Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric Obstructive Sleep Apnea: Knowledge and Attitudes of Medical and Dental Students and Fresh Graduates from Saudi Arabia

This study aimed to assess the knowledge level and attitudes of graduating Saudi medical and dental students and fresh graduates from those faculties about pediatric obstructive sleep apnea (OSA), and the relation of their knowledge level to sociodemographic variables. In this cross-sectional study, 722 graduating students and fresh graduates were requested to answer a questionnaire pretested for validity and reliability. The data were analyzed statistically. Results revealed that medical participants scored 15.45 (out of 22), with 38% of them showing good knowledge about pediatric OSA, while dental participants scored 14.59, with 25.2% of them showing good knowledge. By regression analysis, medical participants (odds ratio (OR): 1.529) were more likely to have good knowledge than dental participants, while participants who belonged to institutions located in the central region (OR: 0.546) were less likely to have good knowledge than those from southern region institutions. In addition, participants from public institutions (OR: 0.290) were less likely to have good knowledge than those from private institutions. Regarding attitudes, medical participants scored 14.13 (out of 20), and dental participants scored 14.64. We detected a significant positive correlation between knowledge and attitude scores of dental participants. Given these findings, the knowledge level of graduating Saudi medical and dental students and fresh graduates about pediatric OSA was not optimal. The college type, institution sector, and location in the kingdom were factors associated with good knowledge. There is a need for further education and training about pediatric OSA in the undergraduate Saudi medical and dental curricula and continuing professional development programs about the topic after graduation.
COVID-19 Subunit Vaccine with a Combination of TLR1/2 and TLR3 Agonists Induces Robust and Protective Immunity

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit vaccines to enhance the magnitude and durability of immune responses. In this study, we determined whether a combination of toll-like receptor (TLR)1/2 and TLR3 agonists (L-pampo) can be a potent adjuvant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. We measured a neutralizing antibody (nAb) and an angiotensin-converting enzyme 2 (ACE2) receptor-blocking antibody against SARS-CoV-2 receptor-binding domain (RBD). We also detected interferon-gamma (IFN-γ) production by using ELISPOT and ELISA assays. By employing a ferret model, we detected nAbs and IFN-γ producing cells and measured viral load in nasal wash after the challenge of SARS-CoV-2. We found that SARS-CoV-2 antigens with L-pampo stimulated robust humoral and cellular immune responses. The efficacy of L-pampo was higher than the other adjuvants. Furthermore, in the ferret model, SARS-CoV-2 antigens with L-pampo elicited nAb response and antigen-specific cellular immune response against SARS-CoV-2, resulting in substantially decreased viral load in their nasal wash. Our study suggests that SARS-CoV-2 antigens formulated with TLR agonists, L-pampo, can be a potent subunit vaccine to promote sufficient protective immunity against SARS-CoV-2.
TGF-β-Induced TMEPAI Promotes Epithelial–Mesenchymal Transition in Doxorubicin-Treated Triple-Negative Breast Cancer Cells via SMAD3 and PI3K/AKT Pathway Alteration

Introduction Epithelial–mesenchymal transition (EMT) and overexpression of drug efflux transporters have been reported to cause doxorubicin resistance. Our previous study indicated that TMEPAI (transmembrane prostate androgen-induced protein) attenuated doxorubicin sensitivity in triple-negative breast cancer cells. However, how TMEPAI contributes to doxorubicin resistance in TNBC remains unclear. Thus, the present study aimed to elucidate the mechanism of TMEPAI in doxorubicin resistance in triple-negative breast cancer cells. Methods We used BT549, triple-negative cells wild type (WT), and BT549 TMEPAI knock-out. Both cells were treated with TGF-β 2 ng/mL for 24 hours, followed by TGF-β 2 ng/mL and doxorubicin 12.9 nM for another 24 hours. Afterward, the cells were harvested and counted. Cells were further lysed and used for RT-PCR and Western blot analysis. We determined the expression levels of proliferation, apoptosis, EMT markers, and drug efflux transporters. Additionally, we investigated the expressions of PI3K as well as SMAD3 and AKT phosphorylation. Results TNBC cells were shown to be less sensitive to doxorubicin in the presence of TMEPAI. TMEPAI was shown to alleviate the mRNA expressions of apoptosis markers: Bax, Bcl2, Caspase-3, and Caspase-9. Our results indicated that the presence of TMEPAI greatly amplifies EMT and increases drug efflux transporter expressions after doxorubicin treatment. Furthermore, our findings demonstrated that TMEPAI reduced the action of doxorubicin in inhibiting SMAD3 phosphorylation. TMEPAI was also shown to modify the effect of doxorubicin by reducing PI3K expressions and Akt phosphorylation in triple-negative breast cancer cells. Conclusion Our findings indicate that TMEPAI promotes EMT and drug efflux transporters at least in part by shifting doxorubicin action from SMAD3 phosphorylation reduction to PI3K/AKT inhibition in triple-negative breast cancer cells.
Ferroptosis Meets Cell–Cell Contacts

Ferroptosis is a regulated form of cell death characterized by iron dependency and increased lipid peroxidation. Initially assumed to be selectively induced in tumour cells, there is increasing evidence that ferroptosis plays an important role in pathophysiology and numerous cell types and tissues. Deregulated ferroptosis has been linked to human diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Along these lines, ferroptosis is a promising pathway to overcoming therapy resistance of cancer cells. It is therefore of utmost importance to understand the cellular signalling pathways and the molecular mechanisms underlying ferroptosis regulation, including context-specific effects mediated by the neighbouring cells through cell–cell contacts. Here, we give an overview on the molecular events and machinery linked to ferroptosis induction and commitment. We further summarize and discuss current knowledge about the role of cell–cell contacts, which differ in ferroptosis regulation between normal somatic cells and cancer cells. We present emerging concepts on the underlying mechanisms, address open questions, and discuss the possible impact of cell–cell contacts on exploiting ferroptosis in cancer therapy.
Plant-Expressed Receptor Binding Domain of the SARS-CoV-2 Spike Protein Elicits Humoral Immunity in Mice

The current 15-month coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has accounted for 3.77 million deaths and enormous worldwide social and economic losses. A high volume of vaccine production is urgently required to eliminate COVID-19. Inexpensive and robust production platforms will improve the distribution of vaccines to resource-limited countries. Plant species offer such platforms, particularly through the production of recombinant proteins to serve as immunogens. To achieve this goal, here we expressed the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein in the glycoengineered-tobacco plant Nicotiana benthamiana to provide a candidate subunit vaccine. This recombinant RBD elicited humoral immunity in mice via induction of highly neutralizing antibodies. These findings provide a strong foundation to further advance the development of plant-expressed RBD antigens for use as an effective, safe, and inexpensive SARS-CoV-2 vaccine. Moreover, our study further highlights the utility of plant species for vaccine development.
How Do We Perceive a Humorous Manager? Manager Humor, Impression Management, and Employee Willingness to Work With the Manager

Humor is a form of communication that is intended to be entertaining and produce positive affective and cognitive responses from receivers. Nonetheless, humor in the workplace is a complicated matter. It has been recognized as a valuable tool for managers because it can activate various favorable outcomes and alter employees’ perception of the manager’s warmth and competence (impression management), but not always to the benefit of the manager. In our studies, the use of humor showed changed attitudes toward a manager’s warmth and competence, and eventually influenced the employee’s behavioral intentions. In Study 1, we tested the use of managerial humor in two emails. The humorous manager was perceived as warm, but not competent. Impression management mediated the employee’s willingness to work with the manager. In Study 2, we tested the use of managerial humor with one introductory email. In this study, we also monitored the gender of both the manager and the employee. Once again, the humorous manager was perceived as warm and humor mediated employees’ behavioral intentions. As for competence, gender moderated the results, such that male employees perceived humorous female managers as more competent, while female employees perceived humorous male managers as less competent. Practical implications are presented.
Disruption of the Interaction between ORF33 and the Conserved Carboxyl-Terminus of ORF45 Abolishes Progeny Virion Production of Kaposi Sarcoma-Associated Herpesvirus

The Open Reading Frame 45 (ORF45) of Kaposi sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus-specific, immediate-early, tegument protein required for efficient viral replication and virion production. We have previously shown that ORF45 interacts with the conserved herpesviral protein ORF33 through the highly conserved C-terminal 19 amino acids (C19) of ORF45. Because the deletion of C19 abolished ORF33 accumulation and viral production, we reasoned that this interaction could be critical for viral production and explored as an antiviral target for gammaherpesviruses. In work described in this article, we characterize this interaction in further detail, first by revealing that this interaction is conserved among gammaherpesviruses, then by identifying residues in C19 critical for its interaction with and stabilization of ORF33. More importantly, we show that disruption of the interaction, either by mutating key residues (W403A or W405A) in C19 or by using competing cell penetration peptide TAT-C19, dramatically reduce the yield of KSHV progeny viruses. Our results not only reveal critical roles of this interaction to viral production but also provide a proof of concept for targeting the ORF33-ORF45 interaction as a novel antiviral strategy against KSHV and other gammaherpesviruses.
A comparison among three maximal mathematical models of the glucose-insulin system

The most well-known and widely used mathematical representations of the physiology of a diabetic individual are the Sorensen and Hovorka models as well as the UVAPadova Simulator. While the Hovorka model and the UVAPadova Simulator only describe the glucose metabolism of a subject with type 1 diabetes, the Sorensen model was formulated to simulate the behaviour of both normal and diabetic individuals. The UVAPadova model is the most known model, accepted by the FDA, with a high level of complexity. The Hovorka model is the simplest of the three models, well documented and used primarily for the development of control algorithms. The Sorensen model is the most complete, even though some modifications were required both to the model equations (adding useful compartments for modelling subcutaneous insulin delivery) and to the parameter values. In the present work several simulated experiments, such as IVGTTs and OGTTs, were used as tools to compare the three formulations in order to establish to what extent increasing complexity translates into richer and more correct physiological behaviour. All the equations and parameters used for carrying out the simulations are provided.
Association of Serum Vitamin B6 with All-Cause and Cause-Specific Mortality in a Prospective Study

There is little evidence regarding the association between serum vitamin B6 concentration and subsequent mortality. We aimed to evaluate the association of serum vitamin B6 concentration with all-cause, cardiovascular disease (CVD), and cancer mortality in the general population using data from the National Health and Nutrition Examination Survey (NHANES). Our study examined 12,190 adults participating in NHANES from 2005 to 2010 in the United States. The mortality status was linked to National Death Index (NDI) records up to 31 December 2015. Pyridoxal 5′-phosphate (PLP) is the biologically active form of vitamin B6. Vitamin B6 status was defined as deficient (PLP < 20 nmol/L), insufficient (PLP ≥ 20.0 and <30.0 nmol/L), and sufficient (PLP ≥ 30.0 nmol/L). We established Cox proportional-hazards models to estimate the associations of categorized vitamin B6 concentration and log-transformed PLP concentration with all-cause and cause-specific mortality by calculating hazard ratios (HRs) and 95% confidence intervals (95%CIs). In our study, serum vitamin B6 was sufficient in 70.6% of participants, while 12.8% of the subjects were deficient in vitamin B6. During follow-up, a total of 1244 deaths were recorded, including 294 cancer deaths and 235 CVD deaths. After multivariate adjustment in Cox regression, participants with higher serum vitamin B6 had a 15% (HR = 0.85, 95%CI = 0.77, 0.93) reduced risk of all-cause mortality and a 19% (HR = 0.81, 95%CI = 0.68, 0.98) reduced risk for CVD mortality for each unit increment in natural log-transformed PLP. A higher log-transformed PLP was not significantly associated with a lower risk for cancer mortality. Compared with sufficient vitamin B6, deficient (HR = 1.37, 95%CI = 1.17, 1.60) and insufficient (HR = 1.19, 95%CI = 1.02, 1.38) vitamin B6 level were significantly associated with a higher risk for all-cause mortality. There was no significant association for cause-specific mortality. Participants with higher levels of vitamin B6 had a lower risk for all-cause mortality. These findings suggest that maintaining a sufficient level of serum vitamin B6 may lower the all-cause mortality risk in the general population.
New Functions of Vav Family Proteins in Cardiovascular Biology, Skeletal Muscle, and the Nervous System

Simple Summary In this review, we provide information on the role of Vav proteins, a group of signaling molecules that act as both Rho GTPase activators and adaptor molecules, in the cardiovascular system, skeletal muscle, and the nervous system. We also describe how these functions impact in other physiological and pathological processes such as sympathoregulation, blood pressure regulation, systemic metabolism, and metabolic syndrome. Abstract Vav proteins act as tyrosine phosphorylation-regulated guanosine nucleotide exchange factors for Rho GTPases and as molecular scaffolds. In mammals, this family of signaling proteins is composed of three members (Vav1, Vav2, Vav3) that work downstream of protein tyrosine kinases in a wide variety of cellular processes. Recent work with genetically modified mouse models has revealed that these proteins play key signaling roles in vascular smooth and skeletal muscle cells, specific neuronal subtypes, and glia cells. These functions, in turn, ensure the proper regulation of blood pressure levels, skeletal muscle mass, axonal wiring, and fiber myelination events as well as systemic metabolic balance. The study of these mice has also led to the discovery of new physiological interconnection among tissues that contribute to the ontogeny and progression of different pathologies such as, for example, hypertension, cardiovascular disease, and metabolic syndrome. Here, we provide an integrated view of all these new Vav family-dependent signaling and physiological functions.
Peptide Derivatives of Platelet-Derived Growth Factor Receptor Alpha Inhibit Cell-Associated Spread of Human Cytomegalovirus

Cell-free human cytomegalovirus (HCMV) can be inhibited by a soluble form of the cellular HCMV-receptor PDGFRα, resembling neutralization by antibodies. The cell-associated growth of recent HCMV isolates, however, is resistant against antibodies. We investigated whether PDGFRα-derivatives can inhibit this transmission mode. A protein containing the extracellular PDGFRα-domain and 40-mer peptides derived therefrom were tested regarding the inhibition of the cell-associated HCMV strain Merlin-pAL1502, hits were validated with recent isolates, and the most effective peptide was modified to increase its potency. The modified peptide was further analyzed regarding its mode of action on the virion level. While full-length PDGFRα failed to inhibit HCMV isolates, three peptides significantly reduced virus growth. A 30-mer version of the lead peptide (GD30) proved even more effective against the cell-free virus, and this effect was HCMV-specific and depended on the viral glycoprotein O. In cell-associated spread, GD30 reduced both the number of transferred particles and their penetration. This effect was reversible after peptide removal, which allowed the synchronized analysis of particle transfer, showing that two virions per hour were transferred to neighboring cells and one virion was sufficient for infection. In conclusion, PDGFRα-derived peptides are novel inhibitors of the cell-associated spread of HCMV and facilitate the investigation of this transmission mode.
Brain Immune Interactions—Novel Emerging Options to Treat Acute Ischemic Brain Injury

Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.
Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells

Immunosuppressants are a mandatory therapy for transplant patients to avoid rejection of the transplanted organ by the immune system. However, there are several known side effects, including alterations of the vasculature, which involve a higher occurrence of cardiovascular events. While the effects of the commonly applied immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (Tac) on mature endothelial cells have been addressed in several studies, we focused our research on the unexplored effects of CsA and Tac on endothelial colony-forming cells (ECFCs), a subgroup of endothelial progenitor cells, which play an important role in vascular repair and angiogenesis. We hypothesized that CsA and Tac induce functional defects and activate an inflammatory cascade via NF-κB signaling in ECFCs. ECFCs were incubated with different doses (0.01 µM–10 µM) of CsA or Tac. ECFC function was determined using in vitro models. The expression of inflammatory cytokines and adhesion molecules was explored by quantitative real-time PCR and flow cytometry. NF-κB subunit modification was assessed by immunoblot and immunofluorescence. CsA and Tac significantly impaired ECFC function, including proliferation, migration, and tube formation. TNF-α, IL-6, VCAM, and ICAM mRNA expression, as well as PECAM and VCAM surface expression, were enhanced. Furthermore, CsA and Tac led to NF-κB p65 subunit phosphorylation and nuclear translocation. Pharmacological inhibition of NF-κB by parthenolide diminished CsA- and Tac-mediated proinflammatory effects. The data of functional impairment and activation of inflammatory signals provide new insight into mechanisms associated with CsA and Tac and cardiovascular risk in transplant patients.
First Molecular Evidence of Pathogens in Fleas Collected from Dogs in Northern Vietnam

Fleas are considered as hosts for a wide range of pathogens that cause emerging and re-emerging zoonotic diseases worldwide. Data on fleas and flea-borne pathogens (FBPs) in the international literature are limited in Vietnam. This study aimed to investigate the species of fleas and the presence of pathogens of interest in fleas in northern Vietnam using PCR and sequence analysis. Out of 200 dogs enrolled in this study, 20% were infested by the flea species Ctenocephalides felis felis. In total, 62 fleas (35 females and 27 males) collected from domestic dogs were molecularly screened for the detection of pathogens. Out of the screened fleas, 39 were positive for Rickettsia felis (62.9%), 9 for Candidatus Mycoplasma hemobos (14.52%), and 6 for Mycoplasma wenyonii (9.68%). This study shows the first molecular detection of the above-mentioned pathogens in fleas collected from the studied areas and the potential risk of infection with examined FBPs in northern Vietnam.
The Impact of Apple Variety and the Production Methods on the Antibacterial Activity of Vinegar Samples

Apple vinegar is a natural product widely used in food and traditional medicine as it contains many bioactive compounds. The apple variety and production methods are two factors that play a major role in determining the quality of vinegar. Therefore, this study aims to determine the quality of apple vinegar samples from different varieties (Red Delicious, Gala, Golden Delicious, and Starking Delicious) prepared by three methods using small apple pieces, apple juice, and crushed apple, through determining the physicochemical properties and antibacterial activity of these samples. The antibacterial activity was studied against five pathogenic bacteria: Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli (ATB: 57), Escherichia coli (ATB: 97), and Pseudomonas aeruginosa, using two methods, disk diffusion and microdilution, for determining the minimum inhibitory concentrations and the minimum bactericidal concentrations. The results of this study showed that the lowest pH value was 3.6 for Stark Delicious, obtained by liquid fermentation, and the highest acetic acid values were 4.7 and 4% for the vinegar of Red Delicious and Golden Delicious, prepared by solid fermentation, respectively. The results of the antibacterial activity showed considerable activity of apple vinegar on the tested strains. Generally, the Staphylococcus aureus strain appears less sensitive and Pseudomonas aeruginosa seems to be very sensitive against all samples, while the other strains have distinct sensitivities depending on the variety studied and the method used. A higher antibacterial activity was found in vinegar obtained by the apple pieces method and the Red Delicious variety, with a low MIC and MBC recorded, at 1.95 and 3.90 µL/mL, respectively. This study has shown that the choice of both apple variety and production method is therefore an essential step in determining and aiming for the desired quality of apple vinegar.