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关键词： Erosive gastroesophageal reflux disease   Multichannel intraluminal impedance pH   High-resolution manometry   Pathophysiology   Surgical outcome  

摘要： Purpose To identify the factors that affect laparoscopic fundoplication (LF) treatment efficacy in patients with erosive gastroesophageal reflux disease (e-GERD) esophagitis, based on the findings of multichannel intraluminal impedance pH (MII-pH) and high-resolution manometry (HRM). Methods The subjects were 102 patients with e-GERD diagnosed by endoscopy, who underwent LF as the initial surgery. To analyze the findings of MII-pH and HRM, the patients were divided into two groups: a cured group (CR), comprised of patients whose esophagitis was cured postoperatively;and a recurrence group (RE), comprised of patients who suffered recurrent esophagitis. Results There were 96 patients in the CR group and 6 in the RE group. MII-pH indicated that the acid reflux time, the longest reflux time, and the number of refluxes longer than 5 min, were significantly higher in the RE group than in the CR group (p = 0.0028, p = 0.0008, p = 0.012, respectively). The HRM indicated that only the distal contractile integral (DCI) was significantly lower in the RE group (p = 0.0109). Conclusion The results of this study indicate that esophageal clearance may affect the treatment outcome of LF. Based on the findings of MII-pH, the longest reflux time and the number of refluxes longer than 5 min were important factors influencing the therapeutic effect, whereas based on the HRM, the DCI value was most important.

关键词： Ovarian cancer   Histopathology   Genomics   Transcriptomics   Proteomics  

摘要： Objective. This study used histopathological image features to predict molecular features, and combined with multi-dimensional omics data to predict overall survival (OS) in high-grade serous ovarian cancer (HGSOC). Methods. Patients from The Cancer Genome Atlas (TCGA) were distributed into training set (n = 115) and test set (n = 114). In addition, we collected tissue microarrays of 92 patients as an external validation set. Quan-titative features were extracted from histopathological images using CellProfiler, and utilized to establish predic-tion models by machine learning methods in training set. The prediction performance was assessed in test set and validation set. Results. The prediction models were able to identify BRCA1 mutation (AUC = 0.952), BRCA2 mutation (AUC = 0.912), microsatellite instability-high (AUC = 0.919), microsatellite stable (AUC = 0.924), and molecular subtypes: proliferative (AUC = 0.961), differentiated (AUC = 0.952), immunoreactive (AUC = 0.941), mesenchymal (AUC = 0.918) in test set. The prognostic model based on histopathological image features could predict OS in test set (5-year AUC = 0.825) and validation set (5-year AUC = 0.703). We next explored the integrative prognostic models of image features, genomics, transcriptomics and proteomics. In test set, the models combining two omics had higher prediction accuracy, such as image features and genomics (5-year AUC = 0.834). The multi-omics model including all features showed the best prediction performance (5-year AUC = 0.911). According to risk score of multi-omics model, the high-risk and low-risk groups had significant survival differences (HR = 18.23, p < 0.001). Conclusions. These results indicated the potential ability of histopathological image features to predict above molecular features and survival risk of HGSOC patients. The integration of image features and multi-omics data may improve prognosis prediction in HGSOC patients. (c) 2021 Elsevier Inc. All rights reserved.

关键词： Canine model   Gliosis   Hemorrhage   Spinal cord injury   Spongiosis  

摘要： Purposes This study aimed to investigate the histopathological changes that occur within 2 weeks following spinal cord injury (SCI) in dogs. Methods Eight adult female Beagle dogs were included in this study, and SCI was induced using an epidural balloon catheter. Two dogs were killed at each of the following four time points: immediately after the procedure and 1 day, 1 week, and 2 weeks after the procedure. Neurological status was evaluated with five categories. Histopathological changes were visually observed for stained sections of formalin-fixed spinal cord to evaluate hemorrhage, spongiosis, necrosis, and gliosis morphologically. Results Along the 2 weeks post-injury, severe hemorrhage was observed at the primary injury site, the average diameter of which expanded quickly from 8 to 10 mm in 1 day and then decreased to 5 mm in 1 week. This indicates that the bleeding cavity expanded at the initial injury site to produce ascending and descending hemorrhage. The hemorrhage at the injury site resolved in 2 weeks. In contrast, spongiosis, parenchymal necrosis, and gliosis were first inconspicuous or mild and then became severe in 1 week or 2 weeks. Hemorrhage, hematoma, and other similar changes occurred at the regions approximately 20-mm rostral and caudal to the primary injury site. These changes were observed in both gray matter and white matter. Conclusions This study is the first to assess the sequential histopathological changes in the acute and intermediate phases following SCI in dogs. Our findings enhance the usefulness of the canine intervertebral disk disease model in the assessment of secondary spinal cord histopathology in human SCI.

关键词： Computational pathology   Deep learning   Semi-supervision   Prostate cancer  

摘要： Convolutional neural networks (CNNs) are state-of-the-art computer vision techniques for various tasks, particularly for image classification. However, there are domains where the training of classification models that generalize on several datasets is still an open challenge because of the highly heterogeneous data and the lack of large datasets with local annotations of the regions of interest, such as histopathology image analysis. Histopathology concerns the microscopic analysis of tissue specimens processed in glass slides to identify diseases such as cancer. Digital pathology concerns the acquisition, management and automatic analysis of digitized histopathology images that are large, having in the order of 100' 000(2) pixels per image. Digital histopathology images are highly heterogeneous due to the variability of the image acquisition procedures. Creating locally labeled regions (required for the training) is time-consuming and often expensive in the medical field, as physicians usually have to annotate the data. Despite the advances in deep learning, leveraging strongly and weakly annotated datasets to train classification models is still an unsolved problem, mainly when data are very heterogeneous. Large amounts of data are needed to create models that generalize well. This paper presents a novel approach to train CNNs that generalize to heterogeneous datasets originating from various sources and without local annotations. The data analysis pipeline targets Gleason grading on prostate images and includes two models in sequence, following a teacher/student training paradigm. The teacher model (a high-capacity neural network) automatically annotates a set of pseudo-labeled patches used to train the student model (a smaller network). The two models are trained with two different teacher/student approaches: semi-supervised learning and semi-weekly supervised learning. For each of the two approaches, three student training variants are presented. The baseline

关键词： COVID-19   SARS-CoV-2   Histopathology   Thrombosis   Inflammation   Obstetrics  

摘要： Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.

关键词： Human astrocyte   Ageing   APOE   Alzheimer’   s disease   iPSC   Post-mortem human brain tissue   Reactive gliosis  

摘要： Ageing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE epsilon 4 is genetically the strongest risk factor for Alzheimer's disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain.

关键词： vaccine   thrombosis   thrombocytopenia   COVID-19   cerebral venous sinus thrombosis   splanchnic vein thrombosis  

摘要： Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel entity that emerged in March 2021 following reports of unusual thrombosis after ChAdOx1 nCoV-19, (AstraZeneca) vaccination. Following the recognition of this syndrome, multiple consensus guidelines have been released to risk stratify patients presenting with possible symptoms after ChAdOx1 nCoV-19 vaccination. All guidelines rapidly identify VITT in patients with the complete triad of thrombocytopenia, thrombosis and elevated D-dimers after ChAdOx1 nCoV-19 vaccination. However, with earlier recognition of the associated symptoms, the clinical manifestations are likely to be more heterogeneous and represent an evolving spectrum of disease. In this setting, current guidelines may lack the sensitivity to detect early cases of VITT and risk missed or delayed diagnoses. The broad clinical phenotype and challenges associated with diagnosis of VITT are highlighted in our present case series of four patients with confirmed VITT. Dependent on the guidance used, each patient could have been classified as a low probability of VITT at presentation. The present study highlights the issues associated with the recognition of VITT, the limitations of current guidance and the need for heightened clinical vigilance as our understanding of the pathophysiology of this novel condition evolves.

关键词： Maternal bias   youth psychopathology   maternal psychopathology  

摘要： Background Mood-state biases in maternal reports of emotional and behavioral problems in their children have been a major concern for the field. However, few studies have addressed this issue from a measurement invariance perspective. Methods Using data from baseline assessment of the Adolescent Brain Cognitive Development (ABCD) study (n = 8,507 mother-child dyads;youth aged 9-11 years), we examined how dimensions of maternal psychopathology, including internalizing problems, were associated with indices of bias in reports of their children's dimensions of internalizing, externalizing, neurodevelopmental, detachment, somatoform psychopathology using moderated non-linear factor analysis. Moderated non-linear factor analyses examined multiple potential biases in maternal reports of youth psychopathology. Results Across analyses, we found very small magnitudes of associations between dimensions of maternal psychopathology and biases in reports of child emotional and behavioral problems. Conclusions Based on these results, we find little psychometric evidence for maternal psychopathology biasing reports of child behavior problems.

关键词： benign myoclonus of early infancy (BMEI)   benign polymorphous movement disorder of infancy (BPMDI)   Fejerman-Lombroso   shuddering attacks   paroxysmal non-epileptic movements   transient infant movements (TIM)  

摘要： Objective. Lombroso and Fejerman, in 1977, described non-epileptic movements in normal infants and named them "benign myoclonus of early infancy", which were recently relabelled by Fernandez-Alvarez as "benign polymorphous movement disorder of infancy" (BPMDI). The focus of our study was to describe, categorize and point out the peculiar clinical representations of these heterogeneous phenomena through our video footage, particularly to those less experienced in paediatric neurology. Methods. We included all infants with a video-EEG performed at our unit or a home video recording of "Fejerman-Lombroso", "benign myoclonus of early infancy", "shuddering attacks" or "paroxysmal non-epileptic movements". Results. Twenty-one children were selected. Age at onset ranged between two and 13 months, age at disappearance ranged between seven and 16 months, age at recording ranged between four and 16 months, and duration of the phenomena ranged between two weeks and 19 months. In total, 85% infants had normal neurodevelopment at onset and follow-up (mean follow-up: 31.47 months) and 15% presented with neuropsychological or neurosensory deficits. We distinguished four different patterns of movements: movement of the head in 50%, shuddering attacks in 30%, tonic brief contractions of the trunk and limbs in 10%, and elevation of the shoulders in 10%. Significance. These motor phenomena do not affect neurological status and are not associated with developmental delay. Considering that clinical interpretation may be challenging, especially relative to epileptic seizures, we present an explanatory video of these characteristic events. We also propose a new definition that is simple to remember: "transient infant movements" (TIM).