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Competing Interests: The authors declare that they have no conflict of interest.

SOX transcription factors are critical regulators of development, homeostasis and disease progression and their dysregulation is a common finding in various cancers. SOX9 belongs to SOXE family located on chromosome 17. MicroRNAs (miRNAs) possess the capacity of regulating different transcription factors in cancer cells by binding to 3'-UTR. Since miRNAs can affect differentiation, migration, proliferation and other physiological mechanisms, disturbances in their expression have been associated with cancer development. In this review, we evaluate the relationship between miRNAs and SOX9 in different cancers to reveal how this interaction can affect proliferation, metastasis and therapy response of cancer cells. The tumor-suppressor miRNAs can decrease the expression of SOX9 by binding to the 3'-UTR of mRNAs. Furthermore, the expression of downstream targets of SOX9, such as c-Myc, Wnt, PI3K/Akt can be affected by miRNAs. It is noteworthy that other non-coding RNAs including lncRNAs and circRNAs regulate miRNA/SOX9 expression to promote/inhibit cancer progression and malignancy. The pre-clinical findings can be applied as biomarkers for diagnosis and prognosis of cancer patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In addition to their educational role, resilient schools have a good capacity in response to disasters. Due to the large student population, the schools can be a safe and secure environment during disasters, in addition to maintaining their performance after. Given the role and importance of the schools, the impact of culture and environment on resilience, without any indigenous and comprehensive tool for measuring the resilience in Iran, the study aimed to design and psychometrically evaluate the measurement tools., Method: This study was conducted using a mixed-method sequential explanatory approach. The research was conducted in two main phases of production on items based on hybrid model and the psychometric evaluation of the tool. The second phase included validity (formal, content and construction) and reliability (multiplex internal similarity, consistency and reliability)., Result: The integration of systematic and qualitative steps resulted in entering 91 items into the pool of items. After formal and content validity, 73 items remained and 44 were omitted in exploratory factor analysis. A questionnaire with 5 factors explained 52.08% of total variance. Finally, after the confirmatory factor analysis, the questionnaire was extracted with 29 questions and 5 factors including "functional", "architectural", "equipment", "education" and "safety". Internal similarity and stability in all factors were evaluated as good., Conclusion: The result showed that the 29-item questionnaire of school resilience in emergencies and disasters is valid and reliable, that can be used to evaluate school resilience. On the other hand, the questionnaire on assessment of school resilience in disasters enables intervention to improve its capacity., Competing Interests: The authors have declared that no competing interests exist.

Although chemotherapy is a first option in treatment of cancer patients, drug resistance has led to its failure, requiring strategies to overcome it. Cancer cells are capable of switching among molecular pathways to ensure their proliferation and metastasis, leading to their resistance to chemotherapy. The molecular pathways and mechanisms that are responsible for cancer progression and growth, can be negatively affected for providing chemosensitivity. Small interfering RNA (siRNA) is a powerful tool extensively applied in cancer therapy in both pre-clinical (in vitro and in vivo) and clinical studies because of its potential in suppressing tumor-promoting factors. As such oncogene pathways account for cisplatin (CP) resistance, their targeting by siRNA plays an important role in reversing chemoresistance. In the present review, application of siRNA for suppressing CP resistance is discussed. The first priority of using siRNA is sensitizing cancer cells to CP-mediated apoptosis via down-regulating survivin, ATG7, Bcl-2, Bcl-xl, and XIAP. The cancer stem cell properties and related molecular pathways including ID1, Oct-4 and nanog are inhibited by siRNA in CP sensitivity. Cell cycle arrest and enhanced accumulation of CP in cancer cells can be obtained using siRNA. In overcoming siRNA challenges such as off-targeting feature and degradation, carriers including nanoparticles and biological carriers have been applied. These carriers are important in enhancing cellular accumulation of siRNA, elevating gene silencing efficacy and reversing CP resistance., (Copyright © 2021. Published by Elsevier Inc.)

Background: Superficial eye disorders are one of the most common complications of improper eye care in intensive care units that can lead to corneal ulcers and permanent eye damage. The aim of this study was to determine the effect of the implementation of eye care protocol on the incidence of infection and superficial eye disorders in patients admitted to intensive care units., Methods: This study was a cross-over clinical trial that was performed on 32 patients admitted to the intensive care unit with reduced or no blink reflex following loss of consciousness or receiving sedatives. The eye of the test group received eye care according to the protocol and the eye of the control group received the routine care of the ward. The data collection form included demographic and clinical information and the clinical score scale of superficial eye disorders, which were completed in 7 days for both eyes. Data analysis was performed by McNemar and Cochran tests with a 95 % confidence interval., Results: In the study of superficial eye disorders, the frequency of dacryorrhea and hyperemia was not significantly different in the second to seventh days in the control and test eyes (P < 0.05). The frequency of xerophthalmia was not significantly different between the control and the test eyes on the second to third days (P < 0.05), but there was a significant difference on the fourth, fifth, sixth, and seventh days (P = 0.0001). Also, the frequency of corneal opacity was not significantly different in the second and third days (P < 0.05), but in the fourth (P < 0.05), fifth, sixth, and seventh days, this difference was significant (P = 0.0001)., Conclusions: Based on the results, although the implementation of eye care protocol has been able to have a significant effect on reducing ocular complications and problems, routine eye care in the intensive care unit also has clinical effectiveness. Therefore, in order to prevent and completely eliminate eye disorders in the intensive care unit, more evidence and research are needed., Trial Registration: The trial was retrospectively registered on https://en.irct.ir/trial/43493 on 13 November 2019 (13.11.2019) with registration number [IRCT20140307016870N5]., (© 2021. The Author(s).)

Any surgical or preoperative treatment and diagnostic procedure may be associated with complications and risks. Therefore, introduction of complicated cases plays an important role in educating those involved in the diagnosis of patients. Generally, if a physician or a nurse is informed that an item is inadvertently left behind in a patient's body during surgery, he/she is obliged to take action by notifying the healthcare system authorities and informing the patient as soon as possible; otherwise, he/she has committed a disciplinary violation. Here we present a 27-year-old female patient with a history of renal failure with prolonged fever following a retained Shaldon catheter in a patient's chest., Competing Interests: The authors declared no potential conflict of interest with respect to the authorship and/or publication of this article.

We employed the density functionaly theory (DFT)-predicted regioselectivity of the intramolecular Scholl reaction in phenanthrene and dibenzo[ g , p ]chrysene frameworks to obtain π-extended mono and double [7]helicenes, respectively. The formation of these helical structures occurs despite the buildup of a large strain energy up to 30 kcal/mol compared with their most stable isomers. The twisted and strained structures were characterized and analyzed by experimental (NMR, UV-vis, emission, electrochemistry, and single-crystal X-ray diffraction) techniques and were further supported by DFT calculations.

The nuclear factor-kappaB (NF-κB) signaling pathway is considered as a potential therapeutic target in cancer therapy. It has been well established that transcription factor NF-κB is involved in regulating physiological and pathological events including inflammation, immune response and differentiation. Increasing evidences suggest that deregulated NF-κB signaling can enhance cancer cell proliferation, metastasis and also mediate radio-as well as chemo-resistance. On the contrary, non-coding RNAs (ncRNAs) have been found to modulate NF-κB signaling pathway under different settings. MicroRNAs (miRNAs) can dually inhibit/induce NF-κB signaling thereby affecting the growth and migration of cancer cells. Furthermore, the response of cancer cells to radiotherapy and chemotherapy may also be regulated by miRNAs. Regulation of NF-κB by miRNAs may be mediated via binding to 3 / -UTR region. Interestingly, anti-tumor compounds can increase the expression of tumor-suppressor miRNAs in inhibiting NF-κB activation and the progression of cancers. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can also effectively modulate NF-κB signaling thus affecting tumorigenesis. It is noteworthy that several studies have demonstrated that lncRNAs and circRNAs can affect miRNAs in targeting NF-κB activation. They can act as competing endogenous RNA (ceRNA) thereby reducing miRNA expression to induce NF-κB activation that can in turn promote cancer progression and malignancy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non-syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease-causing variants in known deafness-associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness-associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high-throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Novel imidazole-chalcone derivatives were designed and synthesized as tubulin polymerization inhibitors and anticancer agents. The antiproliferative activity of the imidazole-chalcone was assessed on some human cancer cell lines including A549 (adenocarcinoma human alveolar basal epithelial cells), MCF-7 (human breast cancer cells), MCF-7/MX (mitoxantrone resistant human breast cancer cells), and HEPG2 (human hepatocellular carcinoma cells). Generally, the imidazole-chalcone derivatives exhibited more cytotoxicity on A549 cancer cells in comparison to the other three cell lines, among them compounds 9j' and 9g showed significant cytotoxicity with IC 50 values ranging from 7.05 to 63.43 μM against all the four human cancer cells. The flow cytometry analysis of A549 cancer cells treated with 9g and 9j' displayed that these compounds induced cell cycle arrest at the G2/M phase at low concentrations and increased the number of apoptotic cells (cells in subG1 phase) at higher concentrations. They have also inhibited tubulin polymerization similar to combretastatin A-4 (CA-4). Annexin V binding staining assay in A549 cancer cells revealed that compound 9j' induced apoptosis (early and late). Finally, molecular docking studies of 9j' into the colchicine-binding site of tubulin presented the probable interactions of these compounds with tubulin., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Molecular compounds with permanent tubular architectures displaying radial π-conjugation are exceedingly rare. Their radial and axial delocalization presents them with unique optical and electronic properties, such as remarkable tuning of their Stokes shifts, and redox switching between global and local aromaticity. Although these tubular compounds display large internal void spaces, these attributes have not been extensively explored, thus presenting future opportunities in the development of materials. By using cutting-edge synthetic methodologies to bend aromatic surfaces, large opportunities in synthesis, property discovery, and applications are expected in new members of this family of conjugated molecular nanotubes., (© 2021 Wiley-VCH GmbH.)

Glioblastoma multiforme (GBM) is one of the worst brain tumors arising from glial cells, causing many deaths annually. Surgery, chemotherapy, radiotherapy and immunotherapy are used for GBM treatment. However, GBM is still an incurable disease, and new approaches are required for its successful treatment. Because mutations and amplifications occurring in several genes are responsible for the progression and aggressive behavior of GBM cells, genetic approaches are of great importance in its treatment. Small interfering RNA (siRNA) is a new emerging tool to silence the genes responsible for disease progression, particularly cancer. SiRNA can be used for GBM treatment by down-regulating genes such as VEGF, STAT3, ELTD1 or EGFR. Furthermore, the use of siRNA can promote the chemosensitivity of GBM cells. However, the efficiency of siRNA in GBM is limited via its degradation by enzymes, and its off-targeting effects. SiRNA-loaded carriers, especially nanovehicles that are ligand-functionalized by CXCR4 or angiopep-2, can be used for the protection and targeted delivery of siRNA. Nanostructures can provide a platform for co-delivery of siRNA plus anti-tumor drugs as another benefit. The prepared nanovehicles should be stable and biocompatible in order to be tested in human studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Carriers of the m.3243A>G variant typically manifest with stroke-like episodes (SLEs), of which the morphological correlate on imaging is the stroke-like lesion (SLL). The pathophysiology of SLLs is poorly understood but acute and chronic stages are delineated. Here we present the case of an m.3243A>G carrier who presented with hypometabolism during his second SLL. The patient was a 56-year-old male who was diagnosed with MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) at the age of 50 upon a third SLE, muscle biopsy, and the detection of the m.3243A>G variant in the muscle. A fluorodeoxyglucose-positron emission tomography (FDG-PET) during the second SLE revealed hypometabolism in the occipital lobes bilaterally. The patient was misdiagnosed for years and was repeatedly exposed to mitochondrion-toxic drugs (metformin, steroids, valproic acid, oxcarbazepine, zolpidem). The previous data and the present findings indicate that the hypometabolism on FDG-PET together with reduced oxygen-extraction fraction (OEF) on OEF-MRI and hyperperfusion on perfusion-weighted imaging (PWI) characterise best the acute stage of an SLL. In conclusion, an acute SLE in m.3243A>G carriers typically manifests with a mismatch between hyperperfusion on PWI or single-photon emission computed tomography (SPECT) and hypometabolism on FDG-PET and hypointensity on OEF-MRI. Since SLEs are not vascular events, they should be managed by a multispecialist approach and not by general or stroke neurologists., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Finsterer et al.)

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor and its induction is of significant importance for protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) stimulate Nrf2 signaling, enhancing the activity of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. These enzymes are associated with retarding oxidative stress. On the other hand, Nrf2 activation in cancer cells is responsible for the development of chemoresistance due to disrupting oxidative mediated-cell death by reducing ROS levels. Cisplatin (CP), cis-diamminedichloroplatinum(II), is a potent anti-tumor agent extensively used in cancer therapy, but its frequent application leads to the development of chemoresistance as well. In the present study, association of Nrf2 signaling with chemoresistance to CP and protection against its deleterious effects is discussed. Anti-tumor compounds, mainly phytochemicals, retard chemoresistance by suppressing Nrf2 signaling. Upstream mediators such as microRNAs can regulate Nrf2 expression during CP chemotherapy regimens. Protection against side effects of CP is mediated via activating Nrf2 signaling and its downstream targets activating antioxidant defense system. Protective agents that activate Nrf2 signaling, can ameliorate CP-mediated ototoxicity, nephrotoxicity and neurotoxicity. Reducing ROS levels and preventing cell death are the most important factors involved in alleviating CP toxicity upon Nrf2 activation. As pre-clinical experiments advocate the role of Nrf2 in chemoprotection and CP resistance, translating these findings to the clinic can provide a significant progress in treatment of cancer patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

Mechanism-based inactivation (MBI) refers to the metabolic bioactivation of a xenobiotic by cytochrome P450s to a highly reactive intermediate which subsequently binds to the enzyme and leads to the quasi-irreversible or irreversible inhibition. Xenobiotics, mainly drugs with specific functional units, are the major sources of MBI. Two possible consequences of MBI by medicinal compounds are drug-drug interaction and severe toxicity that are observed and highlighted by clinical experiments. Today almost all of these latent functional groups (e.g., thiophene, furan, alkylamines, etc.) are known, and their features and mechanisms of action, owing to the vast experimental and theoretical studies, are determined. In the past decade, molecular modeling techniques, mostly density functional theory, have revealed the most feasible mechanism that a drug undergoes by P450 enzymes to generate a highly reactive intermediate. In this review, we provide a comprehensive and detailed picture of computational advances toward the elucidation of the activation mechanisms of various known groups with MBI activity. To this aim, we briefly describe the computational concepts to carry out and analyze the mechanistic investigations, and then, we summarize the studies on compounds with known inhibition activity including thiophene, furan, alkylamines, terminal acetylene, etc. This study can be reference literature for both theoretical and experimental (bio)chemists in several different fields including rational drug design, the process of toxicity prevention, and the discovery of novel inhibitors and catalysts.

Uncontrolled growth and metastasis of cancer cells is an increasing challenge for overcoming cancer, and improving survival of patients. Complicated signaling networks account for proliferation and invasion of cancer cells that need to be elucidated for providing effective cancer therapy, and minimizing their malignancy. Long non-coding RNAs (lncRNAs) are RNA molecules with a length of more than 200 nucleotides. They participate in cellular events, and their dysregulation in a common phenomenon in different cancers. Noteworthy, lncRNAs can regulate different molecular pathways, and signal transducer and activator of transcription 3 (STAT3) is one of them. STAT3 is a tumor-promoting factors in cancers due to its role in cancer proliferation (cell cycle progression and apoptosis inhibition) and metastasis (EMT induction). LncRNAs can function as upstream mediators of STAT3 pathway, reducing/enhancing its expression. This dual relationship is of importance in affecting proliferation and metastasis of cancer cells. The response of cancer cells to therapy such as chemotherapy and radiotherapy is regulated by lncRNA/STAT3 axis. Tumor-promoting lncRNAs including NEAT1, SNHG3 and H19 induces STAT3 expression, while tumor-suppressing lncRNAs such as MEG3, PTCSC3 and NKILA down-regulate STAT3 expression. Noteworthy, upstream mediators of STAT3 such as microRNAs can be regulated by lncRNAs. These complicated signaling networks are mechanistically described in the current review., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Prostate cancer is the second most leading and prevalent malignancy around the world, following lung cancer. Prostate cancer is characterized by the uncontrolled growth of cells in the prostate gland. Prostate cancer morbidity and mortality have grown drastically, and intensive prostate cancer care is unlikely to produce adequate outcomes. The synthetic drugs for the treatment of prostate cancer in clinical practice face several challenges. Quercetin is a natural flavonoid found in fruits and vegetables. Apart from its beneficial effects, its plays a key role as an anti-cancer agent. Quercetin has shown anticancer potential, both alone and in combination. Therefore, the current study was designed to collect information from the literature regarding its therapeutic significance in the treatment of prostate cancer. Studies performed both in vitro and in vivo have confirmed that quercetin effectively prevents prostate cancer through different underlying mechanisms. Promising findings have also been achieved in clinical trials regarding the pharmacokinetics and human applications of quercetin. In the meantime, epidemiological studies have shown a negative correlation between the consumption of quercetin and the incidence of prostate cancer, and have indicated a chemopreventive effect of quercetin on prostate cancer in animal models. The major issues associated with quercetin are its low bioavailability and rapid metabolism, and these require priority attention. Chemoresistance is another main negative feature concerning prostate cancer treatment. This review highlights the chemotherapeutic effect, chemo preventive effect, and chemoresistance elimination potential of quercetin in prostate cancer. The underlying mechanisms for elimination of prostate cancer and eradication of resistance, either alone or in combination with other agents, are also discussed. In addition, the nanoscale delivery of quercetin is underpinned along with possible directions for future study.

Prostate cancer is considered to be the most common solid cancer affecting men worldwide and leading to a significant morbidity and mortality. Metastases are usually seen in bone or lymph nodes. For recurrent disease, PET imaging with 68 Ga-PSMA-11 (also known as HBED-CC, Glu-urea-Lys(Ahx)-HBED-CC, and PSMA-HBED-CC) is widely used. However, preparation of 68 Ga-PSMA ligand requires the presence of radiochemistry facilities and can therefore not be utilized in centers lacking such facilities. Recently, copper labeled prostate-specific membrane antigen positron emission tomography ( 64 Cu-PSMA PET/CT) demonstrated promising results in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. In the present case, a rare manifestation site of a metastatic lesion in a patient with advanced prostate cancer is detected by 64 Cu-PSMA PET/CT., (© 2021 mums.ac.ir All rights reserved.)

Cancer still remains as one of the leading causes of death worldwide. Metastasis and proliferation are abnormally increased in cancer cells that subsequently, mediate resistance of cancer cells to different therapies such as radio-, chemo- and immune-therapy. MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate expression of target genes at post-transcriptional level and capable of interaction with mRNA-coding genes. Vital biological mechanisms including apoptosis, migration and differentiation are modulated by these small molecules. MiRNAs are key players in regulating cancer proliferation and metastasis as well as cancer therapy response. MiRNAs can function as both tumor-suppressing and tumor-promoting factors. In the present review, regulatory impact of miRNA-338-3p on cancer growth and migration is discussed. This new emerging miRNA can regulate response of cancer cells to chemotherapy and radiotherapy. It seems that miRNA-338-3p has dual role in cancer chemotherapy, acting as tumor-promoting or tumor-suppressor factor. Experiments reveal anti-tumor activity of miRNA-338-3p in cancer. Hence, increasing miRNA-338-3p expression is of importance in effective cancer therapy. Long non-coding RNAs, circular RNAs and hypoxia are potential upstream mediators of miRNA-338-3p in cancer. Anti-tumor agents including baicalin and arbutin can promote expression of miRNA-338-3p in suppressing cancer progression. These topics are discussed to shed some light on function of miRNA-338-3p in cancer cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19-24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.

Based on the high incidence and mortality rates of cancer, its therapy remains one of the most vital challenges in the field of medicine. Consequently, enhancing the efficacy of currently applied treatments and finding novel strategies are of great importance for cancer treatment. Venoms are important sources of a variety of bioactive compounds including salts, small molecules, macromolecules, proteins, and peptides that are defined as toxins. They can exhibit different pharmacological effects, and in recent years, their anti-tumor activities have gained significant attention. Several different compounds are responsible for the anti-tumor activity of venoms, and peptides are one of them. In the present review, we discuss the possible anti-tumor activities of venom peptides by highlighting molecular pathways and mechanisms through which these molecules can act effectively. Venom peptides can induce cell death in cancer cells and can substantially enhance the efficacy of chemotherapy and radiotherapy. Also, the venom peptides can mitigate the migration of cancer cells via suppression of angiogenesis and epithelial-to-mesenchymal transition. Notably, nanoparticles have been applied in enhancing the bioavailability of venom peptides and providing targeted delivery, thereby leading to their elevated anti-tumor activity and potential application for cancer therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Sight is one of the most important and vital human senses. Lack of proper eye care (EC) in anesthetized patients can lead to serious ocular complications and even vision loss. Insufficient knowledge, attitude, and skills of nurses are considered as a barrier to providing EC in the intensive care unit (ICU). The aim of the present study was to determine the effect of training EC clinical practice guidelines for ICU patients on nurses' knowledge, attitude, and practice of EC., Methods: This was an interventional study with a pre-post design performed on 60 ICU nurses. For the experimental group, EC clinical guideline training was performed for anesthetized patients in three sessions. The data collection tool included nurses' clinical competence of the EC questionnaire with a possible score range of 0-86. This tool consists of three domains, including knowledge (0-18), attitude (0-28), and practice (0-40), which was completed in a self-assessment manner before and three months after the training program. Data analysis was carried out using SPSS16. Findings . The mean scores of knowledge, attitude, and practice after the intervention in the experimental and control groups were 15.03 ± 2.72 and 11.11 ± 3.50, 25.65 ± 3.47 and 22.07 ± 3.08, and 33.88 ± 4.14 and 28.5 ± 55.08, respectively, which were statistically significant ( P ≤ 0.001). Also, the total score of clinical competence of EC after the intervention in the experimental and control groups was 74.56 ± 7.93 and 61.74 ± 9.66, which showed a significant difference ( P ≤ 0.001)., Conclusion: Training nurses based on EC clinical guidelines for anesthetized patients can improve the knowledge, attitude, and practice of ICU nurses. Evidence-based EC practice requires continuous training based on clinical guidelines and EC practice monitoring by nursing managers according to EC clinical guideline for an anesthetized patient., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zakieh Momeni Mehrjardi et al.)

Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.

Effective cancer therapy requires identification of signaling networks and investigating their potential role in proliferation and invasion of cancer cells. Among molecular pathways, signal transducer and activator of transcription 3 (STAT3) has been of importance due to its involvement in promoting proliferation, and invasion of cancer cells, and mediating chemoresistance. In the present review, our aim is to reveal role of STAT3 pathway in bladder cancer (BC), as one of the leading causes of death worldwide. In respect to its tumor-promoting role, STAT3 is able to enhance the growth of BC cells via inhibiting apoptosis and cell cycle arrest. STAT3 also contributes to metastasis of BC cells via upregulating of MMP-2 and MMP-9 as well as genes in the EMT pathway. BC cells obtain chemoresistance via STAT3 overexpression and its inhibition paves the way for increasing efficacy of chemotherapy. Different molecular pathways such as KMT1A, EZH2, DAB2IP and non-coding RNAs including microRNAs and long non-coding RNAs can function as upstream mediators of STAT3 that are discussed in this review article., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: It is so difficult to formulate human growth hormone (hGH) in a solution with high stability and new drug delivery system (NDDs) due to physiochemical instability. The purpose of this study was to investigate the possibility of using Tris as a hGH stabilizer., Materials and Methods: In this experimental study, the role of tris(hydroxymethyl)aminomethane (Tris) was evaluated as a hGH stabilizing agent in phosphate buffer, as a practical aqueous solution and a media to release NDDs. Highperformance liquid chromatography (HPLC) and enzyme-linked immune sorbent assay (ELISA) were applied to investigate the stability of hGH in solutions and dynamic light scattering (DLS) was used to measure the effect of Tris on the hydrodynamic size of hGH in aqueous solutions. Ultra violet (UV) spectrophotometry was used to check the hGH spectrum. In computational study, formation of ligand-protein complex of the Tris-hGH, and the intermolecular interactions between Tris and hGH were studied by molecular docking modeling., Results: The results demonstrated that Tris at the optimum concentration, increases hGH stability in aqueous solutions. Also, molecular docking modeling confirmed that amino acid residues such as tyrosine (Tyr), proline (Pro), glutamic acid (Glu), aspartic acid (Asp), leucine (Leu), and phenylalanine (Phe) in hGH structure, were linked with Tris as a ligand., Conclusion: It seems that interactions between hGH and Tris are the most important reason for increment of the physicochemical stability of hGH in aqueous solutions containing Tris., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Background: To assess prevalence and predictive factors for Nosocomial Infection (NI) in the military hospitals., Methods: PubMed, Scopus, Cochrane and PreQuest databases were systematically searched for studies published between Jan 1991 and Oct 2017 that reported the prevalence of NI and predictive factors among military hospitals. We performed the meta-analysis using a random effects model. Subgroup analysis was done for heterogeneity and the Egger test to funnel plots was used to assess publication bias., Results: Twenty-eight studies with 250,374 patients were evaluated in meta-analysis. The overall pooled estimate of the prevalence of NI was 8% (95% 6.0-9.0). The pooled prevalence was 2% (95% CI: 2.0-3.0) when we did sensitivity analysis and excluding a study. The prevalence was highest in burn unit (32%) and ICU (15%). Reported risk factors for NI included gender (male vs female, OR: 1.45), age (Age≥65, OR: 2.4), diabetes mellitus (OR: 2.32), inappropriate use of antibiotics (OR: 2.35), received mechanical support (OR: 2.81), co-morbidities (OR: 2.97), admitted into the ICU (OR: 2.26), smoking (OR: 1.36) and BMI (OR: 1.09)., Conclusion: The review revealed a difference of prevalence in military hospitals with other hospitals and shows a high prevalence of NI in burn units. Therefore careful disinfection and strict procedures of infection control are necessary in places that serve immunosuppressed individuals such as burn patient. Moreover, a vision for the improvement of reports and studies in military hospitals to report the rate of these infections are necessary., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2021 Teymourzadeh et al. Published by Tehran University of Medical Sciences.)

Molecular compounds with zigzag carbon nanotube geometries are exceedingly rare. Here we report the synthesis and characterization of carbon-based nanotubes with zigzag geometry, best described as radially oriented [ n ]cyclo- meta -phenylenes, extending the tubularene family of compounds. By the incorporation of edge-sharing benzene rings into the tubularene's radial π-surface, we have uncovered the first step to give rise to the emergence of radial orbital distribution in zigzag nanorings.

The successful use of theranostic twins in neuroendocrine tumors (NET) is the pioneering approach to radionuclide therapy in other tumor types. 64 Cu/ 18 F PSMA for molecular imaging with PET-CT and peptide radioligand therapy (PRLT) with 177Lu labeled PSMA inhibitors are the next theranostic twins in nuclear medicine. 68 Ga/ 64 Cu/ 18 F PSMA PET-CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity and can be used to select patients for PRLT and evaluate therapy response. Radionuclide therapy with 177 Lu-PSMA inhibitors has been shown to be effective in the treatment of metastatic CRPC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Similarity analysis of protein structure is considered as a fundamental step to give insight into the relationships between proteins. The primary step in structural alignment is looking for the optimal correspondence between residues of two structures to optimize the scoring function. An exhaustive search for finding such a correspondence between two structures is intractable. Methods: In this paper, a hybrid method is proposed, namely GADP-align, for pairwise protein structure alignment. The proposed method looks for an optimal alignment using a hybrid method based on a genetic algorithm and an iterative dynamic programming technique. To this end, the method first creates an initial map of correspondence between secondary structure elements (SSEs) of two proteins. Then, a genetic algorithm combined with an iterative dynamic programming algorithm is employed to optimize the alignment. Results: The GADP-align algorithm was employed to align 10 'difficult to align' protein pairs in order to evaluate its performance. The experimental study shows that the proposed hybrid method produces highly accurate alignments in comparison with the methods using exactly the dynamic programming technique. Furthermore, the proposed method prevents the local optimal traps caused by the unsuitable initial guess of the corresponding residues. Conclusion: The findings of this paper demonstrate that employing the genetic algorithm along with the dynamic programming technique yields highly accurate alignments between a protein pair by exploring the global alignment and avoiding trapping in local alignments., (© 2021 The Author(s).)

Background: Suicide is a serious public health concern. An increased risk of suicide ideation previously has been reported among survivors of childhood cancer., Methods: Suicide mortality was assessed for all potentially eligible survivors (those aged ≥18 years who were ≥5 years after their cancer diagnosis; 7312 survivors). Risk factors for acute suicidal ideation were assessed among clinically evaluated survivors (3096 survivors) and the prevalence of acute ideation was compared with that of community controls (429 individuals). The prevalence of 12-month suicidality was assessed among survivors who could be compared with population data (1255 survivors). Standardized mortality ratios compared rates of suicide mortality among survivors with those of the general population. Risk ratios (RRs) and 95% confidence intervals (95% CIs) derived from generalized linear models identified risk factors associated with acute suicidal ideation. Standardized incidence ratios (SIRs) compared the prevalence of 12-month suicidality among survivors with that of a matched sample from the general population., Results: Survivors reported a similar 12-month prevalence of ideation compared with the general population (SIR, 0.68; 95% CI, 0.35-1.01) and a lower prevalence of suicidal behaviors (planning: SIR, 0.17 [95% CI, 0.07-0.27]; attempts: SIR, 0.07 [95% CI, 0.00-0.15]) and mortality (standardized mortality ratio, 0.60; 95% CI, 0.34-0.86). Among survivors, depression (RR, 12.30; 95% CI, 7.89-19.11), anxiety (RR, 2.19; 95% CI, 1.40-3.40), and financial stress (RR, 1.47; 95% CI, 1.00-2.15) were found to be associated with a higher prevalence of acute suicidal ideation., Conclusions: Survivors of childhood cancer were found to be at a lower risk of suicidal behaviors and mortality, yet endorsed a prevalence of ideation similar to that of the general population. These results are in contrast to previous findings of suicidal ideation among survivors and support the need for further research to inform screening strategies and interventions., Lay Summary: The purpose of the current study was to compare the risk of suicidal ideation, behaviors, and mortality in adult survivors of childhood cancer with those of the general population. Risk factors associated with suicidal ideation among survivors of childhood cancer also were examined. Survivors of childhood cancer reported a similar risk of ideation compared with the general population, but a lower risk of suicidal behaviors and mortality. Psychological health and financial stressors were found to be risk factors associated with suicidal ideation. Although adult survivors of childhood cancer did not report a greater risk of suicidality compared with the general population, psychosocial care in survivorship remains essential., (© 2020 American Cancer Society.)

Objectives: Microtubules have key roles in essential cellular processes such as mitosis, cell motion, and intracellular organelle transport. Increasing interest has been given to tubulin binding compounds after the introduction of taxanes into clinical oncology. The object of this study was synthesis and biological evaluation of novel 5,6,7-trimethoxy quinolines as tubulin inhibitors., Materials and Methods: The cytotoxicity of the newly synthesized compounds was assessed against different human cancer cell lines including MCF-7, A2780, MCF-7/MX, A2780/RCIS, and normal cells. Compounds demonstrating the most antiproliferative activity, were chosen to examine their tubulin inhibition activity and their ability to arrest the cell cycle and induce apoptosis. Molecular docking studies and molecular dynamics simulation of compound 7e in the catalytic site of tubulin were performed., Results: Most of the synthesized quinolines showed moderate to significant cytotoxic activity against human cancer cells. Compounds 7e and 7f, possessing N-(4-benzoyl phenyl) and N-(4-phenoxy phenyl), respectively, exhibited the most antiproliferative activity more potent than the other compounds and exhibited similar antiproliferative activity on both resistant and parental cancer cells., Conclusion: Flow cytometry analysis of A2780, A2780/RCIS, MCF-7, and MCF-7/MX cancer cells treated with 7e and 7f exhibited that these compounds arrested the cell cycle (at the G2/M phase) and induced cellular apoptosis in A2780 cancer cells. These quinolines inhibited tubulin polymerization in a way resembling that of CA-4. Molecular dynamics simulation and molecular docking studies of compound 7e into the binding site of tubulin displayed the probable interactions of 7e with the binding site of tubulin.

Background: Rapid reperfusion reduces infarct size and mortality for acute coronary syndrome (ACS), but efficacy is time dependent. The aim of this study was to determine if transportation factors and clinical presentation predicted prehospital delay for suspected ACS, stratified by final diagnosis (ACS vs. no ACS)., Methods: A heterogeneous sample of emergency department (ED) patients with symptoms suggestive of ACS was enrolled at 5 US sites. Accelerated failure time models were used to specify a direct relationship between delay time and variables to predict prehospital delay by final diagnosis., Results: Enrolled were 609 (62.5%) men and 366 (37.5%) women, predominantly white (69.1%), with a mean age of 60.32 (±14.07) years. Median delay time was 6.68 (confidence interval 1.91, 24.94) hours; only 26.2% had a prehospital delay of 2 hours or less. Patients presenting with unusual fatigue [time ratio (TR) = 1.71, P = 0.002; TR = 1.54, P = 0.003, respectively) or self-transporting to the ED experienced significantly longer prehospital delay (TR = 1.93, P < 0.001; TR = 1.71, P < 0.001, respectively). Predictors of shorter delay in patients with ACS were shoulder pain and lightheadedness (TR = 0.65, P = 0.013 and TR = 0.67, P = 0.022, respectively). Predictors of shorter delay for patients ruled out for ACS were chest pain and sweating (TR = 0.071, P = 0.025 and TR = 0.073, P = 0.032, respectively)., Conclusion: Patients self-transporting to the ED had prolonged prehospital delays. Encouraging the use of EMS is important for patients with possible ACS symptoms. Calling 911 can be positively framed to at-risk patients and the community as having advanced care come to them because EMS capabilities include 12-lead ECG acquisition and possibly high-sensitivity troponin assays.

In recent years, the introduction of theranostic twins for specific diagnosis and treatment in patients with neuroendocrine tumors became a nuclear medicine success story. 64 Cu/ 18 F labeled prostate specific membrane antigen (PSMA) for molecular imaging with PET-CT and peptide radioligand therapy with 177 Lu labeled PSMA inhibitors will favorably become the next theranostic twins in nuclear medicine history. 68 Ga/ 64 Cu/ 18 F PSMA PET/CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity. In addition, it can be used to select patients for radioligand therapy and evaluate therapy response. 64 Cu-labeled radiopharmaceuticals such as 64 Cu-PSMA, and 64 Cu-somatostatin analogs are promising imaging tools in the assessment of primary disease and also in the detection of disease recurrence and to evaluate therapy response. The long half-life of 64 Cu allows the distribution of the tracer to PET centers as a satellite concept, who otherwise has no access to 68 Ga generators.

The design and synthesis of a new molecular tweezer (T-tmp) with electron-rich pincers are reported. The stable monocationic radicals and self-assembled dimeric radicals of this molecular tweezer platform were prepared by chemical oxidative titration. With the aid of DFT calculations, it was found that the dimeric radicals with syn-syn-syn conformer has the most stable structure, with the hole primarily delocalized between parallel stacked pyrenyl groups., (© 2020 Wiley-VCH GmbH.)

Objectives: In the present study, a new series of oxazinonaphthalene-3-one analogs was designed and synthesized as novel tubulin inhibitors., Materials and Methods: The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma), A2780/RCIS (cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), and MCF-7/MX (mitoxantrone resistant human breast cancer cells), those compounds which demonstrated the most antiproliferative activity in the MTT test were selected to investigate their tubulin inhibition activity and their effects on cell cycle arrest (at the G2/M phase). Moreover, molecular docking studies of the selected compounds in the catalytic site of tubulin (PDB ID: 4O2B) were carried out to describe the results of biological experiments., Results: Most of our compounds exhibited significant to moderate cytotoxic activity against four human cancer cell lines. Among them, Compounds 4d , 5c , and 5g , possessing trimethoxy phenyl, showed the most antiproliferative activity with IC50 values ranging from 4.47 to 52.8 μM., Conclusion: The flow cytometric analysis of A2780 cancer cell line treated with compounds 4d , 5c , and 5g showed that these compounds induced cell cycle arrest at the G2/M phase. Compound 5g , the most antiproliferative compound, inhibited tubulin polymerization in a dose-dependent manner. Molecular docking studies of 5g into the colchicine-binding site of tubulin displayed a possible mode of interaction between this compound and tubulin.

Herein, we report the synthesis of two new series of angular (all-syn) ladder-type meta -[n]phenylenes (LMP, n = 3-8). One series contains keto groups at the termini bridges, denoted angular keto (AKn), the second contains alkyl groups at all bridge sp 3 carbons, denoted angular alkyl (AAn). Their electronic and structural properties were delineated by a combination of electrochemistry and spectroscopic (UV-Vis and emission) methods and further supported by DFT calculations. Interestingly, experimental and DFT data show that changing the bridging group at the termini from alkyl (AAn) to keto (AKn) gives an increase in the first reduction potentials and LUMO energies, as the π-system is extended. Also, the charge (de)localization behavior is different for these two species; while the AAn compounds stablize charge with Robin-Day class III, the AKn compounds show a clear switch from class III to class II. In comparison with the linear analogues (LKn and LAn), DFT results reveal a shape independency of the charge (de)localization mechanism in acceptor-π-acceptor series (AKn/LKn)., Competing Interests: Conflict of interest There are no conflicts to declare.

The COVID-19 pandemic has now reached most countries. However, the referred patients to a nuclear medicine department will be primarily the asymptomatic ones. We report the case of a patient (84-year-old male) who was sent for 18 F-prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET-CT) with suspicion of recurrent disease after prostate cancer and total prostatectomy 2 years prior to the examination. He suffered from COVID-19 pneumonia 4 weeks prior to PET-CT examination. The 18 F-PSMA PET-CT revealed moderate elevated uptake in the area of previous pneumonia in the right lung. The radiological findings showed ground glass changes in this area indicating possible residual inflammatory disease even weeks after infection., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

In a cross-sectional study, adolescent and young adult females were asked to recall the time of menarche, if experienced. Some respondents recalled the date exactly, some recalled only the month or the year of the event, and some were unable to recall anything. We consider estimation of the menarcheal age distribution from this interval-censored data. A complicated interplay between age-at-event and calendar time, together with the evident fact of memory fading with time, makes the censoring informative. We propose a model where the probabilities of various types of recall would depend on the time since menarche. For parametric estimation, we model these probabilities using multinomial regression function. Establishing consistency and asymptotic normality of the parametric maximum likelihood estimator requires a bit of tweaking of the standard asymptotic theory, as the data format varies from case to case. We also provide a non-parametric maximum likelihood estimator, propose a computationally simpler approximation, and establish the consistency of both these estimators under mild conditions. We study the small sample performance of the parametric and non-parametric estimators through Monte Carlo simulations. Moreover, we provide a graphical check of the assumption of the multinomial model for the recall probabilities, which appears to hold for the menarcheal data set. Our analysis shows that the use of the partially recalled part of the data indeed leads to smaller confidence intervals of the survival function., (© The Author 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The study aimed to assess affecting structural factors on the entrepreneurship behavior of the academic members of healthcare in Qazvin University of Medical Sciences, Central Iran., Methods: This was a descriptive, cross-sectional study conducted among faculty members working in five faculties of Qazvin University of Medical Sciences, Iran in 2018. Data were collected using a three-part standard questionnaire including demographic characteristics, entrepreneurial behavior and structural factors questions. ANOVA and linear regression modeling were used in STATA software version 14., Results: Of 270 academic staff who participated in the study, 204 (73%) completed the questionnaire. The mean score reported for entrepreneurial behavior was 3.76±0.55 considered high tendency toward entrepreneurship. Moreover, the average conditions of the structural elements have been 2.51±0.89 considered average. Linear regression analysis showed that along with increasing age, entrepreneurship behavior increased ( P =0.018, β=0.52), while an increase in educational level led to a decrease in entrepreneurship behaviour ( P =0.001, β=-0.74). In a final model, organizational structure revealed a significant effect on entrepreneurship behavior ( P <0.001, β=0.25). Only physical facilities didn't show a statistical significant effect on entrepreneur-ship score ( P >0.05)., Conclusion: Universities must also pay attention to acquiring and developing the science and technology gained from academic research and transferring them through entrepreneurship channels. Considering the effect of structural elements on entrepreneurial behavior of the academic members, the need for such substructure in the universities and the country's higher education organizations to assist development of entrepreneurial behavior among the academicians is greatly felt., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Mohebifar et al. Published by Tehran University of Medical Sciences.)

Background: The aim of this study was to present challenges of implementing the accreditation model in university and military hospitals in Iran., Methods: In this qualitative study, purposive sampling was used to select hospital managers and implementers of the model working in 3 hospitals affiliated to Kerman University of Medical Sciences and in 3 military hospitals in Kerman, Iran. A total of 39 participants were interviewed, and semi-structured questionnaires and thematic analysis were used for data collection and analysis, respectively., Results: In this study, 5 major codes and 17 subcodes were identified: (1) perspectives on accreditation model with 5 subcodes: a difficult and time-consuming model, less attention to the patient, accreditation as a way of money acquisition, not being cost-effective, and accreditation means incorrect documentation; (2) absence of appropriate executive policy, with 3 subcodes: lack of financial funds and personnel, disregarding local conditions in implementation and evaluation, and absence of the principle of unity of command; (3) training problems of the accreditation model, with 2 subcodes: absence of proper training and incoordination of training and evaluation; (4) human resources problems, with 3 subcodes: no profit for nonphysician personnel, heavy workload of the personnel, and physicians' nonparticipation; (5) evaluation problems, with 4 subcodes: no precise and comprehensive evaluation, inconformity of authorities' perspectives on evaluation, considerable change in evaluation criteria, and excessive reliance on certificates., Conclusions: This study provided useful data on the challenges of implementing hospitals' accreditation, which can be used by health policymakers to revise and modify accreditation procedures in Iran and other countries with similar conditions. The accreditation model is comprehensive and has been implemented to improve the quality of services and patients' safety. The basic philosophy of hospital accreditation did not fully comply with the underlying conditions of the hospitals. The hospital staff considered accreditation as the ultimate goal rather than a means for achieving quality of service. The Ministry of Health and Medical Education performed accreditation hastily for all Iranian hospitals, while the hospitals were not prepared and equipped to implement the accreditation model.

Novel Pt-Cr/Zr( x )-HMS catalysts with different molar ratios of Cr/Zr were synthesized. These catalysts were characterized by necessary techniques including XRD, XRF, NH 3 -TPD, FTIR, H 2 chemisorption, nitrogen sorption and TGA. Moreover, generalization performances of an optimized in-house regularization network and an RSM were compared for the prediction of activity and selectivity versus various molar ratios, feed temperatures and time on stream. The results indicated that the incorporation of Cr promotes the catalyst activity, in which a high amount of 63% conversion was obtained at Cr/Zr = 30 and T = 200 °C. Increasing temperature has an adverse effect on i-C 7 and mono plus multi-branch isomer selectivity nearly in all amounts of molar ratios. The best i-C 7 selectivity (66%), MOB (29.6%) and MUB (32%) were observed at 200 °C and Cr/Zr = 30. Although both modeling methods exhibited outstanding performances, statistical analysis revealed that optimized RN has slightly better performances than RSM., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report the synthesis and characterization of conjugated, conformationally rigid, and electroactive carbon-based nanotubes that we term tubularenes. These structures are constructed from a resorcin[ n b ]arene base. Cyclization of the conjugated aromatic nanotube is achieved in one-pot eight-fold C-C bond formation via Suzuki-Miyaura cross-coupling. DFT calculations indicate a buildup of strain energy in excess of 90 kcal mol -1 . The resulting architectures contain large internal void spaces >260 Å 3 , are fluorescent, and able to accept up to 4 electrons. This represents the first scaffolding approach that provides conjugated nanotube architectures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Mastitis is defined as the inflammation of the mammary gland, which impact directly on the production performance and welfare of dairy cattle. Since, mastitis is a multifactorial complex disease and the molecular pathways underlying this disorder have not been clearly understood yet, a system biology approach was used in this study to a better understanding of the molecular mechanisms behind mastitis., Methods: Publicly available RNA-Seq data containing samples from milk of five infected and five healthy Holstein cows at five time points were retrieved. Gene Co-expression network analysis (WGCNA) approach and functional enrichment analysis were then applied with the aim to find the non-preserved module of genes that their connectivity were altered under infected condition. Hub genes were identified in the non-preserved modules and were subjected to protein-protein interactions (PPI) network construction., Results: Among the 25 modules identified, eight modules were non-preserved and were also biologically associated with inflammation, immune response and mastitis development. Interestingly most of the hub genes in the eight modules were also densely connected in the PPI network. Of the hub genes, 250 genes were hubs in both co-expression and PPI networks and most of them were reported to play important roles in immune response or inflammatory pathways. The blue module was highly enriched in inflammatory responses and STAT1 was suggested to play an important role in mastitis development by regulating the immune related genes in this module. Moreover, a set of highly connected genes were identified such as BIRC3, PSMA6, FYN, F11R, NFKBIZ, NFKBIA, GRO1, PHB, CD3E, IL16, GSN, SOCS2, HCK, VAV1 and TLR6 , which have been established to be critical for mastitis pathogenesis., Conclusion: This study improved the understanding of the mechanisms underlying bovine mastitis and suggested eight non-preserved modules along with several most important genes with promising potential in etiology of mastitis., (Copyright © 2020 Bakhtiarizadeh, Mirzaei, Norouzi, Sheybani and Vafaei Sadi.)

In this paper, a method for the detection and subsequently extraction of neural spikes in an intra-cortically recorded neural signal is proposed. This method distinguishes spikes from the background noise based on the natural difference between their time-domain amplitude variation patterns. According to this difference, a spike mask is generated, which takes on large values over the course of spikes, and much smaller values for the background noise. The "high" part of this mask is designed to be wide enough to contain a complete spike. By multiplying the input neural signal with the spike mask, spikes are amplified with a large factor while the background noise is not. The result is a spike-augmented signal with significantly larger signal-to-noise ratio, on which spike detection is performed much more easily and accurately. According to this detection mechanism, spikes of the original neural signal are extracted.Clinical Relevance-This paper presents an automatic spike detection technique, dedicated to brain-implantable neural recording devices. Such devices are developed for clinical applications such as the treatment of epilepsy, neuro-prostheses, and brain-machine interfacing for therapeutic purposes.

Traumatic brain injuries can lead to long-term mental seizures that are difficult to differentiate from dissociative psychogenic symptoms, respectively, psychogenic nonepileptic seizures. Recent articles have drawn attention to the need of differentiation of psychological and brain trauma-related symptoms in survivors of violence. This case study reflects a diagnostic step in a 20-year-male who reported to have been subjected to torture, including blunt force to the head 2 years before examination. He suffers from episodical headaches followed by mental bouts of aggression and restlessness. We performed a brain 18 F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography to identify a cerebral correlate of the psychogenic seizures. The examination yielded a hypermetabolic focus in the frontal superior parasagittal region. Psychogenic seizures can frequently be observed as culture-specific "idioms of distress" and can challenge diagnostic evaluation, especially in the victims of violence with an additional history of blunt brain trauma. The advances in molecular imaging such as PET can be expected to play a crucial role in forensic and clinical assessment in the increasing number of such patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

Introduction: Several radiolabeled somatostatin analogues have been developed for molecular imaging of neuroendocrine tumors (NETs) with single-photon emission computed tomography (SPECT) and positron-emission tomography (PET). The aim of the present study was to report our first results using 64 Cu-DOTATOC in patients with NETs., Methods: Thirty-three patients with NETs (15 female, 18 male; mean age 64 ± 13 years) were included in this retrospective study. 64 Cu-DOTATOC PET-CT scans were performed on all patients., Results: Five out of 33 patients with a history of NET after surgical removal of the primary lesion showed no pathological lesions on PET-CT imaging and 8/33 patients had enhanced uptake in the area of recurrent meningioma at the skull base. The remaining 20/33 patients had a history of neuroendocrine tumor in the gastrointestinal tract (GEP-NET) and were presented with at least one pathological lesion., Conclusion: The high detection rate of suspected lesions in patients with NETs and the high target-to-background contrast found in this study hold promise for the safe application of 64 Cu-DOTATOC in patients with NET.