracy during calibration of an iBCI decoder for translation and grasping tasks. For both task types, imagery strategy (e.g., reaching vs. wrist movements) had a significant impact on the relative contributions of each array to decoding. Overall, we found some evidence of broad tuning to arm and hand movements; however, there was a clear bias in the amount of information accessible about each movement type in spatially distinct areas of cortex. These results demonstrate that classical concepts of somatotopy can have real consequences for iBCI use, and highlight the importance of considering somatotopy when planning iBCI implantation.
Unveiling the Landscape of Reportable Genetic Secondary Findings in the Spanish Population: A Comprehensive Analysis Using the Collaborative Spanish Variant Server Database
Authors: Carmona Rosario , Pérez-Florido Javier , Roldán Gema , Loucera Carlos , Aquino Virginia , Toro-Barrios Noemí , Fernández-Rueda José L. , Bostlemann Gerrit , López-López Daniel , Ortuño Francisco M. , Morte Beatriz , Peña-Chilet María , Dopazo Joaquín ,   CSVS Crowdsourcing Group
Published: August 2024

ABSTRACTThe escalating adoption of Next Generation Sequencing (NGS) in clinical diagnostics reveals genetic variations, termed secondary findings (SFs), with health implications beyond primary diagnoses. The Collaborative Spanish Variant Server (CSVS), a crowdsourced database, contains genomic data from more than 2100 unrelated Spanish individuals. Following the American College of Medical genetics (ACMG) guidelines, CSVS was analyzed, identifying pathogenic or likely pathogenic variants in 78 actionable genes (ACMG list v3.1) to ascertain SF prevalence in the Spanish population. Among 1129 samples, 60 reportable SFs were found in 5% of individuals, impacting 32 ACMG-listed genes, notably associated with cardiovascular disease (59.4%), cancer (25%), inborn errors of metabolism (6.3%), and other miscellaneous phenotypes (9.4%). The study emphasizes utilizing dynamic population databases for periodic SF assessment, aligning with evolving ACMG recommendations. These findings illuminate the prevalence of significant genetic variants, enriching understanding of secondary findings in the Spanish population.
Within-host modelling of primaquine-induced haemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers
Authors: Watson James A , Mehdipour Parinaz , Moss Robert , Jittamala Podjanee , Zaloumis Sophie , Price David J , Dini Saber , Hanboonkunupakarn Borimas , Leungsinsiri Pawanrat , Poovorawan Kittiyod , Chotivanich Kesinee , Bancone Germana , Commons Robert J , Day Nicholas PJ , Pukrittayakamee Sasithon , Taylor Walter RJ , White Nicholas J , Simpson Julie A 
Published: August 2024

AbstractPrimaquine is the only widely available drug to prevent relapses ofPlasmodium vivaxmalaria. Primaquine is underused because of concerns over oxidant haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency. A pharmacometric trial showed that ascending-dose radical cure primaquine regimens causing ‘slow burn’ haemolysis were safe in G6PD deficient male volunteers. We developed and calibrated a within-host model of primaquine haemolysis in G6PD deficiency, using detailed serial haemoglobin and reticulocyte count data from 23 hemizygote deficient volunteers given ascending-dose primaquine (1,523 individual measurements over 656 unique timepoints). We estimate that primaquine doses of ∼0.75mg base/kg reduce the circulating lifespan of deficient erythrocytes by ∼30 days in individuals with common Southeast AsianG6PDvariants. We predict that 5mg/kg primaquine total dose can be administered safely to G6PD deficient individuals over 14 days with expected haemoglobin drops of 18 to 43% (2.7 to 6.5g/dL drop from a baseline of 15g/dL).
Nanoscale volumetric fluorescence imaging via photochemical sectioning
Authors: Wang Wei , Ruan Xiongtao , Liu Gaoxiang , Milkie Daniel E. , Li Wenping , Betzig Eric , Upadhyayula Srigokul , Gao Ruixuan 
Published: August 2024

AbstractOptical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structures with molecular contrast. However, existing high-resolution fluorescence microscopes have limited imaging depth, which prevents the study of whole-mount specimens without physical sectioning. To address this challenge, we developed “photochemical sectioning,” a spatially precise, light-based sample sectioning process. By combining photochemical sectioning with volumetric lattice light-sheet imaging and petabyte-scale computation, we imaged and reconstructed axons and myelination sheaths across entire mouse olfactory bulbs at nanoscale resolution. An olfactory-bulb-wide analysis of myelinated and unmyelinated axons revealed distinctive patterns of axon degeneration and de-/dysmyelination in the neurodegenerative mouse, highlighting the potential for peta- to exabyte-scale super-resolution studies using this approach.
The effect of parental conflict on imprinted genes inA. lyrata
Authors: Le Veve Audrey , İltaş Ömer , Dutheil Julien Y. , Lafon Placette Clément 
Published: August 2024

AbstractGenomic imprinting is a form of gene regulation resulting in the unequal expression of the two parental alleles. A common assumption is that parental conflict over resource allocation to the offspring promotes directional selection on imprinted genes, but so far, most studies addressing this question have focused on autogamous species, whose parental conflict is expected to be low. Moreover, parental conflict is expected to promote antagonistic coevolution between imprinted genes, but this has never been tested so far. To address these knowledge gaps, we searched for signals of selection on imprinted genes across the Brassicaceae family based on phylogenetic approaches. We then investigated and compared footprints of selection on imprinted genes in allogamous and autogamous populations ofArabidopsis lyrata. Finally, we investigated signals of coevolution across imprinted genes based on phylogenetics and genomics approaches. Overall, we did not find specific signals of selection on imprinted genes in the allogamous populations ofA. lyrata. Despite some exceptions, these genes were overall not associated with directional selection in allogamous populations and were poorly affected by the mating system, suggesting a limited role of parental conflict. Nevertheless, non-imprinted endosperm genes presented typical signals of balancing selection across the Brassicaceae, as expected in the case of unresolved intralocus sexual conflict. Finally, we found imprinted genes showing signals of recent coevolution, but not related to specific sites, suggesting that drivers other than protein interactions lead to the coevolution between imprinted genes.
Drug Metabolism and Transport Capacity of Endothelial Cells, Pericytes, and Astrocytes: Implications for CNS Drug Disposition
Authors: Wilkins Hannah N. , Knerler Stephen A. , Warshanna Ahmed , Ortiz Rodnie Colón , Haas Kate , Orsburn Benjamin C. , Williams Dionna W. 
Published: August 2024

SummaryTherapeutically targeting the brain requires interactions with endothelial cells, pericytes, and astrocytes at the blood brain barrier (BBB). We evaluated regional and cell-type specific drug metabolism and transport mechanisms using rhesus macaques andin vitrotreatment of primary human cells. Here, we report heterogenous distribution of representative drugs, tenofovir (TFV), emtricitabine (FTC), and their active metabolites, which cerebrospinal fluid measures could not reflect. We found that all BBB cell types possessed functional drug metabolizing enzymes and transporters that promoted TFV and FTC uptake and pharmacologic activation. Pericytes and astrocytes emerged as pharmacologically dynamic cells that rivaled hepatocytes and were uniquely susceptible to modulation by disease and treatment. Together, our findings demonstrate the importance of considering the BBB as a unique pharmacologic entity, rather than viewing it as an extension of the liver, as each cell type possesses distinct drug metabolism and transport capacities that contribute to differential brain drug disposition.
Root traits and tree functional groups determine variability in root exudation and N uptake rates in mature temperate trees
Authors: Oh Young E. , Midgley Meghan G. , McCormack M. Luke , Beidler Katilyn V. , McCall Marshall , Henderson Savannah , Braghiere Renato K. , Phillips Richard P. 
Published: August 2024

AbstractRoot exudation and nutrient uptake have profound impacts on soil biogeochemistry, yet quantification of these fluxes in mature trees is rare.We measured exudation and nitrogen (N) uptake rates of 11 tree species - gymnosperms and angiosperms associating with arbuscular mycorrhizal (AM) or ectomycorrhizal (EcM) fungi – at the Morton Arboretum, USA, to explore relationships between root traits, exudation and nitrogen uptake.Exudation rates were affected by phylogenetic group and mycorrhizal type, as EcM-gymnosperms exuded more carbon than the other three groups. Exudation correlated positively with specific root area and negatively with root tissue density. Nitrogen uptake did not differ between phylogenetic groups or mycorrhizal types. Root traits predicting N uptake varied with N form: root tissue density and phylogenetic group predicted ammonium uptake, whereas exudation and phylogenetic group predicted nitrate uptake. In root economic space, exudation and uptake aligned weakly with the fast side of the conservation gradient, though the two processes were not correlated.Our results indicate that exudation and N uptake are dynamic processes not predicted easily by species identity, plant functional groups or root traits. As such, incorporating these processes into trait frameworks and large-scale models may require ancillary information about the soil environment and whole-tree physiology.
The Paleozoic assembly of the holocephalian body plan far preceded post-Cretaceous radiations into the ocean depths
Authors: Brownstein Chase D. , Near Thomas J. , Dearden Richard P. 
Published: August 2024

AbstractAmong cartilaginous fishes,Holocephalirepresents the species-depauperate, morphologically conservative sister to sharks, rays, and skates and the last survivor of a once far greater Paleozoic and Mesozoic diversity. Currently, holocephalian diversity is concentrated in deep-sea species, suggesting this lineage might contain relictual diversity that persisted in the ocean depths. Yet, the relationships of living holocephalians to their extinct relatives and the timescale of diversification of living species remains unclear. Here, we reconstruct the evolutionary history of holocephalians using comprehensive morphological and DNA sequence datasets. Our results suggest that living holocephalians entered and diversified in deep (>1000 m) ocean waters after the Cretaceous-Paleogene mass extinction, contrasting with the hypothesis that this ecosystem has acted as a refugium of ancient cartilaginous fishes. These invasions were decoupled from the evolution of key features of the holocephalian body plan, including crushing dentition, a single frontal clasper, and holostylic jaw suspension, in the Paleozoic Era, and considerably postdated the appearance of the living familes by 150 million years ago during a major period of biotic turnover in oceans termed the Mesozoic Marine Revolution. These results clarify the origins of living holocephalians as the recent diversification of a single surviving clade among numerous Paleozoic lineages.
Assessing the ability of ChatGPT to extract natural product bioactivity and biosynthesis data from publications
Authors: Kalmer Thomas L. , Ancajas Christine Mae F. , Cheng Zihao , Oyedele Abiodun S. , Davis Hunter L. , Walker Allison S. 
Published: August 2024

AbstractNatural products are an excellent source of therapeutics and are often discovered through the process of genome mining, where genomes are analyzed by bioinformatic tools to determine if they have the biosynthetic capacity to produce novel or active compounds. Recently, several tools have been reported for predicting natural product bioactivities from the sequence of the biosynthetic gene clusters that produce them. These tools have the potential to accelerate the rate of natural product drug discovery by enabling the prioritization of novel biosynthetic gene clusters that are more likely to produce compounds with therapeutically relevant bioactivities. However, these tools are severely limited by a lack of training data, specifically data pairing biosynthetic gene clusters with activity labels for their products. There are many reports of natural product biosynthetic gene clusters and bioactivities in the literature that are not included in existing databases. Manual curation of these data is time consuming and inefficient. Recent developments in large language models and the chatbot interfaces built on top of them have enabled automatic data extraction from text, including scientific publications. We investigated how accurate ChatGPT is at extracting the necessary data for training models that predict natural product activity from biosynthetic gene clusters. We found that ChatGPT did well at determining if a paper described discovery of a natural product and extracting information about the product’s bioactivity. ChatGPT did not perform as well at extracting accession numbers for the biosynthetic gene cluster or producer’s genome although using an altered prompt improved accuracy.
BRACE: A novel Bayesian-based imputation approach for dimension reduction analysis of alternative splicing at single-cell resolution
Authors: Wen Sean 
Published: August 2024

AbstractBayesian approach is a powerful tool to solve challenging questions in life sciences. One such area of life sciences in which Bayesian approach has seen an increased utility in the recent years is single-cell biology. Alternative splicing represents an additional layer of complexity underlying gene expression profile that has the potential to reveal insights into the biological mechanisms underpinning heath and disease states. Dimension reduction analysis is the cornerstone of RNA-sequencing analysis and has the ability to guide selection of candidate biomarkers based on segregation of sample groups. Nevertheless, dimension reduction analysis at single- cell resolution remains a significant challenge for alternative splicing datasets, and therefore hitherto preclude the assessment of candidate isoforms. Here, we introduce BRACE (a Bayesian-based imputation approach for dimension Reduction Analysis of alternative splicing at single-CEll resolution). We demonstrated our Bayesian approach represents an improvement over existing methods for imputing missing percent spliced-in values, and subsequently applied our approach for the dimension reduction analysis of alternative splicing events at single-cell resolution. We further demonstrated the application of our Bayesian approach over a range of single-cell datasets with increasing complexity, namely cell populations that are transcriptomically distinct, similar, and heterogenous. We anticipate our approach to enable assessment and selection of cell state- or disease-specific biomarkers for downstream experimental validation.
Increased listening effort and cochlear neural degeneration underlie behavioral deficits in speech perception in noise in normal hearing middle-aged adults
Authors: Zink Maggie E. , Zhen Leslie , McHaney Jacie R. , Klara Jennifer , Yurasits Kimberly , Cancel Victoria , Flemm Olivia , Mitchell Claire , Datta Jyotishka , Chandrasekaran Bharath , Parthasarathy Aravindakshan 
Published: August 2024

AbstractMiddle-age is a critical period of rapid changes in brain function that presents an opportunity for early diagnostics and intervention for neurodegenerative conditions later in life. Hearing loss is one such early indicator linked to many comorbidities later in life. However, current clinical tests fail to capture hearing difficulties for ∼10% of middle-aged adults seeking help at hearing clinics. Cochlear neural degeneration (CND) could play a role in these hearing deficits, but our current understanding is limited by the lack of objective diagnostics and uncertainty regarding its perceptual consequences. Here, using a cross-species approach, we measured envelope following responses (EFRs) – neural ensemble responses to sound originating from the peripheral auditory pathway – in young and middle-aged adults with normal audiometric thresholds, and compared these responses to young and middle-aged Mongolian gerbils, where CND was histologically confirmed. We observed near identical changes in EFRs across species that were associated with CND. Perceptual effects measured as behavioral readouts showed deficits in the most challenging listening conditions and were associated with CND. Additionally, pupil-indexed listening effort increased even at moderate task difficulties where behavioral outcomes were matched. Our results reveal perceptual deficits in middle-aged adults driven by CND and increases in listening effort, which may result in increased listening fatigue and conversational disengagement.
Interferon-γ driven differentiation of monocytes into PD-L1+and MHC II+macrophages and the frequency of Tim-3+tumor-reactive CD8+T cells within the tumor microenvironment predict a positive response to anti-PD-1-based therapy in tumor-bearing mice
Authors: Gabrilo Jelena , Velde Sylvie Vande , Henin Coralie , Denanglaire Sébastien , Azouz Abdulkader , Boon Louis , Van den Eynde Benoit J. , Moser Muriel , Goriely Stanislas , Leo Oberdan 
Published: August 2024

ABSTRACTWhile immune checkpoint inhibitors have demonstrated durable responses in various cancer types, a significant proportion of patients do not exhibit favourable responses to these interventions. To uncover potential factors associated with a positive response to immunotherapy, we established a bilateral tumor model using P815 mastocytoma implanted in DBA/2 mice. In this model, only a fraction of tumor-bearing mice responds favourably to anti-PD-1 treatment, thus providing a valuable model to explore the influence of the tumor microenvironment (TME) in determining the efficacy of immune checkpoint blockade (ICB)-based immunotherapies. Moreover, this model allows for the analysis of a pretreatment tumor and inference of its treatment outcome based on the response observed in the contralateral tumor. Here, we demonstrated that tumor-reactive CD8+T cell clones expressing high levels of Tim-3 were associated to a positive anti-tumor response following anti-PD-1 administration. Our study also revealed distinct differentiation dynamics in tumor-infiltrating myeloid cells in responding and non-responding mice. An IFNγ-enriched TME appeared to promote the differentiation of monocytes into PD-L1posMHC IIhighcells in mice responding to immunotherapy. Monocytes present in the TME of non-responding mice failed to reach the same final stage of differentiation trajectory, suggesting that an altered monocyte to macrophage route may hamper the response to ICB. These insights will direct future research towards a temporal analysis of TAMs, aiming to identify factors responsible for transitions between differentiation states within the TME. This approach may potentially pave the way to novel strategies to enhance the efficacy of PD-1 blockade.
PixelPrint4D: A 3D printing method of fabricating patient-specific deformable CT phantoms for respiratory motion applications
Authors: Im Jessica Y. , Micah Neghemi , Perkins Amy E. , Mei Kai , Geagan Michael , Noël Peter B. 
Published: August 2024

AbstractAll in-vivo medical imaging is impacted by patient motion, especially respiratory motion, which has a significant influence on clinical workflows in diagnostic imaging and radiation therapy. Many technologies such as motion artifact reduction and tumor tracking algorithms have been developed to compensate for respiratory motion during imaging. To assess these technologies, respiratory motion phantoms (RMPs) are required as preclinical testing environments, for instance, in computed tomography (CT). However, current RMPs are highly simplified and do not exhibit realistic tissue structures or deformation patterns. With the rise of more complex motion compensation technologies such as deep learning-based algorithms, there is a need for more realistic RMPs. This work introduces PixelPrint4D, a 3D printing method designed to fabricate lifelike, patient-specific deformable lung phantoms for CT imaging. The phantom demonstrated accurate replication of patient lung structures, textures, and attenuation profiles. Furthermore, it exhibited accurate nonrigid deformations, volume changes, and attenuation changes under compression. PixelPrint4Denables the production of highly realistic RMPs, surpassing existing models to offer more robust testing environments for a diverse array of novel CT technologies.