bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated model of the effects on fitness of beneficial, deleterious, and neutral mutations in sexual populations
Authors: Irlam Gordon 
Published: June 2023

AbstractThe fitness effects of beneficial, deleterious, and neutral mutations have historically been largely analyzed in isolation. Here, an integrated model of the fitness effects of mutations in sexual populations is assembled and analyzed. The model suggests the fitness effects associated with beneficial mutations can not be ignored simply because they are rare. The prospective load is defined as the genetic load associated with beneficial mutations that are feasible, but have yet to occur and begun the process of fixing. The optimal spontaneous mutation rate for a population is shown to occur when the prospective load is approximately equal to the mutational load. This population optimal mutation rate could be brought about through macroevolution. It differs from the as-small-as-possible rate that might be expected from microevolutionary considerations.
Morc1 re-establishes heterochromatin on activated transposons and shapes the host transcriptome in gonocytes
Authors: Uneme Yuta , Maeda Ryu , Nakayama Gen , Narita Haruka , Takeda Naoki , Hiramatsu Ryuji , Nishihara Hidenori , Nakato Ryuichiro , Kanai Yoshiakira , Araki Kimi , Siomi Mikiko C. , Yamanaka Soichiro 
Published: June 2023

SummaryFollowing reprogramming of DNA methylation, numerous transposable elements (TEs) are transiently activated in male prenatal gonocytes. Persistent expression of such TEs to adulthood leads to arrest of germ cell development. However, how these TEs are re-silenced has been unexplored. Here, we found that DNA-binding protein Morc1 re-established H3K9me3-marked heterochromatin on activated TEs, which involved methyltransferase SetDB1. Although Morc1 also triggered DNA methylation, the types of Morc1-targeted TEs for each epigenetic modification were different, suggesting that these two mechanisms were largely independent of each other. Significant overlap between TEs targeted by Morc1 and those by Miwi2, a nuclear PIWI protein, indicated that piRNA-loaded Miwi2 conferred target specificity to Morc1. Activated TEs drove transcription of adjacent genes by acting as ectopiccis-regulatory elements. Such a disrupting effect of TEs on the transcriptome was compensated by Morc1. Thus, Morc1 ensures proper interactions of TEs with host genes through re-establishment of heterochromatin in gonocytes.
Simultaneous Multi-Omics Analysis by Direct Infusion Mass Spectrometry (SMAD-MS)
Authors: Jiang Yuming , Salladay-Perez Ivan , Momenzadeh Amanda , Covarrubias Anthony J. , Meyer Jesse G. 
Published: June 2023

AbstractCombined multi-omics analysis of proteomics, polar metabolomics, and lipidomics requires separate liquid chromatography–mass spectrometry (LC–MS) platforms for each omics layer. This requirement for different platforms limits throughput and increases costs, preventing the application of mass spectrometry-based multi-omics to large scale drug discovery or clinical cohorts. Here, we present an innovative strategy for simultaneous multi-omics analysis by direct infusion (SMAD) using one single injection without liquid chromatography. SMAD allows quantification of over 9,000 metabolitem/zfeatures and over 1,300 proteins from the same sample in less than five minutes. We validated the efficiency and reliability of this method and then present two practical applications: mouse macrophage M1/M2 polarization and high throughput drug screening in human 293T cells. Finally, we demonstrate relationships between proteomic and metabolomic data are discovered by machine learning.
Detection of parasite DNA in soil samples from rural Yucatán, México
Authors: Villanueva-Lizama Liliana , Cruz-Coral Angela , Teh-Poot Christian , Cruz-Chan Vladimir , Mejia Rojelio 
Published: June 2023

ABSTRACTThe soil is the primary environmental reservoir for many parasites transmitted to humans through the fecal-oral route, causing disease. Our environmental study used a high-throughput multi-parallel real-time quantitative PCR (qPCR) assay to detect parasites’ DNA in soil collected from the outdoor built environments of 34 houses. The total parasite prevalence wasAcanthamoeba spp. (53%),Blastocystisspp. (12%),Ascaris lumbricoides(12%),Toxocara canis(9%),Ancylostomaspp. (3%),Trichuris trichiura(3%),Entamoeba histolytica(3%) andGiardia intestinalis(3%). No DNA fromNecator americanus, Strongyloides stercoralis, Toxocara catis, andCryptosporidiumspp was detected. A total of 65% of houses were positive for at least one parasite, 15% had poly-parasites, and up to six different parasites were detected in a single sample. This is the first report of parasites-DNA detected in soil samples from a rural community in Yucatán and suggests higher rates of transmission of parasites with both a zoonotic and medical importance.
Highly divergent and diverse viral community infecting sylvatic mosquitoes from Northeast Brazil
Authors: da Silva Alexandre Freitas , Machado Laís Ceschini , da Silva Luisa Maria Inácio , Dezordi Filipe Zimmer , Wallau Gabriel Luz 
Published: June 2023

AbstractMosquitoes can transmit several pathogenic viruses to humans, but their natural viral community is also composed of a myriad of other viruses such as insect-specific viruses (ISV) and those that infect symbiotic microorganisms. Besides a growing number of studies investigating the mosquito virome the majority are focused on few urban species and relatively little is known about the virome of sylvatic mosquitoes particularly in high biodiverse brazilian biomes. Here, we characterized the RNA virome of 10 sylvatic mosquitos species from Atlantic forest remains at a sylvatic-urban interface in Northeast Brazil employing a metatranscriptomic approach. A total of 16 viral families were detected. The phylogenetic reconstructions of 14 viral families revealed that the majority of the sequences are putative ISVs. The phylogenetic positioning and, in most cases, the association with a high RdRp amino acid divergence from other known viruses suggests that the viruses characterized here represent at least 34 new viral species. Therefore, the sylvatic mosquitoes viral community is majorly composed of highly divergent viruses highlighting the limited knowledge we still have about the natural virome of mosquitoes in general. Moreover, we found that none of the viruses recovered were shared between the species investigated. These findings will help to understand the interactions and coevolution between mosquitoes and viruses in nature.ImportanceMosquitoes are medically important insects as they transmit pathogenic viruses to humans and animals during blood feeding. However, their natural microbiota is also composed of a diverse set of viruses that cause no harm to the insect and other hosts, such as ISVs. In this study, we characterized the RNA virome of sylvatic mosquitoes from Northeast Brazil using unbiased metatranscriptomic sequencing and in depth bioinformatics approaches. Our analysis revealed that these mosquitoes species harbor a diverse set of highly divergent viruses and the majority comprises new viral species. Our findings revealed many new virus lineages characterized for the first time broadening our understanding about the natural interaction between mosquitoes and viruses. Lastly, it also provided several complete genomes that warrants further assessment for mosquito and vertebrate host pathogenicity and their potential interference with pathogenic arboviruses.
A shared linguistic space for transmitting our thoughts from brain to brain in natural conversations
Authors: Zada Zaid , Goldstein Ariel , Michelmann Sebastian , Simony Erez , Price Amy , Hasenfratz Liat , Barham Emily , Zadbood Asieh , Doyle Werner , Friedman Daniel , Dugan Patricia , Melloni Lucia , Devore Sasha , Flinker Adeen , Devinsky Orrin , Nastase Samuel A. , Hasson Uri 
Published: June 2023

AbstractEffective communication hinges on a mutual understanding of word meaning in different contexts. The embedding space learned by large language models can serve as an explicit model of the shared, context-rich meaning space humans use to communicate their thoughts. We recorded brain activity using electrocorticography during spontaneous, face-to-face conversations in five pairs of epilepsy patients. We demonstrate that the linguistic embedding space can capture the linguistic content of word-by-word neural alignment between speaker and listener. Linguistic content emerged in the speaker’s brain before word articulation, and the same linguistic content rapidly reemerged in the listener’s brain after word articulation. These findings establish a computational framework to study how human brains transmit their thoughts to one another in real-world contexts.
Clinical Significance of the Stromatic Component in Ovarian Cancer: Quantity Over Quality in Outcome Prediction
Authors: Lou Emil , Clemente Valentino , Grube Marcel , Svedbom Axel , Nelson Andrew , Blome Freya , Staebler Annette , Kommoss Stefan , Bazzaro Martina 
Published: June 2023

AbstractBackgroundThe tumor stroma is composed of a complex network of non-cancerous cells and extracellular matrix elements that collectively are crucial for cancer progression and treatment response. Within the realm of ovarian cancer, the expression of the stromal gene cluster has been linked to poorer progression-free and overall survival rates. However, in the age of precision medicine and genome sequencing, the notion that the simple measurement of tumor-stroma proportion alone can serve as a biomarker for clinical outcome is a topic that continues to generate controversy and provoke discussion. Our current study reveals that it is the quantity of stroma, rather than its quality, that serves as a clinically significant indicator of patient outcome in ovarian cancer.MethodsThis study leveraged the High-Grade-Serous-Carcinoma (HGSC) cohort of the publicly accessible Cancer Genome Atlas Program (TCGA) along with an independent cohort comprising HGSC clinical specimens in diagnostic and Tissue Microarray formats. Our objective was to investigate the correlation between the Tumor-Stroma-Proportion (TSP) and progression-free survival (PFS), overall survival (OS), and response to chemotherapy. We assessed these associations using H&E-stained slides and tissue microarrays. Our analysis employed semi-parametric models that accounted for age, metastases, and residual disease as controlling factors.ResultsWe found that high TSP (>50% stroma) was associated with significantly shorter progression-free survival (PFS) (p=0.016) and overall survival (OS) (p=0.006). Tumors from patients with chemoresistant tumors were twice as likely to have high TSP as compared to tumors from chemosensitive patients (p=0.012). In tissue microarrays, high TSP was again associated with significantly shorter PFS (p=0.044) and OS (p=0.0001), further confirming our findings. The Area Under the ROC curve for the model predicting platinum was estimated at 0.7644.ConclusionsIn HGSC, TSP was a consistent and reproducible marker of clinical outcome measures, including PFS, OS, and platinum chemoresistance. Assessment of TSP as a predictive biomarker that can be easily implemented and integrated into prospective clinical trial design and adapted to identify, at time of initial diagnosis, patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment.
Implicit reward-based motor learning
Authors: van Mastrigt Nina M. , Tsay Jonathan S. , Wang Tianhe , Avraham Guy , Abram Sabrina J. , van der Kooij Katinka , Smeets Jeroen B. J. , Ivry Richard B. 
Published: June 2023

AbstractBinary feedback, providing information solely about task success or failure, can be sufficient to drive motor learning. While binary feedback can induce explicit adjustments in movement strategy, it remains unclear if this type of feedback also induce implicit learning. We examined this question in a center-out reaching task by gradually moving an invisible reward zone away from a visual target to a final rotation of 7.5° or 25° in a between-group design. Participants received binary feedback, indicating if the movement intersected the reward zone. By the end of the training, both groups modified their reach angle by about 95% of the rotation. We quantified implicit learning by measuring performance in a subsequent no-feedback aftereffect phase, in which participants were told to forgo any adopted movement strategies and reach directly to the visual target. The results showed a small, but robust (2-3°) aftereffect in both groups, highlighting that binary feedback elicits implicit learning. Notably, for both groups, reaches to two flanking generalization targets were biased in the same direction as the aftereffect. This pattern is at odds with the hypothesis that implicit learning is a form of use-dependent learning. Rather, the results suggest that binary feedback can be sufficient to recalibrate a sensorimotor map.
Prediction tendency, eye movements, and attention in a unified framework of neural speech tracking
Authors: Schubert Juliane , Gehmacher Quirin , Schmidt Fabian , Hartmann Thomas , Weisz Nathan 
Published: June 2023

ABSTRACTAuditory speech comprehension is a multi-faceted process in which attention, prediction, and sensorimotor integration (via active sensing) interact with or complement each other. Although different conceptual models that focus on one of these aspects exist, we still lack a unified understanding of their role in speech processing. Here, we first replicated two recently published studies from our lab, confirming 1) a positive relationship between individual prediction tendencies and neural speech tracking, and 2) the phenomenon of ocular speech tracking – the tracking of attended speech by eye movements – and its shared contribution with neural activity to speech processing. In addition, we extended these findings with complementary analyses and investigated these phenomena in relation to each other in a multi-speaker paradigm with continuous, narrative speech. Importantly, prediction tendency and ocular speech tracking seem to be unrelated. In contrast to the shared contributions of oculomotor and neural activity to speech processing over a distributed set of brain regions that are critical for attention, individual prediction tendency and its relation to neural speech tracking seem to be largely independent of attention. Based on these findings, we propose a framework that aims to bridge the gaps between attention, prediction, and active (ocular) sensing in order to contribute to a holistic understanding of neural speech processing. In this speculative framework for listening, auditory inflow is, on a basic level, temporally modulated via active ocular sensing, and incoming information is interpreted based on probabilistic assumptions.
Stochastic coding: a conserved feature of odor representations and its implications for odor discrimination
Authors: Srinivasan Shyam , Daste Simon , Modi Mehrab , Turner Glenn , Fleischmann Alexander , Navlakha Saket 
Published: June 2023

AbstractSparse coding is thought to improve discrimination of sensory stimuli by reducing overlap between their representations. Two factors, however, can offset sparse coding’s advantages. Similar sensory stimuli have significant overlap, and responses vary across trials. To elucidate the effect of these two factors, we analyzed odor responses in the fly and mouse olfactory regions implicated in learning and discrimination — the Mushroom Body (MB) and the Piriform Cortex (PCx). In both species, we show that neuronal responses fall along a continuum from extremely reliable across trials to extremely variable or stochastic. Computationally, we show that the range of observed variability arises from probabilistic synapses in inhibitory feedback connections within central circuits rather than sensory noise, as is traditionally assumed. We propose this coding scheme to be advantageous for coarse– and fine-odor discrimination. More reliable cells enable quick discrimination between dissimilar odors. For similar odors, however, these cells overlap, and do not provide distinguishing information. By contrast, more unreliable cells are decorrelated for similar odors, providing distinguishing information, though this requires extended training with more trials. Overall, we have uncovered a stochastic coding scheme that is conserved in vertebrates and invertebrates, and we identify a candidate mechanism, based on variability in a winner-take-all inhibitory circuit, that improves discrimination with training.
Lipid-based nutrient supplements for prevention of child undernutrition: when less may be more
Authors: Dewey Kathryn G. , Arnold Charles D. , Wessells K. Ryan , Stewart Christine P. 
Published: June 2023

AbstractBackgroundBoth small-quantity (SQ) and medium-quantity (MQ) lipid-based nutrient supplements (LNS) have been used for prevention of child undernutrition. A meta-analysis of 14 trials of SQ-LNS vs no LNS showed effects on length-for-age (LAZ, +0.14 (95% confidence interval 0.11, 0.16)) and weight-for-length (WLZ, +0.08 (0.06, 0.10)) z-scores, as well as prevalence ratios (95% CI) for stunting (LAZ<-2, 0.88 (0.85, 0.91)) and wasting (WLZ < −2, (0.80, 0.93)). However, little is known about the effects of MQ-LNS on growth.ObjectiveWe aimed to examine the effects of preventive MQ-LNS (∼250-499 kcal/d) provided at ∼6-23 mo of age on growth outcomes compared to no LNS or provision of SQ-LNS.MethodsWe conducted a systematic review of studies of MQ-LNS for prevention, and categorized them as providing < 6 mo vs.>6 mo of supplementation; for the latter category we conducted a meta-analysis, with main outcomes being change in WLZ and LAZ, and prevalence of wasting and stunting.ResultsThree studies provided MQ-LNS for 3-5 mo (seasonal) for children 6-36 mo of age, and did not show consistent effects on growth outcomes. Eight studies provided MQ-LNS for 6-18 mo, generally starting at 6 mo of age; in the meta-analysis (max total n=13,673), MQ-LNS increased WLZ (+0.09 (0.05, 0.13)) and reduced wasting (0.89 (0.81, 0.97)), but had no effect on LAZ (+0.04 (−0.02, 0.11)) or stunting (0.97 (0.92, 1.02)) compared to no LNS. Two studies directly compared SQ-LNS and MQ-LNS and showed no significant differences in growth outcomes.ConclusionsThe current evidence suggests that MQ-LNS offers no added benefits over SQ-LNS, although further studies directly comparing MQ-LNS vs. SQ-LNS would be useful. One possible explanation is incomplete consumption of the MQ-LNS ration and thus lower than desirable intake of certain nutrients.RegistryPROSPERO CRD42022382448:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382448
Does physical activity in childhood or adolescence predict future anxiety, depression, or wellbeing? A systematic review of 98 prospective cohort studies
Authors: Knowles Christopher , Paradis Kyle F. , Shannon Stephen , Breslin Gavin , Carlin Angela 
Published: June 2023

AbstractPhysical activity (PA) is a modifiable health behaviour that can support and improve mental health. The tendency for activity levels to track over time suggests that through continued participation, those most active in youth may experience better long-term mental health than less active peers. Exploring the extent to which mental health benefits of child/adolescent PA persevere over time helps advocates and policy-makers determine whether PA promotion in youth constitutes effective allocation of public health resources and a viable means of reducing the global burden of common mental disorders and suboptimal wellbeing across the lifespan. This systematic review synthesised evidence for childhood/adolescent PA as a predictor of future anxiety, depression and wellbeing indicators (PROSPERO: CRD42021242555). Systematic searches of CINAHL, Medline, PsycInfo, and Scopus (conducted 27thOctober 2022) returned 12,703 articles with 98 retained. Included: prospective, quantitative, longitudinal designs; PA measured ages 5-17 years; anxiety, depression, and/or wellbeing indicators measured at least 12 months later; generally healthy populations. Excluded: severe mental illnesses. Risk of bias and quality of evidence were assessed following the GRADE framework. Effect sizes from moderate- and high-quality studies are discussed narratively. Studies are grouped by mental health outcome, PA type, domain, and whether participants adhered to current World Health Organisation PA guidelines. PA was negatively associated with depression in 41/67 studies (61.2%); anxiety in 20/35 studies (57.1%); and positively associated with wellbeing in 25/39 studies (64.1%). Effect sizes for all outcomes were small and evidence quality low across all timeframes. Team sports were the most consistently predictive type of PA. Whether domain-specific activities or guideline (non)adherence have differential effects remains unclear. Heterogeneity was attributed to the vastness of associations tested and psychometric measures used. Current literature offers low-quality partial evidence that childhood/adolescent PA has small beneficial effects for prospective anxiety, depression and wellbeing at least 12 months later.
SpheroScan: A User-Friendly Deep Learning Tool for Spheroid Image Analysis
Authors: Akshay Akshay , Katoch Mitali , Abedi Masoud , Besic Mustafa , Shekarchizadeh Navid , Burkhard Fiona C. , Bigger-Allen Alex , Adam Rosalyn M. , Monastyrskaya Katia , Hashemi Gheinani Ali 
Published: June 2023

AbstractBackgroundIn recent years, three-dimensional (3D) spheroid models have become increasingly popular in scientific research as they provide a more physiologically relevant microenvironment that mimics in vivo conditions. The use of 3D spheroid assays has proven to be advantageous as it offers a better understanding of the cellular behavior, drug efficacy, and toxicity as compared to traditional two-dimensional cell culture methods. However, the use of 3D spheroid assays is impeded by the absence of automated and user-friendly tools for spheroid image analysis, which adversely affects the reproducibility and throughput of these assays.ResultsTo address these issues, we have developed a fully automated, web-based tool called SpheroScan, which uses the deep learning framework called Mask Regions with Convolutional Neural Networks (R-CNN) for image detection and segmentation. To develop a deep learning model that could be applied to spheroid images from a range of experimental conditions, we trained the model using spheroid images captured using IncuCyte Live-Cell Analysis System and a conventional microscope. Performance evaluation of the trained model using validation and test datasets shows promising results.ConclusionSpheroScan allows for easy analysis of large numbers of images and provides interactive visualization features for a more in-depth understanding of the data. Our tool represents a significant advancement in the analysis of spheroid images and will facilitate the widespread adoption of 3D spheroid models in scientific research. The source code and a detailed tutorial for SpheroScan are available athttps://github.com/FunctionalUrology/SpheroScan.Key PointsA deep learning model was trained to detect and segment spheroids in images from microscopes and Incucytes.The model performed well on both types of images with the total loss decreasing significantly during the training process.A web tool called SpheroScan was developed to facilitate the analysis of spheroid images, which includes prediction and visualization modules.SpheroScan is efficient and scalable, making it possible to handle large datasets with ease.SpheroScan is user-friendly and accessible to researchers, making it a valuable resource for the analysis of spheroid image data.