Duck hepatitis B viruses (DHBV), unlike mammalian hepadnaviruses, are thought to lack X genes, which encode transcription-regulatory proteins believed to contribute to the development of hepatocellular carcinoma. A lack of association of chronic DHBV infection with hepatocellular carcinoma development supports this belief. Here, we demonstrate that DHBV genomes have a hidden open reading frame from which a transcription-regulatory protein, designated DHBx, is expressed both in vitro and in vivo. We show that DHBx enhances neither viral protein expression, intracellular DNA synthesis, nor virion production when assayed in the full-length genome context in LMH cells. However, similar to mammalian hepadnavirus X proteins, DHBx activates cellular and viral promoters via the Raf-mitogen-activated protein kinase signaling pathway and localizes primarily in the cytoplasm. The functional similarities as well as the weak sequence homologies of DHBx and the X proteins of mammalian hepadnaviruses strongly suggest a common ancestry of ortho-and avihepadnavirus X genes. In addition, our data disclose similar intracellular localization and transcription regulatory functions of the corresponding proteins, raise new questions as to their presumed role in hepatocarcinogenesis, and imply unique opportunities for deciphering of their still-enigmatic in vivo functions.Since the identification of hepatitis B virus (HBV) in humans, several related viruses have been isolated from mammalian and avian species (9, 53, 68). These viruses, known as hepadnaviruses, display high liver tropism, have a narrow host range, and cause acute and chronic hepatitis. Chronic infection with mammalian hepadnaviruses (orthohepadnaviruses) is associated with the development of liver cancer.The hepadnaviruses are small enveloped DNA viruses with a unique virion ultrastructure. The viral genome is a partially duplexed, relaxed circular DNA molecule (rcDNA) with a size of about 3 kb which upon entry of the cell is converted into a covalently closed circular episome. This covalently closed circular DNA is then transcribed by the host RNA polymerase II, synthesizing subgenomic mRNAs and a greater-than-genomelength RNA known as pregenomic RNA or C-mRNA. Distinctive for all hepadnaviruses is the method of replication by reverse transcription of the pregenomic RNA into rcDNA. Transcripts encoding the envelope proteins, the nucleocapsid protein, the polymerase protein (P protein), and, as exclusively described so far in orthohepadnaviruses, the X protein have been identified. The organization of the viral genome is very compact, with overlapping reading frames and promoters and enhancer elements located within coding regions (20).The X proteins of orthohepadnaviruses affect signal transduction pathways, transcription, cell transformation, and proliferation (1,8,46,70). The HBV-specific X protein (HBx) is expressed in vivo, as shown by immunohistology and indirectly by identification of an HBx-specific immune response in infected individuals (64). In vivo expressio...
BackgroundTo explore the diagnostic performance of triggered angiography non-contrast-enhanced magnetic resonance imaging (TRANCE-MRI) for the evaluation of venous pathology of the lower extremity.MethodsThis was a single-centre prospective cohort study of 25 patients with suspected venous disease in the lower extremities. Each patient received Doppler ultrasonography (for venous evaluation) before the scheduled TRANCE-MRI (for venous and arterial evaluations) on a 1.5 T MR scanner (Philips Ingenia, Philips Healthcare, Best, the Netherlands), followed by lymphography and computed tomography angiography that were arranged according to the diagnostic indications.ResultsThe sensitivity, specificity and accuracy of TRANCE-MRI were 85.7%, 88/9 and 88%, respectively. The inter-rater agreement for deep vein thrombosis (DVT) of the thigh between the ultrasonography and TRANCE-MRI results was substantial agreement (Cohen’s kappa κ, 0.72). In ultrasonography-negative cases, TRANCE-MRI detected four additional cases (16%, 4/25) of DVT; three cases (12%, 3/25) of venous compression caused by pelvic lymphadenopathy, hip prosthesis or knee joint effusion; one case (4%, 1/25) of vena cava anomaly; two cases (8%, 2/25) of occult peripheral artery disease (PAD); and one case (4%, 1/25) of an occluded bypass graft.ConclusionTRANCE-MRI can be used as an alternative and objective tool for assessing lower extremity diseases, especially suspected venous pathology. Compared with ultrasonography, TRANCE-MRI plays a better role in assessing varicose veins of the lower extremities and deep veins of the pelvis and abdomen. However, false-positive results may occur in the left common iliac vein of elderly patients. Finally, occult PAD rarely occurs in patients with suspected lower extremity venous disease. Therefore, we recommend performing the TRANCE-MRV protocol instead of the full protocol (MRV + MRA) in the clinical setting in patients with venous scenarios.
As the performance of current fall risk assessment tools is limited, clinicians face significant challenges in identifying patients at risk of falling. This study proposes an automatic fall risk prediction model based on eXtreme gradient boosting (XGB), using a data-driven approach to the standardized medical records. This study analyzed a cohort of 639 participants (297 fall patients and 342 controls) from Chang Gung Memorial Hospital, Chiayi Branch, Taiwan. A derivation cohort of 507 participants (257 fall patients and 250 controls) was collected for constructing the prediction model using the XGB algorithm. A comparative validation of XGB and the Morse Fall Scale (MFS) was conducted with a prospective cohort of 132 participants (40 fall patients and 92 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. This machine learning method provided a higher sensitivity than the standard method for fall risk stratification. In addition, the most important predictors found (Department of Neuro-Rehabilitation, Department of Surgery, cardiovascular medication use, admission from the Emergency Department, and bed rest) provided new information on in-hospital fall event prediction and the identification of patients with a high fall risk.
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