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Abstract Background Cutibacterium acnes ( C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer’s disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons. Methods In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ1–42) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated. Results C. acnes-infected rats displayed memory deficits and Aβ1–42 deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals. Conclusion Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites. Graphical Abstract

The higher education sector has learnt a great deal in the online delivery shift due to COVID-19, however, student voice has been underrepresented in literature. This paper reveals 15 student perspectives, including both international and domestic students, who were studying a Master of Teaching (Secondary) at one university in Melbourne, Australia, during heightened social distancing restrictions. The inductive thematic qualitative data analysis collected through semi-structured interviews showed opportunities and challenges of learning experiences. Emergent themes found affordances of convenience and challenges of relational and structural aspects of teaching and learning. Relational aspects of learning were more challenging, including peer collaboration, seeking informal advice and feedback from academics, and participation and engagement. We recommend the inclusion of student voice to guide post COVID-19 teacher education design recommend several areas of support to guide a humanising and personal connection into the remote learning environment.

Background: Subarachnoid hemorrhage (SAH) can lead to elevated intracranial pressure (ICP), which poses significant risks of morbidity and mortality. Monitoring ICP is crucial for the early detection and management of these complications in patients with aneurysmal SAH (aSAH). Traditional invasive ICP monitoring techniques, while effective, carry risks associated with infection and other complications. The Schmidt method, a noninvasive ICP monitoring technique, has emerged as a potential alternative to provide reliable measurements without the inherent risks of invasive methods. Methods: From January 2018 to December 2023, the authors performed both invasive (intraventricular catheters) and noninvasive (Schmidt method) ICP monitoring in patients with aSAH and Hunt and Hess (H and H) scores of 3–5. Patients requiring emergent craniotomy, with serious medical comorbidities or coagulopathies, or with noncompliance were excluded from the study. The accuracy and efficacy of the Schmidt method were evaluated by comparing the results of noninvasive monitoring with the results of invasive ICP monitoring. Results: Out of 238 cases with aSAH referred to our neurosurgical center, 105 had H and H scores of 3–5. Noninvasive ICP monitoring using the Schmidt method was performed in 86 cases (48 females, 38 males; mean age 68 ± 8 years). The mean ICP measured by the invasive method was 15.2 ± 6.2 mmHg, whereas the mean ICP measured by the noninvasive method was 16.6 ± 5.4 mmHg. The calculated root mean square error was 3.6 mmHg, and the average Pearson correlation between the estimated and real waveforms was 0.96. Conclusion: The findings of this study suggest that the application of the Schmidt method is a reliable and accurate approach for the assessment of ICP in patients with SAH, potentially eliminating the need for invasive ICP monitoring and reducing the associated risks.

Background: Tuberculosis (TB) remains a significant global health concern, with extrapulmonary manifestations, including central nervous system involvement, posing substantial morbidity and mortality. While medical treatment with anti-TB drugs is the mainstay of therapy, certain TB-related cerebral complications, such as hydrocephalus, abscesses, and large symptomatic tuberculomas, may require surgical intervention. This study aimed to evaluate the outcomes of surgical management in patients with TB-related cerebral disorders. Methods: A retrospective analysis was conducted on 24 patients who underwent surgical intervention for TB-related cerebral disorders, including tuberculomas, hydrocephalus, and abscesses, at a tertiary care center between 2005 and December 2020. Demographic data, clinical presentations, radiological findings, surgical techniques, and treatment outcomes were analyzed. Results: The study cohort had a mean age of 35.8 ± 13.6 years, and the majority (62.5%) were male. Underlying immunodeficiency, primarily HIV infection, was present in 75% of the patients. The most common presenting symptoms were headache (83.3%), focal neurological deficits (75%), and altered mental status (54.2%). Radiological findings revealed 13 (54.2%) tuberculomas, 8 (33.3%) instances of hydrocephalus, and 3 (12.5%) abscesses. VP shunt inserted in 8 (33.3%) cases. Microscopic craniotomy performed in 7 (29.16%) cases. Aspiration through burr hole was done in 3 (12.5%) cases and stereotactic biopsy was performed in 6 (25%) cases. After 12 months of follow-up, favorable outcome achieved in 18 cases (75%) and the mortality occurred in 2 patients (8.3%). Surgical interventions included lesion resection (n = 10), stereotactic biopsy (n = 7), and ventriculoperitoneal (VP) shunt placement (n = 7). At 12-month follow-up, 18 (75%) patients had a favorable outcome, defined as clinical improvement or stabilization. Unfavorable outcomes were observed in 6 (25%) patients, including 2 deaths. Conclusion: Surgical management, in conjunction with appropriate anti-TB medical therapy, may be a valuable component of the comprehensive treatment approach for select patients with TB-related cerebral disorders. The favorable outcome rate observed in this study suggests that timely and tailored surgical intervention can contribute to improved patient outcomes. However, larger, prospective, multicenter studies are needed to further elucidate the role and long-term efficacy of surgical management in this patient population.

Abstract Objective Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. Methods This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. Results Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline. Conclusions This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. Trial registration Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Objective (s): In a situation where the vaccine was not completely accurate and up-to-date against different strains of the virus in all people of the world, compliance with health guidelines was the main key to prevent transmission. But what is clear is that compliance with health protocols is not the same among all communities and depends on factors. This article examines the effects and attitudes of health protocols. Methods: This research was a descriptive-quantitative cross-sectional study, which was conducted among 385 students of Shahid Beheshti University of Medical Sciences, Iran in the last week of May 2022. Factors affecting the adherence to water hygiene behaviors due to covid-19 were investigated using a questionnaire and the results were analyzed and reported in ordinal regression with SPSS 25 software. Results: The ratio of the average score of compliance (19.08) from the total of eight health behaviors to the maximum score (25) was reported as 76%. It was reported that the score of awareness was very high, 94%, and the average score of attitude was about 75%. In the ordinal regression, it was found that having knowledge was not effective in following all health protocols and only two behaviors of avoiding attending gatherings and avoiding losing when meeting acquaintances showed a statistically significant relationship. In other words, with the increase of each score of awareness, the chance of having higher compliance scores in these two behaviors increased by about 1.5 times. On the other hand, the attitude score had a statistically significant relationship with most of the behaviors, except the compliance of coughing and sneezing into a handkerchief or the corner of the arm, and it had a positive simultaneous effect on the compliance of the behaviors. Conclusion: The high level of awareness among the studied community can partially indicate the effectiveness of interventions in increasing awareness, but the gap between awareness, attitude and behavior indicates the need to pay attention to other factors affecting attitude and behavior.

Abstract This paper presents a new methodology for addressing imbalanced class data for failure prediction in Water Distribution Networks (WDNs). The proposed methodology relies on existing approaches including under-sampling, over-sampling, and class weighting as primary strategies. These techniques aim to treat the imbalanced datasets by adjusting the representation of minority and majority classes. Under-sampling reduces data in the majority class, over-sampling adds data to the minority class, and class weighting assigns unequal weights based on class counts to balance the influence of each class during machine learning (ML) model training. In this paper, the mentioned approaches were used at levels other than “balance point” to construct pipe failure prediction models for a WDN with highly imbalanced data. F1-score, and AUC–ROC, were selected to evaluate model performance. Results revealed that under-sampling above the balance point yields the highest F1-score, while over-sampling below the balance point achieves optimal results. Employing class weights during training and prediction emphasises the efficacy of lower weights than the balance. Combining under-sampling and over-sampling to the same ratio for both majority and minority classes showed limited improvement. However, a more effective predictive model emerged when over-sampling the minority class and under-sampling the majority class to different ratios, followed by applying class weights to balance data.

Abstract In the context of early disease detection, machine learning (ML) has emerged as a vital tool. Feature selection (FS) algorithms play a crucial role in ensuring the accuracy of predictive models by identifying the most influential variables. This study, focusing on a retrospective cohort of 4778 COVID-19 patients from Iran, explores the performance of various FS methods, including filter, embedded, and hybrid approaches, in predicting mortality outcomes. The researchers leveraged 115 routine clinical, laboratory, and demographic features and employed 13 ML models to assess the effectiveness of these FS methods based on classification accuracy, predictive accuracy, and statistical tests. The results indicate that a Hybrid Boruta-VI model combined with the Random Forest algorithm demonstrated superior performance, achieving an accuracy of 0.89, an F1 score of 0.76, and an AUC value of 0.95 on test data. Key variables identified as important predictors of adverse outcomes include age, oxygen saturation levels, albumin levels, neutrophil counts, platelet levels, and markers of kidney function. These findings highlight the potential of advanced FS techniques and ML models in enhancing early disease detection and informing clinical decision-making.

ABSTRACT Background Despite remarkable progress in contemporary medical technology and enhanced survival outcomes for various cancer types, pancreatic cancer (PC) continues to stand out as a particularly deadly gastrointestinal malignancy. Given a persistent rise in both incidence and the corresponding mortality rates of PC globally, evaluations of PC burden by sex are of great importance. Here, we used the illness‐death multi‐state model (IDM) to forecast the prevalence of PC through the year 2040. Methods IDM was established based on obtainable data to predict the future prevalence of PC on global, regional, and national scales from 2019 to 2040. Analyses were also performed regarding sex and 95% confidence intervals (CIs) are presented for all estimates. Results The projected prevalence rate for 2040 is anticipated to be 6.093 ([95% CI 5.47–6.786] per 100,000) worldwide, indicating a significant increase of 31.45% since 1990, and a 12.29% increase since 2019. The estimated average annual increase since 2020 was 0.5%. Considering sex differences, females are expected to have a steeper slope in prevalence rate than males. Intriguingly, when considering the percentage changes between the periods of 2019–2040 and 1990–2019 for both sexes, females exhibited 29% and 11% increase relative to males (2.6‐fold greater increase). Conclusions By 2040, it is predicted that the prevalence of PC will increase globally, with women being at higher risk of developing the disease. Considering the percentage changes, regions with lower socioeconomic status are anticipated to face a greater risk of experiencing PC compared to other geographical areas.

Objective (s): The Health Transformation Plan, initiated in 2014 in Iran and sought to protect public assets, promote equitable access to healthcare services, and enhance service quality. This study evaluated the performance indicators of hospitals affiliated with a medical university before and after the implementation of the plan. Methods: This cross-sectional study encompassed 15 teaching medical centers affiliated with Shahid Beheshti University of Medical Sciences in Tehran province, Iran from 2009 to 2019, consisting of five years prior to the implementation of the plan (pre-2014) and five years following its implementation. Seven key performance indicators, including bed occupancy rate, length of stay, admission ratio, number of hospitalized patients, number of hospitalized referrals, number of surgeries, and number of cesarean sections, were investigated as primary variables. Results: The majority of performance indicators exhibited significant increase after the implementation of the Health Transformation Plan, with the exception of the number of cesarean sections and median length of hospital stay. Individual hospital analysis revealed a decrease in median length of stay in most hospitals post-implementation, while the median values of other performance indicators generally showed an increase across different hospitals. Notably, Imam Hossein, Taleghani, and Loghman Hakim hospitals had the highest number of registered beds. Conclusion: The implementation of the Health Transformation Plan demonstrated a relatively positive impact on the performance indicators of hospitals, resulting in favorable changes in trends and medians of these indicators from 2015 to 2019.

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects. Resumen: Objetivo: La COVID-19 ha afectado a toda la población, especialmente a aquellos con enfermedades crónicas, incluyendo a los pacientes con enfermedad de Parkinson (EP). La COVID-19 puede empeorar tanto los signos motores como los síntomas neuropsiquiátricos de los pacientes con EP. El objetivo de este estudio es evaluar diferentes aspectos del impacto de la COVID-19 en los pacientes con EP. Métodos: A través de un cuestionario virtual se evaluó a 647 pacientes con EP de acuerdo con sus presentaciones clínicas relacionadas con la EP y con la COVID-19, además de la historia médica previa durante la pandemia. Se compararon con un grupo de controles sanos de la misma edad que constaba de 673 individuos y una muestra de la población general de 1.215 individuos. Resultados: La prevalencia de la COVID-19 en pacientes con EP fue del 11,28%. La mortalidad fue del 1,23% entre los pacientes con EP. La prevalencia de COVID-19 en pacientes con EP con estimulación cerebral profunda fue del 18,18%. No se encontró una asociación significativa entre la duración de la enfermedad y la prevalencia de COVID-19. Se halló una prevalencia mayor de COVID-19 que fue estadísticamente significativa en pacientes con EP que tuvieron contacto directo con personas infectadas con SARS-CoV-2. No se encontró una asociación estadísticamente significativa entre el empeoramiento de los signos motores y la COVID-19. Los pacientes con EP y la población general podrían diferir en la prevalencia de algunos trastornos psicológicos, incluidos los trastornos de ansiedad y del sueño, y la COVID-19 podría afectar al estado psicológico. Conclusión: Los pacientes con EP posiblemente sigan protocolos preventivos más estrictos, lo que conduce a una menor prevalencia y gravedad de COVID-19 y de sus consecuencias en estos pacientes. Aunque parece que la COVID-19 no afecta los aspectos motores y psicológicos de la EP tanto como se esperaba, se recomienda la realización de evaluaciones más precisas para aclarar tales efectos.

Neurons are interactive cells that connect via ions to develop electromagnetic fields in the brain. This structure functions directly in the brain. Connectome is the data obtained from neuronal connections. Since neural circuits change in the brain in various diseases, studying connectome sheds light on the clinical changes in special diseases. The ability to explore this data and its relation to the disorders leads us to find new therapeutic methods. Artificial intelligence (AI) is a collection of powerful algorithms used for finding the relationship between input data and the outcome. AI is used for extraction of valuable features from connectome data and in turn uses them for development of prognostic and diagnostic models in neurological diseases. Studying the changes of brain circuits in neurodegenerative diseases and behavioral disorders makes it possible to provide early diagnosis and development of efficient treatment strategies. Considering the difficulties in studying brain diseases, the use of connectome data is one of the beneficial methods for improvement of knowledge of this organ. In the present study, we provide a systematic review on the studies published using connectome data and AI for studying various diseases and we focus on the strength and weaknesses of studies aiming to provide a viewpoint for the future studies. Throughout, AI is very useful for development of diagnostic and prognostic tools using neuroimaging data, while bias in data collection and decay in addition to using small datasets restricts applications of AI-based tools using connectome data which should be covered in the future studies.

Introduction: In infectious diseases, there are essential indices used to describe the disease state. In this study, we estimated the basic reproduction number, R0, peak level, doubling time, and daily growth rate of COVID-19. Methods: This ecological study was conducted in 5 provinces of Iran. The daily numbers of new COVID-19 cases from January 17 to February 8, 2020 were used to determine the basic reproduction number (R0), peak date, doubling time, and daily growth rates in all five provinces. A sensitivity analysis was conducted to estimate epidemiological parameters. Result: The highest and lowest number of deaths were observed in Hamedan (657 deaths) and Chaharmahal and Bakhtiari (54 deaths) provinces, respectively. The doubling time of confirmed cases in Kermanshah and Hamedan ranged widely from 18.59 days (95% confidence interval (CI): 17.38, 20) to 76.66 days (95% CI: 56.36, 119.78). In addition, the highest daily growth rates of confirmed cases were observed in Kermanshah (0.037, 95% CI: 0.034, 0.039) and Sistan and Baluchestan (0.032, 95% CI: 0.030, 0.034) provinces. Conclusion: In light of our findings, it is imperative to tailor containment strategies to the unique epidemiological profiles of each region in order to effectively mitigate the spread and impact of COVID-19. The wide variation in doubling times underscores the importance of flexibility in public health responses. By adapting measures to local conditions, we can better address the evolving dynamics of the pandemic and safeguard the well-being of communities.

Despite reaching enormous achievements in therapeutic approaches worldwide, GBM still remains the most incurable malignancy among various cancers. It emphasizes the necessity of adjuvant therapies from the perspectives of both patients and healthcare providers. Therefore, most emerging studies have focused on various complementary and adjuvant therapies. Among them, metabolic therapy has received special attention, and metformin has been considered as a treatment in various types of cancer, including GBM. It is clearly evident that reaching efficient approaches without a comprehensive evaluation of the key mechanisms is not possible. Among the studied mechanisms, one of the more challenging ones is the effect of metformin on apoptosis and senescence. Moreover, metformin is well known as an insulin sensitizer. However, if insulin signaling is facilitated in the tumor microenvironment, it may result in tumor growth. Therefore, to partially resolve some paradoxical issues, we conducted a narrative review of related studies to address the following questions as comprehensively as possible: 1) Does the improvement of cellular insulin function resulting from metformin have detrimental or beneficial effects on GBM cells? 2) If these effects are detrimental to GBM cells, which is more important: apoptosis or senescence? 3) What determines the cellular decision between apoptosis and senescence?

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase belonging to the Rho family. It acts as a binary molecular switch regulating several cellular functions, including cell adhesion and migration. Malfunctions due to the P29S mutation in Rac1 increase the stability of the activated form of Rac1. This sustained activation can drive aberrant cellular processes associated with cancer, such as cell proliferation, survival, and migration. Therefore, finding an inhibitor that can inhibit the mutant form of the protein is very important. Rhein, a natural compound with diverse pharmacological properties, has been studied in relation to Rac1. However, specific interactions between Rhein and Rac1 have not been examined. In this study, we investigated the potential of Rhein, a natural compound, as an inhibitor of two forms of Rac1: the wild type and the P29S mutation, using molecular dynamics simulations. Results indicated that the P29S mutation led to structural changes in the Rac1 protein, which resulted in greater accessibility of the Rhein to the active site. In addition, the binding energy of Rhein to mutant Rac1 was more negative than the native protein. Therefore, it seems that the Rhein has a better inhibitory effect on the P29S-mutated form of the Rac1 protein.

This paper delves into identifying the optimal scenario for the implementation of micro-turbines, specifically Pump-as-Turbines (PaTs), in a water distribution network (WDN) by achieving the highest consensus among the involved stakeholders. Utilising a simulations-optimisation model, the best location, type, and operation hours for micro-turbines were selected within a case study WDN. The objective was to maximise the generated energy, while maintaining the standard hydraulic conditions of the WDN. A total of 84 scenarios were developed, considering the number of installed turbines, allocation of the generated energy, and pricing schemes. The scenarios explore the possibilities of allocating the generated electricity to the water company, national grid, cryptocurrency mining, or electric car charging. Evaluation of the scenarios involves 36 criteria, and the study identifies 18 stakeholders involved in water and energy management within the case study. Stakeholder utility with respect to the criteria was determined through interviews, and weights for each stakeholder were assigned based on previous studies. The utility of each scenario was computed in a matrix, and scenarios were ranked accordingly, revealing that the scenario involving the generation of electricity by five turbines sold to the grid at twice the current price garnered the highest stakeholder support.

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

Background and Aim: Oncolytic viruses, as novel and advanced tools in the field of treating various types of cancer, have played a very important role in medical developments. The term “oncolytic” refers to the ability of these viruses to destroy and damage cancer cells while preserving the surrounding healthy cells. Materials and Methods: To conduct this study, a total of 270 initial results were collected through searching in the PubMed, Scopus, and Google Scholar databases from 2012 to 2024. The primary researcher reviewed 68 relevant articles, extracted and summarized the contents, and finally compiled the findings. Results: The findings from this review study demonstrate that cancer cells possess distinct characteristics that differentiate them from normal cells, including continuous growth signaling, resistance to anti-growth signaling, evasion of apoptosis, increased angiogenesis, and invasion into other body parts. Oncolytic viruses utilize these distinctive features to selectively target and infect cancer cells. Most oncolytic viruses directly eliminate host tumor cells, resulting in viral replication and induction of host antiviral responses. Moreover, these viruses can destroy cancer cells through the production of specific proteins. The cytotoxic potential of oncolytic viruses depends on viral type, genetic manipulation, optimal virus dosage for injection, natural and induced viral tropism, and cancer cell sensitivity to various forms of cell death. The mechanism driving the selective replication of oncolytic viruses in cancer cells likely relates to defects in signaling pathways specific to tumor cells. Phase III clinical trials have demonstrated significant improvements in the treatment outcomes of various cancers, including head and neck cancer, melanoma, glioblastoma, and bladder cancer, through the use of H101 (Oncorine), T-Vec, ECHO-7, and Teserpaturev (Delytact) viruses. Conclusion: Oncolytic viruses are constructed from various types of viruses and are currently being evaluated in laboratory, preclinical, and clinical stages. The use of these viruses for the treatment of cancer as a new and targeted approach has been proposed, which requires further investigation and achievement of more precise mechanisms for their better performance.

The present study uncovered the effect of pyrolysis temperature (400, 500, 600, and 700 °C), and biomass-to-plastic ratio (100:0, 25:75, 50:50, 75:25, 0:100) on the product distribution and synergistic effect during co-pyrolysis of palm kernel shell (PKS) and medical bottle (MB). The highest bio-oil yield of 65.93 wt% was attained at 500 °C and PKS:MB ratio of 25:75. To determine the synergistic effect, the product distributions (yield and chemical composition) were compared with those obtained from pyrolysis of individual components. The positive synergistic effect on the production of hydrocarbons and inhibition of acids were most dominant at PKS:MB ratio of 75:25. The presence of PKS-derived oxygen radicals and hydrogen abstraction from MB can accelerate the formation of hydrocarbons via secondary cracking and deoxygenation reaction. The produced oil at PKS:MB ratio of 50:50 showed better characteristics compared to PKS-derived oil which contains higher carbon (45 % higher), and hydrogen content (66 % higher), and lower oxygen content (71 % lower).

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases, affecting more than one-quarter of people worldwide. Hepatic steatosis can progress to more severe forms of NAFLD, including NASH and cirrhosis. It also may develop secondary diseases such as diabetes and cardiovascular disease. Genetic and environmental factors regulate NAFLD incidence and progression, making it a complex disease. The contribution of various environmental risk factors, such as type 2 diabetes, obesity, hyperlipidemia, diet, and sedentary lifestyle, to the exacerbation of liver injury is highly understood. Nevertheless, the underlying mechanisms of genetic variations in the NAFLD occurrence or its deterioration still need to be clarified. Hence, understanding the genetic susceptibility to NAFLD is essential for controlling the course of the disease. The current review discusses genetics’ role in the pathological pathways of NAFLD, including lipid and glucose metabolism, insulin resistance, cellular stresses, and immune responses. Additionally, it explains the role of the genetic components in the induction and progression of NAFLD in lean individuals. Finally, it highlights the utility of genetic knowledge in precision medicine for the early diagnosis and treatment of NAFLD patients.

Abstract Background Patients in the post-resuscitation period experience critical conditions and require high-quality care. Identifying the challenges that critical care nurses encounter when caring for resuscitated patients is essential for improving the quality of their care. Aim This study aimed to identify the challenges encountered by critical care nurses in providing care during the post-resuscitation period. Methods A qualitative study was conducted using semi-structured interviews. Sixteen nurses working in the intensive care units of three teaching hospitals were selected through purposive sampling. The Data collected were analyzed using qualitative content analysis. Results Participants experienced individual, interpersonal, and organizational challenges when providing post-resuscitation care. The most significant challenges include inadequate clinical knowledge and experience, poor management and communication skills, lack of support from nurse managers, role ambiguity, risk of violence, and inappropriate attitudes of physicians towards nurses’ roles. Additionally, nurses expressed a negative attitude towards resuscitated patients. Conclusion Critical care nurses face several challenges in providing care for resuscitated patients. To enhance the quality of post-resuscitation care, address the challenges effectively and improve long-time survival it is crucial to implement interventions such as In-service education, post-resuscitation briefing, promotion of interprofessional collaboration among healthcare teams, providing sufficient human resources, clarifying nurses’ roles in the post-resuscitation period and increasing support from nursing managers.

Abstract Background Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. Material and methods A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. Results Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. Conclusion Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Network programmability has always been a topic of interest to researchers. After introducing the concept of SDN, control-plane programmability is achieved. However, data-plane programmability remains a challenge in the context of network programmability. Several studies have attempted to deploy data plane programmability in different ways to accommodate and support arbitrary network protocols or to modify the currently supported protocols’ functions. P4 introduced flexible parsing of arbitrary protocol header fields using software-programmable switches. In this study, we propose an autonomous SDN-based framework that achieves the same goal of flexible parsing of arbitrary protocol header fields in real-time using software switches based on the NFV concept. We describe a method based on the proposed framework that makes it possible to add proprietary network protocols or modify and upgrade an existing protocol. We introduce a software switch architecture that can implement data plane programmability based on the proposed method. In this switch architecture, the switches need not be pre-programmed to be able to parse and process the packets rather the desired parsing of the arbitrary protocol header fields and actions for each match are automatically programmed into the switches as needed. A proof-of-concept implementation verifies the expected operation of the method and shows that the network can be autonomously programmed in real-time, and new or customized protocols, above the link layer, can be deployed without network operator involvement.

Abstract Analyzing seismic data in a timely manner is essential for potential eruption forecasting and early warning in volcanology. Here, we demonstrate that unsupervised machine learning methods can automatically uncover hidden details from the continuous seismic signals recorded during Iceland’s 2021 Geldingadalir eruption. By pinpointing the eruption’s primary phases, including periods of unrest, ongoing lava extrusion, and varying lava fountaining intensities, we can effectively chart its temporal progress. We detect a volcanic tremor sequence three days before the eruption, which may signify impending eruptive activities. Moreover, the discerned seismicity patterns and their temporal changes offer insights into the shift from vigorous outflows to lava fountaining. Based on the extracted patterns of seismicity and their temporal variations we propose an explanation for this transition. We hypothesize that the emergence of episodic tremors in the seismic data in early May could be related to an increase in the discharge rate in late April.

Abstract Background Clostridioides difficile infection (CDI) is one of the most common health care-acquired infections. The dramatic increase in antimicrobial resistance of C. difficile isolates has led to growing demand to seek new alternative medicines against CDI. Achillea millefolium L. extracts exhibit strong biological activity to be considered as potential therapeutic agents. In this work, the inhibitory effects of A. millefolium, its decoction (DEC) and ethanol (ETOH) extracts, were investigated on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S) induced inflammation and apoptosis. Methods Phytochemical analysis of extracts was performed by HPLC and GC analysis. The antimicrobial properties of extracts were evaluated against C. difficile RT001. Cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of extracts and Tox-S were examined by MTT assay and microscopy, respectively. Anti-inflammatory and anti-apoptotic effects of extracts were assessed in Tox-S stimulated Caco-2 cells by RT-qPCR. Results Analysis of the phytochemical profile of extracts revealed that the main component identified in both extracts was chlorogenic acid. Both extracts displayed significant antimicrobial activity against C. difficile RT001. Moreover, both extracts at concentration 50 µg/mL had no significant effect on cell viability compared to untreated cells. Pre-treatment of cells with extracts (50 µg/mL) significantly reduced the percentage of Vero cells rounding induced by Tox-S. Also, both pre-treatment and co-treatment of Tox-S stimulated Caco-2 cells with extracts significantly downregulated the gene expression level of IL-8, IL-1β, TNF-α, TGF-β, iNOS, Bax, caspase-9 and caspase-3 and upregulated the expression level of Bcl-2. Conclusion The results of the present study for the first time demonstrate the antimicrobial activity and protective effects of A. millefolium extracts on inflammatory response and apoptosis induced by Tox-S from C. difficile RT001 clinical strain in vitro. Further research is needed to evaluate the potential application of A. millefolium extracts as supplementary medicine for CDI prevention and treatment in clinical setting.

Interactive and interactional metadiscourse are linguistic features used to maintain the coherence in essays. It involved a one-way interaction between the writer and reader, thus a challenge for Second Language (L2) learners to write effectively and comprehensively. A study is done on how the L2 learners produced the metadiscourse features and the usage is compared. A corpus of 200 evaluative essays by UiTM undergraduate students from computer science and business administration courses is analysed based on Hyland's (2005) framework. The purpose is to find out the amount and types of metadiscourse used and whether students from different course groups make any differences in their choices. The analysis revealed that students in both courses produced more interactive than interactional metadiscourse. The most prominent feature is "Self-mention" and the least is "Attitude Markers." The same prominent feature for both courses is "Transition Markers." The business administration course shows the least feature in "Evidentials," whereas "Frame Markers" in computer science. These are evidence as to the importance of metadiscourse in students' academic writings and awareness is shown in its usage. This could lead to a proposition for a metadiscourse writing comparison between secondary schools and universities to gain fascinating outcomes.