Nevin Manimala

Biomed Phys Eng Express. 2021 Jul 27. doi: 10.1088/2057-1976/ac182e. Online ahead of print.

ABSTRACT

Insulin signaling pathways in muscle tissue play a major role in maintaining glucose homeostasis. Dysregulation in these pathways results in the onset of serious metabolic disorders like type 2 diabetes. Robustness is an essential characteristic of insulin signaling pathways that ensures reliable signal transduction in the presence of perturbations as a result of several feedback mechanisms. Integral control, according to control engineering, provides reliable setpoint tracking and disturbance rejection. The presence of negative feedback and integrating process is crucial for biological processes to achieve integral control. The existence of an integral controller leads to the rejection of perturbations which resulted in the robust regulation of biochemical entities within acceptable levels. In the present in silico research work, the presence of integral control in the protein kinase C ζ – insulin receptor substrate-1 (PKC ζ-IRS1) pathway is identified, verified mathematically and model is simulated in Cell Designer. The data is exported to Minitab software and robustness analysis is carried out statistically using the Mann-Whitney test. The p-value of the results obtained with given parameters perturbed by ±1% is greater than the significance level of 0.05 (0.2132 for 1% error in k7(rate constant of IRS1 phosphorylation), 0.2096 for -1% error in k7, 0.9037 for both ±1% error in insulin and 0.9037 for ±1% error in k1(association rate constant of the first molecule of insulin to bind the insulin receptor), indicated that our hypothesis is proved The results satisfactorily indicate that even when perturbations are present, glucose homeostasis in muscle tissue is robust due to the presence of integral regulation in the PKC ζ-IRS1 insulin signaling pathways. In this paper, we have analysed the findings from the framework of robust control theory, which has allowed us to examine that how PKC ζ-IRS1 insulin signaling pathways produces desired output in presence of perturbations.

PMID:34315137 | DOI:10.1088/2057-1976/ac182e

Phys Med Biol. 2021 Jul 27. doi: 10.1088/1361-6560/ac1834. Online ahead of print.

ABSTRACT

Cardiac radioablation offers non-invasive treatments for refractory arrhythmias. However, treatment delivery for this technique remains challenging. In this paper, we introduce the first method for real-time image guidance during cardiac radioablation for refractory atrial fibrillation on a standard linear accelerator. Our proposed method utilizes direct diaphragm tracking on intrafraction images to estimate the respiratory component of cardiac substructure motion. We compare this method to treatment scenarios without real-time image guidance using the 4D-XCAT digital phantom. Pre-treatment and intrafraction imaging was simulated for 8 phantoms with unique anatomies programmed using cardiorespiratory motion from healthy volunteers. As every voxel in the 4D-XCAT phantom is labelled precisely according to the corresponding anatomical structure, this provided ground-truth for quantitative evaluation. Tracking performance was compared to the ground-truth for simulations with and without real-time image guidance using the left atrium as an exemplar target. Differences in target volume size, mean volumetric coverage, minimum volumetric coverage and geometric error were recorded for each simulation. We observed that differences in target volume size were statistically significant (p < 0.001) across treatment scenarios and that real-time image guidance enabled reductions in target volume size ranging from 11 – 24%. Differences in mean and minimum volumetric coverage were statistically insignificant (both p = 0.35) while differences in geometric error were statistically significant (p = 0.039). The results of this study provide proof-of-concept for x-ray based real-time image guidance during cardiac radioablation.

PMID:34315136 | DOI:10.1088/1361-6560/ac1834

J Affect Disord. 2021 Jul 18;294:382-390. doi: 10.1016/j.jad.2021.07.020. Online ahead of print.

ABSTRACT

BACKGROUND: This study examined the global association between the Traditional Japanese Diet Score and suicide rate.

METHODS: Average food supply and energy supply by country were obtained from the Food and Agriculture Organization of the United Nations Statistics Division database (FAOSTAT). Traditional Japanese Diet Score (TJDS) was calculated from food group classifications. Age-standardized suicide rates per 100,000 people by country were obtained from the Global Burden of Disease 2017 database. The 26-year associations between TJDS and suicide rates were examined controlling for covariates using a mixed-effects model in 138 countries with populations of 1 million or greater.

RESULTS: A significant negative association was found in the analysis of the relationship between TJDS and the prevalence of suicide [β (se) = -0.126 (0.031), p < 0.001]. The interaction term between TJDS and year was also significant [β (se) = -0.011 (0.003), p < 0.001]. The change in the effect of TJDS on suicide rates by year was examined. The effect of TJDS was not significant from 1991 to 1999 but became significant after 2000; the slope of the TJDS to suicide rate in 2017 was -0.270 (95% confidence interval -0.382, -0.169, p < 0.001).

LIMITATIONS: This was a national ecological study and did not consider individual differences in sex, age, and lifestyle.

CONCLUSIONS: TJDS may be is a protective factor for depression, which may prevent suicide. The association between TJDS and suicide rates became stronger over time and was inversely associated with suicide rates after 2000.

PMID:34315100 | DOI:10.1016/j.jad.2021.07.020

Eur J Radiol. 2021 Jul 22;142:109867. doi: 10.1016/j.ejrad.2021.109867. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to compare the diagnostic performance of PET/CT imaging performed with ⁶⁸Ga-DOTA-FAPI and ¹⁸FDG in detection of liver metastases in patients with gastrointestinal system (GIS) cancer.

METHODS: A total of 31 patients who underwent ⁶⁸Ga-DOTA-FAPI and ¹⁸F-FDG PET/CT examinations and diagnosed with GIS cancer (15 colorectal, 9 pancreas, 4 stomach and 3 other cancers) were included in the study. The presence of liver metastasis was decided based on histopathologic diagnosis, PET/CT, other radiologic examinations or tumor biomarker findings, and both PET/CT imaging findings were compared on the patient and lesion basis.

RESULTS: Of the 31 patients, 28 were found as true positive with ⁶⁸Ga-DOTA-FAPI-PET/CT and 17 with ¹⁸FDG-PET/CT. Of the 98 metastatic liver lesions determined according to our diagnostic criteria, 92 were found as true positive lesions with ⁶⁸Ga-DOTA-FAPI-PET/CT and 65 with ¹⁸FDG-PET/CT. There was a statistically significant difference between both imaging modalities in the patient and lesion based comparisons (p < 0.05). When semiquantitative values (SUVmax, mlr) obtained from the lesions were compared between the two imaging methods, mlr values showed statistically significant difference in all tumor subgroups (p < 0.05).

CONCLUSION: It was concluded that ⁶⁸Ga-DOTA-FAPI-PET/CT was superior over ¹⁸FDG-PET/CT in detection of liver metastases of GIS cancers and it can be a complementary method especially in negative cases with ¹⁸FDG-PET/CT.

PMID:34315086 | DOI:10.1016/j.ejrad.2021.109867

Chemosphere. 2021 Jul 8;286(Pt 1):131479. doi: 10.1016/j.chemosphere.2021.131479. Online ahead of print.

ABSTRACT

The present work investigates for the first time the presence and isolation of the thermophilic fungi from hydrothermal spring situated at the locality of Guelma, in the Northeast of Algeria. The production of the thermostable proteases and the optimization of culture conditions under agro-wastes solid-state fermentation to achieve optimal production capacity were explored. A statistical experimental approach consisting of two designs was used to determine the optimum culture conditions and to attain the greatest enzyme production. Besides, different agricultural wastes were initially evaluated as a substrate, whereby wheat bran was selected for enzyme production by the isolate under solid-state conditions. The isolate thermophilic fungi were identified as Mycothermus thermophilus by sequencing the ITS region of the rDNA (NCBI Accession No: MK770356.1). Among the various screened variables: the temperature, the inoculum size, and the moisture were proved to have the most significant effects on protease activity. Employing two-level fractional Plackett-Burman and a Box-Behnken designs statistical approach helped in identifying optimum values of screened factors and their interactions. The analysis showed up 6.17-fold improvement in the production of proteases (~1187.03 U/mL) was achieved under the optimal conditions of moisture content 47%, inoculum 5 × 10⁵ spores/g, and temperature at 42 °C. These significant findings highlight the importance of the statistical design in isolation of Mycothermus thermophilus species from a specific location as well as identifying the optimal culture conditions for maximum yield.

PMID:34315081 | DOI:10.1016/j.chemosphere.2021.131479

Chemosphere. 2021 Jul 23;286(Pt 1):131660. doi: 10.1016/j.chemosphere.2021.131660. Online ahead of print.

ABSTRACT

Biochar mediated pollutant removal is gaining attention because of high efficiency of the process. However, effective recycling avenues of the pollutant-saturated biochars are scarce in the knowledge base; while such materials can be a new source of long-range contamination. Therefore, potential of vermitechnology for eco-friendly recycling of pollutant-loaded biochar was assessed by using arsenic-saturated native (NBC) and exfoliated (EBC) biochars as feedstocks for the first time. Interestingly, the bioavailable arsenic fractions (water soluble and exchangeable) considerably reduced by 22-44 % with concurrent increment (~8-15 %) of the recalcitrant (residual and organic bound) fractions in the biochar-based feedstocks. Consequently, ~2-3 folds removal of the total arsenic was achieved through vermicomposting. The earthworm population growth (2.5-3 folds) was also highly satisfactory in the biochar-based feedstocks. The results clearly imply that Eisenia fetida could compensate the arsenic-induced stress to microbial population and greatly augmented microbial biomass, respiration and enzyme activity by 3-12 folds. Moreover, biochar-induced alkalinity was significantly neutralized in the vermibeds, which remarkably balanced the TOC level and nutrient (N, P, and K) availability particularly in EBC + CD vermibeds. Overall, the nutrient recovery potential and arsenic removal efficiency of vermitechnology was clearly exhibited in NBC/EBC + CD (12.5:87.5) feedstocks. Hence, it is abundantly clear that vermitechnology can be a suitable option for eco-friendly recycling of pollutant-saturated sorbing agents, like biochars.

PMID:34315078 | DOI:10.1016/j.chemosphere.2021.131660

Clin Neurophysiol. 2021 Jul 3;132(9):2232-2239. doi: 10.1016/j.clinph.2021.06.012. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore relationship between EEG theta activity and clinical data that imply the degree of genetic determination of epilepsy.

METHODS: Clinical data of interest were epilepsy diagnosis and positive / negative family history of epilepsy. Study groups were: idiopathic generalized epilepsy (IGE), focal epilepsy (FE); FE of unknown etiology (FEUNK), FE of postnatal-acquired etiology (FEPA); all patients with positive / negative family history of epilepsy (FAPALL, FANALL, respectively), disregarding of the syndrome; FAP patients with 1st degree affected relative (FAP1) and those with 2nd degree epileptic relative only (FAP2). Quantitative EEG analysis assessed amount of theta (3.5-7.0 Hz) activity in 180 seconds of artifact-free waking EEG background activity for each patient and group. Group comparison was carried out by nonparametric statistics.

RESULTS: Differences of theta activity were: FAPALL > FANALL (p = 0.01); FAP1 > FAP2 (p = 0.2752). IGE > FE (p = 0.02); FEUNK > FEPA (p = 0.07).

CONCLUSIONS: This was the first attempt to explore and quantitatively ascertain relationship between an EEG variable and clinical data that imply greater or lesser degree of genetic determination in epilepsy.

SIGNIFICANCE: Theta activity is endophenotype that bridges the gap between epilepsy susceptibility genes and clinical phenotypes. Amount of theta activity is indicative of degree of genetic determination of the epilepsies.

PMID:34315064 | DOI:10.1016/j.clinph.2021.06.012

Forensic Sci Int Genet. 2021 Jul 17;54:102564. doi: 10.1016/j.fsigen.2021.102564. Online ahead of print.

ABSTRACT

This study examines the potential of hair shaft proteomic analysis to delineate genetic relatedness. Proteomic profiling and amino acid sequence analysis provide information for quantitative and statistically-based analysis of individualization and sample similarity. Protein expression levels are a function of cell-specific transcriptional and translational programs. These programs are greatly influenced by an individual’s genetic background, and are therefore influenced by familial relatedness as well as ancestry and genetic disease. Proteomic profiles should therefore be more similar among related individuals than unrelated individuals. Likewise, profiles of genetically variant peptides that contain single amino acid polymorphisms, the result of non-synonymous SNP alleles, should behave similarly. The proteomically-inferred SNP alleles should also provide a basis for calculation of combined paternity and sibship indices. We test these hypotheses using matching proteomic and genetic datasets from a family of two adults and four siblings, one of which has a genetic condition that perturbs hair structure and properties. We demonstrate that related individuals, compared to those who are unrelated, have more similar proteomic profiles, profiles of genetically variant peptides and higher combined paternity indices and combined sibship indices. This study builds on previous analyses of hair shaft protein profiling and genetically variant peptide profiles in different real-world scenarios including different human hair shaft body locations and pigmentation status. It also validates the inclusion of proteomic information with other biomolecular substrates in forensic hair shaft analysis, including mitochondrial and nuclear DNA.

PMID:34315035 | DOI:10.1016/j.fsigen.2021.102564

J Neurol Sci. 2021 Jul 21;428:117584. doi: 10.1016/j.jns.2021.117584. Online ahead of print.

ABSTRACT

The majority of radiology studies in neurodegenerative conditions infer group-level imaging traits from group comparisons. While this strategy is helpful to define phenotype-specific imaging signatures for academic use, the meaningful interpretation of single scans of individual subjects is more important in everyday clinical practice. Accordingly, we present a computational method to evaluate individual subject diffusion tensor data to highlight white matter integrity alterations. Fifty white matter tracts were quantitatively evaluated in 132 patients with amyotrophic lateral sclerosis (ALS) with respect to normative values from 100 healthy subjects. Fractional anisotropy and radial diffusivity alterations were assessed individually in each patient. The approach was validated against standard tract-based spatial statistics and further scrutinised by the assessment of 78 additional data sets with a blinded diagnosis. Our z-score-based approach readily detected white matter degeneration in individual ALS patients and helped to categorise single subjects with a ‘blinded diagnosis’ as likely ‘ALS’ or ‘control’. The group-level inferences from the z-score-based approach were analogous to the standard TBSS output maps. The benefit of the z-score-based strategy is that it enables the interpretation of single DTI datasets as well as the comparison of study groups. Outputs can be summarised either visually by highlighting the affected tracts, or, listing the affected tracts in a text file with reference to normative data, making it particularly useful for clinical applications. While individual diffusion data cannot be visually appraised, our approach provides a viable framework for single-subject imaging data interpretation.

PMID:34315000 | DOI:10.1016/j.jns.2021.117584

J Psychiatr Res. 2021 Jul 22;142:40-47. doi: 10.1016/j.jpsychires.2021.07.036. Online ahead of print.

ABSTRACT

Co-occurring posttraumatic stress disorder and alcohol use disorder (PTSD/AUD) is associated with poorer psychosocial functioning than either disorder alone; however, it is unclear if psychosocial functioning improves in treatment for PTSD/AUD. This study examined if psychosocial functioning improved in integrated treatments for PTSD/AUD, and if changes in PTSD severity and percentage heavy drinking days (PHDD) during treatment were associated with functioning outcomes. 119 veterans with PTSD/AUD randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure or Seeking Safety completed measures of functioning (Medical Outcomes Survey SF-36), PTSD (Clinician Administered PTSD Scale for DSM-5), and alcohol use (Timeline Follow-Back) at baseline, posttreatment, 3- and 6-month follow-ups. Our findings suggest that psychosocial functioning improved to a statistically significant degree with no significant differences between conditions. Reductions in PTSD severity during treatment were associated with psychosocial functioning improvements, whereas reductions in PHDD were associated with improvement in role impairment at posttreatment. Although psychosocial functioning improves to a statistically significant degree in interventions designed to treat PTSD/AUD, these improvements do not represent clinically meaningful improvements in patients’ abilities to navigate important roles. Findings underscore the need to study how to best treat psychosocial functioning impairment in PTSD/AUD.

PMID:34314993 | DOI:10.1016/j.jpsychires.2021.07.036