Optimization of machine learning algorithms for proteomic analysis using topsis

The present study focuses on a new application of the TOPSIS method for the optimization of machine learning algorithms, supervised neural networks (SNN), the quick classifier (QC), and genetic algorithm (GA) for proteomic analysis. The main hypotheses are that the change in the weights of alternatives could affect the ranking of algorithms. The obtained data confirmed this hypothesis for their ranking. Moreover, adding labor as a cost criterion to the list of criteria did not affect this ranking. This was because candidate 3 had better fuzzy membership degrees than the two other candidates concerning their criteria. This work showed the importance of the value of the fuzzy membership degrees of the cost criterion of the algorithms in their ranks. The values of the fuzzy membership degrees of the algorithms used for proteomic analysis could determine their priority according to their score differences. One of the advantages of this study was that the studied methods could be compared according to their characteristics. Another advantage was that the obtained results could be related to the new ones after improving these methods. The results of this work could be applied in engineering, where the analysis of proteins would be performed with these methods

Comparing Factors Associated with Increased Stimulant Use in Relation to HIV Status Using a Machine Learning and Prediction Modeling Approach

Stimulant use is an important driver of HIV/STI transmission among men who have sex with men (MSM). Evaluating factors associated with increased stimulant use is critical to inform HIV prevention programming efforts. This study seeks to use machine learning variable selection techniques to determine characteristics associated with increased stimulant use and whether these factors differ by HIV status. Data from a longitudinal cohort of predominantly Black/Latinx MSM in Los Angeles, CA was used. Every 6 months from 8/2014-12/2020, participants underwent STI testing and completed surveys evaluating the following: demographics, substance use, sexual risk behaviors, and last partnership characteristics. Least absolute shrinkage and selection operator (lasso) was used to select variables and create predictive models for an interval increase in self-reported stimulant use across study visits. Mixed-effects logistic regression was then used to describe associations between selected variables and the same outcome. Models were also stratified based on HIV status to evaluate differences in predictors associated with increased stimulant use. Among 2095 study visits from 467 MSM, increased stimulant use was reported at 20.9% (n = 438) visits. Increased stimulant use was positively associated with unstable housing (adjusted [a]OR 1.81; 95% CI 1.27-2.57), STI diagnosis (1.59; 1.14-2.21), transactional sex (2.30; 1.60-3.30), and last partner stimulant use (2.21; 1.62-3.00). Among MSM living with HIV, increased stimulant use was associated with binge drinking, vaping/cigarette use (aOR 1.99; 95% CI 1.36-2.92), and regular use of poppers (2.28; 1.38-3.76). Among HIV-negative MSM, increased stimulant use was associated with participating in group sex while intoxicated (aOR 1.81; 95% CI 1.04-3.18), transactional sex (2.53; 1.40-2.55), and last partner injection drug use (1.96; 1.02-3.74). Our findings demonstrate that lasso can be a useful tool for variable selection and creation of predictive models. These results indicate that risk behaviors associated with increased stimulant use may differ based on HIV status and suggest that co-substance use and partnership contexts should be considered in the development of HIV prevention/treatment interventions

Effect of vitamins A, E, C and omega-3 fatty acids supplementation on the level of catalase and superoxide dismutase activities in streptozotocin-induced diabetic rats

Background: Since free radicals and antioxidant enzymes may play an important role in the development of diabetes, the present study was designed to assess the effect of supplementation with vitamins A, E and C and �-3 fatty acids on catalase and superoxide dismutase activity in streptozotocin (STZ)-induced diabetic rats. Methods: A total of 64 male Wistar rats weighing 250 g were divided into four groups as normal control, diabetic control, diabetic supplemented with vitamin A, E and C and diabetic supplemented with �-3 fatty acids. After four weeks the rats were anesthetized and catalase (CAT) and superoxide dismutase (SOD) activities were investigated in blood samples, liver and heart homogenates. Results: In diabetic rats, the activity levels of heart SOD (p < 0.001) and heart and liver CAT (p < 0.001) were significantly lower than in normal control rats. Supplementation with vitamins A, E and C significantly increased heart CAT (p = 0.05). No significant change was observed in diabetic rats supplemented with �-3 fatty acids. Conclusion: Supplementation with vitamins A, E and C and �-3 fatty acids was found to increase heart CAT activity in diabetic rats and they can be valuable candidates in the treatment of the complications of diabetes

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran)

Background: Several reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19. Methods: Herein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth; hospital admission; AKI onset; ICU admission; hospital discharge; death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death). Results: In this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients. Conclusions: Since the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Therapeutic potential of TLR8 agonist GS-9688 (selgantolimod) in chronic hepatitis B: re-modelling of antiviral and regulatory mediators

Background & Aims: GS‐9688 (selgantolimod) is a toll‐like receptor 8 (TLR8) agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity of GS‐9688 has previously been evaluated in vitro in hepatitis B virus (HBV)‐infected hepatocytes and in vivo in the woodchuck model of CHB. Here we evaluated the potential of GS‐9688 to boost responses contributing to viral control and to modulate regulatory mediators. Approach & Results: We characterised the effect of GS‐9688 on immune cell subsets in vitro in PBMC of healthy controls and CHB patients. GS‐9688 activated dendritic cells and mononuclear phagocytes to produce IL‐12 and other immunomodulatory mediators, inducing a comparable cytokine profile in healthy controls and CHB patients. GS‐9688 increased the frequency of activated natural killer (NK) cells, mucosal‐associated invariant T‐cells (MAITs), CD4+ follicular helper T‐cells (TFH) and, in ~50% of patients, HBV‐specific CD8+T‐cells expressing interferon‐γ (IFNγ). Moreover, in vitro stimulation with GS‐9688 induced NK cell expression of IFNγ and TNFα and promoted hepatocyte lysis. We also assessed whether GS‐9688 inhibited immunosuppressive cell subsets that might enhance antiviral efficacy. Stimulation with GS‐9688 reduced the frequency of CD4+ regulatory T‐cells and monocytic myeloid‐derived suppressor cells (MDSC). Residual MDSC expressed higher levels of negative immune regulators, galectin‐9 and PD‐L1. Conversely, GS‐9688 induced an expansion of immunoregulatory TNF‐related apoptosis‐inducing ligand+ (TRAIL) regulatory NK cells and degranulation of arginase‐I+ polymorphonuclear‐MDSC (PMN‐MDSC). Conclusions: GS‐9688 induces cytokines in human PBMC that are able to activate antiviral effector function by multiple immune mediators (HBV‐specific CD8+T‐cells, TFH, NK cells and MAITs). Whilst reducing the frequency of some immunoregulatory subsets, it enhances the immunosuppressive potential of others, highlighting potential biomarkers and immunotherapeutic targets to optimise the antiviral efficacy of GS‐9688

Effectiveness of methadone maintenance treatment in prevention of hepatitis C virus transmission among injecting drug users

Background: Injecting drug users (IDUs) are a major and most important risk factor for rising hepatitis C virus (HCV) prevalence in Iran. Objectives: The objective of this study was to determine the effectiveness of methadone maintenance treatment (MMT) in prevention of HCV infection transmission among IDUs. Patients and Methods: A mathematical modeling has been used to estimate number of HCV infections averted. The input parameters used in the model were collected by self-reported method from 259 IDUs before registering and one year after MMT. Nonparametric statistical tests have been used to compare risky injecting and sexual behaviors among IDUs before and after participating in MMT program. Deterministic sensitivity analyses were done to show the effects of parameters' uncertainty on outcome. Results: Of the 259 participants, 98.4 (255) were men, the mean age ± SD was 33.1 ± 7.58 years and HCV prevalence was 50. The studied IDUs reported lower rate of risky injecting and sexual behavior after participation in MMT program. The cumulative incidence of HCV per 100 IDUs due to sharing injection and unsafe sexual contact with MMT program were 13.84 (95 CI: 6.17 -21.51), 0.0003 (0.0001 - 0.0005) and without it 36.48 (25.84 - 47.11) and 0.0004 (0.0002-0.0006) respectively. Conclusions: The MMT program is an effective intervention to prevent HCV infection transmission, although it is essential to compare its effectiveness with other interventions before implementing it in nationwide. © 2013, Kowsar Corp.; Licensee Kowsar Ltd

Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China

© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239

Phase Transitions and Their Interaction with Dislocations in Silicon

In this paper, phase transformations (PTs) in silicon were investigated through molecular dynamics (MD) using Tersoff potential. In the first step, simulations of PTs in single crystal silicon under various stress-controlled loading were carried out. Results shows that all instability points under various stress states are described by criteria, which are linear in the space of normal stresses. There is a region in the stress space in which conditions for direct and reverse PTs coincide and a unique homogeneous phase transition (without nucleation) can be realized. Finally, phase transition in bi-crystalline silicon with a dislocation pileup along the grain boundary (GB) was carried out. Results showed that the phase transition pressure first decreases linearly with the number of dislocation pileups and then reaches a plateau with the accumulation of dislocations in the pileup. The maximum reduction of phase transition pressure is 30% compared to that for perfect single crystalline silicon