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Objectives: We performed a virtual screening of olive secoiridoids of the OliveNet TM library to predict SARS-CoV-2 PLpro inhibition. Benchmarked molecular docking protocol that evaluated the performance of two docking programs was applied to execute virtual screening. Molecular dynamics stability analysis of the top-ranked olive secoiridoid docked to PLpro was also carried out., Methods: Benchmarking virtual screening used two freely available docking programs, AutoDock Vina 1.1.2. and AutoDock 4.2.1. for molecular docking of olive secoiridoids to a single PLpro structure. Screening also included benchmark structures of known active and decoy molecules from the DEKOIS 2.0 library. Based on the predicted binding energies, the docking programs ranked the screened molecules. We applied the usual performance evaluation metrices to evaluate the docking programs using the predicted ranks. Molecular dynamics of the top-ranked olive secoiridoid bound to PLpro and computation of MM-GBSA energy using three iterations during the last 50 ps of the analysis of the dynamics in Desmond supported the stability prediction., Results and Discussions: Predictiveness curves suggested that AutoDock Vina has a better predictive ability than AutoDock, although there was a moderate correlation between the active molecules rankings (Kendall's correlation of rank (τ) = 0.581). Interestingly, two same molecules, Demethyloleuropein aglycone, and Oleuroside enriched the top 1 % ranked olive secoiridoids predicted by both programs. Demethyloleuropein aglycone bound to PLpro obtained by docking in AutoDock Vina when analyzed for stability by molecular dynamics simulation for 50 ns displayed an RMSD, RMSF<2 Å, and MM-GBSA energy of -94.54 ± 6.05 kcal/mol indicating good stability. Molecular dynamics also revealed the interactions of Demethyloleuropein aglycone with binding sites 2 and 3 of PLpro, suggesting a potent inhibition. In addition, for 98 % of the simulation time, two phenolic hydroxy groups of Demethyloleuropein aglycone maintained two hydrogen bonds with Asp302 of PLpro, specifying the significance of the groups in receptor binding., Conclusion: AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Head and neck squamous cell carcinoma (HNSC) is one of most common malignancies with high mortality worldwide. Importantly, the molecular heterogeneity of HNSC complicates the clinical diagnosis and treatment, leading to poor overall survival outcomes. To dissect the complex heterogeneity, recent studies have reported multiple molecular subtyping systems. For instance, HNSC can be subdivided to four distinct molecular subtypes: atypical, basal, classical, and mesenchymal, of which the mesenchymal subtype is characterized by upregulated epithelial-mesenchymal transition (EMT) and associated with poorer survival outcomes. Despite a wealth of studies into the complex molecular heterogeneity, the regulatory mechanism specific to this aggressive subtype remain largely unclear. Herein, we developed a network-based bioinformatics framework that integrates lncRNA and mRNA expression profiles to elucidate the subtype-specific regulatory mechanisms. Applying the framework to HNSC, we identified a clinically relevant lncRNA LNCOG as a key master regulator mediating EMT underlying the mesenchymal subtype. Five genes with strong prognostic values, namely ANXA5, ITGA5, CCBE1, P4HA2, and EPHX3 , were predicted to be the putative targets of LNCOG and subsequently validated in other independent datasets. By integrative analysis of the miRNA expression profiles, we found that LNCOG may act as a ceRNA to sponge miR-148a-3p thereby upregulating ITGA5 to promote HNSC progression. Furthermore, our drug sensitivity analysis demonstrated that the five putative targets of LNCOG were also predictive of the sensitivities of multiple FDA-approved drugs. In summary, our bioinformatics framework facilitates the dissection of cancer subtype-specific lncRNA regulatory mechanisms, providing potential novel biomarkers for more optimized treatment of HNSC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: The study of microbial communities and their applications have been leveraged by advances in sequencing techniques and bioinformatics tools. The Oxford Nanopore Technologies long-read sequencing by nanopores provides a portable and cost-efficient platform for sequencing assays. While this opens the possibility of sequencing applications outside specialized environments and real-time analysis of data, complementing the existing efficient library preparation protocols with streamlined bioinformatic workflows is required., Results: Here we present NanoRTax, a Nextflow pipeline for nanopore 16S rRNA gene amplicon data that features state-of-the-art taxonomic classification tools and real-time capability. The pipeline is paired with a web-based visual interface to enable user-friendly inspections of the experiment in progress. NanoRTax workflow and a simulated real-time analysis were used to validate the prediction of adult Intensive Care Unit patient mortality based on full-length 16S rRNA sequencing data from respiratory microbiome samples., Conclusions: This constitutes a proof-of-concept simulation study of how real-time bioinformatic workflows could be used to shorten the turnaround times in critical care settings and provides an instrument for future research on early-response strategies for sepsis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background & Aims: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation., Methods: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria., Results: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index ≥0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (≤1%), and the model had a competitive performance compared with the Baveno VII criteria., Conclusions: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available., Lay Summary: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable ., Competing Interests: There are no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Background: The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and the effects on morbidity and mortality., Aim: The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary center in northern India., Methods: This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr to Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis., Results: A total of 708 patients with COVID-19 fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR = 25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients, respectively. Serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were elevated in 6.92%, 69.91%, and 80.22% of patients, respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate to severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1 IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1 g/dL increase].Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1 g/dL increase] showed significant association with mortality., Conclusion: Liver function abnormalities are common in patients with COVID-19. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Identifying independent and interactive associations of a wide range of diseases and multimorbidity and apolipoprotein E4 (APOE4) with dementia may help promote cognitive health. The main aim of the present study was to investigate associations of such diseases and their multimorbidity with incident dementia., Methods: In this retrospective cohort study, we included 471,485 individuals of European ancestry from the UK Biobank, aged 38-73 years at baseline (2006-10). Dementia was identified using inpatient records and death registers. The follow-up period was between March 16, 2006, and Jan 31, 2021., Findings: During a median follow-up of 11·9 years, 6189 cases of incident all-cause dementia (503 young-onset cases, 5686 late-onset cases) were documented. In multivariable-adjusted analysis, 33 out of 63 major diseases were associated with an increased risk of dementia. The hazard ratio (HR [95% CI]) ranged from 1·12 (1·06-1·19) for obesity to 14·22 (12·33-16·18) for Parkinson's disease. In addition to conventional diseases, respiratory disorders, musculoskeletal disorders, digestive disorders, painful conditions, and chronic kidney disease were associated with increased dementia risk. A larger HR for dementia was observed for a larger number of diseases (3·97 [3·51-4·48] for ≥6 diseases versus no disease). These individual diseases and multimorbidity were more predictive of young-onset dementia than of late-onset dementia. Dementia risk score incorporating multimorbidity, age, and APOE4 status had strong prediction performance (area under the curve [95% CI]: 82·2% [81·7-82·7%]). APOE4 was more predictive of late-onset dementia (HR [95% CI]: 2·90 [2·75-3·06]) than of young-onset dementia (1·26 [1·03-1·54]). Associations of painful conditions, depression, obesity, diabetes, stroke, Parkinson's disease, high cholesterol, and their multimorbidity with incident dementia were stronger among non-APOE4 carriers., Interpretation: Besides conventional diseases, numerous diseases are associated with an increased risk of dementia. These individual diseases and multimorbidity are more predictive of young-onset dementia, whereas APOE4 is more predictive of late-onset dementia. Individual diseases and multimorbidity are stronger predictors of dementia in non-APOE4 carriers. Although multiple risk factors have been adjusted for in the analysis, potential confounding from unknown factors may have biased the associations., Funding: The Fundamental Research Funds of the State Key Laboratory of Ophthalmology, Project of Investigation on Health Status of Employees in Financial Industry in Guangzhou, China (Z012014075), Science and Technology Program of Guangzhou, China (202,002,020,049)., Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (© 2022 The Author(s).)

Background & Aims: There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis., Methods: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period., Results: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) ( P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores., Conclusions: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Grade of brain tumor is thought to be the most significant and crucial component in treatment management. Recent development in medical imaging techniques have led to the introduce non-invasive methods for brain tumor grading such as different magnetic resonance imaging (MRI) protocols. Combination of different MRI protocols with fusion algorithms for tumor grading is used to increase diagnostic improvement. This paper investigated the efficiency of the Laplacian Re-decomposition (LRD) fusion algorithms for glioma grading., Procedures: In this study, 69 patients were examined with MRI. The T1 post enhancement (T1Gd) and diffusion-weighted images (DWI) were obtained. To evaluated LRD performance for glioma grading, we compared the parameters of the receiver operating characteristic (ROC) curves., Findings: We found that the average Relative Signal Contrast (RSC) for high-grade gliomas is greater than RSCs for low-grade gliomas in T1Gd images and all fused images. No significant difference in RSCs of DWI images was observed between low-grade and high-grade gliomas. However, a significant RSCs difference was detected between grade III and IV in the T1Gd, b50, and all fussed images., Conclusions: This research suggests that T1Gd images are an appropriate imaging protocol for separating low-grade and high-grade gliomas. According to the findings of this study, we may use the LRD fusion algorithm to increase the diagnostic value of T1Gd and DWI picture for grades III and IV glioma distinction. In conclusion, this article has emphasized the significance of the LRD fusion algorithm as a tool for differentiating grade III and IV gliomas., Competing Interests: The authors report no declarations of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Data are conflicting regarding the optimal cutoffs of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to predict short-term mortality in patients with sepsis. We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) for English-language reports of studies evaluating adult patients with sepsis, severe sepsis, and septic shock with BNP/NT-proBNP levels and short-term mortality (intensive care unit, in-hospital, 28-day, or 30-day) published from January 1, 2000, to September 5, 2017. The average values in survivors and nonsurvivors were used to estimate the receiver operating characteristic curve (ROC) using a parametric regression model. Thirty-five observational studies (3508 patients) were included (median age, 51-75 years; 12%-74% males; cumulative mortality, 34.2%). A BNP of 622 pg/mL had the greatest discrimination for mortality (sensitivity, 0.695 [95% CI, 0.659-0.729]; specificity, 0.907 [95% CI, 0.810-1.003]; area under the ROC, 0.766 [95% CI, 0.734-0.797]). An NT-proBNP of 4000 pg/mL had the greatest discrimination for mortality (sensitivity, 0.728 [95% CI, 0.703-0.753]; specificity, 0.789 [95% CI, 0.710-0.867]; area under the ROC, 0.787 [95% CI, 0.766-0.809]). In prespecified subgroup analyses, identified BNP/NT-proBNP cutoffs had higher discrimination if specimens were obtained 24 hours or less after admission, in patients with severe sepsis/septic shock, in patients enrolled after 2010, and in studies performed in the United States and Europe. There was inconsistent adjustment for renal function. In this hypothesis-generating analysis, BNP and NT-proBNP cutoffs of 622 pg/mL and 4000 pg/mL optimally predicted short-term mortality in patients with sepsis. The applicability of these results is limited by the heterogeneity of included patient populations., (© 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

The purpose was to analyze the value of quantitative parameters of DCE-MRI in evaluating micro-infiltration of malignant bone tumors., Methods: Thirty-nine New Zealand white rabbits were used to establish malignant bone tumor models by implanting VX2 tumor fragments into the right tibiae. After three weeks, models were examined by conventional MRI and DCE-MRI; then the right tibiae were cut into sagittal sections and partitioned into histology slices for comparison with microscopic findings. Micro-infiltration groups were selected and the range of infiltration was determined under the microscope, and corresponding DCE images analyzed to obtain the quantitative parameters include Ktrans, Kep, v e and v p in parenchyma areas, micro-infiltration areas and simple edema areas. One-way ANOVA was used to compare the differences of the parameters between the three areas. Receiver operating characteristic curves (ROCs) were plotted to determine the accuracy of different parameters by area under curves (AUCs)., Results: 22 cases (22/39, 56.4%) were included in the micro-infiltration group and the infiltration depth ranged from 1.3 mm to 4.6 mm, with an average depth of 3.2 mm ± 0.8 mm. The statistical results of quantitative parameters in the three areas were as follows: Ktrans values were (0.494 ± 0.052), (0.403  ±  0.049), (0.173 ± 0.047) min -1 ( p  = =0.000), Kep values were (1.959 ± 0.65), (1.528 ± 0.372), (1.174 ± 0.486) min -1 ( p  = =0.000), v e values were (0.247 ± 0.068), (0.283 ± 0.057), (0.168 ± 0.062) min -1 ( p  = =0.000), v p values were (0.125 ± 0.036), (0.108 ± 0.033), (0.098 ± 0.025) min -1 ( p  = =0.022), respectively. Ktrans and Kep values had significant difference in the three areas after comparing between-groups, respectively. However, there were no significant difference in v p values between parenchyma and micro-infiltration areas ( p  = =0.078), micro-infiltration and simple edema areas ( p  = =0.315), and v e values between parenchyma and micro-infiltration areas ( p  = =0.056). The v e values were higher in parenchyma and micro-infiltration areas then simple edema areas. Ktrans had highest accuracy in differentiating different areas (AUC > 0.9), respectively., Conclusion: Quantitative parameters Ktrans, Kep and v e can assess the extent of intramedullary invasion of malignant bone tumors. Ktrans have highest accuracy in differentiating different regions., Competing Interests: The authors declare that there are no conflicts of interest., (© 2019 The Authors. Published by Elsevier GmbH.)

Background and Purpose: Dysphagia is a common, severe and dose-limiting toxicity after oncological treatment of head and neck cancer (HNC). This study aims to investigate relationships between radiation doses to structures involved in normal swallowing and patient-reported as well as clinically measured swallowing function in HNC patients after curative (chemo-) radiation therapy (RT) with focus on late effects., Materials and Methods: Patients (n = 90) with HNC curatively treated with RT ± chemotherapy in 2007-2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific symptom score was used to determine patient-reported dysphagia. The Penetration-Aspiration Scale (PAS) was applied to determine swallowing function by VFS (PAS ≥ 4/ ≥ 6 = moderate/severe dysphagia). Thirteen anatomical structures involved in normal swallowing were individually delineated on the patients' original planning CT scans and associated dose-volume histograms (DVHs) retrieved. Relationships between structure doses and late toxicity were investigated through univariable and multivariable logistic regression analysis (UVA/MVA) accounting for effects by relevant clinical factors., Results: Median assessment time was 7 months post-RT (range: 5-34 months). Mean dose to the contralateral parotid gland and supraglottic larynx as well as maximum dose to the contralateral anterior digastric muscle predicted patient-reported dysphagia (AUC = 0.64-0.67). Mean dose to the pharyngeal constrictor muscle, the larynx, the supraglottic larynx and the epiglottis, as well as maximum dose to the contralateral submandibular gland predicted moderate and severe dysphagia by VFS (AUC = 0.71-0.80)., Conclusion: The patients in this cohort were consecutively identified pre-treatment, and were structurally approached and assessed for dysphagia after treatment at a specific time point. In addition to established dysphagia organs-at-risk (OARs), our data suggest that epiglottic and submandibular gland doses are important for swallowing function post-RT. Keeping DVH thresholds below V60 = 60% and V60 = 17%, respectively, may increase chances to reduce occurrence of severe late dysphagia. The results need to be externally validated in future studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Authors.)

Background: Liver failure (LF) is a serious complication of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). This could be influenced by the hemodynamic and functional status of the underlying cirrhotic liver. We evaluated baseline hepatic venous pressure gradient (HVPG) and indocyanine green (ICG) clearance as predictive factors for the development of LF in patients with liver cirrhosis undergoing TACE for HCC., Methods: Forty-two patients with cirrhosis and HCC, referred for TACE, were clinically evaluated including the assessment of Child Turcotte Pugh score (CTP), Model for End-Stage Liver Disease (MELD), HVPG measurement, and ICG retention test. Predictors of development of hepatic failure after TACE were determined., Results: In our study population, the mean age of the patients was 58 years, with mean CTP of 6.60 ± 1.149 and mean MELD score of 9.57 ± 2.923. The mean HVPG and ICG retention at 15 min was 13.57 ± 4.64 mmHg and 21.571 ± 12.434, respectively. Post-TACE Liver Failure (PTLF within 1 month after TACE) developed in 23.80% patients, whereas 76.19% patients did not have PTLF. The statistically significant preprocedure variables that might predict hepatic failure after TACE using univariate analysis were found to be high CTP, MELD score, ICG retention, HVPG, serum bilirubin, serum creatinine, alfa-fetoprotein levels, large tumor size, and low baseline serum albumin. On multivariate analysis, ICG was an independent factor predictive of hepatic failure after TACE., Conclusion: Pretreatment evaluation of routine liver function is of fundamental importance before TACE. Baseline ICG retention test (ICG-R15) is a marker indicating the state of liver function in patients undergoing TACE and is an independent predictor for PTLF. Our study concludes that with a cutoff of 25, ICG-R15 has 92.9% accuracy, 90% sensitivity, and 87.5% specificity to predict hepatic failure after TACE.

Protein-protein interaction (PPI) is an essential mechanism by which proteins perform their biological functions. For globular proteins, the molecular characteristics of such interactions have been well analyzed, and many computational tools are available for predicting PPI sites and constructing structural models of the complex. In contrast, little is known about the molecular features of the interaction between integral membrane proteins (IMPs) and few methods exist for constructing structural models of their complexes. Here, we analyze the interfaces from a non-redundant set of complexes of α-helical IMPs whose structures have been determined to a high resolution. We find that the interface is not significantly different from the rest of the surface in terms of average hydrophobicity. However, the interface is significantly better conserved and, on average, inter-subunit contacting residue pairs correlate more strongly than non-contacting pairs, especially in obligate complexes. We also develop a neural network-based method, with an area under the receiver operating characteristic curve of 0.75 and a Pearson correlation coefficient of 0.70, for predicting interface residues and their weighted contact numbers (WCNs). We further show that predicted interface residues and their WCNs can be used as restraints to reconstruct the structure α-helical IMP dimers through docking for fourteen out of a benchmark set of sixteen complexes. The RMSD100 values of the best-docked ligand subunit to its native structure are <2.5 Å for these fourteen cases. The structural analysis conducted in this work provides molecular details about the interface between α-helical IMPs and the WCN restraints represent an efficient means to score α-helical IMP docking candidates.

Objective: The aim of this study is to investigate the relation between renal indexes and functional MRI in a population of kidney transplant recipients who underwent MR with diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) of the transplanted graft., Method: Study population included 40 patients with single kidney transplant. The patients were divided into 3 groups, on the basis of creatinine clearance (CrCl) values calculated using Cockcroft-Gault formula: group A, including patients with normal renal function (CrCl ≥ 60 mL/min); group B, which refers to patients with moderate renal impairment (CrCl > 30 but <60 mL/min); and, finally, group C, which means severe renal deterioration (CrCl ≤ 30 mL/min). All patients were investigated with a 1.5 Tesla MRI scanner, acquiring DWI and DTI sequences. A Mann-Whitney U test was adopted to compare apparent diffusion coefficients (ADCs) and fractional anisotropy (FA) measurements between groups. Receiver operating characteristic (ROC) curves were created for prediction of normal renal function (group A) and renal failure (group C). Pearson correlation was performed between renal clearance and functional imaging parameter (ADC and FA), obtained for cortical and medullar regions., Results: Mann-Whitney U test revealed a highly significant difference (p < 0.01) between patients with low CrCl (group C) and normal CrCl (group A) considering both medullar ADC and FA and cortical ADC. Regarding contiguous groups, the difference between group B and C was highly significant (p < 0.01) for medullar ADC and significant (p < 0.05) for cortical ADC and medullar FA. No difference between these groups was found considering cortical FA. Analyzing groups A and B, we found a significant difference (p < 0.05) for medullar both ADC and FA, while no difference was found for cortical ADC and FA. Strongest Pearson correlation was found between CrCl and medullar ADC (r = 0.65). For predicting normal renal function or severe renal impairment, highest values of AUC were observed using medullar ADC cut-off values (respectively 0.885 and 0.871); medullar FA showed also high accuracy (respectively 0.831 and 0.853)., Conclusions: DWI and DTI are promising tools for non-invasive monitoring of renal function; medullar ADC proved to be the best parameter for renal function assessment.

The purpose of this study was to evaluate the diagnostic efficiency for hepatocellular carcinoma (HCC) with the combined analysis of alpha-l-fucosidase (AFU), alpha-fetoprotein (AFP) and thymidine kinase 1 (TK1). Serum levels of AFU, AFP and TK1 were measured in: 116 patients with HCC, 109 patients with benign hepatic diseases, and 104 normal subjects. The diagnostic value was analyzed using the logistic regression equation and receiver operating characteristic curves (ROC). Statistical distribution of the three tested tumor markers in every group was non-normally distributed (Kolmogorov-Sminov test, Z = 0.156-0.517, P < 0.001). The serum levels of AFP and TK1 in patients with HCC were significantly higher than those in patients with benign hepatic diseases (Mann-Whitney U test, Z = -8.570 to -5.943, all P < 0.001). However, there was no statistically significant difference of AFU between these two groups (Mann-Whitney U test, Z = -1.820, P = 0.069). The levels of AFU were significantly higher in patients with benign hepatic diseases than in normal subjects (Mann-Whitney U test, Z = -7.984, P < 0.001). Receiver operating characteristic curves (ROC) in patients with HCC versus those without HCC indicated the optimal cut-off value was 40.80 U/L for AFU, 10.86 μg/L for AFP and 1.92 pmol/L for TK1, respectively. The area under ROC curve (AUC) was 0.718 for AFU, 0.832 for AFP, 0.773 for TK1 and 0.900 for the combination of the three tumor markers. The combination resulted in a higher Youden index and a sensitivity of 85.3%. The combined detection of serum AFU, AFP and TK1 could play a complementary role in the diagnosis of HCC, and could significantly improve the sensitivity for the diagnosis of HCC.

The present study was undertaken to detect circulating IgG antibodies to peptide antigens derived from baculoviral IAP repeat-containing protein 5 isoform 2 (BIRC5) and myc proto-oncogene protein (MYC) in cervical cancer. A total of 107 female patients with cervical cancer of stages I and II, and 130 healthy female subjects were recruited for analysis of circulating IgG antibodies to BIRC5 and MYC. Student's t-test showed significant differences in circulating levels of anti-BIRC5 IgG (t = -4.27, df = 235, P < 0.0001) and anti-MYC IgG (t = 3.51, df = 232, P = 0.0005) between the patient group and the control group. Receiver operating characteristic (ROC) analysis showed an area under the ROC curve (AUC) of 0.67 with sensitivity of 23.4% against specificity of 90% for the anti-BIRC5 IgG assay and an AUC of 0.66 with sensitivity of 9.4% against specificity of 90.6% for the anti-MYC IgG assay. Analysis of quality control samples gave an inter-assay deviation of 8.9% in the anti-BIRC5 IgG assay and 9.0% in the anti-MYC IgG assay. This work suggests that anti-BIRC5 IgG could serve as a biomarker for early diagnosis of cervical cancer although a panel of such tumor-associated antigens is needed to develop a highly sensitive test.