bluuebunny/crossref_metadata_2025 huggingface dataset:
Does precrastination explain why some observers are suboptimal in a visual search task?
Authors: Clarke Alasdair D. F. , Nowakowska Anna , Sauerberger Kyle , Rosenbaum David A. , Zentall Thomas R. , Hunt Amelia R.
Published: April 2024

How do we decide where to search for a target? Optimal search relies on first considering the relative informational value of different locations and then executing eye movements to the best options. However, many participants consistently move their eyes to locations that can be easily ascertained to neither contain the target nor provide new information about the target’s location. Here, we asked whether this suboptimal search behaviour represents a specific example of a general tendency towards precrastination: starting sub-goals of a task before they are needed, and in so doing, spending longer time on doing the task than is necessary. To test this hypothesis, we asked 200 participants to do two tasks: retrieve two heavy buckets (one close and one far) and search for a line segment. Precrastination is defined as consistently picking up the closer bucket first, versus the more efficient strategy of picking up the farther bucket first. Search efficiency is the proportion of fixations directed to more cluttered regions of the search array. Based on the pilot data, we predicted an association of precrastination with inefficient search strategies. Personality inventories were also administered to identify stable characteristics associated with these strategies. In the final dataset, there was no clear association between search strategy and precrastination, nor did these correlate strongly with any of the personality measures collected. This article received in-principle acceptance (IPA) at
Royal Society Open Science
on 29 January 2020. The accepted Stage 1 version of the manuscript, not including results and discussion, may be found at
https://osf.io/p2sjx
. This preregistration was performed prior to data collection and analysis.
Noise and opinion dynamics: how ambiguity promotes pro-majority consensus in the presence of confirmation bias
Authors: Steiglechner Peter , Keijzer Marijn A. , E. Smaldino Paul , Moser Deyshawn , Merico Agostino
Published: April 2024

Opinion dynamics are affected by cognitive biases and noise. While mathematical models have focused extensively on biases, we still know surprisingly little about how noise shapes opinion patterns. Here, we use an agent-based opinion dynamics model to investigate the interplay between confirmation bias—represented as bounded confidence—and different types of noise. After analysing where noise can enter social interaction, we propose a type of noise that has not been discussed so far, ambiguity noise. While previously considered types of noise acted on agents either before, after or independent of social interaction, ambiguity noise acts on communicated messages, assuming that socially transmitted opinions are inherently noisy. We find that noise can induce agreement when confirmation bias is moderate, but different types of noise require quite different conditions for this effect to occur. An application of our model to the climate change debate shows that at just the right mix of confirmation bias and ambiguity noise, opinions tend to converge to high levels of climate change concern. This result is not observed with the other types. Our findings highlight the importance of considering and distinguishing between the various types of noise and the unique role of ambiguity in opinion formation.
The quality of caregiver–child interaction is predicted by (caregivers’ perception of) their child’s interests
Authors: Madhavan Rajalakshmi , Mani Nivedita
Published: April 2024

This current study examines the extent to which children’s interests and caregivers’ sensitivity to their children’s interests are associated with the quality of caregiver–child interaction, and subsequent learning. Eighty-one caregiver–child dyads (24–30-month old children) completed an online shared book-reading task where caregivers and children read two e-books with pictures and descriptions of objects from different categories—one previously determined to be of low and one of high interest to the child (with one novel word-object mapping introduced in each book). We also obtained separate behavioural indices of children’s interests and children’s later recognition of newly introduced word-object mappings. Our findings highlight that the quality of caregiver–child interaction is predicted by children’s interests and caregivers’ perception of children’s interests, although we find only limited overlap between our behavioural indices of children’s interests and caregiver perception of children’s interests. Neither of these factors predicted later novel word recognition. Thus, while the dynamics between higher quality of caregiver–child interaction, children’s interests and learning remain inconclusive, caregivers and children appear to be more attentive, enthusiastic and engaged in reading about topics that (caregivers believe) interest the child. Furthermore, learning in itself seems to be successful, regardless of factors involved, through the mere task of shared book reading.
Evolution of bioluminescence in Anthozoa with emphasis on Octocorallia
Authors: DeLeo Danielle M. , Bessho-Uehara Manabu , Haddock Steven H.D. , McFadden Catherine S. , Quattrini Andrea M.
Published: April 2024

Bioluminescence is a widespread phenomenon that has evolved multiple times across the tree of life, converging among diverse fauna and habitat types. The ubiquity of bioluminescence, particularly in marine environments where it is commonly used for communication and defense, highlights the adaptive value of this trait, though the evolutionary origins and timing of emergence remain elusive for a majority of luminous organisms. Anthozoan cnidarians are a diverse group of animals with numerous bioluminescent species found throughout the world's oceans, from shallow waters to the light-limited deep sea where bioluminescence is particularly prominent. This study documents the presence of bioluminescent Anthozoa across depth and explores the diversity and evolutionary origins of bioluminescence among Octocorallia—a major anthozoan group of marine luminous organisms. Using a phylogenomic approach and ancestral state reconstruction, we provide evidence for a single origin of bioluminescence in Octocorallia and infer the age of occurrence to around the Cambrian era, approximately 540 Ma—setting a new record for the earliest timing of emergence of bioluminescence in the marine environment. Our results further suggest this trait was largely maintained in descendants of a deep-water ancestor and bioluminescent capabilities may have facilitated anthozoan diversification in the deep sea.
Alterations in cell arrangements of group B streptococcus due to virulence factor expression can bias estimates of bacterial populations based on colony count measures
Authors: Thapa Ruby , Goh Kelvin G. K. , Desai Devika , Copeman Ellen , Acharya Dhruba , Sullivan Matthew J. , Ulett Glen C.
Published: April 2024

Group B streptococcus (GBS) is a chain-forming commensal bacterium and opportunistic pathogen that resides in the gastrointestinal and genitourinary tract of healthy adults. GBS can cause various infections and related complications in pregnant and nonpregnant women, adults, and newborns. Investigations of the mechanisms by which GBS causes disease pathogenesis often utilize colony count assays to estimate bacterial population size in experimental models. In other streptococci, such as group A streptococcus and pneumococcus, variation in the chain length of the bacteria that can occur naturally or due to mutation can affect facets of pathogenesis, such as adherence to or colonization of a host. No studies have reported a relationship between GBS chain length and pathogenicity. Here, we used GBS strain 874391 and several derivative strains displaying longer chain-forming phenotypes (874391pgapC, 874391ΔcovR, 874391Δstp1) to assess the impact of chain length on bacterial population estimates based on the colony-forming unit (c.f.u.) assay. Disruption of GBS chains via bead beating or sonication in conjunction with fluorescence microscopy was used to compare chaining phenotypes pre- and post-disruption to detect long- and short-chain forms, respectively. We used a murine model of GBS colonization of the female reproductive tract to assess whether chaining may affect bacterial colonization dynamics in the host during chronic infection in vivo. Overall, we found that GBS exhibiting long-chain form can significantly affect population size estimates based on the colony count assay. Additionally, we found that the length of chaining of GBS can affect virulence in the reproductive tract colonization model. Collectively, these findings have implications for studies of GBS that utilize colony count assays to measure GBS populations and establish that chain length can affect infection dynamics and disease pathogenesis for this important opportunistic pathogen.
Effect of Electroacupuncture on Delayed-Onset Muscle Soreness Induced by Eccentric Exercise in Young Untrained Men: Comparison of Contralateral and Ipsilateral Stimulation
Authors: Komine Shoichi , Miura Ikuru , Hu Teng , Ogata Akihiro , Tamai Shinsuke , Tokinoya Katsuyuki , Sugasawa Takehito , Oh Sechang , Wada Shota , Takekoshi Kazuhiro , Ito Go , Isobe Tomonori , Matsui Takashi , Ohmori Hajime
Published: April 2024

Background: Electroacupuncture stimulation is sometimes used to prevent and treat delayed onset muscle soreness (DOMS) induced by exercise; however, the effect is unclear. Using a human biceps brachii muscle pain induction model, we investigated the effect of contralateral electroacupuncture (CEA) versus ipsilateral electroacupuncture (IEA) stimulation on DOMS and muscle injury markers. Methods: Nineteen young men were randomly assigned to receive either CEA or IEA. All participants performed eccentric exercise using the biceps brachii muscle of the nondominant arm to induce muscle damage. Electroacupuncture stimulation (1.5 Hz, 15 minutes) was applied to the dominant arm in the CEA group and the nondominant arm in the IEA group. Electroacupuncture stimulation was applied in both groups from 7 days before exercise to 4 days after exercise. All variables were analyzed at the following seven timepoints: baseline, immediately before exercise, immediately after exercise, and on days 1–4 after exercise. Results: Palpation pain was significantly lower in the IEA group than the CEA group at 72 and 96 hours after exercise. The decrease in the elbow range of motion after exercise was significantly suppressed by electroacupuncture stimulation. The muscle injury markers (creatine kinase, lactate dehydrogenase) increased following exercise, but these changes were not significantly influenced by IEA stimulation. IEA suppressed exercise-induced oxidative stress at 72 hours after exercise. Conclusion: This study suggests that the application of IEA before and after eccentric exercise effectively reduces DOMS. Electroacupuncture might suppress increases in oxidative stress elicited by eccentric exercise.
Characterising time-on-task effects on oscillatory and aperiodic EEG components and their co-variation with visual task performance
Authors: Kopčanová Martina , Thut Gregor , Benwell Christopher SY , Keitel Christian
Published: April 2024

Research on brain-behaviour relationships often makes the implicit assumption that these derive from a co-variation of stochastic fluctuations in brain activity and performance across trials of an experiment. However, challenging this assumption, oscillatory brain activity, as well as indicators of performance, such as response speed, can show systematic trends with time on task. Here we tested whether time-on-task trends explain a range of relationships between oscillatory brain activity and response speed, accuracy as well as decision confidence. Thirty-six participants performed 900 trials of a two-alternative forced choice visual discrimination task with confidence ratings. Pre- and post-stimulus spectral power (1-40Hz) and aperiodic (i.e., non-oscillatory) components were compared across blocks of the experimental session and tested for relationships with behavioural performance. We found that time-on-task effects on oscillatory EEG activity were primarily localised within the alpha band, with alpha power increasing and peak alpha frequency decreasing over time, even when controlling for aperiodic contributions. Aperiodic, broadband activity on the other hand did not show time-on-task effects in our data set. Importantly, time-on-task effects in alpha frequency and power explained variability in single-trial reaction times, and controlling for time-on-task effectively removed these relationships. However, time-on-task effects did not affect other EEG signatures of behavioural performance, including post-stimulus predictors of single-trial decision confidence. Our results dissociate alpha-band brain-behaviour relationships that can be explained away by time-on-task from those that remain after accounting for it - thereby further specifying the potential functional roles of alpha in human visual perception.
Proteome trade-off between primary and secondary metabolism shapes acid stress induced bacterial exopolysaccharide production
Authors: Qiu Sizhe , Yang Aidong , Yang Xinyu , Li Wenlu , Zeng Hong , Wang Yanbo
Published: April 2024

The exopolysaccharide (EPS) produced byLactiplantibacillus plantarumis a high-value bioproduct in food and health industries, and its biosynthesis has been found as a secondary metabolic pathway to mediate acid stress. To quantitatively investigate acid stress response inL. plantarumand model EPS production, this study measured metabolomics, proteomics and growth data forL. plantarumHMX2 cultured at 4 different pH values. The growth and metabolomics data showed that under acid stress, the EPS production flux was evidently enhanced while the glycolysis and cellular growth were inhibited. The following proteomic analysis found that EPS biosynthetic proteins were significantly up-regulated under acid stress and pinpointed Fur as the most probable transcriptional factor controlling EPS biosynthesis inL. plantarum. Furthermore, we identified a proteome trade-off between primary metabolism and EPS biosynthesis, which were then mechanistically depicted by a regulatory proteome constrained flux balance analysis (RPCFBA) model. As the first metabolic model that can simulate secondary metabolism, the RPCFBA model demonstrated good accuracy in predicting growth rates and EPS production fluxes ofL. plantarumHMX2, validated by experimental data. Thein-silicoperturbation on carbon sources further showed the potential of applying the presented modeling framework to the design and control of microbial secondary metabolism.
The Single-cell Pediatric Cancer Atlas: Data portal and open-source tools for single-cell transcriptomics of pediatric tumors
Authors: Hawkins Allegra G. , Shapiro Joshua A. , Spielman Stephanie J. , Mejia David S. , Prasad Deepashree Venkatesh , Ichihara Nozomi , Yakovets Arkadii , Wheeler Kurt G. , Bethell Chante J. , Foltz Steven M. , O’Malley Jennifer , Greene Casey S. , Taroni Jaclyn N.
Published: April 2024

The Single-cell Pediatric Cancer Atlas (ScPCA) Portal (https://scpca.alexslemonade.org/) is a data resource for uniformly processed single-cell and single-nuclei RNA sequencing (RNA-seq) data and de-identified metadata from pediatric tumor samples. Originally comprised of data from 10 projects funded by Alex’s Lemonade Stand Foundation, the Portal currently contains summarized gene expression data for over 500 samples from over 50 types of cancers from ALSF-funded and community-contributed datasets. In addition to gene expression data from single-cell and single-nuclei RNA-seq, the Portal holds data obtained from bulk RNA-seq, spatial transcriptomics, and feature barcoding methods, such as CITE-seq and cell hashing.

ScPCA data are available for download asSingleCellExperimentorAnnDataobjects and are ready for downstream analyses. Objects include raw counts and normalized gene expression data, PCA and UMAP coordinates, and automated cell type annotations. Additionally, all downloads include two summary reports for each library: a quality control report summarizing sample statistics and displaying visualizations of cell metrics and a cell type annotation report with comparisons among cell type annotation methods and diagnostic plots to assess annotation quality. MergedSingleCellExperimentandAnnDataobjects containing all gene expression data and metadata for all samples in an ScPCA project are also available for download. These objects are useful when performing analysis on multiple samples simultaneously. Comprehensive documentation about data processing and the contents of files on the Portal, including a guide to getting started working with an ScPCA dataset, can be found athttp://scpca.readthedocs.io.

All data on the Portal were uniformly processed usingscpca-nf, an open-source and efficient Nextflow workflow that usesalevin-fryto quantify all single-cell and single-nuclei RNA-seq data, any associated CITE-seq or cell hash data, spatial transcriptomics data, and bulk RNA-seq. Any pediatric cancer-relevant data sets processed withscpca-nfare eligible for inclusion on the ScPCA Portal, enabling continuous growth of the ScPCA Portal to help pediatric cancer researchers spend less time finding and processing data and more time answering their pressing research questions.
Synthetic bacterial consortium for degradation of plastic pyrolysis oil waste
Authors: Jia Yunpu , Dou Jingxi , Ballersted Hendrik , Blank Lars M. , Xing Jianmin
Published: April 2024

The plasic crisis is ominipresent, from littering macroplastic to reports that document plastic in every niche of this planet, including the human body. In order to achieve higher recycling quotas, especially of mixed plastic waste, pyrolysis seems to be a viable option. However, depending on the process parameters, plastic pyrolysis oil waste is encountered, which is difficult to valorize, due to the enormous spread of the molecules included. To reduce the molecular heterogeneity, we here artificially compounded, monitored, and optimized the performance of a bacterial consortium, which has the ability to tolerate organic pollutants and use them as energy and carbon sources for their own metabolic activity. The primary constituents of the here used plastic pyrolysis oil waste (PPOW) were alkanes and ε-caprolactam. The bacterial community exhibited noteworthy efficacy in eliminating alkanes of diverse chain lengths ranging from 71% to 100%. Additionally, within 7-days, the microbial community demonstrated a removal efficiency surpassing 50% for various aromatic hydrocarbons, along with complete eradication of ε-caprolactam and naphthalene. Besides, a back-propagation (BP) neural network method is applied to evaluate O2consumption as a measure of microbial activity. The insights gained were used to build a model, which is able to predict O2depletion in long-time experiments and other experimental conditions. The results are discussed in the context of a developing (open) circular plastic economy.

Graphical abstract

Highlight

Synthetic bacterial communities are used to remove plastic hydrolysis oil waste

The optimized biphase reaction system can remove the majority of pollutants

The biodegradation process can be monitored in a real-time bioprocess software

Neural network techniques are used to model and predict the removal process
Mosaic evolution of a learning and memory circuit in Heliconiini butterflies
Authors: Farnworth Max S. , Loupasaki Theodora , Couto Antoine , Montgomery Stephen H.
Published: April 2024

A critical function of central neural circuits is to integrate sensory and internal information to cause a behavioural output. Evolution modifies such circuits to generate adaptive change in sensory detection and behaviour, but it remains unclear how selection does so in the context of existing functional and developmental constraints. Here, we explore this question by analysing the evolutionary dynamics of insect mushroom body circuits. Mushroom bodies are constructed from a conserved wiring logic, mainly consisting of Kenyon cells, dopaminergic neurons and mushroom body output neurons. Kenyon cells carry sensory identity signals, which are modified in strength by dopaminergic neurons and carried forward into other brain areas by mushroom body output neurons. Despite the conserved makeup of this circuit, there is huge diversity in mushroom body size and shape across insects. However, an empirical framework of how evolution modifies the function and architecture of this circuit is largely lacking. To address this, we leverage the recent radiation of a Neotropical tribe of butterflies, the Heliconiini (Nymphalidae), which show extensive variation in mushroom body size over comparatively short phylogenetic timescales, linked to specific changes in foraging ecology, life history and cognition. To understand the mechanism by which such an extensive increase in size is accommodated through changes in lobe circuit architecture, we first combined immunostainings of structural markers, neurotransmitters and neural injections to generate, to our knowledge, the most detailed description of a Papilionoidea butterfly mushroom body lobe. We then provide a comparative, quantitative dataset which shows that some Kenyon cell populations expanded with a higher rate than others inHeliconius, providing an anatomical parallel to specific shifts in behaviour. Finally, we identified an increase in GABA-ergic feedback neurons essential for non-elemental learning and sparse coding, but conservation in dopaminergic neuron number. Taken together, our results demonstrate mosaic evolution of functionally related neural systems and cell types and identify that evolutionary malleability in an architecturally conserved parallel circuit guides adaptation in cognitive ability.
Deep, unbiased and quantitative mass spectrometry-based plasma proteome analysis of individual responses to mRNA COVID-19 vaccine
Authors: Huang Ting , Campos Alex Rosa , Wang Jian , Stukalov Alexey , Díaz Ramón , Maurya Svetlana , Motamedchaboki Khatereh , Hornburg Daniel , Saciloto-de-Oliveira Laura R. , Innocente-Alves Camila , Calegari-Alves Yohana P. , Batzoglou Serafim , Beys-da-Silva Walter O. , Santi Lucélia
Published: April 2024

Global campaign against COVID-19 have vaccinated a significant portion of the world population in recent years. Combating the COVID-19 pandemic with mRNA vaccines played a pivotal role in the global immunization effort. However, individual responses to a vaccine are diverse and lead to varying vaccination efficacy. Despite significant progress, a complete understanding of the molecular mechanisms driving the individual immune response to the COVID-19 vaccine remains elusive. To address this gap, we combined a novel nanoparticle-based proteomic workflow with tandem mass tag (TMT) labeling, to quantitatively assess the proteomic changes in a cohort of 12 volunteers following two doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. This optimized protocol seamlessly integrates comprehensive proteome analysis with enhanced throughput by leveraging the enrichment of low-abundant plasma proteins by engineered nanoparticles. Our data demonstrate the ability of this nanoparticle-based workflow to quantify over 3,000 proteins from 48 human plasma samples, providing the deepest view into COVID-19 vaccine-related plasma proteome study. We identified 69 proteins exhibiting a boosted response to the vaccine after the second dose. Additionally, 74 proteins were differentially regulated between seven volunteers, who contracted COVID-19 despite receiving two doses of the vaccine, and the ones who did not contract COVID-19. These findings offer valuable insights into individual variability in response to vaccination, demonstrating the potential of personalized medicine approaches in vaccine development.
Mechanism and spectrum of inhibition of a 4’-cyano modified nucleotide analog against diverse RNA polymerases of prototypic respiratory RNA viruses
Authors: Gordon Calvin J. , Walker Simon M. , Tchesnokov Egor P. , Kocincova Dana , Pitts Jared , Siegel Dustin S. , Perry Jason K. , Feng Joy Y. , Bilello John P. , Götte Matthias
Published: April 2024

The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5′-triphosphate (TP) metabolite of a 4ʹ-cyano modifiedC-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4ʹ-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1′-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1ʹ-cyano and 4ʹ-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
A conserved lysine/arginine-rich motif in potyviral 6K1 protein is key in engaging autophagy-mediated self-degradation for completing pepper veinal mottle virus infection
Authors: Hu Weiyao , Deng Changhui , Qin Li , Liu Peilan , Wang Linxi , Wang Xiaoqin , Shi Wei , Aziz Asma , Li Fangfang , Cheng Xiaofei , Wang Aiming , Dai Zhaoji , Xiang Xiaohua , Cui Hongguang
Published: April 2024

Potyviruses possess one positive-sense single-stranded RNA genome mainly with polyprotein processing as their gene expression strategy. The resulting polyproteins are proteolytically processed by three virus-encoded proteases into 11 or 12 mature proteins. One of such, 6-kDa peptide 1 (6K1), is an understudied viral factor. Its function in viral infection remains largely mysterious. This study is to reveal part of its roles by using pepper veinal mottle virus (PVMV) as a model virus. Alanine substitution screening analysis revealed that 15 out of 17 conserved residues across potyviral 6K1 sequences are essential for PVMV infection. However, 6K1 protein is less accumulated in virus-infected cells, even though P3-6K1 junction is efficiently processed by NIa-Pro for its release, indicating that 6K1 undergoes a self-degradation event. Mutating the cleavage site to prevent NIa-Pro processing abolishes viral infection, suggesting that the generation of 6K1 along with its degradation might be important for viral multiplication. We corroborated that cellular autophagy is engaged in 6K1’s degradation. Individual engineering of the 15 6K1 variants into PVMV was performed to allow for their expression along with viral infection. Five of such variants, D30A, V32A, K34A, L36A, and L39A, significantly interfere with viral infection. The five residues are enclosed in a conserved lysine/arginine-rich motif; four of them appear to be crucial in engaging autophagy-mediated self-degradation. Based on these data, we envisaged a scenario that potyviral 6K1s interact with an unknown anti-viral component to be co-degraded by autophagy to promote viral infection.

IMPORTANCE

Potyvirusis the largest genus of plant-infecting RNA viruses, which encompasses socio-economically important virus species, such asPotato virus Y,Plum pox virus, andSoybean mosaic virus. Like all picorna-like viruses, potyviruses express their factors mainly via polyprotein processing. Theoretically, viral factors P3 through CP, including 6K1, should share an equivalent number of molecules. The 6K1 is small in size (∼6 kDa) and conserved across potyviruses, but less accumulated in virus-infected cells. This study demonstrates that cellular autophagy is engaged in the degradation of 6K1 to promote viral infection. In particular, we found a conserved lysine/arginine-rich motif in 6K1s across potyviruses that is engaged in this degradation event. This finding reveals one facet of a small protein that help understand the pro-viral role of cellular autophagy in viral infection.
Histopathological evaluation of abdominal aortic aneurysms with deep learning
Authors: Kolbinger Fiona R. , El Nahhas Omar S. M. , Nackenhorst Maja Carina , Brostjan Christine , Eilenberg Wolf , Busch Albert , Kather Jakob Nikolas
Published: April 2024

Computational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis. However, the application of deep learning techniques in vascular pathology remains underexplored. Here, we present a comprehensive evaluation of deep learning-based approaches to analyze digital whole-slide images of abdominal aortic aneurysm samples from 369 patients from three European centers. Deep learning demonstrated robust performance in predicting inflammatory characteristics, particularly in the adventitia, as well as fibrosis grade and remaining elastic fibers in the tunica media. Overall, this study represents the first comprehensive evaluation of computational pathology in vascular disease and has the potential to contribute to improved understanding of abdominal aortic aneurysm pathophysiology and personalization of treatment strategies, particularly when integrated with radiological phenotypes and clinical outcomes.
An increase in aspartate aminotransferase levels can predict worsening disease severity in Japanese patients with COVID-19
Authors: Matsumoto Kengo , Nishida Tsutomu , Okabe Satoru , Sakamoto Naohiro , Fujii Yoshifumi , Osugi Naoto , Sugimoto Aya , Nakamatsu Dai , Yamamoto Masashi , Fukui Koji , Morimura Osamu , Abe Kinya , Okauchi Yukiyoshi , Iwahashi Hiromi , Inada Masami
Published: April 2024

Background

The prognostic significance of liver dysfunction in coronavirus disease 2019 (COVID-19) patients remains unclear. This study aimed to investigate the association between liver function test results and severe disease progression in COVID-19 patients.

Methods

We conducted a retrospective study that included consecutive Japanese COVID-19 patients between February 2020 and May 2021. We identified the predictive variables for severe disease progression by utilizing established factors and multivariate logistic analysis. The Kaplan‒Meier method was used to estimate severe disease-free survival. Furthermore, we evaluated the hazard ratios (HRs) among three aspartate aminotransferase (AST) grades using Cox regression analysis: grade 1, AST < 30 U/L; grade 2, 30 U/L≤ AST < 60 U/L; and grade 3, AST >60 U/L.

Results

After exclusion, 604 symptomatic COVID-19 patients were enrolled during the study period, and 141 (23.3%) of them developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis of the fourteen significant variables revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were significant predictive variables. Severe disease-free survival times were significantly separated according to AST grade severity (HR: grade 2 to grade 1: 4.07 (95% CI: 2.06-8.03); HR: grade 3 to grade 1: 7.66 (95% CI: 3.89-15.1)).

Conclusion

AST levels at admission were an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.
Association between Lithium and thyroid function: a retrospective study
Authors: Agarwal Akanksha , David Arul Kevin Daniel , Mahadevan Jayant , Viswanath Biju
Published: April 2024

Introduction

Bipolar Disorder (BD) is associated with thyroid dysfunction, and literature on the clinical impact of Lithium on thyroid function in BD patients remains inconsistent. Thus, we aimed to systematically estimate the prevalence of thyroid dysfunction in Lithium treated BD patients, explore the clinical factors associated with the development of hypothyroidism and time to detection of thyroid dysfunction after Lithium initiation.

Methods

A retrospective review of BD patients with a follow-up between Jan to Dec 2019 was conducted. Patients with no pre-existing thyroid dysfunction and at least six months of cumulative exposure to Lithium were included. For the included 444 patients, sociodemographic, clinical variables and laboratory assessment values were charted systematically. Patients with TSH > 5 mIU/L were classified as hypothyroid.

Results

27.7% (n=123) developed thyroid dysfunction; 27.3% (n=121) developed hypothyroidism after Lithium exposure. The median duration of detection of hypothyroidism was 33.6 months for females and 38.4 months for males, with no significant difference across genders (p=.52). A significantly higher proportion of females (49.5%) developed hypothyroidism as opposed to males (23.7%). Hypothyroid females differed significantly with respect to comorbid diabetes mellitus and hypertension; from euthyroid females. First-episode depression was associated with hypothyroidism in males. However, multivariate analyses did not detect any associations.

Discussion

One-fourth of Lithium-treated patients developed hypothyroidism. This risk was higher in female patients, with onset close to 33 months, indicating the need for closer monitoring for long durations. The impact of hypothyroidism on prognosis and response to treatment needs further exploration.
Stones in Our Pockets: Mental Health Dimensions of Grief in Contemporary Video Games
Authors: Reay Emma , Ma Minhua , Mankee-Williams Anna , Pavarini Gabriela , Shaughnessy Nicola , Bhui Kamaldeep
Published: April 2024

This article combines the expertise of games studies scholars, medical ethicists, and clinical psychologists to analyse representations of grief in contemporary video games. Grief is a universal human experience, but navigating its psychological, social, and embodied effects can be a challenging task. Constructionist approaches to grief therapy emphasise the importance of metaphors for understanding the experience of loss (Nadeau 2006; Young 2008; Neimeyer 2010; Southall 2013). Paying attention to the metaphorical language used by a client can provide a therapist with key information about the client’s personal and cultural perspectives and world view. Equally, a therapist can work with clients to devise metaphors that shift their perspectives and aid the process of meaning-making. Video games provide players with new metaphors to express and explore grief. Since video games communicate across audio, visual, verbal, haptic, mechanical, and performative modes, they can offer a complete gestalt that touches on the physical, emotional, practical, and systemic impact of loss. In this article, we survey the multimodal metaphors for grief that appear in 14 commercial-off-the-shelf (COTS) video games and identify recurring tropes and themes. We consider 1) what is illuminated by these metaphors? 2) what is obscured by these metaphors? and 3) what are the therapeutic implications of these metaphors? We conclude with a set of recommendations for game developers who want to design ‘serious games’ that explore emotionally fraught topics, and a set of recommendations for grief and bereavement therapists seeking to integrate video games into their practice.
Development of a simple and highly sensitive virion concentration method to detect SARS-CoV-2 in saliva
Authors: Yamazaki Yasuko , Alonso Uxía Alonso , Galay Remil L. , Yamazaki Wataru
Published: April 2024

Background

Controlling novel coronavirus pandemic infection (COVID-19) is a global challenge, and highly sensitive testing is essential for effective control. The saliva is a promising sample for high-sensitivity testing because it is easier to collect than nasopharyngeal swab samples and allows large-volume testing.

Results

We developed a simple SARS-CoV-2 concentration method from saliva samples that can be completed in less than 60 min. We performed a spike test using 12 ml of saliva samples obtained from healthy volunteer people, and the developed method performance was evaluated by comparison using a combination of automatic nucleic acid extraction followed by RT-qPCR detection. In saliva spike tests using a 10-fold dilution series of SARS-CoV-2, the developed method was consistently 100-fold more sensitive than the conventional method.

Conclusions

The developed method can improve the sensitivity of the SARS-CoV-2 test using saliva and speed up and save labor in screening tests by pooling many samples. Furthermore, the developed method has the potential to contribute to the highly sensitive detection of various human and animal viral pathogens from the saliva and various clinical samples.

Highlight

A method has been developed to detect SARS-CoV-2 from human saliva with 100 times higher sensitivity than conventional methods.

The developed method combines simple pretreatment within 60 min with conventional nucleic acid extraction and RT-qPCR.

This method can be applied for more sensitive virus testing from individual saliva.

This method can potentially be applied to screening more than 100 saliva samples while maintaining the equivalent detection power of conventional methods.

The method can be adapted to improve the sensitivity of detecting various pathogens from human and animal saliva.
Hackflex library preparation enables low-cost metagenomic profiling
Authors: Goldman Samantha L. , Sanders Jon G. , Sprockett Daniel D. , Landers Abigail , Yan Weiwei , Moeller Andrew H.
Published: April 2024

Shotgun metagenomic sequencing provides valuable insights into microbial communities, but the high cost of library preparation with standard kits and protocols is a barrier for many. New methods such as Hackflex use diluted commercially available reagents to greatly reduce library preparation costs. However, these methods have not been systematically validated for metagenomic sequencing. Here, we evaluate Hackflex performance by sequencing metagenomic libraries from known mock communities as well as mouse fecal samples prepared by Hackflex, Illumina DNA Prep, and Illumina TruSeq methods. Hackflex successfully recovered all members of the Zymo mock community, performing best for samples with DNA concentrations <1 ng/uL. Furthermore, Hackflex was able to delineate microbiota of individual inbred mice from the same breeding stock at the same mouse facility, and statistical modeling indicated that mouse ID explained a greater fraction of the variance in metagenomic composition than did library preparation method. These results show that Hackflex is suitable for generating inventories of bacterial communities through metagenomic sequencing.
Phages indirectly maintain plant pathogen defense through regulation of the commensal microbiome
Authors: Debray Reena , Conover Asa , Koskella Britt
Published: April 2024

Many infectious diseases are associated with altered communities of bacteriophage viruses (phages). As parasites of bacteria, phages can regulate microbiome diversity and composition and may therefore affect disease susceptibility. Yet observational studies alone do not allow us to determine whether altered phage profiles are a contributor to disease risk, a response to infection, or simply an indicator of dysbiosis. To address this question, we used size-selective filtration to separate plant-associated microbial communities from their respective phages, then transplanted them together or separately onto tomato plants that we subsequently challenged with the bacterial pathogenPseudomonas syringae. Microbial and phage communities together were more disease-protective than either component was alone, an effect that could not be explained by direct effects of phages on eitherP. syringaeor the plant host. Moreover, the protective effect of phages was strongest when microbial and phage communities were isolated from neighboring field locations (allopatric phages), rather than from the same host plant (sympatric phages). This suggests a Goldilocks effect in which moderate rates of phage lysis maintain a microbiome community structure that is most resistant to pathogen invasion. Overall, our results support the idea that phage communities contribute to plant defenses by modulating the microbiome.
The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modificationsin vivo
Authors: Shi Mengyang , Li Jie , Liu Xiuxiu , Liu Kuo , He Lingjuan , Pu Wenjuan , Weng Wendong , Zhang Shaohua , Zhao Huan , Lui Kathy O. , Zhou Bin
Published: April 2024

Cre-loxP technology, a cornerstone in fate mapping andin vivogene function studies, faces challenges in achieving precise and efficient conditional mutagenesis through inducible systems. This study introduces two innovative genetic tools designed to overcome these limitations. The first, roxCre, enables DreER-mediated Cre release, paving the way for intersectional genetic manipulation that permits increased precision and efficiency. The second, loxCre, facilitates conditional gene targeting by allowing any CreER line to induce Cre expression with significantly enhanced efficiency. These tools incorporate a fluorescent reporter for genetic lineage tracing, simultaneously revealing efficient gene knockout in cells marked by the reporter. These strategies hold great potential for precise and efficient exploration of lineage-specific gene functions, marking a significant advancement in genetic research methodologies.
First application of digital-PCR in oenology for the specific detection of intact cells ofBrettanomyces bruxellensisin the winemaking process
Authors: Gruet Cécile , Mattia Jérémy Di , Hiaumet Magali , Pestel Dylan , Araiz Caroline , Saadi Sarah , Ducousso Marie , Courot Olivier
Published: April 2024

Wine is a complex matrix resulting from a fermentation process carried out by specific microbial communities. These communities can be in competition and the development of some microorganisms, as the yeastBrettanomyces bruxellensis, can impact the fermentation process and lead to organoleptic alterations of wine. To manage this risk, microbiological diagnostic methods as microscopic observations, qPCR or flow cytometry are already used in oenology, but remain either not specific enough, or tedious. In this context, IAGE (Ingénierie et Analyses en Génétique Environnementale) has developed the first digital-PCR system enabling the detection and quantification ofB. bruxellensisduring the whole winemaking process. Furthermore, wine DNA extraction was optimized to enable a representative and sensitive analysis ofB. bruxellensisintact cells, as well as an easy-to-implement protocol to cope with the increasing number of samples to analyze. The IAGE workflow forB. bruxellensisquantification has been proven to be successful when analyzing naturally-contaminated samples during the different steps of the winemaking process and offers a robust method to oenologists for appropriate treatments and risk management in wine cellars.

Highlights

Development of a dPCR method led to a highly-specific analysis ofB. bruxellensisintact cells in different steps of the winemaking process.

DNA extraction method has been optimized to be robust across various types of wine with varying concentrations of inhibitors, as well as throughout different stages of the wine making process.

The complete process was proven successful in analyzing a large number of naturally-contaminated samples, giving results in less than 48 hours.
Anatomical circuits for flexible spatial mapping by single neurons in posterior parietal cortex
Authors: Ahmed Bashir , Ko Hee Kyoung , Rüsseler Maria , Smith Jackson E. T. , Krug Kristine
Published: April 2024

Primate lateral intraparietal area (LIP) is critical for cognitive processing. Its contribution to categorization and decision-making has been causally linked to neurons’ spatial sensorimotor selectivity. We reveal the intrinsic anatomical circuits and neuronal responses within LIP that provide the substrate for this flexible generation of motor responses to sensory targets. Retrograde tracers delineate a loop between two distinct operational compartments, with a sensory-like, point-to-point projection from ventral to dorsal LIP and an asymmetric, more widespread projection in reverse. Neurophysiological recordings demonstrate that especially more ventral LIP neurons exhibit motor response fields that are spatially distinct from its sensory receptive field. The different associations of response and receptive fields in single neurons tile visual space. These anatomical circuits and neuronal responses provide the basis for the flexible allocation of attention and motor responses to salient or instructive visual input across the visual field.
Production, analysis, and safety assessment of a soil and plant-based natural material with microbiome- and immune-modulatory effects
Authors: Parajuli Anirudra , Mäkela Iida , Roslund Marja I. , Ringqvist Emma , Manninen Juulia , Sun Yan , Nurminen Noora , Oikarinen Sami , Laitinen Olli H. , Hyöty Heikki , Flodström-Tullberg Malin , Sinkkonen Aki
Published: April 2024

Reduced contact with the microbiota from the natural environment has been suggested to contribute to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in the western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microflora and promotes immunoregulation that may be associated with a reduced risk for IMIDs. To provide a framework for future preclinical studies and clinical trials, this study describes how the preparation of BDB was standardized, its microbial content and safety assessments. Multiple batches of BDB were manufactured and microbial composition analyzed using 16S rRNA gene sequencing. We observed a consistently high alpha diversity and relative abundance of bacteria normally found in soil and vegetation. We also found that inactivation of BDB by autoclaving effectively inactivates human and murine bacteria, viruses and parasites. Finally, we demonstrate that experimental mice prone to develop IMIDs (non-obese diabetic, NOD, mouse model) can be exposed to BDB without causing adverse effects on animal health and welfare. Our study lays the foundation for a safe, sustainable, and affordable way to mimic exposure to natural microbiota that has the potential to have enormous health- and socio-economic impacts.