Introducing π-HelixNovo for practical large-scale de novo peptide sequencing.

De novo peptide sequencing is a promising approach for novel peptide discovery, highlighting the performance improvements for the state-of-the-art models. The quality of mass spectra often varies due to unexpected missing of certain ions, presenting a significant challenge in de novo peptide sequencing. Here, we use a novel concept of complementary spectra to enhance ion information of the experimental spectrum and demonstrate it through conceptual and practical analyses. Afterward, we design suitable encoders to encode the experimental spectrum and the corresponding complementary spectrum and propose a de novo sequencing model $\pi$-HelixNovo based on the Transformer architecture. We first demonstrated that $\pi$-HelixNovo outperforms other state-of-the-art models using a series of comparative experiments. Then, we utilized $\pi$-HelixNovo to de novo gut metaproteome peptides for the first time. The results show $\pi$-HelixNovo increases the identification coverage and accuracy of gut metaproteome and enhances the taxonomic resolution of gut metaproteome. We finally trained a powerful $\pi$-HelixNovo utilizing a larger training dataset, and as expected, $\pi$-HelixNovo achieves unprecedented performance, even for peptide-spectrum matches with never-before-seen peptide sequences. We also use the powerful $\pi$-HelixNovo to identify antibody peptides and multi-enzyme cleavage peptides, and $\pi$-HelixNovo is highly robust in these applications. Our results demonstrate the effectivity of the complementary spectrum and take a significant step forward in de novo peptide sequencing.

Endoscopic removal of esophageal foreign body and endoscopic closure of its associated perforation with early mediastinitis.

A 55-year-old male swallowed fish bone accidentally and subsequently developed retrosternal pain. He underwent chest computed tomography at his local hospital on October 23, 2023, showing esophageal foreign body with suspected esophageal rupture. One day later, he underwent endoscopy at our department, showing a fish bone penetrated into the esophageal wall. After consultation with cardiothoracic surgeons, endoscopy-guided removal of this foreign body was performed under anesthesia. An esophageal ulcer with a length of 2cm was left with overflowing air bubbles, and was closed by three metal clips. Two days later, retrosternal pain disappeared. A tube was intubated to duodenal distal segment under endoscopy, via which enteral nutritional suspension was given. Then, he was discharged.

End-to-end affine registration framework for histopathological images with weak annotations.

BACKGROUND AND OBJECTIVE: Histopathological image registration is an essential component in digital pathology and biomedical image analysis. Deep-learning-based algorithms have been proposed to achieve fast and accurate affine registration. Some previous studies assume that the pairs are free from sizeable initial position misalignment and large rotation angles before performing the affine transformation. However, large-rotation angles are often introduced into image pairs during the production process in real-world pathology images. Reliable initial alignment is important for registration performance. The existing deep-learning-based approaches often use a two-step affine registration pipeline because convolutional neural networks (CNNs) cannot correct large-angle rotations. METHODS: In this manuscript, a general framework ARoNet is developed to achieve end-to-end affine registration for histopathological images. We use CNNs to extract global features of images and fuse them to construct correspondent information for affine transformation. In ARoNet, a rotation recognition network is implemented to eliminate great rotation misalignment. In addition, a self-supervised learning task is proposed to assist the learning of image representations in an unsupervised manner. RESULTS: We applied our model to four datasets, and the results indicate that ARoNet surpasses existing affine registration algorithms in alignment accuracy when large angular misalignments (e.g., 180 rotation) are present, providing accurate affine initialization for subsequent non-rigid alignments. Besides, ARoNet shows advantages in execution time (0.05 per pair), registration accuracy, and robustness. CONCLUSION: We believe that the proposed general framework promises to simplify and speed up the registration process and has the potential for clinical applications.

The advantages of artificial intelligence-based gait assessment in detecting, predicting, and managing Parkinson's disease.

Background: Parkinson's disease is a neurological disorder that can cause gait disturbance, leading to mobility issues and falls. Early diagnosis and prediction of freeze episodes are essential for mitigating symptoms and monitoring the disease. Objective: This review aims to evaluate the use of artificial intelligence (AI)-based gait evaluation in diagnosing and managing Parkinson's disease, and to explore the potential benefits of this technology for clinical decision-making and treatment support. Methods: A thorough review of published literature was conducted to identify studies, articles, and research related to AI-based gait evaluation in Parkinson's disease. Results: AI-based gait evaluation has shown promise in preventing freeze episodes, improving diagnosis, and increasing motor independence in patients with Parkinson's disease. Its advantages include higher diagnostic accuracy, continuous monitoring, and personalized therapeutic interventions. Conclusion: AI-based gait evaluation systems hold great promise for managing Parkinson's disease and improving patient outcomes. They offer the potential to transform clinical decision-making and inform personalized therapies, but further research is needed to determine their effectiveness and refine their use.

Unsupervised domain adaptive tumor region recognition for Ki67 automated assisted quantification.

PURPOSE: Ki67 is a protein associated with tumor proliferation and metastasis in breast cancer and acts as an essential prognostic factor. Clinical work requires recognizing tumor regions on Ki67-stained whole-slide images (WSIs) before quantitation. Deep learning has the potential to provide assistance but largely relies on massive annotations and consumes a huge amount of time and energy. Hence, a novel tumor region recognition approach is proposed for more precise Ki67 quantification. METHODS: An unsupervised domain adaptive method is proposed, which combines adversarial and self-training. The model trained on labeled hematoxylin and eosin (H&E) data and unlabeled Ki67 data can recognize tumor regions in Ki67 WSIs. Based on the UDA method, a Ki67 automated assisted quantification system is developed, which contains foreground segmentation, tumor region recognition, cell counting, and WSI-level score calculation. RESULTS: The proposed UDA method achieves high performance in tumor region recognition and Ki67 quantification. The AUC reached 0.9915, 0.9352, and 0.9689 on the validation set and internal and external test sets, respectively, substantially exceeding baseline (0.9334, 0.9167, 0.9408) and rivaling the fully supervised method (0.9950, 0.9284, 0.9652). The evaluation of automated quantification on 148 WSIs illustrated statistical agreement with pathological reports. CONCLUSION: The model trained by the proposed method is capable of accurately recognizing Ki67 tumor regions. The proposed UDA method can be readily extended to other types of immunohistochemical staining images. The results of automated assisted quantification are accurate and interpretable to provide assistance to both junior and senior pathologists in their interpretation.

Successful treatment of repeated hematemesis secondary to postsclerotherapy esophageal ulcer in a cirrhotic patient: A case report.

Esophageal variceal bleeding is a common lethal complication of cirrhosis. Endoscopic injection sclerotherapy (EIS) is one of the major endoscopic approaches for treating esophageal variceal bleeding. However, complications may occur after EIS, which mainly include retrosternal discomfort/pain, dysphagia, re-bleeding, esophageal ulcer, esophageal strictures, and esophageal perforation, etc. In this article, we reported a 36-year-old male who developed esophageal ulcer related bleeding after EIS. Currently, there is no consensus on the treatment strategy for esophageal ulcer-related bleeding after EIS. In the present case, the following treatment strategy may be effective for ulcer related bleeding. The first step is to inhibit gastric acid secretion and reduce portal pressure by intravenous infusion of esomeprazole and somatostatin, respectively. The second is local hemostasis by oral norepinephrine and lyophilizing thrombin powder. The third is to protect digestive tract mucosa by oral Kangfuxin Ye and aluminum phosphate.

A good response to steroid therapy in IgG4-related sclerosing cholangitis: a case report.

IgG4-related sclerosing cholangitis is a rare autoimmune liver disease. Biliary tract imaging, serum IgG4 concentration, and histopathological examination are the major diagnostic criteria for IgG4-related sclerosing cholangitis. In this paper, we report a male patient with yellowish skin, in whom classical liver-protection drugs were initially given, but the efficacy was poor. After that, IgG4-related sclerosing cholangitis was diagnosed, and he achieved a good response to steroid therapy.

A Small Jejunal Angioleiomyoma Detected by Double-Balloon Enteroscopy: A Case Report.

BACKGROUND Angioleiomyoma in the small intestine is a rare cause of gastrointestinal bleeding. Only 7 cases of angioleiomyoma in the small intestine were reported in the English literature, with 4 of them causing gastrointestinal bleeding. The diagnosis of angioleiomyomas in the small intestine before surgery is difficult. CASE REPORT We report the case of a 42-year-old man with recurrent melena who underwent repeated esophagogastroduodenoscopy and colonoscopy, without positive finding. During a double-balloon enteroscopy, an elevated lesion with a diameter of 6 mm was found in the jejunum. The lesion was resected laparoscopically assisted with double-balloon enteroscpy. A microscopic examination showed fibric membrane of the mass and numerous vascular channels surrounded by proliferated smooth muscle. There were exudative fibrin and many thrombi formed by red blood cells. Immunohistochemistry was positive for SMA and CD34. A pathological diagnosis of jejunal angioleiomyoma with thrombus was established. During a 5-year follow-up, there was no further gastrointestinal bleeding. CONCLUSIONS The gastroenterologists should consider angioleiomyoma in the small intestine when assessing obscure gastrointestinal bleeding.

Should Vasoconstrictors be Considered in a Cirrhotic Patient with Acute Non-variceal Upper Gastrointestinal Bleeding?

Varices manifest as a major etiology of upper gastrointestinal bleeding in patients with chronic liver diseases, such as liver cirrhosis and hepatocellular carcinoma. By contrast, non-variceal upper gastrointestinal bleeding is rare. Pharmacological treatment differs between patients with variceal and non-variceal bleeding. Vasoconstrictors are recommended for the treatment of variceal bleeding, rather than non-variceal bleeding. In contrast, pump proton inhibitors are recommended for the treatment of non-variceal bleeding, rather than variceal bleeding. Herein, we present a case with liver cirrhosis and acute upper gastrointestinal bleeding who had a high risk of rebleeding (i.e., Child-Pugh class C, hepatocellular carcinoma, portal vein thrombosis, low albumin, and high international normalized ratio and D-dimer). As the source of bleeding was obscure, only terlipressin without pump proton inhibitors was initially administered. Acute bleeding episode was effectively controlled. After that, an elective endoscopic examination confirmed that the source of bleeding was attributed to peptic ulcer, rather than varices. Based on this preliminary case report, we further discussed the potential role of vasoconstrictors in a patient with cirrhosis with acute non-variceal upper gastrointestinal bleeding.

Molecular modification of Protein A to improve the elution pH and alkali resistance in affinity chromatography.

Protein A of Staphylococcus aureus has been widely used as an affinity ligand for the purification of immunoglobulin. However, the low elution pH and the sensitivity to alkaline condition restricted the large-scale application of antibody purification. To overcome these disadvantages, the B domain was selected and mutated to Z domain and the recombinant Protein A was reconstructed by linking five Z domains. First, a section of six glycines was inserted into the second loop of Z domain, Z (6G). This increased the elution pH to 4.0-5.0. Then, the site-specific mutagenesis was conducted by replacing the 23rd asparagines to threonine and 30th phenylalanine to alanine, Z (N23T, F30A). These mutations made the recombinant Protein A shown a higher alkaline resistance than the nature Protein A. The work confirmed the modification of Protein A and exhibited the characteristics of recombinant Staphylococcal Protein A for antibody purification.