Miracle-dz/UniFAR-FTUs huggingface dataset:
Simplified Bioprinting-Based 3D Cell Culture Infection Models for Virus Detection

Studies of virus–host interactions in vitro may be hindered by biological characteristics of conventional monolayer cell cultures that differ from in vivo infection. Three-dimensional (3D) cell cultures show more in vivo-like characteristics and may represent a promising alternative for characterisation of infections. In this study, we established easy-to-handle cell culture platforms based on bioprinted 3D matrices for virus detection and characterisation. Different cell types were cultivated on these matrices and characterised for tissue-like growth characteristics regarding cell morphology and polarisation. Cells developed an in vivo-like morphology and long-term cultivation was possible on the matrices. Cell cultures were infected with viruses which differed in host range, tissue tropism, cytopathogenicity, and genomic organisation and virus morphology. Infections were characterised on molecular and imaging level. The transparent matrix substance allowed easy optical monitoring of cells and infection even via live-cell microscopy. In conclusion, we established an enhanced, standardised, easy-to-handle bioprinted 3D-cell culture system. The infection models are suitable for sensitive monitoring and characterisation of virus–host interactions and replication of different viruses under physiologically relevant conditions. Individual cell culture models can further be combined to a multicellular array. This generates a potent diagnostic tool for propagation and characterisation of viruses from diagnostic samples.
Tracing the footsteps of autophagy in computational biology

Abstract Autophagy plays a crucial role in maintaining cellular homeostasis through the degradation of unwanted materials like damaged mitochondria and misfolded proteins. However, the contribution of autophagy toward a healthy cell environment is not only limited to the cleaning process. It also assists in protein synthesis when the system lacks the amino acids’ inflow from the extracellular environment due to diet consumptions. Reduction in the autophagy process is associated with diseases like cancer, diabetes, non-alcoholic steatohepatitis, etc., while uncontrolled autophagy may facilitate cell death. We need a better understanding of the autophagy processes and their regulatory mechanisms at various levels (molecules, cells, tissues). This demands a thorough understanding of the system with the help of mathematical and computational tools. The present review illuminates how systems biology approaches are being used for the study of the autophagy process. A comprehensive insight is provided on the application of computational methods involving mathematical modeling and network analysis in the autophagy process. Various mathematical models based on the system of differential equations for studying autophagy are covered here. We have also highlighted the significance of network analysis and machine learning in capturing the core regulatory machinery governing the autophagy process. We explored the available autophagic databases and related resources along with their attributes that are useful in investigating autophagy through computational methods. We conclude the article addressing the potential future perspective in this area, which might provide a more in-depth insight into the dynamics of autophagy.
Modeling Parkinson’s Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies.
Using Data Assimilation for Quantitative Electroencephalography Analysis

We propose a method based on the ensemble Kalman filter (EnKF) together with quantitative electroencephalogram (QEEG) coherence and power spectrum analysis for evaluating changes in brain activity associated with cognitive processes. Such analysis framework has been widely used in the context of data assimilation (DA) in areas such as geosciences, meteorology, and aerospace. However, the use of this approach is less common in neurosciences. In our case, EnKF highlights the spectral contribution of brain signals that are more likely (according to their coherence analysis) to be related to the cognitive process of interest. The power enhancement, due to the cognitive activity, is later validated in the power spectrum analysis by comparing through statistical tests relevant frequency content in two datasets in which assessing the development of cognitive abilities is of interest: the process of getting concentrated and of learning a new skill. Our results show that our DA-based methodology can highlight important frequency characteristics of the electroencephalogram (EEG) data that have been related to different cognitive processes. Hence, our proposal has the potential to understand of neurocognitive phenomena that is tracked through QEEG.
Kinetic Treatment of the Nucleation in Supersaturated Vapors

The equations of the individual processes of self nucleation are utilized through an electrical analogy to obtain the nucleation frequency. This process is shown to be shorter and less subject to error than that of previous investigators since the appearance of indeterminant integration constants is completely avoided. With the nucleation frequencies of crystals and spheres the Ostwald law of stages is reviewed and modified. In the final section the general resistance image is discussed and mention is made of the relation of the electrical network and Volmer's formula.
High value of mid‐regional proadrenomedullin in COVID‐19: A marker of widespread endothelial damage, disease severity, and mortality

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi‐organs dysfunction. The aim of this study was to evaluate the role of mid‐regional proadrenomedullin (MR‐proADM) as a marker of SARS‐CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS‐CoV‐2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR‐proADM cut‐off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR‐proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR‐proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.
Migration trajectories of the diamondback moth Plutella xylostella in China inferred from population genomic variation.

BACKGROUND The diamondback moth (DBM), Plutella xylostella (Lepidoptera: Plutellidae), is a notorious pest of cruciferous plants. In temperate areas, annual populations of DBM originate from adult migrants. However, the source populations and migration trajectories of immigrants remain unclear. Here, we investigated migration trajectories of DBM in China with genome-wide single nucleotide polymorphisms (SNPs) genotyped using double-digest RAD (ddRAD) sequencing. We first analyzed patterns of spatial and temporal genetic structure among southern source and northern recipient populations, then inferred migration trajectories into northern regions using discriminant analysis of principal components (DAPC), assignment tests and spatial kinship patterns. RESULTS Temporal genetic differentiation among populations was low, indicating sources of recipient populations and migration trajectories are stable. Spatial genetic structure indicated three genetic clusters in the southern source populations. Assignment tests linked northern populations to the Sichuan cluster, and central-eastern populations to the South and Yunnan clusters, indicating that Sichuan populations are sources of northern immigrants and South and Yunnan populations are sources of central-eastern populations. First-order (full-sib) and second-order (half-sib) kin pairs were always found within populations, but about 35-40% of third-order (cousin) pairs were found in different populations. Closely related individuals in different populations were in about 35-40% of cases found at distances of 900 to 1500 km, while some were separated by over 2000 km. CONCLUSION This study unravels seasonal migration patterns in the DBM. We demonstrate how careful sampling and population genomic analyses can be combined to help understand cryptic migration patterns in insects. This article is protected by copyright. All rights reserved.
Pharmacogenomics for Primary Care: An Overview

Most of the prescribing and dispensing of medicines happens in primary care. Pharmacogenomics (PGx) is the study and clinical application of the role of genetic variation on drug response. Mounting evidence suggests PGx can improve the safety and/or efficacy of several medications commonly prescribed in primary care. However, implementation of PGx has generally been limited to a relatively few academic hospital centres, with little adoption in primary care. Despite this, many primary healthcare providers are optimistic about the role of PGx in their future practice. The increasing prevalence of direct-to-consumer genetic testing and primary care PGx studies herald the plausible gradual introduction of PGx into primary care and highlight the changes needed for optimal translation. In this article, the potential utility of PGx in primary care will be explored and on-going barriers to implementation discussed. The evidence base of several drug-gene pairs relevant to primary care will be outlined with a focus on antidepressants, codeine and tramadol, statins, clopidogrel, warfarin, metoprolol and allopurinol. This review is intended to provide both a general introduction to PGx with a more in-depth overview of elements relevant to primary care.
Swimming microorganisms acquire optimal efficiency with multiple cilia

Significance In this study, we clarified energetics of microbial locomotion by computing flow around a spherical swimmer covered with cilia. We showed a scaling law for microbial dynamics and revealed that microorganisms can swim optimally and enlarge their bodies by making multiple cilia. The optimal density of cilia was independent of the body size. Our estimated optimal density of cilia corresponded to those of actual microorganisms, including species of ciliates and microalgae. These results will help us to understand the mechanistic benefits of multiple cilia and open up an area of research that integrates fluid mechanics, biophysics, and microbiology. Planktonic microorganisms are ubiquitous in water, and their population dynamics are essential for forecasting the behavior of global aquatic ecosystems. Their population dynamics are strongly affected by these organisms’ motility, which is generated by their hair-like organelles, called cilia or flagella. However, because of the complexity of ciliary dynamics, the precise role of ciliary flow in microbial life remains unclear. Here, we have used ciliary hydrodynamics to show that ciliates acquire the optimal propulsion efficiency. We found that ciliary flow highly resists an organism’s propulsion and that the swimming velocity rapidly decreases with body size, proportional to the power of minus two. Accordingly, the propulsion efficiency decreases as the cube of body length. By increasing the number of cilia, however, efficiency can be significantly improved, up to 100-fold. We found that there exists an optimal number density of cilia, which provides the maximum propulsion efficiency for all ciliates. The propulsion efficiency in this case decreases inversely proportionally to body length. Our estimated optimal density of cilia corresponds to those of actual microorganisms, including species of ciliates and microalgae, which suggests that now-existing motile ciliates and microalgae have survived by acquiring the optimal propulsion efficiency. These conclusions are helpful for better understanding the ecology of microorganisms, such as the energetic costs and benefits of multicellularity in Volvocaceae, as well as for the optimal design of artificial microswimmers.
Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a “Two-Hit” Non-Genetic Mouse Model of Schizophrenia

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia.
Level of professional ethics awareness and medical ethics competency of dental hygienists and dental hygiene students: the need to add ethics items to the Korean Dental Hygienist Licensing Examination

Purpose This study aimed to evaluate the level of professional ethics awareness and medical ethics competency in order to assess the potential need for ethics items to be included on the Korean Dental Hygienist Licensing Examination. Methods In total, 358 clinical dental hygienists and dental hygiene students completed a structured questionnaire to evaluate their level of ethical awareness and medical ethics competency. The sub-factors of medical ethics were classified into relationships with patients, medical and social relations, and individual specialized fields. Results Only 32.1% of participants indicated that they had taken a course on professional ethics in the university curriculum, but 95.2% of respondents considered professional ethics to be important. The overall score for medical ethics competency was average (3.37 out of 5). The score for relationships with patients was 3.75 points, followed by medical and social relations (3.19 points) and individual specialized fields (3.16 points). The level of professional ethics awareness was higher among participants who had taken a course on professional ethics than among those who had not done so or who did not remember whether they had done so. Conclusion Dental hygienists were aware of the importance of professional ethics, but their medical ethics competency was moderate. Therefore, medical ethics should be treated as a required subject in the university curriculum, and medical ethics competency evaluations should be strengthened by adding ethics items to the Korean Dental Hygienist Licensing Examination.
Information needs and oral epithelial dysplasia: development and psychometric evaluation of a novel instrument.

OBJECTIVES Oral epithelial dysplasia (OED) can lead to significant information needs (IN) related to the risk of cancer development, the need for long-term monitoring and potential intervention. The present study aimed to develop and perform preliminary psychometric testing for a novel IN instrument specific to OED. SUBJECTS AND METHODS Patients diagnosed with OED were invited to complete the Oral Epithelial Dysplasia Informational Needs Questionnaire (ODIN-Q), which was developed based on a known theoretical framework and with items generated via expert input and the literature. Face and content validity were initially assessed prior to finalisation of the tool. ODIN-Q was tested for internal consistency and test-retest reliability along with construct validity. RESULTS ODIN-Q consists of 35 items, categorised under six domains, and rated by dual four-point Likert scales (amount of information received and degree of importance). Internal consistency (Cronbach's alpha) was rated 'excellent' for the scale (0.93) and both subscales (0.92/0.94). For test-retest reliability, moderate agreement was found (κ = 0.49-0.53). Regarding construct validity, a significant but limited relationship was found between ODIN-Q and the Krantz Health Opinion Survey. CONCLUSION ODIN-Q showed adequate psychometric properties of reliability and validity. Further validation is, however, needed to assess its structural validity and responsiveness.
Electrolocation? The evidence for redox‐mediated taxis in Shewanella oneidensis

Shewanella oneidensis is a dissimilatory metal reducing bacterium and model for extracellular electron transfer (EET), a respiratory mechanism in which electrons are transferred out of the cell. In the last 10 years, migration to insoluble electron acceptors for EET has been shown to be nonrandom and tactic, seemingly in the absence of molecular or energy gradients that typically allow for taxis. As the ability to sense, locate, and respire electrodes has applications in bioelectrochemical technology, a better understanding of taxis in S. oneidensis is needed. While the EET conduits of S. oneidensis have been studied extensively, its taxis pathways and their interplay with EET are not yet understood, making investigation into taxis phenomena nontrivial. Since S. oneidensis is a member of an EET‐encoding clade, the genetic circuitry of taxis to insoluble acceptors may be conserved. We performed a bioinformatic analysis of Shewanella genomes to identify S. oneidensis chemotaxis orthologs conserved in the genus. In addition to the previously reported core chemotaxis gene cluster, we identify several other conserved proteins in the taxis signaling pathway. We present the current evidence for the two proposed models of EET taxis, “electrokinesis” and flavin‐mediated taxis, and highlight key areas in need of further investigation.
In Situ Labeling and Distance Measurements of Membrane Proteins in E. coli Using Finland and OX063 Trityl Labels

Abstract In situ investigation of membrane proteins is a challenging task. Previously we demonstrated that nitroxide labels combined with pulsed ESR spectroscopy is a promising tool for this purpose. However, the nitroxide labels suffer from poor stability, high background labeling, and low sensitivity. Here we show that Finland (FTAM) and OX063 based labels enable labeling of the cobalamin transporter BtuB and BamA, the central component of the β‐barrel assembly machinery (BAM) complex, in E coli. Compared to the methanethiosulfonate spin label (MTSL), trityl labels eliminated the background signals and enabled specific in situ labeling of the proteins with high efficiency. The OX063 labels show a long phase memory time (TM) of ≈5 μs. All the trityls enabled distance measurements between BtuB and an orthogonally labeled substrate with high selectivity and sensitivity down to a few μm concentration. Our data corroborate the BtuB and BamA conformations in the cellular environment of E. coli.