Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpretative immune targets and contemporary position for vaccine development against SARS‐CoV‐2: A systematic review

The year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which causes COVID‐19 infection. Soon after the first evidence was reported in Wuhan, China, the World Health Organization declared global public health emergency and imminent need to understand the pathogenicity of the virus was required in limited time. Once the genome sequence of the virus was delineated, scientists across the world started working on the development of vaccines. Although, some laboratories have been using previously developed vaccine platforms from severe acute respiratory syndrome coronavirus (SARS) and middle east respiratory syndrome‐related coronavirus and apply them in COVID‐19 vaccines due to genetic similarities between coronaviruses. We have conducted a literature review to assess the background and current status of COVID‐19 vaccines. The worldwide implementation and strategies for COVID‐19 vaccine development are summarized from studies reported in years 2015–2020. While discussing the vaccine candidates, we have also explained interpretative immune responses of SARS‐CoV‐2 infection. There are several vaccine candidates at preclinical and clinical stages; however, only 42 vaccines are under clinical trials. Therefore, more industry collaborations and financial supports to COVID‐19 studies are needed for mass‐scale vaccine development. To develop effective vaccine platforms against SARS‐CoV‐2, the genetic resemblance with other coronaviruses are being evaluated which may further promote fast‐track trials on previously developed SARS‐CoV vaccines.
Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma

BACKGROUND Identifying factors conferring responses to therapy in cancer is critical to select the best treatment for patients. For immune checkpoint inhibition (ICI) therapy, mounting evidence suggests that the gut microbiome can determine patient treatment outcomes. However, the extent to which gut microbial features are applicable across different patient cohorts has not been extensively explored. METHODS We performed a meta-analysis of 4 published shotgun metagenomic studies (Ntot = 130 patients) investigating differential microbiome composition and imputed metabolic function between responders and nonresponders to ICI. RESULTS Our analysis identified both known microbial features enriched in responders, such as Faecalibacterium as the prevailing taxa, as well as additional features, including overrepresentation of Barnesiella intestinihominis and the components of vitamin B metabolism. A classifier designed to predict responders based on these features identified responders in an independent cohort of 27 patients with the area under the receiver operating characteristic curve of 0.625 (95% CI: 0.348–0.899) and was predictive of prognosis (HR = 0.35, P = 0.081). CONCLUSION These results suggest the existence of a fecal microbiome signature inherent across responders that may be exploited for diagnostic or therapeutic purposes. FUNDING This work was funded by the Knut and Alice Wallenberg Foundation, BioGaia AB, and Cancerfonden.
Vibrational Spectroscopy of Cyanide-Bridged, Iron(II) Spin-Crossover Coordination Polymers: Estimation of Vibrational Contributions to the Entropy Change Associated with the Spin Transition†

A series of cyanide-bridged, iron(II) spin-crossover coordination polymers of formula Fe(py)2[M(CN)4] (M = Pd or Pt; py = pyridine) and Fe(pz)[M(CN)4]·2H2O (M = Ni, Pd, or Pt; pz = pyrazine) have been studied by recording the Raman and infrared (IR) spectra of their low-spin (LS) and high-spin (HS) forms in the solid state. Spectral changes upon metal and ligand substitution were used to guide the assignment of vibrational modes. Vibrational entropy changes upon spin transition were analyzed within the harmonic approximation. The results confirm the major contribution of the Fe−ligand vibrations to the overall entropy change associated with the spin transition (∼60%), butcontrary to expectationsreveal significant changes in other intra- and intermolecular vibrations, of possible relevance to the high cooperativity of the spin transition.
Association of Red Meat Intake with the Risk of Cardiovascular Mortality in General Japanese Stratified by Kidney Function: NIPPON DATA80

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46–0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function.
Pathological Functions of LRRK2 in Parkinson’s Disease

Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are common genetic risk factors for both familial and sporadic Parkinson’s disease (PD). Pathogenic mutations in LRRK2 have been shown to induce changes in its activity, and abnormal increase in LRRK2 kinase activity is thought to contribute to PD pathology. The precise molecular mechanisms underlying LRRK2-associated PD pathology are far from clear, however the identification of LRRK2 substrates and the elucidation of cellular pathways involved suggest a role of LRRK2 in microtubule dynamics, vesicular trafficking, and synaptic transmission. Moreover, LRRK2 is associated with pathologies of α-synuclein, a major component of Lewy bodies (LBs). Evidence from various cellular and animal models supports a role of LRRK2 in the regulation of aggregation and propagation of α-synuclein. Here, we summarize our current understanding of how pathogenic mutations dysregulate LRRK2 and discuss the possible mechanisms leading to neurodegeneration.
Satisfaction, Enjoyment and Boredom with Physical Education as Mediator between Autonomy Support and Academic Performance in Physical Education

The purpose of this study was to analyze the mediating effect of satisfaction/enjoyment and boredom between the perception of autonomy support and academic performance in physical education. The sample consisted of 374 girls (Mage = 13.99; SD = 0.30) and 374 boys (Mage = 14.02; SD = 0.33) from the state of Nuevo León, Mexico. The instruments used were the Questionnaire for Autonomy Support in Physical Education (CAA-EF), Sport Satisfaction Intrinsic in Physical Education (SSI-EF) and the physical education performance of the students. The instrument’s validity tests were analyzed using confirmatory procedures. Descriptive, reliability, and validity analyses were carried out for each instrument, and the mediating effect was examined; a mediation analysis was performed using the PROCESS V.3. 5 macro. The main results revealed that autonomy support is not a direct indicator of physical education performance, but rather that students must feel satisfied with physical education for there to exist a forecast for a positive physical education performance. Satisfaction with physical education was found to have a mediating effect between autonomy support and physical education performance. However, boredom did not have a mediating effect between autonomy support and the student’s performance in physical education class.
Sensorimotor dysfunction in a mild mouse model of cortical contusion injury without significant neuronal loss is associated with increases in inflammatory proteins with innate but not adaptive immune functions

Traumatic brain injury is a leading cause of mortality and morbidity in the United States. Acute trauma to the brain triggers chronic secondary injury mechanisms that contribute to long‐term neurological impairment. We have developed a single, unilateral contusion injury model of sensorimotor dysfunction in adult mice. By targeting a topographically defined neurological circuit with a mild impact, we are able to track sustained behavioral deficits in sensorimotor function in the absence of tissue cavitation or neuronal loss in the contused cortex of these mice. Stereological histopathology and multiplex enzyme‐linked immunosorbent assay proteomic screening confirm contusion resulted in chronic gliosis and the robust expression of innate immune cytokines and monocyte attractant chemokines IL‐1β, IL‐5, IL‐6, TNFα, CXCL1, CXCL2, CXCL10, CCL2, and CCL3 in the contused cortex. In contrast, the expression of neuroinflammatory proteins with adaptive immune functions was not significantly modulated by injury. Our data support widespread activation of innate but not adaptive immune responses, confirming an association between sensorimotor dysfunction with innate immune activation in the absence of tissue or neuronal loss in our mice.
Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells

Abstract Context The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown. Objective This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway. Materials and methods Sixteen-month-old male Wistar rats in the Heshouwuyin group and the natural-aging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group (n = 10). The testicular tissue and spermatogenic cells were studied. Results The immunofluorescence results revealed that the insulin receptor (INSR)- (0.056 ± 0.00548), insulin receptor substrate 1(IRS1)- (0.251 ± 0.031), IRS2 (0.230 ± 0.019)- and insulin-like growth factor 1 (IGF1)-positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031; p < 0.01), and the IGF-binding protein 3 (IGFBP3)-positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group (p < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells. Conclusions Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.
The Role of Efflux Pumps in the Transition from Low-Level to Clinical Antibiotic Resistance

Antibiotic resistance is on the rise and has become one of the biggest public health challenges of our time. Bacteria are able to adapt to the selective pressure exerted by antibiotics in numerous ways, including the (over)expression of efflux pumps, which represents an ancient bacterial defense mechanism. Several studies show that overexpression of efflux pumps rarely provides clinical resistance but contributes to a low-level resistance, which allows the bacteria to persist at the infection site. Furthermore, recent studies show that efflux pumps, apart from pumping out toxic substances, are also linked to persister formation and increased spontaneous mutation rates, both of which could aid persistence at the infection site. Surviving at the infection site provides the low-level-resistant population an opportunity to evolve by acquiring secondary mutations in antibiotic target genes, resulting in clinical resistance to the treating antibiotic. Thus, this emphasizes the importance and challenge for clinicians to be able to monitor overexpression of efflux pumps before low-level resistance develops to clinical resistance. One possible treatment option could be an efflux pump-targeted approach using efflux pump inhibitors.
Convolutional Network With Twofold Feature Augmentation for Diabetic Retinopathy Recognition From Multi-Modal Images

Objective: With the scenario of limited labeled dataset, this paper introduces a deep learning-based approach that leverages Diabetic Retinopathy (DR) severity recognition performance using fundus images combined with wide-field swept-source optical coherence tomography angiography (SS-OCTA). Methods: The proposed architecture comprises a backbone convolutional network associated with a Twofold Feature Augmentation mechanism, namely TFA-Net. The former includes multiple convolution blocks extracting representational features at various scales. The latter is constructed in a two-stage manner, i.e., the utilization of weight-sharing convolution kernels and the deployment of a Reverse Cross-Attention (RCA) stream. Results: The proposed model achieves a Quadratic Weighted Kappa rate of 90.2% on the small-sized internal KHUMC dataset. The robustness of the RCA stream is also evaluated by the single-modal Messidor dataset, of which the obtained mean Accuracy (94.8%) and Area Under Receiver Operating Characteristic (99.4%) outperform those of the state-of-the-arts significantly. Conclusion: Utilizing a network strongly regularized at feature space to learn the amalgamation of different modalities is of proven effectiveness. Thanks to the widespread availability of multi-modal retinal imaging for each diabetes patient nowadays, such approach can reduce the heavy reliance on large quantity of labeled visual data. Significance: Our TFA-Net is able to coordinate hybrid information of fundus photos and wide-field SS-OCTA for exhaustively exploiting DR-oriented biomarkers. Moreover, the embedded feature-wise augmentation scheme can enrich generalization ability efficiently despite learning from small-scale labeled data.
ClipKIT: A multiple sequence alignment trimming software for accurate phylogenomic inference

Highly divergent sites in multiple sequence alignments (MSAs), which can stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Thus, several different trimming strategies have been developed for identifying and removing these sites prior to phylogenetic inference. However, a recent study reported that doing so can worsen inference, underscoring the need for alternative alignment trimming strategies. Here, we introduce ClipKIT, an alignment trimming software that, rather than identifying and removing putatively phylogenetically uninformative sites, instead aims to identify and retain parsimony-informative sites, which are known to be phylogenetically informative. To test the efficacy of ClipKIT, we examined the accuracy and support of phylogenies inferred from 14 different alignment trimming strategies, including those implemented in ClipKIT, across nearly 140,000 alignments from a broad sampling of evolutionary histories. Phylogenies inferred from ClipKIT-trimmed alignments are accurate, robust, and time saving. Furthermore, ClipKIT consistently outperformed other trimming methods across diverse datasets, suggesting that strategies based on identifying and retaining parsimony-informative sites provide a robust framework for alignment trimming.
Revisiting the evolutionary history of domestic and wild ducks based on genomic analyses

Although domestic ducks have been important poultry species throughout human history, their origin remains enigmatic, with mallards and/or Chinese spot-billed ducks being proposed as the direct wild ancestor(s) of domestic ducks. Here, we analyzed 118 whole genomes from mallard, Chinese spot-billed, and domestic ducks to reconstruct their evolutionary history. We found pervasive introgression patterns among these duck populations. Furthermore, we showed that domestic ducks separated from mallard and Chinese spot-billed ducks nearly 38 thousand years ago (kya) and 54 kya, respectively, which is considerably outside the time period of presumed duck domestication. Thus, our results suggest that domestic ducks may have originated from another wild duck population that is currently undefined or unsampled, rather than from present-day mallard and/or Chinese spot-billed ducks, as previously thought. Overall, this study provides new insight into the complex evolution of ducks.
An Overview of Current Knowledge on the Properties, Synthesis and Applications of Quaternary Chitosan Derivatives

Chitosan, a chitin-derivative polysaccharide, known for its non-toxicity, biocompatibility and biodegradability, presents limited applications due to its low solubility in neutral or basic pH medium. Quaternization stands out as an alternative to modify this natural polymer, aiming to improve its solubility over a wide pH range and, consequently, expand its range of applications. Quaternization occurs by introducing a quaternary ammonium moiety onto or outside the chitosan backbone, via chemical reactions with primary amino and hydroxyl groups, under vast experimental conditions. The oldest and most common forms of quaternized chitosan involve N,N,N-trimethyl chitosan (TMC) and N-[(2-hydroxy-3-trimethyl ammonium) propyl] chitosan (HTCC) and, more recently, quaternized chitosan by insertion of pyridinium or phosphonium salts. By modifying chitosan through the insertion of a quaternary moiety, permanent cationic charges on the polysaccharide backbone are achieved and properties such as water solubility, antimicrobial activity, mucoadhesiveness and permeability are significantly improved, enabling the application mainly in the biomedical and pharmaceutical areas. In this review, the main quaternized chitosan compounds are addressed in terms of their structure, properties, synthesis routes and applications. In addition, other less explored compounds are also presented, involving the main findings and future prospects regarding the field of quaternized chitosans.
Liked for their looks: evaluative conditioning and the generalisation of conditioned attitudes in early childhood

ABSTRACT Recent studies explored whether attitude formation in early childhood can be explained in terms of evaluative conditioning (EC), the change in liking that is due to the pairing of stimuli. This study sought to replicate and extend this line of research by investigating whether and under what conditions preschool children generalise EC effects from conditioned to novel stimuli. Specifically, two experiments were conducted in which 3- to 6-year-old children (N = 139) observed the pairing of two cartoon characters with two positive and negative images. Afterwards, children evaluated the paired characters as well as other novel characters, which were not previously presented, that varied systematically in their perceptual similarity to the conditioned stimuli (Experiments 1 & 2), or that could be grouped by a categorisation rule (Experiment 2). It was found that children generalised attitudes to perceptually similar stimuli, but not to stimuli related by a categorisation rule, despite evidence for rule-learning. Implications of these findings for attitude development are discussed.
Overcoming the gap between child and adult mental health services: The Reggio Emilia experience in an early intervention in psychosis program

Early intervention in psychosis (EIP) can reduce severity and persistence of illness. From September 2012, the Reggio Emilia Department of Mental Health developed the ‘Reggio Emilia At‐Risk Mental States’ (ReARMS) protocol as a specific EIP infrastructure in all its adult and child/adolescent mental health services. Aims of this study were (a) to describe the ReARMS macroscopic organization and (b) to analyse some specific process indicators (i.e., the amount of individuals referred to the ReARMS program, the number of subjects who met defined diagnostic criteria of early psychosis and accepted the intervention, and the 1‐year drop‐out rate) during the first 5 years of its clinical activity, in order to examine feasibility and quality of its procedures on the adolescent help‐seeking subgroup.
Dependence of TiO2 Nanoparticle Preparation Methods and Annealing Temperature on the Efficiency of Dye-Sensitized Solar Cells

Performances of dye-sensitized solar cells prepared from nanoporous TiO2 films with different TiO2 nanoparticle preparation methods and different annealing temperatures are studied with various film thicknesses. The results show that the solar cells prepared at higher annealing temperatures have higher energy conversion efficiencies. Regarding film thickness, thin film electrode solar cells annealed at low-temperature show comparable efficiencies with those of the cells annealed at high temperature. The difference of the efficiency between the cells with the film annealed at different temperatures increases with the film thickness. To explain the observations, the surface area of the films, the amount of the adsorbed dye, and the diffusion coefficient and lifetime of electrons are measured. The amount of adsorbed dye per unit area is found to be independent of annealing temperature, while the diffusion coefficient and lifetime increase with the temperature. With trapping models, the measured increases of .
Drosophila MICOS knockdown impairs mitochondrial structure and function and promotes mitophagy in muscle tissue

ABSTRACT The mitochondrial contact site and cristae organizing system (MICOS) is a multi-protein interaction hub that helps define mitochondrial ultrastructure. While the functional importance of MICOS is mostly characterized in yeast and mammalian cells in culture, the contributions of MICOS to tissue homeostasis in vivo remain further elucidation. In this study, we examined how knocking down expression of Drosophila MICOS genes affects mitochondrial function and muscle tissue homeostasis. We found that CG5903/MIC26-MIC27 colocalizes and functions with Mitofilin/MIC60 and QIL1/MIC13 as a Drosophila MICOS component; knocking down expression of any of these three genes predictably altered mitochondrial morphology, causing loss of cristae junctions, and disruption of cristae packing. Furthermore, the knockdown flies exhibited low mitochondrial membrane potential, fusion/fission imbalances, increased mitophagy, and limited cell death. Reductions in climbing ability indicated deficits in muscle function. Knocking down MICOS genes also caused reduced mtDNA content and fragmented mitochondrial nucleoid structure in Drosophila. Together, our data demonstrate an essential role of Drosophila MICOS in maintaining proper homeostasis of mitochondrial structure and function to promote the function of muscle tissue. Summary: Drosophila MICOS knockdown impairs mitochondrial structure and function and promotes mitophagy in muscle tissue.