bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of socio-economic factors on elementary school student COVID-19 infections in Ontario, Canada
Authors: Srivastava Prachi , Lau Tsz Tan , Ansari Daniel , Thampi Nisha 
Published: February 2022

ABSTRACTBackgroundThe prevalence of SARS-CoV-2 infections in Ontario is disproportionately concentrated in areas with lower-income and racialized groups. We examined whether school-level and area-level socio-economic factors were associated with elementary school student infections in Ontario.MethodsWe performed multi-level modeling analyses using data from the Ministry of Education on school-based infections in Ontario in the 2020-21 school year and on school-level demographics, the Ontario Marginalization Index, and census data to estimate the variability of the cumulative incidence of SARS-CoV-2 infections amongst elementary school students attributable to individual schools (school level, Level 1) and forward sortation areas (FSAs) of schools (area level, Level 2). We explored whether socio-economic factors within individual schools and/or factors common to schools within FSAs predicted the incidence of elementary school student infections.ResultsAt the school level, the proportion of students from low-income households within a school was positively related with the cumulative incidence of SARS-CoV-2 elementary school student infections (β = .083, p < 0.001). At the area level, the dimensions of FSA marginalization were significantly related with cumulative incidence. Ethnic concentration (β = .454, p < 0.001), residential instability (β = .356, p < 0.001), and material deprivation (β = .212, p < 0.001) were positively related. Area-related variables were more likely to explain variance in cumulative incidence than school-related variables (58% versus 1%, respectively).InterpretationSocio-economic characteristics of the geographic location of schools were more important in determining the cumulative incidence of SARS-CoV-2 elementary school student infections than individual school characteristics. Given inequitable effects of protracted education disruption, schools in marginalized areas should be prioritized for infection prevention measures and education continuity and recovery plans.
Nociception-dependent CCL21 induce dorsal root ganglia axonal growth via CCR7-ERK activation
Authors: Mesquida-Veny Francina , Martinez-Torres Sara , Del Rio Jose Antonio , Hervera Arnau 
Published: February 2022

AbstractWhile chemokines were originally described for their ability to induce cell migration, many studies show how chemokines also take part in a variety of other cell functions, acting as adaptable messengers in the communication between a diversity of cell types. In the nervous system, chemokines participate both in physiological and pathological processes, and while their expression is often described on glial and immune cells, growing evidence describe the expression of chemokines and their receptors in neurons, highlighting, their potential in auto- and paracrine signalling. In this study we analysed the role of nociception in the neuronal chemokinome, and their role in axonal growth. We found that stimulating TRPV1+ nociceptors induces a transient increase in CCL21. Interestingly we found that, this CCL21 increases neurite growth of large diameter proprioceptors in vitro. Consistent with this, we show that proprioceptors express the CCL21 receptor CCR7, and a CCR7 neutralizing antibody dose-dependently attenuates CCL21-induced neurite outgrowth. Mechanistically, we found that CCL21 binds locally to its receptor CCR7 at the growth cone, activating the downstream MEK-ERK pathway, that in turn activates N-WASP, triggering actin filament ramification in the growth cone, resulting in increased axonal growth.
Single-value scores of memory-related brain activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging
Authors: Richter Anni , Soch Joram , Kizilirmak Jasmin M. , Fischer Larissa , Schütze Hartmut , Assmann Anne , Behnisch Gusalija , Feldhoff Hannah , Knopf Lea , Raschick Matthias , Schult Annika , Seidenbecher Constanze I. , Yakupov Renat , Düzel Emrah , Schott Björn H. 
Published: February 2022

AbstractMemory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and a composite measure comprising pro-active inhibition, episodic memory, tonic alertness, flexibility, and working memory. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in global cognitive function. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.
Selective influence of dopamine on electrocortical signatures of error monitoring: a combined EEG and immersive virtual reality study in Parkinson’s disease
Authors: Pezzetta R. , Ozkan D.G. , Era V. , Tieri G. , Zabberoni S. , Taglieri S. , Costa A. , Peppe A. , Caltagirone C. , Aglioti S.M. 
Published: February 2022

AbstractDetecting errors in one’s own and other’s actions is likely linked to the discrepancy between intended or expected and produced or observed output. To detect and process the occurrence of salient events seems associated to the release of dopamine, the balance of which is profoundly altered in Parkinson’s disease (PD). EEG studies in healthy participants indicate that the occurrence of errors in observed actions triggers a variety of electrocortical indices (like mid-frontal theta activity, error-related delta and the Error Positivity, oPe), that seem to map different aspects of error detection and performance monitoring. Whether these indices are differently modulated by dopamine in the same individual has never been investigated. To explore this issue, we recorded EEG markers of error detection by asking healthy controls (HCs) and PD patients to observe ecological reach-to-grasp a glass actions performed by a virtual arm seen in first person perspective. PD patients were tested under their dopaminergic medication (‘on-condition’), and after dopaminergic withdrawal (‘off-condition’). HCs showed a clear oPe and an increase of delta and theta power during the observation of erroneous vs. correct actions. In PD patients, oPe and delta responses were always preserved. Crucially, however, an error-related increase of theta power was found in ‘on’ but not in ‘off’ state PD patients. Thus, different EEG error signatures may index the activity of independent systems and error related theta power is selectively modulated by dopamine depletion. Our findings may pave the way to the discovery of dopamine-related biomarkers of higher-order motor cognition dysfunctions that may have crucial theoretical and clinical implications.Significance StatementDopaminergic neurons respond to salient events during performance monitoring. Yet, the impact of dopamine depletion on the human reactivity to observed errors is still unclear. We recorded EEG in patients with Parkinson’s Disease (PD) under dopaminergic treatment (‘on-condition’) and medication withdrawal (‘off-condition’) while they observed correct and erroneous goal-related actions performed by a virtual limb. Analysis of Error Positivity (oPe) and theta and delta power increase, markers of physiological error-monitoring, indicates that while the formers were intact, the latter was preserved in the ‘on’ and altered in the ‘off’ condition. Thus, different EEG markers of error monitoring likely rely on independent circuits. Moreover, mid-frontal theta activity alterations may represent a marker of dopamine-related neurophysiological impairments of higher-order cognition.
Genesis of bursting activity: Role of inhibitory constraints on persistent Na+ currents
Authors: Neveu Curtis L. , Baxter Douglas A. , Byrne John H. 
Published: February 2022

SUMMARYSome neurons express a plateau of spike activity greatly outlasting a stimulus, whereas others do not. This difference could be due to differential expression of ion channels (e.g., persistent Na+, and Ca2+) or similar expression of channels that differ in their properties. We compared three Aplysia neurons with varying capacity to generate plateau potentials: B51 with self-terminating plateaus, B64 with plateau potentials that do not self-terminate, and the regular spiking neuron B8. Our results indicate the three neurons expressed outward currents IA and ID, voltage-gated Ca2+ currents ICaL and ICaR, and persistent inward INaP. The most notable difference observed was a larger IA, ID, and IKCa currents in B8, and the plateau generating B64 did not express IKCa. Computational models suggest outward currents suppress and temporally constrain the plateau potential and that inward Ca2+ currents suppress plateau potentials when coupled with IKCa.
Chlamydomonas RABL4/IFT27 Mediates Phototaxis via Promoting BBSome-dependent Ciliary Export of Phospholipase D
Authors: Liu Yan-Xia , Xue Bin , Fan Zhen-Chuan 
Published: February 2022

AbstractPhospholipase D (PLD) interacts with the BBSome for loading onto retrograde intraflagellar transport (IFT) trains to exit cilia in Chlamydomonas reinhardtii. PLD ciliary retention and depletion of Rab-like 4 (RABL4) GTPase IFT27 cause the same non-phototactic phenotype but not impair IFT and ciliation. Here, we show that the IFT-B1 subunit IFT27 binds its partner IFT25 to form the heterodimeric IFT25/27 in an IFT27 nucleotide state-independent manner. IFT25/27, IFT-A, and IFT-B are irrelevant for maintaining the stability of one another. GTP-loading onto IFT27 enhances the IFT25/27 affinity for IFT-B1 in cytoplasm, while GDP-loaded IFT27 does not prevent IFT25/27 from entering and cycling through cilia by integrating into IFT-B1. Upon at the ciliary tip, IFT25/27 cycles on and off IFT-B1 and this process is irrelevant with the nucleotide state of IFT27. During BBSome remodeling at the ciliary tip, IFT25/27 promotes BBSome reassembly independent of IFT27 nucleotide state, making post-remodeled BBSomes available for PLD to interact with. Therefore, IFT25/27 facilitates BBSome-dependent PLD export from cilia via controlling availability of intact BBSomes at the ciliary tip, providing a regulatory mechanism for IFT27 to mediate phototaxis in C. reinhardtii.
Perception of RNA Nanotechnology among students and recommendations towards improved educational outreach
Authors: Kozlov Seraphim 
Published: February 2022

AbstractTranslating new technologies to industrial and biomedical applications requires a highly skilled workforce. In the past, colleges and graduate schools played a primary role in preparing students for various areas of industry and medicine. The learning process and introduction of new concepts have recently extended beyond college education. High schools saw the rise of specialized career programs, while both high and middle school curricula got infused with challenging concepts. Nucleic acids, such as DNA and RNA, are broadly known for their role in the foundation of life. However, nucleic acid nanotechnology, an area of material science manipulating DNA and RNA to create complex structures with controlled properties, is less known. Herein, I report the results of a study investigating the perception of RNA nanotechnology among school students and suggest educational resources to improve understanding of RNA nanotechnology.
Improving breast cancer diagnostics with artificial intelligence for MRI
Authors: Witowski Jan , Heacock Laura , Reig Beatriu , Kang Stella K. , Lewin Alana , Pyrasenko Kristine , Patel Shalin , Samreen Naziya , Rudnicki Wojciech , Łuczyńska Elżbieta , Popiela Tadeusz , Moy Linda , Geras Krzysztof J. 
Published: February 2022

AbstractDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a very high sensitivity in detecting breast cancer, but it often leads to unnecessary biopsies and patient workup. In this paper, we used an artificial intelligence (AI) system to improve the overall accuracy of breast cancer diagnosis and personalize management of patients undergoing DCE-MRI. On the internal test set (N=3,936 exams), our system achieved an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% CI: 0.92-0.93). In a retrospective reader study, there was no statistically significant difference between 5 board-certified breast radiologists and the AI system (mean ΔAUROC +0.04 in favor of the AI system). Radiologists’ performance improved when their predictions were averaged with AI’s predictions (mean ΔAUPRC [area under the precision-recall curve] +0.07). Those hybrid predictions also increase interreader agreement (Fleiss’ kappa Δ +0.21 (0.16-0.26)). We demonstrated the generalizability of the AI system using multiple data sets from Poland and the US. In subgroup analysis, we observed consistent results across different cancer subtypes and patient demographics. Using the decision curve analysis, we showed that the AI system can reduce unnecessary biopsies in the range of clinically relevant risk thresholds. This would lead to avoiding benign biopsies in up to 20% of all BI-RADS category 4 patients. Finally, we performed an error analysis, investigating situations where AI predictions were mostly incorrect. This exploratory work creates a foundation for deployment and prospective analysis of AI-based models for breast MRI.One Sentence SummaryWe developed and evaluated an AI system for predicting breast cancer in MRI that matches the performance of board-certified radiologists and has the potential to prevent unnecessary biopsies.
Post-acute sequelae of COVID-19 and adverse psychiatric outcomes: an etiology and risk systematic review protocol
Authors: Effiong Andem 
Published: February 2022

ABSTRACTIntroductionThe post-acute sequelae of COVID-19 (PASC) is a syndrome characterized by persistent COVID-19 symptoms or the onset of new symptoms following recovery from the initial or acute phase of the illness. Such symptoms often occur four or more weeks after being diagnosed with COVID-19. Although a lot of work has gone into understanding the long-term mental health effects of PASC, many questions related to the etiology and risk of this condition remain. Thus, this protocol is for a systematic review assessing the association between PASC and adverse psychiatric outcomes and whether people with PASC are at greater risk of developing an adverse psychiatric outcome than those without PASC.Methods and analysisVarious medical databases (e.g., PubMed and EMBASE) will be searched for eligible articles using predefined search criteria. Gray literature will also be explored. Epidemiological observational studies and secondary analyses of randomized controlled trials that report a quantitative relationship between PASC and at least one adverse psychiatric outcome will be included. The Population, Exposure of interest, Comparator, and Outcome (PECO) framework will be used as a standardized framework for the inclusion criteria. The Joanna Briggs Institute (JBI) critical appraisal tools will be used to assess methodological quality and critically appraise the risk of bias in included studies. A random-effects meta-analysis will be conducted if possible. A formal narrative synthesis will be performed if a meta-analysis is impossible due to substantial heterogeneity across studies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to rate the cumulative certainty of the evidence for all outcomes.Ethics and DisseminationEthical approval is not required for this study. The study results will be published in a peer-reviewed journal.Prospero registration numberCRD42022308737Strengths and limitations of this study▪This study documents and addresses etiology, risk factors, and long-term symptoms of COVID-19 among people with post-acute sequelae of COVID-19 (PASC).▪It focuses on a key priority area for new evidence syntheses on the clinical management of COVID-19 and pandemic-related conditions.▪It will include evidence on non-hospitalized and hospitalized patients with a history of PASC.▪Substantial heterogeneity across studies may limit the ability to perform a meta-analysis.▪Findings will inform disease prevention, decision-making, healthcare policy, and clinical research.
A novel pathway phenotype of temporal lobe epilepsy and comorbid psychiatric disorders: results of precision nomothetic medicine
Authors: Maes Michael , Barbosa Décio Sabbatini , Kanchanatawan Buranee 
Published: February 2022

AbstractNo precision medicine models of temporal lobe epilepsy (TLE) and associated mental comorbidities were developed to date. This observational 11study aimed to develop a precision nomothetic, data driven comorbid TLE model with endophenotype classes and pathways phenotypes that may have prognostic and therapeutical implications. We recruited forty healthy controls and 108 TLE patients for this research and assessed TLE and psychopathology (PP) features as well as oxidative stress (OSTOX, e.g., malondialdehyde or MDA, lipid hydroperoxides, and advanced oxidation protein products) and antioxidant (paraoxonase 1 or PON1 status, -SH groups, and total radical trapping potential or TRAP) biomarkers. A large part (57.2%) of the variance in a latent vector (LV) extracted from the above TLE and PP features was explained by these OSTOX and antioxidant biomarkers. The PON1 Q192R genetic variant showed indirect effects on this LV which were completely mediated by PON1 activity and MDA. Factor analysis showed that a common core could be extracted from TLE, PP, OSTOX and antioxidant scores, indicating that these features are manifestations of a common underlying construct, i.e., a novel pathway phenotype of TLE. Based on the latter we constructed a new phenotype class that is characterized by increased severity of TLE, PP and OSTOX features and lowered antioxidant defenses. A large part of the variance in episode frequency was explained by increased MDA, lowered antioxidant, and nitric oxide metabolite levels. In conclusion a) PP symptoms belong to the TLE phenome and signal increased severity; and b) cumulative effects of aldehyde formation and lowered antioxidants determine epileptogenic kindling.
Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy
Authors: Miller Annie L. , Fuller-Carter Paula I. , Masarini Klaudija , Samardzija Marijana , Carter Kim W. , Rashwan Rabab , Brunet Alicia A. , Chopra Abha , Ram Ramesh , Grimm Christian , Ueffing Marius , Carvalho Livia S. , Trifunović Dragana 
Published: February 2022

AbstractInherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6ccpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD, to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in the development of a broad class of novel therapies to slow cone degeneration.
Creativity in Verbal Associations is Linked to Semantic Control
Authors: Krieger-Redwood Katya , Steward Anna , Gao Zhiyao , Wang Xiuyi , Halai Ajay , Smallwood Jonathan , Jefferies Elizabeth 
Published: February 2022

AbstractWhile memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unique versus stereotypical patterns of retrieval. Less creative responses to strongly associated word pairs were associated with greater engagement of episodic memory: in highly familiar situations, semantic and episodic stores converge on the same information. This pattern of retrieval was associated with greater engagement of core default mode network. In contrast, more creative responses to weakly associated word pairs were associated with the controlled retrieval of less dominant semantic information and greater recruitment of the semantic control network, which overlaps with the dorsomedial subsystem of default mode network. Consequently, although both creative/controlled and stereotypical/more automatic patterns of retrieval are associated with activation within default mode network, these processes show little overlap in activation. These findings show that creativity emerges from controlled aspects of semantic cognition.
The C-terminal domain of Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase
Authors: Knighton Laura E. , Nitika  , Omkar Siddhi , Truman Andrew. W. 
Published: February 2022

AbstractThe Hsp70 family of molecular chaperones is well-conserved and expressed in all organisms. In budding yeast, cells express four highly similar cytosolic Hsp70s Ssa1, 2, 3 and 4 which arose from gene duplication. Ssa1 and 2 are constitutively expressed while Ssa3 and 4 are induced upon heat shock. Recent evidence suggests that despite their amino acid similarity, these Ssas have unique roles in the cell. Here we examine the relative importance of Ssa1-4 in the regulation of the enzyme ribonucleotide reductase (RNR). We demonstrate that cells expressing either Ssa3 or Ssa4 as their sole Ssa are compromised for their resistance to DNA damaging agents and activation of DDR transcription. In addition, we show that the steady state levels and stability of RNR small subunits Rnr2 and Rnr4 are reduced in Ssa3 or Ssa4-expressing cells, a result of decreased Ssa-RNR interaction. Interaction between the Hsp70 co-chaperone Ydj1 and RNR is correspondingly decreased in cells only expressing Ssa3 and 4. Through studies of Ssa2/4 domain swap chimeras, we determined that the C-terminal domain of Ssas are the source of this functional specificity. Taking together, our work suggests a distinct role for Ssa paralogs in regulating DNA replication mediated by C-terminus sequence variation.Author SummaryCells require molecular chaperones to fold proteins into their active conformation. A major mystery however is why cells express so many highly-related and apparently redundant Hsp70 paralogs. We examined the role of four Hsp70 paralogs in budding yeast (Ssa1, 2, 3 and 4) on the activity of the ribonucleotide reductase (RNR complex). Importantly, we demonstrate there is selectivity of RNR subunits for Ssa1 and Ssa2 subunits, which is dictated by the co-chaperone Ydj1. Taken together, our work provides new insight into the functional specificity of Hsp70 paralogs using a native client protein.