bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Vaccination and Previous Infection Against Omicron Infection and Severe Outcomes in Children Under 12 Years of Age
Authors: Lin Dan-Yu , Xu Yangjianchen , Gu Yu , Zeng Donglin , Wheeler Bradford , Young Hayley , Moore Zack , Sunny Shadia K 
Published: January 2023

ABSTRACTBackgroundData on the protection conferred by Covid-19 vaccination and previous SARS-CoV-2 infection against omicron infection and severe outcomes in children can inform prevention strategies.MethodsWe obtained vaccination records and clinical outcomes for 1,368,721 North Carolina residents 11 years of age or younger from October 29, 2021 to January 6, 2023. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and previous infection on the risks of omicron infection, hospitalization, and death.ResultsFor children 5–11 years of age, the effectiveness of primary vaccination against infection was 59.9% (95% confidence interval [CI], 58.5 to 61.2), 33.7% (95% CI, 32.6 to 34.8), and 14.9% (95% CI, 12.3 to 17.5) at 1, 4 and 10 months after the first dose; the effectiveness of a monovalent or bivalent booster dose after 1 month was 24.4% (95% CI, 14.4 to 33.2) or 76.7% (95% CI, 45.7 to 90.0); and the effectiveness of omicron infection against reinfection was 79.9% (95% CI, 78.8 to 80.9) and 53.9% (95% CI, 52.3 to 55.5) after 3 and 6 months, respectively. For children 0–4 years of age, the effectiveness of primary vaccination against infection was 63.8% (95% CI, 57.0 to 69.5) and 58.1% (95% CI, 48.3 to 66.1) at 2 and 5 months after the first dose, and the effectiveness of omicron infection against reinfection was 77.3% (95% CI, 75.9 to 78.6) and 64.7% (95% CI, 63.3 to 66.1) after 3 and 6 months, respectively. For both age groups, vaccination and previous infection had better effectiveness against hospitalization and death than against infection.ConclusionsCovid-19 vaccination was effective against omicron infection and severe outcomes in children under the age of 12 years, although the effectiveness decreased over time. Bivalent boosters were more effective than monovalent boosters. Immunity acquired via omicron infection was very high and waned gradually over time.
Hepatocyte-specific miR-33 deletion attenuates NAFLD-NASH-HCC progression
Authors: Fernández-Tussy Pablo , Sun Jonathan , Cardelo Magdalena P. , Price Nathan L. , Goedeke Leigh , Xirouchaki Chrysovalantou E. , Yang Xiaoyong , Pastor-Rojo Oscar , Bennett Anton M. , Tiganis Tony , Suárez Yajaira , Fernández-Hernando Carlos 
Published: January 2023

ABSTRACTThe complexity of the multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) progression remains a significant challenge for the development of effective therapeutics. miRNAs have shown great promise as regulators of biological processes and as therapeutic targets for complex diseases. Here, we study the role of hepatic miR-33, an important regulator of lipid metabolism, during the progression of NAFLD. We report that miR-33 is overexpressed in hepatocytes isolated from mice with NAFLD and demonstrate that its specific suppression in hepatocytes (miR-33HKO) improves multiple aspects of the disease, including insulin resistance, steatosis, and inflammation and limits the progression to non-alcoholic steatohepatitis (NASH), fibrosis and hepatocellular carcinoma (HCC). Mechanistically, we find that hepatic miR-33 deficiency reduces lipid biosynthesis and promotes mitochondrial fatty acid oxidation to reduce lipid burden in hepatocytes. Additionally, miR-33 deficiency improves mitochondrial function, reducing oxidative stress. In miR-33 deficient hepatocytes, we found an increase in AMPKα activation, which regulates several pathways resulting in the attenuation of liver disease. The reduction in lipid accumulation and liver injury resulted in decreased transcriptional activity of the YAP/TAZ pathway, which may be involved in the reduced progression to HCC in theHKOlivers. Together, these results suggest suppressing hepatic miR-33 may be an effective therapeutic approach at different stages of NAFLD/NASH/HCC disease progression.
Uncovering hidden biological processes by probabilistic filtering of single-cell data
Authors: Piran Zoe , Nitzan Mor 
Published: January 2023

AbstractElucidating underlying biological processes in single-cell data is an ongoing challenge and the number of methods that recapitulate dominant signals in such data has increased significantly. However, cellular populations encode multiple biological attributes, related to their spatial configuration, temporal trajectories, cell-cell interactions, and responses to environmental cues, which may be overshadowed by the dominant signal and thus much harder to recover. To approach this task, we developed SiFT (SIgnal FilTering), a method for filtering biological signals in single-cell data, thus uncovering underlying processes of interest. Utilizing existing prior knowledge and reconstruction tools for a specific biological signal, such as spatial structure, SiFT filters the signal and uncovers additional biological attributes. SiFT is applicable to a wide range of tasks, from the removal of unwanted variation in the data as a pre-processing step to revealing hidden biological structures. Applied for pre-processing, SiFT outperforms state-of-the-art methods for the removal of nuisance signals and cell cycle effects. To recover underlying biological structure, we use existing prior knowledge regarding liver zonation to filter the spatialsignalfrom single-cell liver data thereby enhancing the temporal circadian signal the cells are encoding. Lastly, we showcase the applicability of SiFT in the case-control setting for studying COVID-19 disease. Filtering the healthysignal, based on reference samples from healthy donors, exposes disease-related dynamics in COVID-19 data and highlights disease informative cells and their underlying disease response pathways.
Lagrangian Formalism in Biology: II. Non-Standard and Null Lagrangians for Nonlinear Dynamical Systems and their Role in Population Dynamics
Authors: Pham D. T. , Musielak Z. E. 
Published: January 2023

AbstractNon-standard Lagrangians do not display any discernible energy-like terms, yet they give the same equations of motion as standard Lagrangians, which have easily identifiable energy-like terms. A new method to derive non-standard Lagrangians for second-order nonlinear differential equations with damping is developed and the limitations of this method are explored. It is shown that the limitations do not exist only for those nonlinear dynamical systems that can be converted into linear ones. The obtained results are applied to selected population dynamics models for which non-standard Lagrangians and their corresponding null Lagrangians and gauge functions are derived, and their roles in the population dynamics are discussed.
Distinct Neural Signatures of Multimodal Resizing Illusions: Implications for Chronic Pain Treatment
Authors: Hansford Kirralise J. , Baker Daniel H. , McKenzie Kirsten J. , Preston Catherine E. J. 
Published: January 2023

AbstractIllusory body resizing typically uses multisensory integration to change the perceived size of a body part. Previous studies associate such multisensory body illusions with frontal theta oscillations and parietal gamma oscillations for dis-integration and integration of multisensory signals, respectively. However, recent studies support illusory changes of embodiment from visual-only stimuli. Multisensory resizing illusions can also reduce chronic pain, potentially through modulation of cortical body representations. This preregistered study (N=48) investigated differences between multisensory visuo-tactile and uni-modal visual resizing illusions using EEG. We hypothesised (1) stronger illusion in multisensory compared to uni-modal, and uni-modal compared to asynchronous (dis-integration) conditions, (2) greater parietal gamma during multisensory compared to uni-modal, and (3) greater frontal theta during asynchronous compared to baseline conditions. Results partially supported EEG hypotheses, finding increased parietal gamma activity comparing multisensory to unimodal visual conditions, whilst finding increased parietal theta activity when comparing asynchronous to non-illusion conditions. While results demonstrated that only 27% of participants experienced the illusion with visual-only stimuli, further analysis suggested that those who experience visual-only illusions exhibit a different neural signature to those who do not. Our results support the importance of multisensory integration for illusory changes in perceived body size. However, we also suggest that visual-only illusions can influence cortical body representations for a significant proportion of participants, which may have implications for the development of accessible visual-only chronic pain treatments.
Tiered Sympathetic Control of Cardiac Function Revealed by Viral Tracing and Single Cell Transcriptome Profiling
Authors: Sharma Sachin , Littman Russell , Tompkins John , Arneson Douglas , Contreras Jaime , Dajani Al-Hassan , Ang Kaitlyn , Tsanhani Amit , Sun Xin , Jay Patrick Y. , Herzog Herbert , Yang Xia , Ajijola Olujimi A. 
Published: January 2023

SUMMARYThe cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) Npy-expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.
Near-surface wind variability over spatiotemporal scales relevant to plume tracking insects
Authors: Houle Jaleesa , van Breugel Floris 
Published: January 2023

ABSTRACTOdor plume tracking is an important biological process for many organisms, and flying insects have served as popular model systems for studying these behaviors both in the field and in lab settings. The shape and statistics of the airborne odor plumes that insects follow are largely governed by the wind that advects them. Prior atmospheric studies have investigated aspects of microscale wind patterns with an emphasis on characterizing pollution dispersion, enhancing weather prediction models, and for assessing wind energy potential. Here, we aim to characterize microscale wind dynamics through the lens of short-term ecological functions by focusing on spatial and temporal scales most relevant to an insect actively searching for an odor source. We collected and compared near-surface wind data across three distinct environments (sage steppe, forest, and urban) in locations across Northern Nevada. Our findings show that near-surface wind direction variability decreases with increasing wind speeds and increases in environments with greater surface complexity. Across environments, there is a strong correlation between the variability in wind speed (i.e. turbulence intensity) and wind direction (i.e. the standard deviation in wind direction). In some environments, the standard deviation in wind direction varied as much as 15° to 75° on time scales of 1-10 minutes. We draw insights between our findings and previous plume tracking experiments to provide a general intuition for future field research and guidance for wind tunnel experimental design. From our analyses, we hypothesize that there may be an ideal range of wind speeds and environment complexity in which insects will be most successful when tracking an odor plume to its source.
Fast and robust metagenomic sequence comparison through sparse chaining with skani
Authors: Shaw Jim , Yu Yun William 
Published: January 2023

AbstractSequence comparison algorithms for metagenome-assembled genomes (MAGs) often have difficulties dealing with data that is high-volume or low-quality. We presentskani(https://github.com/bluenote-1577/skani), a method for calculating average nucleotide identity (ANI) using sparse approximate alignments. skani is more accurate than FastANI for comparing incomplete, fragmented MAGs while also being > 20 times faster. For searching a database of > 65, 000 prokaryotic genomes, skani takes only seconds per query and 6 GB of memory. skani is a versatile tool that unlocks higher-resolution insights for larger, noisier metagenomic data sets.
Frontotemporal Dementia Patient Neurons With Progranulin Deficiency Display Protein Dyshomeostasis
Authors: Elia Lisa , Herting Bianca , Alijagic Amela , Buselli Christina , Wong Leela , Morrison Grace , Prado Miguel A. , Paulo Joao A. , Gygi Steven P. , Finley Daniel , Finkbeiner Steven 
Published: January 2023

AbstractHaploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), a devastating neurodegenerative disease with no effective treatment. PGRN is required for efficient proteostasis, as loss of neuronal PGRN results in dysfunctional lysosomes and impaired clearance and cytoplasmic aggregation of TDP-43, a protein involved in neurodegeneration in FTD. These and other events lead to neurodegeneration and neuroinflammation. However, the detailed mechanisms leading to protein dyshomeostasis in PGRN-deficient cells remain unclear. We report here the development of human cell models of FTD with PGRN-deficiency to explore the molecular mechanisms underlying proteostasis breakdown and TDP-43 aggregation in FTD. Neurons differentiated from FTD patient induced pluripotent stem cells (iPSCs) have reduced PGRN levels, and the neurons recapitulate key disease features, including impaired lysosomal function, defective TDP-43 turnover and accumulation, neurodegeneration, and death. Proteomic analysis revealed altered levels of proteins linked to the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS) in FTD patient neurons, providing new mechanistic insights into the link between PGRN-deficiency and disease pathobiology.
Evolutionary selection of proteins with two folds
Authors: Schafer Joseph W. , Porter Lauren L. 
Published: January 2023

AbstractAlthough most globular proteins fold into a single stable structure1, an increasing number have been shown to remodel their secondary and tertiary structures in response to cellular stimuli2. State-of-the-art algorithms3-5predict that these fold-switching proteins assume only one stable structure6,7, missing their functionally critical alternative folds. Why these algorithms predict a single fold is unclear, but all of them infer protein structure from coevolved amino acid pairs. Here, we hypothesize that coevolutionary signatures are being missed. Suspecting that over-represented single-fold sequences may be masking these signatures, we developed an approach to search both highly diverse protein superfamilies–composed of single-fold and fold-switching variants–and protein subfamilies with more fold-switching variants. This approach successfully revealed coevolution of amino acid pairs uniquely corresponding to both conformations of 56/58 fold-switching proteins from distinct families. Then, using a set of coevolved amino acid pairs predicted by our approach, we successfully biased AlphaFold25to predict two experimentally consistent conformations of a candidate protein with unsolved structure. The discovery of widespread dual-fold coevolution indicates that fold-switching sequences have been preserved by natural selection, implying that their functionalities provide evolutionary advantage and paving the way for predictions of diverse protein structures from single sequences.
The impact of similarity metrics on cell type clustering in highly multiplexed in situ imaging cytometry data
Authors: Willie Elijah , Yang Pengyi , Patrick Ellis 
Published: January 2023

AbstractHighly multiplexedin situimaging cytometry assays have enabled researchers to scru-tinize cellular systems at an unprecedented level. With the capability of these assays to simultaneously profile the spatial distribution and molecular features of many cells, unsuper-vised machine learning, and in particular clustering algorithms, have become indispensable for identifying cell types and subsets based on these molecular features. However, the most widely used clustering approaches applied to these novel technologies were developed for cell suspension technologies and may not be optimal forin situimaging assays. In this work, we systematically evaluated the performance of various similarity metrics used to quan-tify the similarity between cells when clustering. Our results demonstrate that performance in cell clustering varies significantly when different similarity metrics were used. Lastly, we propose FuseSOM, an ensemble clustering algorithm employing hierarchical multi-view learning of similarity metrics and self-organizing maps (SOM). Using a stratified subsam-pling analysis framework, FuseSOM exhibits superior clustering performance compared to the current best-practice clustering approaches forin situimaging cytometry data analysis.
Andes virus genome mutations that are likely associated with animal-model attenuation and human person-to-person transmission
Authors: Bellomo Carla M. , Alonso Daniel O. , Pérez-Sautu Unai , Prieto Karla , Kehl Sebastian , Coelho Rocio M. , Periolo Natalia , Di Paola Nicholas , Ferressini-Gerpe Natalia , Kuhn Jens H. , Sanchez-Lockhart Mariano , Palacios Gustavo , Martínez Valeria P. 
Published: January 2023

STRUCTURED ABSTRACTAbstractWe performed whole-genome sequencing with bait-enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo; early, intermediate, and late cell-culture passages of an ANDV isolate from that animal; and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino-acid substitutions related to cell-culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Mutations in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased pathogenesis in the small animal model. Finally, we identified three amino-acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with person-to-person efficient transmission. Our results indicate that there are virulence-associated and transmission-associated single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility.ImportanceSeveral orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public-health concern because it is associated with the highest case-fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
ADHD and family life: a cross-sectional study of ADHD prevalence among pupils in China and factors associated with parental stress
Authors: Lv Tao , Leavey Gerard , Li Longlong , Tang Ying 
Published: January 2023

AbstractBackgroundAttention Deficit Hyperactivity Disorder (ADHD) is increasingly recognized as a major problem for children and their families in China. However, its influence on parental stress has been seldom explored.ObjectiveTo examine the prevalence of attention deficit hyperactivity disorder in a community sample of children aged 6-13 years, and the extent to which it impacts parental depression.MethodCross-sectional study of primary school pupils (number=2497) in Deyang, Sichuan Province, South-West China. We used standardized instruments to identify children with ADHD symptoms and parent depression.ResultsThe prevalence of ADHD was 9.8%. Factors associated with the likelihood of ADHD, included family environment(P=0.003), time spent with children(P=0.01), parenting style(P=0.01), and parental relationship, pupils self-harm and lower academic ability (P=0.001). After controlling for other factors, having a child with ADHD increased the likelihood of parents’ depression (OR=4.35, CI=2.68∼7.07), additional factors included parent relationship.ConclusionsADHD may be a common disorder among Chinese children, the symptoms of which may increase the likelihood of parent depression. There is a need for greater detection of ADHD in schools and an acknowledgement of the challenges the disorder creates for academic success and family wellbeing.
Serotonin blocker Ketanserin reduces coral reef fishCtenochaetus striatusaggressive behaviour during between-species social interactions
Authors: Staubli Virginie , Bshary Redouan , Triki Zegni 
Published: January 2023

AbstractA multitude of species engages in social interactions not only with their conspecifics but also with other species. Such interspecific interactions can be either positive, like helping, or negative, like aggressive behaviour. However, the physiological mechanisms of these behaviours remain unclear. Here, we manipulated the serotonin system, a well-known neurohormone for regulating intraspecific aggressive behaviour, to investigate its role in interspecific aggression. We tested whether serotonin blockade affects the aggressive behaviour of a coral reef fish species (Ctenochaetus striatus) that engages in mutualistic interactions with another species, the cleaner fish (Labroides dimidiatus). Although this mutualistic cleaning relationship may appear positive, cleaner fish do not always cooperate and remove ectoparasites from the other coral reef fish (“clients”) but tend to cheat and bite the client’s protective layer of mucus. Client fish thus often apply control mechanisms, like chasing, to deter their cleaner fish partners from cheating. Our findings show that blocking serotonin receptors 5-HT2A and 5-HT2C with ketanserin reduced the client fish’s aggressive behaviour towards cleaner fish, but in the context where the latter did not cheat. These results are evidence of the involvement of serotonin in regulating aggressive behaviour at the between-species social interactions level. Yet, the direction of effect we found here is the opposite of previous findings using a similar experimental set-up and ecological context but with a different client fish species (Scolopsis bilineatus). Together, it suggests that serotonin’s role in aggressive behaviour is complex, and at least in this mutualistic ecological context, the function is species-dependent. This warrants, to some extent, careful interpretations from single-species studies looking into the physiological mechanisms of social behaviour.