Search

Ayman Mubarak,1 Bahauddeen Alrfaei,2 Abdullah Aljurayyan,3 Mahfoudh M Alqafil,1 Mohamed A Farrag,1 Maaweya E Hamed,1 Bandar Alosaimi,4 Fahad Almajhdi,1 Wael Alturaiki5 1Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia; 2Stem Cells Unit, Department of Cellular Therapy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Science, MNGHA, Riyadh, Saudi Arabia; 3Immunology and HLA Department, Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia; 4Research Center, King Fahad Medical City, Riyadh, Saudi Arabia; 5Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaCorrespondence: Wael AlturaikiDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi ArabiaEmail w.alturaiki@mu.edu.saBackground: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate.Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array.Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels.Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α 2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5).Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL.Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.Keywords: MERS-CoV, proinflammatory cytokines, regulatory cytokines, anti-DPP4, IFNs, A549 lung cells

Objectives The spread of misinformation through the internet can lead to dangerous behavioral changes and erode trust in reliable sources, especially during public health crises like coronavirus disease 2019 (COVID-19). To combat this issue, innovative strategies that leverage information technology are essential. This study focused on developing and evaluating a mobile application (app), COVID-Iran, aimed at countering COVID-19 misinformation by delivering accurate, reliable, and credible information. Methods The development of the app involved a multi-step, user-centered approach that integrated qualitative expert consultations with quantitative survey research to pinpoint and validate key features. The app was initially prototyped using Enterprise Architect software and subsequently developed using Android Studio and MySQL. We conducted a usability evaluation using the System Usability Scale (SUS), where participants engaged in various tasks related to information seeking, self-assessment, and health management. Data were analyzed using descriptive statistics in SPSS version 19. Results The findings revealed a high usability level (SUS score of 81.35), with participants reporting ease of use and learnability. The app effectively countered misinformation by providing access to trusted sources and evidence-based counterarguments. User feedback emphasized the app’s strengths in clarity, accuracy, trustworthiness, and its comprehensive approach. Plans for future improvements include the integration of artificial intelligence to deliver personalized content. Conclusions Despite limitations such as the small sample size and potential self-selection bias, this study highlights the significant potential of mHealth apps to provide reliable health information and combat misinformation.

The last decennia have witnessed spectacular advances in our knowledge about the influence of the gut microbiome on the development of a wide swathe of diseases that extend beyond the digestive tract, including skin diseases like psoriasis, atopic dermatitis, acne vulgaris, rosacea, alopecia areata, and hidradenitis suppurativa. The novel concept of the gut-skin axis delves into how skin diseases and the microbiome interact through inflammatory mediators, metabolites, and the intestinal barrier. Elucidating the effects of the gut microbiome on skin health could provide new opportunities for developing innovative treatments for dermatological diseases. Psoriasis is a complex disease with multiple factors contributing to its development, such as diet, lifestyle, genetic predisposition, and the microbiome. This paper has a dual purpose. First, we outline the current knowledge on the unique gut microbiota patterns implicated in the pathogenesis of psoriasis. Second, and of equal importance, we briefly discuss the reciprocal impact of psoriasis treatment and gut microbiome. In addition, this review explores potential therapeutic targets based on microbial interventions, which hold promise for providing new treatment options for psoriasis.

Abstract Deep learning neural networks are often described as black boxes, as it is difficult to trace model outputs back to model inputs due to a lack of clarity over the internal mechanisms. This is even true for those neural networks designed to emulate mechanistic models, which simply learn a mapping between the inputs and outputs of mechanistic models, ignoring the underlying processes. Using a mechanistic model studying the pharmacological interaction between opioids and naloxone as a proof-of-concept example, we demonstrated that by reorganizing the neural networks’ layers to mimic the structure of the mechanistic model, it is possible to achieve better training rates and prediction accuracy relative to the previously proposed black-box neural networks, while maintaining the interpretability of the mechanistic simulations. Our framework can be used to emulate mechanistic models in a large parameter space and offers an example on the utility of increasing the interpretability of deep learning networks.

Abstract This study explores the influence of inter-dot tunneling effects within a quantum dot molecule on the Fresnel diffraction phenomenon. Our findings indicate that the Fresnel diffraction of the output probe Gaussian field can be manipulated by adjusting the inter-dot tunneling parameter’s strength and the characteristics of the coupling field. The inter-dot tunneling effect establishes a closed-loop system, setting conditions for the interference of the applied fields. We specifically examine a Laguerre–Gaussian (LG) coupling field, investigating how its properties-such as strength, value, and sign of the orbital angular momentum (OAM)-impact the Fresnel diffraction of the output probe field. Increasing the inter-dot tunneling parameter and the coupling LG field’s strength allows for control over the spatial distribution of the Fresnel diffraction pattern. Notably, the inter-dot tunneling parameter can disturb the symmetry of the diffraction patterns. Additionally, considering a negative OAM for the coupling LG field transforms the diffraction pattern into its inverse shape. This suggests that, in the presence of the inter-dot tunneling effect, the Fresnel diffraction pattern is contingent on the direction of rotation of the helical phase front of the coupling LG field. Our results offer insights into quantum control of Fresnel diffraction patterns and the identification of OAM in LG beams, presenting potential applications in quantum technologies.

High-order harmonic generation (HHG) in semiconductor thin films from ultrashort mid-infrared laser drivers holds the potential for the realization of integrated sources of extreme ultraviolet light. Here, we demonstrate solid-state HHG in zinc oxide thin films synthesized by the radiofrequency reactive magnetron sputtering process directly on the cleaved facets of optical fibers. Harmonics 3 to 13 of the radiation from a fiber-based laser system delivering 500 kW, 96 fs pulses at 3130 nm are produced in the thin film and guided along the fiber. A proper choice of the laser wavelength and fiber material allows for filtering out the mid-IR pump laser and achieving the HHG mode selection. The possibility to nanostructure the fiber exit by, e.g., focused ion beam milling paves the way to an increased control over the HHG spatial mode.

Key Clinical Messages Early diagnosis of cryptococcal infection is the key to improving outcomes, any newly diagnosed HIV patient presenting with subacute or chronic headache, particularly those who are CD4‐deplete, should be investigated for cryptococcal meningitis. We had some delay in our patient management, including delay in HIV diagnosis, delay in doing LP and delay in initiation of anti‐cryptococcal treatment and also early start of ART before specific cryptococcal treatment exacerbated IRIS in the patient. So, paying attention to these points can improve the prognosis of such patients. Abstract Cryptocccus is a fungal pathogen and the causative agent of Cryptococcosis among human immunodeficiency virus (HIV) positive people. Meningoencephalitis is the most common manifestation of cryptococcal infection, while pulmonary cryptococcosis is often neglected due to nonspecific clinical and radiological presentation leading to a delay in diagnosis and disseminated disease. Here, we reported a 67‐year‐old man with newly diagnosed HIV who presented with concurrent cryptococcal meningoencephalitis and pulmonary cryptococcosis that admitted with the complaint of dyspnea and productive cough for 1.5 months, worsening shortness of breath, fever and weight loss since 15 days prior to admission. He also had severe oral candidiasis. Lung computed tomography (CT) revealed ill‐defined subpleural cavitary lesion in left lower zone with bilateral diffuse ground glass opacity and air bronchogram. His HIV PCR test was positive with absolute CD4 count less than 50 cells/mm3. After starting antiretroviral therapy (ART), he gradually developed a headache and decreased level of consciousness. Cerebrospinal fluid (CSF) analysis revealed 450 cells, predominantly lymphocytes, with protein of 343 mg/dL and glucose of 98 mg/dL (corresponding blood glucose 284 mg/dL). CSF India ink staining was positive for crypococcus spp. Liposomal amphotericin B in combination with fluconazole (due to the unavailability of flucytosin) was stated. He was intubated because of hypoxia and his bronchoalveolar lavage was positive for Cryptococcus spp. too. He died 2 weeks after starting antifungal therapy based on this study it should be mentioned that neurologic and respiratory symptoms may be the first presentation of acquired immunodeficiency syndrome.

Wetting front (WF) and redistribution wetting front (RWF) depend on different parameters such as soil type, soil layering, land slope, and emitter discharge rate. Experiments were conducted on the physical model applying constant 24 litres of irrigation water, three different slopes (0, 10, and 20%), and three different discharge rates (2, 4, and 8 L/h). Three homogeneous soils with light, medium, and heavy textures, and two non-homogeneous soils with horizontal layers (LMH: a light texture in the top layer, a medium texture in the middle layer, and a heavy texture in the bottom layer; HML: a heavy texture in the upper layer, a medium texture in the middle layer, and a light texture in the lower layer) were used. The results showed that when the dripper flow rate doubled, in LMH soil, where the light texture was in the top layer, the amount of wetting depth was, on average, 20% higher than HML soil in which the top layer had a heavy texture. In all experiments, the highest increases in the maximum wetting depths of the RWF in five measurement stages within 24 h after irrigation were related to slopes of 0%, 10%, and 20%, respectively. A comparison between homogeneous and non-homogeneous soils showed that the change in soil layering has a significant effect on the radius and depth of wetting. This matter needs to be considered in the design of drip irrigation systems.

High-harmonic generation is a light up-conversion process occurring in a strong laser field, leading to coherent bursts of extreme ultrashort broadband radiation [Lewenstein et al., Phys. Rev. A 49, 2117 (1994)]. As a new perspective, we propose that ultrafast strong-field electronic or photonic processes such as high-harmonic generation can potentially generate nonclassical states of light well before the decoherence of the system occurs [Gorlach et al., Nat. Commun. 11, 4598 (2020); Stammer et al., Phys. Rev. Lett. 128, 123603 (2022)]. This could address fundamental challenges in quantum technology such as scalability, decoherence, or the generation of massively entangled states [Lewenstein et al., Luca Argenti Michael Chini, 27 (2024)]. Here, we report experimental evidence of the nonclassical nature of the harmonic emission in several semiconductors excited by a femtosecond infrared laser. By investigating single- and double-beam intensity cross-correlation [Loudon, Rep. Prog. Phys. 43, 913 (1980)], we measure characteristic nonclassical features in the single-photon statistics. We observe two-mode squeezing in the generated harmonic radiation, which depends on the laser intensity that governs the transition from super-Poissonian to Poissonian photon statistics. The measured violation of the Cauchy-Schwarz inequality realizes a direct test of multipartite entanglement in high-harmonic generation [Wasak, Phys. Rev. A 90, 033616 (2014)]. This result is supported by the theory of multimodal detection and the Hamiltonian from which the effective squeezing modes of the harmonics can be derived [Gonoskov et al., Phys. Rev. B 109, 125110 (2024); Christ et al. New J. Phys. 13, 033027 (2011)]. With this work, we show experimentally that high-harmonic generation is a new quantum bosonic platform that intrinsically produces nonclassical states of light with unique features such as multipartite broadband entanglement or multimode squeezing. The source operates at room temperature, using standard semiconductors and a standard commercial fiber laser, opening up new routes for the quantum industry, such as optical quantum computing, communication, and imaging.

Abstract Background Short-term exposure to PM2.5 has been associated with human health risks. However, evidence on the association between short-term exposure to PM2.5 and the risk of chronic obstructive pulmonary disease (COPD) remains limited and controversial. This study aimed to specifically assess the relationship between exposure to PM2.5 and the risk of hospitalization due to COPD. Methods A systematic search was conducted in PubMed, Web of Science, and Google Scholar databases from January 1, 2010 to May 1, 2022. The odds ratio (OR) statistic was calculated as a common measure of effect size. Publication bias was also examined in all eligible studies on COPD hospitalization using funnel plots and Egger’s test, as well as trim-and-fill method for missing studies on COPD hospitalization. Results A total of 19 studies were included in this meta-analysis. Random-effects models were plotted to calculate the pooled effect size by measuring OR (χ2 = 349.95; df = 18; I2 = 94.86%; P = 0.007; Z = 2.68; P

BackgroundOne of the common concerns of healthcare systems is the potential for re-admission of COVID-19 patients. In addition to adding costs to the healthcare system, re-admissions also endanger patient safety. Recognizing the factors that influence re-admission, can help provide appropriate and optimal health care. The aim of this study was to assess comorbidities that affect re-admission and survival in COVID-19 patients using a joint frailty model.MethodsThis historical cohort study was done using data of patients with COVID-19 who were re-hospitalized more than twice in a referral hospital in North of Iran. We used the joint frailty model to investigate prognostic factors of survival and recurrence, simultaneously using R version 3.5.1 (library "frailtypack"). P-values less than 0.05 were considered as statistically significant.ResultsA total of 112 patients with mean (SD) age of 63.76 (14.58) years old were recruited into the study. Forty-eight (42.9%) patients died in which 53.83% of them were re-admitted for a second time. Using adjusted joint model, the hazard of re-admission increased with cancer (Hazard ratio (HR) = 1.92) and hyperlipidemia (HR = 1.22). Furthermore, the hazard of death increased with hyperlipidemia (HR = 4.05) followed by age (HR = 1.76) and cancer (HR = 1.64). It Also decreased with lung disease (HR = 0.11), hypothyroidism (HR = 0.32), and hypertension (HR = 0.97).ConclusionConsidering the correlation between re-admission and mortality in the joint frailty model, malignancy and hyperlipidemia increased the risk of both re-admission and mortality. Moreover, lung disease probably due to the use of corticosteroids, was a protective factor against both mortality and re-admission.

Background and purpose: Today, development of telemedicine technology has led to wide use of smartphone to connect patients and health care teams to improve patient care. The aim of this study was to determine the effect of a self-care application on pain and mobility rehabilitation in patients following total knee arthroplasty surgery. Materials and methods: A randomized controlled clinical trial was carried out in 100 patients who were candidates for knee arthroplasty surgery at Tehran Baqiyatullah (Aj) Hospital. In this study, the experimental group was provided with a self-care application and the control group received routine hospital care. At days 7 and 14 after the surgery, the two groups were evaluated for pain and mobility rehabilitation using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Von Korff Pain Intensity and Disability Score. Results: Out of 100 people, 30 were men and 70 were women with an average age of 48.66±15.62. Findings showed significant differences between the two groups, at day 14 after the surgery, in mobility rehabilitation (P= 0.004) and pain (P= 0.001) at 95% confidence interval. Conclusion: According to this study, the self-care application improved pain and motor recovery after total knee arthroplasty surgery. (Clinical Trials Registry Number: IRCT20210724051973N1)

HIV maturation inhibitors such as bevirimat (BVM) interfering with Gag processing are emerging as alternative anti-retroviral drug candidates. Here, the authors report structures of assemblies of HIV-1 Gag fragments spanning the CA C-terminal domain and SP1 region bound to BVM.

Over the course of the Coronavirus disease 2019 (COVID-19) pandemic, numerous complications have been documented. In this report, we have detailed an unexpected complication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in a 73-year-old female patient who was simultaneously afflicted with mucormycosis and another unanticipated problem. Due to the lack of recovery of the patient after receiving mucormycosis treatment and continued fever, cough and hemoptysis, bronchoscopy was performed for her. During bronchoscopy, we encountered a foreign body that was the cause of the patient’s fever, cough, and hemoptysis. Rigid bronchoscopy was performed and the foreign body was removed from the left main bronchus. The lack of a favorable treatment response after administering antifungal therapy suggested that the presence of a foreign body could potentially act as an underlying nidus, thus influencing the suboptimal therapeutic outcome. Mucormycosis is usually characterized by distinct radiological patterns. However, this case did not present predictable imaging findings, further complicating the diagnostic process associated with this invasive fungal infection.

Abstract Background and Aim Scientific collaborations play a vital role in advancing research in various disciplines, including medical informatics, health information management, medical librarianship, and information sciences. This study aims to provide an overview of Iranian researchers' scientific output in three disciplines and their collaboration networks. Methods The study utilized data from Scopus database and analyzed 2086 records of Iranian researchers' research outcomes over 10 years. Each article's citations were averaged to determine its impact factor. The study also reviewed the number of articles and citations in the past decade. Results The findings show that scientific output in the disciplines of medical informatics, health information management, medical librarianship, and information sciences has significantly increased among Iranian researchers in the past decade. The analysis of collaboration networks indicates a strong connection between these disciplines, with medical informatics having the highest degree of collaboration. Conclusion This study provides valuable insights into the scientific collaborations among Iranian researchers in medical informatics, health information management, medical librarianship, and information sciences. The findings can be used to inform future research and collaboration initiatives in these disciplines. The results suggest that Iranian researchers in these disciplines have made significant progress in scientific output and collaboration. However, further efforts are required to improve the quality and impact of their research.

Key Clinical Message Although immunodeficient patients are less prone to develop Coronavirus disease 2019 (COVID‐19)‐mediated cytokine storm, secondary infections can cause serious complications in this vulnerable population. They are more likely to develop opportunistic infections that can mimic the symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Herein, we presented a 27‐year‐old male patient of SARS‐CoV‐2 infection, who was complicated with Pneumocystis jirovecii pneumonia (PJP), following treatment with rituximab. First, he was hospitalized for 5 days with fever, cough, and dyspnea due to COVID‐19 infection, and treated with remdesivir and glucocorticoid. Then, he has been referred to our center with cough, dyspnea, body pain, and fever. Due to persistent fever, the progression of pulmonary lesions, and reduced oxygen saturation, we began treatment with piperacillin + tazobactam, vancomycin, and levofloxacin. Nevertheless, the patient's fever did not stop after the aforementioned empiric treatment and his condition got worse and he was admitted to the intensive care unit. The result of BAL fluid, tested for P. jirovecii by RT‐PCR, turned out to be positive. Therefore, we started trimethoprim‐sulfamethoxazole and dexamethasone, which improved his condition. We hope this article helps clinicians consider causes other than COVID‐19, especially opportunistic infections such as PJP, in patients with respiratory symptoms and fever.

The continuing emergence or re-emergence of vector-borne zoonotic Q fever (caused by Coxiella burnetii) and Crimean Congo hemorrhagic fever (CCHF, caused by Orthonairovirus) include indispensable extraordinary threat around the world. Low infectious dose and long-term environmental residence are major risks. Wildlife and domestic livestock act as hosts or reservoirs of the CCHF virus and ticks are carriers. The disease also poses a threat to public health services owing to its epidemic potential, high case fatality ratio (up to 40%) as well as difficulties in treatment, prevention, and control. Q fever is another zoonotic febrile disease mainly affecting workers involved in farming livestock. The causative agent of Q fever causes abortion in livestock. The pathogen is shed in large numbers in the waste of infected animals (amniotic fluids and placenta during parturition) and is transmitted by inhalation of contaminated aerosols. Vaccination is the most effective way of protecting against Q fever. The main way to prevent Q fever is to avoid contact with animals, especially while animals are giving birth, or consumption of unpasteurized milk and contaminated dairy products. Due to the increasing importation of livestock to meet the growing demand for dairy and meat products, new diseases are likely to be introduced. In our growing globalized world, where trade between countries increases, it is necessary to conduct more research on zoonotic diseases and to monitor any possible disease introduction to new areas. A continuing surveillance program and pathogen testing are important in tracking the emergence of new pathogens.

BackgroundDespite the increasing development of different smartphone apps in the health care domain, most of these apps lack proper evaluation. In fact, with the rapid development of smartphones and wireless communication infrastructure, many health care systems around the world are using these apps to provide health services for people without sufficient scientific efforts to design, develop, and evaluate them. ObjectiveThe objective of this study was to evaluate the usability of CanSelfMan, a self-management app that provides access to reliable information to improve communication between health care providers and children with cancer and their parents/caregivers, facilitating remote monitoring and promoting medication adherence. MethodsWe performed debugging and compatibility tests in a simulated environment to identify possible errors. Then, at the end of the 3-week period of using the app, children with cancer and their parents/caregivers filled out the User Experience Questionnaire (UEQ) to evaluate the usability of the CanSelfMan app and their level of user satisfaction. ResultsDuring the 3 weeks of CanSelfMan use, 270 cases of symptom evaluation and 194 questions were recorded in the system by children and their parents/caregivers and answered by oncologists. After the end of the 3 weeks, 44 users completed the standard UEQ user experience questionnaire. According to the children’s evaluations, attractiveness (mean 1.956, SD 0.547) and efficiency (mean 1.934, SD 0.499) achieved the best mean results compared with novelty (mean 1.711, SD 0.481). Parents/caregivers rated efficiency at a mean of 1.880 (SD 0.316) and attractiveness at a mean of 1.853 (SD 0.331). The lowest mean score was reported for novelty (mean 1.670, SD 0.225). ConclusionsIn this study, we describe the evaluation process of a self-management system to support children with cancer and their families. Based on the feedback and scores obtained from the usability evaluation, it seems that the children and their parents find CanSelfMan to be an interesting and practical idea to provide reliable and updated information on cancer and help them manage the complications of this disease.

Background: The present study aimed to investigate the one-year prevalence of SARS-CoV-2, common comorbidities and demographic information among negative- and positive rRT-PCR in health care workers (HCW), hospitalized and outpatients. Also, the association between SARS-CoV-2 cycle threshold (Ct) and the outcomes of patients were analyzed in Babol, northern Iran. Methods: This large retrospective cross-sectional study was performed between March 2020 and March 2021. The records of 19232 hospitalized, outpatients and HCW suspected to COVID-19 were collected from teaching hospitals in the North of Iran. Results: Out of the 19232 suspected to COVID-19 patients, 7251 (37.7%) had a positive rRT-PCR result; 652 (9%), 4599 (63.4%) and 2000 (27.6%) of those were categorized as HCW, hospitalized and outpatients, respectively. Moreover, between the hospitalized and the outpatient group, 10.2 and 0.8% cases died, whereas no death cases were reported in the HCW. Furthermore, it seems that death rate was significantly different between the three groups of Ct value, the highest mortality in those with Ct between 21 and 30 (group B=7.6%) and the lowest in the group with the highest Ct (between 31 and 40 = 5.5%) (p

Abstract Background This study aimed to determine the characteristics, vaccination status, and outcomes of confidence interval (COVID‐19) patients, admitted to a tertiary hospital in Iran during the predominant severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) Delta variant period. Methods This retrospective study assessed the medical records of all hospitalized COVID‐19 patients, who were admitted to a tertiary hospital from July 10 to September 15, 2021. Adjusted binary logistic regression analyses were conducted to determine factors associated with poor outcomes. Results More than 25% of hospitalized patients received at least one vaccine dose of SARS‐CoV‐2. The Sinopharm BIBP vaccine (China) was the most commonly received vaccine (73.3%). After adjusting for age and comorbidities, the adjusted odds ratio (AOR) for poor outcomes was significantly lower in hospitalized patients who received Remdesivir compared to those not receiving Remdesivir (AOR: 0.35; 95% confidence interval [CI]: 0.15, 0.78; p

Monkeypox is a zoonotic disease caused by a double-stranded DNA virus belonging to the genus Orthopoxvirus. Despite being endemic in Central and West Africa, the disease has received relatively little research attention until recent times. As the Coronavirus disease 2019 (COVID-19) pandemic continues to affect the world, the rising number of monkeypox cases in non-endemic countries has further stoked global public health concerns about another pandemic. Unlike previous outbreaks outside Africa, most patients in the present outbreak had no history of travel to the endemic regions. The overwhelming majority of patients were initially identified amongst homosexual men, who had attended large gatherings. Mutations in the coding regions of the viral genome may have resulted in fitness adaptation, enhancement of immune evasion mechanisms, and more efficient transmissibility of the 2022 monkeypox virus. Multiple factors such as diminished cross-protective herd immunity (cessation of smallpox vaccination), deforestation, civil war, refugee displacement, farming, enhanced global interconnectedness, and even climate change may facilitate the unexpected emergence of the disease. In light of the increasing number of cases reported in the present outbreak, healthcare professionals should update their knowledge about monkeypox disease, including its diagnosis, prevention, and clinical management. Herein, we provide an overview of monkeypox, with a focus on the 2022 outbreak, to serve as a primer for clinical practitioners who may encounter the disease in their practice.

This study aimed to evaluate the effectiveness of a Persian Medicine-based dietary protocol (PM diet) in patients infected with COVID-19. A randomized clinical trial was performed from July 2020 to January 2021 in Tehran, Iran. Eighty patients admitted due to pulmonary dysfunction caused by COVID-19 were randomly allocated into two groups: the PM diet or the common hospital (CH) diet. Eight beds in 2 rooms were considered for each group. Patients were randomly hospitalized in these rooms and received these diets up to discharge or death. The details of the PM diet were published before (Hospital diet for COVID-19, an acute respiratory infectious disease: An evidence-based Protocol of a Clinical Trial). O2 saturation level and duration of hospitalization, the rate of mortality, duration of fever, and duration of cough were considered as the primary and secondary outcomes, respectively. O2 Saturation and fever durationwere not different between groups (P-value= 0.08, 0.312, respectively). But the duration of hospitalization and the duration of cough in the PM diet group were significantly shorter than in the CH diet (P-value= 0.002, 0.009, and HR=2.02, 1.86 respectively). The mortality rate was significantly lower in the PM diet group than in the CH diet group (Odds ratio: 0.12, P-value=0.026). PM diet caused a lower mortality rate, shorter hospital stay, and better improvement in cough, but did not have a significant effect on O2 saturation and fever.

An upward trend in the incidence of Parkinson’s disease (PD), known as one of the most prominent neurodegenerative maladies, has evoked great concerns among medical community over the past decades. Recently, studies have suggested the initiation of PD in the gastrointestinal tract decades before the advent of manifestations. Accumulating evidence suggests that intracellular deposition of α-synuclein (α-syn) in patients with PD is associated with systemic inflammation leading to the neuroinflammation and neuropsychiatric disorders. The α-syn protein accumulation can be initiated from GI cells and distribute into CNS cells through trans-synaptic cell to cell transmission. Without doubt, gut microbiota affects the enteric nervous system (ENS) known as the “second brain”. Patients with PD have a different balance of bacteria in their intestines, as compared to healthy population. Metabolites from gut microbiota affect the enteric wall such as neurodegeneration. Probiotics have a substantial role in the neutralization or inhibition of reactive oxygen species (ROS) and free radicals and thus improve the PD symptoms. The anti-inflammatory role of probiotics also inhibits the neurodegeneration and PD development. Hence, probiotics contribute to the improvement of PD through several mechanisms which need more in-depth verification.

Objective(s): This study aimed to evaluate antibiotic resistance profiles and presence of virulence genes among Salmonella enterica serovar Enteritidis (S. Enteritidis) isolated from patients with gastroenteritis in various regions of Iran. Moreover, genetic relatedness among the strains was assessed by pulsed-field gel electrophoresis (PFGE).Materials and Methods: From April through September 2017, 59 Salmonella strains were isolated from 2116 stool samples. Of these strains, 27 S. Enteritidis were recovered. These strains were subjected to disk diffusion tests, polymerase chain reaction (PCR) for detection of virulence genes (invA, hilA, pefA, rck, stn, ssrA, ssaR, sefA, spvC, sipA, sipC, sopB, sopE, and sopE2), and PFGE.Results: High prevalence of resistance towards cefuroxime (n = 20, 74.1%) and ciprofloxacin (n = 13, 48.2%) were demonstrated. All tested strains possessed invA, hilA, sefA, sipA, sopB, and sopE. The least prevalent virulence gene was rck (n = 6; 22.2%). Based on combinations of virulence genes, 12 virulotypes were observed. The most common virulotype was VP2 (n = 12; 44.4%), harboring all of the virulence genes except for rck. PFGE typing showed only two distinct fingerprints among tested strains. Each fingerprint had completely different virulotypes. Notably, VP4 (harboring all genes except for rck and spvC) was only presented in pulsotype A, while VP2 was confined to pulsotype B.Conclusion: S. Enteritidis strains were derived from a limited number of clones, suggesting that it is highly homogenous. Future works should consider combinations of other genotyping methods together with larger sample sizes from more diverse sources.

Abstract Protozoan diseases such as malaria, leishmaniasis, Chagas disease, and sleeping sickness still levy a heavy toll on human lives. Deplorably, only few classes of anti-protozoan drugs have thus far been developed. The problem is further compounded by their intrinsic toxicity, emergence of drug resistance, and the lack of licensed vaccines. Thus, there is a genuine exigency to develop novel anti-protozoan medications. Over the past years, melittin, the major constituent in the venom of European honeybee Apis mellifera, has gathered the attention of researchers due to its potential therapeutic applications. Insofar as we are aware, there has been no review pertinent to anti-protozoan properties of melittin. The present review outlines the current knowledge about anti-protozoan effects of melittin and its underlying mechanisms. The peptide has proven to be efficacious in killing different protozoan parasites such as Leishmania, Plasmodium, Toxoplasma, and Trypanosoma in vitro. Apart from direct membrane-disruptive activity, melittin is capable of destabilizing calcium homeostasis, reducing mitochondrial membrane potential, disorganizing kinetoplast DNA, instigating apoptotic cell death, and induction of autophagy in protozoan pathogens. Emerging evidence suggests that melittin is a promising candidate for future vaccine adjuvants. Transmission-blocking activity of melittin against vector-borne pathogens underscores its potential utility for both transgenic and paratransgenic manipulations. Nevertheless, future research should focus upon investigating anti-microbial activities of melittin, alone or in combination with the current anti-protozoan medications, against a far broader spectrum of protozoan parasites as well as pre-clinical testing of the peptide in animal models.

Abstract Background Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines. Methods This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH). Results Five men and five women with a mean age of 57.30 ± 18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60% ± 3.94% and increased to 92.13% ± 3.28% after them (p

Abstract Background Severe side effects after vaccination with coronavirus disease 2019 (COVID‐19) vaccines are rare but can be fatal. To date, vaccine‐induced immune thrombotic thrombocytopenia (VITT) cases have been reported after injection of mRNA and adenoviral vectors COVID‐19 vaccines. Here, we report the second suspected case of VITT after vaccination with the Sinopharm vaccine, an inactive vaccine. Key Clinical Question The Key Clinical Question was to determine whether inactivated COVID‐19 vaccines could induce VITT and how to diagnose and treat such cases. Clinical Approach and Conclusions Our patient developed deteriorating symptoms the day after vaccination and was admitted to the emergency department on day 5 after vaccination. After performing laboratory analysis, thrombosis with thrombocytopenia was suggested, further confirmed by highly positive anti‐heparin–platelet factor 4 antibodies assay and color Doppler ultrasonography. He was then treated with high‐dose intravenous immunoglobulin, corticosteroid, and nonheparin anticoagulant.

BackgroundThe unique features of smartphones have extended their use in different fields, especially in the health care domain. These features offer new opportunities to support patients with chronic conditions by providing them with information, education, and self-management skills. We developed a digital self-management system to support children with cancer and their caregivers in Iran (low- and middle-income country). ObjectiveThis study is aimed at the development and preliminary evaluation of a cancer self-management system (CanSelfMan) tailored to the needs of children with cancer and their parents or caregivers. MethodsThis study was conducted in collaboration with a multidisciplinary team between January and February 2020 at MAHAK’s Pediatric Cancer Treatment and Research Center. We developed a self-management system in six stages: requirement analysis, conformity assessment, preparation of educational content, app prototyping, preliminary evaluation, and developing the final version. ResultsA total of 35 people (n=24, 69% parents and n=11, 31% children) volunteered to participate in the study. However, only 63% (15/24) of parents and 73% (8/11) of children were eligible to participate. By adopting a user-centered design approach, we developed a mobile app, CanSelfMan, that includes five main modules (knowledge base, self-management tips, self-assessment report, ask a question, and reminders) that provide access to reliable information about acute lymphocytic leukemia and the self-management skills required for side effect measurement and reporting. A web-based dashboard was also developed for oncologists and included a dashboard to monitor users’ symptoms and answer their questions. ConclusionsThe CanSelfMan app can support these groups by providing access to reliable information about cancer, facilitating communication between children or parents and health care providers, and helping promote medication adherence through a reminder function. The active participation of the target group can help identify their needs. Therefore, through the involvement of stakeholders such as patients, caregivers, and oncologists in the design process, we improved usability and ensured that the final product was useful. This app is now ready to proceed with feasibility studies.

BackgroundGastric cancer is one of the most common gastrointestinal cancers. Patients with gastric cancer experience disabilities and complications that lead to reduced quality of life. Empowering these patients by providing them with information and self-management skills can help reduce side effects and improve their quality of life. ObjectiveThe aim of this study was to identify the user requirements for developing a mobile-based self-management app to support patients with gastric cancer. MethodsData were analyzed using descriptive statistics and frequency distribution reports using IBM SPSS Statistics software. ResultsAll of the data elements and functional requirements except “data recording times” and “weight changes in graphs” were identified as essential by clinical experts and patients. Among the functional requirements required in a gastric cancer self-management app, the capabilities related to informing, announcing warnings, and reminders are included. In the demographic data section, most patients (14/26, 53%) did not comment on the importance of recording data such as name, surname, and place of residence, and the demographic data section was met with less agreement from patients than clinicians. ConclusionsApplying the requirements mentioned in this study can improve the self-management of patients with gastric cancer. Such apps can play an important role in empowering patients and improving their quality of life. However, the apps need to be designed and implemented to see how they can meet users’ requirements.

The electrochemical CO2 reduction reaction (CO2RR) on polycrystalline copper (Cu) electrode was performed in a CO2-saturated 0.10 M Na2CO3 aqueous solution at 278 K in the absence and presence of low-frequency high-power ultrasound (f = 24 kHz, PT ~ 1.23 kW/dm3) in a specially and well-characterized sonoelectrochemical reactor. It was found that in the presence of ultrasound, the cathodic current (Ic) for CO2 reduction increased significantly when compared to that in the absence of ultrasound (silent conditions). It was observed that ultrasound increased the faradaic efficiency of carbon monoxide (CO), methane (CH4) and ethylene (C2H4) formation and decreased the faradaic efficiency of molecular hydrogen (H2). Under ultrasonication, a ca. 40% increase in faradaic efficiency was obtained for methane formation through the CO2RR. In addition, and interestingly, water-soluble CO2 reduction products such as formic acid and ethanol were found under ultrasonic conditions whereas under silent conditions, these expected electrochemical CO2RR products were absent. It was also found that power ultrasound increases the formation of smaller hydrocarbons through the CO2RR and may initiate new chemical reaction pathways through the sonolytic di-hydrogen splitting yielding other products, and simultaneously reducing the overall molecular hydrogen gas formation.

Abstract Background Egyptian Upper Cretaceous waste clay samples from Yunis Mines, Qusseir vicinity, Eastern Desert, were investigated for their chemical and mineralogical compositions as well as for firing. These investigations were carried out to assess the suitability to use the waste clays for the production of lightweight bricks. X-ray fluorescence (XRF), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) techniques were applied for characterizing chemical and mineral compositions of the raw clays. On the other side, densification parameters of the fired samples up to 1100 °C were examined by using Archimedes water-saturation methods and by determining the density and crushing strength of the fired bodies. Results Two types of concrete were prepared using different grain sizes: coarse and a mix of coarse and fine aggregates. Concrete batches were prepared, and the mechanical strength and the bulk density were determined. Mineralogically, the waste samples consist of montmorillonite as the predominant clay mineral, with quartz, calcite, fluorapatite, anhydrite, and pyrite as impurities. Bulk density and apparent porosity of the fired clay sample at 1100 °C were 0.89 g/cm3 and 67.19%, respectively, while the bulk density of the two types of concrete range from 0.76 g/cm3 in coarse type with no fines to 0.90 g/cm3 in the coarse with 20% fine fraction. The crushing strength of both types is 25 kg/cm2 for coarse type and 45 kg/cm2 for coarse and fine types, respectively. Conclusions The results showed that the data provides a useful application of waste clay ramps of ancient Yunis mining tunnels in Qussier area with an additional mean to assess their suitability for the production of lightweight brick concretes to reduce density and their relatively good strength in modern buildings for non-loading building units and to enhance the thermal insulation of buildings.

Abstract Nano-structures excited by light can enhance locally the electric field when tuned to plasmonic resonances. This phenomenon can be used to boost non-linear processes such as harmonic generation in crystals or in gases, Raman excitation, and four wave mixing. Here we present a theoretical investigation of the near-field phase matching of attosecond pulses emitted by high-order harmonic generation (HHG) of an atom immersed in a multi-cycle femtosecond infrared laser field and a spatially inhomogeneous plasmonic field. We demonstrate that the spatial inhomogeneity factor of the plasmonic field strongly affects the electron trajectory and recombination time which can be used to control the attosecond emission. For further insight into the plasmonic field effect, we monitor the phase of each quantum path as a function of the inhomogeneity strength. Moreover, we investigate the attosecond emission as a function of near-field phase matching effects. This is achieved by calculating the coherent field superposition of attosecond pulses emitted from various intensities or field inhomogeneities. Finally, far-field and near-field phase matching effects are combined to modulate the harmonic spectral phase towards the emission of a single attosecond pulse.

Background: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) worldwide, especially among children and debilitated populations. The present study aimed to investigate a loop-mediated isothermal amplification (LAMP) technique for rapid detection of M. pneumoniae in clini-cal specimens collected from patients with pneumonia. Methods: Throat swabs were collected from 110 outpatients who suffered from pneumonia. Throat swab samples were obtained from patients referred to the hospital outpatient clinics of Tehran University hospitals, Iran in 2017. The presence of M. pneumoniae in the clinical specimens was evaluated by LAMP, PCR and culture methods. Sensitivity and specificity of the LAMP and PCR assays were also determined. Results: Out of 110 specimens, LAMP assay detected M. pneumoniae in 35 specimens. Detection limit of the LAMP assay was determined to be 33fg /μL or ~ 40 genome copies/reaction. Moreover, no cross-reaction with genomic DNA from other bacteria was observed. Only 25 specimens were positive by the culture method. The congruence between LAMP assay and culture method was ‘substantial’ (κ=0.77). Specificity and sensitivity of LAMP assay were 88.2%, 100% in compare with culture. However, the con-gruence between LAMP assay and PCR assay was ‘almost perfect’ (κ=0.86). Specificity and sensitivity of LAMP assay were 92.5%, 100% in compare with PCR. Conclusion: Overall, the LAMP assay is a rapid and cost-efficient laboratory test in comparison to other methods including PCR and culture. Therefore, the LAMP method can be applied in identification of M. pneumoniae isolates in respiratory specimens.

The nucleation and growth of sol-gel derived TiO2 colloidal nanoparticles have been studied using experiment and theory as well. In this study, the temperature effect on the formation of TiO2 nanoparticles was discussed and some effective parameters such as the supply rate of solute (Q0), the mean volumic growth rate of stable nuclei during the nucleation period (u), the diffusion coefficient of [Ti]+4 ions and the nucleus size were determined. The formation of TiO2 nanoparticles in three different temperatures (60, 70 and 80°C) was studied. The obtained results showed that the process temperature has a considerable impact on the nucleation and growth of TiO2 nanoparticles. It can be concluded that increasing the temperature leads to a decrease of the supersaturation and an increase of the nucleus size, supply rate of monomer, nanoparticles density and growth rate as evident from LaMer diagram.

Stainless steels (SUS) and dual-phase (DP) steels have tension-compression asymmetry (TCA) in mechanical responses to full loading cycles. This phenomenon can significantly influence sheet metal forming of such metals, however, it is difficult to describe this behaviour analytically. In this research, a novel analytical method for asymmetric elastic-plastic pure bending using the Cazacu–Barlat 2004 asymmetric yield function is proposed. It only uses material parameters in tension along with an asymmetry coefficient related to the yield function. Bending operations of SUS304 and DP980 are investigated as two case studies. In the pure bending for both SUS304 and DP980, moment–curvature diagrams are analytically obtained. Furthermore, linear and nonlinear springback behaviours of SUS304 are analytically investigated. Moreover, using the analytical model as a user-defined material, a numerical model is developed for both steels under pure bending. In the V-bending case of SUS304 with and without TCA effects, the springback behaviours of the material are investigated numerically. In addition, considering friction effects, the analytical method is further modified for predicting springback behaviours in the V-bending of 16 types of SUS304 with various strengths are determined. All the analytical and numerical results have good agreement with those experimental results from literature for validation.

Letter to the Editor

The use of artificial neural networks has increased in many areas of engineering. In particular, this method has been applied to many geotechnical engineering problems and demonstrated some degree of success. A review of the literature reveals that it has been used successfully in modeling soil behavior, site characterization, earth retaining structures, settlement of structures, slope stability, design of tunnels and underground openings, liquefaction, soil permeability and hydraulic conductivity, soil compaction, soil swelling and classification of soils. The method of conjugate gradients provides a very effective way to optimize large, deterministic systems by gradient descent. In its standard form, however, it is not amenable to stochastic approximation of the gradient. Here we explore a number of ways to adopt ideas from conjugate gradient and Back Propagation in the stochastic setting, using fast Hessian-vector products to obtain curvature information effectively. In our benchmark experiments the resulting highly scalable algorithms converge about an order of magnitude faster than ordinary stochastic gradient descent. The objective of this paper is to provide a general view to describe this method in predicting mechanical behavior and constitutive modeling issues in geo-mechanical behavior of cohesive soil to be used in geo-mechanics. In this research the Batching Back Propagation method (BBP) has been employed and the characterized parameters are introduced as initial void ratio, liquid limit, plasticity index, natural density, moisture percent, solid density of grain, over consolidation ratio, and pre-consolidation pressure. The paper also intends to present how much the input memory may cover the accuracy of predicted behavior of standard triaxial drained and undrained tests. The paper also discusses the strengths and limitations of the proposed method compared to the other modeling approaches. Also, the sensitivity of intended parameters is investigated.

The increasing availability of volunteered geographic information (VGI) enables novel studies in many scientific domains. However, inconsistent VGI can negatively affect these studies. This paper describes a workflow that checks the consistency of Volunteered Phenological Observations (VPOs) while considering the synchrony of observations (i.e., the temporal dispersion of a phenological event). The geographic coordinates, day of the year (DOY) of the observed event, and the accumulation of daily temperature until that DOY were used to: (1) spatially group VPOs by connecting observations that are near to each other, (2) define consistency constraints, (3) check the consistency of VPOs by evaluating the defined constraints, and (4) optimize the constraints by analysing the effect of inconsistent VPOs on the synchrony models derived from the observations. This workflow was tested using VPOs collected in the Netherlands during the period 2003⁻2015. We found that the average percentage of inconsistent observations was low to moderate (ranging from 1% for wood anemone and pedunculate oak to 15% for cow parsley species). This indicates that volunteers provide reliable phenological information. We also found a significant correlation between the standard deviation of DOY of the observed events and the accumulation of daily temperature (with correlation coefficients ranging from 0.78 for lesser celandine, and 0.60 for pedunculate oak). This confirmed that colder days in late winter and early spring lead to synchronous flowering and leafing onsets. Our results highlighted the potential of synchrony information and geographical context for checking the consistency of phenological VGI. Other domains using VGI can adapt this geocomputational workflow to check the consistency of their data, and hence the robustness of their analyses.

Recent improvements in online information communication and mobile location-aware technologies have led to the production of large volumes of volunteered geographic information. Widespread, large-scale efforts by volunteers to collect data can inform and drive scientific advances in diverse fields, including ecology and climatology. Traditional workflows to check the quality of such volunteered information can be costly and time consuming as they heavily rely on human interventions. However, identifying factors that can influence data quality, such as inconsistency, is crucial when these data are used in modeling and decision-making frameworks. Recently developed workflows use simple statistical approaches that assume that the majority of the information is consistent. However, this assumption is not generalizable, and ignores underlying geographic and environmental contextual variability that may explain apparent inconsistencies. Here we describe an automated workflow to check inconsistency based on the availability of contextual environmental information for sampling locations. The workflow consists of three steps: (1) dimensionality reduction to facilitate further analysis and interpretation of results, (2) model-based clustering to group observations according to their contextual conditions, and (3) identification of inconsistent observations within each cluster. The workflow was applied to volunteered observations of flowering in common and cloned lilac plants (Syringa vulgaris and Syringa x chinensis) in the United States for the period 1980 to 2013. About 97% of the observations for both common and cloned lilacs were flagged as consistent, indicating that volunteers provided reliable information for this case study. Relative to the original dataset, the exclusion of inconsistent observations changed the apparent rate of change in lilac bloom dates by two days per decade, indicating the importance of inconsistency checking as a key step in data quality assessment for volunteered geographic information. Initiatives that leverage volunteered geographic information can adapt this workflow to improve the quality of their datasets and the robustness of their scientific analyses.

Background: The MI-GENES clinical trial (NCT01936675), in which participants at intermediate risk of coronary heart disease (CHD) were randomized to receive a Framingham risk score (FRS g , n=103), or an integrated risk score (IRS g , n=104) that additionally included a polygenic risk score (PRS), demonstrated that after 6 months, participants randomized to IRS g had higher statin initiation and lower low-density lipoprotein cholesterol (LDL-C)., Objectives: In a post hoc 10-year follow-up analysis of the MI-GENES trial, we investigated whether disclosure of a PRS for CHD was associated with a reduction in adverse cardiovascular events., Methods: Participants were followed from randomization beginning in October 2013 until September 2023 to ascertain adverse cardiovascular events, testing for CHD, and changes in risk factors, by blinded review of electronic health records. The primary outcome was the time from randomization to the occurrence of the first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and non-fatal stroke. Statistical analyses were conducted using Cox proportional hazards regression and linear mixed-effects models., Results: We followed all 203 participants who completed the MI-GENES trial, 100 in FRS g and 103 in IRS g (mean age at the end of follow-up: 68.2±5.2, 48% male). During a median follow-up of 9.5 years, 9 MACEs occurred in FRS g and 2 in IRS g (hazard ratio (HR), 0.20; 95% confidence interval (CI), 0.04 to 0.94; P =0.042). In FRS g , 47 (47%) underwent at least one test for CHD, compared to 30 (29%) in IRS g (HR, 0.51; 95% CI, 0.32 to 0.81; P =0.004). IRS g participants had a longer duration of statin therapy during the first four years post-randomization and a greater reduction in LDL-C for up to 3 years post-randomization. No significant differences between the two groups were observed for hemoglobin A1C, systolic and diastolic blood pressures, weight, and smoking cessation rate during follow-up., Conclusions: The disclosure of an IRS that included a PRS to individuals at intermediate risk for CHD was associated with a lower incidence of MACE after a decade of follow-up, likely due to a higher rate of initiation and longer duration of statin therapy, leading to lower LDL-C levels., Competing Interests: Disclosure of Interest The authors declare no conflict of interest.

Severe hypercholesterolemia/possible familial hypercholesterolemia (FH) is relatively common but underdiagnosed and undertreated. We investigated whether implementing clinical decision support (CDS) was associated with lower low-density lipoprotein cholesterol (LDL-C) in patients with severe hypercholesterolemia/possible FH (LDL-C ≥ 190 mg/dL). As part of a pre-post implementation study, a CDS alert was deployed in the electronic health record (EHR) in a large health system comprising 3 main sites, 16 hospitals and 53 clinics. Data were collected for 3 months before ('silent mode') and after ('active mode') its implementation. Clinicians were only able to view the alert in the EHR during active mode. We matched individuals 1:1 in both modes, based on age, sex, and baseline lipid lowering therapy (LLT). The primary outcome was difference in LDL-C between the two groups and the secondary outcome was initiation/intensification of LLT after alert trigger. We identified 800 matched patients in each mode (mean ± SD age 56.1 ± 11.8 y vs. 55.9 ± 11.8 y; 36.0% male in both groups; mean ± SD initial LDL-C 211.3 ± 27.4 mg/dL vs. 209.8 ± 23.9 mg/dL; 11.2% on LLT at baseline in each group). LDL-C levels were 6.6 mg/dL lower (95% CI, -10.7 to -2.5; P = 0.002) in active vs. silent mode. The odds of high-intensity statin use (OR, 1.78; 95% CI, 1.41-2.23; P < 0.001) and LLT initiation/intensification (OR, 1.30, 95% CI, 1.06-1.58, P = 0.01) were higher in active vs. silent mode. Implementation of a CDS was associated with lowering of LDL-C levels in patients with severe hypercholesterolemia/possible FH, likely due to higher rates of clinician led LLT initiation/intensification., (© 2024. The Author(s).)

Background: Genetic factors are not included in prediction models for coronary heart disease (CHD)., Objectives: The authors assessed the predictive utility of a polygenic risk score (PRS) for CHD (defined as myocardial infarction, coronary revascularization, or cardiovascular death) and whether the risks due to monogenic familial hypercholesterolemia (FH) and family history (FamHx) are independent of and additive to the PRS., Methods: In UK-biobank participants, PRS CHD was calculated using metaGRS, and 10-year risk for incident CHD was estimated using the pooled cohort equations (PCE). The area under the curve (AUC) of the receiver operator curve and net reclassification improvement (NRI) were assessed. FH was defined as the presence of a pathogenic or likely pathogenic variant in LDLR , APOB , or PCSK9 . FamHx was defined as a diagnosis of CHD in first-degree relatives. Independent and additive effects of PRS CHD , FH, and FamHx were evaluated in stratified analyses., Results: In 323,373 participants with genotype data, the addition of PRS CHD to PCE increased the AUC from 0.759 (95% CI: 0.755-0.763) to 0.773 (95% CI: 0.769-0.777). The AUC and NRI Event for PRS CHD were higher before the age of 55 years. Of 199,997 participants with exome sequence data, 10,000 had a PRS CHD  ≥95th percentile (PRS P95 ), 673 had FH, and 46,163 had FamHx. The CHD risk associated with PRS P95 was independent of FH and FamHx. The risks associated with combinations of PRS CHD , FH, and FamHx were additive and comprehensive estimates could be obtained by multiplying the risk from each genetic factor., Conclusions: Incorporating PRS CHD into the PCE improves risk prediction for CHD, especially at younger ages. The associations of PRS CHD , FH, and FamHx with CHD were independent and additive., Competing Interests: This study was funded by grants U01HG06379 from the 10.13039/100000051National Human Genome Research Institute and K24HL137010 from the 10.13039/100000050National Heart Lung and Blood Institute. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: Incorporating a PRS into the PCE improves CHD risk prediction, particularly in younger individuals and lower-risk individuals (10-year risk <20%). TRANSLATIONAL OUTLOOK: Since the effect of PRS, FH, and family history are independent and additive, these can be used together to obtain a comprehensive assessment of CHD risk., (© 2023 The Authors.)

Prediabetes is an increase-risk state for diabetes that is associated with an increase in blood glucose levels to more than normal, but not increased enough to be termed as type 2 diabetes mellitus (T2DM). A timely intervention and management of prediabetes can stop its further progression to the diabetic state. Many cytokines are involved in diseases including diabetes, however, their role in prediabetes is unknown. In this study, we attempted to analyze numerous proinflammatory cytokines in prediabetic patients. A total of 60 adult Saudi prediabetes patients and healthy control individuals were included in this study. To better understand the role of the proinflammatory cytokines in prediabetes patients and its potential link to the disease outcome, the variations in the levels of these cytokines were investigated using Multi-Analyte ELISA technique. The T helper cells (Th1 and Th2) immune response expression profiling of 84 genes was done using Real Time-quantitative PCR (RT-qPCR) technique. The present finding showed that serum Interleukin IL-2, IL-1β, and IL-1α levels of all prediabetes patients were increased when compared with healthy control cases (P < 0.05). Inductions of proinflammatory cytokines and upregulation of Th1 and Th2 immune genes might play a potential role during prediabetes status and may be linked to the disease outcome. Further studies are needed to investigate the underlying mechanism of these proinflammatory cytokines in diabetes development. A strong positive correlation was found between IL and 1α with glucose levels than with IL-1β and IL-2. In conclusion, cytokines, especially IL-1, may play a critical role in the development of diabetes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Infection with SARS-CoV-2 may perturb normal microbiota, leading to secondary infections that can complicate the viral disease. The aim of this study was to probe the alteration of nasopharyngeal (NP) microbiota in the context of SARS-CoV-2 infection and obesity and to identify other respiratory pathogens among COVID-19 cases that may affect patients' health., Methods: A total of 107 NP swabs, including 22 from control subjects and 85 from COVID-19 patients, were processed for 6S amplicon sequencing. The respiratory pathogens causing secondary infections were identified by RT-PCR assay, using a kit that contained specific primers and probes combinations to amplify 33 known respiratory pathogens., Results: No significant (p > 0.05) difference was observed in the alpha and beta diversity analysis, but specific taxa differed significantly between the control and COVID-19 patient groups. Genera of Sphingomonas, Kurthia, Microbacterium, Methylobacterium, Brevibacillus, Bacillus, Acinetobacter, Lactococcus, and Haemophilus was significantly abundant (p < 0.05) in COVID-19 patients compared with a healthy control group. Staphylococcus was found in relatively high abundance (35.7 %) in the COVID-19 patient groups, mainly those treated with antibiotics. A relatively high percentage of Streptococcus was detected in COVID-19 patient groups with obesity or other comorbidities. Respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Salmonella species, along with Pneumocystis jirovecii fungal species were detected by RT-PCR mainly in the COVID-19 patients. Klebsiella pneumoniae was commonly found in most of the samples from the control and COVID-19 patients. Four COVID-19 patients had viral coinfections with human adenovirus, human rhinovirus, enterovirus, and human parainfluenza virus 1., Conclusions: Overall, no substantial difference was observed in the predominant NP bacterial community, but specific taxa were significantly changed between the healthy control and COVID-19 patients. Comparatively, an increased number of respiratory pathogens were identified in COVID-19 patients, and NP colonization by K. pneumoniae was probably occurring in the local population., Competing Interests: Competing interests None declared., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia., Competing Interests: The authors declare no conflict of interest.

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection that emerged in the Middle East in 2012. Symptoms range from mild to severe and include both respiratory and gastrointestinal illnesses. The virus is mainly present in camel populations with occasional zoonotic spill over into humans. The severity of infection in humans is influenced by numerous factors, and similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underlying health complications can play a major role. Currently, MERS-CoV and SARS-CoV-2 are coincident in the Middle East and thus a rapid way of sequencing MERS-CoV to derive genotype information for molecular epidemiology is needed. Additionally, complicating factors in MERS-CoV infections are coinfections that require clinical management. The ability to rapidly characterize these infections would be advantageous. To rapidly sequence MERS-CoV, an amplicon-based approach was developed and coupled to Oxford Nanopore long read length sequencing. This and a metagenomic approach were evaluated with clinical samples from patients with MERS. The data illustrated that whole-genome or near-whole-genome information on MERS-CoV could be rapidly obtained. This approach provided data on both consensus genomes and the presence of minor variants, including deletion mutants. The metagenomic analysis provided information of the background microbiome. The advantage of this approach is that insertions and deletions can be identified, which are the major drivers of genotype change in coronaviruses. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in late 2012 in Saudi Arabia. The virus is a serious threat to people not only in the Middle East but also in the world and has been detected in over 27 countries. MERS-CoV is spreading in the Middle East and neighboring countries, and approximately 35% of reported patients with this virus have died. This is the most severe coronavirus infection so far described. Saudi Arabia is a destination for many millions of people in the world who visit for religious purposes (Umrah and Hajj), and so it is a very vulnerable area, which imposes unique challenges for effective control of this epidemic. The significance of our study is that clinical samples from patients with MERS were used for rapid in-depth sequencing and metagenomic analysis using long read length sequencing.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1β, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1β, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alosaimi, Mubarak, Hamed, Almutairi, Alrashed, AlJuryyan, Enani, Alenzi and Alturaiki.)

Background: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes., Methods: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels., Results: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2)., Conclusions: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.