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Many wheelchair people depend on others to control the movement of their wheelchairs, which significantly influences their independence and quality of life. Smart wheelchairs offer a degree of self-dependence and freedom to drive their own vehicles. In this work, we designed and implemented a low-cost software and hardware method to steer a robotic wheelchair. Moreover, from our method, we developed our own Android mobile app based on Flutter software. A convolutional neural network (CNN)-based network-in-network (NIN) structure approach integrated with a voice recognition model was also developed and configured to build the mobile app. The technique was also implemented and configured using an offline Wi-Fi network hotspot between software and hardware components. Five voice commands (yes, no, left, right, and stop) guided and controlled the wheelchair through the Raspberry Pi and DC motor drives. The overall system was evaluated based on a trained and validated English speech corpus by Arabic native speakers for isolated words to assess the performance of the Android OS application. The maneuverability performance of indoor and outdoor navigation was also evaluated in terms of accuracy. The results indicated a degree of accuracy of approximately 87.2% of the accurate prediction of some of the five voice commands. Additionally, in the real-time performance test, the root-mean-square deviation (RMSD) values between the planned and actual nodes for indoor/outdoor maneuvering were 1.721 × 10−5 and 1.743 × 10−5, respectively.

Very few studies have been concerned with assessing the prevalence of burnout and depressive symptoms, especially during an infectious outbreak on non-frontline health care workers, such as a psychiatrist. In such instances, the role of psychiatrists and other mental health providers as a source of psychological support to the public and frontline workers is indispensable and valuable. This study aims to assess the prevalence of burnout and depressive symptoms, and their correlation, during the COVID-19 pandemic among psychiatry residents in Saudi Arabia. A total of 121 out of 150 psychiatry residents in Saudi Arabia completed the Maslach Burnout Inventory and Patient’s Health Questionnaire for the assessment of burnout and depressive symptoms. Burnout symptoms were found in 27.3%, and another 27.3% reported having depression symptoms. In addition, 16.5% reported having both burnout and depressive symptoms, with a significant relationship between them. Participants in the first 2 years of training and having a history of receiving mental health treatment in the past 2 years were at higher risk. The need is urgent to increase investment in mental health services and to construct a plan to reduce this risk of burnout and depression among psychiatrists by developing preventative strategies to prevent burnout and promote wellness is more important than ever.

Research on native Arabic speakers’ perception of non-native English phonemic contrasts has manifested various conclusions. Some studies have revealed that native Arabic speakers experience difficulty in the perception of non-native English phonemic contrasts, where others have concluded that they largely do not experience such difficulty. Due to this discrepancy, the current study aimed to examine the overall perceptual accuracy of only the English labial categories /p, b, f, and v/ in onset positions performed by native Arabic speakers. The study also examined the potential effects of the phonetic contexts and the familiarity of the stimuli being tested on the participants’ perceptual performance. Twenty-four Saudi male participants completed consonantal phoneme identification and discrimination tasks. The findings revealed that the participants experienced difficulty in the perception of the categories /p/ and /v/, confusing them with their counterparts /b/ and /f/. The findings also revealed that neither phonetic context nor familiarity had any effect on the participants’ perceptual accuracy of all of the categories in question, except in the context in which the category /v/ was followed by back vowels. In this specific context, the participants’ performance tended to be lower, which could be attributed to the influence of lip rounding, which results in coarticulation with the fricative noise associated with this category (/v/). Lastly, the results obtained in this study provide additional crucial insights into auditory phonetics and present additional explanation on how the human auditory system recognizes speech sounds.

Currently, antiviral drugs and/or vaccines are not yet available to treat or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we narrated the available data, from credible publishers, regarding the possible role of polyphenols and natural extracts-containing polyphenols in the prevention of coronavirus disease 2019 (COVID-19), and their immune-boosting properties. It was revealed that polyphenols could be considered as promising biologically active substances for the prevention of COVID-19. The underlying potential mechanism behind this action is mostly due to the antiviral activities and the immune-regulation functions of polyphenols against COVID-19-infections. Antivirus polyphenolic-based medications can mitigate SARS-CoV-2-enzymes, which are vital for virus duplication and infection. It was also found that triterpenoid, anthraquinone, flavonoids, and tannins are possible keys to scheming antiviral therapies for inhibiting SARS-CoV-2-proteases. The identified pharmacophore structures of polyphenols could be utilized in the explanation of novel anti-COVID-19 designs. The advantage of using mixtures containing polyphenols is related to the high-safety profile without having major side-effects, but further randomized controlled trials are required in the upcoming studies., Highlights • Polyphenols possess many potential health benefits, including antiviral effects. • Polyphenols consider promising bioactive substances for COVID-19 prevention. • Polyphenol-rich foods will be helpful during the COVID-19's treatment. • Polyphenols assist as blocking agent for protease's enzymatic activity of COVID-19.

Background: The objective was to evaluate the level of awareness regarding systemic lupus erythematosus (SLE) among the general population in the Al-Qassim region, Kingdom of Saudi Arabia (KSA).Methods: This was a cross-sectional study carried out between March and April 2021 and conducted among the general population at Al-Qassim region, KSA. A valid pre-tested electronic questionnaire was distributed through social media among the targeted population that included socio-demographic characteristics and questionnaires measuring awareness, attitude and their belief about SLE. All statistical analyses were performed using SPSS version 26.Results: A total of 377 participants were enrolled. The most common age group was more than 40 years old (39%), with slightly females (52.5%) than males. The prevalence of participants who had heard about SLE was 52.5%. Of those who have heard about SLE, a poor level of awareness was detected among 69.2% of participants, while 30.8% were at a good level. Factors associated with an increased level of awareness were having diagnosed been with SLE and those who indicated their doctor as their sources of SLE information.Conclusions: The awareness of the general population in the Al-Qassim region regarding SLE was insufficient. Obtaining SLE information from their doctor and having been diagnosed with SLE are associated with better awareness. We propose that awareness campaigns should be promoted.

Background Th appropriate placement and size selection of mitral prostheses in transcatheter mitral valve implantation (TMVI) is critical, as encroachment on the left ventricular outflow tract (LVOT) may lead to flow obstruction. Recent advances in computed tomography (CT) can be employed for pre-procedural planning of mitral prosthetic valve placement. This study aims to develop patient-specific computational fluid dynamics models of the left ventricle (LV) in the presence of a mitral valve prosthesis to investigate blood flow and LVOT pressure gradient during systole. Methods Patient-specific computational fluid dynamics simulations of TMVI with varied cardiac anatomy and insertion angles were performed (n = 30). Wide-volume full cycle cardiovascular CT images prior to TMVI were used as source anatomical data (n = 6 patients). Blood movement was governed by Navier-Stokes equations and the LV endocardial wall deformation was derived from each patient's CT images. Results The computed pressure gradients in the presence of the mitral prosthesis compared well with clinically measured gradients. Analysis of the effects of prosthetic valve angulation, aorto-mitral annular angle, ejection fraction, LV size and new LVOT area (neo-LVOT) after TMVI in silico revealed that the neo-LVOT area (p < 0.001) was the most significant factor affecting LVOT pressure gradient. Angulation of the mitral valve can substantially mitigate LVOT gradient. Conclusions Computational fluid dynamics simulation is a promising method to aid in pre-TMVI planning and understanding the factors underlying LVOT obstruction.

The first case of COVID-19 originated in Wuhan, China, after which it spread across more than 200 countries. By 21 July 2020, the rapid global spread of this disease had led to more than 15 million cases of infection, with a mortality rate of more than 4.0% of the total number of confirmed cases. This study aimed to predict the prevalence of COVID-19 and to investigate the effect of awareness and the impact of treatment in Saudi Arabia. In this paper, COVID-19 data were sourced from the Saudi Ministry of Health, covering the period from 31 March 2020 to 21 July 2020. The spread of COVID-19 was predicted using four different epidemiological models, namely the susceptible&ndash, infectious&ndash, recovered (SIR), generalized logistic, Richards, and Gompertz models. The assessment of models&rsquo, fit was performed and compared using four statistical indices (root-mean-square error (RMSE), R squared (R2), adjusted R2 (&nbsp, Radj2), and Akaike&rsquo, s information criterion (AIC)) in order to select the most appropriate model. Modified versions of the SIR model were utilized to assess the influence of awareness and treatment on the prevalence of COVID-19. Based on the statistical indices, the SIR model showed a good fit to reported data compared with the other models (RMSE = 2790.69, R2 = 99.88%, Radj2 = 99.98%, and AIC = 1796.05). The SIR model predicted that the cumulative number of infected cases would reach 359,794 and that the pandemic would end by early September 2020. Additionally, the modified version of the SIR model with social distancing revealed that there would be a reduction in the final cumulative epidemic size by 9.1% and 168.2% if social distancing were applied over the short and long term, respectively. Furthermore, different treatment scenarios were simulated, starting on 8 July 2020, using another modified version of the SIR model. Epidemiological modeling can help to predict the cumulative number of cases of infection and to understand the impact of social distancing and pharmaceutical intervention on the prevalence of COVID-19. The findings from this study can provide valuable information for governmental policymakers trying to control the spread of this pandemic.

Atovaquone is a FDA-approved antimalarial agent that has also shown potent anticancer properties. In the current study, we demonstrate that atovaquone is a prime candidate for treatment of high-grade serous ovarian cancer. We have tested atovaquone against a panel of ovarian cancer cells lines and shown that this drug inhibits proliferation and induces apoptosis at IC50 concentrations between 10-20 microM. Exposure to atovaquone results in increased apoptosis as indicated by an increase in cleaved caspase 3 and other relevant apoptotic markers. Additionally, our data also suggest that atovaquone is able to reactivate p53. Inhibition of p53 attenuates the cytotoxicity of atovaquone. However, the primary event that occurs in atovaquone-treated cells is the rapid surge in intracellular oxygen radicals. Imaging cytometry experiments conclusively demonstrate that the oxygen radical surge originates in the mitochondria. The oxidative stress caused by atovaquone is responsible for DNA damage and p53 activation. The atovaquone-induced oxygen radical surge also leads to damage to the Na+/K+-ATPase, perturbing the ability of the cancer cells to maintain an optimal membrane potential. This increase in oxygen radicals occurs because atovaquone targets the oxidative phosphorylation pathway in the mitochondria and blocks electron transport. Measurements conducted on the Seahorse analyzer show decreased consumption of oxygen and lower levels of ATP in the atovaquone-treated cells. In the malarial parasite, atovaquone targets mitochondrial complex III. In ovarian cancer cells, supplying succinate did not reverse atovaquone-induced inhibition of oxidative phosphorylation. On the other hand, when cells were supplemented with the substrate for complex IV, the oxygen consumption rate normalized in atovaquone-exposed cells. These experiments suggest that atovaquone is likely inhibiting complex I-III of mitochondria. Atovaquone is a naphthoquinone with significant structural similarity with the electron transporter ubiquinone. In silico modeling experiments indicate that atovaquone can bind to the ubiquinone binding pocket on complexes I-III. Based on these experiments, we propose that atovaquone is competing with ubiquinone to inhibit efficient electron transport and thereby increasing the intracellular oxygen radicals. Ovarian tumor-bearing mice tolerated prolonged treatment with Mepron®, the clinical formulation of atovaquone. Daily treatment of ID8 tumor-bearing C57BL/6 mice with atovaquone for 3-4 weeks resulted in a significant decrease in tumor growth. Additionally, we also show decreased proliferation of human ovarian tumors treated ex vivo with atovaquone. These experiments indicate that atovaquone can be used as a safe and effective drug for chemoprevention and chemotherapy of ovarian tumors. Citation Format: Arvinder Kapur, Mildred Felder, Yousef Alharbi, Allegra Cappuccini, Bikash Pattnaik, Lisa Barroilhet, Manish Patankar. Antimalarial agent, atovaquone, inhibits cancer cell proliferation by targeting oxidative phosphorylation and is a candidate for chemoprevention and chemotherapy of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B36.

With their role in connecting disease-associated antigens to the cellular immune response, antibodies hold considerable promise as therapeutic agents. This chapter discusses three classes of therapeutic antibodies that have been developed for use in ovarian cancer therapy. The first includes antibodies selected against tumor-associated antigens such as MUC16/CA125, mesothelin, epithelial cell adhesion molecule, and folate receptor α‎. Antibodies in the second class target proteins such as CTLA-4 and PD1 that act as immune response checkpoint receptors. The third class of antibodies target secreted factors that promote tumor growth: targets in this class include vascular endothelial growth factor, cytokines, and chemokines. The development of each of these is described. The chapter also discusses the complications presented by soluble antigens, which serve to limit the applicability of antigens (such as MUC16/CA125) that are both cell-surface associated and circulating and the prospects for the combination of antibody-based immunotherapy and chemotherapy.

Aerobic glycolysis is an important metabolic adaptation in tumors. However, there is mounting evidence that oxidative phosphorylation (OXPHOS) also contributes to metabolism in cancer cells. Therefore, agents targeting OXPHOS can serve as novel anticancer agents. We will present data on small molecule agents that inhibit the proliferation of ovarian and other cancer cells by inhibiting mitochondrial electron transport. We have focused our attention on citral, plumbagin, curcumin, cinnamaldehyde, piperlongumine, perillaldehyde, nonenal and other naturally occurring agents. All of these molecules share a common molecular epitope, the unsaturated carbonyl that participates in redox reactions. Cancer cells treated with these agents show a marked decrease in oxygen consumption rate and an increase in extracellular acidification. The redox ratio (NADH/FAD) and cellular ATP levels also decrease in response to these small molecule agents. In our search for additional and more potent OXPHOS inhibitors we have discovered that the FDA-approved anti-malarial drug atovaquone is an efficient inhibitor of electron transport in ovarian cancer cells. Chronic administration of atovaquone decreases the growth of ID8 tumors in C57BL/6 mice. Investigation in to the mechanism of action of the unsaturated carbonyl compounds indicates that their initial effect in cancer cells is the immediate and substantial rise in oxygen radicals as a result of OXPHOS inhibition. This increase in reactive oxygen causes extensive oxidative damage leading to DNA strand breaks. Subsequently, we have observed activation of p53-mediated apoptosis. These experiments are suggesting that inhibition of OXPHOS and the subsequent increase in intracellular oxygen radicals can result in the reactivation of the tumor suppressive responses of at least a subset of the p53 mutants. Additionally, our studies also indicate that the oxidative stress occurring as a result of OXPHOS inhibition directly leads to inhibition of ion transport through the Na+/K+-ATPase. As a result of this inhibition, cancer cells are unable to maintain a normal membrane potential. Studies are currently underway to determine if the inability to maintain membrane potential also contributes to apoptotic cancer cell death induced by these unsaturated carbonyl-containing compounds. Oxidative stress caused by these compounds leads to an increase in superoxide dismutase, catalase and glutathione synthesis via the activation of Nrf-2. Inhibition of Nrf-2 results in an increase in the potency of the unsaturated carbonyl compounds. We are therefore examining Nrf-2 increase as a form of chemoresistance mechanism that likely impinges on the anti-cancer activity of the unsaturated carbonyl compounds. These studies are allowing us to develop medicinal chemistry-based approaches to develop novel molecules with increased potency and targetability as OXPHOS inhibitors for the treatment of ovarian cancer. Citation Format: Arvinder Kapur, Amruta Nayak, Mildred Felder, Allegra Cappucini, Spencer Ericksen, Yousef Alharbi, Bikash Pattnaik, Lisa Barroilhet, and Manish S. Patankar. TARGETING OVARIAN TUMORS WITH OXPHOS INHIBITORS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-103.

Plumbagin and atovaquone are chemotoxic to ovarian, breast and other tumors. Both molecules inhibit oxidative phosphorylation causing a rapid increase in intracellular oxygen radicals and apoptosis. Oxidative stress is also known to inhibit the activity of Na+/K+-ATPase (NKA), the ion channel that maintains the membrane potential. Here, we investigate if the oxidative stress mediated by plumbagin and atovaquone also leads to inhibition of NKA activity. We confirm that plumbagin and atovaquone inhibit proliferation of three human (OVCAR-3, SKOV-3 and TYKNu) and one mouse (ID8) ovarian cancer cell lines. Using SKOV-3 and OVCAR-3 as models for ovarian cancer, we demonstrate that oxygen radical scavenger, N-acetylcysteine (NAC) attenuated the cytotoxicity of plumbagin and atovaquone. Using whole cell patch clamping we demonstrate that plumbagin and atovaquone inhibit outward and inward current flowing through NKA in SKOV-3 and OVCAR-3. Both drugs decrease cellular ATP. Providing exogenous ATP (5 mM) in the pipet solution used during patch clamping did not recover NKA activity in the plumbagin or atovaquone treated SKOV-3 and OVCAR-3 cells. However, pretreatment of the cells with NAC completely abrogated the NKA inhibitory activity of plumbagin and atovaquone. Exposure of the SKOV-3 cells to either of the drugs for 1-2 h resulted in a significant decrease in the expression of NKA. We conclude that oxidative stress caused by plumbagin and atovaquone degrades NKA and hence the membrane potential cannot be optimally maintained. Evaluation of compounds that induce oxidative stress should therefore consider contribution of NKA inhibition to the cytotoxic activity of such agents. Citation Format: Yousef Alharbi, Arvinder Kapur, Mildred Felder, Lisa Barroilhet, Bikash Pattnaik, Manish S. Patankar. Plumbagin and atovaquone inhibit Na+/K+-ATPase through the generation of oxidative stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 891.

Background: Delay in seeking medical care has many negative effects on the patient’s condition and medical cost, and it reduces the potential benefits of early interventions. Delay in seeking medical care, which is affected by many factors, is a common global problem. This study aimed to study the prevalence and causes of delay in seeking medical care in Al-Madina, Saudi Arabia. Method: This research was a cross-sectional study conducted among Al-Madina population using a self-administrated questionnaire which was only administered when the inclusion and exclusion criteria for the study have been met by the participants. The questionnaire collected the demographic characteristics and information about the prevalence and the reasons of delaying in seeking medical care in Al-Madina, Saudi Arabia. Results: The study included 441 subjects out of which 61.9% were females while 38.1% were males. Seventy-eight and point two percent had university education level. Only 27.4% of participants always seek medical care as soon as they feel they need it. Delayed seeking medical care due to a financial impediment was stated by 26.1% of the subjects. Merely 25.2% had health insurance. The language was the most important criteria when choosing health service providers for 42% of patients. Severe pain forces 40.1% of participants to seek medical care, while moderate pain drives only 4.3% to seek medical care while 58.9% seek medical care when the pain or discomfort increases with time. Conclusion: There was a high prevalence of delay in seeking medical care among Al-Medina population, Saudi Arabia. Economic factors and lack of health insurance are among the main obstacles in seeking medical care. Acute pain serves as the principal reason in seeking medical care among Al- Madina population.

The correct placement of mitral prostheses in transcatheter mitral valve replacement (TMVR) is crucial, since any obstruction of the left ventricular outflow tract (LVOT) by the mitral device may decrease the LVOT area, leading to flow obstruction. Recent advances in patient-specific modelling based

Cardiac glycosides (CG) are potent inhibitors of Na+/K+-ATPase (NKA), inducing apoptosis through the inhibition of ion current. We developed a synthetic CG, CEN09-106, with enhanced cytotoxic potential over conventional CGs such as oubain and others. For specific delivery to the tumor, CEN09-106 was conjugated through a stable chemical linker to antibodies targeted against cell surface proteins that form complexes with NKA. Due to this molecular design CEN09-106 is locally presented to the tumor and inhibits NKA activity. Internalization of CEN09-106 is not required for its cytotoxicity, and hence we refer to this family of antibody-CG complexes as extracellular drug conjugates (EDC). Ovarian tumors overexpress FXYD5, a modulator of NKA activity. We have developed EDC1 to target FXYD5. Here, we demonstrate the ability of EDC1 to target ovarian tumors and confirm its mechanism of action. First, we compared the activity of oubain, CEN09-106, and EDC1 in cell viability assays. While the potency of oubain was approximately 1-10 mM, CEN09-106 and EDC1 both had IC50 between 1-2.5 nM when tested against OVCAR-5, OV2008, and SKOV3 cells. Expression of FXYD5 in these cell lines was confirmed by flow cytometry. The inhibition of cell viability was attributed to apoptosis induced by CEN09-106 and EDC1 as measured by increase in cleaved caspase3 and annexin V binding and decrease in Bcl-2 expression. CEN09-106 and EDC1 also inhibited viability of the cisplatin-resistant C13 (IC50 ~2.5 nM) cells. Whole-cell patch-clamp recording of cancer cells revealed NKA ionic current in SKOV-3 and OV2008 cells after inhibition of majority of the cell surface ion transporters and channels. Outward ion current detected in SKOV3 and OV2008 prior to treatment with CEN09-106 and EDC1 was in the range of 500-1000 pA. Upon treatment with CEN09-106 and EDC1 (2.5 nM, each), the current in these two cell lines decreased to only 200-400 pA, a 60-75% decrease. In vivo administration of EDC1 in nonhuman primates established its low general toxicity profile. In vivo studies in xenograft mouse models are currently under way and are showing promising results with significant inhibition of SKOV3 and OV2008 tumors when CEN09-106 and EDC1 were administered intraperitoneally. In ongoing work, we are screening additional platinum-sensitive and -resistant ovarian cancer lines for their responses to EDC1. These basic and translational studies will serve as the foundation to demonstrate the clinical value of EDC1 in the treatment of patients with ovarian tumors. Citation Format: Yousef Alharbi, Arvinder Kapur, Jim Prudent, David Marshall, Mildred felder, Bikash Pattnaik, Manish Patankar. Antibody-conjugated cardiac glycosides: Potent agents for treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B11.