Miracle-dz/UniFAR-FTUs huggingface dataset:
Ngn3-Positive Cells Arise from Pancreatic Duct Cells

The production of pancreatic β cells is the most challenging step for curing diabetes using next-generation treatments. Adult pancreatic endocrine cells are thought to be maintained by the self-duplication of differentiated cells, and pancreatic endocrine neogenesis can only be observed when the tissue is severely damaged. Experimentally, this can be performed using a method named partial duct ligation (PDL). As the success rate of PDL surgery is low because of difficulties in identifying the pancreatic duct, we previously proposed a method for fluorescently labeling the duct in live animals. Using this method, we performed PDL on neurogenin3 (Ngn3)-GFP transgenic mice to determine the origin of endocrine precursor cells and evaluate their potential to differentiate into multiple cell types. Ngn3-activated cells, which were marked with GFP, appeared after PDL operation. Because some GFP-positive cells were aligned proximally to the duct, we hypothesized that Ngn3-positive cells arise from the pancreatic duct. Therefore, we next developed an in vitro pancreatic duct culture system using Ngn3-GFP mice and examined whether Ngn3-positive cells emerge from this duct. We observed GFP expressions in ductal organoid cultures. GFP expressions were correlated with Ngn3 expressions and endocrine cell lineage markers. Interestingly, tuft cell markers were also correlated with GFP expressions. Our results demonstrate that in adult mice, Ngn3-positive endocrine precursor cells arise from the pancreatic ducts both in vivo and in vitro experiments indicating that the pancreatic duct could be a potential donor for therapeutic use.
Slow Life History Strategies and Increases in Externalizing and Internalizing Problems During the COVID‐19 Pandemic

The COVID‐19 pandemic is but one of many instances of environmental adversities that have recurred in human history. Biobehavioral resource allocation strategies, known as fast (reproduction‐focused) versus slow (development‐focused) life history (LH) tradeoff strategies, evolved to deal with environmental challenges such as infectious diseases. Based on 141 young people and their mothers observed prior to (ages 9 and 13) and during (age 20) COVID‐19, we investigated longitudinal relations involving slow LH strategies. The results support the adaptive role of slow LH strategies in reducing COVID‐related increases in externalizing problems. In addition, the effect of early adversity on COVID‐related increases in externalizing was mediated, and the effect on COVID‐related increases in internalizing was moderated, by slow LH strategies.
Burnout of Physicians, Pharmacists and Nurses in the Course of the COVID-19 Pandemic: A Serbian Cross-Sectional Questionnaire Study

This research was a prospective, cross-sectional observational study of 128 health workers in the central part of the Republic of Serbia. The study surveyed health workers (physicians, pharmacists and nurses) who worked during peaks of the COVID-19 pandemic in the Republic of Serbia in June and November 2020. The Maslach Burnout Survey for Medical Personnel addresses three scales: (a) emotional exhaustion (EE) measures feelings of being emotionally overextended and exhausted by one’s work; (b) depersonalization (DP) measures an unfeeling and impersonal response toward recipients of one’s service, care treatment, or instruction; and (c) personal accomplishment (PA) measures feelings of competence and successful achievement in one’s work. Linear regression and the chi-square test were used to test a relationship between the input variables (x) and the single output variable (y). We can conclude that most health workers had a high degree of emotional exhaustion, but also a low degree of depersonalization and a high degree of sense of personal achievement. Nurses and physicians had similar answers on the pandemic during their work, but pharmacists had different answers.
MD simulation and MM/PBSA identifies phytochemicals as bifunctional inhibitors of SARS-CoV-2

Abstract The global spread of SARS-CoV-2 has resulted in millions of fatalities worldwide, making it crucial to identify potent antiviral therapeutics to combat this virus. We employed structure-assisted virtual screening to identify phytochemicals that can target the two proteases which are essential for SARS-CoV-2 replication and transcription, the main protease and papain-like protease. Using virtual screening and molecular dynamics, we discovered new phytochemicals with inhibitory activity against the two proteases. Isoginkgetin, kaempferol-3-robinobioside, methyl amentoflavone, bianthraquinone, podocarpusflavone A, and albanin F were shown to have the best affinity and inhibitory potential among the compounds, and can be explored clinically for use as inhibitors of novel coronavirus SARS-CoV-2. Communicated by Ramaswamy H. Sarma
Metal-Based Nanomaterials: Work as Drugs and Carriers against Viral Infections

Virus infection is one of the threats to the health of organisms, and finding suitable antiviral agents is one of the main tasks of current researchers. Metal ions participate in multiple key reaction stages of organisms and maintain the important homeostasis of organisms. The application of synthetic metal-based nanomaterials as an antiviral therapy is a promising new research direction. Based on the application of synthetic metal-based nanomaterials in antiviral therapy, we summarize the research progress of metal-based nanomaterials in recent years. This review analyzes the three inhibition pathways of metal nanomaterials as antiviral therapeutic materials against viral infections, including direct inactivation, inhibition of virus adsorption and entry, and intracellular virus suppression; it further classifies and summarizes them according to their inhibition mechanisms. In addition, the use of metal nanomaterials as antiviral drug carriers and vaccine adjuvants is summarized. The analysis clarifies the antiviral mechanism of metal nanomaterials and broadens the application in the field of antiviral therapy.
Assessment of Dysphonia in Children with Pompe Disease Using Auditory-Perceptual and Acoustic/Physiologic Methods

Bulbar and respiratory weakness occur commonly in children with Pompe disease and frequently lead to dysarthria. However, changes in vocal quality associated with this motor speech disorder are poorly described. The goal of this study was to characterize the vocal function of children with Pompe disease using auditory-perceptual and physiologic/acoustic methods. High-quality voice recordings were collected from 21 children with Pompe disease. The Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale was used to assess voice quality and ratings were compared to physiologic/acoustic measurements collected during sustained phonation tasks, reading of a standard passage, and repetition of a short phrase at maximal volume. Based on ratings of grade, dysphonia was present in 90% of participants and was most commonly rated as mild or moderate in severity. Duration of sustained phonation tasks was reduced and shimmer was increased in comparison to published reference values for children without dysphonia. Specific measures of loudness were found to have statistically significant relationships with perceptual ratings of grade, breathiness, asthenia, and strain. Our data suggest that dysphonia is common in children with Pompe disease and primarily reflects impairments in respiratory and laryngeal function; however, the primary cause of dysphonia remains unclear. Future studies should seek to quantify the relative contribution of deficits in individual speech subsystems on voice quality and motor speech performance more broadly.
How Do French Parents Determine Portion Sizes for Their Pre-Schooler? A Qualitative Exploration of the Parent–Child Division of Responsibility and Influencing Factors

Large portion sizes can make children overeat, alter their self-regulation abilities and induce weight gain. However, little is known about how parents determine portion sizes for their children. Using semi-structured interviews with 5 fathers and 32 mothers of pre-schoolers, this study examined French parents’ food portioning practices. The division of responsibility between parent and child in deciding portion sizes was explored, as well as the influencing factors and possible sources of information. Parents described a wide range of practices. For most, determining portion sizes is an intuitive action that depends on habits and mainly arises from experiences with feeding their child and his/her appetitive traits. Few parents grant autonomy to their child for portioning and serving food, especially for the first serving. Many influencing factors were identified, including child-related (e.g., appetite, food preferences), parent-related (e.g., avoiding food waste), and external factors (e.g., influence of siblings, French food culture). Most parents do not search for information/recommendations to guide their practices. Stimulating optimal self-regulation of eating in children is important and parents can play a crucial role in this. This study identified barriers and facilitators to guide parents in providing appropriate portion sizes and help include children in this decision process.
Prediction Model for Tumor Budding Status Using the Radiomic Features of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Cervical Cancer

Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of 18F-FDG PET/CT in patients with cervical cancer. Materials and Methods: Seventy-six patients with cervical cancer who underwent radical hysterectomy and preoperative 18F-FDG PET/CT were included. We assessed the status of intratumoral budding (ITP) and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Three conventional metabolic parameters and fifty-nine features were extracted and analyzed. Univariate analysis was used to identify significant metabolic parameters and radiomic findings for TB status. The prediction model for TB status was built using 3 machine learning classifiers (random forest, support vector machine, and neural network). Results: Univariate analysis led to the identification of 2 significant metabolic parameters and 12 significant radiomic features according to intratumoral budding (ITB) status. Among these parameters, following multivariate analysis for the ITB status, only compacity remained significant (odds ratio, 5.0047; 95% confidence interval, 1.1636–21.5253; p = 0.0305). Two conventional metabolic parameters and 25 radiomic features were selected by the Lasso regularization, and the prediction model for the ITB status had a mean area under the curve of 0.762 in the test dataset. Conclusion: Radiomic features of 18F-FDG PET/CT were associated with the ITB status. The prediction model using radiomic features successfully predicted the TB status in patients with cervical cancer. The prediction models for the ITB status may contribute to personalized medicine in the management of patients with cervical cancer.
Genome-Wide Expression Patterns of Rhoptry Kinases during the Eimeria tenella Life-Cycle

Kinome from apicomplexan parasites is composed of eukaryotic protein kinases and Apicomplexa specific kinases, such as rhoptry kinases (ROPK). Ropk is a gene family that is known to play important roles in host–pathogen interaction in Toxoplasma gondii but is still poorly described in Eimeria tenella, the parasite responsible for avian coccidiosis worldwide. In the E. tenella genome, 28 ropk genes are predicted and could be classified as active (n = 7), inactive (incomplete catalytic triad, n = 12), and non-canonical kinases (active kinase with a modified catalytic triad, n = 9). We characterized the ropk gene expression patterns by real-time quantitative RT-PCR, normalized by parasite housekeeping genes, during the E. tenella life-cycle. Analyzed stages were: non-sporulated oocysts, sporulated oocysts, extracellular and intracellular sporozoites, immature and mature schizonts I, first- and second-generation merozoites, and gametes. Transcription of all those predicted ropk was confirmed. The mean intensity of transcription was higher in extracellular stages and 7–9 ropk were specifically transcribed in merozoites in comparison with sporozoites. Transcriptional profiles of intracellular stages were closely related to each other, suggesting a probable common role of ROPKs in hijacking signaling pathways and immune responses in infected cells. These results provide a solid basis for future functional analysis of ROPK from E. tenella.
Possible Protective Effect of LOXL1 Variant in the Cohort of Chernobyl Catastrophe Clean-Up Workers

Ionising radiation (IR) is an environmental factor known to alter genomes and therefore challenge organisms to adapt. Lithuanian clean-up workers of the Chernobyl nuclear disaster (LCWC) experienced high doses of IR, leading to different consequences. This study aims to characterise a unique protective genomic variation in a relatively healthy LCWC group. This variation influenced their individual reaction to IR and potentially protects against certain diseases such as exfoliation syndrome and glaucoma. Clinical and IR dosage data were collected using a questionnaire to characterise the cohort of 93 LCWC. Genome-wide genotyping using Illumina beadchip technology was performed. The control group included 466 unrelated, self-reported healthy individuals of Lithuanian descent. Genotypes were filtered out from the microarray dataset using a catalogue of SNPs. The data were used to perform association, linkage disequilibrium, and epistasis analysis. Phenotype data analysis showed the distribution of the most common disease groups among the LCWC. A genomic variant of statistical significance (Fishers’ exact test, p = 0.019), rs3825942, was identified in LOXL1 (NM_005576.4:c.458G>A). Linkage disequilibrium and epistasis analysis for this variant identified the genes LHFPL3, GALNT6, PIH1D1, ANKS1B, and METRNL as potentially involved in the etiopathogenesis of exfoliation syndrome and glaucoma, which were not previously associated with the disease. The LOXL1 variant is mostly considered a risk factor in the development of exfoliation syndrome and glaucoma. The influence of recent positive selection, the phenomenon of allele-flipping, and the fact that only individuals with the homozygous reference allele have glaucoma in the cohort of the LCWC suggest otherwise. The identification of rs3825942 and other potentially protective genomic variants may be useful for further analysis of the genetic architecture and etiopathogenetic mechanisms of other multifactorial diseases.
Effects of a Sodium Phosphate Electrolyte Additive on Elevated Temperature Performance of Spinel Lithium Manganese Oxide Cathodes

LiMn2O4 (LMO) spinel cathode materials suffer from severe degradation at elevated temperatures because of Mn dissolution. In this research, monobasic sodium phosphate (NaH2PO4, P2) is examined as an electrolyte additive to mitigate Mn dissolution; thus, the thermal stability of the LMO cathode material is improved. The P2 additive considerably improves the cyclability and storage performances of LMO/graphite and LMO/LMO symmetric cells at 60 °C. We explain that P2 suppresses the hydrofluoric acid content in the electrolyte and forms a protective cathode electrolyte interphase layer, which mitigates the Mn dissolution behavior of the LMO cathode material. Considering its beneficial role, the P2 additive is a useful additive for spinel LMO cathodes that suffer from severe Mn dissolution.
Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 μM) than hACE2 receptor (1.12 μM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin’s interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2’s entry into human cells.
Roles of Clara cell 10-kD protein and type 2 innate lymphoid cells in allergic rhinitis

ABSTRACT This study examined the potential roles of CC10 (Clara cell 10-kD protein) and ILC2s (type 2 innate lymphoid cells) in allergic rhinitis (AR). After ovalbumin was used to construct the AR model, microarray analysis was performed to reveal the key differentially expressed genes. The phenotypic changes of nasal mucosa were examined by H&E staining. Western blot analysis, qRT-PCR, ELISA and immunohistochemistry were performed to identify the levels of cytokines. The lineage markers (CD127 and CD117) of ILC2s were detected using immunofluorescence. The microarray analysis and qRT-PCR results showed that CC10 overexpression inhibited the expression of A20, BAFF, and IL-4 R in vivo. Also, CC10 overexpression was found to ameliorate the damage of nasal mucosa in AR mice. Investigations revealed that the ILC2s were activated in AR mice and AR patients with high levels of IgE, IgG1, IL-4, IL-5, IL-13, IL-25, and IL-33. Moreover, CD127+ was found to activate ILC2s. However, CC10 overexpression suppressed the activation of ILC2s. In conclusion, this research suggested that CC10 could suppress the activation of ILC2s to attenuate the damage of nasal mucosa and that CD127+ may be a biomarker of the activation of ILC2s in AR mice and AR patients.
Peptide Sequence Mapping around Bisecting GlcNAc-Bearing N-Glycans in Mouse Brain

N-glycosylation is essential for many biological processes in mammals. A variety of N-glycan structures exist, of which, the formation of bisecting N-acetylglucosamine (GlcNAc) is catalyzed by N-acetylglucosaminyltransferase-III (GnT-III, encoded by the Mgat3 gene). We previously identified various bisecting GlcNAc-modified proteins involved in Alzheimer’s disease and cancer. However, the mechanisms by which GnT-III acts on the target proteins are unknown. Here, we performed comparative glycoproteomic analyses using brain membranes of wild type (WT) and Mgat3-deficient mice. Target glycoproteins of GnT-III were enriched with E4-phytohemagglutinin (PHA) lectin, which recognizes bisecting GlcNAc, and analyzed by liquid chromatograph-mass spectrometry. We identified 32 N-glycosylation sites (Asn-Xaa-Ser/Thr, Xaa ≠ Pro) that were modified with bisecting GlcNAc. Sequence alignment of identified N-glycosylation sites that displayed bisecting GlcNAc suggested that GnT-III does not recognize a specific primary amino acid sequence. The molecular modeling of GluA1 as one of the good cell surface substrates for GnT-III in the brain, indicated that GnT-III acts on N-glycosylation sites located in a highly flexible and mobile loop of GluA1. These results suggest that the action of GnT-III is partially affected by the tertiary structure of target proteins, which can accommodate bisecting GlcNAc that generates a bulky flipped-back conformation of the modified glycans.
Trail Conditions and Community Use: Utilizing Geospatial Video to Guide the Adoption of a Spatial-Temporal Trail Audit Tool (STAT)

Physical activity (PA), associated with all-cause mortality, morbidity, and healthcare costs, improves vitamin D absorption, immune response, and stress when completed outdoors. Rural communities, which experience PA inequities, rely on trails to meet PA guidelines. However, current trail audit methods could be more efficient and accurate, which geospatial video may support. Therefore, the study purpose was (1) to identify and adopt validated instruments for trail audit evaluations using geospatial video and a composite score and (2) to determine if geospatial video and a composite score motivate (influence the decision to use) specific trail selection among current trail users. Phase 1 used a mixed-method exploratory sequential core design using qualitative data, then quantitative data for the development of the Spatial-temporal Trail Audit Tool (STAT). Geospatial videos of two Northeast Ohio trails were collected using a bicycle-mounted spatial video camera and video analysis software. The creation of STAT was integrated from Neighborhood Environment Walkability Scale (NEWS), Walk Score, and Path Environment Audit Tool (PEAT) audit tools based on four constructs: trail accessibility, conditions, amenities, and safety. Scoring was determined by three independent reviewers. Phase 2 included a mixed-method convergent core design to test the applicability of STAT for trail participant motivation. STAT has 20 items in 4 content areas computing a composite score and was found to increase trail quality and motivation for use. STAT can evaluate trails for PA using geospatial video and a composite score which may spur PA through increased motivation to select and use trails.
Strategic Analysis of Participants in the Provision of Elderly Care Services—An Evolutionary Game Perspective

Population aging poses challenges to the immature elderly care service system in many countries. The strategic behaviors of different participants in the provision of elderly care services in a long-term and dynamic situation have not been well studied. In this paper, an evolutionary game model is developed to analyze the strategic behaviors of two types of participants—the government sectors and the private sectors in provision of elderly care services. Firstly, eight scenarios are analyzed, and the evolutionary process and stable strategies are identified. Then, the behavioral strategies of the two types of participants under demand disturbance and dynamic subsidy strategy are analyzed. Simulation experiments are conducted to explore the influence of different initial conditions and parameter changes on the evolutionary process and results. The obtained observations are not only conducive to a systematic understanding of the long-term dynamic provision of elderly care services but also to the policymaking of the government.