bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Volume Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors
Authors: Dong Zhijie , Li Shuangliang , Duan Xiaoyu , Lowerison Matthew R. , Huang Chengwu , You Qi , Chen Shigao , Zou Jun , Song Pengfei 
Published: March 2023

Abstract3-D ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. Although many 3-D ultrasound imaging techniques have been developed in the last several decades, a low-cost and accessible solution with high imaging volume rate and imaging quality remains elusive. Recently we proposed a new, high volume rate 3-D ultrasound imaging technique: Fast Acoustic Steering via Tilting Electromechanical Reflectors (FASTER), which uses a water-immersible and fast-tilting acoustic reflector to steer ultrafast plane waves in the elevational direction to achieve high volume rate 3-D ultrasound imaging with conventional 1-D array transducers. However, the initial implementation of FASTER imaging only involves a single fast-tilting acoustic reflector, which is inconvenient to use because the probe cannot be held in the regular upright position. Also, conventional FASTER imaging can only be performed inside a water tank because of the necessity of using water for acoustic conduction. To address these limitations of conventional FASTER, here we developed a novel ultrasound probe clip-on device that encloses a fast-tilting reflector, a redirecting reflector, and an acoustic wave conduction medium. The new FASTER 3-D imaging device can be easily attached to or removed from clinical ultrasound transducers, allowing rapid transformation from 2-D to 3-D ultrasound imaging.In vitroB-mode imaging studies demonstrated that the proposed method provided comparable imaging quality (e.g., spatial resolution and contrast-to-noise ratio) to conventional, mechanical-translation-based 3-D imaging while providing a much faster 3-D volume rate (e.g., 300 Hz vs ∼10 Hz). In addition to B-mode imaging, we also demonstrated 3-D power Doppler imaging and 3-D super-resolution ultrasound localization microscopy with the newly developed FASTER device. Anin vivoimaging study showed that the FASTER device could clearly visualize the 3-D anatomy of the basilic vein of a healthy volunteer, and customized beamforming was implemented to accommodate the speed of sound difference between the acoustic medium and the imaging object (e.g., soft tissue). These results suggest that the newly developed redirecting reflector and the clip-on device could overcome key hurdles for future clinical translation of the FASTER 3-D imaging technology.
Data-driven representations using deep network-coherent methylation autoencoders to identify robust disease and risk factor signatures
Authors: Martínez-Enguita David , Dwivedi Sanjiv K. , Jörnsten Rebecka , Gustafsson Mika 
Published: March 2023

ABSTRACTData analysis in systems medicine often employs knowledge-driven approaches, which leverage prior biological insights to guide and inform the study of large omic sets. However, the current state of knowledge in biology is still partial and biased. For example, cancer-associated genes are overrepresented in protein interaction networks. As a result, these approaches may fail to capture novel or unexpected phenomena. In this study, we present a data-driven workflow for the functional analysis of large DNA methylation data using deep autoencoders with biologically relevant latent embeddings (network-coherent autoencoders, NCAEs). We observed an increasing gene co-localization gradient, consistent with the human interactome, within the learned representation of a deep methylation autoencoder. We showcased the capacity of this coherent compressed space to discover signatures for classification associated with aging, smoking, and disease. We believe this approach can improve the understanding of complex epigenetic processes and help develop more effective diagnostic and therapeutic strategies.
Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity
Authors: Hoving D. , Marques A.H.C. , Huisman W. , Nosoh B.A. , de Kroon A.C. , van Hengel O.R.J. , Wu B.R. , van Helden P.M. , Urban B.C. , Dhar N. , Ferreira D.M. , Kwatra G. , Hokke C.H. , Jochems S.P. 
Published: March 2023

AbstractBacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25+ cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14Streptococcus pneumoniaeor 5Streptococcus agalactiaeserotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM+) memory B cells and vaccine-inefficientS. pneumoniaeserotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence ofS. agalactiaeinvasive disease, compared to European donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy.
Crosstalkr: An open-source R package to facilitate drug target identification
Authors: Weaver Davis T. , Scott Jacob G. 
Published: March 2023

ABSTRACTIn the last few decades, interest in graph-based analysis of biological networks has grown substantially. Protein-protein interaction networks are one of the most common biological networks, and represent the molecular relationships between every known protein and every other known protein. Integration of these interactomic data into bioinformatic pipelines may increase the translational potential of discoveries made through analysis of multi-omic datasets. Crosstalkr provides a unified toolkit for drug target and disease subnetwork identification, two of the most common uses of protein protein interaction networks. First, crosstalkr enables users to download and leverage high-quality protein-protein interaction networks from online repositories. Users can then filter these large networks into manageable subnetworks using a variety of methods. For example, network filtration can be done using random walks with restarts, starting at the user-provided seed proteins. Affinity scores from a given random walk with restarts are compared to a bootstrapped null distribution to assess statistical significance. Random walks are implemented using sparse matrix multiplication to facilitate fast execution. Next, users can perform in-silico repression experiments to assess the relative importance of nodes in their network. At this step, users can supply protein or gene expression data to make node rankings more meaningful. The default behavior evaluates the human interactome. However, users can evaluate more than 1000 non-human protein-protein interaction networks as a result of integration with StringDB. It is a free, open-source R package designed to allow users to integrate functional analysis using the protein-protein interaction network into existing bioinformatic pipelines. A beta version of crosstalkr available on CRAN (https://cran.rstudio.com/web/packages/crosstalkr/index.html).
Elevational and latitudinal range extensions of the puna mouse,Punomys(Cricetidae), with the first record of the genus from Chile
Authors: Quiroga-Carmona Marcial , Storz Jay F. , D’Elía Guillermo 
Published: March 2023

ABSTRACTWe report an elevational record for the Andean sigmodontine puna mousePunomys, which is also the first record of the genus in Chile. The record is based on a mummified specimen that we discovered at an elevation of 5,461 m (17,917’) in the caldera of Volcán Acamarachi, Región de Antofagasta, Chile. Results of a morphological suggest that the specimen can be provisionally referred to the speciesP. lemminus. This new record also extends the known geographic distribution of the genus by 700 km to the south and brings the known Chilean mammal richness to a total of 170 living species and 88 genera. This finding highlights the need for increased survey efforts in more remote, high-elevation regions and demonstrates that there is still much to be learned about the mammal fauna of the Andean Altiplano.
The Voltage-gated sodium channel in Drosophila, Para, localizes to dendrites as well as axons in mechanosensitive chordotonal neurons
Authors: Ravenscroft Thomas A. , Jacobs Ashleigh , Gu Mingxue , Eberl Daniel F. , Bellen Hugo J. 
Published: March 2023

AbstractThe fruit flyDrosophila melanogasterhas provided important insights into how sensory information is transduced by Transient Receptor Potential (TRP) channels in the Peripheral Nervous System (PNS). However, TRP channels alone have not been able to completely model mechanosensitive transduction in mechanoreceptive chordotonal neurons (CN). Here we show that, in addition to TRP channels, the sole voltage-gated sodium channel (NaV) inDrosophila, Para, is localized to the dendrites of CNs. Para is localized to the distal tip of the dendrites in all CNs, from embryos to adults, and is colocalized with the mechanosensitive TRP channels No mechanoreceptor potential C (NompC) and Inactive/Nanchung (Iav/Nan). Para localization also demarcates spike initiation zones (SIZ) in axons and the dendritic localization of Para is indicative of a likely dendritic SIZ in fly CNs. Para is not present in the dendrites of other peripheral sensory neurons. In both multipolar and bipolar neurons in the PNS, Para is present in a proximal region of the axon, comparable to the axonal initial segment in vertebrates, 40-60μm from the soma in multipolar neurons and 20-40μm in bipolar neurons. Whole-cell reduction ofparaexpression using RNAi in CNs of the adult Johnston’s organ severely affects sound-evoked potentials. However, the duality of Para localization in the CN dendrites and axons identifies a need to develop resources to study compartment-specific roles of proteins that will enable us to better understand Para’s role in mechanosensitive transduction.Significance StatementSeveral transient receptor potential (TRP) channels have been shown to localize to dendrites ofDrosophilamechanosensitive chordotonal neurons (CN). Here, we show that the fly voltage-gated sodium channel, Para co-localizes with the TRP channels NompC and iav and a possible dendritic spike initiation zone (SIZ) in CN dendrites. This dendritic localization is unique to CNs, is not seen in other peripheral neurons, and may account for some aspects of mechanotransduction. Para also localizes to a SIZ at an axonal initial segment-like region, which is shared amongst many peripheral neurons.
Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer’s disease
Authors: Ocañas Sarah R. , Pham Kevin D. , Cox Jillian E.J. , Keck Alex W. , Ko Sunghwan , Ampadu Felix A. , Porter Hunter L. , Ansere Victor A. , Kulpa Adam , Kellogg Collyn M. , Machalinski Adeline H. , Chucair-Elliott Ana J. , Freeman Willard M. 
Published: March 2023

AbstractBackgroundMicroglia, the brain’s principal immune cells, have been implicated in the pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared transcriptomic and translatomic sex effects in young and old murine hippocampal microglia.MethodsHippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5-6 month-old [mo]) and old (22-25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic and translatomic findings.ResultsThere were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally-and autosomally-encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Normalized gene expression values can be accessed through a searchable web interface (https://neuroepigenomics.omrf.org/). Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP.ConclusionsThese data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.
An atlas of gene regulatory networks for memory CD4+T cells in youth and old age
Authors: Wayman Joseph A. , Thomas Alyssa , Bejjani Anthony , Katko Alexander , Almanan Maha , Godarova Alzbeta , Korinfskaya Svetlana , Cazares Tareian A. , Yukawa Masashi , Kottyan Leah C. , Barski Artem , Chougnet Claire A. , Hildeman David A. , Miraldi Emily R. 
Published: March 2023

AbstractAging profoundly affects immune-system function, promoting susceptibility to pathogens, cancers and chronic inflammation. We previously identified a population of IL-10-producing, T follicular helper-like cells (“Tfh10”), linked to suppressed vaccine responses in aged mice. Here, we integrate single-cell (sc)RNA-seq, scATAC-seq and genome-scale modeling to characterize Tfh10 – and the full CD4+memory T cell (CD4+TM) compartment – in young and old mice. We identified 13 CD4+TM populations, which we validated through cross-comparison to prior scRNA-seq studies. We built gene regulatory networks (GRNs) that predict transcription-factor control of gene expression in each T-cell population and how these circuits change with age. Through integration with pan-cell aging atlases, we identified intercellular-signaling networks driving age-dependent changes in CD4+TM. Our atlas of finely resolved CD4+TM subsets, GRNs and cell-cell communication networks is a comprehensive resource of predicted regulatory mechanisms operative in memory T cells, presenting new opportunities to improve immune responses in the elderly.
CircRNA-disease inference using deep ensemble model based on triple association
Authors: Fu Laiyi , Du Hongkai , Wang Ying , Peng Qinke 
Published: March 2023

AbstractAccumulating evidence indicates more and more circular RNAs (i.e. circRNAs) have played a vital role in regulating gene expression and are related to diseases through different biological procedures. Predicting circRNA-disease associations helps to conjecture possible disease related circRNA and facilitate human disease diagnosis and downstream treatment. Nevertheless, little effort was made to uncover the interaction between various diseases and circRNAs. In our work, human circRNA-disease association network is first generated using known miRNA-circRNA interactions and disease related miRNA (microRNA) information. Then we further integrated this information to compute similarity scores between human diseases and circRNAs. Here, we proposed one deep ensemble model called DeepInteract, which first used two stacked auto-encoders to explore hidden features utilizing similarity information, and adopted a 3-layer neuron network to predict the final association. Our method is capable of capturing more complex non-linear features comparing to other approaches. Our results indicate the proposed method is superior to other previous competitors. Many prediction results have been validated by some biological experiments using our model.
Microsatellites used in forensics are located in regions unusually rich in trait-associated variants
Authors: Link Vivian , Zavaleta Yuómi Jhony A. , Reyes Rochelle-Jan , Ding Linda , Wang Judy , Rohlfs Rori V. , Edge Michael D. 
Published: March 2023

AbstractThe 20 short tandem repeat (STR) markers of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS markers are thought to contain information relevant to identification only (such as a human fingerprint would), with little information about ancestry or traits. However, in the past 20 years, a quickly growing field has identified hundreds of thousands of genotype-trait associations. Here we conduct a survey of the landscape of such associations surrounding the CODIS loci as compared with non-CODIS STRs. We find that the regions around the CODIS markers are enriched for both known pathogenic variants (>90th percentile) and for SNPs identified as trait-associated in genome-wide association studies (GWAS) (≥95th percentile in 10kb and 100kb flanking regions), compared with other random sets of autosomal tetranucleotide-repeat STRs. Although it is not obvious how much phenotypic information CODIS would need to convey to strain the “DNA fingerprint” analogy, the CODIS markers, considered as a set, are in regions unusually dense with variants with known phenotypic associations.
NDC80 status pinpoints mitotic kinase inhibitors as emerging therapeutic options in clear cell renal cell carcinoma
Authors: Hu Cheng , Lin Weiming , Zhao Kemeng , Tian Guiyou , Kong Xiangquan , Luo Guangcheng , Wolf Dieter A. , Cheng Yabin 
Published: March 2023

SUMMARY∼30% of clear cell renal cell carcinoma (ccRCC) patients present with metastatic disease at the time of diagnosis, causing a dire 5-year survival rate of 13%. Whereas anti-PD-1 immunotherapy has improved survival, a strong need remains for new therapeutic options. Using integrated network analysis, we identified the mitotic regulator NDC80 as a predictor of ccRCC progression. Overexpression of NDC80 fosters the malignant phenotype by promoting cell cycle progression through S phase as well as boosting glycolysis and mitochondrial respiration. Despite high levels of immune infiltration, particularly derived from tumor resident CD8+ T cells with an exhausted phenotype, NDC80 defines a class of ccRCCs that poorly respond to immune checkpoint blockade. Instead, bioinformatics identified NDC80-high ccRCCs as sensitive to inhibitors of mitotic kinases, PLK1 and AURK, therapeutic approaches we validated in cell lines and mouse xenograft studies. Thus, NDC80 status pinpoints mitotic kinase inhibitors as promising therapeutic options in difficult-to-treat ccRCCs.
Comparison of volumetric brain analysis in subjects with rheumatoid arthritis and ulcerative colitis
Authors: Cox Jennifer G. , de Groot Marius , Kempton Matthew J. , Williams Steven C. R. , Cole James H. 
Published: March 2023

AbstractObjectivesRheumatoid arthritis (RA) and ulcerative colitis (UC) are two autoimmune diseases where patients report high levels of fatigue, pain, and depression. The effect of systemic inflammation from these diseases is likely affecting the brain, however, it is unknown whether there are measurable neuroanatomical changes and whether these are a contributing factor to these central symptoms.MethodsWe included 258 RA patients with 774 age and sex matched controls and 249 UC patients with 747 age and sex matched controls in a case control study utilising the UK Biobank dataset. We used imaging derived phenotypes (IDPs) to determine whether there were differences in (1) hippocampal volume and (2) additional subcortical brain volumes between patients compared to controls and if there were common regions affected between these two diseases.ResultsPatients with UC had moderately smaller hippocampi compared to age and sex matched controls (difference: 134.15 mm3, SD ± 64.76, p = 0.035). This result was not seen in RA patients. RA patients had a significantly smaller amygdala volume than age and sex matched controls (difference: 91.27 mm3, SD ± 30.85, p = 0.0021, adjusted p value = 0.012). This result was not seen in UC patients. All other subcortical structures analysed were comparable between the patients and control groups.ConclusionThese results indicate there are subcortical brain differences between UC, RA and controls but different regions of the limbic system are preferentially affected by UC and RA. This study may provide evidence for different neurodegenerative mechanisms in distinct autoimmune diseases.Key MessagesCentral effects such as fatigue and pain place significant burden on patients with autoimmune diseasesRheumatoid arthritis patients have smaller amygdala volumes compared to matched controls.Ulcerative colitis patients have smaller hippocampal volumes compared to matched controls.
Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease
Authors: Saad-Roy Chadi M. , Morris Sinead E. , Baker Rachel E. , Farrar Jeremy , Graham Andrea L. , Levin Simon A. , Wagner Caroline E. , E. Metcalf C. Jessica. , Grenfell Bryan T. 
Published: March 2023

AbstractAs the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or ‘evolution-proof’) immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable, and broadly-protective vaccine.