Search

BackgroundThe kallikrein-kinin system (KKS) is a complex biochemical pathway that plays a crucial role in regulating several physiological processes, including inflammation, coagulation, and blood pressure. Dysregulation of the KKS has been associated with several pathological conditions such as hereditary angioedema (HAE), hypertension, and stroke. Developing an accurate quantitative model of the KKS may provide a better understanding of its role in health and disease and facilitate the rapid and targeted development of effective therapies for KKS-related disorders.ObjectivesHere, we present a novel, detailed mechanistic model of the plasma KKS, elucidating the processes of Factor XII (FXII) activation, the kallikrein feedback loop, cleavage of high molecular weight kininogen leading to bradykinin (BK) production, and the impact of inhibitors.MethodsThe model incorporates both surface and solution-phase reactions of all proteins in the KKS, describing how binding site concentration affects the rate of surface reactions. The model was calibrated and validated using a variety of published and in-house experimental datasets, which encompass a range of dextran sulphate (DXS) concentrations to initiate contact activation and various KKS inhibitors to block bradykinin production.ResultsOur mathematical model showed that a trace amount of activated FXII is required for subsequent FXII activation. The model also reveals a bell-shaped curve relationship between the activation of the KKS and the number of DXS surface binding sites. Simulations of BK generation in healthy and HAE plasma demonstrated the impact of C1 esterase inhibitor (C1inh) deficiency via increased peak BK levels and accelerated formation in HAE plasma. The efficacy of KKS inhibitors, such as CSL312, ecallantide, and C1inh, was also evaluated, with CSL312 showing the most potent inhibition of BK generation.ConclusionsThe present model represents a valuable framework for studying the intricate interactions within the plasma KKS and provides a better understanding of the mechanism of action of various KKS-targeted therapies.

ABSTRACT Background and Aim Delay in diagnosis and treatment of lung cancer is thought to be a major cause of its poor outcomes. We evaluated the delays within the presentation to the initiation of diagnostic and therapeutic interventions amongst lung cancer patients in Southern Iran. Methods This cross‐sectional study was conducted from March 2019 to March 2021. The data collected through interview included socio‐demographic, medical and clinical findings, and the time intervals needed to visit physician, refer to specialist, request diagnostic procedures, reach diagnosis of lung cancer, and hospitalization. Results Eighty‐nine patients (58 males and 31 females) with a mean age of 61.01 ± 12.25 years were included. The median time of symptom presentation and first physician visit interval was 25 days. Sixty‐five days were spent for requesting, performing, and evaluating the diagnostic procedures. The median interval between diagnosis and initiation of treatment was 16 days. Totally, it took an average of 122 days from the presentation to the definite diagnosis of lung cancer. Patient‐, diagnosis‐, and treatment‐related delays were not significantly correlated with any of the demographic, socioeconomic, and clinical (disease stage, symptom) variables, as well as the diagnosis tool and the first physician who visited the patient (p > 0.05). Conclusions There was a significant delay but relatively similar to other countries in the diagnosis and treatment of lung cancer patients in Southern Iran. The largest portion of delay could be attributed to the raising clinical suspicion in the physicians, referral for diagnostic assessments, and the diagnosis process.

Abstract Purpose Malignant Mesothelioma (MM) is a rare malignancy of the serosa membranes with a high mortality rate and long latent period. The relationship between a group of mineral fibers known as asbestos and mesothelioma is now well accepted in which people can be exposed to these fibers by various means during their lifetime and has been its usage has banned in many countries, such as Iran, which announced its gradual elimination from 1999 over a period of 7 years by using safe substitutes. However, the mineral particles are able to sustain itself in the environment, air, water, and soil and on the other hand, symptoms may take up to half a century to develop in exposed individuals. Also, there remains a shortage of comprehensive investigation on the effects of asbestos exposure within the familial context (household or domestic exposure) or on individuals residing in proximity to asbestos mines or factories (environmental exposure). Based on the high number of MM cases in Iran, and also our hypothesis that residuals of asbestos in the environment and petroleum products may be the etiological factor for MM, we conducted this study to evaluate the clinic epidemiological features of MM in the south of Iran its relation to possible asbestos exposure. Methods In this study, we analyzed the demographic features and occupations of confirmed cases of MM in Shiraz, southern Iran along with the follow‐up of the patients’ disease from 2008 to 2018, while also comparing the features of our patients with a control group compromising of 105 non‐MM patients. Results Among the 35 confirmed cases of MM, with an average age of 61 years, 9 (25.7%) were female, and 26 (74.3%) were male. During our assessment, 12 patients had already died, with a mean time of 11.26 months post‐diagnosis. Our findings revealed a higher prevalence of MM among housekeepers and employees of oil companies. In comparison to the control group, individuals with occupational exposure and those residing near refinery locations were at a heightened risk of developing MM. However, based on regression analysis, only occupations associated with refineries exhibited a significant correlation with MM (p = 0.028; OR: 14.602; 95% CI: 1.328–160.499). Conclusion Both occupational and para‐occupational exposure demonstrated a significant correlation with MM, whereas our regression analysis did not affirm geographical and environmental factors as contributors to MM. Despite the industry's prohibition of direct asbestos usage, the persistent existence of asbestos particles in the environment for decades, coupled with the long latency period of MM, warrants further investigation. Health authorities and policymakers should recognize this potential hazard, prompting an enhancement of early detection within at‐risk groups.

Background: Diffuse large B cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin's lymphoma, characterized by remarkable molecular heterogeneity. This study evaluates the prevalence of MYC, BCL2, and BCL6 gene rearrangements among Iranian DLBCL patients.Method: This historical cohort study encompassed 152 patients drawn from six reference hospitals who participated in the research. Interphase dual-color break-apart fluorescence in situ hybridization (FISH) was applied to formalin-fixed paraffin-embedded DLBCL specimens categorized as "not otherwise specified" alongside 20 normal controls. Survival data was analyzed using the Kaplan-Meier method and the Log-Rank test.Results: Among the patients, 7 (4.8%), 4 (2.9%), and 15 (10.2%) exhibited MYC, BCL2, and BCL6 rearrangements, respectively. Additionally, 1.5% of the patients demonstrated double-hit (DH) characteristics with both MYC and BCL2 rearrangements, while no triple rearrangements were observed. The presence of rearrangements appeared to be independent of clinicopathological variables. Patients with rearrangements experienced reduced survival durations, with reductions of 26.6, 31.2, 9.1, and 34.2 months for MYC, BCL2, BCL6-rearranged, and DH tumors, respectively (P > 0.05). Adverse prognosis was associated with age, activated B-cell-like phenotype, disease stage, B symptoms, lactate dehydrogenase levels, and risk grouping according to the National Comprehensive Cancer Network (NCCN) International Prognostic Index.Conclusion: DLBCL cases featuring MYC, BCL2, and/or BCL6 translocations are relatively rare. Patients harboring these rearrangements tend to exhibit aggressive disease progression with shortened overall survival. However, these differences did not reach statistical significance, necessitating further research to validate the incorporation of such tests into the routine workup of DLBCL patients.

Under the influence of psychology and learning theories, education and the field of education have experienced significant changes; Thus, paying attention to the internal processes in learning provides a platform for dealing with topics such as “discussion”. The current research was conducted with the aim of identifying the components of discussion skills in the form of indicators, goals and dimensions and how to use them in architectural design education. The current research strategy is of qualitative type and for data analysis meta-composition and content analysis methods have been used consecutively. The results of the coding of documentary data and interviews in NVIVO software show that the components of discussion skills include 9 indicators, 3 goals and 2 dimensions. Indicators include: “participatory discussion”, “constructivist discussion”, “discussion connection and memory function”, “discussion link and accurate expression skills”, “discussion role in professional activities”, “discussion as an oral test”, “discussion as a design language”, “discussion as an interactive aspect of the design process” and “discussion as a visual test”. The purpose of the discussion has three basic reasons: first, to inform; second, to convince; third, to solve the problem. Finally, due to the special and unique nature of the visual sense in the field of architecture, if the two dimensions of “verbal discussion” and “visual discussion” are used in teaching architectural design at the same time based on the provided educational solutions, in addition to the attractiveness of learning and its potential cognitive benefits, it causes effective areas of learning development.

Abstract Currently, breast carcinoma is the most common form of malignancy and the main cause of cancer mortality in women worldwide. The metastasis of cancer cells from the primary tumor site to other organs in the body, notably the lungs, bones, brain, and liver, is what causes breast cancer to ultimately be fatal. Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%. Many researchers have focused on brain metastasis, but due to its complexities, many aspects of this process are still relatively unclear. To develop and test novel therapies for this fatal condition, pre-clinical models are required that can mimic the biological processes involved in breast cancer brain metastasis (BCBM). The application of many breakthroughs in the area of tissue engineering has resulted in the development of scaffold or matrix-based culture methods that more accurately imitate the original extracellular matrix (ECM) of metastatic tumors. Furthermore, specific cell lines are now being used to create three-dimensional (3D) cultures that can be used to model metastasis. These 3D cultures satisfy the requirement for in vitro methodologies that allow for a more accurate investigation of the molecular pathways as well as a more in-depth examination of the effects of the medication being tested. In this review, we talk about the latest advances in modeling BCBM using cell lines, animals, and tissue engineering methods.

Abstract The important association of erythropoietin (EPO) serum levels and chronic obstructive pulmonary disease (COPD) with anemia has been inadequately studied and remains a controversial issue. We aimed to shed light on this matter by comparing EPO levels in anemic and non-anemic COPD patients, along with a review of published literature. This cross-sectional study was conducted on COPD patients referred to the pulmonary clinic of Shahid Faghihi Hospital and Motahari clinic, Shiraz, Iran, for one year. We measured complete blood count, red blood cell indices, serum iron, TIBC and ferritin levels, serum EPO levels, and body mass index. Among 35 patients in this study, 28 males and 7 females were enrolled with a mean age of 54.57 ± 8.07 years. The average Forced expiratory volume in first second (FEV1) was 37.26 ± 7.33% and FEV1/FVC was 0.46 ± 0.12. Mean EPO levels were 30.29 ± 2.066 mU/mL. No statistically significant association was observed among erythropoietin levels and Hb, COPD severity, and age. There was no significant difference in EPO levels between anemic and non-anemic patients. EPO level, against the traditional expectation, didn’t increase in COPD patients. EPO production also didn’t compensate for the anemia of chronic disease which considers as a common comorbid disorder in these patients.

Abstract Background Recurrence of multiple myeloma is among the most challenging issues for patients and treating physicians reported after autologous stem cell transplantation. However, extramedullary involvement after chemotherapy and transplantation has been rarely reported, especially as pleural manifestations. Protein electrophoresis indicated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case. Case presentation A 48-year-old middle-eastern man was referred to our clinic with cough, dyspnea, fever, and left side pleural effusion. A year after chemotherapy and autologous bone marrow transplantation, the patient presented with features in favor of pleural relapse, without bone marrow involvement. Protein electrophoresis demonstrated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case. The patient was effectively treated with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide with no notable adverse effects. Conclusion Physicians should be aware of various presentations of multiple myeloma relapse, especially in autologous stem cell transplantation patients. Atypical and unique presentations such as the pleural involvement warrant further reporting of evidence to provide early management and treatment options.

در چند دهۀ اخیر، هویت کالبدی شهرهای ایرانی و بحران در ساختارهای معماری و شهرسازی ایران موضوع بحث و گفتگو صاحب‌نظران بوده است؛ درحالی‌که در حوزۀ معماری، کمبود قابل‌توجه در مطالعات مؤثر، دیده می‌شود. بررسی تحقیقات انجام‌شده و منابع مرتبط، نشان از عدم‌وجود مؤلفه‌ها و شاخص‌های روشن و مشخص در تبیین معماری ایرانی – اسلامی دارد و تناقض نظرات و عدم وجود توافق‌نظر در این زمینه نیز قابل تأکید است. این پژوهش با رویکرد فراترکیب به بررسی و تحلیل نظرات صاحب‌نظران در تحقیقات انجام‌شدۀ معتبر و با هدف تشخیص مؤلفه‌ها و شاخص‌های معماری ایرانی – اسلامی انجام پذیرفته است. یافته‌های تحقیق نشان می‌دهد که در میان مؤلفه‌ها «نظم» با 47 ارجاع، «تعامل معماری با طبیعت» با 39 ارجاع و «نمادگرایی» با 37 ارجاع، دارای بیشترین فراوانی هستند. علاوه‌بر فراوانی ارجاعات در این پژوهش، جهت افزایش دقت در وزن‌دهی به کدها از تکنیک آنتروپی شانون استفاده شده است؛ بنابراین با توجه به وزن‌دهی مؤلفه‌ها بر این اساس اولویت مؤلفه‌ها به این ترتیب شامل: تعامل معماری با طبیت، درون‌گرایی، نظم، ... می‌باشد که در 4 محور «رابطۀ انسان با خدا»، «رابطۀ انسان با اجتماع»، «رابطۀ انسان و محیط مصنوع» و «رابطۀ انسان و محیط طبیعی» تقسیم‌بندی شده است.اهداف پژوهش:شناخت مؤلفه‌ها و شاخص‌های معماری ایرانی –اسلامی.ارائۀ اولویت‌بندی مؤلفه‌های معماری ایرانی –اسلامی.سؤالات پژوهش:مؤلفه‌ها و شاخص‌های معماری ایرانی –اسلامی کدامند؟اولویت‌بندی مؤلفه‌های معماری ایرانی –اسلامی کدامند؟

Background: Creativity has an underlying role in architectural design and fostering creativity in architectural design is one of the important tasks of the education system in this field. Despite the great importance of the creativity, we see the multiplicity of incoherent and sometimes contradictory views on the definition of creativity and how it flourishes in students during the design process. Aims: The main purpose of this study was to identify the components of recognizing students' ability in designing creative architecture. Method: his research has an applied goal, and it has been conducted using an exploratory mixed method. The research is applied in terms of purpose and terms of the method is mixed research that was conducted in two main steps: qualitative (meta-synthesis) and quantitative (confirmatory factor analysis). The research community in the qualitative section includes documentary studies through Persian and Latin articles related to the research field, which were selected according to the inclusion criteria. In the quantitative part, the data collection tool was a researcher-made questionnaire that was distributed among the research community consisting of 150 professors of architectural design who were selected in a simple random method in 2020 after the collective approval of experts. The obtained model of this part of the research was confirmed Results: In the qualitative part, using meta-synthesis, for the components of capability in creative architectural design; Knowledge (implicit and explicit), skills (presentation skills, analytical analysis, self-regulation and social), thinking (creative, critical, visual-spatial, and analytical thinking), and motivation (internal and external) were extracted, which is a small part by a questionnaire with Using confirmatory factor analysis, all four components of knowledge, skills, thinking and motivation and their components were confirmed with 95% confidence level (p = 0.001) Conclusions: To promote the creativity of architectural design in students, it is necessary to cultivate not only the component of thinking but also knowledge, skills, and motivation.

Abstract Background Non‐small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with smoking being a critical risk factor. The identification of NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations, sensitized to tyrosine kinase inhibitors, has revolutionized treatment plans, resulting in improved clinical responses and reduced chemotherapy toxicity. This study aimed to assess the relationship between EGFR mutations and smoking patterns in patients diagnosed with lung adenocarcinoma referred to major pathologic laboratories. Methods This cross‐sectional study included 217 NSCLC patients aged above 18 years. Molecular abnormalities of the EGFR gene were analyzed by polymerase chain reaction amplification of exons 18–21 accompanied by Sanger sequencing. Then, the data were analyzed using the SPSS 26 software. Logistic regression analysis, χ2 test, and Mann–Whitney U test were used to evaluate the relation between EGFR mutations and smoking patterns. Results EGFR mutations were identified in 25.3% of patients, predominantly involving deletion in exon 19 (61.8%). For most of the mutant EGFR patients, the majority were nonsmokers (81.8%), and 52.7% were female patients. Besides, the median duration of smoking was 26 years and the median frequency of smoking was 23 pack‐years in the mutant EGFR group, both of which were lower compared to the wild mutant group. Moreover, female gender, current, and heavy smoking were significantly correlated with EGFR mutations based on the univariate logistic regression analysis (p: 0.004, 0.005, and 0.001, respectively). Conclusions Female gender and nonsmoker status were strongly associated with positive EGFR mutations. While guidelines traditionally recommended EGFR testing primarily for female nonsmokers with advanced NSCLC, our study in line with the recently published evidence has shown a significant prevalence of positive EGFR mutations among male patients and smokers. Therefore, routine mutation testing is suggested for all NSCLC patients. Considering the limited access to EGFR testing laboratories in developing countries, the results of such epidemiological surveys can assist oncologists in choosing the most suitable treatment plan.

In December 2019, the coronavirus disease-2019 (COVID-19) outbreak emerged in Wuhan, China. The World Health Organization officially declared it a pandemic on March 11, 2020. Reports indicated that the associated mortality of the infection is quite higher in the elderly, individuals with specific comorbidities (such as diabetes mellitus), and generally the ones with a compromised immune system. A cohort study in Wuhan, China, reported a dysregulated immune response in 452 patients with laboratory-confirmed COVID-19. As a result of this suppressed immune response, an increase in neutrophil to lymphocyte ratio, T lymphopenia, and a decrease in CD4+ T cells were all common laboratory findings, especially in severe cases.On the other hand, there is substantial evidence of T cell exhaustion in critically ill patients. Accordingly, the immune system seems to play an important role in the prognosis and pathogenesis of the disease. Therefore, this study aims to review the evidence on the immune response dysregulation in COVID-19 infection and the potential role of immunoregulatory treatments such as immune checkpoint inhibitors, interferons, and CD200 inhibitors in altering disease prognosis, especially in critically ill patients.

Background: All stages of an architectural design process, from research and analysis to form generation, require creativity. Therefore, in architecture, it is crucial to be familiar with creativity and use it correctly. Despite conducting various researches in this field, there is still no common understanding of how to evaluate creativity in architecture and most of the evaluations are based on subjective criteria, which has led to uncertainties and the impossibility of correct evaluation of the work. Aims: This study is aimed at identifying and prioritizing the components and indicators affecting the evaluation of architects' creativity. Method: This research has a applied goal, and it has been conducted using an exploratory mixed method. In the first step, the components and indicators were identified using the meta-synthesis method. By searching the databases with purposive sampling. In the quantitative section, data were collected using the questionnaire designed in 2020, and the questionnaires were distributed among 110 participants, including professors, architects, and the staff of the architecture-related management organizations in the city of Mashhad, Iran, who were selected using the cluster sampling method. After collecting the questionnaires and investigating them, they were subjected to confirmatory factor analysis. Results: The results approved the conceptual model, including the components; novelty, practicability, usefulness and the artistic aspect )P = .001(. Conclusions: The results approved novelty, practicability, usefulness and artistic aspect are the important components for the evaluation of architects' creativity in architectural design

Contemporary cities are increasingly involved in cut-throat competition in globalisation, with architecture playing an increasingly important role in this competition, despite insufficient attention paid to this in Iranian cities. Experts believe that contemporary architecture can create a variety of grounds for economic growth for citizens and attracting tourists. The present study aims to study how large-scale architectural projects effect urban development, and is based on available data from two large-scale buildings in Mashhad. The main question is how large-scale architectural projects can be effective in the development of urban economics, and how to identify and measure the added values created by architectural projects. The approach is quantitative, and based on the hedonic model and Difference in Differences method as an effective tool to measure the economic impact of architectural projects, the spill-over effects of architectural projects have been measured and evaluated. Based on the findings of this study, constructing large-scale buildings has resulted in a 50 percent increase in the value of adjacent apartment units, and had an impact on the pricing pattern of apartments in their vicinity. This increase is inversely proportional to the distance from projects in a radius of up to 500 to 750 meters, causing an increase of 15 to 25 percent in affected property values.The results indicate significant upwards effects of the formation of large-scale architecture projects on local business prosperity, which can be seen as effective in the growth of the urban economy.

In this research a novel four-coordinated silver(I) complex with N-donor chelating ligands with formula [Ag(L1)(L2)]NO3, (where 4,5-diazafluoren-9-one = L1 and N-(4,5-diazafluoren-9-ylidene)aniline = L2) has been prepared and characterized with spectroscopic methods (UV-Vis, FT-IR and 1HNMR), elemental analysis, and molar conductivity measurement. The DNA-complex binding mode has been investigated by electronic absorption titration, luminescence titration, and thermodynamic studies and the relationship between the structure and the biological properties has been discussed. The binding constants (Kb) and thermodynamic parameters (enthalpy, entropy, and Gibbs free energy changes) have been calculated. The theoretical studies of the complex structure in the DFT framework have predicted the tetrahedral N4 coordination geometry for Ag(I) center. The molecular docking has been carried out to determine the binding mode and the best orientation of the complex with DNA. The experimental and theoretical results reveal that the Ag(I) complex binds to CT-DNA with a moderate intercalation capability with the partial insertion of the planar ligands between the double-stranded DNA bases and binding constant of 1.66×105 M-1.

Ewing sarcoma (ES) is a highly aggressive bone and soft tissue tumor that occurs mainly in young children and adolescents and is associated with primary and metastatic disease. Intramedullary ES (either primary or secondary) is rare, and the ideal management remains inconclusive. We herein report intramedullary and extramedullary metastatic ES in a single patient. A 46-year-old woman was referred to our outpatient clinic from the oncology clinic with progressive paraparesis and paresthesia for 1 week prior to presentation. She had developed left clavicular ES 2 years earlier for which surgery and chemoradiotherapy had been performed. At the present evaluation, she was diagnosed with intramedullary thoracic and lumbar extradural masses. Thoracic surgery was performed, and a biopsy of the lesion was obtained. The diagnosis of ES was confirmed histopathologically, and she underwent adjuvant chemotherapy. Her neurological status did not improve after surgery, and she underwent rehabilitation and physical therapy. The lumbar lesion resolved with chemotherapy. Metastasis of ES to the spinal cord, especially intramedullary lesions, is extremely rare, and there is no standard management guideline. However, surgical decompression and adjuvant chemotherapy are the main treatments in these cases.

Abstract Epithelioid hemangioendothelioma is considered an uncommon tumor originating from vascular tissues. Although this disease is an extremely rare malignant cancer, its pleural subtype is even less common. We discuss a 68‐year‐old man with isolated pleural epithelioid hemangioendothelioma, along with a literature review of all similar cases.

Abstract Introduction Mental health problems as a consequence of cancer lower the quality of life of cancer patients. Despite increasing studies of breast cancer‐focused mobile health applications (m‐Health apps), there is less research on breast cancer patients' quality of life or well‐being. The purpose of this study is to develop and evaluate the usability and quality of an educational m‐Health app aimed at improving the resilience of breast cancer in women. Methods This study was conducted in four phases. It included extracting the requirements of the app through the nominal group technique. Based on these results, an m‐Health app was developed and evaluated in terms of usability and quality by two scales, System Usability Scale and Mobile App Rating Scale questionnaires, respectively. Finally, the role of patients' age and educational backgrounds in the use of the app was assessed. The relationship between learnability and usability of the app was measured by the T‐Test. Results The app was developed with three user interfaces. Its usability developed from the patient's point of view scored a remarkable score of 83.20 with a 95% confidence interval. This value was too indicative of high satisfaction with the usefulness and the possibility of recommending it to other cancer survivors. The results of the quality evaluation from an expert's point of view showed that this app had good functionality. Evaluation of the role of demographic information in the use of the app showed that it can be used for all age groups with different levels of education. The app did not differ significantly between learnability and usability. Conclusion The development of m‐Health apps, based on usability principles that are suitable for all age groups with different levels of education, is welcomed by cancer patients.

Abstract Background Although life-threatening hemorrhage is a usual manifestation of acute promyelocytic leukemia (APL), thrombotic events seem to be more common in APL compared to other subtypes of acute leukemia. The treatment and prophylaxis of thrombosis are controversial due to the high risk of bleeding caused by disseminated intravascular coagulation (DIC) and thrombocytopenia. To the best of our knowledge we report the first case of APL in a patient with prosthetic heart valves successfully treated with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). We hope this case report helps clinicians to manage different spectra of coagulopathy in APL successfully. Case presentation A 38-year-old Asian man presented with diagnosis of APL confirmed by bone marrow biopsy. He was on warfarin due to prosthetic mitral and aortic valves. He was at risk of both hemorrhagic events due to DIC and life-threatening valve thrombosis. Our management regimen included unfractionated heparin adjusted according to the platelet count to prevent both valve thrombosis and bleeding events. The patient tolerated treatment well without any hemorrhagic or thrombotic events, and complete molecular remission was achieved by ATRA and ATO without the need for chemotherapeutic agents. Conclusion Although this case is exceptional, a precise evaluation may be needed to select the appropriate dose and type of anticoagulant to treat a patient with APL.

Abstract Background Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response. Methods In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. “Control” group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). “Intervention” group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery. Results In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the “intervention” group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident. Conclusion Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the “intervention” group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity. Trial registration This trial was prospectively registered in IRCT.ir ( IRCT2017100136491N1 ). Date of registration: 19 November 2017.

Abstract Background Autophagy is a conserved recycling process in cells. However, the effects of autophagy on the remission and treatment response of acute myeloid leukemia (AML) patients have not been clarified. Methods The expression of MAP1LC3B, ATG5, ATG10, RB1CC1, and AMBRA1 genes was assessed in 32 newly diagnosed AML patients, 18 complete remission (CR) patients, and seven relapsed patients, as well as 15 controls, by real‐time polymerase chain reaction (PCR). Results The expression of all five genes was significantly higher in the newly diagnosed AML patients as compared to the controls (p

Background. Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim. The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods. In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results. Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control group) were used in the final analysis. Our findings showed that in the intervention and control groups, LVEF was dropped from 61.28 ± 7.36 to 51.57 ± 7.67 (difference (D) = −9.71 ± 11.95, p=0.003) and from 57.9 ± 7.29 to 50.2 ± 7.02% (D = −7.7 ± 5.93; p=0.001), respectively (between-group difference = −2.01%, p=0.26). CTRCD was detected in 11 patients in the control group (42.8%) and 10 in the intervention group (41.6%, p=0.51). Conclusion. Consumption of sildenafil for primary prevention of anthracycline-induced cardiac toxicity seems to be unbeneficial. This trial is registered with IRCT20180506039554N1.

Background: Lung cancer (LC) is the second most common and deadliest cancer in the world. Despite the control of the progressive course of LC in developed countries, studies indicate an increase in the incidence of the disease in developing countries. We designed a stepwise approach-based surveillance system for registering LC in our region (fars lung cancer registry “FaLCaRe” Project). Materials and Methods: A questionnaire was designed and agreed upon by the steering committee using the Delphi method. Variables in nine fields were divided into three groups based on their importance: core, expanded core, and optional. The web-based data bank software was designed. The informative site about LC and team services was designed and launched for professional and community (www.falcare.org) educational purposes. Results: 545 variables in nine fields were designed (20 core variables). Primary data of 39 LC patients (24 men and 15 women) with a mean age of 62 years were analyzed. Twenty-six patients had a history of smoking. Moreover, 39% and 26% of patients had a history of hookah smoking and opium use, respectively. Adenocarcinoma was the most prevalent pathologic findings in cases. More than 80% of patients were diagnosed in stages 3 and 4 of cancer. Conclusion: FaLCaRe Project with the capabilities seen in it can be used as a model for national LC registration. With continuous valid data registry about LC, it is possible to make decisions at the national level for control and management its consequences while drawing the natural history of the LC.

Aims & Backgrounds: Today, environmental developments, climate change, and energy problems are major challenges in the world. Although Iran has been at the beginning of sustainable development regarding the buildings sustainability evaluation systems and has developed general guidelines and standards in this area, no effective action has been taken about schools. The present study aim is to determine priorities and sustainability indicators of designing sustainable educational spaces in Iran. Methodology: This study is descriptive-analytical in nature and descriptive applied-development in terms of purpose. The method of data collection is library-based and questionnaires are completed by experts. Analytic Hierarchy Process (AHP) is used to determine the importance and weighting of components and indicators. Findings: Based on the hierarchical analysis of the components and indicators obtained from previous research, three components of energy, water and site design, as well as three indicators of water recycling, using renewable energy and optimizing water use for landscaping and irrigation were ranked as first to third. Conclusion: The tables and analytical charts showed that the priority and the rating of the effective factors on environmental sustainability in Iranian educational spaces include: energy, water, site design, indoor quality, materials, regional priority and design innovation. Among indicators, water recycling, renewable energy use and optimization of water use for landscaping and irrigation are ranked first to third.

As smart cities (SCs) emerge, the Internet of Things (IoT) is able to simplify more sophisticated and ubiquitous applications employed within these cities. In this regard, we investigate seven predominant sectors including the environment, public transport, utilities, street lighting, waste management, public safety, and smart parking that have a great effect on SC development. Our findings show that for the environment sector, cleaner air and water systems connected to IoT-driven sensors are used to detect the amount of CO2, sulfur oxides, and nitrogen to monitor air quality and to detect water leakage and pH levels. For public transport, IoT systems help traffic management and prevent train delays, for the utilities sector IoT systems are used for reducing overall bills and related costs as well as electricity consumption management. For the street-lighting sector, IoT systems are used for better control of streetlamps and saving energy associated with urban street lighting. For waste management, IoT systems for waste collection and gathering of data regarding the level of waste in the container are effective. In addition, for public safety these systems are important in order to prevent vehicle theft and smartphone loss and to enhance public safety. Finally, IoT systems are effective in reducing congestion in cities and helping drivers to find vacant parking spots using intelligent smart parking.

Background: In March 2020, the World Health Organization declared the novel COVID-19 infection a pandemic. Among high-risk patients infected by the virus, breast cancer patients are vulnerable to present more severe infections. Iran is among the countries with a high incidence of COVID-19 , and most of the routine activities of medical centers are affected by the epidemic disease. Thus, there is a need to make some modifications to international protocols for dealing with breast cancer in the affected countries. Methods: The headings of breast cancer management protocols have been discussed among the university-affiliated professors in different disciplines involved in breast cancer management. The discussions were done through a “WhatsApp” group considering the tiles and the latest news about COVID-19. Under each title, we provide the consensus of all members in the related disciplines. Recommendations and Conclusion: In each specialty, all members agreed to choose minimal intervention. The modifications aim to reduce the workload of the medical centers as well as to provide the least interface of the patients with the medical centers. The members know that some recommendations may interfere with the routine best-practice recommendations and decrease the quality measures in the patient's outcome. Therefore, these recommendations are valid just in epidemic COVID-19 situation in the country.

Introduction: Endovenous laser treatment (ELT) is a new treatment method for the reflux of the great saphenous vein. A successful ELT is dependent on the selection of optimum parameters required to achieve optimal vein damage while avoiding side effects including skin burns. The mathematical modeling of ELT can be used to understand the process of ELT. This study was conducted to examine the effect of laser pullback speed and the distance between the vein and skin on the performance of ELT. Material and Methods: The finite element method was used to develop optical-thermal damage models and simulate the process of ELT process. Firstly, light distribution was modeled using the diffusion approximation of the transport theory. On the second step, temperature rise was determined by solving the bioheat equation. Considering the temperature field, the extension of laser-induced tissue damage was estimated using Arrhenius model. Results: Regarding the results, pullback speed and the distance between the vein and the skin distance can affect the process of ELT. Moreover, the pullback speed of 1 mm/s, 2 mm/s, and 4mm/s were suitable for the treatment of varicose veins located in a depth of 15 mm, 10 mm, and 5 mm, respectively. Conclusion: In the ELT method, the pullback speed should be determined considering the geometry of the varicose vein segments, especially the distance between the skin and vein.

Primary renal carcinoid tumors are quite rare. The pathogenesis of these tumors is unknown due to lack of enterochromaffin cells in the kidney. Because of nonspecific clinical manifestations and radiologic features, they are commonly misdiagnosed. Hence, Primary renal carcinoid tumors should be considered in differential diagnosis of any renal mass. In the present case, a 26-year-old woman was presented with a renal mass and constipation. After partial nephrectomy, diagnosis of carcinoid tumor was confirmed.

Objectives: Stroke is the leading cause of long-term disability. Hand motor impairment resulting from chronic stroke may have extensive physical, psychological, financial, and social implications despite available rehabilitative treatments. The best time to start treatment for stroke, is in sub-acute period. Repetitive transcranial magnetic stimulation (rTMS) is a method of stimulating and augmenting the neurophysiology of the motor cortex in order to promote the neuroplastic changes that are associated with motor recovery. The purpose of this study was to compare the effects of repetitive transcranial magnetic stimulation protocols plus routine rehabilitation on hand motor functions and hand corticomotor excitability in stroke patients with hemiplegia with pure routine rehabilitation programs. Methods: This study was a randomized clinical trial which was performed on 24 patients with hemiplegia who were randomly divided in to three groups. One group (n=7), received high frequency repetitive transcranial magnetic stimulation (Hf rTMS) on lesioned M1 with routine rehabilitation program, and the other group (n=7), received rehabilitation program with low frequency repetitive transcranial magnetic stimulation stimulation (Lf rTMS) on nonlesined M1, and a control group (n=10), who were given only routine rehabilitation programs. The treatment was performed for 10 sessions, three times peri-test, Post and follow-up about neurophysiological contralesional hemisphere evaluations using record of MEP wave indices by single pulse TMS, and assessing functional wolf test and hand grip power of disabled hand by dynamometer. Results: The results demonstrated that the rest MEP threshold reduction in experimental group which received high frequency magnetic stimulation was statistically significant (P

Stable crystalline phosphorus ylides were obtained in excellent yields from the 1:1:1 addition reactions between triphenylphosphine and dialkyl acetylenedicarboxylates, in the presence of NH-heterocyclic compound, such as 6-chloro-2-benzoxazolethiol. These stable ylides exist in solution as a mixture of the two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. In the recent work, NMR study and the stability of the Z- and E-isomers were undertaken for the two rotamers of phosphorus ylides involving 6-chloro-2-benzoxazolethiol by atoms in molecules (AIM) and natural population analysis (NPA) methods. The relative energy for the two Z and E isomers was calculated at both HF/6-31G (d,p) and B3LYP/6-311++G (d,p) in the presence of a solvent medium (ethyl acetate) and gas phases. The results were in good agreement with those that obtained by the 1H, 31P and 13C NMR experimental data.

Background: Breast cancer is the most common cause of cancer in women. This tumor is hormone dependent tumor and oncologists use estrogen receptor (ER), progesterone receptor (PR) and HER2 for treatment of this malignancy. Androgens like testosterone and their receptors (AR) have a role in the pathophysiology of breast cancer but their clinical values are not clear. Method: AR expression was evaluated in 49 patients with breast cancers using immunohistochemistry. Testosterone was evaluated with ELISA. The relation of clinical characteristics and biomarkers with AR and testosterone were analyzed. According to the percentage of stained cells AR categorized to: AR-absent (0%), AR-poorly (1%-10%), AR-moderately (>10%-50%), and AR-highly (>50%) positive. Results: Among 49 patients with breast cancer, 34% were AR-positive and 44% of ERpositive and 22% of ER negative patients were AR-positive. There was no significant association between mean of testosterone and AR, ER, PR and HER2. AR was positive more frequently but not significantly statistically in older patients and patients less than 45 years of age. Testosterone level was higher in ER positive patients than ER negative and lower in AR positive patients than AR negative patients, but these findings were not statistically significant. ten persent of breast cancers were triple negative and AR was negative in all of them. Conclusion: Androgens and AR have role in pathophysiology of breast cancer and in the future one can use the potency of this pathway for the treatment of breast cancer.

Several novel mononuclear Zn(II) complexes, [Zn(bpy)L2], where bpy=2,2’-bipyridine and L=monoanions of phenylcyanamide (pcyd), 4-methylphenylcyanamide (4-Mepcyd), 3,5-dimethylphenylcyanamide(3,5-Me2pcyd),4-methoxyphenylcyanamide(4-MeOpcyd), 3,5-dimeth-oxyphenylcyanamide (3,5-MeO2pcyd), 3-chlorophenylcyanamide (3-Clpcyd), 2,3-dichlorophenyl-cyanamide (2,3-Cl2pcyd), 4-bromophenylcyanamide (4-Brpcyd), 1-naphthylcyanamide (1-ncyd), azophenylcyanamide (apcyd) and a dinuclear Zn(II) complex, [{Zn(terpy)}2(μ-adicyd)](PF6)2, where terpy = 2,2´:6´,2´´-terpyridine and adicyd = azodi (phenylcyanamide) dianion have been synthesized and characterized by elemental analysis, UV-vis, IR, 1H-NMR spectroscopic techniques and cyclicvoltammetry.The presence of only one sharp and intense absorption band for υ(N=C=N) around 2100-2180 cm-1 for all the monomer complexes provide evidence that both cyanamide legend are equivalent in the solid state and coordinated end-on by nitride nitrogen to Zn(II). This is also indicated by 1H-NMR spectra of the complexes. UV-vis spectra show one MLCT band that are associated with Zn(II)-pyridyl chromophores(t2g6 →π*). Blue shift of this band with increasing the polarity of solvent from CH3OH to DMSO is the reason for this assignment. The Zn(II) ion is redox innocent therefore, two irreversible oxidation peaks at positive potential and one reduction couple at the negative potential are assigned to sequential oxidation of two phenylcyanamide ligands and reduction of bipyridine, respectively.

Bioactive glass air abrasion is a conservative technique to remove initial decalcified tissue and caries. This study examined the shear bond strength of composite resin to sound and decalcified enamel air-abraded by bioactive glass (BAG) or alumina using etch-and-rinse and self-etch adhesives.Forty-eight permanent molars were root-amputated and sectioned mesiodistally. The obtained 96 specimens were mounted in acrylic resin; the buccal and lingual surfaces remained exposed. A demineralizing solution was used to decalcify half the specimens. Both sound and decalcified specimens were divided into two groups of alumina and bioactive glass air abrasion. In each group, the specimens were subdivided into two subgroups of Clearfil SE Bond or OptiBond FL adhesives (n=12). Composite resin cylinders were bonded on enamel surfaces cured and underwent thermocycling. The specimens were tested for shear bond strength. Data were analyzed using SPSS 16.0 and three-way ANOVA (α=0.05). Similar to the experimental groups, the enamel surface of one specimen underwent SEM evaluation.No significant differences were observed in composite resin bond strength subsequent to alumina or bioactive glass air abrasion preparation techniques (P=0.987). There were no statistically significant differences between the bond strength of etch-and-rinse and self-etch adhesive groups (P=1). Also, decalcified or intact enamel groups had no significant difference (P=0.918). However, SEM analysis showed much less enamel irregularities with BAG air abrasion compared to alumina air abrasion.Under the limitations of this study, preparation of both intact and decalcified enamel surfaces with bioactive glass air abrasion results in similar bond strength of composite resin in comparison with alumina air abrasion using etch-&-rinse or self-etch adhesives.

Malignant pleural effusion is one of the most common complications of advanced malignancies, leading to decreased quality of life and life expectancy. With the advent of new therapies, patients with malignant pleural effusion appear to be living longer than previously thought. In this cohort study,26 patients, with malignant pleural effusion at the initial diagnosis of primary cancer, who were referred to the Lung Cancer Clinic of Shahid Motahari Clinic affiliated with Shiraz University of Medical Sciences , were studied Information on age, sex, tumor type, mortality, survival rate after malignant pleural effusion, EGFR mutation (in lung cancer patients), and metastasis were evaluated. In the present study, 12 patients (46.2%) were male and 14 patients (53.8%) were female. The median survival of patients was 2 years (interquartile range 1-3 years). Five patients (19.2%) had breast cancer, 19 patients (77.1%) had lung cancer, and two patients (7.7%) had lymphoma. The highest survival after diagnosis was related to one of the lymphoma patients (five years). In lung and breast cancer patients, the median survival was two years (interquartile range 1.5, 3) and one year (interquartile range 1, 2.5), respectively. Although the present study was a small single-center study, due to the appropriate lifespan of malignant pleural effusion patients with new therapies, more comprehensive studies are needed to re-evaluate the survival of patients with malignant pleural effusion.