To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203). Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.

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These authors contributed equally to this work. ⇤ Corresponding authors.Gastric cancer is among the malignant tumors with the highest incidence and mortality rates.Early detection and accurate histopathological diagnosis of gastric cancer are essential factors that can help increase the chances of successful treatment. While the worldwide shortage of pathologists has imposed burdens on the current histopathology service, it also offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. To the best of our knowledge, there has not been a clinically applicable histopathological assistance system with high accuracy, and can generalize to whole slide images created with diverse digital scanner models from different hospitals. Here, we report the clinically applicable artificial intelligence assistance system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated whole slide images. The model achieved a sensitivity near 100% and an average specificity of 80.6% on a real world test dataset, which included 3,212 whole slide images digitalized with three scanner models. We showed that the system would aid pathologists in improving diagnostic accuracy and preventing misdiagnosis. Moreover, we demonstrated that our system could perform robustly with 1,582 whole slide images from two other medical centers. Our study proves the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer death 1 . There is a wide geographic difference in its incidence, with the highest incidence rate in East Asian populations 2 . In China, about 498,000 new cases were diagnosed in 2015, which was the second leading cause of cancer-associated mortality 3 . As early detection, accurate diagnosis and surgical intervention are crucial factors to reduce gastric cancer mortality, robust

Background and AimsImmunotherapy with PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) has been proven to be effective against advanced hepatocellular carcinoma (HCC). The aim of this study was to identify the feasibility and safety of subsequent salvage surgery after this combination therapy.Methods and PatientsA retrospective analysis was performed on patients with primary HCC with major vascular invasion between 2018 and 2019. All cases were treated with a combination of a PD-1 inhibitor and TKI agents and subsequent surgery.ResultsA total of 10 HCC cases with major vascular invasion met the successful conversion criteria after the combination therapy, and eight patients underwent subsequent salvage surgery after both radiology and 3D quantitative oncological assessment. Partial response (PR) was recorded in 7 of 10 patients and complete response (CR) in 3 of 10 patients before salvage surgery. Salvage surgery included right hepatectomy, left hepatectomy, and anatomic segmental hepatectomy. The mean intraoperative blood loss was 1,650 ml (50–3,000 ml). No complications beyond Clavien–Dindo level III or postoperative mortality were observed. The viable tumor cell rate of the PR cases (modified response evaluation criteria in solid tumors, mRECIST) varied from 1.5% to 100%, and only one patient had pathology-proven pathological complete response (pCR). The postoperative median follow-up time was 19.7 months (9.1–24.9 months). The 12-month recurrence-free survival rate of all cases who underwent salvage surgery was 75%.ConclusionSalvage surgery was effective and safe after conversion therapy with PD-1 inhibitors plus TKIs and may increase the long-term oncological benefit for patients with unresectable HCC.