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Ectopic Pituitary Neuroendocrine Tumors/Adenomas Around the Sella Turcica 蝶鞍周围异位垂体神经内分泌肿瘤/腺瘤
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 Epub Date: 2024-03-08 DOI: 10.4274/balkanmedj.galenos.2024.2023-11-90
Mustafa Kemal Demir, Önder Ertem, Deniz Kılıç, Okan Akıncı, Özge Ecertaştan, Deniz Konya, Türker Kılıç

Functional or non-secretory ectopic pituitary neuroendocrine tumors (PitNET) can form around the sella turcica during the development of the adenohypophysis by differentiating and detaching from the pharyngeal roof. These tumors usually appear in the sphenoid sinus, clivus, cavernous sinus, infundibulum, and suprasellar cistern. Ectopic PitNETs typically display the characteristic magnetic resonance imaging findings of pituitary adenomas. However, preoperative diagnosis of PitNETs is usually challenging because of the variety of clinical and imaging presentations, locations, and sizes. Ectopic suprasellar PitNETs resemble mass lesions in the pituitary stalk. Ectopic cavernous sinus of PitNETs are typically microadenomas in the medial wall. Ectopic sphenoclival tumors are characterized by more aggressive tumor activity than the other ectopic PitNETs. Although ectopic PitNETs are exceedingly rare, they should be considered as a differential diagnosis for masses around the sella turcica. Treatment of the disease should be individualized and may include medical care, surgical resection, gamma-knife radiosurgery, and radiotherapy.

功能性或非分泌性异位垂体神经内分泌肿瘤(PitNET)可在腺嗜铬细胞发育过程中通过分化并脱离咽顶而在蝶鞍周围形成。这些肿瘤通常出现在蝶窦、蝶窦、海绵窦、蝶窦内和蝶窦上。异位垂体网状细胞瘤通常具有垂体腺瘤的磁共振成像特征。然而,由于 PitNET 的临床和影像学表现、位置和大小各不相同,因此术前诊断通常具有挑战性。异位星上垂体网类似于垂体柄的肿块病变。异位海绵窦 PitNET 通常是内侧壁的微腺瘤。与其他异位PitNET相比,异位海绵窦肿瘤的特点是肿瘤活动更具侵袭性。虽然异位 PitNET 非常罕见,但应将其作为蝶鞍周围肿块的鉴别诊断。该病的治疗应因人而异,可能包括药物治疗、手术切除、伽马刀放射外科手术和放射治疗。
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引用次数: 0
Giant Left Atrium in an Octogenarian with a Complex Etiology 病因复杂的八旬老人左心房巨大。
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 Epub Date: 2024-03-18 DOI: 10.4274/balkanmedj.galenos.2024.2024-1-64
Angelina Borizanova, Elena Kinova, Plamen Getsov, Assen Goudev
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引用次数: 0
Present and Future of Artificial Intelligence in Pathology. 病理学中人工智能的现状与未来。
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 DOI: 10.4274/balkanmedj.galenos.2024.2024.060324
Ufuk Usta, Ebru Taştekin
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引用次数: 0
Thymic Stromal Lymphopoietin Activates Mouse Dendritic Cells Through the JAK/SYK Pathway in Promoting Th17 Response in Psoriasis. 胸腺基质淋巴细胞生成素通过 JAK/SYK 通路激活小鼠树突状细胞,促进银屑病的 Th17 反应
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 DOI: 10.4274/balkanmedj.galenos.2024.2024-1-96
Cuihao Song, Jie Sun, Zhenkai Zhao, Xu Zhang, Xiangyu Ding, Xiaoqiang Liang, Jia Bai, Liyuan Xing, Lingling Gong, Chengxin Li, Biwen Lin

Background: Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others.

Aims: To investigate the role of TSLP in the pathogenesis of psoriasis.

Study design: In vitro and in vivo study.

Methods: To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4+ T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4+ T cells.

Conclusion: These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.

背景:银屑病是一种无法治愈的慢性炎症性皮肤病。虽然银屑病的具体病因尚不清楚,但免疫细胞和炎性细胞因子之间的相互作用被认为是银屑病发病机制的重要因素。胸腺基质淋巴细胞生成素(TSLP)是一种由上皮细胞产生的细胞因子,对树突状细胞(DCs)有深远影响,并与过敏和炎症性疾病有关。在一些研究中,它在银屑病患者皮肤中的表达量较高,而在另一些研究中,与未接受治疗的患者相比,接受治疗的银屑病患者中的表达量增加:研究设计:体外和体内研究:为了研究TSLP在体内对银屑病的影响,使用了小鼠银屑病模型和靶向TSLP的shRNA来减少其表达。体外培养小鼠原代骨髓树突状细胞(BMDCs),用于研究 TSLP 激活的信号通路。结果:我们发现,减少银屑病皮肤中 TSLP 的表达可减轻疾病的严重程度。TSLP 激活了银屑病皮肤中的 Janus 激酶 (JAK)/SYK 通路。用BMDCs进行的体外研究表明,TSLP通过JAK/SYK途径增加了DC的成熟度,并激活了DC分泌的细胞因子,这些细胞因子通过激活STAT3信号刺激CD4+ T细胞发育成T辅助17(Th17)细胞。JAK/SYK通路抑制剂降低了TSLP激活BMDCs和促进CD4+ T细胞Th17分化的作用:这些研究结果表明,TSLP通过JAK/SYK途径对银屑病发挥免疫调节作用。
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引用次数: 0
Spot Diagnosis for Suspected COVID-19 Cases: Is there a Place for a Traditional Weapon in Modern Combat? COVID-19 疑似病例的定点诊断:传统武器在现代战斗中是否有用武之地?
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 Epub Date: 2024-01-29 DOI: 10.4274/balkanmedj.galenos.2024.2023-11-133
Petros V. Vlastarakos, Alexandros Delides, Giorgos Sideris, Sotirios Tsiodras
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引用次数: 0
Genetic Landscape of Hearing Loss in the Caribbean: A Narrative Review. 加勒比地区听力损失的遗传情况:叙述性综述。
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 DOI: 10.4274/balkanmedj.galenos.2024.2024-2-110
LéShon Peart, Mustafa Tekin

The Caribbean region has a diverse population of about 40 million people, spread over 13 sovereign states. This review aims to describe the existing studies on hereditary hearing loss (HL) in the Caribbean population. We systematically reviewed scientific articles on HL prevalence, genetic causes, technology use, and environmental effects in Caribbean nations and the Caribbean diaspora in the United States. Key findings show that HL rates, with diverse genetic variables, vary across Puerto Rico, Cuba, and the Dominican Republic. Local resources and technology have been used to diagnose HL, particularly in rural areas. Environmental factors tend to affect HL prevalence in various regions. This literature review of Caribbean-focused studies helps guide future research and healthcare strategies, particularly concerning genetic drift caused by migration to the United States. Understanding these factors can help diagnose and treat HL in America's diverse population.

加勒比海地区拥有约 4000 万人口,分布在 13 个主权国家。本综述旨在介绍有关加勒比海地区遗传性听力损失(HL)的现有研究。我们系统回顾了有关加勒比海国家和散居美国的加勒比海人 HL 患病率、遗传原因、技术使用和环境影响的科学文章。主要研究结果表明,波多黎各、古巴和多米尼加共和国的 HL 患病率各不相同,遗传变量也各不相同。当地资源和技术被用于诊断 HL,尤其是在农村地区。环境因素往往会影响不同地区的 HL 患病率。这篇以加勒比海地区为重点的研究文献综述有助于指导未来的研究和医疗策略,尤其是有关移民美国所导致的基因漂移的研究。了解这些因素有助于诊断和治疗美国不同人群的 HL。
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引用次数: 0
Radiological Features for Predicting the Status of CD8-Positive Lymphocytes in HER2 Positive Breast Cancer. 预测 HER2 阳性乳腺癌 CD8 阳性淋巴细胞状态的放射学特征
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 DOI: 10.4274/balkanmedj.galenos.2024.2024-2-64
Yuhong Fan, Xiaoguang Li, Peng Zhong, Hong Guo, Dong Han, Wuguo Tian, Jingqin Fang

Background: The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response.

Aims: To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC.

Study design: Retrospective cohort study.

Methods: This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility.

Results: Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p < 0.001, US_ADC vs. ADC).

Conclusion: US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8+-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.

背景:目的:研究HER2阳性乳腺癌(BC)患者的超声(US)和磁共振成像(MRI)特征与CD8阳性TILs(CD8+-TILs)水平之间的关系:研究设计:回顾性队列研究:这项回顾性研究包括155名HER2阳性BC女性患者。患者分为两组:CD8+-TIL低(< 35%)组和CD8+-TIL高(≥ 35%)组。使用 BI-RADS 词典评估 US 和 MRI 特征,并使用 RadiAnt 软件计算表观弥散系数(ADC)值。单变量和多变量分析显示了预测 CD8+-TIL 水平的最佳 US 和 MRI 特征。接收者操作特征分析和德隆检验用于比较 US 和 MRI 特征的诊断性能。此外,采用提名图将提高临床实用性:US特征的单变量分析显示,两组患者在形状、方向和后方回声方面存在显著差异;但在边缘、内部回声和微钙化方面没有显著差异。多因素分析显示,形状、方向和后方回声是独立的风险因素,几率比分别为 11.62、2.70 和 0.16。就磁共振成像特征而言,ADC是CD8+-TIL水平的独立预测因子。这三个 US 特征和 ADC 表现良好,曲线下面积 (AUC) 值分别为 0.802 和 0.705。与单独使用 US 或 ADC 相比,US 和 ADC 值的组合具有更高的预测效力(AUC = 0.888)(p = 0.009,US_ADC vs. US;p < 0.001,US_ADC vs. ADC):结论:US特征(形状、方向和后方回声)和ADC值可能是估计HER2阳性BC中CD8+-TIL水平的重要工具。该提名图可帮助临床医生做出决策。
{"title":"Radiological Features for Predicting the Status of CD8-Positive Lymphocytes in HER2 Positive Breast Cancer.","authors":"Yuhong Fan, Xiaoguang Li, Peng Zhong, Hong Guo, Dong Han, Wuguo Tian, Jingqin Fang","doi":"10.4274/balkanmedj.galenos.2024.2024-2-64","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-2-64","url":null,"abstract":"<p><strong>Background: </strong>The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response.</p><p><strong>Aims: </strong>To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8<sup>+</sup>-TILs) in patients with HER2-positive BC.</p><p><strong>Study design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8<sup>+</sup>-TIL<sub>low</sub> (< 35%) and CD8<sup>+</sup>-TIL<sub>high</sub> (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8<sup>+</sup>-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility.</p><p><strong>Results: </strong>Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8<sup>+</sup>-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (<i>p</i> = 0.009, US_ADC vs. US; <i>p</i> < 0.001, US_ADC vs. ADC).</p><p><strong>Conclusion: </strong>US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8<sup>+</sup>-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"41 3","pages":"213-221"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emphysematous Urinary Tract Infections in Diabetics 糖尿病患者的气肿性尿路感染。
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 Epub Date: 2024-03-18 DOI: 10.4274/balkanmedj.galenos.2024.2024-1-81
Vitorino Modesto Dos Santos, Lister Arruda Modesto Dos Santos
{"title":"Emphysematous Urinary Tract Infections in Diabetics","authors":"Vitorino Modesto Dos Santos, Lister Arruda Modesto Dos Santos","doi":"10.4274/balkanmedj.galenos.2024.2024-1-81","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-81","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"230-231"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats. 水飞蓟素在减轻紫杉醇诱导的肝毒性和肾毒性方面的治疗潜力:洞察大鼠体内的氧化应激、炎症和细胞凋亡
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 DOI: 10.4274/balkanmedj.galenos.2024.2024-1-60
Seda Yakut, Tuğçe Atcalı, Cüneyt Çaglayan, Aykut Ulucan, Fatih Mehmet Kandemir, Adem Kara, Turgut Anuk

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits.

Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways.

Study design: Experimental animal model.

Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models.

Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05).

Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

背景:紫杉醇(PAX)是一种广泛用于治疗各种癌症的化疗药物,但通常会对多个器官系统产生严重毒性。水飞蓟素(SIL)是一种天然类黄酮,因其多种益处而显示出治疗潜力。目的:评估水飞蓟素在减轻 PAX 诱导的大鼠肝脏和肾脏损伤方面的疗效,重点关注氧化应激、炎症和细胞凋亡途径:研究设计:实验动物模型:大鼠分为四组:对照组、SIL 组、PAX 组和 PAX + SIL 组,每组七只。大鼠腹腔注射 PAX,剂量为每公斤体重 2 毫克,连续注射 5 天,然后口服 SIL,剂量为每公斤体重 200 毫克,连续口服 10 天。我们使用自动分析仪和大鼠专用试剂盒检测了 SIL 对特定血清生化指标的影响。分光光度法用于研究肾脏和肝脏组织中的氧化应激指标。使用Aquaporin-2 (AQP-2)、B细胞淋巴瘤-2 (Bcl-2)、半胱氨酸天冬氨酸特异性蛋白酶-3 (caspase-3)、白细胞介素-6 (IL-6)、核因子卡巴B (NF-κB)和链霉亲和素-生物素染色来评估PAX诱导的肝脏和肾脏损伤模型的免疫反应性:结果:SIL 能明显降低血清中丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、肌酐、尿素和 C 反应蛋白的水平,这表明它能有效治疗 PAX 引起的肝肾损伤。SIL 能提高超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽等基本抗氧化指标,从而明显降低氧化应激。它还降低了 SIL-PAX 组肝脏和肾脏组织中的丙二醛水平(p < 0.05)。服用 SIL 可降低 NF-κB、caspase-3 和 IL-6 的表达,同时提高 SIL 和 PAX 组大鼠肝脏和肾脏组织中 Bcl-2 和 AQP2 的水平(p < 0.05):我们的研究结果表明,SIL 有可能通过减少氧化应激、炎症和细胞凋亡过程来减轻 PAX 诱导的大鼠肝脏和肾脏损伤。
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引用次数: 0
Binding Activity Classification of Anti-SARS-CoV-2 Molecules using Deep Learning Across Multiple Assays 利用深度学习对多种检测方法中的抗 SARS-CoV-2 分子进行结合活性分类。
IF 1.9 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-03 Epub Date: 2024-03-11 DOI: 10.4274/balkanmedj.galenos.2024.2024-1-73
Bilge Eren Yamasan, Selçuk Korkmaz
<p><strong>Background: </strong>The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has urgently necessitated effective therapeutic solutions, with a focus on rapidly identifying and classifying potential small-molecule drugs. Given traditional methods’ labor-intensive and time-consuming nature, deep learning has emerged as an essential tool for efficiently processing and extracting insights from complex biological data.</p><p><strong>Aims: </strong>To utilize deep learning techniques, particularly deep neural networks (DNN) enhanced with the synthetic minority oversampling technique (SMOTE), to enhance the classification of binding activities in anti-SARS-CoV-2 molecules across various bioassays.</p><p><strong>Methods: </strong>We used 11 bioassay datasets covering various SARS-CoV-2 interactions and inhibitory mechanisms. These assays ranged from spike-ACE2 protein-protein interaction to ACE2 enzymatic activity and 3CL enzymatic activity. To address the prevalent class imbalance in these datasets, the SMOTE technique was employed to generate new samples for the minority class. In our model-building approach, we divided the dataset into 80% training and 20% test sets, reserving 10% of the training set for validation. Our approach involved employing a DNN that integrates ReLU and sigmoid activation functions, incorporates batch normalization, and uses Adam optimization. The hyperparameters and architecture of the DNN were optimized through various tests on layers, minibatch sizes, epoch sizes, and learning rates. A 40% dropout rate was incorporated to mitigate overfitting. For model evaluation, we computed performance metrics, such as balanced accuracy (BACC), precision, recall, F1 score, Matthews’ correlation coefficient (MCC), and area under the curve (AUC).</p><p><strong>Results: </strong>The performance of the DNN across 11 bioassay test sets revealed varying outcomes, significantly influenced by the ratios of active-to-inactive compounds. Assays, such as AlphaLISA and CoV-PPE, demonstrated robust performance across various metrics, including BACC, precision, recall, and AUC, when configured with more balanced ratios (1:3 and 1:1, respectively). This suggests the effective identification of active compounds in both cases. In contrast, assays with higher imbalance ratios, such as 3CL (1:38) and cytopathic effect (1:15), demonstrated higher recall but lower precision, highlighting challenges in accurately identifying active compounds among numerous inactive compounds. However, even in these challenging settings, the model achieved favorable BACC and recall scores. Overall, the DNN model generally performed well, as indicated by the BACC, MCC, and AUC values, especially when considering the degree of dataset imbalance in each assay.</p><p><strong>Conclusion: </strong>This study demonstrates the significant impact of deep learning, particularly DNN models enhanced with SMOTE, i
背景:由严重急性呼吸系统综合征-冠状病毒-2(SARS-CoV-2)引起的冠状病毒病-2019(COVID-19)大流行迫切需要有效的治疗解决方案,重点是快速识别和分类潜在的小分子药物。目的:本研究旨在利用深度学习技术,特别是利用合成少数超采样技术(SMOTE)增强的深度神经网络(DNN),来提高抗SARS-CoV-2分子在各种生物测定中结合活性的分类能力:我们使用了 11 个生物测定数据集,涵盖了各种 SARS-CoV-2 相互作用和抑制机制。这些测定包括尖峰-ACE2 蛋白-蛋白相互作用、ACE2 酶活性和 3CL 酶活性。为了解决这些数据集中普遍存在的类不平衡问题,我们采用了 SMOTE 技术为少数类生成新样本。在建立模型的方法中,我们将数据集分为 80% 的训练集和 20% 的测试集,并保留 10% 的训练集用于验证。我们采用的 DNN 方法整合了 ReLU 和 sigmoid 激活函数、批量归一化和亚当优化。通过对层数、最小批量大小、历时大小和学习率进行各种测试,对 DNN 的超参数和架构进行了优化。我们还加入了 40% 的辍学率,以减少过度拟合。为了对模型进行评估,我们计算了性能指标,如平衡准确率(BACC)、精确度、召回率、F1 分数、马修斯相关系数(MCC)和曲线下面积(AUC):结果:DNN 在 11 个生物测定测试集中的表现显示出不同的结果,其中活性与非活性化合物的比例对其影响很大。AlphaLISA 和 CoV-PPE 等检测方法在配置更均衡的比例(分别为 1:3 和 1:1)时,在 BACC、精确度、召回率和 AUC 等各种指标上都表现出强劲的性能。这表明在这两种情况下都能有效识别活性化合物。相比之下,3CL(1:38)和细胞病理效应(1:15)等不平衡比率较高的检测方法的召回率较高,但精确度较低,这凸显了在众多非活性化合物中准确识别活性化合物所面临的挑战。不过,即使在这些具有挑战性的环境中,该模型也取得了良好的 BACC 和召回分数。总体而言,正如 BACC、MCC 和 AUC 值所显示的那样,DNN 模型总体表现良好,尤其是考虑到每个检测中数据集的不平衡程度时:本研究表明,深度学习,特别是使用 SMOTE 增强的 DNN 模型,在改进 COVID-19 药物发现的生物测定数据集中活性化合物的鉴定方面具有重大影响,其表现优于传统的机器学习模型。此外,本研究还凸显了先进计算技术在解决高通量筛选数据不平衡方面的功效。
{"title":"Binding Activity Classification of Anti-SARS-CoV-2 Molecules using Deep Learning Across Multiple Assays","authors":"Bilge Eren Yamasan, Selçuk Korkmaz","doi":"10.4274/balkanmedj.galenos.2024.2024-1-73","DOIUrl":"10.4274/balkanmedj.galenos.2024.2024-1-73","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has urgently necessitated effective therapeutic solutions, with a focus on rapidly identifying and classifying potential small-molecule drugs. Given traditional methods’ labor-intensive and time-consuming nature, deep learning has emerged as an essential tool for efficiently processing and extracting insights from complex biological data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;To utilize deep learning techniques, particularly deep neural networks (DNN) enhanced with the synthetic minority oversampling technique (SMOTE), to enhance the classification of binding activities in anti-SARS-CoV-2 molecules across various bioassays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used 11 bioassay datasets covering various SARS-CoV-2 interactions and inhibitory mechanisms. These assays ranged from spike-ACE2 protein-protein interaction to ACE2 enzymatic activity and 3CL enzymatic activity. To address the prevalent class imbalance in these datasets, the SMOTE technique was employed to generate new samples for the minority class. In our model-building approach, we divided the dataset into 80% training and 20% test sets, reserving 10% of the training set for validation. Our approach involved employing a DNN that integrates ReLU and sigmoid activation functions, incorporates batch normalization, and uses Adam optimization. The hyperparameters and architecture of the DNN were optimized through various tests on layers, minibatch sizes, epoch sizes, and learning rates. A 40% dropout rate was incorporated to mitigate overfitting. For model evaluation, we computed performance metrics, such as balanced accuracy (BACC), precision, recall, F1 score, Matthews’ correlation coefficient (MCC), and area under the curve (AUC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The performance of the DNN across 11 bioassay test sets revealed varying outcomes, significantly influenced by the ratios of active-to-inactive compounds. Assays, such as AlphaLISA and CoV-PPE, demonstrated robust performance across various metrics, including BACC, precision, recall, and AUC, when configured with more balanced ratios (1:3 and 1:1, respectively). This suggests the effective identification of active compounds in both cases. In contrast, assays with higher imbalance ratios, such as 3CL (1:38) and cytopathic effect (1:15), demonstrated higher recall but lower precision, highlighting challenges in accurately identifying active compounds among numerous inactive compounds. However, even in these challenging settings, the model achieved favorable BACC and recall scores. Overall, the DNN model generally performed well, as indicated by the BACC, MCC, and AUC values, especially when considering the degree of dataset imbalance in each assay.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study demonstrates the significant impact of deep learning, particularly DNN models enhanced with SMOTE, i","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"186-192"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Balkan Medical Journal
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