bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of high-resolution perfusion imaging using Arterial Spin Labelling MRI at 3 Tesla
Authors: Kashyap Sriranga , Oliveira ĺcaro Agenor Ferreira , Uludağ Kâmil 
Published: August 2023

ABSTRACTCerebral blood flow (CBF) is a critical physiological parameter of brain health and it can be non-invasively measured with arterial spin labelling (ASL) MRI. In this study, we evaluated and optimised whole-brain, high-resolution ASL as an alternative to the low-resolution ASL employed in the routine assessment of CBF in both healthy participants and patients. Two high-resolution protocols (i.e., pCASL and FAIR-Q2TIPS (PASL) with 2 mm isotropic voxels) were compared to a default clinical pCASL protocol (3.4 × 3.4 × 4mm3), all of whom had an acquistion time of ≈ 5 min. We assessed the impact of high-resolution acquisition on reducing partial voluming and improving sensitivity to the perfusion signal, and evaluated the effectiveness of z-deblurring on the ASL data. We compared the quality of whole-brain ASL acquired using three available head coils with differing number of receive channels (i.e., 20, 32 and 64 ch). We found using higher coil counts (32 and 64 ch coils as compared to 20 ch) offer improved SNR and improved acceleration capabilities that are beneficial for ASL imaging at 3T. The inherent reduction in partial voluming effects with higher resolution acquisitions improves the resolving power of perfusion without impacting sensitivity. In conclusion, our results suggest that high-resolution ASL (2 - 2.5 mm isotropic) has the potential to become a new standard for perfusion imaging at 3 T and increase its adoption into clinical research and cognitive neuroscience applications.
Self-regulation of attention in children in a virtual classroom environment: a feasibility study
Authors: Guedj Carole , Tyrand Rémi , Badier Emmanuel , Planchamp Lou , Stringer Madison , Zimmermann Myriam Ophelia , Férat Victor , Leuchter Russia Ha-Vinh , Grouiller Frédéric 
Published: August 2023

ABSTRACTAttention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. When this sustained ability to direct attention is impaired, individuals face significant challenges in everyday life. This is the case for children with Attention Deficit Hyperactivity Disorder (ADHD), a complex neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are currently the most effective treatment for ADHD, they often come with unwanted side effects, and sustaining the benefits can be difficult for many children. Therefore, it is imperative to explore non-pharmacological treatments that offer longer-lasting outcomes. Here, we proposed a groundbreaking protocol that combines electroencephalography-based neurofeedback (EEG-NFB) with virtual reality (VR) as an innovative approach to treating attention deficits. By integrating a virtual classroom environment, we aimed to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrated the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in children diagnosed with ADHD. Encouragingly, the preliminary findings indicated high engagement rates and positive feedback from the children participating in the study. Additionally, the pre-and post-protocol assessments using EEG and fMRI recordings appeared to converge towards an improvement in attentional function. Although further validation is required to establish the efficacy of the proposed protocol, it represents a significant advancement in the field of neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD.
Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity
Authors: Shi Wenqiang , Liu Nan , Liu Zexin , Yang Yuqi , Zeng Qiongya , Wang Yang , Song Luyao , Zhu Jianwei , Lu Huili 
Published: August 2023

AbstractImmunocytokines, such as anti-PD-L1/IL-15, have shown promising efficacy in preclinical studies, but their clinical development still faces severe safety concerns, with the problem not easily overcome by simply reducing the cytokine activity. We proposed a next-generation immunocytokine concept of designing a tumor-conditional anti-PD-L1/IL-15 prodrug (LH05), which innovatively masks IL-15 with steric hindrance of its flanking moieties of anti-PD-L1 and IL-15Rα-sushi domain. The design successfully attenuated the ‘cytokine sink’ effect of IL-15 and resulted in a significantly reduced systemic toxicity when compared to wild-type anti-PD-L1/IL-15. LH05 would be specifically cleaved in the tumor microenvironment (TME) to release the active IL-15/IL-15Rα-sushi domain (ILR) in a proteolytic cleavage-dependent manner and exhibited potent antitumor effects in mouse syngeneic models. Mechanistically, the antitumor efficacy of LH05 was dependent on both innate and adaptive immunity, which altered the TME to Th1-type by recruiting and stimulating both NK and CD8+T cells and fired up cold tumors. LH05 also showed superior efficacy in restoring immunotherapy response in a refractory U251 xenograft model. Collectively, we introduced a novel next-generation immunocytokine strategy for tumor immunotherapy, contributing to the establishment of optimal treatment for patients with resistance to immune checkpoint inhibitors or cold tumors.
Hypothalamic CRH Neurons Modulate Sevoflurane Anesthesia and The Post-anesthesia Stress Responses
Authors: Jiang Shan , Chen Lu , Qu Wei-Min , Huang Zhi-Li , Chen Chang-Rui 
Published: August 2023

AbstractGeneral anesthesia is an indispensable procedure necessary for safely and compassionately administering a significant number of surgical procedures and invasive diagnostic tests. However, the undesired stress response associated with general anesthesia (GA) causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRHneurons), is discovered to play a role in regulating sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVHCRHneurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVHCRHneurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRHneurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVHCRHneurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.Impact statementDiscovery of critical brain nodes regulating sevoflurane general anesthesia and the post-anesthesia stress responses.
Highly scalable and standardized organ-on-chip platform with TEER for biological barrier modeling
Authors: Nguyen Hoang-Tuan , Rissanen Siiri-Liisa , Peltokangas Mimosa , Laakkonen Tino , Kettunen Jere , Barthod Lara , Sivakumar Ragul , Palojärvi Anniina , Junttila Pauliina , Talvitie Jussi , Bassis Michele , Nickels Sarah L. , Schwamborn Jens C. , Mosser Sebastien , Singh Prateek 
Published: August 2023

AbstractThe development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS).Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods.Together with automated confocal imaging and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine’s efficacy, toxicity, and permeability under physiological conditions.
The multi-Siglec inhibitor AL009 reprograms suppressive macrophages and activates innate and adaptive tumor immunity
Authors: Nalle Sam C. , Lam Helen , Leung Ling , Liang Spencer , Maslyar Daniel , Rosenthal Arnon 
Published: August 2023

AbstractSialic acid–binding immunoglobulin-type lectins (Siglecs) are cell surface receptors that regulate innate and adaptive immunity, with inhibitory Siglecs promoting immune tolerance. In the tumor microenvironment, overexpression of sialic acid glycans exploits inhibitory Siglec signaling, leading to a cancer-permissive phenotype. AL009 is an engineered Siglec-9-Fc fusion molecule that functions as a sialic acid trap and reprograms suppressive macrophages to activate an anti-tumor immune response. AL009 treatment of human myeloid-derived suppressor cells, an in vitro model of tumor-associated macrophages, resulted in an increase in proinflammatory cytokines and chemokines, changes in cell surface markers, and potent relief of T cell inhibition in a co-culture assay. In syngeneic mouse (Mus musculus) tumor models, AL009 engineered with a mouse Fc (AL009m) reduced tumor growth as a monotherapy and in combination with the checkpoint inhibitor anti-PD-L1. In addition, AL009m synergized with the tumor-targeting therapy anti-TRP1 to reduce lung nodules in the B16-F10 intravenous model. Pharmacodynamic marker analysis in syngeneic and humanized mouse tumor models supported an AL009 mechanism of action based on reprogramming tumor-associated macrophages and enhanced T cell activation. Future clinical studies are warranted to further elucidate the safety and efficacy of AL009.
CellGO: A novel deep learning-based framework and webserver for cell type-specific gene function interpretation
Authors: Li Peilong , Wei Junfeng , Zhu Ying 
Published: August 2023

AbstractInterpreting the function of genes and gene sets identified from omics experiments remains a challenge, as current pathway analysis tools often fail to account for complex interactions across genes and pathways under specific tissues and cell types. We introduce CellGO, a tool for cell type-specific gene functional analysis. CellGO employs a deep learning model to simulate signaling propagation within a cell, enabling the development of a heuristic pathway activity measuring system to identify cell type-specific active pathways given a single gene or a gene set. It is featured with additional functions to uncover pathway communities and the most active genes within pathways to facilitate mechanistic interpretation. This study demonstrated that CellGO can effectively capture cell type-specific pathways even when working with mixed cell-type markers. CellGO’s performance was benchmarked using gene knockout datasets, and its implementation effectively infers the cell type-specific pathogenesis of risk genes associated with neurodevelopmental and neurodegenerative disorders, suggesting its potential in understanding complex polygenic diseases. CellGO is accessible through a python package and a four-mode web interface for interactive usage with pretrained models on 71 single-cell datasets from human and mouse fetal and postnatal brains.
SCD inhibition preferentially eradicates AML displaying high de novo fatty acid desaturation and synergizes with chemotherapy
Authors: Dembitz Vilma , Lawson Hannah , Burt Richard , Philippe Céline , James Sophie C. , Atkinson Samantha , Durko Jozef , Wang Lydia M. , Campos Joana , Magee Aoife M. S. , Woodley Keith , Austin Michael , Rio-Machin Ana , Casado-Izquierdo Pedro , Bewicke-Copley Findlay , Blanco Giovanny Rodriguez , Martins Diego Pereira , Oudejans Lieve , Boet Emeline , von Kriegsheim Alex , Schwaller Juerg , Finch Andrew J. , Patel Bela , Sarry Jean-Emmanuel , Tamburini Jerome , Schuringa Jan Jacob , Hazlehurst Lori , Copland John A. , Yuneva Mariia , Peck Barrie , Cutillas Pedro , Fitzgibbon Jude , Rouault-Pierre Kevin , Kranc Kamil , Gallipoli Paolo 
Published: August 2023

AbstractIdentification of specific and therapeutically actionable vulnerabilities in acute myeloid leukaemia (AML) is needed to improve patients’ outcome. These features should be ideally present in many patients independently of mutational background. Here we identifyde novofatty acid (FA) desaturation, specifically stearoyl-CoA desaturase (SCD) inhibition, as a therapeutic vulnerability across multiple AML modelsin vitroandin vivo. We use the novel clinical grade SCD inhibitor SSI-4 to show that SCD inhibition induces AML cell deathviapleiotropic effects, and sensitivity is based on their dependency on FA desaturation regardless of mutational profile. SSI-4 efficacy is enhanced by driving FA biosynthesisin vitrowhile stroma confers protective effects that extend toin vivomodels. SCD inhibition increases DNA damage and its combination with standard DNA damage-inducing chemotherapy prolongs survival in aggressive murine AML models. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their therapeutic potential.One Sentence SummarySCD inhibition is toxic to AML cells with high rates of fatty acid desaturation and in combination with chemotherapy prolongs survival in murine AML models.
Constraint and innovation in color evolution among species and among plumage patches in five avian radiations
Authors: Eliason Chad M. , Marcondes Rafael S. , Eaton Muir D. , Maia Rafael , Burns Kevin J. , Shultz Allison J. 
Published: August 2023

AbstractUnderstanding the causes and limits of phenotypic diversification remains a key challenge in evolutionary biology. Color patterns are some of the most diverse phenotypes in nature. In birds, recent work within families has suggested that plumage complexity might be a key innovation driving color diversity. Whether these patterns hold at larger taxonomic scales remains unknown. Here, we assemble a large database of UV-Vis spectral data across five diverse clades of birds (45791 spectra, 1135 species). Using multivariate phylogenetic comparative methods, we compare evolutionary rates and color space occupancy (i.e., quantification of observed colors) among these clades. Novel color-producing mechanisms have enabled clades to occupy new regions of color space, but using more coloration mechanisms did not result in overall more color space occupancy. Instead, the use of more color-producing mechanisms resulted in faster rates of color evolution and less integrated color among plumage regions. Flexible Bayesian modeling further allowed us to assess the relationship between interpatch and interspecific directions of color variation. We find that interpatch variation generally diverges from interspecies cladewise trends in males but not females, suggesting developmental or selective constraints operating in females across evolutionary scales. By comparing rates among clades and assessing both interpatch and interspecies color variation, we reveal how innovations and constraints operate across evolutionary and developmental scales.
Pathogen lifestyle determines host genetic signature of quantitative disease resistance loci in oilseed rape (Brassica napus)
Authors: Jacott Catherine N. , Schoonbeek Henk-jan , Sidhu Gurpinder Singh , Steuernagel Burkhard , Kirby Rachel , Zheng Xiaorong , von Tiedermann Andreas , Macioszek Violetta K. , Kononowicz Andrzej K. , Fell Heather , Fitt Bruce D.L. , Mitrousia Georgia K. , Stotz Henrik U. , Ridout Christopher J. , Wells Rachel 
Published: August 2023

SummaryCrops are affected by several pathogens, but these are rarely studied in parallel to identify common and unique genetic factors controlling diseases. Broad-spectrum quantitative disease resistance (QDR) is desirable for crop breeding as it confers resistance to several pathogen species.Here, we use associative transcriptomics (AT) to identify candidate gene loci associated withBrassica napusQDR to four contrasting fungal pathogens:Alternaria brassicicola,Botrytis cinerea,Pyrenopeziza brassicaeandVerticillium longisporum.We did not identify any loci associated with broad-spectrum QDR to fungal pathogens with contrasting lifestyles. Instead, we observed QDR dependent on the lifestyle of the pathogen—hemibiotrophic and necrotrophic pathogens had distinct QDR responses and associated loci, including some loci associated with early immunity. Furthermore, we identify a genomic deletion associated with resistance toV. longisporumand potentially broad-spectrum QDR.This is the first time AT has been used for several pathosystems simultaneously to identify host genetic loci involved in broad-spectrum QDR.We highlight candidate loci for broad-spectrum QDR with no antagonistic effects on susceptibility to the other pathogens studies as candidates for crop breeding.
Seasonally migratory songbirds have different historic population size characteristics than resident relatives
Authors: Winker Kevin , Delmore Kira 
Published: August 2023

AbstractModern genomic methods enable estimation of a lineage’s long-term effective population sizes back to its origins. This ability allows unprecedented opportunities to determine how adoption of a major life-history trait affects lineages’ populations relative to those without the trait. We used this novel approach to study the population effects of the life-history trait of seasonal migration across evolutionary time. Seasonal migration is a common life-history strategy, but its effects on long-term population sizes relative to lineages that don’t migrate are largely unknown. Using whole-genome data, we estimated effective population sizes over millions of years in closely related seasonally migratory and resident lineages in a group of songbirds. Our main predictions were borne out: Seasonal migration is associated with larger effective population sizes (Ne), greater long-term variation inNe, and a greater degree of initial population growth than among resident lineages. Initial growth periods were remarkably long (0.63-4.29 Myr), paralleling the expansion and adaptation phases of taxon cycles, a framework of lineage expansion and eventual contraction over time encompassing biogeography and evolutionary ecology. Heterogeneity among lineages is noteworthy, despite geographic proximity (including overlap) and close relatedness. Seasonal migration imbues these lineages with fundamentally different population size attributes through evolutionary time compared to closely related resident lineages.
Lack of early animal fossils: insights from taphonomic experiments on placozoans and their traces
Authors: Naimark E.B. , Lyupina Yu.V. , Nikitin M.A. , Finoshin A.D. 
Published: August 2023

ABSTRACTPlacozoa are simple two-layered multicellular animals. Can such a simple animal preserve in the fossil record? The results of our taphonomic experiments showed that it is chemically possible; however, the chances of the presevation are negligible for two reasons. Firstly, the resistance of livingTrichoplaxto lethal factors turned out to be quite high. Secondly, post-mortem changes in the body ofTrichoplaxpreclude preservation. We observed these changes for the first time: their bodies immediately disintegrated into a cloud of individual dead cells, apparently unrecognizable in the fossil record. We hypothesized that the absence of a basement membrane, which unites each cell layer into the epithelia, is a key factor in this dramatic disintegration. This hypothesis adds an option to the explainations of the gap between the time of emergence of metazoan body fossils and the reconstructed time of metazoan divergence from a single-celled ancestor. However, it is theoretically possible to find ichnofossils ofTrichoplax-like locomotion. For the first time, we observed traces ofTrichoplaxon a soft substrate and identified a previously unknown type of traces. They were 3D chains of compacted round lumps of the substrate, similar in some features to the Precambrian meniscus ichnofossils.
An Integrated Platform for in vivo Electrophysiology in Spatial Cognition Experiments
Authors: Brea Guerrero A. , Oijala M. , Moseley S. C. , Tang T. , Fletcher F. , Zheng Y. , Sanchez L.M. , Clark B. J. , Mcnaughton B. L. , Wilber A. A. 
Published: August 2023

AbstractSpatial cognition research requires behavioral paradigms that can distinguish between different navigational elements, such as allocentric (map-like) navigation and egocentric (e.g., body centered) navigation. To fill this need, we developed a flexible experimental platform that can be quickly modified without the need for significant changes to software and hardware. In this paper, we present this inexpensive and flexible behavioral platform paired with software which we are making freely available.Our behavioral platform serves as the foundation for a range of experiments, and though developed for assessing spatial cognition, it also has applications in the non-spatial domain of behavioral testing. There are two components of the software platform, ‘Maze’ and ‘Stim Trigger’. Both programs can work in conjunction with electrophysiology acquisition systems, allowing for precise time stamping of neural events with behavior. The Maze program includes functionality for automatic reward delivery based on user defined zones. ‘Stim Trigger’ permits control of brain stimulation via any equipment that can be paired with an Arduino board. We seek to share our software and leverage the potential by expanding functionality in the future to meet the needs of a larger community of researchers.Significance StatementThis paper presents an innovative and cost-effective behavioral platform designed to distinguish between different navigational elements, addressing the crucial need for better spatial cognition research paradigms. The platform’s flexibility allows for quick modifications without major software or hardware changes. Additionally, the freely available software, comprising ‘Maze’ and ‘Stim Trigger’ components, enables precise time stamping of neural events with behavior, while facilitating automatic reward delivery and brain stimulation control. Beyond spatial cognition assessment, the platform’s adaptability extends to non-spatial behavioral testing. By openly sharing this software, the authors aim to foster collaboration and encourage future developments, promoting its application to a broader community of researchers. This platform represents a significant advancement in spatial cognition research and behavioral experimentation methods.