bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and evaluation of an open-source, standards-based approach to explainable artificial intelligence for managing co-morbidity and clinical guidelines using argumentation techniques and the Transition-based Medical Recommendation model
Authors: Domínguez Jesús , Prociuk Denys , Marović Branko , Čyras Kristijonas , Cocarascu Oana , Ruiz Francis , Mi Ella , Mi Emma , Ramtale Christian , Rago Antonio , Darzi Ara , Toni Francesca , Curcin Vasa , Delaney Brendan 
Published: December 2022

I.AbstractA.ObjectiveClinical Decision Support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. We aimed to develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial Electronic Health Record (EHR) system in a middle-income country.B.Materials and MethodsWe used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage COPD with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists.C.ResultsPulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities were suggested in the future along with customisation of the level of explanation with expertise.D.ConclusionAn ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.E.FundingThe project was funded by the British government through the Engineering and Physical Sciences Research Council (EPSRC) – Global Challenges Research Fund.1
Potential policy interventions for slowing the spread of artemisinin-resistantpfkelchR561H mutations in Rwanda
Authors: Zupko Robert J. , Nguyen Tran Dang , Ngabonziza J. Claude S. , Kabera Michee , Li Haojun , Tran Thu Nguyen-Anh , Tran Kien Trung , Uwimana Aline , Boni Maciej F. 
Published: December 2022

AbstractArtemisinin combination therapies (ACTs) are highly effective at treating uncomplicatedPlasmodium falciparummalaria. However, the emergence of a novelpfkelch13R561H mutation in Rwanda, with associated delayed parasite clearance, suggests that drug policy interventions are needed to delay the fixation and slow the spread of this mutation. Using a spatial, stochastic, individual-based model calibrated and validated for the Rwanda’s malaria epidemiology, we evaluate seventeen strategies aimed at minimizing treatment failures and delaying the spread of R561H. The primary measures evaluated are projected treatment failures and R561H allele frequency over three, five, and ten years. Lengthening courses of treatment, deploying multiple first-line therapies, and custom rotation strategies all provide a benefit when compared to the status quo. The best intervention options, five years into the future, result in slower spread of R561H (0.16 allele frequency difference) and absolute treatment failure counts that are 44% lower than projected under the status quo.
Seroprevalence of SARS-CoV-2 antibodies and retrospective mortality in two African settings: Lubumbashi, Democratic Republic of the Congo and Abidjan, Côte d’Ivoire
Authors: Simons Erica , Nikolay Birgit , Ouedraogo Pascal , Pasquier Estelle , Tiemeni Carlos , Adjaho Ismael , Badjo Colette , Chamman Kaouther , Diomandé Mariam , Dosso Mireille , Doumbia Moussa , Izia Yves Asuni , Kakompe Hugues , Katsomya Anne Marie , Kij Vicky , Akissi Viviane Kouakou , Mambula Christopher , Mbala-Kingebeni Placide , Muzinga Jacques , Ngoy Basile , Penali Lou , Pini Alessandro , Porten Klaudia , Salou Halidou , Sevede Daouda , Luquero Francisco , Gignoux Etienne 
Published: December 2022

AbstractBackgroundAlthough seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan.MethodsThe studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan).ResultsIn Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey.ConclusionAlthough circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.
Regenerative capacity of neural tissue scales with changes in tissue mechanics post injury
Authors: Carnicer-Lombarte Alejandro , Barone Damiano G. , Fawcett James W. , Franze Kristian 
Published: December 2022

AbstractSpinal cord injuries have devastating consequences for humans, as mammalian neurons of the central nervous system (CNS) cannot regenerate. In the peripheral nervous system (PNS), however, neurons may regenerate to restore lost function following injury. While mammalian CNS tissue softens after injury, how PNS tissue mechanics changes in response to mechanical trauma is currently poorly understood. Here we characterised mechanical rat nerve tissue properties before and afterin vivocrush and transection injuries using atomic force microscopy-based indentation measurements. Unlike CNS tissue, PNS tissue significantly stiffened after both types of tissue damage, likely mainly due to an increase in collagen I levels. Schwann cells, which crucially support PNS regeneration, became more motile and proliferative on stiffer substratesin vitro, suggesting that changes in tissue stiffness may play a key role in facilitating or impeding nervous system regeneration.
Effect of transcranial direct current stimulation (tDCS) on FRN and P2 during the performance of auditory monetary incentive delay task
Authors: Grigoreva Anastasia , Gorin Aleksei , Klyuchnikov Valery , Dutov Ivan , Shestakova Anna 
Published: December 2022

AbstractTranscranial electrical stimulation (tES) serves as a powerful technique for assessing the causal role of specific brain regions in behavior, including decision-making. While tES studies investigating sensorimotor function yield unequivocal results, cognitive research reveals considerable ambiguity and diversity in stimulation-related effects. The consequences of transcranial direct current stimulation (tDCS) on cognitive functioning are not consistently predictable based on the current direction (cathodal or anodal), which limits its applicability in cognitive research.In the present study, we further explored tES effect ambiguity in cognitive tasks by modulating medial frontal cortex (MFC) activity in an auditory monetary incentive delay (MID) task, where participants responded to acoustic cues encoding expected monetary losses using cathodal tDCS. We analyzed feedback-related negativity (FRN), reflecting prediction error processing when participants encountered losses compared to no losses during two subsequent MID task sessions, and exogenous P2 response to stimulus onset unrelated to anticipated monetary incentives. We anticipated an inhibitory cathodal tDCS effect on both P2 response and FRN.Contrary to our expectations, we observed a facilitatory effect of cathodal tDCS on FRN, replicating our earlier results (Gorin et al., 2022). No effect of stimulation was observed on P2; however, tDCS influenced the learning effect of P2. The difference in P2 amplitude between the first and second sessions, observed in the sham group, was absent in the group that received cathodal tDCS. We offered the interpretation of the complex picture of tES effects during auditory MID performance in light of brain plasticity theory for P2 and reward-learning mechanisms for FRN. Importantly, our findings regarding the multidirectionality of tDCS effects on cognitive function challenge the utility of tES as a readily employable method for testing brain causality in highly complex neurocognitive events, such as decision-making.
Enhancing detectable fluorescence fluctuation for high-throughput and four-dimensional live-cell super-resolution imaging
Authors: Zhao Weisong , Zhao Shiqun , Han Zhenqian , Ding Xiangyan , Hu Guangwei , Wang Xinwei , Mao Heng , Jiu Yaming , Hu Ying , Tan Jiubin , Ding Xumin , Guo Changliang , Chen Liangyi , Li Haoyu 
Published: December 2022

ABSTRACTSuper-resolution (SR) imaging with high-throughput is invaluable to fast and high-precision profiling in a wide range of biomedical applications. However, prevalent SR methods require sophisticated acquisition devices and specific imaging control, and may cost a fairly long time on a single field-of-view. These essentially increase the construction difficulty, including challenges in imaging throughput, system establishment, and automation. Using the natural photophysics of fluorescence, fluctuation-based microscopy techniques can routinely break the diffraction limit with no need for additional optical components, but its long acquisition time still poses a challenge for high-throughput imaging or visualizing transient organelle dynamics. Here, we propose anSR method based on theAuto-Correlation with two-stepDeconvolution (SACD) that reduces the number of frames required by maximizing the detectable fluorescence fluctuation behavior in each measurement, with further removal of tunable parameters by a Fourier ring correlation analysis. It only needs 20 frames for twofold lateral and axial resolution improvements, while the SR optical fluctuation imaging (SOFI) needs more than 1000 frames. By capturing raw images for ∼10 minutes, we record an SR image with ∼128 nm resolution that contains 2.4 gigapixels covering an area of ∼2.0 mm × 1.4 mm, including more than 2,000 cells. Beyond that, by applying continuity and sparsity joint constraint, the Sparse deconvolution-assisted SACD enables 4D live-cell SR imaging of events such as mitochondrial fission and fusion. Overall, as an open-sourced module, we anticipate SACD can offer direct access to SR, which may facilitate the biology studies of cells and organisms with high-throughput and low-cost.
Alpha-band lateralization and microsaccades elicited by exogenous cues do not track attentional orienting
Authors: Balestrieri Elio , Michel René , Busch Niko A. 
Published: December 2022

AbstractWe explore the world by constantly shifting our focus of attention towards salient stimuli, and then disengaging from them in search of new ones. The alpha rhythm (8-13 Hz) has been suggested as a pivotal neural substrate of these attentional shifts, due to its local synchronization and desynchronization that suppresses irrelevant cortical areas and facilitates relevant areas, a phenomenon called alpha lateralization. Whether alpha lateralization tracks the focus of attention from orienting toward a salient stimulus to disengaging from it is still an open question. In this study, we addressed this question by leveraging the well-established phenomenon of Inhibition of Return (IOR), consisting of an initial facilitation in response times (RTs) for target stimuli appearing at an exogenously cued location, followed by a suppression of that location. Our behavioral data showed a typical IOR effect with both early facilitation and subsequent inhibition. By contrast, alpha was lateralized only in the cued direction, but never re-lateralized in a manner compatible with the behavioral inhibition effect. Importantly, also the initial lateralization towards the cue ocurred too late to account for the behavioral facilitation effect. Furthermore, we analyzed the interaction between alpha lateralization and microsaccades: at the same time when alpha was lateralized towards the cued location, microsaccades were mostly oriented away from the cued location. Crucially, the two phenomena showed a significant positive correlation. These results indicate that alpha lateralization reflects primarily the processing of salient stimuli, challenging the view that alpha lateralization is directly involved in exogenous attentional orienting per se. We discuss the relevance of the present findings for an oculomotor account of alpha lateralization as a modulator of cortical excitability in preparation of a saccade.
Regulation of neuroinflammation by astrocyte-derived cholesterol
Authors: Wang Hao , Kulas Joshua A. , Higginbotham Holden , Kovacs Michael A. , Ferris Heather A. , Hansen Scott B. 
Published: December 2022

AbstractNeurodegeneration and its concomitant loss of cognitive function is associated with inflammation and an accumulation of lipids, in particular cholesterol. In the brain, cholesterol is made in astrocytes and transported to surrounding cells by apolipoprotein E (apoE). Elevated cholesterol promotes inflammation in peripheral tissues, but whether astrocyte cholesterol can drive inflammation in the brain is unclear. Here we show that pro-inflammatory cytokines induce cholesterol synthesis in astrocytes. The astrocytes release the cholesterol and immune cells take it up, which causes clustering of proinflammatory receptors in lipid rafts, perpetuating the inflammatory signal. Knockout of cholesterol synthesis in astrocytes blocks the production of inflammatory cytokines in an AD mouse brain and reduces neuroinflammation induced by peripheral injection of lipopolysaccharide (LPS) into the mouse. We conclude that astrocyte cholesterol is a paracrine signal to microglia and tissue-resident macrophages, resulting in increased neuroinflammation.
Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation
Authors: Yang Anlan , Liu Shengjie , Zhang Yuqi , Chen Jia , Feng Shan , Wu Jianping , Hu Qi 
Published: December 2022

SummaryPalmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for the RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of DHHC9 by GCP16 is not clear. Here we report the cryo-EM structures of the human DHHC9-GCP16 complex and its yeast counterpart — the Erf2-Erf4 complex, demonstrating that GCP16 and Erf4 are not directly involved in the catalytic process but stabilize the architecture of DHHC9 and Erf2, respectively. We found that a phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on three residues (C24, C25, and C288) were essential for the catalytic activity of the DHHC9-GCP16 complex. Furthermore, we showed that GCP16 also formed complexes with DHHC14 and 18 to catalyze RAS palmitoylation. These findings provide insights into the regulation mechanism of RAS palmitoyltransferases.
Gut bacteria impact host uric acid burden and its association with atherosclerosis
Authors: Kasahara Kazuyuki , Kerby Robert L. , Zhang Qijun , Pradhan Meenakshi , Mehrabian Margarete , Lusis Aldons , Bergström Göran , Bäckhed Fredrik , Rey Federico E. 
Published: December 2022

AbstractHumans with metabolic and inflammatory diseases, including atherosclerosis harbor dysbiotic gut communities. However, the microbes and microbial pathways that influence disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is in part driven by the gut microbiota and it is associated with circulating levels of the proinflammatory molecule uric acid both in mice and humans. We identify bacterial taxa present in the gut spanning multiple phyla, includingBacillota(Firmicutes),FusobacteriotaandPseudomonadota(Proteobacteria), that use uric acid and adenine– a key precursor of nucleic acids in intestinal cells, as carbon and energy sources anaerobically, and uncover a gene cluster encoding key steps of purine degradation that is widely distributed among gut dwelling bacteria. Furthermore, we demonstrate that colonization of germ-free mice with purine-degrading bacteria modulates levels of uric acid and other purines in the gut and systemically. Altogether this work demonstrates that gut microbes are important drivers of host global purine homeostasis and uric acid levels, and suggests that gut bacterial catabolism of purines may represent a novel mechanism by which the gut microbiome influences host health.
Inhibition of early-acting autophagy genes inC. elegansneurons improves protein homeostasis, promotes exopher production, and extends lifespan via the ATG-16.2 WD40 domain
Authors: Yang Yongzhi , Arnold Meghan Lee , Choy Elizabeth H. , Lange Caitlin M. , Poon Karie , Broussalian Michael , Sun Ling-Hsuan , Moreno Tatiana M. , Singh Anupama , Driscoll Monica , Kumsta Caroline , Hansen Malene 
Published: December 2022

ABSTRACTWhile autophagy is key to maintain cellular homeostasis, tissue-specific roles of individual autophagy genes are less understood. To study neuronal autophagyin vivo, we inhibited autophagy genes specifically inC. elegansneurons, and unexpectedly found that knockdown of early-acting autophagy genes, i.e., involved in formation of the autophagosome, except foratg-16.2, decreased PolyQ aggregates and increased lifespan, albeit independently of the degradation of autophagosomal cargo. Neuronal aggregates can be secreted from neurons via vesicles called exophers, and we found that neuronal inhibition of early-acting autophagy genesatg-7andlgg-1/Atg8, but notatg-16.2increased exopher formation. Moreover,atg-16.2mutants were unable to form exophers, andatg-16.2was required for the effects of early autophagy gene reduction on neuronal PolyQ aggregation, exopher formation, and lifespan. Notably, neuronal expression of full-length ATG-16.2 but not ATG-16.2 without a functional WD40 domain, important for non-canonical functions of ATG16L1 in mammalian cells, restored these phenotypes. Collectively, we discovered a specific role forC. elegansATG-16.2 and its WD40 domain in exopher biogenesis, neuronal proteostasis, and lifespan determination, highlighting a possible role for non-canonical autophagy functions in both exopher formation and in aging.
Development of AlissAID system targeting GFP or mCherry fusion protein
Authors: Ogawa Yoshitaka , Nishimura Kohei , Obara Keisuke , Kamura Takumi 
Published: December 2022

ABSTRACTConditional control of target proteins using the auxin-inducible degron (AID) system provides a powerful tool for investigating protein function in eukaryotes. Here, we established an Affinity-linker based super-sensitive auxin-inducible degron (AlissAID) system in budding yeast by using a single domain antibody (a nanobody). In this system, target proteins fused with GFP or mCherry were degraded depending on a synthetic auxin, 5-Adamantyl-IAA (5-Ad-IAA). In AlissAID system, nanomolar concentration of 5-Ad-IAA induces target degradation, thus minimizing the side effects from chemical compounds. In addition, in AlissAID system, we observed few basal degradations which was observed in other AID systems including ssAID system. Furthermore, AlissAID based conditional knockdown cell lines are easily generated by using budding yeast GFP Clone Collection. From these advantages, the AlissAID system would be an ideal protein-knockdown system in budding yeast cells.
How neuronal morphology impacts the synchronisation state of neuronal networks
Authors: Gowers Robert P , Schreiber Susanne 
Published: December 2022

AbstractThe biophysical properties of neurons not only affect how information is processed within cells, they can also impact the dynamical states of the network. Specifically, the cellular dynamics of action-potential generation have shown relevance for setting the (de)synchronisation state of the network. The dynamics of tonically spiking neurons typically fall into one of three qualitatively distinct types that arise from distinct mathematical bifurcations of voltage dynamics at the onset of spiking. Accordingly, changes in ion channel composition or even external factors, like temperature, have been demonstrated to switch network behaviour via changes in the spike onset bifurcation and hence its associated dynamical type. A thus far less addressed modulator of neuronal dynamics is cellular morphology. Based on simplified and anatomically realistic mathematical neuron models, we show here that the extent of dendritic arborisation has an influence on the neuronal dynamical spiking type and therefore on the (de)synchronisation state of the network. Specifically, larger dendritic trees prime neuronal dynamics for in-phase-synchronised or splayed-out activity in weakly coupled networks, in contrast to cells with otherwise identical properties yet smaller dendrites. Our biophysical insights hold for generic multicompartmental classes of spiking neuron models (from ball-and-stick-type to anatomically reconstructed models) and establish a direct mechanistic link between neuronal morphology and the susceptibility of neural tissue to synchronisation in health and disease.Significance StatementCellular morphology varies widely across different cell types and brain areas. In this study, we provide a mechanistic link between neuronal morphology and the dynamics of electrical activity arising at the network level. Based on mathematical modelling, we demonstrate that modifications of the size of dendritic arbours alone suffice to switch the behaviour of otherwise identical networks from synchronised to asynchronous activity. Specifically, neurons with larger dendritic trees tend to produce more stable phase relations of spiking across neurons. Given the generality of the approach, we provide a novel, morphology-based hypothesis that explains the differential sensitivity of tissue to epilepsy in different brain areas and assigns relevance to cellular morphology in healthy network computation.