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Extended Abstract Background: Human activities, climate variability, and environmental stress have strongly affected forest ecosystems worldwide. Forest fires are among the major factors of global ecosystem destruction. Fires in the forest, whether of human or natural origin, have been raised as a serious crisis in recent years. Hence, fire risk assessment plays an important role in forest fire management because knowing where the highest risk is essential to minimize threats to resources, lives, and property. Integration of spatial information from different sources using statistical analysis in the GIS environment is a suitable tool for managing and spreading forest fires, which is one of the main natural hazards in northern Iran. Therefore, it is necessary to prepare a fire risk assessment map for the planning and protection of forests. Methods: The current practical research concerning its nature is a combination of documentary, descriptive, and quantitative model-based methods regarding the research method. In this study, fuzzy and hierarchical (AHP) logic models were combined to investigate the risk of forest fire in Mazandaran province in five classes, very high, high, medium, low, and very low, respectively, using four main criteria and nine sub-criteria, namely topography (height, slope, direction, and rivers), climatic factors (peak temperature and precipitation), human factors (residential areas and the network of communication roads), and biological factors (vegetation). To obtain the net vegetation cover, the Normalized Difference Vegetation Index (NDVI) was applied to the Sentinel-2 satellite image set in a 5-year period (2017-2022) in the GEE web system. The height, slope, and slope direction maps of the study area were prepared from the digital elevation model (DEM) of 12.5 m from the ALOS AVNIR-2 dataset. The distance from rivers, residential areas, and the road network was calculated using the Euclidean distance tool in ArcMAP software. The geographic location of meteorological synoptic stations was obtained from the Meteorological Organization, and its information was used as meteorological input data. In the ArcMap environment, a map of average annual precipitation and maximum temperature was prepared from synoptic stations through interpolation for the period from 2007 to 2021. Based on this modeling method, experts' opinions were used for the relative importance and priority of criteria and sub-criteria in the risk of forest fire in the study area to obtain the fuzzy weight of criteria and sub-criteria. Based on the weighting coefficients applied in the present plan, the final weights of the criteria and sub-criteria affecting forest fire from the highest to the lowest weights belong to the topographical, biological, climatic, and human criteria. Among the sub-criteria, the highest and lowest weights belong to vegetation and slope, respectively. The consistency rate (CR) for the matrices of the affecting factors is equal to 6.25%, which is less than 10%, actually indicating that the weight of the criteria is proportionate and reliable. The highest weights were obtained for the vegetation cover and the slope direction, and the lowest weights belonged to the distance from the river and the slope. Finally, the fire risk assessment map was prepared by combining the fuzzy maps of the sub-criteria in GIS. Results: Overall, medium to very high fire risk potential was found in 72% of the studied area. From a total area of about 2373189 hectares, very low (8.4%), low (18.3%), medium (23.66%), high (25.62), and very high (24%) vulnerability rates were identified in Mazandaran province. Higher fire potential was detected in the East and Southeast parts than in other parts of the study area. The aforementioned fuzzy layers clearly show that the height, slope, and amount of precipitation are low and the density of residential areas and the network of communication roads are high in these parts, with high temperatures. In fact, these factors have increased the risk of fire in these areas. In the present study, the highest fire potential was observed at low altitudes, which could have resulted from the concentration of human activities at low altitudes. Moreover, most fires occurred on low slopes in the studied area. The distance layer from waterways also plays a dual role in the occurrence of fire. The results of the model show an inverse correlation between the distance from roads and fire potential. Based on the results of the fuzzy AHP model, the probability of fire increased with the decrease in precipitation and the increase in annual temperature. A decrease in the amount of precipitation causes a decrease in soil moisture and vegetation, elevating the possibility of fire. On the other hand, the increase in temperature causes the drying of vegetation and reduces humidity, thereby increasing the possibility of fire. Conclusion: It can be concluded that preparing a fire risk assessment map can help managers and planners in identifying areas with high potential and in crisis management in vulnerable areas. The obtained fire risk assessment map can be used as a decision-making support system to predict future fires in the study area.

In the present study, the impact of geometric variables and structural features of stents on hemodynamic parameters is investigated. Intravascular stent implantation is a treatment method whose success largely depends on the geometric structure of the stent and its effect on hemodynamic parameters. Medical devices called stents are inserted into arteries to restore blood flow when an artery is blocked. In this research, an optimal stent was designed and its effect compared to the common commercial stent used for coronary arteries was investigated and compared. It has been found that the geometry of the stent has an effective impact on the wall shear stress in the stented artery. Therefore, in this article, the importance of stent structures in the treatment of the coronary artery disease is discussed. For this purpose, first, an optimal stent is created with the topology optimization technique to find the best structure in the stent design. Finally, the optimized stent is numerically verified with ANSYS software and compared with existing commercial stents, and then the prototype is fabricated using additive manufacturing techniques. Commercial software ABAQUS, SolidWorks, and ANSYS are used in this research. The results showed that in optimizing a square plate, a sample with a minimum residual volume limit equal to 10 and 7 % can be selected as the optimal state. The results indicate that the new design can improve the distribution of wall shear stresses to reduce the adverse hemodynamic changes. Therefore, the proposed stent geometric structure can help improve the treatment. Finally, the optimized stent along with a commercial stent was made with the 3D printing method.

This paper aims to incorporate Greimassian semiotics of passions in current cognitive science. Concepts such as passional codes, the canonical passional schema, and other central Greimassian notions in the domain of passions are mapped against ideas such as frames and layers of meaning within cognitive science. By integrating the two fields artificially kept apart, the authors endeavour to show how the resulting synergy could shed new light on the study of passions.

Background: Improper use of standards for measurement instruments can impact the accuracy of study results. Objectives: This study systematically reviews the Instruments for measuring pain intensity during venous catheter insertion in preschool children. Methods: In this systematic review, conducted from October 2023 to January 2023, an open search was carried out for articles in domestic databases, such as scientific information database (SID), MagIran, and Iran Medex, and international databases, including PubMed, CINAHL, Web of Science, and Scopus using the following keywords: Preschool period, pain intensity, cannulation, vein removal, pain scale, pain relief, pain perception, and pain sensation. The objective of this search was to examine the measurement tools utilized to assess pain intensity during venipuncture in preschool-aged children without a time restriction. Duplicate articles were excluded, and other studies meeting the inclusion criteria were reviewed. Articles were assessed by two researchers, and any discrepancies were resolved by a third author. Results: Among all the reviewed studies, 21 articles that were conducted between 2001 and 2023 met the inclusion criteria. The tools utilized in these studies to assess pain intensity during venous catheter insertion in preschool children included face, legs, activity, cry, and consolability (FLACC), Wong-Baker, Oucher scale, visual analog scale, and Poker Chip scale. The Wong-Baker instrument was a self-assessment, FLACC were assessed by both the researcher and a reviewer, Oucher was a self-assessment, the visual analog scale was assessed by parents and reviewers, and the Poker Chip scale was a self-assessment. Conclusions: Researchers who do not adhere to tool standards often opt to utilize tools based on the methods of other studies or their requirements, which could potentially impact the outcomes of their studies

Abstract The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of ‘Ghost’ neurons endowed with atypical molecular and functional identity. Compared to ‘classical’ Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are ‘invisible’ to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.

Abstract Background Limb girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders with a very variable clinical presentation and overlapping traits. The clinical symptoms of LGMD typically appear in adolescence or early adulthood. Genetic variation in the dysferlin gene (DYSF) has been associated with LGMD. Methods We characterized a recessive LGMD in a young adult from consanguineous Irani families using whole-exome sequencing (WES) technology. Sanger sequencing was performed to verify the identified variant. Computational modeling and protein-protein docking were used to investigate the impact of the variant on the structure and function of the DYSF protein. Results By WES, we identified a novel homozygous missense variant in DYSF (NM_003494.4: c.5876T > C: p. Leu1959Pro) previously been associated with LGMD phenotypes. Conclusions The identification and validation of new pathogenic DYSF variant in the present study further highlight the importance of this gene in LGMD.

Background: This study aimed to evaluate the impact of photodynamic therapy (PDT) using two photosensitizers, methylene blue and indocyanine green, on the microtensile bond strength of a universal adhesive to caries-affected dentin. Methods: The occlusal enamel of 60 third molars was cut to expose the inner one-third of the dentin. Artificial caries were induced through a pH cycling process. The samples were divided into three groups: M (Methylene blue+ diode laser), I (Indocyanine green agents+ diode laser irradiation), and control. Each group was further divided into two subgroups according to the adhesive protocol (self-etch, total-etch). After restoring with Gradia composite resin, teeth were sectioned and exposed to 5000 thermal cycles. Microtensile bond strength was measured using a universal testing machine. The data were subjected to two- and one-way ANOVA and paired comparisons were performed by the Tamhane and Tukey tests. Results: The study found significant effects of the photosensitizer, etching pattern, and their interactions on the microtensile bond strength of composite resin to caries-affected dentin (P < 0.001). In the self-etching mode, PDT with indocyanine green exhibited significantly higher bond strength values compared to PDT with methylene blue (P = 0.001) and the control groups (P < 0.001). However, no significant differences were observed in the total-etch mode. (P = 0.54). Conclusions: The etching mode played a more significant role in the bond strength when using the universal adhesive alongside PDT with methylene blue and indocyanine green. Employing two photosensitizers in PDT during the self-etch mode significantly increased the bond strength values.

The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.

Abstract This study introduces and compares computational fluid dynamics of Newtonian and non‐Newtonian blood flows in coronary arteries, with and without considering stents. Three blood flow models, including Newtonian, Carreau, and non‐Newtonian power‐law models, were simulated to investigate their effect, and the solution algorithm includes drawing the geometry, creating the desired mesh, and then simulating Newtonian and non‐Newtonian blood flow different models and comparing them with each other, is presented in the article. A Newtonian fluid model has been commonly used in the simulation of blood flow, whereas blood has non‐Newtonian properties due to the nature of a solution containing suspended particles. The goal of this research is to investigate the differences between the models built with Newtonian and non‐Newtonian fluid assumptions. In addition, a stent was designed and the effect of the stent on blood flow parameters was investigated for all three flow models, including Newtonian, Carreau, and non‐Newtonian power‐law models. Stents are medical devices that can be placed in arteries to open up blood flow in a blocked vessel. Stents can affect the wall shear stress. Knowing the slight deformation of the shear stress makes the importance of stent implantation and also helps to optimize the design of the intravascular stent, which can affect the occlusion of the vessels. The distribution of the velocity, pressure, and wall shear stress in all blood flow models with and without considering the effect of stents have been investigated and finally compared. Therefore, in general, the innovation of this article is to find the effect of implanted stents on blood flow parameters with different blood flow models, both Newtonian and non‐Newtonian. A comparison of Newtonian and non‐Newtonian flows showed that in the case of the Carreau non‐Newtonian model, the wall shear stress was higher. In addition, in the results of the geometric model with a stent effect compared to the geometric model without a stent effect, it is evident that there was a higher velocity and wall shear stress.

Abstract The immunotherapeutic application of interleukin-2 (IL-2) in cancer treatment is limited by its off-target effects on different cell populations and insufficient activation of anti-tumor effector cells at the site of the tumor upon tolerated doses. Targeting IL-2 to the tumor microenvironment by generating antibody-cytokine fusion proteins (immunocytokine) would be a promising approach to increase efficacy without associated toxicity. In this study, a novel nanobody-based immunocytokine is developed by the fusion of a mutant (m) IL-2 with a decreased affinity toward CD25 to an anti-vascular endothelial growth factor receptor-2 (VEGFR2) specific nanobody, denoted as VGRmIL2-IC. The antigen binding, cell proliferation, IFN-γ-secretion, and cytotoxicity of this new immunocytokine are evaluated and compared to mIL-2 alone. Furthermore, the pharmacokinetic properties are analyzed. Flow cytometry analysis shows that the VGRmIL2-IC molecule can selectively target VEGFR2-positive cells. The results reveal that the immunocytokine is comparable to mIL-2 alone in the stimulation of Primary Peripheral Blood Mononuclear Cells (PBMCs) and cytotoxicity in in vitro conditions. In vivo studies demonstrate improved pharmacokinetic properties of VGRmIL2-IC in comparison to the wild or mutant IL-2 proteins. The results presented here suggest VGRmIL2-IC could be considered a candidate for the treatment of VEGFR2-positive tumors.

Conjugated polymers such as polypyrrole, polyaniline, and polythiophene have developed as capable candidates for scaffold fabrication due to their electrical conductivity, tunable surface properties, and ability to deliver bioactive molecules. When blended with other biomaterials and nanoparticles enables the formation of composites that leverage the advantages of both components. The main focus areas of the review include the use of conjugated polymer-based composites (CPCs) for tissue engineering e.g., neural, cardiac, bone, and skin. Within each section, specific examples are provided of conjugated polymer-biomolecule composite systems that have been explored along with a discussion of their composition, fabrication, and performance for supporting cell growth and tissue regeneration. Finally, current challenges and future perspectives are discussed in applying CPCs toward engineering clinically relevant tissues and organs. Overall, this comprehensive review covers fundamental design considerations in developing conjugated polymer composite scaffolds and their emerging applications in tissue engineering.

Background: Falling is a significant cause of occupational injuries and fatalities among farmers, and falling from trees is one of the most common causes of injury resulting in a high number of visits to health centers. Despite this, there is limited evidence on the factors associated with falling from walnut trees. Therefore, this study aimed to identify the factors that contribute to falling from walnut trees from the perspective of farmers and farmworkers.Methods: This qualitative study was conducted using conventional content analysis. Data were collected through semi-structured interviews with 20 farmers and farmworkers who had experienced falling from walnut trees as recorded in the National Accidents Record Program from September to October 2017 in Tuyserkan county, Iran. Participants were selected through purposive sampling. Moreover, data rigor was ensured through participant and external checks. All interviews were recorded and analyzed using content analysis methods.Results: Data analysis led to the extraction of six themes, including psychological factors, physical factors, behavioral and habitual factors, economic factors, factors related to walnut trees, and atmospheric agents, along with 18 subthemes for behavioral, human, and environmental factors.Conclusion: The findings of this study suggest that with appropriate interventions and training, farmers and farmworkers can be guided and assisted so as to prevent the occurrence of falling from walnut trees. In addition to educational interventions, health promotion measures such as providing safety equipment and insurance coverage can be essential in reducing injuries.

Rapid damage assessment after an earthquake is crucial for allocating and prioritizing emergency actions. Building damage due to an earthquake depends on the seismic hazard and the building’s strength. While it is now possible to promptly access acceleration data as seismic input through online strong motion networks in urban areas, good models are necessary to evaluate the damage in different zones of the affected area. This study aims to present a rapid method for such an urban-scale building collapse evaluation by conducting a nonlinear dynamic analysis of modeled buildings. Based on the Nagato and Kawase model, this study estimates the yield shear strength of 3-story steel buildings, 3-story reinforced concrete buildings, and 1-story masonry buildings in Sarpol-e-Zahab City after the 2017 Mw7.3 earthquake. The damage ratio is calculated through nonlinear dynamic analyses using estimated records from the main earthquake shock in different city zones. The research found that the seismic yield shear strength of steel and reinforced concrete buildings might be weaker than that of the Iranian seismic code’s standard value. Conversely, masonry-building resistance is stronger than the guidelines assumed. The constructed numerical models can be used for the rapid building damage assessment immediately after a damaging earthquake.

Abstract Background and Aim Staging liver fibrosis is important, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning‐Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C patients. Methods We propose a method based on a selection of machine learning classification methods including multilayer perceptron (MLP) neural network, Naive Bayesian (NB), decision tree, and deep learning. Initially, the synthetic minority oversampling technique (SMOTE) is performed to address the imbalance in the dataset. Afterward, the integration of MLP and TLBO is implemented. Results We propose a novel algorithm that reduces the number of required patient features to seven inputs. The accuracy of MLP using 12 features is 0.903, while that of the proposed MLP with TLBO is 0.891. Besides, the diagnostic accuracy of all methods, except the model designed with the Bayesian network, increases when the SMOTE balancer is applied. Conclusion The decision tree‐based deep learning methods show the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and seven features, MLP reached an accuracy rate of 0.891, which is quite satisfactory when compared with those of similar studies. The proposed model provides high diagnostic accuracy, while reducing the required number of properties from the samples. The results of our study show that the recruited algorithm of our study is more straightforward, with a smaller number of required properties and similar accuracy.

Abstract Background Hypomyelinating leukodystrophy‐9 (HLD‐9) is caused by biallelic pathogenic variants in RARS1, which codes for the cytoplasmic tRNA synthetase for arginine (ArgRS). This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with RARS1‐related disease and determine probable genotype–phenotype relationships. Methods We identified three patients with RARS1 homozygous pathogenic variants. Furthermore, we performed a comprehensive review of the literature. Results Homozygous variants of RARS1 (c.2T>C (p.Met1Thr)) were identified in three patients with HLD‐9. Clinical symptoms were severe in all patients. Following the literature review, thirty HLD‐9 cases from eight studies were found. The 33 patients' main symptoms were hypomyelination, language delay, and intellectual disability or developmental delay. The mean age of onset for HLD9 in the group of 33 patients with a known age of onset was 5.8 months (SD = 8.1). The interquartile range of age of onset was 0–10 months. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 11 patients. Conclusion Pathogenic variants in RARS1 decrease ArgRS activity and cause a wide range of symptoms, from severe, early onset epileptic encephalopathy with brain atrophy to a mild condition with relatively maintained myelination. These symptoms include the classic hypomyelination presentation with nystagmus and spasticity. Furthermore, the pathogenicity of the variation c.2T>C (p.Met1Thr) has been shown.

Key clinical message Subungual Onycholemmal Cyst (SOC) is a rare nail abnormality with different clinical presentations which can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. It is necessary for dermatologists and dermatopathologist to be aware of this pathology to make the proper diagnosis and treatment. SOC is a rare nail abnormality which affects the dermis of the nail bed. SOC has different clinical presentations, including onychodystrophy, ridging, clubbing, thickening, pigmentation, or even normal appearance. It can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. In this report, we describe a 54‐year‐old man with unilateral second right finger nail onychodystrophy and onycholysis for 1 year. He did not have any history of recent trauma, pain, or bleeding. It was completely resected by surgery. Nail biopsy can contribute to the early diagnosis of SOC and improvement of treatment outcomes.

Abstract Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

Objectives: To investigate the level of troponin I and its association with mortality in patients with sepsis, severe sepsis, and septic shock. Materials and Methods: In general, 148 patients with sepsis, severe sepsis, and septic shock admitted to Kowsar hospital of Semnan in 2017-2019 were recruited in this study. Serum troponin levels were measured during the first 24 hours of admission. The second measurement was done in the next 48 hours, which aimed at increasing the likelihood of positive troponin over time. However, if the troponin was positive just once, the patient would be in the category of positive troponin. In addition, the patient’s prognosis was recorded within 30 days. Results: Based on the results, 27.7% had troponin levels higher than normal. The mortality rate in patients with normal and abnormal levels of troponin was 5.6% and 17.1%, respectively, which was a significant difference. The age of dead patients was significantly higher than the age of the living patients and the results showed that among the variables of gender, normal or abnormal level of troponin, age, and type of underlying infection, only age had a significant relationship with patients’ vital status. Conclusions: High levels of troponin were not effective in determining the prognosis of patients with sepsis, and only age had a significant relationship with patients’ vital status while the confirmation or rejection of this hypothesis will need further studies.