bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Artificial Intelligence (AI)-basedin silicotools for variant classification in clinically actionable NSCLC variants
Authors: Kim Eugene , Duarte Samantha E , Yu Emma , Hong Ilene , Lee Grace , Chae Young Kwang 
Published: April 2024

AbstractIntroduction/BackgroundGenetic variants beyond FDA-approved drug targets are often identified in non-small cell lung cancer (NSCLC) patients. Although the performances ofin silicotools in predicting variant pathogenicity have been analyzed in previous studies, they have not been analyzed for actionable targets of FDA-approved therapies for NSCLC. The aim of this study is to compare the performance of commonly usedin silicotools in classifying the pathogenicity of actionable variants in NSCLC.Materials and MethodsWe evaluated the performance of the followingin silicotools: Polyphen-2 (HumDiv, HumVar), Align-GVGD, MutationTaster2021, CADD, CONDEL, and REVEL. A curated set of targetable NSCLC missense variants (n=236) was used. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Matthews correlation coefficient (MCC) of eachin silicotool was determined.ResultsThe most recently released MutationTaster2021 demonstrated the highest performance in terms of accuracy, specificity, PPV, and MCC, but was outperformed by CADD for both sensitivity and NPV. Although some tools demonstrated high sensitivities, all tools except MutationTaster2021 displayed markedly low overall specificities, as low as 23%.ConclusionThe collective results indicate that the evaluatedin silicotools can provide guidance in predicting the pathogenicity of NSCLC missense variants, but are not fully reliable. The tools analyzed in this study could be acceptable to rule out pathogenicity in variants given their higher sensitivities, but are limited when it comes to identifying pathogenicity in variants due to low specificities.HighlightsMutationTaster2021 demonstrated the highest overall performanceCADD demonstrated the highest sensitivity (99.19%) and NPV (96.55%).All tools but MutationTaster2021 demonstrated low specificities, as low as 23%An individual predictor outperformed 3 meta predictorsPerformance variability suggests caution when usingin silicotools in the clinic
The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures
Authors: Yun S , Kiffer FC , Bancroft GL , Guzman CS , Soler I , Haas HA , Shi R , Patel R , Lara-Jiménez J , Kumar PL , Tran FH , Ahn KJ , Rong Y , Luitel K , Shay JW , Eisch AJ 
Published: April 2024

ABSTRACTGalactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew’s longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.
SleepInvestigatoR: A flexible R function for analyzing scored sleep in rodents
Authors: Gamble Mackenzie C. , Williams Benjamin R. , McKenna James T. , Logan Ryan W. 
Published: April 2024

AbstractAnalyzing scored sleep is a fundamental prerequisite to understanding how sleep changes between health and disease. Classically, this is accomplished by manually calculating various measures (e.g., percent of non-rapid eye movement sleep) from a collection of scored sleep files. This process can be tedious and error prone especially when studies include a large number of animals or involve long recording sessions. To address this issue, we present SleepInvestigatoR, a versatile tool that can quickly organize and analyze multiple scored sleep files into a single output. The function is written in the open-source statistical language R and has a total of 25 parameters that can be set to match a wide variety of experimenter needs. SleepInvestigatoR delivers a total of 22 unique measures of sleep, including all measures commonly reported in the rodent literature. A simple plotting function is also provided to quickly graph and visualize the scored data. All code is designed to be implemented with little formal coding knowledge and step-by-step instructions are provided on the corresponding GitHub page. Overall, SleepInvestigatoR provides the sleep researcher a critical tool to increase efficiency, interpretation, and reproducibility in analyzing scored rodent sleep.
Does hybridisation with an invasive species threaten Europe’s most endangered reptile? Genomic assessment of Aeolian lizards on Vulcano island
Authors: Paris Josephine R , Ficetola Gentile Francesco , Obiol Joan Ferrer , Rocha Iolanda Silva- , Carretero Miguel Angel , Salvi Daniele 
Published: April 2024

AbstractInterspecific hybridisation can be consequential for rare and insular endemic species. The Critically Endangered Aeolian wall lizard,Podarcis raffonei, severely declined due to interactions with the invasive Italian wall lizard,Podarcis siculus. The largest population ofP. raffoneisurvives on a narrow peninsula (Capo Grosso) that is mildly connected to the island of Vulcano, which has been entirely invaded byP. siculus. Recent observation of individuals with an intermediate phenotype raised concern over the risk that hybridisation might swamp this last stronghold. We genetically characterised lizards from Vulcano using genome-wide SNPs, considering individuals showing multiple phenotypes (native, invasive, and “intermediate”). Hybridisation rate was low (∼3%), with just two F1 hybrids and two backcrosses. However, pureP. raffoneishowed extremely low genetic diversity, a very small effective population size, and a low NE/NCratio. Management strategies are urgently needed to control invasive species and maintain the genetic diversity ofP. raffonei.
Role and modulation of various spinal pathways for human upper limb control in different gravity conditions
Authors: Bruel Alice , Bacha Lina , Boehly Emma , De Trogoff Constance , Represa Luca , Courtine Gregoire , Ijspeert Auke 
Published: April 2024

AbstractHumans can perform movements in various physical environments and positions (corresponding to different experienced gravity), requiring the interaction of the musculoskeletal system, the neural system and the external environment. The neural system is itself comprised of several interactive components, from the brain mainly conducting motor planning, to the spinal cord (SC) implementing its own motor control centres through sensory reflexes. Nevertheless, it remains unclear whether similar movements in various environmental dynamics necessitate replanning modulation at the brain level, correcting modulation at the spinal level, or both. Here, we addressed this question by focusing on upper limb motor control in various gravity conditions (magnitudes and directions) and using neuromusculoskeletal simulation tools. We integrated supraspinal sinusoidal commands with a modular SC model controlling a musculoskeletal model to reproduce recorded elbow flexion-extension trajectories (kinematics and EMGs) in different contexts. We first studied the role of various spinal pathways (such as stretch reflexes) in movement smoothness and robustness against perturbation. Then, we optimised the supraspinal sinusoidal commands without and with a fixed SC model including stretch reflexes to reproduce a target trajectory in various gravity conditions. Inversely, we fixed the supraspinal commands and optimised the spinal synaptic strengths in the different environments. In the first optimisation context, the presence of SC resulted in easier optimisation of the supraspinal commands (faster convergence, better performance). The main supraspinal commands modulation was found in the flexor sinusoid’s amplitude, resp. frequency, to adapt to different gravity magnitudes, resp. directions. In the second optimisation context, the modulation of the spinal synaptic strengths also remarkably reproduced the target trajectory for the mild gravity changes. We highlighted that both strategies of modulation of the supraspinal commands or spinal stretch pathways can be used to control movements in different gravity environments. Our results thus support that the SC can assist gravity compensation.
Poseidon – A framework for archaeogenetic human genotype data management
Authors: Schmid Clemens , Ghalichi Ayshin , Lamnidis Thiseas C. , Mudiyanselage Dhananjaya B. A. , Haak Wolfgang , Schiffels Stephan 
Published: April 2024

1AbstractThe study of ancient human genomes, archaeo- or palaeogenetics, has accelerated in the last ten years, with now thousands of new ancient genomes being released each year. Operating at the interface of genetics, anthro-pology and archaeology, this data includes features from all three fields, including rich meta- and context-data, for example regarding spatiotemporal provenience. While archives and standards for genetic sequencing data al-ready exist, no such infrastructure exists for combined genetic and meta-data that could ensure FAIR principles across the field. Here, we present Poseidon, a framework for open and FAIR data handling in archaeogenetics, including a specified package format, software tools, and public, community-maintained online archives. Poseidon emphasises human- and machine-readable data storage, the development of convenient and interoperable command line software, and a high degree of source granularity to elevate the original data publication to the main unit of long-term curation.
What underlies exceptional memory function in older age? No evidence for aging-specific relationships to hippocampal atrophy and retrieval activity
Authors: Fjell Anders M. , Sneve Markus H. , Amlien Inge K , Grydeland Håkon , Mowinckel Athanasia M. , Vidal-Piñeiro Didac , Sørensen Øystein , Walhovd Kristine B. 
Published: April 2024

AbstractSome older adults show superior memory performance compared to same-age peers, even performing on par with young participants. These are often referred to asSuperAgers. It is not known whether their superior memory function is caused by special features of their brains in aging, or whether superior memory has the same brain foundation throughout adult life. To address this, we measured hippocampal volume and atrophy, microstructural integrity by diffusion tensor imaging, and activity during an episodic memory encoding and retrieval task, in 277 cognitively healthy adults (age 20.1-81.5 years at baseline, mean 49.2 years). For quantification of hippocampal atrophy, all participants had repeated MRIs, from two to seven examinations, covering a mean of 9.3 years between first and last scan (2.5-17.3 years). 15.7% of the participants above 60 years had episodic memory scores above the mean of the young and middle-aged participants and were classified as SuperAgers. We found that superior memory in older adults was associated with higher retrieval activity in the anterior hippocampus and less hippocampal atrophy. However, there were no significant age-interactions, suggesting that the relationships reflected stable correlates of superior memory function. Although SuperAgers had superior memory compared to their same-age peers, they still performed worse than the best-performing young participants. Further, age-memory performance curves across the full age-range were similar for participants with superior memory performance compared to those with normal and low performance. These trajectories were based on cross-sectional data, but do not indicate preserved memory among the superior functioning older adults. In conclusion, the current results confirm that aspects of hippocampal structure and function are related to superior memory across age, without evidence to suggest that SuperAgers have special features compared to their younger counterparts.
A deep learning pipeline for time-lapse camera monitoring of insects and their floral environments
Authors: Bjerge Kim , Karstoft Henrik , Mann Hjalte M. R. , Høye Toke T. 
Published: April 2024

AbstractArthropods, including insects, represent the most diverse group and contribute significantly to animal biomass. Automatic monitoring of insects and other arthropods enables quick and efficient observation and management of ecologically and economically important targets such as pollinators, natural enemies, disease vectors, and agricultural pests. The integration of cameras and computer vision facilitates innovative monitoring approaches for agriculture, ecology, entomology, evolution, and biodiversity. However, studying insects and their interactions with flowers and vegetation in natural environments remains challenging, even with automated camera monitoring.This paper presents a comprehensive methodology to monitor abundance and diversity of arthropods in the wild and to quantify floral cover as a key resource. We apply the methods across more than 10 million images recorded over two years using 48 insect camera traps placed in three main habitat types. The cameras monitor arthropods, including insect visits, on a specific mix ofSedumplant species with white, yellow and red/pink colored of flowers. The proposed deep-learning pipeline estimates flower cover and detects and classifies arthropod taxa from time-lapse recordings. However, the flower cover serves only as an estimate to correlate insect activity with the flowering plants. Color and semantic segmentation with DeepLabv3 are combined to estimate the percent cover of flowers of different colors. Arthropod detection incorporates motion-informed enhanced images and object detection with You-Only-Look-Once (YOLO), followed by filtering stationary objects to minimize double counting of non-moving animals and erroneous background detections. This filtering approach has been demonstrated to significantly decrease the incidence of false positives, since arthropods, occur in less than 3% of the captured images.The final step involves grouping arthropods into 19 taxonomic classes. Seven state-of-the-art models were trained and validated, achievingF1-scores ranging from 0.81 to 0.89 in classification of arthropods. Among these, the final selected model, EfficientNetB4, achieved an 80% average precision on randomly selected samples when applied to the complete pipeline, which includes detection, filtering, and classification of arthropod images collected in 2021. As expected during the beginning and end of the season, reduced flower cover correlates with a noticeable drop in arthropod detections. The proposed method offers a cost-effective approach to monitoring diverse arthropod taxa and flower cover in natural environments using time-lapse camera recordings.
Snorkel-tag Based Affinity Chromatography for Recombinant Extracellular Vesicle Purification
Authors: Bobbili Madhusudhan Reddy , Görgen André , Yan Yan , Vogt Stefan , Gupta Dhanu , Corso Giulia , Barbaria Samir , Patrioli Carolina , Weilner Sylvia , Pultar Marianne , Jacak Jaroslaw , Hackl Matthias , Schosserer Markus , Grillari Regina , Kjems Jorgen , EL Andaloussi Samir , Grillari Johannes 
Published: April 2024

AbstractExtracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine are still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue-specific EV cargo information. Here, we present CD81, an EV surface marker protein, genetically fused to series of tags with additional transmembrane domain to be displayed on the EV surface, which we term Snorkel-tag. This system enables to affinity purify EVs from complex matrices in a non-destructive form. In future applications, this strategy will allow generating transgenic animals to enable tracing and analyzing EVs, and their cargo in physiological and pathophysiological set-ups, and facilitate the development of EV based diagnostic tools in murine models which can be translated to humans.
Chromatin accessibility variation provides insights into missing regulation underlying immune-mediated diseases
Authors: Jeong Raehoon , Bulyk Martha L. 
Published: April 2024

AbstractMost genetic loci associated with complex traits and diseases through genome-wide association studies (GWAS) are noncoding, suggesting that the causal variants likely have gene regulatory effects. However, only a small number of loci have been linked to expression quantitative trait loci (eQTLs) detected currently. To better understand the potential reasons for many trait-associated loci lacking eQTL colocalization, we investigated whether chromatin accessibility QTLs (caQTLs) in lymphoblastoid cell lines (LCLs) explain immune-mediated disease associations that eQTLs in LCLs did not. The power to detect caQTLs was greater than that of eQTLs and was less affected by the distance from the transcription start site of the associated gene. Meta-analyzing LCL eQTL data to increase the sample size to over a thousand led to additional loci with eQTL colocalization, demonstrating that insufficient statistical power is still likely to be a factor. Moreover, further eQTL colocalization loci were uncovered by surveying eQTLs of other immune cell types. Altogether, insufficient power and context-specificity of eQTLs both contribute to the ‘missing regulation.’
Influenza virus antibodies inhibit antigen-specificde novoB cell responses in mice
Authors: Goodwin Eileen , Gibbs James S. , Yewdell Jonathan W. , Eisenlohr Laurence C. , Hensley Scott E. 
Published: April 2024

AbstractAntibody responses to influenza vaccines tend to be focused on epitopes encountered during prior influenza exposures, with little production ofde novoresponses to novel epitopes. To examine the contribution of circulating antibody to this phenomenon, we passively transferred a hemagglutinin (HA)-specific monoclonal antibody (mAb) into mice before immunizing with whole inactivated virions. The HA mAb inhibitedde novoHA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to a second antigen in the vaccine, neuraminidase (NA), were uninhibited. The HA mAb potently inhibitedde novoantibody responses against epitopes near the HA mAb binding site. The HA mAb also promoted IgG1 class switching, an effect that, unlike the inhibition of HA responses, relied on signaling through Fc-gamma receptors. These studies suggest that circulating antibodies inhibitde novoB cell responses in an antigen-specific manner, which likely contributes to differences in antibody specificities elicited during primary and secondary influenza virus exposures.
Association of 10 VEGF Family Genes with Alzheimer’s Disease Endophenotypes at Single Cell Resolution
Authors: Wu Yiyang , Libby Julia B , Dumitrescu Logan , De Jager Philip L. , Menon Vilas , Schneider Julie A. , Bennett David A. , Hohman Timothy J 
Published: April 2024

AbstractThe cell-type specific role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer’s disease (AD) is not well characterized. In this study, we utilized a single-nucleus RNA sequencing dataset from Dorsolateral Prefrontal Cortex (DLFPC) of 424 donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP) to investigate the effect of 10 VEGF genes (VEGFA, VEGFB, VEGFC, VEGFD, PGF, FLT1, FLT4, KDR, NRP1, andNRP2) on AD endophenotypes. Mean age of death was 89 years, among which 68% were females, and 52% has AD dementia. Negative binomial mixed models were used for differential expression analysis and for association analysis with β-amyloid load, PHF tau tangle density, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated signaling was profiled using CellChat. We discovered prefrontal corticalFLT1expression was upregulated in AD brains in both endothelial and microglial cells. HigherFLT1expression was also associated with worse cross-sectional global cognitive function, longitudinal cognitive trajectories, and β-amyloid load. Similarly, higher endothelialFLT4expression was associated with more β-amyloid load. In contrast to the receptors,VEGFBshowed opposing effects on β-amyloid load whereby higher levels in oligodendrocytes was associated with high amyloid burden, while higher levels in inhibitory neurons was associated with lower amyloid burden. Finally, AD cells showed significant reduction in overall VEGF signaling comparing to those from cognitive normal participants. Our results highlight key changes in VEGF receptor expression in endothelial and microglial cells during AD, and the potential protective role of VEGFB in neurons.