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Key Clinical Message The co‐occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Abstract Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co‐occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co‐occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67‐year‐old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti‐AchR‐Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late‐onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x‐ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co‐occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.

Abstract Drought is associated with adverse environmental and societal impacts across various regions. Therefore, drought monitoring based on a single variable may lead to unreliable information, especially about the onset and persistence of drought. Previous studies show vapor pressure deficit (VPD) data can detect drought onset earlier than other drought indicators such as precipitation. On the other hand, soil moisture (SM) is a robust indicator for assessing drought persistence. This study introduces a nonparametric multivariate drought index Vapor Pressure Deficit Soil moisture standardized Drought Index (VPDSDI) which is developed by combining VPD with SM information. The performance of the multivariate index in terms of drought onset detection is compared with the Standardized Precipitation Evapotranspiration Index (SPEI) and the Standardized Precipitation Index (SPI) for six major drought events across the United States including three rapidly developing drought events (this term refers to flash droughts that develop on monthly scales) and three conventional drought events. Additionally, the performance of the proposed index in detecting drought persistence is compared with the Standardized Soil moisture Index (SSI), which is an agricultural drought index. Results indicate the multivariate index detects drought onset always earlier than SPI for conventional events, but VPDSDI detects drought onset earlier than or about the same time as SPEI for rapidly developing droughts. In terms of persistence, VPDSDI detects persistence almost identical to SSI for both rapidly developing and conventional drought events. The results also show that combining VPD with SM reduces the high variability of VPD and produces a smoother index which improves the onset and persistence detection of drought events leveraging VPD and SM information.

Introduction: The extract of Thymus kotschyanus Boiss, in addition to its antioxidant properties, also has a marvellous anti-amyloidogenic effectthat can be used for the treatment of amyloidosis. The aim of this study was to prepare silver nanoparticles from the aqueous extract of mountain thyme (Thymus kotschyanus Boiss), to investigate its antioxidant and inhibitory effect on the production of amyloid nanofibrils (bovine serum album (BSA) as a model protein). Material & Methods: This study was conducted experimentally in the laboratory of Payam Noor University in Qom Province in 2022. First, nanoparticles were prepared from aqueous thyme extract and added to AgNo3 silver nitrate solution (one millimolar). ThenFTIR, EDX, DLSand SEM methods were used to study the properties and size of the nanoparticles. The removing of free radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was used to study the antioxidant effects of the extract and the Concorde absorption method was used to study the production of amyloid nanofibrils. The chemical composition of the extract was analysed using the gas chromatography method. For statistical analysis, descriptive statistics and ANOVA tests were used with SPSS software version 23. Findings: The phytochemical analysis of the extract revealed seven compounds. Most compounds were associated with 5,4-alpha-epoxy-3-methoxy (43.53%), 2-ethyl-piperidine-1-methyl (31.02%) and thymol (23.65%). The UV-Vis spectrum showed the highest absorbance at 460 nm. The SEM results confirmed the production of spherical nanoparticles with a size of 70-93 nm. The concentrations of 0.8 and 1 mg/ml of the extract were able to inhibit DPPH by more than 50%. The highest antioxidant activity in the sample containing 2 ml of the nanoparticle solution (sample 5) was 56.82%. The highest inhibition of amyloid nanofibril production was observed at a concentration of 2 mg/ml with 95%. Discussion & Conclusion: Thus, the synthesized nanoparticles have potent antioxidant and anti-amyloidogenic properties and can be used as antioxidants.

IntroductionSustainability is one of the considerable challenges we widely face these days. Transformation into a more vibrant life provides a city for social, economic, and environmental interaction in which people can prosper, and hence sustainable transportation comes into play. Accordingly, public concerns about sustainable solutions in the urban transportation industry have increased, followed by discussions on public transportation, taxi apps, and ride-sharing. On the other hand, with the increasing emergence and development of social networks, customers can freely express their opinions without being bound by predefined issues. Moreover, social network analytics is an opportunity for organizations to understand the priorities of a large portion of their customers while spending less time and money compared to traditional research methods such as surveys. Twitter is now an accessible and valuable resource to access customers' feedback and what is on their minds. The present study has tried to identify the mentality of users of a transportation system by using data mining and text mining on Twitter so that the factors affecting the tendency of people to use any urban transportation mode have been investigated and prioritized. This article provides a model for improving the sustainability of urban transportation systems.MethodologyGiven that conducting field research or quantitative studies is very expensive, and the information obtained in this way is limited to certain customers, analyzing the contents produced by users on social media is a necessity for any organization. Compared to conventional methods of communication, social media have unique features. This study used Twitter since it has the highest growth rate among all social media platforms. Using the sentiment analysis, we determine what aspects of the organizations' management should improve to ensure their sustainable performance. Twitter sentiment analysis provides an easy and reliable way for businesses to monitor people's feelings towards their brands, businesses, and stake holders.This research is of a based type and tries to design and develop a model for the purpose of evaluating sustainable transportation. used as data related to transportation and collected all the required information sources using hashtags and with the help of text mining technique which is also known as text analysis and sought to extract high-quality and desired information in the form of Structured use and then with the help of sentiment analysis, we explored the recognition of positive, negative and neutral emotions about transportation issues in the texts. In fact, by analyzing emotions, opinions, feelings, behaviors, tendencies and emotions written with a written language, we analyze them and proceed to the final analysis. The result of the analysis provides sustainable transportation tools for use by policy makers and transportation network investors.Results and DiscussionThe results of this analysis show that the price factor, according to Twitter users' feedback, has the greatest impact on choosing the type of transportation while maintaining stability. Other main and important factors besides "price", according to the statistics published in the analysis, are "air pollution", "traffic", "vehicle fuel", "vehicle model", "driver age", "salary" and passenger age, employment and usage, routing, parking and driver gender, and vehicle monitoring are ranked next in terms of the number of Twitter users, respectively.ConclusionContrary to the idea, in addition to important issues such as price, pollution, traffic and parking, car model, driver's age and even driver's gender and car cleanliness are also important for passengers. On the other hand, the salary and age of the passenger are also important for drivers. The placement of these indicators together leads to the belief that in today's society, as the society grows older, the complexity and tastes also increase, but on the other hand, the exchange of information becomes easier with the advancement of technology. The results of this study can be provided to investors, policy makers and customers of taxi applications to improve the sustainable transportation system. With the help of these results, investors design and invest in sustainable transportation systems and marketing programs according to the characteristics expected by customers and advance their advertising. Customers' willingness to use such a sustainable system will guide policy makers to develop sound policies regarding investors, customers, and citizens, and identify the needs of transportation customers to increase their satisfaction. Knowing the indicators, tastes and priorities of people in using means of transportation can be an opportunity for entrepreneurs and investors for entrepreneurship and investment in the field of urban transportation.

The purpose of this research was to design a distribution channel selection system in the supply chain of the oil industry using the combination of adaptive neural-fuzzy network and meta-heuristic algorithms (Case study: National Oil Products Distribution Company of the dual regions of West Azerbaijan). This research was based on the purpose of the research, developmental-applicative and based on the descriptive-modeling research method. The statistical population of this research was 185 axis sales, Sekodar and fuel supply stations in the two regions of North and South of West Azarbaijan province. In this research, questionnaires and documents were used to collect data. In order to analyze the data, confirmatory factor analysis, adaptive neural-fuzzy network in basic mode and adaptive neural-fuzzy network combined with genetic meta-heuristic algorithms and particle swarm have been used. In this research, first, the combined distribution channel selection system was designed, and then using the system designed based on the least error, the traditional distribution channel and the branding plan of the fuel stations were evaluated based on the input scores. The results show that the best system for selecting the distribution channel was the adaptive neural-fuzzy network combined with the particle swarm algorithm. By comparing the performance of the branding plan and the traditional method, it was determined that the branding plan has a better performance and is a suitable distribution channel for the National Oil Products Distribution Company of the dual regions of West Azerbaijan.Extended AbstractIntroductionRapid changes in consumer purchasing behavior, along with supply chain redesign, have caused both existing and new retailers to implement a variety of new inventory management strategies (Zhang et al., 2017; Melis et al., 2015). According to Forbes magazine, companies like Wal-Mart are known as the biggest companies in terms of sales (Forbes, 2014). The success of these companies is strongly related to the strategy and proper operations of the supply chain (Bogenrief, 2012). Some companies around the world (such as Amazon, Apple, Coca-Cola, Dell and Nike) attribute at least part of their success to supply chain management. At the same time, the results of the survey conducted in 2012 show that less than half of company managers recognize supply chain management as a strategic asset. In general, companies that recognize supply chain management as a strategic asset and use it in their daily processes, on average, achieve 70% higher financial performance (Kozlenkova et al., 2015). Since one of the main concerns of marketing is providing value to the consumer and the final user, an efficient supply chain is perhaps the most essential marketing function. Any mistake anywhere in the supply chain can have two-way effects for the company and its customers (Ellis, 2011). On the other hand, an effective and efficient supply chain allows companies to deliver higher value to final customers and improve results for the company.Marketing distribution channels are where the process of creating customer value in the supply chain is more prominent (Kozlenkova et al., 2015). Distribution channels and their proper use can help to increase the competitiveness of companies (Gong et al., 2023); therefore, distribution channel management is considered as an important task (Berling et al., 2023; Chen et al., 2014; Chiang, et al., 2003).Based on the above discussions, the approach of paying attention to the distribution channels in the supply chain is a problem that has led the researcher to conduct this research. This issue originated from two main areas. On one hand, the researcher's studies show that there is a lack of research in the field of choosing distribution channels in supply chain management, and the knowledge gap in this field is clearly visible. On the other hand, due to the fact that the National Oil Products Distribution Company of Iran, in a new approach, is looking for branding and creation of oil products distribution chain companies, which is the first of its kind in Iran; in such a situation, the need to design a supply chain distribution channel selection system in distribution companies can make it possible for managers of oil products distribution companies to choose appropriate distribution channels, develop appropriate cooperation, and understand priorities in relation to the members of the channel and identify the desired channel. In such a situation, methods such as artificial intelligence can be helpful. One of the methods of artificial intelligence is adaptive neural-fuzzy networks.Research methodologyThis research is applicable in terms of purpose, and descriptive-modeling in terms of the research method. Based on the nature of research variables, the statistical population of this research has been investigated in two parts. In the first part, the main statistical population of this research was axis sales, Sekodar and fuel supply stations in the two regions of North and South of West Azarbaijan Province.To determine the validity of the questionnaire, two relative coefficients of content validity and content validity index were used. The results of these two coefficients indicate the elimination of some measures and confirm the validity of the questionnaire. The final parameters of the research based on inputs and outputs are shown in table (3).Cronbach's alpha coefficient has been used to determine reliability. Reliability was determined based on the original sample, and the results showed that the value of Cronbach's alpha coefficient for all the main components was greater than 0.7, and based on this, the reliability of the questionnaire was confirmed.In order to analyze the data in this research, the ANFIS method and its combination with genetic meta-heuristic algorithm and particle swarm were used to design the supply chain distribution channel selection system in the National Oil Products Distribution Company.FindingsConfirmatory factor analysisIn order to verify the main components through the measured reagents, confirmatory factor analysis was used in Lisrel software. For confirmatory factor analysis, two categories of fit indices of the confirmatory model and factor loadings indicating the relationship between the main component and the indicators have been used. For the fit of the confirmatory model, the root mean square error of estimation (RMSEA) index, root mean square residual (RMR) index, goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI) and the normalized fit index (NFI) was used. The root mean square index of the estimation error should be less than 0.09, the residual mean square root index should be less than 0.05, and the values ​​of the goodness of fit, adjusted goodness of fit, comparative fit and normalized fit indices should be greater than 0.9; to be able to claim that the verification model correctly verifies the main component. In the second part, factor loadings and t values ​​have been used to investigate the relationship between the main component and the variables. From an empirical point of view, the value of each factor load should be greater than 0.5, and from a statistical point of view, the corresponding t value of each factor load should be greater than 1.96. The results are shown in table (4).The results of the suitability indices of the verification models in Table (4) show that the value of RMSEA is smaller than 0.09, the value of the RMR index is smaller than 0.05, the value of the goodness of fit indices, the adjusted goodness of fit, Adaptive fit and normalized fit are greater than 0.9. Also, the relative chi-square value was calculated smaller than 3, which indicated the appropriateness of all the verification models and the verification of the main input and output components in the model. Examining the relationship between the main component and the determinants through factor loadings also shows that all factor loadings are greater than 0.5. The statistical analysis of factor loadings through t values ​​also shows that the t value obtained for all factor loadings is greater than 1.96 and is significant. Therefore, the results obtained for the reagents and the main components can be confirmed in general. As an example, the output of the software for operating loads and t values ​​of the main component of channel tasks are shown in figures (3) and (4).Discussion and conclusionThis article was formed based on this main question: how is the appropriate system for choosing distribution channels in the supply chain of the oil industry using the combination of adaptive neural-fuzzy network and meta-heuristic algorithms in the National Oil Products Distribution Company of the dual regions of West Azerbaijan? To answer, first the literature and theoretical foundations of the research were reviewed; and in line with that, the variables and indicators affecting the selection of distribution channels in the supply chain of the distribution companies of the National Oil Products Distribution Company were extracted. In the next step, confirmatory factor analysis was used to confirm the main components through the measured indicators in the studied statistical population. After confirming the main components and specifying the inputs and outputs of the supply chain distribution channel selection system in distribution companies, first the adaptive neuro-fuzzy system in the basic state was implemented, and the error of each system using the indices of mean square error and root mean square error were calculated to determine the performance of each of them. After identifying the best adaptive neural-fuzzy system in the base state, in the second stage, the adaptive neural-fuzzy system is combined with meta-heuristic algorithms and finally the best distribution channel selection system in the supply chain of the National Oil Products Distribution Company in two regions of West Azarbaijan was determined based on the designed hybrid system.Based on the results obtained, it is suggested to the executives to increase the quality of the distribution channel in the supply chain by factors such as creating mutual trust, attention should be paid to the infrastructure and facilities of the place when granting representation, the quality of the human resources of the placeholders and the level of capital submitted by the placeholders, and, evaluate each of these cases with a detailed investigation. In the branding method, in order to promote the brand, it is necessary to establish mutual trust between the main brand and the established brand, and the established brand defines its identity based on the original brand. The use of specialized and trained manpower in the branding method to increase the quality of distribution is one of the main requirements in the issue of distribution in the branding method, which needs to be addressed by providing multiple trainings to the existing employees. Also, the main brand can help the incumbents in accessing financial resources and new investments in the form of low interest loans.

The conquest of Andalusia was completed during the caliphate of Walid bin Abdul Malik (86-96 A. H) and under the leadership of Musa bin Nasir (19-97 A. H) and Tariq bin Ziyad (101-50 A. H) during the years 92-95 A. H. As a result of this conquest, many tribes entered Andalusia. This article examines the report of Bayt Zul-Aqfal in Toledo aiming the how of different ethnic groups entering Andalusia and their influence in compiling historical reports.The findings of the research done through the descriptive-analytical method and analysis of historical documents, show that the conquest of Andalusia and the new ethnic and cultural composition of the inhabitants of this region led to the fictional stories and narratives taken from the historical culture of these people were added to the historiography of Andalusia. Therefore, the report of Bayt Zul-Aqfal in the conquest of Toledo is one of the fabricated narratives of the conquest of Andalusia, the story of which arosed from this cultural mixture and found its way into the historical sources.

Abstract Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients.

The question of time has always been one of the greatest questions of philosophers and physicists throughout history. Undoubtedly, every philosophical thought is manifested in different forms in literary and artistic works, and among them there are writers and artists who use philosophy as the basis of their works. Samuel Beckett is one of the most influential writers in shaping the school of thought of Absurd Theater, which has its roots in philosophy. This article purports to examine and express the issue of time in the play Waiting for Godot using the ideas of Martin Heidegger. Martin Heidegger looks at the question of "time" from an ontological point of view and in his divisions, he considers "time" in both original and non-original forms for Dasein (existence). As in the play Waiting for Godot, the most important action of the play "the issue of time" is the characters' conflict in the form of two Dasein. Thus, according to Heidegger's definition of the original and non-original "time" with which Dasein is involved in life, "time" was examined as the most important element in the play Waiting for Godot. To achieve this analysis, it was first necessary to provide an exhaustive definition of "time" in the philosophical thought of Heidegger and the philosophers before him, and then by examining the issue of wait and its meaning in Heidegger's "time", the play Waiting for Godot and the characters' continuous wait were interpreted. Analytical research has been used in this study and by examining Heidegger's thoughts and Samuel Beckett's the play Waiting for Godot, and using descriptive-analytical method, it has been tried to find the common ground between Beckett's thought on writing and performing the scenes of this play and Heidegger's philosophical thoughts to shed new light on its analysis and conducting.

Abstract Introduction The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. Methods In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. Results The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. Discussion A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.

Abstract Facilitated purification of proteins, at a low cost and a short time, is one of the key steps in the industrial production of recombinant proteins. In the current study, polydopamine nanoparticles (PDA-NPs) are considered in the synthesis of magnetic beads for purifying recombinant proteins due to advantages such as biocompatibility/ biodegradability, easy synthesis, as well as the ability to directly chelate metal ions. They were synthesized in Tris buffer (pH: 8:5), then chelated with Fe3+(20 mg) and Ni2+ ions at concentrations of 2, 3, 5, and 7 mg/ml. Prepared nanoparticles were characterized through scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), Inductively Coupled Plasma (ICP), and vibrating sample magnetometer (VSM). The size distribution of the particles was reported in the narrow range of 120–140 nm and 200 to 220 nm by the SEM image and DLS analysis, respectively. The chelation of ions on the surface of the nanoparticle was confirmed by the ICP technique with a magnetization of 35.42 emu/g. The highest adsorption rate of Ni2+ ions to polydopamine was obtained at a ratio of 1.4. The SDS-PAGE and western blot analysis confirmed the purification of eGFP and Hsp40 by PDA/Fe3+/Ni2+ at 26 and 40 kDa compared to the commercial nickel column. Moreover, the concentration of purified eGFP by PDA/Fe3+/Ni2+ was reported 138.83 µg/ml by the fluorescent signals, which is almost equal to or more than the protein purified by commercial Ni-NTA column (108.28 µg/ ml). The stability of PDA/Fe3+/Ni2+ has also been evaluated by ICP-OES for 10 days, and the result suggested that PDA magnetic beads were stable. Therefore, it can be concluded that PDA/Fe3+/Ni2+ have the ability to purify recombinant proteins in one less step and shorter time.

X-ray radiolytic labeling uses broadband X-rays for in situ hydroxyl radical labeling to map protein interactions and conformation. High flux density beams are essential to overcome radical scavengers. However, conventional sample delivery environments, such as capillary flow, limit the use of a fully unattenuated focused broadband beam. An alternative is to use a liquid jet, and we have previously demonstrated that use of this form of sample delivery can increase labeling by tenfold at an unfocused X-ray source. Here we report the first use of a liquid jet for automated inline quantitative fluorescence dosage characterization and sample exposure at a high flux density microfocused synchrotron beamline. Our approach enables exposure times in single-digit microseconds while retaining a high level of side-chain labeling. This development significantly boosts the method's overall effectiveness and efficiency, generates high-quality data, and opens up the arena for high throughput and ultrafast time-resolved in situ hydroxyl radical labeling.

Kalateh Pialeh prospect area is located in the Kopeh Dagh zone, approximately 15 km northeastern of Esfarayen city. The area is composed of sedimentary rocks deposited during the Jurassic, Cretaceous, and Tertiary periods, which include microconglomerate, dolomitic limestone, sandy limestone, limestone, conglomerate, and marl. Mineralization occurs as epigenetic deposits hosted by dolomitic limestone and limestone. Two mineralization stages were identified. The first stage consists of a pyrite-galena-sphalerite assemblage with replacement and breccia textures, and the second stage comprising a galena-sphalerite assemblage with vein-veinlet, open space filling, and replacement textures. Dolomite and calcite are the most abundant gangue minerals associated with lesser amount of quartz and barite. Main alterations consist of calcitization and dolomitization. Galena mineral exhibits maximum geochemical anomalies of 1843 ppm for zinc, 7 ppm for arsenic, and 11 ppm for copper. Microthermometric studies on primary fluid inclusions (LV) reveal homogenization temperatures ranging from 180°C to 265°C for stage 1, and from 167°C to 214°C for stage 2. Salinities for these stages were found to be between 7.8 wt.% to 14.5 wt.% NaCl equiv., and 11.7 wt.% to 12.2 wt.% NaCl equiv., respectively. Based on evidence such as structurally controlled mineralization, the type of alterations and their linear expansion, simple mineralogy of ore, geochemistry, and fluid inclusion data, Kalateh Pialeh prospect area is similar to lead-zinc epithermal deposits. Introduction Sediment-hosted Pb–Zn deposits are typically found in clastic-carbonate (Sedex type deposits) and carbonate (Irish type and Mississippi Valley-type (MVT) deposits) rocks (e.g., Goodfellow & Lydon, 2007). In Iran, the wide distribution of clastic and carbonate rocks has led to the formation of various types of sedimentary-hosted lead and zinc deposits.These deposits occur in Cretaceous carbonate units, including Malayer-Esfahan, Tabas- Poshte-Badam, Yazd-Anarak, and Central Alborz metallogenic belts (Rajabi et al., 2012). Kalateh Pialeh prospect area, located in Kopeh Dagh zone, about 15 km northeastern of Esfarayen city, is the first report of lead and zinc mineralization in this zone. Kopeh Dagh zone is characterized by the absence of magmatic activity, the presence of limestone formations, and abundant hydrocarbon reserves (such as Khangiran Gas Field). This study summarizes the alteration, mineralogy, geochemistry, and fluid inclusion studies, and then discuss the ore genesis of Kalateh Pialeh prospect area. Material and methods Following field work, thin sections and polished slabs from the host rocks, veins and veinlets were studied using optical microscope. Red alizarin was also used to differentiate between calcite and dolomite. Galena minerals were seperated from host rock by using standard techniques involving crushing and handpicking under a binocular microscope at Ferdowsi University of Mashhad. Minor and rare element metal concentrations from galena were analyzed using ICP-OES techniques on five samples at Zarazma laboratory in Iran, while XRD analysis of the samples was done at the same laboratory. Microthermometric analysis of fluid inclusions was carried out on seven samples using a Linkam THM 600 heating-freezing stage combined with an Olympus TH4–200 microscope stage at Ferdowsi University of Mashhad, Mashhad, Iran. Results and Discussion The area comprises sedimentary units of microconglomerate, dolomitic limestone, sandy limestone, limestone, conglomerate, and marl. Vein-type epigenetic mineralization occurs along fault zones with trending NW–SE/vertical dip in dolomitic limestone and limestone. Mineralization can be divided into two stages: Pyrite-galena-sphalerite assemblage (with replacement and breccia textures), and galena-sphalerite assemblage (with vein-veinlet, open space filling, and replacement textures). The main alterations consist of calcitization and dolomitization. The oxidation and weathering processes have resulted in the formation of hemimorphite, smithsonite, cerussite, goethite, and hematite in the ore zones. Gangue minerals consist of calcite and dolomite with lesser amounts of barite and quartz. Geochemical analyses of the galena mineral reveal maximum anomalies for zinc (1843 ppm), arsenic (7 ppm), and copper (11 ppm). Microthermometric studies on primary fluid inclusions (LV) show homogenization temperatures ranging from 180 to 265°C and from 167 to 214°C for stages 1 and 2, respectively. The fluid salinities for these stages range from 7.8 to 14.5 wt.% NaCl and from 11.7 to 12.2 wt.% NaCl, indicating a wide range of salinities.The temperature of ore-forming fluids in MVT deposits varies from 50 to 250°C, with the majority falling within the 70 to 170°C range , and their salinity is between 10 and 30 wt. % NaCl (Leach et al., 2010). In Kalateh Pialeh sam ples, primary fluid inclusions hosted in quartz crystals homogenize to the liquid phase at temperatures ranging from 167°C to 265°C, (mostly in the range of 80 to 200°C) and the average salinity of 11 wt. % NaCl. The salinity of the hydrothermal fluids at studied area varies from 7.8 to 14.5 wt. % NaCl. This wide range can be attributed to the mixing of two fluids with different salinities. These salinities can be divided into two groups with low salinity (7.8 to 10 wt. % NaCl) and high salinity (13.9 to 14.5 wt. % NaCl). The presence of two types of primary inclusions with different salinity but similar homogenization temperature is a sign of isothermal mixing of two fluids.

مقدمه: از هر چهار بیمار مبتلا به اختلالات روانپزشکی، یک نفر به درمان استاندارد پاسخ کافی نمی دهد و این امر منجر به بارهای فردی و اجتماعی می شود. مطالعه حاضر با هدف بررسی اثربخشی تقویت درمان فراشناختی با تحریک جریان مستقیم ترانس کرانیال (tDCS) در اختلال افسردگی اساسی انجام شد.روش کار: جامعه آماری این کارآزمایی بالینی را بیماران سرپایی مبتلا به اختلال افسردگی اساسی در شهر مشهد تشکیل می دادند. 45 بیمار به روش نمونه گیری هدفمند انتخاب و به طور تصادفی در سه گروه (گروه فعال (درمان فراشناخت غنی شده با tDCS)، گروه شم (درمان فراشناخت غنی شده با tDCS) و گروه فراشناخت قرار گرفتند. مداخله در 10 جلسه آموزشی 90 دقیقه ای انجام شد. همه بیماران به پرسشنامه افسردگی بک (BDI-II) و مقیاس افسردگی همیلتون (HAM-D) در مراحل پیش آزمون، پس آزمون و پیگیری پاسخ دادند. داده ها با استفاده از تحلیل کوواریانس چند متغیره و ANOVA برای اندازه گیری های مکرر مورد تجزیه و تحلیل قرار گرفت.یافته ها: نتایج نشان داد که بین نمرات افسردگی در سه مرحله تفاوت معنی داری وجود دارد (01/0> P). همچنین بین نمرات افسردگی در گروه های مذکور تفاوت معنی داری وجود داشت و این تفاوت در درمان فراشناختی غنی شده با tDCS بیشتر است.نتیجه‌گیری: بر اساس یافته‌ها، افزودن تحریک جریان مستقیم ترانس کرانیال (tDCS) به درمان فراشناختی تأثیر مثبتی بر درمان افسردگی در بیماران مبتلا به اختلال افسردگی اساسی دارد.

Abstract BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of Braf V600E in the intestinal tissue of an inducible mouse model. We show that Braf V600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, Braf V600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its increased expression in human serrated lesions. Functionally, the cholesterol lowering drug atorvastatin prevents the establishment of intestinal crypt hyperplasia in Braf V600E -mutant mice. Overall, our work unveils the long-term impact of Braf V600E expression in intestinal tissue and suggests that colorectal cancers with mutations in BRAF might be prevented by statins.

Background: Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with trastuzumab or develop resistance to it.Objective: To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index.Methods: The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared.Results: UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab.Conclusion: Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1.

Background: There are many debates on socioeconomic indicators influencing trauma outcomes.Objectives: This study aimed to determine the association between education as a socioeconomic indicator and trauma outcomes.Methods: This descriptive-analytical study was conducted on 30,448 trauma patients during 2016-2021. The data were based on the minimum dataset of the National Trauma Registry of Iran (NTRI) from six different trauma centers in various cities of the country. The variables used in this study included age, education level, marital status, cause of injury, Glasgow Coma Scale (GCS), intensive care unit (ICU) admission, Injury Severity Score (ISS), and in-hospital mortality. Logistic regression was used to investigate the association between independent variables and trauma outcomes.Results: The study included 30,448 trauma patients with male predominance (75.8%). The mean age was 36.9 years. The most frequent education level was secondary education, with 14,228 (46.6%). Education levels had significant relationships with ISS, death, and ICU admission (P

In this paper, systems of multivariate interval linear equations with complex interval coefficients are examined, and a novel linear algebra-based approach for locating all of their solutions is proposed. The key concept is to convert the system into a crisp polynomial system that is equivalent and allows for the use of the innovative computational features of Gröbner bases. It is possible to calculate all of the system's precise solutions at once after an appropriate Gröbner basis has been determined. Design is a condition for the presence of a solution in complex interval linear systems. In addition, an algorithm is devised to retrieve all solutions using the eigenvalue approach. In addition, a proportional case is solved using the provided approach to demonstrate its efficiency and efficacy. The given approach can locate all solutions for linear systems with complex intervals. Additionally, it determines the presence or absence of a solution for the system. We use the aforementioned technique in the context of circuit analysis to demonstrate the effectiveness of the findings obtained.