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Determining the success of infectious disease outbreak prevention is dependent mainly on public knowledge and compliance regarding the guidelines of precautionary behaviors and practices. While the current literature about the COVID-19 pandemic extensively addresses clinical and laboratory-based studies, a gap remains still present in terms of evaluating the general public knowledge and behaviors towards the COVID-19 pandemic. The aim of this review was to form a preliminary and contemporary understanding of the general public knowledge, attitude, and behaviors towards the COVID-19 pandemic globally. A systematic search was conducted in various databases until May 2020. Each study's characteristics including the sample size, region, and study type were examined individually. A meta-analysis with a random-effects model and pooled prevalence with 95% confidence interval (CI) of all evaluated outcomes such as adequate knowledge, positive feelings, worrisome about the COVID-19 pandemic, and practice were recorded and reported from each study. Parameters such as random distribution, blinding, incomplete outcome data, selective reporting, and other biases were utilized to assess the quality of each retrieved record. Both Begg's and Egger's tests were employed to evaluate symmetry of funnel plots for assessment of publication bias. The overall quality of evidence was evaluated using GRADEpro software. A total of 26 studies with 67,143 participants were analyzed. The overall prevalence of knowledge, positive attitude, worrisome, and practice of precautionary measures were 0.87 (95%CI, 0.84-0.89), 0.85 (95%CI, 0.77-0.92), 0.71 (95%CI, 0.61-0.81), and 0.77 (95%CI, 0.70-0.83), respectively. Subgroup analysis demonstrated that social distancing was less practiced in Africa than other regions (p = 0.02), while knowledge of prevention of COVID-19 was reported higher in Asia (p = 0.001). Furthermore, people in developing countries had a higher prevalence of worrisome towards the COVID-19 pandemic with a p-value of less than 0.001. The quality of evidence was noted to be of low certainty in practice domain but moderate in the remaining outcomes. Assessing the public's risk perception and precautionary behaviors is essential in directing future policy and health population research regarding infection control and preventing new airborne disease outbreaks.

Melanoma stem cells (MSCs) are characterized by their unique cell surface proteins and aberrant signaling pathways. These stemness properties are either in a causal or consequential relationship to melanoma progression, treatment resistance and recurrence. The functional analysis of CD133+ and CD133− cells in vitro and in vivo revealed that melanoma progression and treatment resistance are the consequences of CD133 signal to PI3K pathway. CD133 signal to PI3K pathway drives two downstream pathways, the PI3K/Akt/MDM2 and the PI3K/Akt/MKP-1 pathways. Activation of PI3K/Akt/MDM2 pathway results in the destabilization of p53 protein, while the activation of PI3K/Akt/MKP-1 pathway results in the inhibition of mitogen-activated protein kinases (MAPKs) JNK and p38. Activation of both pathways leads to the inhibition of fotemustine-induced apoptosis. Thus, the disruption of CD133 signal to PI3K pathway is essential to overcome Melanoma resistance to fotemustine. The pre-clinical verification of in vitro data using xenograft mouse model of MSCs confirmed the clinical relevance of CD133 signal as a therapeutic target for melanoma treatment. In conclusion, our study provides an insight into the mechanisms regulating MSCs growth and chemo-resistance and suggested a clinically relevant approach for melanoma treatment.

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% of melanomas demonstrating the BRAF mutation (BRAFV600E). While the successful targeting of BRAFV600E does improve overall survival, the long-term efficacy of available therapeutic options is limited due to adverse side effects and reduced clinical efficacy. Additionally, drug resistance develops rapidly via mechanisms involving fast feedback re-activation of MAPK signaling pathways. This article updates information relevant to the mechanisms of melanoma progression and resistance and particularly the mechanistic role of CSCs in melanoma progression, drug resistance, and recurrence.

Objective To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS). Methods Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS). Results Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group ( p  < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome. Conclusion Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.

This study aimed to compile all the relevant studies of patients presenting with pericardial tamponade before or after diagnosis of lymphoma, describe the clinical presentations of patients with lymphoma and cardiac tamponade, and assess the difference in overall survival based on the timing of cardiac tamponade diagnosis. A comprehensive search strategy was conducted in the following databases: PubMed and Cochrane Library, using the following

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed.

According to the World Food Program, even before the war started, Yemen had one of the highest rates of malnutrition in the Arabian Peninsula.2 With the ongoing war, malnutrition is rising and hunger now affects almost half of the population.

According to a survey from UNICEF and the Government of Yemen, in 2006, 14% and 52% of girls are married before the ages of 15 years and 18 years, respectively.1,2 Some have reported even younger cases of child marriage, such as 8-year-old Rawan.2 Although child marriage continues to plague rural areas in Yemen, officials either deny or promise to establish a new law to define a minimum age of marriage in the country.

Background Tumor response to immunotherapy is the consequence of a concerted crosstalk between cytokines and effector cells. Interferon gamma (IFNγ) is one of the common cytokines coordinating tumor immune response and the associated biological consequences. Although the role of IFNγ in the modulation of tumor immunity has been widely documented, the mechanisms regulating IFNγ-induced cell death, during the course of immune therapy, is not described in detail. Results IFNγ triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly, IFNγ induced the loss of mitochondrial membrane potential (Δ ψ m) and increased accumulation of reactive oxygen species (ROS). The cytokine also induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N-terminal kinase (JNK) and NF-κB pathways and the transcription factors STAT1, interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-κB and p53, and expression of Noxa protein. Furthermore, IFNγ was found to trigger endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring-1α (IRE1α) pathways. Using specific inhibitors, we identified a potential role for IDO as apoptotic mediator in the regulation of IFNγ-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells via Noxa-mediated mitochondrial dysregulation and ER stress. Conclusion In addition to the elucidation of the role of IDO in the modulation of apoptosis, our study provides new insights into the molecular mechanisms of IFNγ-induced apoptosis of HNSCC cells during the course of immune therapy.

Introduction Benidipine and amlodipine are two well-known drugs used in hypertensive patients with chronic kidney disease (CKD). Aim In this systematic review we aimed to compare benidipine and amlodipine in terms of efficacy in the management of hypertensive patients. Methods We searched PubMed, Cochrane CENTRAL, SCOPUS and Web of Science for relevant clinical trials and excluded observational studies. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using the Cochrane’s risk of bias tool. We included the following outcomes: Systolic blood pressure, diastolic blood pressure, heart rate, estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio. Data were pooled as mean differences (MD) with relative 95% confidence intervals (CI). Results Eight studies were eligible for our meta-analysis. We found no significant difference between both drugs regarding systolic (MD = − 0.21 [− 1.48, 1.89], (P = 0.81) and diastolic (MD = 0.01[− 0.51, 0.53], (P = 0.97)) blood pressure measurements. The overall heart rate did not differ as well (MD = − 0.03 [− 1.63, 1.57], (P = 0.97)). We found that benidipine was statistically better than amlodipine in terms of eGFR (MD = 1.07 [0.43, 1.71], (P = 0.001)), and urinary albumin/creatinine ratio (MD = − 43.41 [− 53.53, − 33.29], (P < 0.00001)). Conclusions Finally we conclude that benidipine seems to show more positive and promising results in the management of hypertensive patients with chronic kidney disease.