Search results for: psoriasis mechanism of action

Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

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Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

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Authors: Rania A. R. Soudan, Easter Joury

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Introduction: Psoriasis is a common chronic dermatologic disease. It may affect the mucous membranes. The presence of oral mucosal lesions has been a subject of controversy. The aim: To determine possible association between oral mucosal lesions and psoriasis, and to correlate the same with different types of psoriasis and severity of the disease. Materials and Methods: The oral mucosa was clinically examined in 100 randomly selected Syrian psoriatic patients presented to the Dermatological Diseases Hospital in Damascus University, Syria (February 2009 - December 2010), and in 100 matched controls. PASI index was used to evaluate the disease severity. Chi-square and Student t-test were used to compare differences between groups. Results: Oral mucosal lesions were observed in 72% of the psoriasis cases, while 46% of the control group’s subjects had oral lesions. Fissured tongue, geographic tongue, and red lesions were detected in 36%, 25%, and 7% of the examined psoriatics, respectively. These lesions were significantly more frequent in the psoriatics than in the controls. A correlation was found between furred tongue and the age of the psoriasis patients. However, an association was observed for fissured tongue, furred tongue with the severity of the disease, and for fissured tongue, white lesions, cheilitis with nail involvement. However, no correlation with the psoriasis types was recorded. Conclusion: Some oral mucosal lesions were associated with psoriasis, so these lesions may be considered as oral manifestations of this disease, and should be taken into account in new studies as possible predictors or markers of this dermatitis. Further studies are recommended to confirm these oral manifestations.

Keywords: psoriasis, tongue, mucosa, lesions

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Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Afsaneh Bayat, Amin Asadi Hieh

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The purpose of this research was to investigate the pattern of structural relationships of quality of life based on anxiety and rumination with the mediation of personality types in psoriasis patients. Methods: The community of this research is made up of the members of Psoriasis Society of Iran - Sadafak. In the sample size of 2266 people, according to Morgan's table, 327 people will be considered as a statistical sample. To assess the quality of life, the 26-item questionnaire of the World Health Organization, anxiety with software SPSS and appropriate to the conditions were used to test the hypotheses, correlation matrix tests and factor analysis. Results: There is a relationship between quality of life with anxiety and rumination in psoriasis patients. The mediating role of personality types showed Psychotic annoyance has a significant relationship with anxiety (physical and emotional symptoms). Extraversion, agreeing and being conscientious play a mediating role in a significant relationship between quality of life in psoriasis patients. Also, irritability plays a mediating role in a meaningful relationship between rumination in psoriasis patients. Conclusion: According to the obtained results, it can be said that psoriasis patients with physical and emotional symptoms of anxiety and rumination have a low quality of life. Also, negative personality types (perfectionism and neuroticism) can cause or aggravate skin disorders in these patients. In other words, psychological factors are considered predisposing, accelerating and perpetuating factors in psoriasis skin disorders, so it is suggested to pay attention to these variables in the success of treating patients with psoriasis.

Keywords: quality of life, anxiety, rumination, personality types, psoriasis.

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Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

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Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: D. Gvozdikov

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The purpose of this study is an attempt to describe an online action as a system that combines disjointed events and behavioral chains into a whole. The research focuses on patterns of naturally-formed chains of actions united by an orientation towards the online environment. A key characteristic of the system of online action is that it acts as an attractor for separate actions and chains of behavioral repertoire accumulating time and efforts made by users. The article demonstrates how the chains of online-offline actions are combined into a single pattern due to a simple identifiable mechanism, a positive feedback system. Using methods of digital ethnography and analyzing the content of the Instagram application and media blogs, the research reveals how through the positive feedback mechanism the entire system of online action acquires stability and can expand involving new spheres of human activity.

Keywords: digital anthropology, internet studies, systems theory, social media

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Authors: Manik Konch

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Actions are generally evaluated from moral point of view. Either the action is praised or condemned, but in all cases it involves the agent who performs it. The agent is held morally responsible for bringing out an action. This paper is an attempt to explore the Aristotle’s notion of action and its relation with moral development in response to modern philosophical moral psychology. Particularly, the distinction between voluntary, involuntary, and non-voluntary action in the Nicomachean Ethics with some basic problems from the perspective of moral psychology: the role of choice, moral responsibility, desire, and akrasia for an action. How to do a morally right action? Is there any role of virtue, character to do a moral action? These problems are analyzed and interpreted in order to show that the Aristotelian theory of action significantly contributes to the philosophical study of moral psychology. In this connection, the paper juxtaposes Aristotle’s theory of action with response from David Charles, John R. Searle’s, and Alfred Mele theorization of action in the mechanism of human moral behaviours. To achieve this addressed problem, we consider, how the recent moral philosophical moral psychology research can shed light on Aristotle's ethics by focusing on theory of action. In this connection, we argue that the desire is the only responsible for the akratic action. According to Aristotle, desire is primary source of action and it is the starting point of action and also the endpoint of an action. Therefore we are trying to see how desire can make a person incontinent and motivate to do such irrational actions. Is there any causes which we can say such actions are right or wrong? To measure an action we have need to see the consequences such act. Thus, we discuss the relationship between akrasia and action from the perspective of contemporary moral psychologists and philosophers whose are currently working on it.

Keywords: action, desire, moral psychology, Aristotle

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Authors: Boonsri Lertviriyachit

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The objective of this research is to investigate the treatment of psoriasis through Thai traditional medicine in the selected areas of 2 east coast provinces; Samudprakarn Province and Chantaburi Province. The informants in this study were two famous and accepted Thai traditional doctors, who have more than 20 year experiences. Data were collected by in depth interviews and participant-observation method. The research instrument included unstructured interviews, camera, and cassette tape to collect data analyzed by descriptive statistics. The results revealed that the 2 Thai traditional doctors were 54 and 85 years old with 25 and 45 years of treatment experiences. The knowledge of Thai traditional medicine was transferred from generations to generations in the family. The learning process was through close observation as an apprentice with the experience ones and assisted them in collecting herbs and learning by handling real case in individual situations. Before being doctors, they had to take exam to get the Thai traditional medical certificate. Knowledge of being Thai traditional doctors included diagnosis and find to the suitable way of treatment. They have to look into disorder physical fundamental factors such as blood circulation, lymph, emotion, and food consumption habit. It is important that the treatment needs to focus on balancing the fundamental factors and to observe contraindication.

Keywords: Thai traditional medicine, psoriasis, Samudprakarn Province, Chantaburi Province

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Authors: F. O’Dowd, G. Murphy, M. Roche, E. Shudell, F. Keane, M. O’Kane

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Intoduction: Apremilast (Otezla®) is an oral phosphodiesterase-4 (PDE4) inhibitor indicated for treatment of adult patients with moderate to severe plaque psoriasis who have contraindications to have failed or intolerant of standard systemic therapy and/or phototherapy; and adult patients with active psoriatic arthritis. Apremilast influences intracellular regulation of inflammatory mediators. Two randomized, placebo-controlled trials evaluating apremilast in 1426 patients with moderate to severe plague psoriasis (ESTEEM 1 and 2) demonstrated that the commonest adverse reactions (AE’s) leading to discontinuation were nausea (1.6%), diarrhoea (1.0%), and headaches (0.8%). The overall proportion of subjects discontinuing due to adverse reactions was 6.1%. At week 16 these trials demonstrated significant more apremilast-treated patients (33.1%) achieved the primary end point PASI-75 than placebo (5.3%). We began prescribing apremilast in July 2015. Aim: To evaluate efficacy and tolerability of apremilast in an Irish teaching hospital psoriasis population. Methods: A proforma documenting clinical evaluation parameters, prior treatment experience and AE’s; was completed prospectively on all patients commenced on apremilast since July 2015 – July 2017. Data was collected at week 0,6,12,24,36 and week 52 with 20/71 patients having passed week 52. Efficacy was assessed using Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). AE’s documented included GI effects, infections, changes in weight and mood. Retrospective chart review and telephone review was utilised for missing data. Results: A total of 71 adult subjects (38 male, 33 female; age range 23-57), with moderate to severe psoriasis, were evaluated. Prior treatment: 37/71 (52%) were systemic/biologic/phototherapy naïve; 14/71 (20%) has prior phototherapy alone;20/71 (28%) had previous systemic/biologic exposure; 12/71 (17%) had both psoriasis and psoriatic arthritis. PASI responses: mean baseline PASI was 10.1 and DLQI was 15.Week 6: N=71, n=15 (21%) achieved PASI 75. Week 12: N= 48, n=6 (13%) achieved a PASI 100%; n=16 (34.5%) achieved a PASI 75. Week 24: N=40, n=10 (25%) achieved a PASI 100; n=15 (37.5%) achieved a PASI 75. Week 52: N= 20, n=4 (20%) achieved a PASI 100; n= 16 (80%) achieved a PASI 75. (N= number of pts having passed the time point indicated, n= number of pts (out of N) achieving PASI or DLQI responses at that time). DLQI responses: week 24: N= 40, n=30 (75%) achieved a DLQI score of 0; n=5 (12.5%) achieved a DLQI score of 1; n=1 (2.5%) achieved a DLQI score of 10 (due to lack of efficacy). Adverse Events: The proportion of patients that discontinued treatment due to AE’s was n=7 (9.8%). One patient experienced nausea alleviated by dose reduction; another developed significant dysgeusia for certain foods, both continued therapy. Two patients lost 2-3 kg. Conclusion: Initial Irish patient experience of Apremilast appears comparable to that observed in trials with good efficacy and tolerability.

Keywords: Apremilast, introduction, Ireland, clinical audit

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Authors: Imran Ali

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General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

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Authors: Jian-Xiu Wan, Yao Yin

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In complex terrain and poor geological conditions areas, Railway, highway and other transportation constructions are still strongly developing. However, various geological disasters happened such as landslide, rock heap and so on. According to the results of geological investigation, the form of skirt (trapezoidal), semicircle and triangle rock heaps are mainly due to complex internal force and external force, in a certain extent, which is related to the terrain, the nature of the rock mass, the supply area and the surface shape of rock heap. Combined with the above factors, discrete element numerical simulation of rock mass is established under different terrain conditions based on 3DEC, and accelerated formation process of rock heap under seismic action is simulated. The fragmentation structure supply area is calculated, in which the most dangerous area is located. At the same time, the formation mechanism and development process are studied in different terrain conditions, and the structure of rock heap is judged by section, which can provide a strong theoretical and technical support for the prevention and control of geological disasters.

Keywords: 3DEC, fragmentation structure, rock heap, slope, seismic action

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Authors: Sevcan Ozturk

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The aim of this paper is to analyze the twentieth-century Muslim philosopher Muhammad Iqbal’s philosophy of action in the light of the main issues of contemporary philosophy of action. Iqbal is one of the most celebrated and eminent figures of modern Islamic thought. However, a review of the works on Iqbal shows that most of the central concepts of his philosophy have not received enough attention. His notion of ‘action’ in its philosophical context is one of these concepts. One of the main characteristics of Iqbal’s approach is that he develops his discussion around the main themes of contemporary philosophy of action, which includes ontological and conceptual questions regarding the nature of human actions. He also discusses that action is the only way to develop human personality, and that the human being can only achieve immortality promised by Islam through his actions. Therefore, while presenting an approach that can be read in the light of contemporary philosophy of action, which has become one of the significant parts of modern philosophical discussions in the west particularly since the nineteenth century, he, at the same time, develops his own philosophy of action in the light of Islamic resources. Consequently, these two main characteristics of his discussion of the notion of action make his philosophy of action an important contribution to contemporary philosophy of action, a field that ignores the discussions of Muslim philosophers on action. Therefore, this paper aims at highlighting Iqbal’s contribution to the modern debate of action by analysing Iqbal’s notion of action in the light of the contemporary issues of philosophy of action. This will, first of all, include an examination of contemporary action theory. Although the main discussions of contemporary philosophy of action will provide the methodology of this study, the main paradigms of Iqbal’s approach to the notion of action will also be considered during the examination of the discussions of philosophy of action. Then, Iqbal’s own philosophy of action will be established in the light of the contemporary philosophy of action. It is hoped that this paper will cultivate a dialogue between Iqbal scholars and those working in the field of philosophy of action, and that it will be a contribution to the fields of Iqbal studies, philosophy of action, and intercultural philosophy.

Keywords: action, development of personality, Muhammad Iqbal, philosophy of action

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Hanjun Hu, Jinxiang Zhang

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With the decline of "growthism", China's urbanization process has shifted from the stage of spatial expansion to the stage of optimization of built-up spaces, and urban renewal has gradually become a new wave of China's urban movement in recent years. The ongoing urban renewal movement in China not only needs to generate new motivation for urban development but also solve the backlog of social problems caused by rapid urbanization, which provides an opportunity for the transformation of China's urban governance model. Unlike previous approaches that focused on physical space and functional renewal, such as urban reconstruction, redevelopment, and reuse, the key challenge of urban renewal in the post-growth era lies in coordinating the complex interest relationships between multiple stakeholders. The traditional theoretical frameworks that focus on the structural relations between social groups are insufficient to explain the behavior logic and mutual cooperation mechanism of various groups and individuals in the current urban renewal practices. Therefore, based on the long-term tracking of the urban renewal practices in the Old City of Nanjing (OCN), this paper introduces the "collective action" theory to deeply analyze changes in the urban renewal governance model in OCN and tries to summarize the governance strategies that promote the formation of collective action within recent practices from a micro-scale. The study found that the practice in OCN experienced three different stages "government-led", "growth coalition" and "asymmetric game". With the transformation of government governance concepts, the rise of residents' consciousness of rights, and the wider participation of social organizations in recent years, the urban renewal in OCN is entering a new stage of "collective renewal action". Through the establishment of the renewal organization model, incentive policies, and dynamic negotiation mechanism, urban renewal in OCN not only achieves a relative balance between individual interests and collective interests but also makes the willingness of residents the dominant factor in formulating urban renewal policies. However, the presentation of "collective renewal action" in OCN is still mainly based on typical cases. Although the government is no longer the dominant role, a large number of resident-led collective actions have not yet emerged, which puts forward new research needs for a sustainable governance policy innovation in this action.

Keywords: urban renewal, collective action theory, governance, cooperation mechanism, China

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Authors: YangHui

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Foreign teachers play an important role in the process of internationalization of higher education in China. Based on the method of literature analysis, firstly study the contents about the mechanism of the foreign teachers’ administration in our country, then secondly analyze the main barriers of the foreign teacher’s administration mechanism. Finally, it is suggested that the international exchange department in universities should constantly improve the employment mechanism, training mechanism, appraisal mechanism and incentive mechanism to promote the internationalization of higher education.

Keywords: internationalization of higher education, mechanism, administration of foreign teachers, colleges and universities, China

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Authors: Guoliang Lu, Changhou Lu, Xueyong Li

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In action recognition, previous studies have demonstrated the effectiveness of using multiple features to improve the recognition performance. We focus on two practical issues: i) most studies use a direct way of concatenating/accumulating multi features to evaluate the similarity between two actions. This way could be too strong since each kind of feature can include different dimensions, quantities, etc; ii) in many studies, the employed classification methods lack of a flexible and effective mechanism to add new feature(s) into classification. In this paper, we explore an unified scheme based on recently-proposed multi-dimensional dynamic time warping (MD-DTW). Experiments demonstrated the scheme's effectiveness of combining multi-feature and the flexibility of adding new feature(s) to increase the recognition performance. In addition, the explored scheme also provides us an open architecture for using new advanced classification methods in the future to enhance action recognition.

Keywords: action recognition, multi features, dynamic time warping, feature combination

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Tian Zhang

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Unsupervised object segmentation aims at segmenting objects in sequential images and obtaining the mask of each object without any manual intervention. Unsupervised segmentation remains a challenging task due to the lack of prior knowledge about these objects. Previous methods often require manually specifying the action of each object, which is often difficult to obtain. Instead, this paper does not need action information of objects and automatically learns the actions and relations among objects from the structured environment. To obtain the object segmentation of sequential images, the relationships between objects and images are extracted to infer the action and interaction of objects based on the multi-head attention mechanism. Three types of objects’ relationships in the object segmentation task are proposed: the relationship between objects in the same frame, the relationship between objects in two frames, and the relationship between objects and historical information. Based on these relationships, the proposed model (1) is effective in multiple objects segmentation tasks, (2) just needs images as input, and (3) produces better segmentation results as more relationships are considered. The experimental results on multiple datasets show that this paper’s method achieves state-of-art performance. The quantitative and qualitative analyses of the result are conducted. The proposed method could be easily extended to other similar applications.

Keywords: unsupervised object segmentation, attention mechanism, contrastive learning, structured environment

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Authors: Scott Andersen

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Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

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Authors: Walaa Mohammed Metwally

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This case study used the action research concept as a tool to integrate the innovation in a learning experience on a design course. The action research was investigated at Prince Sultan University, College of Engineering in the Interior Design and Architecture Department in January 2015, through the Higher Education Academy program. The action research was presented first with the definition of the research, leading to how it was used and how solutions were found. It concluded by showing that once the action research application in interior design and architecture were studied it was an effective tool to improve student’s learning, develop their practice in design courses, and it discussed the negative and positive issues that were encountered.

Keywords: action research, innovation, intervention, learning experience, peer review

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Authors: Li Qiaoming

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The outbreak of Coronavirus disease 2019 (COVID-19) in early 2020 brought new opportunities to the development of the digital creative industry in China. Based on the realistic foundation of the development of the digital creative industry in China, an analysis was conducted on the mechanism of action of the pandemic on this industry from both sides of supply and demand by sorting out its concept, connotation, and related theories. To be specific, the demand side experienced changes due to the changes in the consumption habits of residents, the sharp increase in gross domestic time (GDT), the satisfaction of the psychological needs of users, search for substitutes for offline consumption, and other factors. An analysis was carried out on the mechanism of action of the pandemic on the digital creative industry from the production link, supply subjects, product characteristics, and transmission link of the supply side. Then, a detailed discussion was held on the manifestation forms of the impact of the pandemic from the dimensions of time and space. Finally, this paper discussed the main development focuses of the digital creative industry in the post-pandemic era from the aspects of the government, industries, and enterprises.

Keywords: COVID-19, demand and supply relationship, digital creative industries, industry shocks

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Authors: Mohamed Amine Ben Abdallah, Imed Khemili, Nizar Aifaoui

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This work denotes an insight into dynamic synthesis of multibody systems. A set of mechanism parameters design variable are synthetized based on a desired mechanism response, such as, velocity, acceleration and bodies deformations. Moreover, knowing the work space, for a robot, and mechanism response allow defining optimal parameters mechanism handling with the desired target response. To this end, evolutionary genetic algorithm has been deployed. A demonstrative example for imperfect mechanism has been treated, mainly, a slider crank mechanism with a flexible connecting rod. The transversal deflection of the connecting rod has been chosen as response to identify the mechanism design parameters.

Keywords: dynamic response, evolutionary genetic algorithm, flexible bodies, optimization

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Authors: Kaisar Akhir, Azhar Slamet

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This study aims to provide recommendations for addressing marine plastic litter at the ocean tourism destinations in Indonesia sustainably through technological interventions in the framework of the National Action Plan for Marine Litter Management 2018-2025. In Indonesia, marine tourism is a rapidly growing economic sector. However, marine tourism destinations are facing a global challenge called marine plastic litter. Marine plastic litter is a threat to those destinations since it has potential impacts on the reduction of marine environmental sustainability, the health of tourists and local communities as well as tourism business income. Since 2018, the Indonesian government has passed and promulgated the National Plan of Action on Marine Litter Management 2018-2025. This national action plan consists of three important key aspects of interventions (i.e., societal effort, technological application, and institutional coordination) and five strategies for addressing marine litter in Indonesia, in particular, to address 70% of marine plastic litter by 2025. The strategies include 1) National movement for raising awareness of stakeholders, 2) Land-based litter management, 3) Litter management at the sea and coasts, 4) Funding mechanism, institutional strengthening, monitoring, and law enforcement, and 5) Research and development. In this study, technological interventions around the world and in Indonesia are reviewed and analyzed on their relevance to the national action plan based on five criteria. As a result, there are twelve kinds of technological interventions recommended to be implemented for addressing marine plastic litter in the marine tourism destinations in Indonesia.

Keywords: marine litter management, marine plastic litter, national action plan, ocean sustainability, ocean tourism destination, technological interventions

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Authors: Shaukat Ali, Kanber Sedef, Mustafa Yilmaz

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This work analyzes a finger mechanism for a prosthetic hand that will help in improving the living standards of people who have lost their hands for a variety of reasons. The finger mechanism is single degree of freedom and hence has advantages such as compact size, reduced mass and less energy consumption. The proposed finger mechanism is a six bar linkage actuated by a single motor. The kinematic, static and dynamic analyses have been done by using the conventional methods of mechanism analysis. The kinematic results present the motion of the proposed finger mechanism and location of the fingertip. The static and dynamic analyses provide the useful information about the gripping force at the fingertip for various configurations and the selection of motor that will move the finger over its range of configuration. This single motor finger mechanism is simple and resembles the human finger’s motion suitable for grasping operation. This study can be used in the optimization of geometrical parameters of the proposed mechanism to obtain the desired configurations with minimum torque and enhanced griping.

Keywords: dynamics, finger mechanism, grasping, kinematics

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Authors: Ilaisa Kacivakanadina, Samson Viulu, Brad Carte, Katy Soapi

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Two bioactive compounds namely Vulgamycin (also known as enterocin A) and 5-deoxyenterocin were purified from a marine bacterial strain 1903. Strain 1903 was isolated from marine sediments collected from the Solomon Islands. Morphological features of strain 1903 showed that it belongs to the genus Streptomyces. The two secondary metabolites were extracted using EtOAc and purified by chromatographic methods using EtOAc and hexane solvents. Mass spectrum and NMR data of pure compounds were used to elucidate the chemical structures. In this study, results showed that both compounds were strongly active against Wild Type Staphylococcus aureus (WTSA) (MIC < 1 µg/mL) and in Brine shrimp assays (BSA) (MIC < 1 µg/mL). 5-deoxyenterocin was also active against Rifamycin resistant Staphylococcus aureus (RRSA) (MIC, 250 µg/mL) while vulgamycin showed bioactivity against Methicillin resistant Staphylococcus aureus (MRSA) (MIC 250 µg/mL). To the best of our knowledge, this is the first study that showed the bio-activity of 5-deoxyenterocin. This is also the first time that Vulgamycin has been reported to be active in a BSA. There has not been any mechanism of action studies for these two compounds against pathogens. This warrants further studies on their mechanism of action against microbial pathogens.

Keywords: 5-deoxyenterocin, bioactivity, brine shrimp assay (BSA), vulgamycin

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Authors: C. Park, H. Lee, Y-J. Lee

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Aim: This study presents Interdisciplinary Collaborative Innovation Mechanism as a medium to enable the effective generation of innovations for sustainability challenges facing humanities. Background: Interdisciplinary approach of fusing disparate knowledge and perspectives from diverse expertise and subject areas is one of the key requirements to address the intricate nature of sustainability issues. There is a lack of rigorous empirical study of the systematic structure of interdisciplinary collaborative innovation for sustainability to date. Method: To address this research gap, the action research approach is adopted to develop the Interdisciplinary Collaborative Innovation Mechanism (ICIM) framework based on an empirical study of a total of 28 open innovation competitions in the format of MAKEathons between 2016 to 2023. First, the conceptual framework was formulated based on the literature findings, and the framework was subsequently tested and iterated. Outcomes: The findings provide the ICIM framework composed of five elements: Discipline Diversity Quadruple; Systematic Structure; Inspirational Stimuli; Supportive Collaboration Environment; and Hardware and Intellectual Support. The framework offers a discussion of the key elements when attempting to facilitate interdisciplinary collaboration for sustainability innovation. Contributions: This study contributes to two burgeoning areas of sustainable development and open innovation studies by articulating the concrete structure to bridge the gap. In practice, the framework helps facilitate effective innovation processes and positive social and environmental impact created for real-world sustainability challenges.

Keywords: action research, interdisciplinary collaboration, open innovation, problem-solving, sustainable development, sustainability challenges

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Authors: Aishrith Rao

Abstract:

Human activity recognition is an important aspect of video analytics, and many approaches have been recommended to enable action recognition. In this approach, the model is used to identify the action of the multiple people in the frame and classify them accordingly. A few approaches use RNNs and 3D CNNs, which are computationally expensive and cannot be trained with the small datasets which are currently available. Multi-person action recognition has been performed in order to understand the positions and action of people present in the video frame. The size of the video frame can be adjusted as a hyper-parameter depending on the hardware resources available. OpenPose has been used to calculate pose estimate using CNN to produce heap-maps, one of which provides skeleton features, which are basically joint features. The features are then extracted, and a classification algorithm can be applied to classify the action.

Keywords: human activity recognition, computer vision, pose estimates, convolutional neural networks

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Authors: Seham Alsaif, Susan Wray

Abstract:

Obesity is a worldwide disorder influencing women’s health and childbearing. There is a close relation between obesity and pregnancy related complications. Dyslipidemia and adipokine dysregulation are core environmental changes that may mechanistically link these complications with obesity in pregnant women. We have previously found that visfatin has a relaxant effect on mouse, rat and human myometrial contractility. We hypothesised that visfatin inhibits mouse myometrial contractility through the NAD+ pathway. This study was designed to examine the mechanism of action of visfatin on myometrial contractility. To examine the NAD+ pathway, FK866 which is a potent inhibitor of NAD+ biosynthesis was used. Methods: Myometrial strips from term pregnant mice were dissected, superfused with physiological saline and the effects of visfatin (10nM) on oxytocin-induced contractions (0.5nM) alone and after the infusion of FK866 (10uM) were studied. After regular contractions were established, contractility was examined for control (100%) and test response at 37 °C for 10 min each. Results: FK866 was found to inhibit the effect of visfatin on myometrial contractility (the AUC increased from 89±2% of control, P=0.0009 for visfatin alone to 97±4% of control, P>0.05 for visfatin combined with FK866, n=8). In conclusion, NAD+ pathway appears to be involved in the mechanism of action of visfatin on mouse myometrium. This could have a role in making new targets to prevent obesity-related complications.

Keywords: myometrium, obesity, oxytocin, pregnancy, visfatin

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