Forward Stepwise Multiple Linear Regression Research Articles

Low ankle-brachial index is associated with early-stage chronic kidney disease in type 2 diabetic patients independent of albuminuria.

AimsThe role of low ankle-brachial index (ABI) in early-stage chronic kidney disease (CKD) is not fully known. This study was designed to investigate the prevalence of low ABI in early-stage CKD defined as an estimated glomerular filtration rate (eGFR) between 60–89 ml/min/1.73 m2 of type 2 diabetic patients without albuminuria and to determine the association between the low ABI and mildly decreased eGFR.MethodsThe cross-sectional study enrolled 448 type 2 diabetic patients with normoalbuminuria. The patients were stratified into two groups according to the CKD-EPI eGFR level: the normal group with eGFR level ≥90 mL/min/1.73 m2 and the lower group with eGFR of 60–89. ABI was categorized as normal (1.0–1.39), low-normal (0.9–0.99), and low (<0.9). Both stepwise forward multiple linear regression and binary logistic regression analyses were performed to examine the association between ABI categories and eGFR levels and to assess the relation of low ABI and early-stage CKD.ResultsThe prevalence of low ABI in early-stage CKD of type 2 diabetic patients without albuminuria was 39.5%. Low ABI was associated with an approximate 3-fold greater risk of early-stage CKD in bivariate logistic regression analysis, and remained significantly associated with a 2.2 fold risk (95% confidence interval: 1.188–4.077; P = 0.012) after adjusting traditional chronic kidney disease risk factors.ConclusionsThere was a high prevalence of low ABI in early-stage CKD patients of type 2 diabetes with normoalbuminuria and a close relation between low ABI and early-stage CKD, suggesting that we should pay much more attention to the patients who have only mildly decreased eGFR and normoalbuminuria but have already had a low ABI in clinic work and consider the preventive therapy in early stage.

Automatic Non-destructive Quality Inspection System for Oil Palm Fruits

Abstract In this research a non-destructive, rapid and cost effective examination machine for the estimation of the ripeness fraction, oil content and free fatty acid level in oil palm fresh fruits bunch was developed. The automatic machine-vision based inspection system provided consistency, rapid estimation and acceptable accuracy results in non-destructive manner. Fresh fruits bunch samples from Tenera cultivar (7 to 20 years trees) were taken from Cimulang plantation, Bogor, Indonesia. Two statistical analysis methods were used: a forward stepwise multiple linear regression analysis and a multilayer-perceptron artificial neural network analysis. The best prediction of ripeness and oil content models were obtained using the latter method, while the best free fatty acid prediction model was developed by the first method. The models were then employed in the machine-vision inspection systems of the machine. The system best prediction accuracy of ripeness, oil content and free fatty acid models was 93.5, 96.41, and 89.32%, with standard error of prediction being 0.065, 0.044 and 0.068, respectively. The system was tested through a series of field tests, and successfully examined more than 12 t of fruits bunch per hour, without causing damage.

Antipsychotic induced metabolic changes & treatment response: A prospective study

BackgroundMetabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association. Methods100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2–4 weeks (n=71) and 8–12 weeks (n=39). ResultsSubjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2–4 weeks) increase in appetite and triglyceride levels (R2=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2–4 weeks) increase in triglyceride levels (R2=0.169; p=0.009). ConclusionsEarly appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade.

QSAR Guided Semi-synthesis and In-Vitro Validation of Anticancer Activity in Ursolic Acid Derivatives

As a part of our anticancer drug discovery programme, QSAR models were developed for the prediction of anticancer activities of ursolic acid derivatives against the human hepatocellular carcinoma HepG2, breast carcinoma MDA-MB-231 and the human ductal breast epithelial T47D cancer cell lines followed by wet lab semi-synthesis of virtually active derivatives, their in-vitro biological evaluation and apoptosis. The development of QSAR models was carried out by forward stepwise multiple linear regression method using a leave-one-out approach. Virtually active derivatives were semi synthesized, spectroscopically characterized and then in-vitro tested against human cancer cell lines. Active derivatives were checked via DNA fragmentation assay. The results exhibited regression coefficients (r(2)) and the cross-validation regression coefficients (rCV(2)) for the human HepG2, MDA-MB-231 and T47D cancer cell lines as .95 and .90; .92 and .87; .89 and .83 respectively showing the prediction accuracy of the models against biological activities. Computational molecular modeling is a valid modern approach, widely used in the identification of potential drug leads. The most active virtual derivatives of UA were semi- synthesized and their in-vitro and ex-vivo evaluation showed similar results with the predicted one, validating our QSAR models. Out of several active derivatives, the three UA2, UA7 and UA10 were potentially active against the above human cancer cell lines. These findings may be of immense importance in the anticancer drug development of an inexpensive and widely available natural product, ursolic acid.

Estimation of forest structure and canopy fuel parameters from small-footprint full-waveform LiDAR data

Precise knowledge of fuel conditions is important for predicting fire hazards and simulating fire growth and intensity across the landscape. We present a methodology to retrieve and map forest canopy fuel and other forest structural parameters using small-footprint full-waveform airborne light detection and ranging (LiDAR) data. Full-waveform LiDAR sensors register the complete returned backscattered signal through time and can describe physical properties of the intercepted objects. This study was undertaken in a mixed forest dominated by Douglas-fir, occasionally mixed with other conifers, in north-west Oregon (United States). We extracted two sets of LiDAR metrics using pulse detection and waveform modelling and then constructed several predictive models using forward stepwise multiple linear regression. The resulting models explained ~80% of the variability for many of the canopy fuel and forest structure parameters: aboveground biomass (R2=0.84), quadratic mean diameter (R2=0.82), canopy height (R2=0.79), canopy base height (R2=0.78) and canopy fuel load (R2=0.79). The lowest performing models included basal area (R2=0.76), stand volume (R2=0.73), canopy bulk density (R2=0.67) and stand density index (R2=0.66). Our results indicate that full-waveform LiDAR systems show promise in systematically characterising the structure and canopy fuel loads of forests, which may enable accurate fire behaviour forecasting that in turn supports the development of prevention and planning policies.

Prognostic Factors for Visual Outcomes after Crosslinking for Keratoconus and Post-LASIK Ectasia

To determine the prognostic factors associated with better visual outcomes 1 year after corneal collagen crosslinking (CXL) for keratoconus and post-laser-assisted in situ keratomileusis (LASIK) ectasia. The study cohort comprised 75 eyes from 50 patients with keratoconus or post-LASIK ectasia who underwent CXL. The outcomes measured were visual response, change of corrected distance visual acuity (CDVA), and CDVA 1 year after CXL. The cohort was divided into groups based on the change in CDVA postoperatively. The visual responders were the patients with visual improvement of at least 1 line Snellen CDVA at 1 year postoperatively, and the visual nonresponders were the patients with a gain of less than 1 line, no change, or loss of Snellen lines CDVA at 1 year postoperatively. Univariate analysis was performed to determine the association between the preoperative parameters and visual response. Correlation analyses and forward stepwise regression analyses were performed to evaluate the effect of the preoperative factors on CDVA and the improvement of CDVA at 1 year. There was significant visual improvement from 0.257 ± 0.29 logMAR to 0.159 ± 0.208 logMAR (p<0.001; paired t test) at 1 year postoperatively with a mean change in CDVA of -0.098 ± 0.151 logMAR. The visual responders (46 cases, 61.3%) had poorer preoperative CDVA (p = 0.023), thinner minimal corneal thickness (p = 0.041), and thinner central corneal thickness (p = 0.012) compared to the visual nonresponders (29 cases, 38.7%). Forward stepwise multiple linear regression analysis indicated that the preoperative CDVA significantly affected both the postoperative change in CDVA (standardized β = 0.614; p<0.001) and the postoperative CDVA (standardized β = 0.893; p<0.001). Crosslinking for keratoconus and post-LASIK ectasia can lead to significant visual improvement 1 year after treatment. The preoperative CDVA was a significant prognostic factor for the visual outcome.

QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 &amp;#946;-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549

For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r(2)) and prediction accuracy (rCV(2)) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

BackgroundHealth-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction.MethodsParticipants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL.ResultsPhysical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001).ConclusionsThis study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts.Trial registrationAustralian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415.

Impact of Renal Function and Demographic/Anthropomorphic Variables on Peak Thyrotropin After Recombinant Human Thyrotropin Stimulation: A Stepwise Forward Multiple-Regression Analysis

When applying the recommended standard doses of recombinant human thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with differentiated thyroid cancer (DTC), the resulting peak TSH levels vary extensively. Previous studies applying multivariate statistics identified patient-inherent variables influencing the rhTSH/peak TSH relation. However, those results were inconclusive and partly conflicting. Notably, no independent role of renal function was substantiated, despite the fact that the kidneys are known to play a prominent role in TSH clearance from blood. Therefore, the study's aim was to investigate the impact of renal function on the peak TSH concentration after the standard administration of rhTSH used in the management of thyroid cancer. The second objective was to calculate a ranking regarding the effect sizes of the selected variables on the peak TSH. There were 286 patients with DTC included in the study. Univariate and multivariate analyses were performed, testing the correlation of serum creatinine and glomerular filtration rate (GFR) as surrogate parameters of renal function, age, sex, weight, height, and body surface area (BSA) with the peak TSH level. In six additional patients, the subsequent TSH pharmacokinetics after the TSH peak were measured and qualitatively compared. By univariate analyses, TSH correlated negatively with BSA, GFR, weight, and height, and positively with age, female sex, and serum creatinine (p<0.001). On the multivariate analysis, the stepwise forward multiple linear regression revealed BSA and renal function as the two most influential independent variables, followed by age, sex, and height. The pharmacokinetic datasets indicated that these identified parameters also influence the TSH decline over time. Identifying those patients with a favorable combination of parameters predicting a high-peak TSH is the first step toward an individualization of rhTSH dosing. Additionally, the subsequent TSH decrease over time needs to be taken into account. A complete understanding of the interrelation of the identified key parameters and both the TSH peak and subsequent TSH pharmacokinetics might allow for a more personalized rhTSH dosage strategy to achieve sufficient TSH levels instead of the fixed dosing procedure used at present.

Plasma thrombin-antithrombin complex, prothrombin fragments 1 and 2, and D-dimer levels are elevated after endovascular but not open repair of infrarenal abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is associated with hypercoagulability, evidenced by increased markers of coagulation activation, including thrombin-antithrombin complex (TAT), prothrombin fragments 1 and 2 (F1+2), and D-dimer. Our aim was to compare the effect of endovascular aneurysm repair (EVAR) and open aneurysm repair (OAR) on changes in coagulation activation markers after intervention. Consecutive patients with AAAs reaching their intervention threshold in a tertiary vascular referral unit in the United Kingdom were invited to participate. The coagulation markers TAT, F1+2, and D-dimer were measured in venous blood collected at baseline and at 5 months after intervention. A forward stepwise multiple linear regression model was used to identify whether treatment by OAR or EVAR had an effect on changes in coagulation factors, independent of significant covariates. The study included 47 patients (14 EVAR, 33 OAR; 85% men) who were a median age of 76 years (range, 69.5-80 years). Aortic diameter at intervention was 5.9 cm (range, 5.5-6.8 cm). There were no significant differences in clinical, anthropometric, or hematologic parameters between groups. At baseline, TAT (P= .13), F1+2 (P= .08), and D-dimer (P= .11) were similar in EVAR and OAR patients. Postintervention, there was a significant increase in TAT (3.0 [2.1-6.0] vs 7.2 [6.3-8.4] ng/mL; P= .03), F1+2 (242 [189-323] vs 392 [312-494] ng/mL; P= .003), and D-dimer (457 [336-615] vs 1197 [840-1509] ng/mL; P= .002) in the EVAR group. No significant changes were observed after intervention in the OAR group. AAA-related hypercoagulability persists after intervention, with increased TAT, F1+2, and D-dimer levels after EVAR. These findings suggest a potential period of increased cardiovascular risk in the postoperative period after EVAR.

1336 – Early metabolic side effects as predictors of antipsychotic treatment response: a 2-month prospective study

Metabolic side-effects of antipsychotics increase morbidity and non-compliance rates. Interestingly, preliminary evidence suggests that metabolic side-effects correlate with response to antipsychotic treatment. Few studies have examined the nature of this association in a prospective study design. We conducted an exploratory, naturalistic, prospective, trans- diagnostic study to examine this association. To study the relation between metabolic side-effects and clinical improvement with antipsychotics, in psychotic illnesses [non-affective psychoses and mania-1st episode]. 100 (84 drug-free for at least one month) patients with psychosis initiated on antipsychotic treatment alone (65% on risperidone) were assessed on Brief Psychiatric Rating Scale (BPRS), visual analogue scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and serum lipid and glucose profiles at baseline, 2-4 weeks (n = 71) and 8-12weeks (n = 39). Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4weeks) increase in appetite and triglyceride levels (R 2 = 0.257; p = 0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R 2 = 0.169; p = 0.009) alone. Early appetite and triglyceride changes predicted antipsychotic treatment response. Future research should (a) examine neural mechanisms that operate in both appetite regulation and antipsychotic action to further the understanding of psychosis and its treatment, and (b) identify early markers of treatment response

Corneal Collagen Cross-linking Demarcation Line Depth Assessed by Visante OCT After CXL for Keratoconus and Corneal Ectasia

To report the demarcation line depth after corneal collagen cross-linking (CXL) for keratoconus and postoperative LASIK ectasia with Visante (Carl Zeiss Meditec) optical coherence tomography (OCT) and investigate correlations between this depth and preoperative parameters and postoperative visual and keratometry outcomes. Retrospective interventional case series of 40 eyes with keratoconus or postoperative LASIK ectasia treated with riboflavin ultraviolet-A CXL. Ophthalmic evaluation included uncorrected distance visual acuity, corrected distance visual acuity (CDVA), corneal topography (Pentacam, Oculus Optikgeräte GmbH), and postoperative anterior segment OCT. Correlation analyses were performed. Statistical significance was indicated by P<.05. At 6 months postoperative, mean demarcation line depth was 281.4±53.3 μm. Thinner minimal corneal thickness (r=0.413, P=.008), older age (r=-0.490, P=.001), higher grading of ectasia (for both keratoconus and postoperative LASIK ectasia) (r=-0.332, P=.044), female sex (r=0.343, P=.030), postoperative LASIK ectasia (r=-0.420, P=.007), and longer duration of disease (r=-0.377, P=.023) were correlated with shallower demarcation line depth. Forward stepwise multiple linear regression analysis showed that among all preoperative factors, minimal corneal thickness (standardized β=0.473, P=.003) and age (standardized β=-0.317, P=.036) were significantly associated with demarcation line depth. The CXL demarcation line depth and change in CDVA (r=-0.16, P=.325) and change of the steepest keratometry at 6 months (r=0.084, P=.637) were not correlated. The Visante OCT can be used for assessing CXL demarcation line depth. The demarcation line depth may decrease with the severity of ectasia and age.

Pedotransfer functions to estimate soil bulk density for Northern Africa: Tunisia case

Countries should provide regularly national inventories of greenhouse gas emissions and sinks and, and for the agriculture and forestry sectors this comprise national estimates of soil organic carbon (C) stocks. Estimation of soil C stock requires soil bulk density (Db) values. However, direct measurement of Db is often lacking mainly for soils in arid and semi-arid conditions. Much effort has been made in finding alternative solution to predict Db, either improving in situ determinations, either improving estimation procedures based on other soil properties. Regression models or pedotransfer functions (PTFs) based on easily measured soil properties constitute an adequate tool to assess Db, since it needs a minimum data set of indicators. A forward stepwise multiple linear regression routine was used to predict Db from physico-chemical soil properties. In this study, a soil database was organised from published and unpublished data from Tunisia. The database consisted of 238 soil profiles corresponding to 707 soil horizons from Tunisia. A general regression model fitted with all the data showed that OC, Clay, coarse-Sand and pH were the principal contributors to Db prediction (R2 = 0.55, standard error of prediction = 0.14). Additional models based on different set of variables are also provided providing alternative solutions for different levels of soil information. Predictions of the models were often improved when the data were partitioned into groups by soil depth (0–40 and 40–100 cm) and soil orders. This study also showed that CaCO3 might be an important predictor for deeper soil horizon. The proposed PTFs for Tunisia might be useful for a larger range of soil from arid and sub arid regions.

Pharmacophore, QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity

In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient (r(2)) and the cross-validation regression coefficient (rCV(2)) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation (r(2) = 0.99 and rCV(2) = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values.

Evaluation of arrow release in highly skilled archers using an acoustic measurement system

During aiming, an archer holds the stretched bow while a small piece of metal - the clicker - presses the arrow lateral against the bow. At the end of the aiming phase, the archer pulls the arrow back until the clicker slips over the arrowhead and causes a click, and then the archer shoots. To investigate the precision of the timing of this motor program, an acoustic measurement system has been developed. The system is composed of a modular microphone (AKG C 480 B comb-ULS/61), and an external FireWire Audio Interface (Focusrite Saffire LE 24Bit / 96kHz). From the audio signal, the time of the clicker's fall, the release of the shot and the hit of the target can be detected. Seven elite archers (two males, five female) performed 30 shots (ten ends of three arrows without any time limit) at 18 m indoors. Means and coefficients of variation (CV) were calculated from average speed and clicker time, i.e. the time between the click and the release of the shot. Forward stepwise multiple linear regression analysis was done to determine mean scores. CV of the clicker time accounted for 66% of the variability in scoring. A “leave-one-out” cross validation procedure revealed consistent estimate of the model (all corrected R2 were in a range of 0.66 and 0.75 with p<0.03). It has been shown that a highly precise timing in arrow release in terms of small CVs of clicker time is important for high mean scoring.

Relationship between anthropometric parameters with vertical jump in male elite volleyball players due to game’s position

The objective of this study was to examine the association between physical and anthropometric profiles and vertical jump performance in elite volleyball players. Thirty-three elite male volleyball players (21±1 y, 76.9±5.2 kg, 186.5±5 cm) were studied. Several anthropometric measurements (body mass, stature, body mass index, lower limb length and sitting height) together with jumping height anaerobic power of counter movement jump with arm swing (CMJarm) were obtained from all subjects. Forward stepwise multiple linear regression analysis was performed to determine if any of the anthropometric parameters were predictive of CMJarm. Anaerobic power was significantly higher (P≤0.05) in the tallest players relative to their shorter counterparts. A significant relationship was observed between CMJarm and lower limb length (r2=0.69; P<0.001) and between the lower limb length and anaerobic power obtained with CMJarm (r2=0.57; P<0.01). While significantly correlated (P≤0.05) with CMJarm performance, stature, lower limb length/stature and sitting height/stature ratios were not significant (P>0.05) predictors of CMJarm performance. This study demonstrates that lower limb length is correlated with CMJarm in elite male volleyball players. The players with longer lower limbs have the better vertical jump performances and their anaerobic power is higher. These results could be of importance for trained athletes in sports relying on jumping performance, such as basketball, handball or volleyball. Thus, the measurement of anthropometric characteristics, such as stature and lower limb length may assist coaches in the early phases of talent identification in volleyball.

A QSPR Study of Association Constants of Macrocycles toward Sodium Cation

The association constant (logK) of 53 chelates of new macrocycles (hemispherands, cryptahemispherands, and bridged calix-4) with sodium cation is predicted by a statistically validated QSPR modeling approach. The applied multiple linear regression is based on a variety of theoretical molecular descriptor selected from 6 classes of Dragon software with a forward stepwise multiple linear regression as a feature selection technique. For external validation we applied self organizing maps (SOM) to split the original data set into training and test set. The best four-dimensional model is developed on a training set of 40 macrocycles. The external validation was performed on test set of 13 macrocycles. The QSPR model presented in this study showed good predictions with the leave one out cross validated variance (Q 2 loo-cv = 0.94) and the external-validated variance (Q 2 ext = 0.92). The applicability domain (AD) of the model is analysed by leverage method.

QSAR studies on Withanolide analogs for anticancer activity

AbstractWithanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian systems of medicine. Withanolides are basically steroidal lactones (highly oxygenated C-28 phytochemicals) and similar to ginsenosides activity. Some of the withanolides that have been reported possess immunomodulatory, and anticancer activities. In the present investigation, a quantitative structure activity relationship (QSAR) model based on forward stepwise multiple linear regression (MLR) has been developed against the MCF7, MCF7/BUS, and SK-Br-3 human solid tumor breast cancer cell lines. Relationship correlation coefficient (r2) and cross validation correlation coefficient (r2CV) of QSAR model were 0.77 and 0.73 for MCF7, 0.91 and 0.85 for MCF7/BUS, 0.93 and 0.90 for SK-Br-3 respectively. Developed QSAR model was also evaluated for prediction accuracy through internal, external and randomization validation methods. The QSAR study indicates that chemical descriptors viz., atom count (all atoms), connectivity index (order 2, standard), for MCF7, Connectivity Index (order 0, standard), Dipole Vector X (debye), Molar Refractivity, Shape Index (basic kappa, order 2) for SK-Br-3 and Atom Count (all atoms), Dielectric Energy (kcal/mole), Total Energy (Hartree), Heat of Formation (kcal/mole) for MCF7/BUS are correlate well with the breast cancer activity, Moreover, on the basis of screening for oral bioavailability, in silico ADME and toxicity risk assessment, we concluded that compounds W3, W4, W8 have markedly higher anticancer activity compared to control. These results can offer useful references for directing the molecular design of lead compound(s) based on withanolide or analogous template with improved activity.

Near-Infrared Spectroscopic Determination of Degradation in Vegetable Oils Used To Fry Various Foods

Near-infrared (NIR) spectroscopic methods for measuring degradation products, including total polar materials (TPMs) and free fatty acids (FFAs), in soy-based frying oil used for frying various foods have been successfully developed. Calibration models were developed using forward stepwise multiple linear regression (FSMLR) and partial least-squares (PLS) regression techniques and then tested with an independent set of validation samples. The results show that the quality of oil used for frying different foods can be measured with a single model. First-derivative treatments improved results for TPM measurement. In addition, PLS models gave better prediction results than FSMLR models. For PLS models, the best correlations (r) between the NIR-predicted data and the chemical method data for TPMs and FFAs in oils were 0.995 and 0.981, respectively. For FSMLR models, the best r values for TPMs and FFAs in oils were 0.993 and 0.963, respectively.

Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity

Immunomodulation refers to an alteration in the immune response due to the intrusion of foreign molecules into the body. In the present communication, QSAR and docking studies of gallic acid derivatives were performed in relation to their immunomodulatory activities. Screening through the use of a QSAR model suggested that the compounds G-4, G-7, G-9, G-10, G-12, and G-13 possess immunomodulatory activity. Activity was predicted using a statistical model developed by the forward stepwise multiple linear regression method. The correlation coefficient (r(2)) and the prediction accuracy (rCV(2)) of the QSAR model were 0.99 and 0.96, respectively. The QSAR study indicated that chemical descriptors-dipole moment, steric energy, amide group count, λ(max) (UV-visible) and molar refractivity-are well correlated with activity, while decreases in the dipole moment, steric energy, and molar refractivity were negatively correlated. A molecular docking study showed that the compounds had high binding affinities for the INFα-2, IL-6, and IL-4 receptors. Binding site residues formed H-bonds with the designed gallic acid derivatives G-3, G-4, G-5, G-6, G-7, and G-10. Moreover, based on screening for oral bioavailability, in silico ADME, and toxicity risk assessment, we concluded that compound G-7 exhibits marked immunomodulatory activity, comparable to levamisole.