bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fishing for a reelGene: evaluating gene models with evolution and machine learning
Authors: Schulz Aimee J , Zhai Jingjing , AuBuchon-Elder Taylor , El-Walid Mohamed , Ferebee Taylor H , Gilmore Elizabeth H , Hufford Matthew B , Johnson Lynn C , Kellogg Elizabeth A , La Thuy , Long Evan , Miller Zachary R , Romay M Cinta , Seetharam Arun S. , Stitzer Michelle C , Wrightsman Travis , Buckler Edward S , Monier Brandon , Hsu Sheng-Kai 
Published: September 2023

AbstractAssembled genomes and their associated annotations have transformed our study of gene function. However, each new assembly generates new gene models. Inconsistencies between annotations likely arise from biological and technical causes, including pseudogene misclassification, transposon activity, and intron retention from sequencing of unspliced transcripts. To evaluate gene model predictions, we developed reelGene, a pipeline of machine learning models focused on (1) transcription boundaries, (2) mRNA integrity, and (3) protein structure. The first two models leverage sequence characteristics and evolutionary conservation across related taxa to learn the grammar of conserved transcription boundaries and mRNA sequences, while the third uses conserved evolutionary grammar of protein sequences to predict whether a gene can produce a protein. Evaluating 1.8 million gene models in maize, reelGene found that 28% were incorrectly annotated or nonfunctional. By leveraging a large cohort of related species and through learning the conserved grammar of proteins, reelGene provides a tool for both evaluating gene model accuracy and genome biology.
Ventrointermediate thalamic stimulation improves motor learning in humans
Authors: Voegtle Angela , Terzic Laila , Farahat Amr , Hartong Nanna , Galazky Imke , Hinrichs Hermann , Nasuto Slawomir J. , de Oliveira Andrade Adriano , Knight Robert T. , Ivry Richard B. , Voges Jürgen , Deliano Matthias , Buentjen Lars , Sweeney-Reed Catherine M. 
Published: September 2023

AbstractVentrointermediate thalamic stimulation (VIM-DBS) modulates oscillatory activity in a cortical network including primary motor cortex, premotor cortex, and parietal cortex. Here we show that, beyond the beneficial effects of VIM-DBS on motor execution, this form of invasive stimulation facilitates production of sequential finger movements that follow a fixed sequence but not when the sequence is selected at random. These results highlight the role of thalamo–cortical activity in motor learning.
Virtual electrode or virtual scalpel? A cancellation-based approach to data analysis and source localization
Authors: de Cheveigné Alain 
Published: September 2023

AbstractThe “virtual electrode” is an appealing metaphor as it suggests that we can – with the right tools and skills – use macroscopic recording techniques such as EEG or MEG to place an electrode anywhere in the brain, and record from it as if it were a real, microscopic electrode. Like every good metaphor, it can sometimes lead us astray. This short paper reviews what we can, and cannot, expect of a “virtual electrode”. It is suggested that a more accurate metaphor – if less appealing – is that of a “virtual scalpel” by which activity from a source within the brain can be suppressed within the macroscopic recording. WithJchannels, up toJ− 1 sources can be suppressed while still retaining some information about other sources. In addition, with appropriate source and forward models, it may be possible to accurately localize any source that can be accurately suppressed. This paper sets out the possibilities and limits of what linear analysis applied to multichannel data can, or cannot, achieve.
Auditory selective attention during a working memory task with melodies: a MEG study
Authors: Aurélien de la Chapelle , Salomé Serres-Blain , Alma ElShafei , Denis Schwartz , Sébastien Daligault , Julien Jung , Perrine Ruby , Anne Caclin , Aurélie Bidet-Caulet 
Published: September 2023

AbstractWorking memory and attention are jointly needed in most everyday life tasks and activities. They have however mostly been studied separately. Here we investigate how auditory working memory and selective attention interact using a recently introduced paradigm (MEMAT) that combines a classic working memory paradigm, the delayed-matching-to-sample task, and selective attention, with distractors presented during the encoding phase. All stimuli are four-tone melodies. Twenty-two participants performed the MEMAT task during MEG recordings. We manipulate the difficulty of the memory task and of attentional filtering.When memory task difficulty increases, the amplitude of the CNV in anticipation of the melody to encode increases and the decrease in alpha power during encoding and maintenance in a left fronto-temporal network is reduced.When attentional filtering difficulty increases, the amplitude of the sustained evoked response during encoding increases, whereas the differential processing of relevant and irrelevant sounds in auditory areas is less pronounced, and frontal theta power during encoding and maintenance is higher. In the left auditory cortex, we could directly observe the result of the interaction between auditory memory and attention: the facilitation of relevant sound processing in the easy filtering condition was reduced when the memory task difficulty increased. This pattern mirrors the observed behavioral effects. Overall brain dynamics highlight reciprocal influences of working memory and selective attention processes, in keeping with shared cognitive resources between them.
Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes
Authors: Lauby Samantha C. , Lapp Hannah E. , Salazar Melissa , Semyrenko Sofiia , Chauhan Danyal , Margolis Amy E. , Champagne Frances A. 
Published: September 2023

AbstractBisphenols (BPs), including BPA and “BPA-free” structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal BP exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal BP exposure and postnatal maternal care on neurodevelopment and behavior. Our findings suggest that the effects of prenatal BP exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal BP exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal BP exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal BP exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal BP exposure and improve health and well-being in human populations.
Manifesto of Transparent Mathematical Modeling: From Ecology to General Science
Authors: Kalmykov V. L. , Kalmykov L. V. 
Published: September 2023

AbstractMathematical black box models, which hide the structure and behavior of the subsystems, currently dominate science. Errors and paradoxes, such as the biodiversity paradox and the limiting similarity hypothesis, often arise from subjective interpretations of these hidden mechanisms. To address these problems, we have developed transparent mathematical models of the white box type. Here we justify the hypothesis that transparent mathematical models of the white box type can be built by means of logical deterministic cellular automata whose rules are based on the general theory of the corresponding domain. Using white box models, we were able to directly identify the mechanisms of interspecific competition, test the principle of competitive exclusion and the hypothesis of limiting similarity, resolve the paradox of biodiversity, and formulate for the first time the general principle of competitive coexistence. As a basis for reproducing and further developing the method, we present two transparent mathematical models of an ecosystem with one and two competing species. C++ code for our models provided. Cellular automata thinking can be traced back from ancient cellular board games in the histories of all civilizations. The transparent mathematical modeling opens a rational approach to ensuring the safety, reliability, and trustworthiness of automatic decisions. A shift to transparency in the mathematical modeling paradigm has the potential to revolutionize scientific research and to advance knowledge and technology in a wide variety of domains.
Matrix Nanoscale Mechanics Regulates Exosome Production by Mesenchymal Stem Cells
Authors: Chrysanthou Alexandra , Gautrot Julien E. 
Published: September 2023

AbstractComplex biotherapeutics such exosomes offer attractive opportunities for cell-free treatment of disease and conditions difficult to address with single, defined compounds. However their production remains challenging as adherent cells proposed to secrete therapeutic extra cellular vesicles require scalable platforms. In addition, the role of biomaterials design parameters on processes regulating vesicular secretory phenotypes is unclear. Here we propose the use of bioactive microdroplets, or bioemulsions, as microcarriers for the culture of mesenchymal stem cells and production of exosomes. We demonstrate 100% increase in the output of extracellular vesicles on bioemulsions. The impact of matrix mechanics on this process is then investigated, and in particular interfacial shear mechanical properties of corresponding liquid-liquid interfaces forming microdroplets. We find that such local nanoscale mechanics regulates not only cell adhesion, but also exosome output. We find that exosomes generated by cells cultured on bioemulsion microdroplets retain a high content of protein and RNA cargos. Finally, we demonstrate that the cold-shock protein YBox 1, previously associated with RNA packaging, is modulated by matrix mechanics and regulates exosome production. Together, these results demonstrate the impact of local interfacial mechanics on the adhesion and secretory machinery and provide a proof of concept for the application of bioemulsions for the production of complex biotherapeutics.
Resting state aperiodic slope predicts Research Domain Criteria Social Processes in young typically developing adults
Authors: Ford Talitha C. , Hill Aron T. , Parrella Nina-Francesca , Kirkovski Melissa , Donaldson Peter , Enticott Peter G. 
Published: September 2023

AbstractBackgroundThe aperiodic exponent has been utilised to demonstrate differences in brain excitation-inhibition (E/I) in ageing, cognition, and neuro- and psycho-pathology. Furthermore, E/I imbalance has been associated with social communication difficulties in clinical and non-clinical cohorts. No work to date, however, has explored the association between aperiodic activity and social communication difficulties.MethodsA total of 40 typically developing young adults aged 18-24 (24 female; age mean=21.6, SD=1.9) each underwent 5 minutes each of eyes open and eyes closed resting state EEG using a 64-channel HydroCel Geodesic Sensor Net. Participants also completed Research Domain Criteria Social Processes measures: Social Responsiveness Scale (SRS), Reading the Mind in the Eyes task (RME), and Penn Emotional Recognition Task (ER-40).ResultsSex differences in aperiodic exponent and offset were observed, with steeper exponent and greater offset observed in males, suggestive of greater inhibitory tone (ps<.05). Whole-brain aperiodic activity was not associated with SRS, RME, or ER-40. There was some support for increased SRS scores and steeper exponent in right social brain (suggestive of greater excitatory tone), however, this was not significant (p=.068).ConclusionsThese preliminary data show promise for supporting the notion that brain E/I is associated with social communication and processing difficulties, however, larger samples are needed to validate these findings.
Multi-omics analysis reveals signatures of selection and loci associated with complex traits in pigs
Authors: Yi Guoqiang , Liu Lei , Yao Yilong , Liu Yuwen , Li Jiang , Yang Yalan , Fang Lingzhao , Mo Delin , Zhang Longchao , Liu Yonggang , Niu Yongchao , Wang Liyuan , Qu Xiaolu , Pan Zhangyuan , Wang Lei , Chen Muya , Fan Xinhao , Chen Yun , Zhang Yongsheng , Li Xingzheng , Wang Zhen , Tang Yijie , Huang Hetian , Yuan Pengxiang , Liao Yuying , Li Xinjian , Yin Zongjun , Liu Di , Zhang Dongjie , Zhou Quanyong , Wu Wangjun , Jiang Jicai , Gao Yahui , Liu George E. , Wang Lixian , Chen Yaosheng , Groenen Martien A M , Tang Zhonglin 
Published: September 2023

AbstractSelection signatures that contribute to phenotypic diversity, especially morphogenesis in pigs, remain to be further elucidated. To reveal the regulatory role of genetic variations in phenotypic differences between Eastern and Western pig breeds, we performed a systematic analysis based on seven high-qualityde novoassembled genomes, 1,081 resequencing data representing 78 domestic breeds, 162 methylomes, and 162 transcriptomes of skeletal muscle from Tongcheng (Eastern) and Landrace (Western) pigs at 27 developmental stages. Selective sweep uncovers different genetic architectures behind divergent selection directions for the Eastern and Western breeds. Notably, two loci showed functional alterations by almost fixed missense mutations. By integrating time-course transcriptome and methylome, we revealed differences in developmental timing during myogenesis between Eastern and Western breeds. Genetic variants under artificial selection have critical regulatory effects on progression patterns of heterochronic genes likeGHSRandBDH1, by the interaction of local DNA methylation status, particularly during embryonic development. Altogether, our work not only provides valuable resources for understanding pig complex traits, but also contributes to human biomedical research.
MMD-DTA: A multi-modal deep learning framework for drug-target binding affinity and binding region prediction
Authors: Liu Liwei , Zhang Qi , Wei Yuxiao , Zhang Shengli , Liao Bo 
Published: September 2023

AbstractThe prediction of drug-target affinity (DTA) plays an important role in the development of drugs and the discovery of potential drug targets. In recent years, computer-assisted DTA prediction has become an important method in this field. In this work, we propose a multi-modal deep learning framework for drug-target binding affinity and binding region prediction, namely MMD-DTA. The model can predict DTA while unsupervised learning of drug-target binding regions. The experimental results show that MMD-DTA performs better than the existing models on the main evaluation metrics. In addition, external validation results show that MMD-DTA improves the generalization ability of the model by integrating sequence information and structural information of drugs and targets, and the model trained on the benchmark dataset can be well generalized to independent virtual screening tasks. Visualization of drug-target binding region prediction shows the powerful interpretability of MMD-DTA, which has important implications for exploring the functional regions of drug molecules acting on proteins.
Atazanavir/ritonavir increased tizoxanide exposure from oral nitazoxanide through pharmacokinetic interaction in healthy volunteers
Authors: Akinloye Abdulafeez , Oyedeji Timothy , Eniayewu Oluwasegun , Adeagbo Babatunde , Bolaji Oluseye , Rannard Steve , Owen Andrew , Olagunju Adeniyi 
Published: September 2023

ABSTRACTAimsNitazoxanide is a broad-spectrum antiviral with potential application in a number of viral infections. Its use is limited by gastrointestinal side effects associated with increasing dose. In this study, we investigated the possibility of enhancing the exposure of its active metabolite, tizoxanide, through pharmacokinetic interaction with atazanavir/ritonavir.MethodThis was a crossover drug-drug interaction study, 18 healthy participants received a single dose of 1000 mg of nitazoxanide alone in period 1 and in combination with 300/100 mg atazanavir/ritonavir in period 2 after a washout period of 21 days. On both days, blood samples for intensive pharmacokinetic analyses were collected before and at 0.25, 0.5, 1, 2, 4, 6, and 12 h after dose. To explore the utility of dried blood spots (DBS) as alternative to plasma for tizoxanide quantification, 50 µL of blood from some participants was spotted on DBS cards. Pharmacokinetic parameters were derived by non-compartmental analysis and compared between periods 1 and 2. The correlation between tizoxanide concentration in plasma and DBS was also evaluated.ResultsCo-administration of nitazoxanide with atazanavir/ritonavir resulted in a significant increase in tizoxanide plasma exposure. The geometric mean ratios (90% CI) of tizoxanide AUC0-12h, Cmaxand C12hwere 1.872 (1.870 – 1.875), 2.029 (1.99 – 2.07) and 3.14 (2.268 – 4.352) respectively, were all outside the 0.8 – 1.25 interval, implying clinically significant interaction. DBS concentration (%CV) was 46.3% (5.6%) lower than plasma concentrations, with a strong correlation (R = 0.89, P < 0.001). Similarly, DBS- derived plasma concentration and plasma concentrations displayed very strong correlation with linearity (R = 0.95, P<0.001).ConclusionCo-administration with atazanavir/ritonavir enhanced tizoxanide exposure with no report of adverse events in healthy volunteers.
Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome
Authors: Hong Hyejeong , Schulze Katharina V. , Copeland Ian E. , Atyam Manasa , Kamp Kendra , Hanchard Neil A. , Belmont John , Ringel-Kulka Tamar , Heitkemper Margaret , Shulman Robert J. 
Published: September 2023

AbstractIrritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants inTREH,SI, SLC5A1andSLC2A5that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB,andSLC5A1)as well as candidate disease genes (MGAMandSLC5A2),providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.
A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
Authors: Taba Nele , Fischer Krista ,   Estonian Biobank research team, Org Elin , Aasmets Oliver 
Published: September 2023

AbstractAssessing causality is undoubtedly one of the key questions in microbiome studies for the upcoming years. Since randomised trials in human subjects are often unethical or difficult to pursue, analytical methods to derive causal effects from observational data deserve attention. As simple covariate adjustment is not likely to account for all potential confounders, the idea of instrumental variable (IV) analysis is worth exploiting. Here we propose a novel framework of antibiotic instrumental variable regression (AB-IVR) for estimating the causal relationships between microbiome and various diseases. We rely on the recent studies showing that antibiotic treatment has a cumulative long-term effect on the microbiome, resulting in individuals with higher antibiotic usage to have a more perturbed microbiome. We apply the AB-IVR method on the Estonian Biobank data and show that the microbiome has a causal role in numerous diseases including migraine, depression and irritable bowel syndrome. We show with a plethora of sensitivity analyses that the identified causal effects are robust, and propose ways for further methodological developments.
Converting between the International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite (EPIC) Urinary Subscales: Modeling and External Validation
Authors: Windisch Paul , Becker Ivo , Tang Hongjian , Schröder Christina , Buchali André , Aebersold Daniel M. , Zwahlen Daniel R. , Förster Robert , Shelan Mohamed 
Published: September 2023

AbstractBackgroundThe 50-item Expanded Prostate Cancer Index Composite (EPIC) and the International Prostate Symptom Score (IPSS) are two widely used options to assess prostate-related quality of life (QoL), but there is no method to convert between the two. We, therefore, developed and externally validated models for this purpose.Methods347 consecutive patients who had previously received radiotherapy and surgery for prostate cancer at two institutions in Switzerland and Germany were contacted via mail and instructed to complete both questionnaires. The Swiss cohort was used to train and internally validate different machine learning models using 4-fold cross-validation. The German cohort was used for external validation.ResultsConverting between the EPIC Urinary Irritative/Obstructive subscale and the IPSS using linear regressions resulted in mean absolute errors (MAEs) of 3.88 and 6.12 below the respective previously published minimal important differences (MIDs) of 5.2 and 10 points. Converting between the EPIC Urinary Summary and the IPSS was less accurate with MAEs of 5.13 and 10.45, similar to the MIDs. More complex model architectures did not result in improved performance.ConclusionsLinear regressions can be used to convert between the IPSS and the EPIC Urinary subscales. While the equations obtained in this study can be used to compare results across clinical trials, they should not be used to inform clinical decision-making in individual patients.