ABSTRACT
Background/Aims@#Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. @*Methods@#We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. @*Results@#The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. @*Conclusions@#Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
ABSTRACT
Severe acute pancreatitis [SAP] is a serious systemic disease with high mortality. This study aims to investigate the role of the chemokine, fractalkine [FKN], in the pathogenesis of SAP and the effects of intervention by ulinastatin on FKN expression in an SAP rat model. We randomly divided 72 Sprague Dawley rats into the following groups: SAP, ulinastatin treatment [UT], and control [C]. The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bili-pancreatic ducts of the rats. Rats in the UT group were injected with ulinastatin immediately after establishment of the SAP model. Serum FKN levels were detected by ELISA at various time points. Histopathological analyses of the pancreas and lung were performed. Expressions of FKN mRNA in the tissues of the pancreas and lung were detected by real-time ??uorescence quantitative polymerase chain reaction [RT-qPCR] at various time points for each group. Serum levels of FKN at 3 h after surgery in the SAP subgroup were significantly higher than those in the C group [P < 0.05]. There were no significant differences between the UT and C groups observed at various time points. Expression levels of FKN mRNA in the pancreatic tissues of the SAP group increased gradually. Although we observed no difference between the SAP and C groups [P > 0.05] at 1 hour h after surgery, mRNA levels of FKN in the lung tissues at 3, 6, and 12 h post-surgery in the SAP subgroups were significantly higher than those in the C group for the same time points [P < 0.05]. Pathological injury of the pancreatic tissues was more remarkable in the SAP group compared to the UT group. FKN may play an important role in the pathogenesis of SAP and SAP-related acute lung injury [ALI]. Ulinastatin ef??ciently interferes with SAP and SAP-related ALI and may be related to inhibition of FKN expression
Subject(s)
Male , Animals, Laboratory , Chemokines , Chemokine CX3CL1 , Glycoproteins , Rats, Sprague-Dawley , Taurocholic Acid , Gene ExpressionABSTRACT
<p><b>AIM</b>To study the structure and crystal forms of chlorobenzylidine.</p><p><b>METHODS</b>Karl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine.</p><p><b>RESULTS</b>Chlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms.</p><p><b>CONCLUSION</b>The studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.</p>