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.

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.

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.