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Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single-molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation and neurite orientation dispersion and density imaging diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 versus 0.57, difference 0.036, 95% CI: 0.029-0.043, P < 0.001). Lesion volume (Spearman's rho rs= 0.38, P < 0.001) and g-ratio (rs= 0.24, P < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) [11/23 (48%) versus 2/15 (13%), P < 0.05]. These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity and help to identify individuals with a high degree of axonal damage at disease onset.

Evacuation modelling is a tool for measuring the performance of building design for safe evacuation of occupants during emergencies such as fires. The first evacuation modelling efforts date back to the mid-70s. To date, a wide range of evacuation models have been developed, with numerous problems having been studied in various scientific disciplines. In the present study, a database of 152 original papers was developed through a systematic search in the field of evacuation modelling, and their data was used to answer three key questions. The first question was that of the role of architectural design in the entire body of research. Architectural design issues are one of the five fields in evacuation modelling research being considered in a variety of scales in the design process. The second question was that of important elements of evacuation modelling. This was answered by data analysis. From the perspective of variables and their relationship, it was found that several elements have been considered as independent variables in evacuation modelling, with their design features being considered as measures to explain other dependent parameters. The third question was that of the relationship between architectural elements and other modelling parameters. When a modelling is aimed at evaluation of a design, the results can cause significant changes in the original design.Modelling methods are also relevant to the levels of design development. In early stages, macroscopic modelling can lead to the rejection or acceptance of a design alternative or schema, or demonstrate whether or not the design conforms to the required performance criteria. In more advanced stages, microscopic modelling is applied as a tool to make fine tunings of dimensions, configuration details and layouts of columns and furniture. The results showed that the swarm intelligence-based methods are the emerging field among microscopic models that can result in lower computational cost and more accurate results.

Introduction: Considering the significant role of higher education, particularly medical sciences education, in the health and development of society, the educational system should be planned in a way that maximally caters to the community's needs. The goal of this article is to present a responsive and justice-centered education model in medical sciences education.Methods: In the quantitative phase, data from 335 faculty members of Payambar-e Azam Hospital in Hormozgan were collected using stratified random sampling and a questionnaire that identified components within a Likert scale. The content validity and structural validity of the questionnaire were confirmed through confirmatory factor analysis. The Cronbach's alpha coefficient exceeded 0.70, indicating reliability. The data were analyzed using structural equation modeling with SmartPLS-3 software.Results: Equity-centered, universality, needs assessment, content, and principled are characteristics of equity-based education. According to the T-value modeling results, the factor loads of all model variables were above 0.96 and, at a 95% confidence level, were statistically significant. The highest factor load was related to enabling and inhibitory factors, with a factor load of 0.54 and variance of 0.23. In contrast, the lowest factor load was related to the dimensions of responsiveness and equity-based education with a factor load of 0.12 and a variance of 0.02.Conclusion: Universality, needs assessment, and content should be considered in equity-based and principled education in the planning of educational programs at medical universities.

Introduction: Sea cucumber is one of the important aquatic animals that has many nutritional and medicinal properties and is of medical importance due to the presence of compounds with therapeutic and antibacterial effects. The purpose of this study was to investigate the antibacterial effect of selenium hybrid nanoparticles and sea cucumber extract on Escherichia coli, Micrococcus luteus and Bacillus cereus bacteria. Methods: MIC evaluation method was determined for the cytotoxic effect of sea cucumber extract on microbial cells. To carry out this research, after collecting and extracting sea cucumbers, the cytotoxicity of this extract on microbial cells was determined using the MIC method. Then, the antibacterial effect of sea cucumber extract, selenium hybrid nanoparticle and the combined effect of sea cucumber extract and selenium hybrid nanoparticle on Escherichia coli, Micrococcus luteus and Bacillus cereus bacteria were evaluated. Statistical analysis was done using SPSS version 16 software. Results: The results of the experiments showed that sea cucumber extract with different dilutions had an antibacterial effect on Escherichia coli bacteria, Micrococcus luteus and Bacillus cereus. These results also applied to the tests performed with selenium nanomedicine. Interestingly, after combining a certain amount of sea cucumber extract and selenium nanomedicine, a greater antibacterial effect was observed on the above-mentioned 3 bacteria. Conclusion: The synergistic effect of sea cucumber extract and selenium nanoparticles has a higher level of antibacterial properties.

Background: The ability to experience and express emotions is considered a key factor in mental health, and difficulty in effective emotion regulation is a major symptom of many psychiatric disorders. Objective: The present study aimed to investigate the role of reality therapy on emotion regulation difficulty and academic self-handicapping in high school students. Materials & Methods: This quasi-experimental research adopted a pretest-posttest control group design. The statistical population included all male high school students of Ahvaz in 2021, 30 of whom were selected through cluster random sampling and were then randomly assigned to an experimental group and a control group (15 participants per group). For the pretest, participants from both groups completed the Self-Handicapping Scale and the Difficulties in Emotion Regulation Scale. The 10-session reality therapy intervention was then implemented in the experimental group, whereas the control group received no intervention. At the end of therapy sessions, the posttest was given to participants in both groups. Data analysis was performed using Analysis of covariance (ANCOVA). Results: The adjusted posttest mean score of difficulty in emotion regulation among intervention and control groups were 77.5 (95%CI: 75.1-79.9) and 113.35 (95%CI: 110.9-115.7), respectively. The values for academic self-handicapping in the intervention and control groups were 75.1 (95%CI: 72.8-78.4) and 97.3 (95%CI: 92.4-99), respectively. According to the result of ANCOVA, reality therapy had significant effects on academic self-handicapping (F=87.79, P=0.001, η2=0.78) and emotion regulation difficulty (F=461.15, P=0.001, η2=0.95) among students. Conclusions: Reality therapy mitigated academic self-handicapping and difficulties in emotion regulation among male high school students. It is recommended that schools help students improve emotion regulation and control self-handicapping by providing appropriate conditions for implementing reality therapy sessions.

Introduction: Oral squamous cell carcinoma, which is known as the most common cancer of the oral cavity, is associated with high morbidity and mortality rate. To date, many efforts have been made to find effective methods to stop the growth of cancer cells. One of the emerging methods in this field is the application of low-level lasers. Materials and Methods: Human head and neck carcinoma cell lines were prepared and irradiated with four different wavelengths of low-level laser with a density of 1 j/cm2 and a power of 100 mW. The expression of the Bcl-2 and Bax genes and the Bax/Bcl-2 ratio were investigated by real-time PCR. Results: The highest percentage of Bcl-2 gene expression was related to 660nm wavelength and the highest percentage of Bax gene expression was related to 810 nm infrared wavelength. The lowest level of expression of the Bcl-2 gene related to the 810nm infrared wavelength and the Bax gene related to the 532nm wavelength was obtained. The lowest Bax/Bcl-2 ratio was obtained at the wavelength of 660nm and the highest ratio was obtained at the wavelength of 810nm. Conclusion: Despite the extensive studies conducted in the field of low-level laser application in oncology, more studies are needed to investigate the effect of this technology on cancer cells. Keywords: Low-level laser therapy; Low-level light therapy; Squamous cell carcinoma; Squamous cell carcinoma of head and neck.

BackgroundThe role of vitamin D3 (VitD3) in modulating innate and adaptive immunity has been reported in different disease contexts. Since the start of the coronavirus disease-2019 (COVID-19) pandemic, the role of VitD3 has been highlighted in many correlational and observational studies. However, the exact mechanisms of action are not well identified. One of the mechanisms via which VitD3 modulates innate immunity is by regulating the NLRP3-inflammasome pathway, being a main underlying cause of SARS-CoV-2-induced hyperinflammation.Aims and main methodsBlood specimens of severe COVID-19 patients with or without VitD3 treatment were collected during their stay in the intensive care unit and patients were followed up for 29 days. qPCR, western blot, and ELISA were done to investigate the mechanism of action of VitD3 on the NLRP3 inflammasome activation.Key findingsWe here report the ability of VitD3 to downregulate the NLRP3-inflammsome pathway in severe COVID-19 patients. Lower inflammasome pathway activation was observed with significantly lower gene and protein expression of NLRP3, cleaved caspase-1, ASC and IL-1β among severe COVID-19 patients treated with VitD3. The reduction of the inflammasome pathway was associated with a reduction in disease severity markers and enhancement of type I IFN pathway.SignificanceOur data reveals an important anti-inflammatory effect of VitD3 during SARS-CoV-2 infection. Further investigations are warranted to better characterize the ability of VitD3 to control disease pathogenesis and prevent progression to severe states. This will allow for a more efficient use of a low cost and accessible treatment like VitD3.

Summary: The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids (HH32 and HH33) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies.

The contribution of adipose-derived FGF21 to energy homeostasis is unclear. Here we show that browning of inguinal white adipose tissue (iWAT) by β-adrenergic agonists requires autocrine FGF21 signaling. Adipose-specific deletion of the FGF21 co-receptor β-Klotho renders mice unresponsive to β-adrenergic stimulation. In contrast, mice with liver-specific ablation of FGF21, which eliminates circulating FGF21, remain sensitive to β-adrenergic browning of iWAT. Concordantly, transgenic overexpression of FGF21 in adipocytes promotes browning in a β-Klotho-dependent manner without increasing circulating FGF21. Mechanistically, we show that β-adrenergic stimulation of thermogenic gene expression requires FGF21 in adipocytes to promote phosphorylation of phospholipase C-γ and mobilization of intracellular calcium. Moreover, we find that the β-adrenergic-dependent increase in circulating FGF21 occurs through an indirect mechanism in which fatty acids released by adipocyte lipolysis subsequently activate hepatic PPARα to increase FGF21 expression. These studies identify FGF21 as a cell-autonomous autocrine regulator of adipose tissue function.

Abstract Motivated by recent experimental demonstrations of Floquet topological insulators, there have been several theoretical proposals for using structured light, either spatial or spectral, to create other properties such as flat bands and vortex states. In particular, the generation of vortex states in a massive Dirac fermion insulator irradiated by light carrying nonzero orbital angular momentum (OAM) has been proposed. Here, we evaluate the orbital magnetization and optical conductivity as physical observables for such a system. We show that the OAM of light induces nonzero orbital magnetization and current density. The orbital magnetization density increases linearly as a function of the OAM degree. In certain regimes, we find that orbital magnetization density is independent of the system size, width, and Rabi frequency of light. It is shown that the orbital magnetization arising from our Floquet theory is large and can be probed by magnetometry measurements. Furthermore, we study the optical conductivity for various types of electron transitions between different states such as vortex, edge, and bulk that are present in the system. Based on the peaks in conductance, a scheme for the detection of vortex states is proposed.

Nowadays, by expanding the application of thin layers in industry and medical sciences, their fabrication methods have also received attention. One of those methods is the vaporizing material method with the help of an electron gun. The most important part in the electron gun is the electron optic, which is responsible for producing and accelerating electrons, so that it becomes possible to vaporize refractory materials in a shorter period of time by better modifying and controlling the electron beam (the shape and diameter of the electron beam) at the target location. The reduction and control of the beam diameter in this evaporation source depends on various parameters such as device geometry, magnetic field intensity, electric power, etc. Therefore, in this research, the effect of those parameters was investigated by conducting experiments and using finite element and modeling software. The simulation results revealed that the effect of the effective parameters on the beam diameter can be predicted to a good extent, so that the diameter of the electron beam decreases by changing the geometrical shape, size and displacement of the output beam components. Then, the new electron gun, compared to the existing prototype, is optimized by applying these changes in the construction of the device and conducting experiments, and its beam diameter is reduced by 40% to be more focused.

Abstract Open quantum systems have been shown to host a plethora of exotic dynamical phases. Measurement-induced entanglement phase transitions in monitored quantum systems are a striking example of this phenomena. However, naive realizations of such phase transitions requires an exponential number of repetitions of the experiment which is practically unfeasible on large systems. Recently, it has been proposed that these phase transitions can be probed locally via entangling reference qubits and studying their purification dynamics. In this work, we leverage modern machine learning tools to devise a neural network decoder to determine the state of the reference qubits conditioned on the measurement outcomes. We show that the entanglement phase transition manifests itself as a stark change in the learnability of the decoder function. We study the complexity and scalability of this approach in both Clifford and Haar random circuits and discuss how it can be utilized to detect entanglement phase transitions in generic experiments.

Abstract Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in a convenience sample of 1,411 patients receiving medical treatment in the emergency departments of five university hospitals in North Rhine-Westphalia, Germany, in August/September 2022. 62% reported underlying medical conditions and 67.7% were vaccinated according to German COVID-19 vaccination recommendations (13.9% fully vaccinated, 54.3% one booster, 23.4% two boosters). We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0%, and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was 5.6- and 23.4-fold lower compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. We explored previous vaccinations and infections as correlates of BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given a rather moderate adherence to COVID-19 vaccination recommendations, this analysis highlights the need to improve vaccine-uptake to reduce the COVID-19 risk of immune evasive variants. The study was registered as clinical trial (DRKS00029414).

Coronavirus disease as a persistent epidemic of acute respiratory syndrome posed a challenge to global healthcare systems. Many people have been forced to stay in their homes due to unprecedented quarantine practices around the world. Since most people used social media during the Coronavirus epidemic, analyzing the user-generated social content can provide new insights and be a clue to track changes and their occurrence over time. An active area in this space is the prediction of new infected cases from Coronavirus-generated social content. Identifying the social content that relates to Coronavirus is a challenging task because a significant number of posts contain Coronavirus-related content but do not include hashtags or Corona-related words. Conversely, posts that have the hashtag or the word Corona but are not really related to the meaning of Coronavirus and are mostly promotional. In this paper, we propose a semantic approach based on word embedding techniques to model Corona and then introduce a new feature namely semantic similarity to measure the similarity of a given post to Corona in semantic space. Furthermore, we propose two other features namely fear emotion and hope feeling to identify the Coronavirus-related posts. These features are used as statistical indicators in a regression model to estimate the new infected cases. We evaluate our features on the Persian dataset of Instagram posts, which was collected in the first wave of Coronavirus, and demonstrate that the consideration of the proposed features will lead to improved performance of the Coronavirus incidence rate estimation.

Background: The diagnosis of cervical cancer significantly affects the health-related quality of life (HRQOL) of women. This study aimed to investigate the relationships between chronic fatigue syndrome (CFS) and experiential avoidance (EA) with HRQOL, mediated by depression in women with cervical cancer.Methods: This descriptive-correlational study selected 261 cervical cancer cases in Mashhad, Iran in 2021, using purposive sampling from October 10, 2021 to December 24, 2021. The research tools include the SF-36 Questionnaire, the Chalder Fatigue Scale, the Brief Experiential Avoidance Questionnaire, and Beck Depression Inventory. Data analysis was done using Pearson correlation coefficient and structural equation modeling in SPSS version 27 and AMOS version 24.Results: The results indicated that all direct paths, with the exception of CFS, significantly correlated with HRQOL (P

The psychological refractory period (PRP) effect occurs when two stimuli that require separate responses are presented sequentially, particularly with a short and variable time interval between them. Fatigue is a suboptimal psycho-physiological state that leads to changes in strategies. In recent years, numerous studies have investigated the effects of transcranial direct current stimulation (tDCS) on motor control. The present study aimed to investigate the effects of two tDCS methods, anodal and cathodal, on PRP in ten different conditions of stimulus-onset asynchronies (SOAs) under non-fatigue and mental fatigue conditions. The participants involved 39 male university students aged 19 to 25 years. In the pre-test, they were assessed using the PRP measurement tool under both non-fatigue and mental fatigue conditions. The mental fatigue was induced by a 30-min Stroop task. The test consisted of two stimuli with different SOAs (50, 75, 100, 150, 300, 400, 600, 900, 1200, and 1500 ms). The first was a visual stimulus with three choices (letters A, B, and C). After a random SOA, the second stimulus, a visual stimulus with three choices (colors red, yellow, and blue), was presented. Subsequently, participants were randomly assigned to the anodal, cathodal, and sham stimulation groups and underwent four consecutive sessions of tDCS stimulation. In the anodal and cathodal stimulation groups, 20 min of tDCS stimulation were applied to the PLPFC area in each session, while in the sham group, the stimulation was artificially applied. All participants were assessed using the same measurement tools as in the pre-test phase, in a post-test phase one day after the last stimulation session, and in a follow-up phase four days after that. Inferential statistics include mixed ANOVA, one-way ANOVA, independent, and dependent t-tests. The findings indicated that the response time to the second stimulus was longer at lower SOAs. However, there was no significant difference between the groups in this regard. Additionally, there was no significant difference in response time to the second stimulus between the fatigue and non-fatigue conditions, or between the groups. Therefore, tDCS had no significant effect. There was a significant difference between mental fatigue and non-fatigue conditions in the psychological refractory period. Moreover, at lower SOAs, the PRP was longer than at higher SOAs. In conditions of fatigue, the active stimulation groups (anodal and cathodal) performed better than the sham stimulation group at higher SOAs. Considering the difference in response to both stimuli at different SOAs, some central aspects of the response can be simultaneously parallel. Fatigue also affects parallel processing. This study supports the response integration phenomenon in PRP, which predicts that there will be an increase in response time to the first stimulus as the interval between the presentation of the two stimuli increases. This finding contradicts the bottleneck model. In this study, the effectiveness of cathodal and anodal tDCS on response time to the second stimulus and PRP was found to be very small.

Curcumin, an important natural component of turmeric, has been known for a long time for its antimicrobial properties. This study aimed to investigate the anti-biofilm action of the niosome-encapsulated curcumin and explore the involved anti-biofilm mechanism. In silico investigations of ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) were first performed to predict the suitability of curcumin for pharmaceutical application. Curcumin showed low toxicity but at the same time, low solubility and low stability, which, in turn, might reduce its antimicrobial activity. To overcome these intrinsic limitations, curcumin was encapsulated using a biocompatible niosome system, and an encapsulation efficiency of 97% was achieved. The synthesized curcumin-containing niosomes had a spherical morphology with an average diameter of 178 nm. The niosomal curcumin was capable of reducing multi-drug resistant (MDR) Staphylococcus aureus biofilm 2–4-fold compared with the free curcumin. The encapsulated curcumin also demonstrated no significant cytotoxicity on the human foreskin fibroblasts. To understand the interaction between curcumin and S. aureus biofilm, several biofilm-related genes were analyzed for their expression. N-acetylglucosaminyl transferase (IcaD), a protein involved in the production of polysaccharide intercellular adhesion and known to play a function in biofilm development, was found to be downregulated by niosomal curcumin and showed high binding affinity (-8.3 kcal/mol) with curcumin based on molecular docking analysis. Our study suggests that the niosome-encapsulated curcumin is a promising approach for the treatment of MDR S. aureus biofilm and can be extended to biofilms caused by other pathogens.