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Zaki F Aref,1 Shamardan Ezzeldin Sayed Bazeed,2 Asmaa Nafady,3 Dalia Fahim Mohammed Fahim,4 Ali A Ghweil,5 Mennatallah Ali Abdelrhman Sayed,6 Heba Mohammad Qubaisy,7 Mahmoud Khalefa,8 Usama A Arafa,9 Badawy Shahat Badawy,10 Ahmed Shawkat Abdelmohsen,11 Mohammed H Hassan,12 Aida A Abdelmaksoud1 1Department of ENT, Faculty of Medicine, South Valley University, Qena, Egypt; 2Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, South Valley University, Qena, Egypt; 3Department of Clinical and Chemical Pathology, Faculty of Medicine, South Valley University, Qena, Egypt; 4Audiovestibular Medicine, Faculty of Medicine, Minia University, Minia, Egypt; 5Tropical Medicine and Gastroenterology, Faculty of Medicine, South Valley University, Qena, Egypt; 6King Salman International University, Faculty of Medicine, El Tor, Egypt; 7Department of Pediatrics, Faculty of Medicine, South Valley University, Qena, Egypt; 8Department of ENT, Faculty of Medicine, Aswan University, Aswan, Egypt; 9Department of Internal Medicine, Faculty of Medicine, Sohag University, Sohag, Egypt; 10Department of ENT, Faculty of Medicine, Luxor University, Luxor, Egypt; 11Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt; 12Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, EgyptCorrespondence: Mohammed H Hassan, Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt, Tel +20 1009097968, Email mohammedhosnyhassaan@yahoo.com; mohammedhosnyhassaan@med.svu.edu.egBackground: Helicobacter pylori is assumed to cause many gastric and extragastric diseases. We aimed to assess the possible association role of H. pylori in Otitis media with effusion (OME), nasal polyps and adenotonsillitis.Patients and Methods: A total of 186 patients with various ear, nose and throat diseases were included. The study comprised 78 children with chronic adenotonsillitis, 43 children with nasal polyps and 65 children with OME. OME patients were assigned to two subgroups: those who have and those who did not have adenoid hyperplasia. Among the patients with bilateral nasal polyps, 20 individuals had recurrent nasal polyps and 23 had de novo nasal polyps. Patients who have chronic adenotonsillitis were divided into three groups: those with chronic tonsillitis and those who underwent tonsillitis, those with chronic adenoiditis and adenoidectomy was performed, and those with chronic adenotonsillitis and underwent adenotonsillectomy. In addition to examination of H. pylori antigen in stool samples of all included patients, real-time polymerase chain reaction (RT-PCR) for detection of H. pylori in the effusion fluid was performed, additionally, Giemsa stain was used for detection of H. pylori organism within the tissue samples when available.Results: Frequency of H. pylori in effusion fluid was 28.6% in patients with OME and adenoid hyperplasia, while in those with OME it was only 17.4% with a p value of 0.2. Nasal polyp biopsies were positive in 13% patients of denovo, and 30% patients with recurrent nasal polyps, p=0.2. De novo nasal polyps were more prevalent in the positive stools than recurrent ones, p=0.7. All adenoid samples were negative for H. pylori, only two samples of tonsillar tissue (8.3%) were positive for H. pylori, and stool analysis was positive in 23 patients with chronic adenotonsillitis.Conclusion: Lack of association between Helicobacter pylori and occurrence of OME, nasal polyposis or recurrent adenotonsillitis.Keywords: Helicobacter pylori, otitis media with effusion, nasal polyps, adenotonsillitis

Zaki F Aref,1 Shamardan Ezz Eldin S Bazeed,2 Mohammed H Hassan,3 Abeer S Hassan,4 Ali A Ghweil,2 Mennatallah Ali Abdelrhman Sayed,5 Alaa Rashad,6 Haggagy Mansour,6 Aida A Abdelmaksoud1 1ENT Department, Faculty of Medicine, South Valley University, Qena, Egypt; 2Tropical Medicine and Gastroenterology Department, Faculty of Medicine, South Valley University, Qena, Egypt; 3Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 5King Salman International University, El Tor, Egypt; 6Department of Chest Diseases and Tuberculosis, Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Mohammed H Hassan, Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt, Tel +20 1098473605, Email Mohammedhosnyhassaan@yahoo.com; mohammedhosnyhassaan@med.svu.edu.egPurpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia.Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group “ivermectin group” included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients “placebo group” who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done.Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05.Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment.Trial Registration No: NCT04951362.Keywords: post-COVID-19 anosmia, ivermectin, nanosuspension mucoadhesive nasal spray

Zaki F Aref,1 Shamardan Ezz Eldin S Bazeed,2 Mohammed H Hassan,3 Abeer S Hassan,4 Alaa Rashad,5 Rehab G Hassan,6 Aida A Abdelmaksoud1 1ENT Department, Faculty of Medicine, South Valley University, Qena, Egypt; 2Tropical Medicine and Gastroenterology Department, Faculty of Medicine, South Valley University, Qena, Egypt; 3Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 5Department of Chest Diseases and Tuberculosis, Faculty of Medicine, South Vally University, Qena, Egypt; 6Department of Public Health and Community Medicine, Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Mohammed H HassanDepartment of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, EgyptTel +201098473605Email mohammedhosnyhassaan@med.svu.edu.egBackground: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro.Objective: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19.Methods: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later.Results: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001).Conclusion: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration.Clinicaltrials.gov Identifier: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.Keywords: ivermectin nanosuspension, nasal spray, COVID-19, biochemical and molecular

Hamdy A Azim,1 Ashraf Omar,2 Hesham Atef,1,† Heba Zawahry,3 Mohamed K Shaker,4 AH Kamel Abdelmaksoud,5 Mohamed EzzElarab,6 Omar Abdel-Rahman,7 Mohamed Ismail,8 Loay Kassem,1 Imam Waked9 1Department of Clinical Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt; 3Department of Medical Oncology, National Cancer Institute, Cairo, Egypt; 4Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Diagnostic and Intervention Radiology, Cairo University, Cairo, Egypt; 6National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; 7Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Clinical Oncology Department, Cairo Oncology Center, Cairo, Egypt; 9Institute of Liver Disease, Menoufiya University, Menoufiya, Egypt †Dr Hesham Atef passed away on November 16, 2017, during the preparation of the manuscript Background: Phase II trials found that tegafur–uracil (UFT) is an effective drug in hepatocellular carcinoma (HCC), while preclinical data suggested that its combination with sorafenib may have a promising activity. Our Phase II randomized trial aimed to evaluate efficacy and tolerability of sorafenib plus UFT vs sorafenib in advanced HCC.Methods: Patients with advanced HCC, with no prior systemic therapy, were randomized to receive either UFT at 125 mg/m2 twice daily for 4 out of 5 weeks plus sorafenib at 400 mg twice daily (arm 1) or single agent sorafenib at 400 mg twice daily (arm 2). Primary end point was time to progression (TTP).Results: Between March 2012 and March 2014, 76 eligible patients – out of 143 preplanned – were randomized. The study was terminated early because of futility. This is the final analysis of the study, after a median follow-up of 10.2 months and death of 86% of randomized patients (n=64). Median TTP was 7.5 months and 8.2 months in arms 1 and 2 respectively (HR: 1.07; 95% CI, 0.52–2.22; P=0.855), while the median overall survival was 8.2 months and 10.5 months respectively (HR: 1.58; 95% CI: 0.90–2.76, P=0.112). Nine patients (25%) in the combination arm discontinued treatment because of toxicity vs eight patients (21.1%) in the sorafenib monotherapy arm (P=0.899).Conclusion: In patients with advanced HCC, adding UFT to sorafenib is feasible, but it did not improve efficacy outcome over sorafenib monotherapy. Keywords: advanced hepatocellular carcinoma, sorafenib, tegafur/uracil, Egypt

Abstract Renal fibrosis (RF) represents the most widespread pathological condition in chronic kidney disease (CKD). Recently, protein prenylation has been implicated in the fibrosis’s progression. The research examined the renoprotective effect of zoledronic acid (ZA) (50 µg/kg/week) in a rat model of carbon tetrachloride (CCl4)-induced RF through targeting protein prenylation. Forty Wistar male rats were split up into the control group, vehicle-treated group, model-RF group, and RF-ZA group. Mean arterial blood pressure (MBP), BUN, serum creatinine, and urine albumin–creatinine ratio (uACR), protein levels of farnesyl pyrophosphate (FPP), tumour necrosis factor-alpha (TNF-α), transforming growth factor-β (TGF-β), and malondialdehyde (MDA), and catalase and gene expression of farnesyl pyrophosphate synthase (FPPS) and nuclear factor-kB (NF-κB) were measured. Immunohistochemical staining for renal interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and caspase-3, as well as histopathological alterations, were assessed. ZA considerably ceased the reduction in MBP, markedly reduced uACR, serum creatinine, BUN, and expression of FPPS, FPP, NF-κB, TGF-β, TNF-α, and MDA, and significantly increased catalase levels compared to the model-RF rats. ZA ameliorated the CCl4-induced histopathological alterations and suppressed the expression of caspase-3, α-SMA, and IL-6. In conclusion, ZA preserved renal function and prevented renal fibrosis in a rat model. These were achieved through targeting protein prenylation mainly by inhibiting FPPS.

Abstract Machine learning and remote sensing techniques are widely accepted as valuable, cost-effective tools in lithological discrimination and mineralogical investigations. The current study represents an attempt to use machine learning classification along with several remote sensing techniques being applied to Landsat-8/9 satellite data to discriminate the various outcropping lithological rock units at the Duwi Shear Belt (DSB) area in the Central Eastern Desert of Egypt. Multi-class machine learning classification, multiple conventional remote sensing mapping techniques, spectral separability analysis based on the Jeffries-Matusita (J-M) distance measure, fieldwork, and petrographic investigations were integrated to enhance the lithological discrimination of the exposed rock units at DSB area. The well-recognized machine learning classifier (Support Vector Machine—SVM) was adopted in this study, with training data determined carefully based on enhancing the lithological discrimination attained from various remote sensing techniques of False Color Composites (FCC), Principal Component Analysis (PCA), and Minimum Noise Fraction (MNF), along with the fieldwork data and the previously published geologic maps. High overall accuracy of the SVM classification was obtained, however, inspection of the individual rock unit classes’ accuracies revealed lower accuracy for certain types of rock units which were also found associated with lower separability scores as well. Among the least separable rock units were; metagabbro rocks that showed high spectral similarity with the volcaniclastic metasediments rocks, and the metaultramafics of the ophiolitic mélange showed spectral attitude of high correlation to that of the Hammamat volcanosedimentary rocks. Target-oriented Color Ratio Composites (CRC) technique was implemented to better discriminate these hardly separable rock units. A final integrated geological map was obtained comprising the various discriminated Neoproterozoic basement rock units of the DSB area. The successfully mapped litho-units include; Meatiq Group (amphibolites, gneissic granitoids, and mylonitized granitoids), ophiolitic mélange (metaultramafics, metagabbro-amphibolites, and volcaniclastic metasediments), Dokhan volcanics, Hammamat sediments, and granites. An adequate description of these rock units was also given in light of the conducted intense fieldwork and petrographic investigations.

Abstract Background Eating disorders (EDs) are complex mental health conditions with significant implications for the physical and psychological well-being of youth. This study aimed to determine the prevalence of eating disorders among a sample of Egyptian youth and explore the association between anxiety, social support, and sociodemographic characteristics with eating disorder behaviors. Results The findings revealed a significant prevalence of eating disorders among the youth participants, with 13.3% meeting the diagnostic criteria. Bulimia Nervosa was the most commonly diagnosed eating disorder, affecting 8.4% of the participants, followed by 1.4% experiencing Binge Eating Disorder. No cases of Anorexia Nervosa were reported. There were no statistically significant sex differences in the prevalence of different types of eating disorders. Higher body mass index (BMI) values and greater anxiety levels were associated with an increased likelihood of having an eating disorder. Conclusions This study highlights a significant prevalence of eating disorders among Egyptian youth, with Bulimia Nervosa being the most common type. These findings emphasize the need for targeted interventions and support systems to address the mental health challenges faced by Egyptian youth and promote healthy relationships with food and body image.

Abstract Drug delivery is the process or method of delivering a pharmacological product to have therapeutic effects on humans or animals. The use of nanoparticles to deliver medications to cells is driving the present surge in interest in improving human health. Green nanodrug delivery methods are based on chemical processes that are acceptable for the environment or that use natural biomaterials such as plant extracts and microorganisms. In this study, zinc oxide-superparamagnetic iron oxide-silver nanocomposite was synthesized via green synthesis method using Fusarium oxysporum fungi mycelia then loaded with sorafenib drug. The synthesized nanocomposites were characterized by UV-visibile spectroscopy, FTIR, TEM and SEM techniques. Sorafenib is a cancer treatment and is also known by its brand name, Nexavar. Sorafenib is the only systemic medication available in the world to treat hepatocellular carcinoma. Sorafenib, like many other chemotherapeutics, has side effects that restrict its effectiveness, including toxicity, nausea, mucositis, hypertension, alopecia, and hand-foot skin reaction. In our study, 40 male albino rats were given a single dose of diethyl nitrosamine (DEN) 60 mg/kg b.wt., followed by carbon tetrachloride 2 ml/kg b.wt. twice a week for one month. The aim of our study is using the zinc oxide-superparamagnetic iron oxide-silver nanocomposite that was synthesized by Fusarium oxysporum fungi mycelia as nanocarrier for enhancement the sorafenib anticancer effect.

Summary: Pancreatic adenocarcinoma (PDAC) is one the most intractable cancers, in part due to its highly inflammatory microenvironment and paucity of infiltrating dendritic cells (DCs). Here, we find that genetic ablation or antibody blockade of tumor necrosis factor receptor 1 (TNFR1) enhanced intratumor T cell activation and slowed PDAC growth. While anti-PD-1 checkpoint inhibition alone had little effect, it further enhanced intratumor T cell activation in combination with anti-TNFR1. The major cellular alteration in the tumor microenvironment in the absence of TNFR1 signaling was a large increase in DC number and immunostimulatory phenotype. This may reflect a direct effect on DCs, because TNF induced TNFR1-dependent apoptosis of bone-marrow-derived DCs. The therapeutic response to anti-TNFR1 alone was superior to the combination of DC-activating agonistic anti-CD40 and Flt3 ligand (Flt3L). These observations suggest that targeting TNFR1, perhaps in concert with other strategies that promote DC generation and mobilization, may have therapeutic benefits.

Background/Objectives: Attention Deficit Hyperactivity Disorder (ADHD) imposes hidden public health problems that should be addressed. This study aimed to assess the prevalence of ADHD and to explore the association between video game addiction & other predictors and ADHD among medical university students in Egypt. Methods: A cross-sectional study was performed using a self-administered questionnaire between July and November 2023. ADHD was assessed by the Adult ADHD Self-Reporting Scale (ASRS). A seven-item Game Addiction Scale (GAS-7) was used to determine the level of game addiction. Results: We studied 1765 medical students with a mean age of 20.2 ± 1.2 years. The majority of them are females (67.8%). This study found a high rate of probable ADHD (35%) among Egyptian medical students. ADHD was associated with female sex and lower academic performance. Video game addiction prevalence was 24.7%, more common in younger students. Conclusion: In conclusion, this study found a high prevalence of probable ADHD and video game addiction among Egyptian medical students. Increased awareness and targeted interventions are needed to support medical students with ADHD and address video game addiction.

Abstract Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. Here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. Enzymatic assays confirm the inhibition of multiple KDMs with the highest selectivity for KDM3B. Structural similarity search of P3FI-63 identifies P3FI-90 with improved solubility and potency. Biophysical binding of P3FI-90 to KDM3B is demonstrated using NMR and SPR. P3FI-90 suppresses the growth of FP-RMS in vitro and in vivo through downregulating PAX3-FOXO1 activity, and combined knockdown of KDM3B and KDM1A phenocopies P3FI-90 effects. Thus, we report KDM inhibitors P3FI-63 and P3FI-90 with the highest specificity for KDM3B. Their potent suppression of PAX3-FOXO1 activity indicates a possible therapeutic approach for FP-RMS and other transcriptionally addicted cancers.

Background: Frailty indicates increased susceptibility to stress secondary to the declines of physiological homeostatic reserve with aging due to cumulative cellular damage over the individuals' life. Objectives: assessment of using the 5-item and 11-item modified frailty indices (mFI-5 and mFI-11) and the Clinical Frailty Scale (CFS) for early prediction of complications during lumbar spinal surgery. Patients and Method: 137 files were reviewed to extract the perioperative data and 6-m follow-up findings concerning pain as evaluated by the Numerical Rating Scale (NRS) and Oswestry Disability Index (ODI). ΔNRS and ΔODI were calculated and at cutoff point of ≥50% indicated procedure success. The incidence and multiplicity of complications were recorded. Statistical analyses were applied to evaluate the relation between FIs and the frequency of complications. Results: NRS and ODI scores were decreased by ≥50% in 113 (82.5%) and 71 (51.8%), respectively and were negatively correlated with patients' age, BMI, the presence and multiplicity of medical disorders. Statistical analyses defined the presence of multiple medical disorders as the negative significant predictor for spinal surgery success. The mFI-11 defined significantly higher percentage of frail patients (65.7%) than the mFI-5 (40.9%) and CFS (41%). Statistical analyses defined high mFI-11 score as the significant predictor for getting multiple complications. Conclusion: Spinal surgery success is inversely related patients' age, BMI and the presence of multiple chronic medical illnesses. The incidence and multiplicity of surgery-related complications were positively related to the FI scorings. The mFI-11 showed the highest predictability for complication and is better to be applied for preoperative evaluation.

It is undeniable that the development of robot manipulators has gained significant attention due to its numerous applications in various sectors. In order to address and resolve several issues for robotic manipulators, this paper provides a review of recent control approaches that have been conducted. In the beginning, a succinct comprehensive introduction of the pertinent terminology, configurations, components, advantages/disadvantages, and applications is given. A state-of-the-art review of the various control strategies for robotic manipulator systems is then presented, along with potential solutions when the systems are faced with various obstacles and impediments. An analytical study is discussed showing percentages of the papers discussed in this study in terms of the different control strategies, link types, models, applications, and degrees of freedom of robotic manipulators. For academic, research, medical, and industrial uses, some off-the-shelf developments in robotic manipulators are also presented.

Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443–0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189–1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

For the deployment of Sixth Generation (6G) networks, integrating Massive Multiple-Input Multiple-Output (Massive MIMO) systems with Intelligent Reflecting Surfaces (IRS) is highly recommended due to its significant benefits in reducing communication losses for Non-Line-of-Sight (NLoS) conditions. However, the use of passive IRS presents challenges in channel estimation, mainly due to the significant feedback overhead required in Frequency Division Duplex (FDD)-based Massive MIMO systems. To address these challenges, this paper introduces a novel Denoising Gated Recurrent Unit with a Dropout-based Channel state information Network (DGD-CNet). The proposed DGD-CNet model is specifically designed for FDD-based IRS-aided Massive MIMO systems, aiming to reduce the feedback overhead while improving the channel estimation accuracy. By leveraging the Dropout (DO) technique with the Gated Recurrent Unit (GRU), the DGD-CNet model enhances the channel estimation accuracy and effectively captures both spatial structures and time correlation in time-varying channels. The results show that the proposed DGD-CNet model outperformed existing models in the literature, achieving at least a 26% improvement in Normalized Mean Square Error (NMSE), a 2% increase in correlation coefficient, and a 4% in system accuracy under Low-Compression Ratio (Low-CR) in indoor situations. Additionally, the proposed model demonstrates effectiveness across different CRs and in outdoor scenarios.