Abnormal α-Synuclein Aggregates Cause Synaptic- and Microcircuit-Specific Deficits in the Retinal Rod Pathway
α-Synuclein (α-Syn) is a key determinator of Parkinson disease (PD) pathology, but synapse and microcircuit pathologies in the retina underlying visual dysfunction are poorly understood. Using the old transgenic M83 PD model (mice aged 16 to 18 months) coupled with histochemical and ultrastructura l analyses and ophthalmologic measurements, we revealed that abnormal α-Syn aggregation in the outer plexiform layer (OPL) was associated with degeneration in the CtBP2+ ribbon synapses of photoreceptor terminals and protein kinase Cα+ rod bipolar cell terminals, whereas α-Syn aggregates in the i nner retina correlated with ...
Source: American Journal of Pathology - February 21, 2024 Category: Pathology Authors: Tao Xu, Xin Liu, Xin Lin, Jiayi Xiao, Di Zhang, Fenfen Ye, Fan Lu, Jia Qu, Jun Zhang, Jiang-Fan Chen Tags: Regular article Source Type: research

Abnormal Alpha-Synuclein Aggregates Cause Synaptic- and Microcircuit-specific Deficits in the Retinal Rod Pathway
Alpha-synuclein ( α-Syn) is a key determinator of Parkinson’s disease (PD) pathology, but synapse and microcircuit pathologies in the retina underlying visual dysfunction are poorly understood. Using the old transgenic M83 PD model (16-18 monthes) coupled with histochemical and ultra-structural analyses and ophtha lmologic measurements, we revealed that abnormal α-Syn aggregation in the outer plexiform layer (OPL) was associated with degeneration in the CtBP2+ ribbon synapses of photoreceptor terminals and PKCα+ rod bipolar cells terminals while α-Syn aggregates in the inner retina correlated with the redu ction and ...
Source: American Journal of Pathology - February 21, 2024 Category: Pathology Authors: Tao Xu, Xin Liu, Xin Lin, Jiayi Xiao, Di Zhang, Fenfen Ye, Fan Lu, Jia Qu, Jun Zhang, Jiang-Fan Chen Tags: Regular Article Source Type: research

A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning
Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image –based histopathologic images and identifies Silva patterns with high accuracy. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 19, 2024 Category: Pathology Authors: Qingqing Liu, Xiaofang Zhang, Xuji Jiang, Chunyan Zhang, Jiamei Li, Xuedong Zhang, Jingyan Yang, Ning Yu, Yongcun Zhu, Jing Liu, Fengxiang Xie, Yawen Li, Yiping Hao, Yuan Feng, Qi Wang, Qun Gao, Wenjing Zhang, Teng Zhang, Taotao Dong, Baoxia Cui Tags: Regular article Source Type: research

A histopathological image analysis for the classification of endocervical adenocarcinoma Silva patterns depend on weakly supervised deep learning
The objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole-slide-image-based histopathological images and identifies Silva patterns with high accuracy. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 19, 2024 Category: Pathology Authors: Qingqing Liu, Xiaofang Zhang, Xuji Jiang, Chunyan Zhang, Jiamei Li, Xuedong Zhang, Jingyan Yang, Ning Yu, Yongcun Zhu, Jing Liu, Fengxiang Xie, Yawen Li, Yiping Hao, Yuan Feng, Qi Wang, Qun Gao, Wenjing Zhang, Teng Zhang, Taotao Dong, Baoxia Cui Tags: Regular Article Source Type: research

Correction
The authors of the article entitled, “Myofiber Damage Precedes Macrophage Infiltration after in Vivo Injury in Dysferlin-Deficient A/J Mouse Skeletal Muscle” (Volume 185, pages 1686–1698 of the June 2015 issue of The American Journal of Pathology; DOI: https://doi.org/10.1016/j.ajpath.2015.02.020) have requested the replacement of Figure 2 as they noticed an accidental duplication of the images within the original image. The uninjured leg of an A/J mouse at 24 hours was duplicated in the panel showing the uninjured leg of that mouse at day 7. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 15, 2024 Category: Pathology Tags: Correction Source Type: research

Reviewer Acknowledgment
The Editors gratefully acknowledge the generous assistance of the following reviewers who served The American Journal of Pathology between January 1 and December 31,  2023. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 15, 2024 Category: Pathology Tags: Reviewer acknowledgment Source Type: research

Editorial Board
(Source: American Journal of Pathology)
Source: American Journal of Pathology - February 15, 2024 Category: Pathology Source Type: research

Table of Contents
(Source: American Journal of Pathology)
Source: American Journal of Pathology - February 15, 2024 Category: Pathology Source Type: research

This Month in AJP
The anti-inflammatory cytokine transforming growth factor β1 (TGFβ1) is released endogenously upon infection or tissue injury; however, the underlying pathogenesis of ischemia reperfusion injury is unclear. Using a mouse model of myocardial ischemia (MI) and reperfusion, Redgrave et al (Am J Pathol, AJPA-D-23-00437) studied the protective effects of TGFβ 1 when administered exogenously following MI. Administration of TGFβ1 as well as its mimic, HpTGM, resulted in a reduction in infarct size and inflammatory cytokines. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 9, 2024 Category: Pathology Tags: This Month in AJP Source Type: research

Transient Receptor Potential Vanilloid-1 Channels Facilitate Axonal Degeneration of Corneal Sensory Nerves in Dry Eye
Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in  vitro, but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout mice, which developed comparable corneal epithelial damage and reduced tear secretion. (Source: American ...
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Manuela Pizzano, Alexia Vereertbrugghen, Agostina Cernutto, Florencia Sabbione, Irene A. Keitelman, Carolina M. Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Mirta N. Giordano, Anal ía S. Trevani, Jeremías G. Galletti Tags: Regular article Source Type: research

Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole Slide Images in Adult Patients with Diffuse Glioma
Isocitrate dehydrogenase gene (IDH) mutation is one of the most important molecular markers of glioma. Accurate detection of IDH status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. A clustering-based hybrid of a convolutional neural network and a vision transformer deep learning model was developed to detect IDH mutation status from annotation-free hematoxylin and eosin –stained whole slide pathologic images of 2275 adult patients with diffuse gliomas. For comparison, we also assessed a pure convolutional neural network, a pure vision transformer, and a classic multiple-instance learning mode...
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Yuanshen Zhao, Weiwei Wang, Yuchen Ji, Yang Guo, Jingxian Duan, Xianzhi Liu, Dongming Yan, Dong Liang, Wencai Li, Zhenyu Zhang, Zhi-Cheng Li Tags: Regular article Source Type: research

Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole-Slide Images in Adult Patients with Diffuse Glioma
Isocitrate dehydrogenase gene (IDH) mutation is one of the most important molecular markers of glioma. Accurate detection of IDH status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. A clustering-based hybrid of a convolutional neural network (CNN) and a vision transformer (ViT) deep learning model was developed to detect IDH mutation status from annotation-free hematoxylin& eosin-stained whole-slide pathological images (WSIs) of 2275 adult patients with diffuse gliomas. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Yuanshen Zhao, Weiwei Wang, Yuchen Ji, Yang Guo, Jingxian Duan, Xianzhi Liu, Dongming Yan, Dong Liang, Wencai Li, Zhenyu Zhang, Zhi-Cheng Li Tags: Regular Article Source Type: research

WSB1, a Hypoxia-Inducible E3 Ligase, Promotes Myofibroblast Accumulation and Attenuates Alveolar Epithelial Regeneration in Mouse Lung Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease for which there is no curative therapy available. Repetitive alveolar epithelial injury repair, myofibroblast (MYF) accumulation and excessive collagen deposition are key pathological features of IPF, eventually leading to cellular hypoxia and respiratory failure. The precise mechanism driving this complex maladaptive process remains inadequately understood. WSB1 (WD repeat and SOCS box containing 1) is an E3 ubiquitin ligase, the expression of which is strongly associated with hypoxia, and forms a positive feedback loop with HIF-1 α under anox...
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Lei Chong, Lihui Zou, Liyan Xiang, Xinyue Song, Wanqi Miao, Xihua Yan, Ming Xu, Gongxia Ling, Elie El Agha, Saverio Bellusci, Zhenkun Lou, Hailin Zhang, Jin-San Zhang Tags: Regular Article Source Type: research

Ninjurin 2 Modulates Tumorigenesis, Inflammation, and Metabolism via Pyroptosis
The nerve injury induced protein 2 (NINJ2) belongs to a family of homophilic adhesion molecules and was initially found to be involved in nerve regeneration. However, the role of NINJ2 in other cellular process are not well studied. Here, by generating a Ninj2-deficient mouse model, we showed that mice deficient in Ninj2 have a short lifespan and are prone to spontaneous tumors, systemic inflammation and metabolic defects. To better understand the metabolic traits that contributes to these phenotypes, we performed comprehensive carbohydrate and lipid metabolic analyses. (Source: American Journal of Pathology)
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Jin Zhang, Xiangmudong Kong, Hee Jung Yang, Weici Zhang, Mingyi Chen, Xinbin Chen Tags: Regular Article Source Type: research

TRPV1 channels facilitate axonal degeneration of corneal sensory nerves in dry eye
Corneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout (Trpv1KO) mice, which developed comparable corneal epithelial damage and reduced tear secretion. (Source: Am...
Source: American Journal of Pathology - February 5, 2024 Category: Pathology Authors: Manuela Pizzano, Alexia Vereertbrugghen, Agostina Cernutto, Florencia Sabbione, Irene A. Keitelman, Carolina M. Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Mirta N. Giordano, Anal ía S. Trevani, Jeremías G. Galletti Tags: Regular Article Source Type: research