On Pseudo-Random Number Generators Using Elliptic Curves and Chaotic Systems

Elliptic Curve Cryptography (ECC) is a relatively recent branch of cryptography which is based on the arithmetic on elliptic curves and security of the hardness of the Elliptic Curve Discrete Logarithm Problem (ECDLP). Elliptic curve cryptographic schemes are public-key mechanisms that provide encryption, digital signature and key exchange capabilities. Elliptic curve algorithms are also applied to generation of sequences of pseudo-random numbers. Another recent branch of cryptography is chaotic dynamical systems where security is based on high sensitivity of iterations of maps to initial conditions and parameters. In the present work, we give a short survey describing state-of-the-art of several suggested constructions for generating sequences of pseudorandom number generators based on elliptic curves (ECPRNG) over finite fields of prime order. In the second part of the paper we propose a method of generating sequences of pseudorandom points on elliptic curves over finite fields which is driven by a chaotic map. Such a construction improves randomness of the sequence generated since it combines good statistical properties of an ECPRNG and a CPRNG (Chaotic Pseudo- Random Number Generator). The algorithm proposed in this work is of interest for both classical and elliptic curve cryptography

Application of Intelligent Multi Agent Based Systems For E-Healthcare Security

In recent years, availability and usage of extensive systems for Electronic Healthcare Record (EHR) is increased. In medical centers such hospitals and other laboratories, more health data sets were formed during the treatment process. In order to enhance the standard of the services provided in healthcare, these records where shared and can be used by various users depends on their requirements. As a result, notable issues in the security and privacy where obtained which should be monitored and removed in order to make the use of EHR more effectively. Various researches have been done in the past literature for improving the standards of the security and privacy in E-health systems. In spite of this, it is not completely enhanced. In this paper, a comprehensive analysis is done by selecting the existing approaches and models which were proposed for the security and privacy of the E-healthcare systems. Also, a novel Intelligent-based Access Control Security Model (IBAC) based on multi agents is proposed to maintain and support the security and privacy of E-healthcare systems. This system uses agents in order to maintain security and privacy while accessing the E-health data between the users.Comment: 6 pages, 3 figures, 1 table, journa

Effect of Inherent Anisotropy on Shear Strength Following Crushing of Natural Aqaba Subgrade Sand

Inherent anisotropy affects the overall shear strength of sand deposits. Soil inherent anisotropy was evaluated for pre-crushed Aqaba subgrade sand by deposition of soil grains onto an inclined surface. Crushing of Aqaba sand was induced by one-dimensional compression. Sand characteristic properties (mineralogical properties, grain size and crushing resistance strength) were determined by standard laboratory testing. Particle breakage factors and inter-particle void ratio were calculated from the initial and final gradations of the soil samples. Moreover, shear strength components for sand specimens were resolved. Inspection of the residual shear strength parameters showed an increase, where the amount of particle crushing increased regardless the level of the normal stress being applied. Furthermore, examining the effect of inherent anisotropy showed that a considerable amount of the dilation occurs when the particles tend to lie orthogonal to the horizontal plane regardless the extent of breakage

Aplastic anemia secondary to adjuvant Osimertinib therapy: a case report and a review of literature

Aplastic anemia is a rare hematological disorder characterized by suppressed hematopoiesis and pancytopenia. Although several drugs have been associated with aplastic anemia, its occurrence in response to Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is extremely rare. We present a case report of a 63-year-old patient with locally advanced non-small cell lung cancer (NSCLC) who developed aplastic anemia following adjuvant treatment with Osimertinib. Extensive investigations ruled out infectious etiology, and the absence of bone marrow involvement or other identifiable causes suggested a drug-induced etiology, specifically Osimertinib. This case report emphasizes the importance of recognizing this adverse event and considering it as a potential complication of Osimertinib therapy. Vigilant monitoring and prompt management are essential for optimizing patient outcomes. Further studies are needed to better understand the risk factors, underlying mechanisms, and management strategies for Osimertinib-induced aplastic anemia in the adjuvant settings

Natural Immunomodulators Treat the Cytokine Storm in SARS-CoV-2

Recently, the world has been dealing with a destructive global pandemic Coronavirus disease 2019 (COVID-19) infection, since 2020; there were millions of infections and hundreds of thousands of deaths worldwide. With sequencing generations of the virus, around 60% are expected to become infected during the pandemic. Unfortunately, no drug or vaccine has been approved because no real evidence from clinical trials in treatment was reached. According to current thinking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mortality is caused by a cytokine storm syndrome in patients with hyper-inflammatory conditions, resulting in acute respiratory distress and finally death. In this review, we discuss the various types of natural immune-modulatory agents and their role in the management of SARS-CoV-2, and cytokine storm syndrome. For example, Polyphenols as natural products can block the binding of SARS-CoV-2 spike protein to host cell receptor ACE2, stop viral entry into the host cell and block viral RNA replication. Also, saikosaponins (A, B2, C, and D), triterpene glycosides, which are isolated from medicinal plants exert antiviral action against HCoV-22E9, and Houttuynia cordata water extract has antiviral effects on SARS-CoV. Moreover, eucalyptus oil has promising potential for COVID-19 prevention and treatment. There is an urgent need for research to improve the function of the human immune system all over the world. As a result, actions for better understanding and improving the human immune system are critical steps toward mitigating risks and negative outcomes. These approaches will be strongly recommended for future emerging viruses and pathogens

Assessment of Eating Habits and Lifestyle during Coronavirus Pandemic in the MENA region: A Cross-Sectional Study

© The Authors 2020. The coronavirus disease (COVID-19) has rapidly spread globally, forcing countries to apply lockdowns and strict social distancing measures. The aim of this study was to assess eating habits and lifestyle behaviors among residents of the Middle East and North Africa (MENA) region during the lockdown. A cross-sectional study among adult residents of the MENA region was conducted using an online questionnaire designed on Google Forms during April 2020. A total of 2970 participants from 18 countries participated in the current study. During the pandemic, over 30% reported weight gain, 6.2% consumed five or more meals per day compared to 2.2% before the pandemic (p\u3c0.001), and 48.8% did not consume fruits on daily basis. Moreover, 39.1% did not engage in physical activity, over 35% spent more than five hours per day on screens. A significant association between the frequency of training during the pandemic and the reported change in weight was found (p \u3c 0.001). A significantly higher percentage of participants reported physical and emotional exhaustion, irritability, and tension either all the time or a large part of the time during the pandemic (p \u3c 0.001). Although a high percentage of participants reported sleeping more hours per night during the pandemic, 63% had sleep disturbances. The study highlights that the lockdown due to the COVID-19 pandemic caused a variety of lifestyle changes, physical inactivity, and psychological problems among adults in the MENA region

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p<0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p<0.0001; Nectin-2, p<0.0001; NT5E, p<0.0001; Siglec-7, p<0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p<0.0001; MICA, p<0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients.This research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-20-507 and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p&lt;0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p&lt;0.0001; Nectin-2, p&lt;0.0001; NT5E, p&lt;0.0001; Siglec-7, p&lt;0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p&lt;0.0001; MICA, p&lt;0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients