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Clinical and Biochemical Heterogeneity in Hemoglobin H Disease: A Comprehensive Analysis of α-Globin Mutations and Transfusion Requirements 2 2 Background: Hemoglobin H (Hb H) disease, a subtype of α-thalassemia, demonstrates marked clinical heterogeneity primarily driven by underlying genotypic differences. While non-deletional mutations are typically associated with more severe phenotypes, considerable variability is observed even among patients with similar mutation classes. This study aimed to examine genotype–phenotype correlations in Hb H disease by assessing the relationship between α-globin mutations, transfusion dependency, and a range of hematologic and biochemical markers. Methods: Ninety patients with confirmed Hb H disease were evaluated. Genotyping was performed via multiplex gap-PCR, Sanger sequencing, and MLPA. Patients were classified by transfusion need into transfusion-dependent (TDT), occasionally transfused (OTDT), and non-transfusion-dependent (NTDT) groups. Genotypically, patients were categorized as non-deletional homozygotes (ND/ND), compound heterozygotes (ND/D), and deletional homozygotes (D/D). Complete blood count, hemoglobin fractions, iron profile, liver enzymes, and C-reactive protein (CRP) levels were measured and analyzed. Results: Significant differences in hematologic and biochemical parameters were observed across genotypes. ND/ND patients had the highest hemoglobin (10.70 ± 1.83 g/dL), MCV (66.06 ± 8.43 fL), and HbA levels (93.72 ± 5.13%), and the lowest reticulocyte counts and Hb H percentages (p < 0.01). ND/D patients exhibited lower HbA, higher Hb H, and elevated ferritin (438.66 ± 840.60 ng/mL) and CRP (3.97 ± 4.75 mg/L) levels (p < 0.05), indicating greater erythropoietic stress. Transfusion dependence was most frequent in ND/D patients, though not statistically significant (p = 0.34). Conclusion: This study highlights substantial phenotypic variability within genotypic groups, challenging the binary classification of deletional versus non-deletional mutations. Integrating molecular data with functional and inflammatory biomarkers may enhance risk stratification and support individualized management of Hb H disease. 1 12 2025/04/11 1404/1/22 2025/05/22 1404/3/1 Elaheh saniei Elaheh saniei Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq. elahetisaniei@uomustansiriyah.edu.iq Abdulkareem H. Issa Abdulkareem H. Issa Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq. Azita Azarkeivan Azita Azarkeivan Iranian Blood Transfusion Organization (IBTO), High Institute for Research and Education in Transfusion Medicine, Thalassemia Clinic, Tehran, Iran. Hassan Abolghasemi Hassan Abolghasemi Department of pediatrics, Baqiyatallah University of Medical Sciences, Tehran, Iran. Morteza Karimipoor Morteza Karimipoor Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Alpha-Thalassemia Alpha-Globins Mutation Harteveld CL, Higgs DRJOjord. α-thalassaemia. 2010;5:1-21.##Higgs DRJCSHpim. The molecular basis of α-thalassemia. 2013;3(1):a011718.##Lal A, Goldrich ML, Haines DA, Azimi M, Singer ST, Vichinsky EPJNEJoM. Heterogeneity of hemoglobin H disease in childhood. 2011;364(8):710-8.##Galanello R, Cao AJGim. Alpha-thalassemia. 2011;13(2):83-8.##Musallam KM, Rivella S, Vichinsky E, Rachmilewitz EAJh. Non-transfusion-dependent thalassemias. 2013;98(6):833.##Viprakasit V, Ekwattanakit SJHOC. Clinical classification, screening and diagnosis for thalassemia. 2018;32(2):193-211.##Chen FE, Ooi C, Ha SY, Cheung BM, Todd D, Liang R, et al. 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Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. 2016;44(D1):D733-D45.##Rivella SJB, The Journal of the American Society of Hematology. Iron metabolism under conditions of ineffective erythropoiesis in β-thalassemia. 2019;133(1):51-8.##Gardenghi S, Marongiu MF, Ramos P, Guy E, Breda L, Chadburn A, et al. Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. 2007;109(11):5027-35.##Khandros E, Weiss MJJHocoNA. Protein quality control during erythropoiesis and hemoglobin synthesis. 2010;24(6):1071.##Vichinsky EJAotNYAoS. Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy. 2010;1202(1):180-7.##Sollaino MC, Paglietti ME, Perseu L, Giagu N, Loi D, Galanello RJH. 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Under Pressure: A Rare Portrait of Cardiac Strain and Respiratory Distress in Mediastinal Neuroblastoma 2 2 Background: Neuroblastoma is the most common extracranial solid tumor in children, typically arising from the adrenal glands or abdominal sympathetic chain. Thoracic involvement, particularly in the posterior mediastinum, is rare and may present with nonspecific respiratory symptoms. When adjacent cardiac structures are compressed, clinical severity increases, posing diagnostic and therapeutic challenges. Case Presentation: A one-year-old girl presented with persistent wheezing and recurrent pneumonia unresponsive to antibiotics. Initial imaging suggested pulmonary sequestration, but further evaluation—including echocardiography and angiography—revealed a posterior mediastinal mass compressing the left atrium and ventricle. Biopsy confirmed neuroblastoma. No metastasis was found on staging. Classified as intermediate-risk, she was treated per the Children’s Oncology Group (COG) A3961 protocol with chemotherapy. Treatment was well-tolerated, symptoms improved, and follow-up imaging showed significant tumor reduction without complications or recurrence. Conclusion: Posterior mediastinal neuroblastoma may mimic common respiratory illnesses, delaying diagnosis. Cardiac compression can worsen symptoms and increase risks. Early recognition, accurate diagnosis, and multidisciplinary care are essential for favorable outcomes, as demonstrated by this case with no treatment complications or tumor recurrence on follow-up. 13 23 2025/04/112025/03/25 1404/1/5 2025/05/222025/06/15 1404/3/25 Mohsen Rahmanian Mohsen Rahmanian School of Medicine, North Khorasan University of Medical Sciences, Bojnord, Iran. Sarah Khosropanah Sarah Khosropanah School of Medicine, North Khorasan University of Medical Sciences, Bojnord, Iran Amir Muhammad Khuban Azghadi Amir Muhammad Khuban Azghadi School of Medicine, North Khorasan University of Medical Sciences, Bojnord, Iran Hamid Farhangi Hamid Farhangi Department of Pediatrics Hematology and Oncology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran FarhangiH@mums.ac.ir Neuroblastoma Chemotherapy Pediatrics Cardiac Compression Thoracic Tumors Vishwapriya Mahadev Godkhindi, M.M.B., Kamran Khan, Kiran Thorat, Adult Neuroblastoma-Case Report and Literature Review. Journal of Clinical and Diagnostic Research, 2016. 10(12): p. ED01-ED02.##Davis, S., M.A. Rogers, and T.W. Pendergrass, The incidence and epidemiologic characteristics of neuroblastoma in the United States. Am J Epidemiol, 1987. 126(6): p. 1063-74.##Heck, J.E., et al., The epidemiology of neuroblastoma: a review. Paediatric and Perinatal Epidemiology, 2009. 23(2): p. 125-143.##Sbeih, A.H., et al., Epidemiological and Clinical Data in Low and Intermediate Risk Neuroblastoma: A Single Institution Experience and Survival Outcomes in Jerusalem. Asian Pac J Cancer Care, 2020. 5(3): p. 139-144.##Ait Si Abdessadeq J, C.H., Ouassil S, Ahmanna H, Zouita B, Basraoui D, et al., Posterior Mediastinal Neuroblastoma in Children: An Unusual Location. Scholars J Med Case Rep. , 2025. 13: p. 1121-1124.##Singh, V., L. Tyngkan, and A.R. Bhat, Rare Atypical Presentation of a Neuroblastoma of Posterior Mediastinum. Int J Recent Surg Med Sci., 2021. 7.##Bargujar, P., J. Upadhyay, and H.R. Pahadiya, Posterior mediastinal neuroblastoma presenting with spinal cord compression as oncoemergency. J Pediatr Crit Care, 2023. 10(4).##Feki, J., et al., An uncommon breast metastasis of mediastinal neuroblastoma within a child: A case report. Breast J, 2021. 27(4): p. 377-379.##Ko, S.F., et al., Juvenile fibromatosis of the posterior mediastinum with intraspinal extension. AJNR Am J Neuroradiol, 1996. 17(3): p. 522-4.##Atwal, S.S., Neuroblastoma of posterior mediastinum: classical imaging findings. J Clin Diagn Res, 2014. 8(10): p. Rj01.##Kazemian, M., et al., Neonatal neuroblastoma presented with respiratory distress, a case report. Respir Med Case Rep, 2019. 28: p. 100874.##McLatchie, G.R. and D.G. Young, Presenting features of thoracic neuroblastoma. Arch Dis Child, 1980. 55(12): p. 958-62.##Stetsenko, T., et al., The case of Kinsburn's Encephalopathy in a child with neuroblastoma of posterior mediastinum. Mod Pediatr Ukr, 2024(1 (137)): p. 138-142.##Tang, J., et al., Clinical characteristics and therapeutic outcomes of mediastinal neuroblastoma with intraspinal extension: a retrospective study. Transl Pediatr, 2021. 10(4): p. 715-722.##Fatimi, S.H., S.A. Bawany, and A. Ashfaq, Ganglioneuroblastoma of the posterior mediastinum: a case report. J Med Case Rep, 2011. 5: p. 322.##Kinsella, C., et al., Neuroblastoma and life-threatening tracheal obstruction: A case report and literature review. Int J Pediatr Otorhinolaryngol Extra, 2011. 6(3): p. 146-148.##Ochi, T., et al., Successful all robotic-assisted excision of highly malignant mediastinal neuroblastoma in a toddler: A case report. Asian J Endosc Surg, 2023. 16(3): p. 542-545.##Rudolf, J.W. and M. Thapa, Thoracic neuroblastoma. Radiol Case Rep, 2011. 6(2): p. 440.##Yahya, F.S. and H.A. Al-Shami, Posterior mediastinal neuroblastoma masked as flaccid paraparesis in a 3 year child. Neurosciences (Riyadh), 2019. 24(4): p. 320-323.##Vantankhah, A., et al., A life-threatening encounter: an uncommon case of ruptured hydatid cyst presenting as anaphylactic shock and respiratory distress in a 12-year-old boy. Annals of Medicine and Surgery, 2023. 85(11): p. 5742-5747.##Han, W. and H.M. 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Zinc Sulphate for Prevention of Breast Cancer Radiation Therapy-Induced Dermatitis: A Three-arm Triple-blinded Randomized Clinical Trial 2 2 Background: Radiation therapy (RT)-induced dermatitis is a common side effect in breast cancer patients that impacts quality of life and treatment compliance. Although zinc sulphate has shown potential for reducing skin lesions in preclinical studies, clinical evidence is still limited. Methods: In this three-arm triple-blinded randomized trial, 180 breast cancer patients scheduled for whole breast RT were allocated to receive zinc sulphate 150mg/day (n=60), zinc sulphate 100 mg/day (n=60), or placebo (n=60) during RT. The primary outcome was dermatitis severity per Radiation Therapy Oncology Group (RTOG) criteria at pre-specified time points through weeks 1 to 5 during RT and months 1 and 2 after RT cessation. Results: Dermatitis severity was significantly lower in both zinc sulphate arms versus placebo from weeks 3-5 of RT (p<0.01). Moreover, the 150 mg/day arm showed lower dermatitis severity versus 100 mg/day in week 5 of RT (p<0.001), with mean RTOG scores of 0.33±0.47 for 150 mg/day, 0.75±0.62 for 100 mg/day, and 1.30±0.74 for the placebo group. Analysis of dermatitis trends revealed a dose-dependent pattern, with 150 mg/day showing an earlier plateau in severity escalation. No significant drug adverse effects were observed. Conclusions: Zinc sulphate supplementation during breast cancer RT mitigates the incidence and severity of acute radiation dermatitis in a potentially dose-dependent manner, which demonstrates the potential to improve patient quality of life by reducing RT-related skin toxicity. Further research on optimal dosing and long-term effects is warranted. 24 33 2025/04/112025/03/252025/04/27 1404/2/7 2025/05/222025/06/152025/06/25 1404/4/4 Sarah Aflatoonian Sarah Aflatoonian Department of Radiation Oncology, Kerman University of Medical Sciences, Kerman, Iran. Sarah.aflatoonian@gmail.com Sara Shamsi Sara Shamsi Department of Radiation Oncology, Kerman University of Medical Sciences, Kerman, Iran. Mehran Ilaghi Mehran Ilaghi Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. Samira Yazdani Samira Yazdani Department of Radiation Oncology, Kerman University of Medical Sciences, Kerman, Iran. Mostafa Eghbalian Mostafa Eghbalian Department of Epidemiology and Biostatistics, Faculty of Public Health, Social Determinants of Health Research Center, Gonabad University of Medical Sciences, Gonabad, Iran. Maryam Bahador Maryam Bahador Department of Radiation Oncology, Kerman University of Medical Sciences, Kerman, Iran. maryamb2003@yahoo.com Radiation Therapy Dermatitis Skin Toxicity Breast Cancer Zinc Sulphate Clinical Trial Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast cancer: targets and therapy. 2019:151-64.##Dehesh T, Fadaghi S, Seyedi M, Abolhadi E, Ilaghi M, Shams P, et al. The relation between obesity and breast cancer risk in women by considering menstruation status and geographical variations: a systematic review and meta-analysis. BMC women's health. 2023;23(1):392.##Balaji K, Subramanian B, Yadav P, Radha CA, Ramasubramanian V. Radiation therapy for breast cancer: Literature review. Medical Dosimetry. 2016;41(3):253-7.##Zare SA, Bahador M, Yazdani S. Comparison of lung and contralateral scattered breast dose between field-in-field and wedge techniques in patients with early breast cancer. Frontiers in Biomedical Technologies. 2024;11(3):486-91.##Burke G, Faithfull S, Probst H. Radiation induced skin reactions during and following radiotherapy: A systematic review of interventions. Radiography. 2022;28(1):232-9.##Rzepecki A, Birnbaum M, Ohri N, Daily J, Fox J, Bodner W, et al. Characterizing the effects of radiation dermatitis on quality of life: a prospective survey-based study. Journal of the American Academy of Dermatology. 2022;86(1):161-3.##Lucey P, Zouzias C, Franco L, Chennupati SK, Kalnicki S, McLellan BN. Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States. Supportive Care in Cancer. 2017;25(9):2857-62.##Purswani JM, Nwankwo C, Adotama P, Gutierrez D, Perez CA, Tattersall IW, et al. Radiation-induced skin changes after breast or chest wall irradiation in patients with breast cancer and skin of color: a systematic review. Clinical Breast Cancer. 2023;23(1):1-14.##Yee C, Wang K, Asthana R, Drost L, Lam H, Lee J, et al. Radiation-induced skin toxicity in breast cancer patients: a systematic review of randomized trials. Clinical Breast Cancer. 2018;18(5):e825-e40.##Arribas Lopez E, Zand Fard N, Ojo O, Kochhar T. A systematic review and meta-analysis of the effect 2 of zinc on wound healing. British Medical Journal (The BMJ). 2024.##Costa MI, Sarmento-Ribeiro AB, Gonçalves AC. Zinc: from biological functions to therapeutic potential. International Journal of Molecular Sciences. 2023;24(5):4822.##Kim B, Lee W-W. Regulatory role of zinc in immune cell signaling. Molecules and cells. 2021;44(5):335-41.##Dhaliwal S, Nguyen M, Vaughn AR, Notay M, Chambers CJ, Sivamani RK. Effects of zinc supplementation on inflammatory skin diseases: a systematic review of the clinical evidence. American journal of clinical dermatology. 2020;21(1):21-39.##Ertekin MV, Tekin SB, Erdoğan F, Karslioğlu I, Gepdiremen A, Sezen O, et al. The effect of zinc sulphate in the prevention of radiation-induced dermatitis. Journal of radiation research. 2004;45(4):543-8.##Kandaz M, Ertekin MV, Karslıoğlu İ, Erdoğan F, Sezen O, Gepdiremen A, et al. Zinc sulfate and/or growth hormone administration for the prevention of radiation-induced dermatitis: a placebo-controlled rat model study. Biological Trace Element Research. 2017;179(1):110-6.##Gorgu S, Ilknur A, Sercan O, Rahsan H, Nalan A. The effect of zinc sulphate in the prevention of radiation induced oral mucositis in patents with head and neck cancer. International Journal of Radiation Research. 2013;11(2):111.##Moslemi D, Babaee N, Damavandi M, Pourghasem M, Moghadamnia A. Oral zinc sulphate and prevention of radiation-induced oropharyngealmucositis in patients with head and neck cancers: A double blind, randomized controlled clinical trial. International Journal of Radiation Research. 2014;12(3):235-41.##Glutsch V, Hamm H, Goebeler M. Zinc and skin: an update. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2019;17(6):589-96.##_g##Tayal S, Kaur N, Kaur T, Chadha VD. Zinc as an adjunct in radiation-based therapies: Evidences of radioprotection and mechanistic insights. Nutrition and Health. 2025:02601060251329404.##Searle T, Ali FR, Al-Niaimi F. Zinc in dermatology. Journal of Dermatological Treatment. 2022;33(5):2455-8.##Ogawa Y, Kinoshita M, Shimada S, Kawamura T. Zinc and skin disorders. Nutrients. 2018;10(2):199.##Penny ME. Zinc supplementation in public health. Annals of Nutrition and Metabolism. 2013;62(Suppl. 1):31-42.##Anandhi P, Sharief RM, Rahila C. The benefit of zinc sulfate in oropharyngeal mucositis during hyperfractionated accelerated concomitant boost radiotherapy with concurrent cisplatin for advanced-stage oropharyngeal and hypopharyngeal cancers. Indian Journal of Palliative Care. 2020;26(4):437.##Ertekin MV, Koç M, Karslioǧlu I, Sezen O. Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study. International Journal of Radiation Oncology* Biology* Physics. 2004;58(1):167-74.##Sangthawan D, Phungrassami T, Sinkitjarurnchai W. 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Enhancing Cancer Zone Diagnosis in MRI Images: A Novel SOM Neural Network Approach with Block Processing in the Presence of Noise 2 2 Background: Brain tumors are a specific disease that directly affects the brain. Magnetic Resonance Imaging (MRI) is considered the most effective imaging technique for diagnosing brain tumors, providing crucial information about tumor size, location, and type. However, accurately segmenting and extracting the tumor region from MRI images is a challenging task for radiologists and physicians, impacting the overall accuracy of diagnosis. Methods: This research focuses on addressing the challenges of brain tumor detection and segmentation in MRI images. In line with the recent trend of big data analysis, neuroimaging data, including MRI images, are considered an important subset of big data due to their volume, velocity, and variety. The proposed approach utilizes the Self Organizing Maps (SOM) Neural Network, a powerful concept in image processing, to handle noise and artifacts in brain MRI. Results: The proposed method employs image segmentation to focus on smaller parts of the brain and utilizes the SOM neural network for noise reduction, enhancing the processing of noisy brain images. The approach incorporates block processing to effectively approximate the suspected cancer zone, facilitating accurate medical diagnosis. The algorithm achieves precise specification of brain image zones by learning the unique SOM algorithm and setting an edge detection threshold. Experimental results demonstrate the superior performance of the proposed method, surpassing previous approaches, with a precision of over 10% in diagnosing abnormal brain areas. Conclusion: The study highlights the importance of MRI in brain tumor diagnosis and the challenges associated with accurate tumor segmentation. The proposed approach using the SOM Neural Network effectively addresses these challenges by reducing noise, enabling block processing, and enhancing the precision of tumor detection. Results indicate the potential of the proposed method to significantly improve brain tumor diagnosis and contribute to advancements in medical imaging for neuroimaging applications. 34 45 2025/04/112025/03/252025/04/272025/04/22 1404/2/2 2025/05/222025/06/152025/06/252025/06/14 1404/3/24 Payam Porkar Payam Porkar Institute of Artificial Intelligence, Shaoxing University, Zhejiang, China. Rezaieh.Porkar@gmail.com Faranak Mehrabipour Faranak Mehrabipour Computer Department, Islamic Azad University, Damavand Branch, Damavand, Iran. Mohammad Hossein Pourasad Mohammad Hossein Pourasad School of paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran. Ali Akbar Movassagh Ali Akbar Movassagh Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Kobra nazari Kobra nazari Department of mathematics, Vali-E-Asr university of Rafsanjani, Rafsanjani, Iran. Pasha Porkar Pasha Porkar Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven 5600 MB, Netherlands. Mustafa Ghaderzadeh Mustafa Ghaderzadeh Boukan Faculty of Medical Sciences, Urmia University of Medical Sciences, Urmia, Iran. Mustaf.ghaderzadeh@sbmu.ac.ir Mehdi Gheisari Mehdi Gheisari Institute of Artificial Intelligence, Shaoxing University, Zhejiang, China. mehdi.gheisari61@gmail.com Cirruse Salehnasab Cirruse Salehnasab Assistant Professor of Medical Informatics, Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran. sohrab almasi sohrab almasi National Center for Health Insurance Research, Tehran, Iran. 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Artificial Intelligence in Gynecologic Cancer: A Review of Applications and Advancements 2 2 Gynecologic cancers, including cervical, ovarian, endometrial, vaginal, and vulvar malignancies, remain a major global health burden, accounting for substantial morbidity and mortality among women. Despite advances in conventional treatments such as surgery, chemotherapy, and radiotherapy, survival outcomes remain suboptimal, particularly in cases diagnosed at advanced stages. In recent years, artificial intelligence (AI) has emerged as a transformative tool in gynecologic oncology, offering novel approaches to enhance diagnostic accuracy, stratify risk, personalize treatment strategies, and streamline clinical workflows. This narrative review provides a comprehensive overview of the current and emerging applications of AI in the management of gynecologic cancers. Key developments are discussed, including deep learning models for imaging interpretation, AI-driven biomarker analysis for early detection, and predictive algorithms for assessing treatment response and toxicity risk. Additionally, the use of AI in automating cytopathology and optimizing resource allocation is explored. While early findings are promising, challenges remain regarding the generalizability of AI models across diverse populations, the need for standardized datasets, and the integration of AI tools into routine clinical practice. Addressing these limitations is essential to ensure safe, equitable, and effective implementation. Overall, this review underscores the potential of AI to significantly improve patient outcomes and clinical efficiency in gynecologic oncology. Future research and interdisciplinary collaboration will be critical in translating these innovations into real-world clinical benefit. 46 57 2025/04/112025/03/252025/04/272025/04/222025/05/7 1404/2/17 2025/05/222025/06/152025/06/252025/06/142025/05/29 1404/3/8 Milad Rahimi Milad Rahimi Health and Biomedical Informatics Research Center, Urmia University of Medical Sciences, Urmia, Iran. Kasra Kashani Kasra Kashani Health and Biomedical Informatics Research Center, Urmia University of Medical Sciences, Urmia, Iran. Vahid Hosseinpour Vahid Hosseinpour Department of Emergency Medicine, Urmia University of Medical Sciences, Urmia, Iran. Elahe Gozali Elahe Gozali Assistant Professor, Department of Health Information Technology, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, Iran. Corresponding Author. ORCID: https://orcid.org/0000-0002-9211-5934. Email: gozali_e@umsu.ac.ir. gozali_e@umsu.ac.ir Gynecologic cancers Oncology Malignancy Artificial intelligence Deep learning Machine learning Taddese AA, Tilahun BC, Awoke T, Atnafu A, Mamuye A, Mengiste SA. Deep-learning models for image-based gynecological cancer diagnosis: a systematic review and meta-analysis. Frontiers in Oncology. 2024;13:1216326.##Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer. 2015;136(5):E359-E86.##Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.##Wardle J, Robb K, Vernon S, Waller J. Screening for prevention and early diagnosis of cancer. 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A Comprehensive Study of Prostate Cancer and Epstein-Barr Virus Infection: A Systematic Review and Meta-analysis 2 2 This systematic review and meta-analysis examine the potential link between Epstein-Barr virus infection and prostate cancer development, highlighting its role in the second most common malignancy in developed countries. A complete literature search was conducted using PubMed, EMBASE, Scopus, and Web of Science to identify relevant studies published between 2002 and 2024. The study incorporated publications from various countries, peer-reviewed studies, systematic reviews, and meta-analyses as supplementary sources to identify additional relevant studies. The study analyzed data from 16 articles, involving 1,340 PC cases, assessing EBV detection based on geographical distribution, publication year, and EBV-positive cases. The odds ratio for EBV-associated PC was 26.79%, with a global prevalence of 0.38. The study indicates regional variations in EBV positivity among PC cases, suggesting a possible link between EBV infection and PC, but further research is needed to clarify its role. 58 69 2025/04/112025/03/252025/04/272025/04/222025/05/72025/05/23 1404/3/2 2025/05/222025/06/152025/06/252025/06/142025/05/292025/06/21 1404/3/31 Abolfazl Jafari-Sales Abolfazl Jafari-Sales Department of Microbiology, Kaz.C., Islamic Azad University, Kazerun, Iran. Parisa Shiri Aghbash Parisa Shiri Aghbash Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Zahra Sadeghi-Deylamdeh Zahra Sadeghi-Deylamdeh Department of Biology, Faculty of Sciences, Malayer Branch, Malayer, Iran Fatemeh Jahangirimehr Fatemeh Jahangirimehr Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran Sayed Mohsen Hosseini Sayed Mohsen Hosseini Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran Nooshin Amini Nooshin Amini Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran. Mehrdad Pashazadeh Mehrdad Pashazadeh Department of Medical Laboratory Sciences and Microbiology, Faculty of Medical Sciences, TaMS.C., Islamic Azad University, Tabriz, Iran. mehrdadpashazadeh85@gmail.com Hamidreza Fathi Hamidreza Fathi Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 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Oncogenes as Diagnostic Biomarkers in Breast Cancer: A Review of Molecular Detection and Clinical Utility 2 2 Breast cancer management has been revolutionized by the identification of key oncogenes which serve as critical diagnostic and prognostic biomarkers. These molecular alterations influence tumor behavior, treatment response, and patient outcomes, enabling personalized therapeutic strategies. This review comprehensively examined the most prominent oncogenes—HER2, PIK3CA, MYC, and BRCA1/2—implicated in breast carcinogenesis, the technologies used for their detection, and their implications for precision oncology. HER2 amplification, found in 15-20% of breast cancers, is associated with aggressive disease but responds well to targeted therapies like trastuzumab. While IHC and FISH remain standard detection methods, emerging technologies such as NGS improve sensitivity. PIK3CA mutations, common in HR+ tumors, drive therapy resistance but can be targeted with PI3K inhibitors, though clinical responses vary. The MYC oncogene promotes tumor proliferation and poor prognosis, but its therapeutic targeting remains challenging due to its complex role. BRCA1/2 mutations significantly increase hereditary breast cancer risk, particularly in TNBC and HR+ subtypes. PARP inhibitors have shown remarkable efficacy in BRCA-mutated cancers, highlighting the importance of genetic testing. Despite these advances, challenges such as tumor heterogeneity, assay standardization, and biomarker validation persist. Future directions include multi-omics integration, liquid biopsy development, and AI-driven diagnostics to refine precision oncology approaches. 70 82 2025/04/112025/03/252025/04/272025/04/222025/05/72025/05/232025/06/2 1404/3/12 2025/05/222025/06/152025/06/252025/06/142025/05/292025/06/212025/06/27 1404/4/6 Amir Abbas Esmaeilzadeh Amir Abbas Esmaeilzadeh Department of Research of Salamat Yar Behesht Dayan, Dayanbiotech Co, Iran. ab.esmailzadeh@yahoo.com Dorsa Azizikhezri Dorsa Azizikhezri Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Zahra Fatahi Zahra Fatahi Imam reza hospital, kermanshah university of medical science, kermanshah, iran Hamed Saeidi Hamed Saeidi Department of Biology, Damghan Branch, Islamic Azad University, Iran Mohammadtaghi Fazel Mohammadtaghi Fazel Department of Research, Ocean Pharmaceutical Products Company, Tehran, Iran. Fatemeh Nasirzadeh Fatemeh Nasirzadeh Department of Life Science Engineering, Tehran University, Iran. 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Natural killer cell-based Immunotherapy for Solid tumors: A Comprehensive Review 2 2 Natural Killer Celle (NK) are innate immune cells with potent cytotoxic activity against tumor cells, making them attractive candidates for cancer immunotherapy. While NK cell-based therapies have shown promise in hematologic malignancies, their efficacy against solid tumors remains challenging due to the immunosuppressive tumor microenvironment (TME) and limited NK cell persistence. This review discusses recent advances in NK cell-based immunotherapies, including adoptive NK cell transfer, NK cell engagers, and genetic modifications to enhance their anti-tumor activity. We also explore the barriers to effective NK cell therapies in solid tumors and potential strategies to overcome these limitations. 83 98 2025/04/112025/03/252025/04/272025/04/222025/05/72025/05/232025/06/22025/05/15 1404/2/25 2025/05/222025/06/152025/06/252025/06/142025/05/292025/06/212025/06/272025/06/28 1404/4/7 Vinod Kumar Singh Vinod Kumar Singh TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. drvinodkumarsingh85@gmail.com Seema Awasthi Seema Awasthi TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. Sonika Sharma Sonika Sharma TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. Natural Killer (NK) Cells Adoptive NK Cell Transfer Tumor Microenvironment Immunosuppressive Factors Rojas-Quintero J, Díaz MP, Palmar J, Galan-Freyle NJ, Morillo V, Escalona D, González-Torres HJ, Torres W, Navarro-Quiroz E, Rivera-Porras D, Bermúdez V. Car T Cells in Solid Tumors: Overcoming Obstacles. Int J Mol Sci. 2024 Apr 10;25(8):4170##Yu Y. 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Efficacy and Safety of Ensartinibin ALK-positive Non-Small Cell Lung Cancer Patients: A Systematic Review and Meta-analysis 2 2 Background: NSCLC accounts for a significant proportion of global cancer mortality, with ALK-positive NSCLC constituting approximately 9% of cases. Ensartinib has demonstrated promising systemic and central CNS efficacy in clinical trials. Methods: A systematic review and meta-analysis were performed following PRISMA guidelines, using PubMed, Web of Science, Cochrane, and Scopus databases. RCTs and cohort studies reporting outcomes such as OS, PFS, RR, and adverse events in ALK-positive NSCLC patients treated with ensartinib were included. Data were synthesized using CMA software, and heterogeneity was assessed using chi-square tests and I² statistics. Results: Six studies encompassing 1,246 patients met the inclusion criteria. Pooled analysis revealed a RR of 56% (95% CI: 45–67%) and significant improvements in OS (Mean = 41.71 months, 95% CI: 31.64–51.77) and PFS (Mean = 8.88 months, 95% CI: 4.48–13.28). Common adverse events included rash (69%), nausea (19%), vomiting (15%), and transaminitis, with ALT (49%) and AST (42%) elevations. Conclusions: Ensartinib exhibits significant efficacy in improving OS and PFS in ALK-positive NSCLC, with manageable adverse effects. Its robust systemic and CNS activity supports its clinical utility as a second-generation ALK inhibitor. Further studies with bigger, diverse populations are warranted to validate these findings and explore long-term outcomes. ./files/site1/files/Suplemenatry_Table_1.pdf   99 109 2025/04/112025/03/252025/04/272025/04/222025/05/72025/05/232025/06/22025/05/152025/05/6 1404/2/16 2025/05/222025/06/152025/06/252025/06/142025/05/292025/06/212025/06/272025/06/282025/06/14 1404/3/24 Vinod Kumar Singh Vinod Kumar Singh TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. drvinodkumarsingh85@gmail.com Seema awasthi Seema awasthi TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. seemaawasthi285@gmail.com Jigar Haria Jigar Haria TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. jigarharia332@gmail.com Prithpal Singh Prithpal Singh TMMC;RC, Teerthanker Mahaveer University, Moradabad, UP, India. singhmatrejaprithpal@gmail.com NSCLC Immunotherapy Biomarkers EGFR Metastasis    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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Visual and Tumor Outcomes After Surgical Intervention in Optic Pathway Gliomas: A Systematic Review 2 2 Background: Optic pathway gliomas (OPGs) are rare tumors predominantly affecting children and are often associated with neurofibromatosis type 1 (NF1). Their variable clinical course and critical visual and neuroendocrine pathway involvement present significant management challenges. This systematic review aims to evaluate the role of surgical intervention in OPGs, focusing on its impact on visual outcomes, postoperative tumor status, and treatment-related complications. Methods: A systematic review was conducted following PRISMA guidelines. Data were extracted from peer-reviewed studies reporting surgical outcomes in OPG patients, including Dodge classification, type of surgical approach, intervention details, visual outcomes, tumor progression, progression-free survival (PFS), overall survival (OS), and complications. Results: A total of 13 studies comprising 661 patients were included. Dodge Type III tumors were the most commonly reported. Surgical interventions included biopsy, subtotal resections, gross total resection (GTR), and debulking. Visual outcomes were variable; visual improvement was observed in a minority of cases, stable vision was the most commonly reported outcome, and others documented visual deterioration. Tumor status after surgery was stable in a majority of patients (up to 62,8%). Reported PFS and OS show 5-year OS rates ranging from 84.1% to 97.7% and PFS rates from 47.7% to 70.6%, indicating high survival with moderate variability in disease progression. Reported complications included visual loss, endocrine dysfunction, shunt failure, and mortality in a small subset. Conclusion: Surgical intervention in OPGs is mainly diagnostic or decompressing. Visual improvement is uncommon; stability is more frequent. Aggressive surgery risks deterioration, highlighting the need for careful planning and standardized studies to guide management. 110 123 2025/04/112025/03/252025/04/272025/04/222025/05/72025/05/232025/06/22025/05/152025/05/62025/05/26 1404/3/5 2025/05/222025/06/152025/06/252025/06/142025/05/292025/06/212025/06/272025/06/282025/06/142025/06/13 1404/3/23 Alivery Raihanada Armando Alivery Raihanada Armando Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Tedy Apriawan Tedy Apriawan Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Drtedyapri@gmail.com Maimanah Zumaro Ummi Faiqoh Maimanah Zumaro Ummi Faiqoh Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Venansya Maulina Praba Venansya Maulina Praba Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. Ramadhani Rizki Zamzam Ramadhani Rizki Zamzam Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia. 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