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Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. 用于 COVID-19 治疗的潜在药物和疫苗的临床前和临床研究:全面回顾与最新进展
IF 1.9 Q3 PATHOLOGY Pub Date : 2024-07-26 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241263054
Md Easin Mia, Mithu Howlader, Farzana Akter, Md Murad Hossain

The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.

由 COVID-19 大流行引发的全球医疗保健危机需要社会、生态和医学界迅速做出努力,以阻止或减少不断上升的死亡人数。许多基于 mRNA 的疫苗和病毒载体疫苗已被许可用于紧急状况,它们对预防 SARS-CoV-2 感染的有效率在 90% 到 95% 之间。然而,安全问题、对疫苗的不情愿和怀疑仍然是使大规模疫苗接种成功治疗 COVID-19 的主要问题。因此,需要替代疗法来消除 COVID-19 在发达国家和低资源国家造成的全球负担。重新利用现有药物和候选药物可能是治疗 SARS-CoV-2 的一个更可行的选择,因为这些疗法之前已通过了药物开发和患者护理方面的一些重要检查点。除疫苗外,本综述还关注了替代治疗药物的潜在用途,包括抗病毒、抗寄生虫和抗菌药物、蛋白酶抑制剂、神经氨酸酶抑制剂和单克隆抗体,这些药物目前正在进行临床前和临床研究,以评估其治疗 COVID-19 的有效性和安全性。在重新使用的药物中,雷米替韦被认为是最有前途的药物,而法非比拉韦、莫鲁吡拉韦、帕克洛维和洛匹那韦/利托那韦在清除病毒方面的治疗效果有所改善。然而,使用奥司他韦、乌米诺韦、双硫嘧啶、替考拉宁和伊维菌素治疗的效果并不显著。值得注意的是,在治疗 COVID-19 患者时,多种药物的联合治疗效果显著。Tocilizumab 目前被用于治疗 COVID-19 相关肺炎患者。许多抗病毒药物(如加利地韦、格列菲新和thapsigargin)正在临床试验中,这些药物有望用于治疗症状严重的COVID-19患者。对 COVID-19 患者的支持性治疗可能包括使用皮质类固醇、康复血浆、干细胞、集合抗体、维生素和天然物质。这项研究提供了 SARS-CoV-2 药物治疗的最新进展,为发明针对 COVID-19 的新型干预措施提供了重要指导。
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引用次数: 0
Safeguarding Accuracy: The Impact of Interventions on Reducing Blood Culture Contamination. 保障准确性:干预措施对减少血培养污染的影响。
IF 1.9 Q3 PATHOLOGY Pub Date : 2024-07-26 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241265857
Fareeha Adnan, Nazia Khursheed, Moiz Ahmed Khan, Nazia Parveen

Introduction: Blood culture is the gold standard for diagnosing bacteremia and direct the physicians to select appropriate antimicrobials. In hospitals, blood culture contamination (BCC) is a common problem that has a detrimental effect on patient outcomes. Hence, we implemented strategies in our tertiary care setup, for training phlebotomists and nurses in proper blood sampling techniques, and assessed their effectiveness in reducing BCC rates.

Methods: This interventional study was conducted at the Indus Hospital, Karachi, Pakistan from 1st January 2021 to 30th June 2023. All blood cultures received from different departments of the hospital were included. The 2.5-year study period was divided into pre-intervention and intervention periods, with monthly monitoring of BCC. The BCC data between 1st January 2021 and 31st December 2021 was taken as the baseline pre-intervention period and the next 1.5 years comprised the intervention period (1st January 2022-30th June 2023). To improve compliance, various strategies were implemented, such as regular training sessions, didactic sessions, and re-competencies.

Results: A total of 86 774 Blood cultures were received from all departments of the hospital, out of which n = 30 672 were received in the pre-intervention period whereas, n = 56 102 were received in the intervention period. Mean BCC rate in the pre-intervention period was found to be 4.6%. However, after the implementation of different measures to reduce BCC, the contamination rate decreased to a mean of 3.1% by the end of the intervention period. Emergency department accounted for the highest proportion of BCC in the pre-intervention and intervention periods.

Conclusion: We decreased BCC in our tertiary care setup by implementing a simple and inexpensive collaborative intervention, and came to the conclusion that the higher incidence of BCC was probably caused by factors unique to the emergency department and provided measures to successfully address them.

导言:血培养是诊断菌血症的金标准,可指导医生选择适当的抗菌药物。在医院中,血液培养污染(BCC)是一个常见问题,会对患者的治疗效果产生不利影响。因此,我们在三级医疗机构中实施了一些策略,对抽血员和护士进行正确的血液采样技术培训,并评估其在降低 BCC 感染率方面的效果:这项干预性研究于 2021 年 1 月 1 日至 2023 年 6 月 30 日在巴基斯坦卡拉奇印度河医院进行。从医院不同科室接收的所有血液培养物均被纳入研究范围。为期 2.5 年的研究分为干预前和干预期,每月对 BCC 进行监测。2021 年 1 月 1 日至 2021 年 12 月 31 日期间的 BCC 数据作为干预前的基线,接下来的 1.5 年为干预期(2022 年 1 月 1 日至 2023 年 6 月 30 日)。为提高依从性,实施了各种策略,如定期培训课程、说教课程和再能力课程:医院各科室共收到 86 774 份血培养,其中干预前收到 30 672 份,干预后收到 56 102 份。干预前的平均 BCC 感染率为 4.6%。然而,在采取不同措施减少 BCC 后,到干预期结束时,污染率下降到平均 3.1%。在干预前和干预期间,急诊科的 BCC 比例最高:我们通过实施一项简单、廉价的合作干预措施,降低了三级医疗机构的 BCC 感染率,并得出结论认为 BCC 感染率较高可能是由急诊科特有的因素造成的,并提供了成功应对这些因素的措施。
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引用次数: 0
A Diagnostic Perplexity in Primary Pelvic Hydatid Disease, Mimicking Tumor and Tuberculosis: A Case Report. 原发性盆腔包虫病的诊断难题--模仿肿瘤和结核:病例报告。
IF 1.9 Q3 PATHOLOGY Pub Date : 2024-07-26 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241253232
Sweta Bahadure, Anand Hatgaonkar, Nandkishor Bankar, Tejas Sadavarte, Yugeshwari Tiwade, Avinash Rinait

The differential diagnosis of cystic echinococcosis should be considered in the suspected case of a pelvic mass presenting with vague symptoms. Primary pelvic hydatid cyst is rare, and the achievement of early diagnosis is important, as the involvement of bone in the pelvis is difficult to treat, and the probability of recurrences is greater. This case report presents a rare case of a primary pelvic hydatid cyst in a male in his 30s. The patient presented vague symptoms of difficulty in micturition and chronic pelvic pain. First-line radiological imaging techniques diagnosed it as a neoplastic mass and tuberculosis, while MRI revealed it as a cystic disease, probably a hydatid cyst. Surgical excision and histopathological examination confirmed the diagnosis of a primary pelvic hydatid cyst. Acquaintance with the varied presentation of cystic echinococcosis helps to obtain an accurate diagnosis and thus decreases the severe complication associated with the disease. This case report highlights the importance of considering parasitic infections in the differential diagnosis of cystic pelvic masses, even in regions with low endemicity.

盆腔肿块伴有模糊症状的疑似病例应考虑囊性棘球蚴病的鉴别诊断。原发性盆腔包虫囊肿非常罕见,早期诊断非常重要,因为累及盆腔骨骼的包虫囊肿很难治疗,而且复发的可能性更大。本病例报告介绍了一例罕见的原发性盆腔包虫囊肿病例,患者为一名 30 多岁的男性。患者有排尿困难和慢性盆腔疼痛的模糊症状。一线放射成像技术诊断为肿瘤性肿块和结核病,而核磁共振成像显示为囊性疾病,可能是包虫囊肿。手术切除和组织病理学检查证实了原发性盆腔包虫囊肿的诊断。了解囊性棘球蚴病的各种表现有助于获得准确诊断,从而减少与该病相关的严重并发症。本病例报告强调了在盆腔囊性肿块的鉴别诊断中考虑寄生虫感染的重要性,即使在寄生虫流行率较低的地区也是如此。
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引用次数: 0
Intramuscular Lipoma of the Sternocleidomastoid Muscle: A Rare Entity Revisited. 胸锁乳突肌肌内脂肪瘤:罕见病例再探
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-06-10 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241260200
Jad Hosri, Yara Yammine, Nadine El Hadi, Jessica Aoun, Marc Mourad, Usamah Hadi

Intramuscular lipomas, typically found in subcutaneous tissue, rarely affect deeper muscular planes, especially those of the head and neck region. The following are 3 cases of intramuscular lipomas involving the sternocleidomastoid muscle. The first 2 patients presented with painless, palpable masses confirmed by diagnostic imaging as well-circumscribed intramuscular lipomas. One was treated surgically, while the other was managed conservatively with monitoring and close follow-up. The third patient reported dysphagia associated with occasional dyspnea and mild pain. The mass was identified as infiltrative lipoma and was resected surgically. Complete tumor removal with no recurrence at 6 months was observed for the first and last cases. The second case was serially followed at 3 and 6 months with no interval changes. We report the largest case series on intramuscular lipomas of the sternocleidomastoid muscle to enhance our understanding of this rare entity.

肌内脂肪瘤通常发生在皮下组织,很少影响深层肌肉平面,尤其是头颈部。以下是 3 例涉及胸锁乳突肌的肌肉内脂肪瘤病例。前两名患者表现为无痛、可触及的肿块,经影像诊断证实为环绕性肌内脂肪瘤。其中一名患者接受了手术治疗,另一名患者接受了保守治疗,并进行了监测和密切随访。第三位患者报告吞咽困难,并伴有偶尔的呼吸困难和轻微疼痛。肿块被确定为浸润性脂肪瘤,并进行了手术切除。第一例和最后一例患者的肿瘤完全切除,6 个月后无复发。对第二个病例进行了 3 个月和 6 个月的连续随访,结果没有发生间隔变化。我们报告了胸锁乳突肌肌内脂肪瘤的最大病例系列,以加深我们对这一罕见病例的了解。
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引用次数: 0
Seborrheic Keratosis: Report of a Rare Presentation and Reminder of the Current Knowledge of the Problem. 脂溢性角化病:报告罕见病例,提醒人们关注这一问题。
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-05-25 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241255874
Bahaeddine Lahbacha, Salwa Nechi, Abir Chaabane, Amina Bani, Majdi Kchaou, Fadhel Chtourou, Mohamed Karim Mfarrej, Amel Douggaz, Emna Chelbi

A 75-year-old man presented with an abdominal enlarging painless tumor of the skin evolving over the last 30 years. His past medical history was unremarkable. Physical examination revealed a brownish pedunculated cutaneous mass which had an irregular keratotic warty surface with no discharge or ulceration. The mass was clinically presumed to be a melanocytic tumor, or a verrucous carcinoma. A monoblock excision of the mass was performed with a good outcome. The specimen was then sent to our pathology department to rule out malignancy. Macroscopic examination revealed a brownish tumor of 7.5 × 7 × 1.5 cm which had fissures and cauliflower-like appearance. Final histological report concluded to a giant seborrheic keratosis.

一名 75 岁的男子因腹部增大的无痛性皮肤肿瘤就诊,该肿瘤在过去 30 年中不断发展。既往病史无异常。体格检查显示,他的皮肤肿块呈褐色块状,表面呈不规则角化疣状,无分泌物或溃疡。临床推测该肿块为黑色素细胞瘤或疣状癌。对肿块进行了单块切除,结果良好。标本随后被送往病理科,以排除恶性肿瘤的可能性。显微镜检查发现,肿瘤呈褐色,大小为 7.5 × 7 × 1.5 厘米,有裂隙和菜花状外观。最终的组织学报告得出结论:这是一个巨大的脂溢性角化病。
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引用次数: 0
Public Health Emergence: Challenges and Prospects for the Future of Herd Immunity to Reduce the Negative Impact of Disease X in Low- and Middle-Income Countries. 公共卫生的兴起:在低收入和中等收入国家减少 X 病负面影响的群体免疫未来的挑战和前景》(Public Health Emergence: Challenges and Prospects for the Future of Herd Immunity to Reduce the Negative Impact of Disease X)。
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-05-14 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241254961
Proma Rani Das, Sakif Ahamed Khan, Mohammad Safiqul Islam, Syed Masudur Rahman Dewan
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引用次数: 0
Appendiceal Diverticulitis Mimics Cecal Diverticulitis Diagnosed Preoperatively. 术前诊断的阑尾憩室炎模仿盲肠憩室炎
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-04-19 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241248909
Phu Cuong Pham, Hoang Anh Thi Van, Van Trung Hoang, The Huan Hoang, Duc Duy Nguyen, Duc Thanh Hoang

Appendiceal diverticulitis is an uncommon condition that clinically resembles acute appendicitis. However, it is an incidental finding in histopathological studies and is rarely diagnosed preoperatively by imaging studies. In this article, we present the clinical and imaging findings of a male patient presenting with right upper quadrant pain with a preoperative imaging diagnosis of appendiceal diverticulitis. He underwent laparoscopic appendectomy and confirmed the diagnosis of appendiceal diverticulitis. This is a rare preoperative diagnosis. The management is often like typical appendicitis which is appendectomy. It is important to differentiate it from diverticulitis of the small intestine or colon because these diseases usually require only conservative treatment.

阑尾憩室炎是一种不常见的疾病,临床上类似于急性阑尾炎。然而,它在组织病理学研究中只是偶然发现,很少在术前通过影像学检查确诊。在本文中,我们介绍了一名男性患者的临床和影像学检查结果,该患者因右上腹疼痛而在术前被影像学诊断为阑尾憩室炎。他接受了腹腔镜阑尾切除术,确诊为阑尾憩室炎。这是一种罕见的术前诊断。治疗方法通常与典型的阑尾炎相似,即阑尾切除术。重要的是要将其与小肠或结肠憩室炎区分开来,因为这些疾病通常只需要保守治疗。
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引用次数: 0
Recurrent Adamantinoma With Fibrous Dysplasia-like Feature. 复发性金刚烷瘤伴纤维增生异常样特征
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-04-07 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241240391
Anja Petaros, Veljko Šantić, Anita Savić Vuković, Petar Perić, Nives Jonjić

Adamantinoma (AD) is a rare, slow-growing primary malignant bone tumor characterized by a biphasic morphology of clusters of epithelial cells and spindle cell osteofibrous components. A strong relationship between AD and osteofibrous dysplasia (OFD) has been proposed, while fibrous dysplasia (FD) has been rarely associated with AD. We present an AD case that was followed and histologically evaluated 3 times over 6 years with different morphological patterns. The tumor in the primary biopsy and after complete resection showed classical features of AD and osteofibrous-like pattern, while the recurrent lesion presented with exclusively spindle cell morphology and was thus diagnosed as FD. However, the extensive immunohistochemical analysis in all 3 lesions revealed strong reactivity for pancytokeratin, vimentin, p63, and podoplanin, which are characteristic for AD. Although, in the FD-like section of the tumor from the first recurrence the positivity of podoplanin was stronger than pancitokeratin, which was variably positive on spindle cells. The present case highlights the problem of diagnosing AD based on a single biopsy with one tumor's component predominating over the other, and at the same time emphasizes the importance of using immunohistochemical staining for keratin and podoplanin when the histopathological features of (osteo)fibrous lesion can be linked to AD.

金刚瘤(Adamantinoma,AD)是一种罕见的、生长缓慢的原发性恶性骨肿瘤,其特征是上皮细胞簇和纺锤形细胞骨纤维成分的双相形态。有人认为AD与骨纤维发育不良(OFD)关系密切,而纤维发育不良(FD)很少与AD相关。我们报告了一个AD病例,该病例在6年中接受了3次随访和组织学评估,其形态模式各不相同。原发活检和完全切除后的肿瘤显示出 AD 的典型特征和骨纤维样形态,而复发病灶仅表现为纺锤形细胞形态,因此被诊断为 FD。然而,对这 3 个病灶进行的大量免疫组化分析表明,Pancytokeratin、vimentin、p63 和 podoplanin 具有很强的反应性,而这正是 AD 的特征。不过,在第一次复发的 FD 样肿瘤切片中,荚膜印迹蛋白的阳性反应强于胰角蛋白,而胰角蛋白在纺锤形细胞上呈不同程度的阳性反应。本病例凸显了根据单次活检诊断AD的问题,即一种肿瘤成分比另一种肿瘤成分更主要,同时强调了当组织病理学特征(骨)纤维性病变可能与AD有关时,使用免疫组化染色法检测角蛋白和荚膜磷脂的重要性。
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引用次数: 0
The Relationship Between Tumor Budding and Patient's Survival in Breast Cancer. 肿瘤萌发与乳腺癌患者生存期的关系
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241235543
Mohammad Ranaee, Hossein Torabi, Narges Azhganzad, Kasra Shirini, Akram Sadat Hosseini, Karimollah Hajian

Introduction: Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate.

Materials and methods: This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied.

Results and discussion: The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade.

Conclusion: Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio.

导言乳腺癌是一种严重威胁生命的疾病,每年都有许多妇女患上乳腺癌。最近,人们注意到并研究了作为这种癌症诊断预测指标的一个因素,即肿瘤芽的数量以及该因素与患者生存率的关系:本研究包括 150 名 18 岁以上的女性乳腺癌患者,平均年龄(53.99±12.56)岁,这些患者在不同的医疗中心(包括鲁哈尼医院本身)确诊,并转诊至伊朗巴博勒的鲁哈尼医院医疗中心。患者显微切片中的瘤内芽和瘤周芽数量被存档,并与苏木精和伊红(H&E)切片上的肿瘤微环境一起进行评估,同时与其他临床病理结果进行比较。本文精确研究了瘤内芽和瘤周芽数量与患者 5 年生存率之间的关系。同时,还研究了年龄、肿瘤分期、分级、大小、受累淋巴结数量以及是否存在转移与瘤内和瘤周芽数量之间的关系:结果表明,瘤内芽和瘤周芽数量与肿瘤大小、肿瘤分期、有无转移、受累淋巴结数量和 5 年生存率之间存在明显的统计学关联。另一方面,瘤内和瘤周芽的数量与年龄和肿瘤分级之间没有明显的统计学关系:结论:我们的调查显示,瘤芽数量与患者的生存率之间存在明显的统计学关系。因此,应将这一因素视为重要因素,以帮助患者提高生存率。
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引用次数: 0
Deep Learning for Subtypes Identification of Pure Seminoma of the Testis. 用深度学习识别纯睾丸精原细胞瘤的亚型
IF 1.3 Q3 PATHOLOGY Pub Date : 2024-02-18 eCollection Date: 2024-01-01 DOI: 10.1177/2632010X241232302
Kirill E Medvedev, Paul H Acosta, Liwei Jia, Nick V Grishin

The most critical step in the clinical diagnosis workflow is the pathological evaluation of each tumor sample. Deep learning is a powerful approach that is widely used to enhance diagnostic accuracy and streamline the diagnosis process. In our previous study using omics data, we identified 2 distinct subtypes of pure seminoma. Seminoma is the most common histological type of testicular germ cell tumors (TGCTs). Here we developed a deep learning decision making tool for the identification of seminoma subtypes using histopathological slides. We used all available slides for pure seminoma samples from The Cancer Genome Atlas (TCGA). The developed model showed an area under the ROC curve of 0.896. Our model not only confirms the presence of 2 distinct subtypes within pure seminoma but also unveils the presence of morphological differences between them that are imperceptible to the human eye.

临床诊断工作流程中最关键的一步是对每个肿瘤样本进行病理评估。深度学习是一种强大的方法,被广泛用于提高诊断准确性和简化诊断流程。在我们之前利用 omics 数据进行的研究中,我们发现了纯精原细胞瘤的 2 个不同亚型。精原细胞瘤是睾丸生殖细胞肿瘤(TGCTs)中最常见的组织学类型。在此,我们开发了一种深度学习决策工具,用于利用组织病理切片识别精原细胞瘤亚型。我们使用了癌症基因组图谱(TCGA)中纯精原细胞瘤样本的所有可用切片。开发的模型显示 ROC 曲线下面积为 0.896。我们的模型不仅证实了纯精原细胞瘤中存在两种截然不同的亚型,还揭示了它们之间存在肉眼难以察觉的形态学差异。
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引用次数: 0
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Clinical Pathology
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