Miracle-dz/UniFAR-FTUs huggingface dataset:
The Oral Microbiome in Periodontal Health

The estimation of oral microbiome (OM) taxonomic composition in periodontally healthy individuals can often be biased because the clinically periodontally healthy subjects for evaluation can already experience dysbiosis. Usually, they are included just based on the absence of clinical signs of periodontitis. Additionally, the age of subjects is used to be higher to correspond well with tested groups of patients with chronic periodontitis, a disorder typically associated with aging. However, the dysbiosis of the OM precedes the clinical signs of the disease by many months or even years. The absence of periodontal pockets thus does not necessarily mean also good periodontal health and the obtained image of “healthy OM” can be distorted.To overcome this bias, we taxonomically characterized the OM in almost a hundred young students of dentistry with precise oral hygiene and no signs of periodontal disease. We compared the results with the OM composition of older periodontally healthy individuals and also a group of patients with severe periodontitis (aggressive periodontitis according to former classification system). The clustering analysis revealed not only two compact clearly separated clusters corresponding to each state of health, but also a group of samples forming an overlap between both well-pronounced states. Additionally, in the cluster of periodontally healthy samples, few outliers with atypical OM and two major stomatotypes could be distinguished, differing in the prevalence and relative abundance of two main bacterial genera: Streptococcus and Veillonella. We hypothesize that the two stomatotypes could represent the microbial succession from periodontal health to starting dysbiosis. The old and young periodontally healthy subjects do not cluster separately but a trend of the OM in older subjects to periodontitis is visible. Several bacterial genera were identified to be typically more abundant in older periodontally healthy subjects.
A Perspective on Mature Gratitude as a Way of Coping With COVID-19

Aim and Methods This perspective presents evidence of mature gratitude as a way of coping with the threats and boundaries of coronavirus disease 2019 (COVID-19). This narrative, non-systematic review will be based on studies from the COVID-19 period in association with more general literature on the characteristics of mature gratitude related to good mental health. Results The results from the literature suggest that a confrontation with our existential vulnerability during a pandemic is not only a crisis but also an opportunity to view our lives in a different way. Mature gratitude, as proposed in this perspective, can help us in coping with the threats and boundaries that are part of our lives due to the COVID-19 pandemic. This time of crisis gives us the opportunity to self-reflect on our current life and plans for the future and to reframe them through a positive lens which can encourage individuals to actively strengthen their psychological resilience and coping skills. Conclusion Cultivating an attitude of mature gratitude through actions of kindness, expressing being thankful for life and God, and enjoying all the small things in life helps in coping with the current threats of COVID-19 and building lifelong resilience for the future. Knowledge about these associations can help psychologists, counselors, and coaches to support people who experience psychological issues due to the current pandemic and all crises to come.
Attitudes and Practices of Immune Checkpoint Inhibitors in Chinese Patients With Cancer: A National Cross-Sectional Survey

Immune-checkpoint inhibitors (ICIs) are revolutionizing the field of immuno-oncology. Side effects and tumor microenvironment currently represent the most significant obstacles to using ICIs. In this study, we conducted an extensive cross-sectional survey to investigate the concept and practices regarding the use of ICIs in cancer patients in China. The results provide real-world data on the adverse events (AEs) of ICIs and the factors influencing the use of ICIs. This survey was developed by the Expert Committee on Immuno-Oncology of the Chinese Society of Clinical Oncology (CSCO-IO) and the Expert Committee on Patient Education of the Chinese Society of Clinical Oncology (CSCO-PE). The surveys were distributed using a web-based platform between November 29, 2019 and December 21, 2019. A total of 1,575 patients were included. High costs (43.9%), uncertainty about drug efficacy (41.2%), and no reimbursement from medical insurance (32.4%) were the factors that prevented the patients from using ICIs. The patients were most concerned about the onset time or effective duration of ICIs (40.3%), followed by the indications of ICIs and pre-use evaluation (33.4%). Moreover, 9.0, 57.1, 21.0, and 12.9% of the patients reported tumor disappearance, tumor volume reduction, no change in tumor volume, and increased tumor volume. Among the patients who received ICIs, 65.7% reported immune-related AEs (irAEs); 96.1% reported mild-to-moderate irAEs. Cancer patients in China had a preliminary understanding of ICIs. Yet, the number of patients treated with ICIs was small.
Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.
Neural Differentiation of Mouse Embryonic Stem Cells—An in vitro Approach to Profile DNA Methylation of Reprogramming Factor Sox2-SRR2

Sox2 is one of the core transcription factors maintaining the embryonic stem cells (ES) pluripotency and, also indispensable for cellular reprogramming. However, limited data is available about the DNA methylation of pluripotency genes during lineage-specific differentiations. This study investigated the DNA methylation of Sox2 regulatory region 2 (SRR2) during directed differentiation of mouse ES into neural lineage. ES cells were first grown to form embryoid bodies in suspension which were then dissociated, and cultured in defined medium to promote neural differentiation. Typical neuronal morphology together with the up-regulation of Pax6, neuroepithelial stem cell intermediate filament and β-tubulin III and, down-regulation of pluripotency genes Oct4, Nanog and Sox2 showed the existence of neural phenotype in cells undergoing differentiation. Three CpGs in the core enhancer region of neural-specific SRR2 were individually investigated by direct DNA sequencing post-bisulfite treatment and, found to be unmethylated in differentiated cells at time-points chosen for analysis. This analysis does not limit the possibility of methylation at other CpG sites than those profiled here and/or transient methylation. Hence, similar analyses exploring the DNA methylation at other regions of the Sox2 gene could unravel the onset and transitions of epigenetic signatures influencing the outcome of differentiation pathways and neural development. The data presented here shows that in vitro neural differentiation of embryonic stem cells can be employed to study and characterize molecular regulatory mechanisms governing neurogenesis by applying diverse pharmacological and toxicological agents.
Orexin/Hypocretin and MCH Neurons: Cognitive and Motor Roles Beyond Arousal

The lateral hypothalamus (LH) is classically implicated in sleep-wake control. It is the main source of orexin/hypocretin and melanin-concentrating hormone (MCH) neuropeptides in the brain, which have been both implicated in arousal state switching. These neuropeptides are produced by non-overlapping LH neurons, which both project widely throughout the brain, where release of orexin and MCH activates specific postsynaptic G-protein-coupled receptors. Optogenetic manipulations of orexin and MCH neurons during sleep indicate that they promote awakening and REM sleep, respectively. However, recordings from orexin and MCH neurons in awake, moving animals suggest that they also act outside sleep/wake switching. Here, we review recent studies showing that both orexin and MCH neurons can rapidly (sub-second-timescale) change their firing when awake animals experience external stimuli, or during self-paced exploration of objects and places. However, the sensory-behavioral correlates of orexin and MCH neural activation can be quite different. Orexin neurons are generally more dynamic, with about 2/3rds of them activated before and during self-initiated running, and most activated by sensory stimulation across sensory modalities. MCH neurons are activated in a more select manner, for example upon self-paced investigation of novel objects and by certain other novel stimuli. We discuss optogenetic and chemogenetic manipulations of orexin and MCH neurons, which combined with pharmacological blockade of orexin and MCH receptors, imply that these rapid LH dynamics shape fundamental cognitive and motor processes due to orexin and MCH neuropeptide actions in the awake brain. Finally, we contemplate whether the awake control of psychomotor brain functions by orexin and MCH are distinct from their “arousal” effects.
Knowing Is Not Enough: A Mixed-Methods Study of Antimicrobial Resistance Knowledge, Attitudes, and Practises Among Maasai Pastoralists

Global, national, and local efforts to limit antimicrobial resistance (AMR) often stress the importance of raising awareness among users, sellers, and prescribers of antimicrobial drugs. This emphasis is founded upon two assumptions. First, awareness is limited, particularly concerning the links between antimicrobial use (AMU) and AMR. Second, “filling the awareness gaps” will motivate practises that will limit AMR. The first assumption is supported by knowledge, attitudes, and practises (KAP) surveys but these same studies provide mixed support for the second, with several studies finding that knowledge and attitudes are not correlated with related practises. This disconnect may arise as these surveys typically do not collect data on the cultural or historical contexts that pattern AMU. To explore how these contexts impact KAP related to AMU and AMR, we use a mixed-methods approach to examine veterinary practises among Maasai pastoralists in Tanzania. We combine a quantitative KAP survey (N = 195 households) with extensive qualitative data from focus group discussions (N = 55 participants). Results document limited awareness of AMR but also find that knowledge and attitudes are not correlated with practise. Thematic analysis of qualitative data pointed to three reasons behind this disconnect, including (1) Maasai self-perceptions as veterinary experts, (2) the central role of livestock in Maasai culture, and (3) the use of ethnoveterinary knowledge in animal health treatment. We argue that mixed-method approaches will be critical to developing the targeted awareness campaigns needed to limit the emergence and transmission of AMR.
A Rapid and Efficient Screening System for Neutralizing Antibodies and Its Application for SARS-CoV-2

After the pandemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 have been developed for the prophylactic and therapeutic purposes. However, few methodologies are described in detail on how to rapidly and efficiently generate effective NAbs to SARS-CoV-2. Here, we integrated and optimized a strategically screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific NAbs within 6 days, followed by additional 9 days for antibody production and function analysis. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited advanced neutralizing potency and high affinity, with the top two NAbs showing half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides an effective methodology with high applicable value for discovering potential preventative and therapeutic NAbs for the emerging infectious diseases.
Isothermal and Scanning Calorimetry Measurements on ‚-Lactoglobulin

The denaturation and aggregation of β-lactoglobulin was studied by isothermal calorimetry. Experiments with several β-lactoglobulin concentrations (15−100 g/L) were performed at temperatures in the range 62−68.5 °C. Even a small change in temperature had a tremendous effect on the shape of the thermograms, depending also very strongly on the β-lactoglobulin concentration used. The measured thermograms were modeled using the kinetic model for the denaturation and aggregation of β-lactoglobulin recently developed by Roefs and De Kruif. In this kinetic model we recognize four consecutive steps: dissociation, unfolding, exchange of disulfide bonds, and aggregation. The numerical calculations yielded results that were in qualitative and quantitative agreement with typical experimental isothermal calorimetry curves. DSC curves and the decrease in concentration of native β-lactoglobulin as a function of time could also be reproduced well. We think that isothermal calorimetry, in combination with this kinetic mo.
Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage

Collagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.
Treatment Outcomes of 9,994 Patients With Extensive-Disease Small-Cell Lung Cancer From a Retrospective Nationwide Population-Based Cohort in the Korean HIRA Database

To investigate the efficacy of irinotecan-based (IP) and etoposide-based (EP) platinum combinations, and of single-agent chemotherapy, for treatment of extensive-disease small cell lung cancer (ED-SCLC), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2008, to November 30, 2016. A total of 9,994 patients were allocated to ED-SCLC and analyzed in this study. The primary objectives were to evaluate the survival outcomes of systemic first-line treatments for ED-SCLC. For first-line treatment, patients who received IP showed a better time to first subsequent therapy (TFST) of 8.9 months (95% confidence interval [CI], 8.50–9.40) than those who received EP, who had a TFST of 6.8 months (95% CI, 6.77–6.97, P < 0.0001). In terms of overall survival (OS), IP was superior to EP (median OS, 10.8 months; 95% CI, 10.13–11.33 vs. 9.5 months; 95% CI, 9.33–9.73; P < 0.0001). Taken together, in the Korean population, first-line IP combination chemotherapy had significantly favorable effects on OS and TFST.
A Systematic Review on the Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Memory and Extinction

Anxiety disorders are among the most prevalent mental disorders. Present treatments such as cognitive behavior therapy and pharmacological treatments show only moderate success, which emphasizes the importance for the development of new treatment protocols. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been probed as therapeutic option for anxiety disorders in recent years. Mechanistic information about their mode of action, and most efficient protocols is however limited. Here the fear extinction model can serve as a model of exposure therapies for studying therapeutic mechanisms, and development of appropriate intervention protocols. We systematically reviewed 30 research articles that investigated the impact of rTMS and tDCS on fear memory and extinction in animal models and humans, in clinical and healthy populations. The results of these studies suggest that tDCS and rTMS can be efficient methods to modulate fear memory and extinction. Furthermore, excitability-enhancing stimulation applied over the vmPFC showed the strongest potential to enhance fear extinction. We further discuss factors that determine the efficacy of rTMS and tDCS in the context of the fear extinction model and provide future directions to optimize parameters and protocols of stimulation for research and treatment.
Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate and adaptive immunity. Cytotoxic function of NK cells is compromised in patients with SLE. Herein, we characterized the phenotypic alterations of SLE NK cells in a comprehensive manner to further delineate the mechanisms underlying the cytotoxic dysfunction of SLE NK cells and identify novel potential therapeutic targets. Therefore, we examined PBMC from SLE patients and matched healthy controls by single-cell mass cytometry to assess the phenotype of NK cells. In addition, we evaluated the cell function of NK cells (degranulation and cytokine production) and the killing of B cell subpopulations in a B cell-NK cell in vitro co-culture model. We found that SLE NK cells expressed higher levels of CD38 and were not able to adequately upregulate SLAMF1 and SLAMF7 following activation. In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system. Overall, our data indicated that dysregulated expression of CD38, SLAMF1 and SLAMF7 on SLE NK cells is associated with an altered interplay between SLE NK cells and plasma cells, thus suggesting their contribution to the accumulation of (auto)antibody producing cells. Accordingly, targeting SLAMF7 and CD38 may represent novel therapeutic approaches in SLE by enhancing NK cell function and promoting elimination of circulating plasma cell.
De novo Prediction of Moonlighting Proteins Using Multimodal Deep Ensemble Learning

Moonlighting proteins (MPs) are a special type of protein with multiple independent functions. MPs play vital roles in cellular regulation, diseases, and biological pathways. At present, very few MPs have been discovered by biological experiments. Due to the lack of data sample, computation-based methods to identify MPs are limited. Currently, there is no de-novo prediction method for MPs. Therefore, systematic research and identification of MPs are urgently required. In this paper, we propose a multimodal deep ensemble learning architecture, named MEL-MP, which is the first de novo computation model for predicting MPs. First, we extract four sequence-based features: primary protein sequence information, evolutionary information, physical and chemical properties, and secondary protein structure information. Second, we select specific classifiers for each kind of feature. Finally, we apply the stacked ensemble to integrate the output of each classifier. Through comprehensive model selection and cross-validation experiments, it is shown that specific classifiers for specific feature types can achieve superior performance. For validating the effectiveness of the fusion-based stacked ensemble, different feature fusion strategies including direct combination and a multimodal deep auto-encoder are used for comparative purposes. MEL-MP is shown to exhibit superior prediction performance (F-score = 0.891), surpassing the existing machine learning model, MPFit (F-score = 0.784). In addition, MEL-MP is leveraged to predict the potential MPs among all human proteins. Furthermore, the distribution of predicted MPs on different chromosomes, the evolution of MPs, the association of MPs with diseases, and the functional enrichment of MPs are also explored. Finally, for maximum convenience, a user-friendly web server is available at: http://ml.csbg-jlu.site/mel-mp/.
The Relationship Between Breast Milk Components and the Infant Gut Microbiota

The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a “window of opportunity” to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.