bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-wide neural recordings in mice navigating physical spaces enabled by a cranial exoskeleton
Authors: Hope James , Beckerle Travis , Cheng Pin-Hao , Viavattine Zoey , Feldkamp Michael , Fausner Skylar , Saxena Kapil , Ko Eunsong , Hryb Ihor , Carter Russell , Ebner Timothy , Kodandaramaiah Suhasa 
Published: June 2023

ABSTRACTComplex behaviors are mediated by neural computations occurring throughout the brain. In recent years, tremendous progress has been made in developing technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales. However, these technologies are primarily designed for studying the mammalian brain during head fixation – wherein the behavior of the animal is highly constrained. Miniaturized devices for studying neural activity in freely behaving animals are largely confined to recording from small brain regions owing to performance limitations. We present a cranial exoskeleton that assists mice in maneuvering neural recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. Force sensors embedded within the headstage are used to detect the mouse’s milli-Newton scale cranial forces which then control the x, y, and yaw motion of the exoskeleton via an admittance controller. We discovered optimal controller tuning parameters that enable mice to locomote at physiologically realistic velocities and accelerations while maintaining natural walking gait. Mice maneuvering headstages weighing up to 1.5 kg can make turns, navigate 2D arenas, and perform a navigational decision-making task with the same performance as when freely behaving. We designed an imaging headstage and an electrophysiology headstage for the cranial exoskeleton to record brain-wide neural activity in mice navigating 2D arenas. The imaging headstage enabled recordings of Ca2+activity of 1000s of neurons distributed across the dorsal cortex. The electrophysiology headstage supported independent control of up to 4 silicon probes, enabling simultaneous recordings from 100s of neurons across multiple brain regions and multiple days. Cranial exoskeletons provide flexible platforms for largescale neural recording during the exploration of physical spaces, a critical new paradigm for unraveling the brain-wide neural mechanisms that control complex behavior.
New genomic techniques, old divides: stakeholder attitudes towards new biotechnology regulation in the EU and UK
Authors: Menary Jonathan , Fuller Sebastian S. 
Published: June 2023

AbstractThe European Union and United Kingdom are in the process of establishing new regulation regarding the use of new genomic techniques in crop and animal breeding. As part of this process, consultations have been launched to understand the views of stakeholders and the wider public towards the use of new genomic techniques in plant and animal breeding. The responsible research and innovation framework emphasises the importance of dialogue between technology developers and stakeholders, including the public, but what are the opinions of stakeholders towards the regulation of NGTs in Europe and do they view these consultations as opportunities to engage with technology governance?We conducted semi-structured interviews with experts from a range of agri-food stakeholder groups in the European Union and United Kingdom to understand current attitudes towards new biotechnology regulation, how they viewed the process of consultation in both places and what influence they felt they had in shaping regulations. We found that the discussion is similar in both EU and UK, with predictable and fixed opinions determined by attitudes towards the perceived risks associated with direct mutagenesis.Both UK and EU consultations were considered to have the same weaknesses and stakeholders discussed a desire for more dialogic forms of engagement. We highlight several options for new forms of involvement in biotechnology regulation by exploring relevant responsible research and innovation literature.
Photosynthetic CO2response characteristics in canopy ofLarix principis-rupprechtiiMayr. tree and practicability of three Models
Authors: Ma Xuemei , Wu Chaofeng , Liu Qiang , Huang Xuanrui 
Published: June 2023

AbstractAccurately predicting the crown photosynthesis of trees is important to understand the tree growth status and carbon circle in terrestrial ecosystem. However, modeling the photosynthetic carbon dioxide (CO2) response curves for individual tree are still challenging due to the complex canopy structure and changeable environmental conditions. Therefore, taking 16-old yearLarix principis-rupprechtii Mayr. as the research material, the dynamic CO2response models of photosynthesis, including rectangular hyperbolic model (RHM), the non-rectangular hyperbolic model (NRHM) and the modified rectangular hyperbolic model (MRHM), were used to simulate CO2response curves of the crown. The fitting accuracy of the models depend on the comparison of determinants coefficients (R2), mean square errors (MSE) and Akaike information criterion (AIC). The results showed that the mean value ofR2(R2=0.9939 ∼ 0.9964) of MRHM was the highest, whereasMSEvalue (MSE=0.2185∼0.2627) andAICvalue (AIC=-13.18∼-8.03) were the lowest. The CO2-saturated gross photosynthetic rate (Amax) and the saturation point (CiSP) obtained by MRHM were closest to the measured value respectively. Therefore, the MRHM fitted the CO2response data well, and calculated the photosynthetic parameters directly and accurately, the fitted result showed α,Amax,CiSP, CiCPandRPwere 0.04, 7.51 μmol·m-2s-1, 938.97 μmol·m-2, 67.54 μmol·m-2and 0.60 μmol·m-2s-1, respectively. In addition, the difference on the photosynthetic CO2response parameters values showed somewhat among different layers and orientations. In all, all data suggested that the modified rectangular hyperbolic model (MRHM) was an ideal model to fit the crown photosynthetic CO2response curve ofLarix principis-rupprechtiiMayr. These results are of great significance for parameter calibration of photosynthetic model and robust prediction of photosynthetic response in forest.
Investigating miRNA signatures in metastatic breast cancer: Anin-silicoanalysis
Authors: Harini Lakshminarasimhan , Madhav Lekshmi , Srivastava Sweta , Ramaswamy Gopalakrishna , Ramesh Rakesh 
Published: June 2023

ABSTRACTmiRNAs are small non-coding RNAs that regulate most cellular processes. Tumorigenesis disrupts the normal balance in the cell, which leads to changes in the cell cycle, cell signalling, activation of growth factors, miRNA deregulation, etc. Thus, the variations in miRNA expression between normal and tumor stages can be used to predict, diagnose, detect and identify different cancer stages, thereby suggesting the potential use of the miRNAs as biomarkers or potential therapeutic targets for cancer.In this study we aim to identify differentially expressed miRNAs which could serve as potential biomarkers or therapeutic targets for breast cancer.Microarray-based expression analysis was performed on tissue samples from patients with early and locally advanced breast cancer and nCounter analysis was performed to detect differentially expressed miRNA. Additionally, functional enrichment analysis, miRNA linked gene prediction, and in silico analysis for miRNA expression in cancer databases were carried out. This analysis revealed increased expression of Hsa-miR-199a and b. Further these miRs had increased expression levels across various cancer. Importantly, genes such as CALR, SSR2, and YWHAZ predicted as miR’s target were highly expressed in breast cancer. However, these genes lack therapeutic drugs targeting them. Overall, our study identified previously unexplored miRNAs and their gene targets, which could be exploited as potential targets for future therapeutic interventions.
Large vessel occlusions of milder severity show better collaterals and reduced harm from thrombectomy transfer delays
Authors: Rowling Hannah , Italiano Dominic , Churilov Leonid , Palanikumar Logesh , Harvey Jackson , Kleinig Timothy , Parsons Mark , Mitchell Peter , Davis Stephen , Kruyt Nyika , Campbell Bruce , Zhao Henry 
Published: June 2023

AbstractBackground and PurposePatients with large vessel occlusion (LVO) stroke of milder baseline clinical severity are often missed by pre-hospital severity-based triage tools. We examined whether these patients had differences in 1) markers of collateral circulation and 2) the relative harm of transfer delays on outcome, compared to patients with clinically more severe baseline deficits.MethodsRegistry data from two large Australian thrombectomy centers was used to identify all directly presenting and transferred LVO patients undergoing endovascular thrombectomy, divided into those with milder baseline deficits (NIHSS <10) and severe baseline deficits (NIHSS ≥10). Baseline CT-perfusion markers of collateral circulation and the association between transfer status and functional outcome (using the 90-day modified Rankin Scale) were compared.ResultsOf 1210 included LVO patients, 273 (22.6%) had milder severity. Milder LVO patients showed smaller median ischemic core volumes (12.6 [IQR 0.0-17.9] vs 27.5 [IQR 6.5-37.1] mL, p<0.001)), higher median perfusion mismatch ratio (148.3 [IQR 5.0-500.0] vs 66.2 [IQR 3.6-17.2], p<0.001) and lower median hypoperfusion intensity ratio (0.25 [IQR 0.18-0.38] vs 0.40 [IQR 0.22-0.57], p<0.001). Transferred patients had a lower odd of excellent outcome than primary presenters, when deficits were severe deficits (aOR 0.759 [95% CI 0.576-0.999]) but not when deficits were milder (aOR 1.357 [95% CI 0.764-2.409], pinteraction=0.122).ConclusionsPatients with LVO stroke of milder clinical severity have significantly better imaging markers of collateral circulation compared to high-severity patients. Despite high rates of thrombolytics, secondary transfer to thrombectomy-center was only associated with poorer 90-day functional outcomes in higher-severity patients. Failure of pre-hospital screening tools to detect lower-severity LVO patients for immediate pre-hospital bypass to a thrombectomy center may not deleteriously affect their outcome.
Lesion network localization of a stable personality trait
Authors: Palm Stephan T. , Khosravani Sanaz , Campanella Fabio , Cohen Alexander L. , Drew William , Fabbro Franco , Pottanat Roger , Urgesi Cosimo , Ferguson Michael A. , Siddiqi Shan H. 
Published: June 2023

AbstractObjectiveTo identify a convergent neuroanatomical substrate for novelty seeking (NS), a stable personality trait, which could serve as a therapeutic target for transcranial magnetic stimulation (TMS).MethodsWe analyzed two independent datasets (total n=136) in which the Temperament and Character Inventory (TCI) was used to document alterations across 7 stable personality traits before and after brain lesions surgically induced by glioma resection. Using lesion network mapping, we examined whether alterations in NS were causally associated with lesions to specific brain networks. We assessed for strength of replication across datasets and specificity against other personality traits.ResultsLesion locations that are linked to NS map to a common brain with its largest cluster in the dorsal cingulate. This map was specific to NS relative to other personality traits and overlapped with prior published neuroimaging findings related to the term “novelty”. Utilizing a pre-computed connectome, we also derived a map highlighting potential targets for non-invasive brain stimulation that may alter this stable personality trait.ConclusionsWe derived and cross-validated a brain network that is functionally connected to lesions that are causally responsible for the stable personality trait “novelty seeking”. Lesions to this network were associated with changes in NS. This includes a superficial node within the dorsolateral prefrontal cortex that may serve as a promising TMS target to modulate or protect against abnormal NS.
Differential usage of DNA modifications in neurons, astrocytes, and microglia
Authors: Tooley Kyla B. , Chucair-Elliott Ana J. , Ocañas Sarah R. , Machalinski Adeline H. , Pham Kevin D. , Stanford David R. , Freeman Willard M. 
Published: June 2023

AbstractBackgroundCellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. This is especially true as for DNA modifications where most data are derived from bisulfite sequencing that cannot differentiate between DNA methylation and hydroxymethylation. In this study, we developed anin vivotagging mouse model (Camk2a-NuTRAP) for paired isolation of neuronal DNA and RNA without cell sorting and then used this model to assess epigenomic regulation of gene expression between neurons and glia.ResultsAfter validating the cell-specificity of the Camk2a-NuTRAP model, we performed TRAP-RNA-Seq and INTACT whole genome oxidative bisulfite sequencing to assess the neuronal translatome and epigenome in the hippocampus of young mice (3 months old). These data were then compared to microglial and astrocytic data from NuTRAP models. When comparing the different cell types, microglia had the highest global mCG levels followed by astrocytes and then neurons, with the opposite pattern observed for hmCG and mCH. Differentially modified regions between cell types were predominantly found within gene bodies and distal intergenic regions, with limited differences occurring within proximal promoters. Across cell types there was a negative correlation between DNA modifications (mCG, mCH, hmCG) and gene expression at proximal promoters. In contrast, a negative correlation of mCG with gene expression within the gene body while a positive relationship between distal promoter and gene body hmCG and gene expression was observed. Furthermore, we identified a neuron-specific inverse relationship between mCH and gene expression across promoter and gene body regions.ConclusionsIn this study, we identified differential usage of DNA modifications across CNS cell types, and assessed the relationship between DNA modifications and gene expression in neurons and glia. Despite having different global levels, the general modification-gene expression relationship was conserved across cell types. The enrichment of differential modifications in gene bodies and distal regulatory elements, but not proximal promoters, across cell types highlights epigenomic patterning in these regions as potentially greater determinants of cell identity.
DanioCTC: Injection of circulating tumor cells from metastatic breast cancer patients in zebrafish xenografts for analysis of metastasis
Authors: Reinhardt Florian , Coen Luisa , Rivandi Mahdi , Franken André , Sawitning Ayu Setyono Eunike , Lindenberg Tobias , Eberhardt Jens , Fehm Tanja , Niederacher Dieter , Knopf Franziska , Neubauer Hans 
Published: June 2023

AbstractCirculating tumor cells (CTCs) are considered as metastatic precursor cells, and zebrafish xenografts provide anin vivomodel to study cancer cell spread. Currently, the low number of patient-derived CTCs limits their analysis in animal models. We present DanioCTC, a xenograft workflow for injecting CTCs from metastatic breast cancer (MBC) patients into zebrafish embryos to study cell disseminationin vivo. The study successfully adapts existing workflows and combines diagnostic leukapheresis (DLA), the Parsortix microfluidic system, flow cytometry, and the automated cell micromanipulator CellCelector setup to enrich and isolate MBC-derived CTCs and to finally inject them into Zebrafish embryos, where their dissemination was tracked up to 3 days post-injection. MDA-MB-231 cells were used as a standard xenotransplantation control, and these cells were frequently found in the head and blood-forming regions of the tail. Using DLA aliquots spiked with MBA-MB-231 cells, the newly established DanioCTC workflow confirmed the dissemination of MDA-MB-231 cells into these regions. CTCs from an MBC patient were then enriched by DLA, Parsortix, and flow cytometry, isolated with the CellCelectorTM and xenografted into zebrafish embryos. CTCs were mainly detected in the head and trunk, unlike MDA-MB-231 cells, which were present in the head and tail. DanioCTC presents a significant breakthrough in the use of zebrafish embryos as a model to study CTC disseminationin vivo, which can be used for patient-derived CTCs instead of cell culture-derived cancer cells as a crucial step towards understanding the biology of metastatic breast cancer.Statement of significanceDanioCTC is a novel workflow to inject patient-derived CTCs into zebrafish, enabling studies on CTC dissemination and personalized treatmentin vivo, therefore advancing our toolkit to fight metastatic cancer.
Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition
Authors: Alegre-Zurano Laia , Caceres-Rodriguez Alba , Berbegal-Sáez Paula , Lassalle Olivier , Manzoni Olivier , Valverde Olga 
Published: June 2023

ABSTRACTBackgroundA single usage of a drug of abuse can have lasting effects on both the brain and behavior, continuing even after the drug has been metabolized and eliminated from the body. A single dose of cocaine can abolish endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 hours of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit.MethodsOur study employed adult male mice to investigate the effects of a single dose of cocaine (20 mg/kg) on eCB-LTD, saccharin preference, and social interactions 24 hours after administration. We also examined the gene expression in components of the eCB system. The pharmacological increase of anandamide was evaluated using the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg).ResultsAfter a single dose of cocaine, mice displayed altered plasticity, social interactions, and preference for saccharin and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. We discovered that the FAAH inhibitor URB597 (1 mg/kg) successfully reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect their saccharin preference.ConclusionsOverall, this research underlines the neuroplastic changes and subsequent behavioral alterations that occur after the initial use of cocaine, while also suggesting a potential role for anandamide in the early impairments caused by cocaine. The findings highlight the importance of understanding the mechanisms underlying the initiation of drug use and offer a potential therapeutic target.
Mediating Effect of Physical Activity on Relation between Cardio-respiratory Fitness and Physical Function Capacity of Older Adults
Authors: Aloko Eric A. , Ansah Edward W. , Apaak Daniel , Sarpong Emmanuel O. , Seibu Munkaila , Sorkpor Stephen R. 
Published: June 2023

AbstractThe ageing process is normally accompanied by several physiological changes like a decline in physical function and increased risk of chronic health conditions. In older adults, maintaining physical function and cardiovascular health is essential for maintaining independence and quality of life. Cardio-respiratory fitness and physical functional capacity (PFC) are two important indicators of physical health in older adults. This study aims to investigate the mediating effect of physical activity (PA) on the relationship between CRF and PFC in older adults. Using quantitative cross-sectional design, we employed a multistage sampling strategy to recruit 998 older adults from Navrongo for this study. The senior fitness test battery, international physical activity questionnaire (IPAQ) short form for elderly, weighing scale and tape measure were used to collect the data. The findings revealed that, 53.4% and 53.9% of these older adults had reduced PFC and CRF respectively. It was also found that PA partially mediates the relationship between CRF and PFC of the older adults with an indirect effect of CRF on PFC as β = .0030, t = 1.579 p < .05, with a direct effect of CRF on PFC, β = .867, t = 42.954, p < .05, and the total effect, β = .872, t = 43.110, p < .05. We concluded that physical activity partially mediates the relationship between CRF and PFC among older adults in Navrongo. Therefore, there is the need for evidenced-based intervention to promote PA among these older adults to improve their PFC and quality of life.
Labour Care Guide implementation as a decision-making tool for monitoring labour among health care providers in Southwestern Uganda: A protocol for a multisite Effectiveness-Implementation study
Authors: Mugyenyi GR , Mulogo EM , Tumuhimbise W , Atukunda EC , Kayondo M , Ngonzi J , Byamugisha J , Yarine F 
Published: June 2023

AbstractBackgroundThe new WHO Labour Care Guide, also regarded as the “next-generation partograph” basing on recent evidence has been recorded as a core component of the 2018 consolidated set of guidelines on intrapartum care for positive child birth experience. The Ugandan Ministry of Health is in the process of adopting the new WHO Labour Care Guide (LCG) with no local context specific data to inform this transition. This study will employ evidence-based research frameworks to identify challenges, and potential opportunities that would inform and refine the implementation strategy and scale-up of this highly promising LCG. We will also seek to utilize best practices to evaluate implementation effectiveness of the new LCG, through employing measurable implementation matrices (implementation, service, patient outcomes).MethodsThis study will be a multisite effectiveness-implementation study across all basic and comprehensive emergency obstetric and newborn care facilities in Mbarara district and Mbarara City in Southwestern Uganda. We will employ both quantitative and qualitative methods to evaluate the use of the newly recommended WHO Labor Care Guide in monitoring labor among all health care providers actively engaged in deliverying women across all public maternity health facilities in Mbarara district and Mbarara City. No participant has been recruited at hie point in timeResults and DiscussionThis study will offer an opportunity to ascertain whether the new WHO Labour Care Guide tool is an effective decision-making tool to monitor labor among healthcare providers conducting routine deliveries in publicly funded facilities in Southwestern Uganda. We will also identify practical, context-specific and actionable strategies for achieving optimal implementation effectiveness in a rural low resource setting.