Category: Nevin Manimala

ACS Pharmacol Transl Sci. 2023 Feb 24;6(3):399-409. doi: 10.1021/acsptsci.2c00212. eCollection 2023 Mar 10.

ABSTRACT

Breast cancer is one of the major causes of death in women worldwide. It is a diverse illness with substantial intersubject heterogeneity, even among individuals with the same type of tumor, and customized therapy has become increasingly important in this sector. Because of the clinical and physical variability of different kinds of breast cancers, multiple staging and classification systems have been developed. As a result, these tumors exhibit a wide range of gene expression and prognostic indicators. To date, no comprehensive investigation of model training procedures on information from numerous cell line screenings has been conducted together with radiation data. We used human breast cancer cell lines and drug sensitivity information from Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases to scan for potential drugs using cell line data. The results are further validated through three machine learning approaches: Elastic Net, LASSO, and Ridge. Next, we selected top-ranked biomarkers based on their role in breast cancer and tested them further for their resistance to radiation using the data from the Cleveland database. We have identified six drugs named Palbociclib, Panobinostat, PD-0325901, PLX4720, Selumetinib, and Tanespimycin that significantly perform on breast cancer cell lines. Also, five biomarkers named TNFSF15, DCAF6, KDM6A, PHETA2, and IFNGR1 are sensitive to all six shortlisted drugs and show sensitivity to the radiations. The proposed biomarkers and drug sensitivity analysis are helpful in translational cancer studies and provide valuable insights for clinical trial design.

PMID:36926455 | PMC:PMC10012252 | DOI:10.1021/acsptsci.2c00212

Virus Evol. 2023 Mar 7;9(1):vead007. doi: 10.1093/ve/vead007. eCollection 2023.

ABSTRACT

Transmission trees can be established through detailed contact histories, statistical or phylogenetic inference, or a combination of methods. Each approach has its limitations, and the extent to which they succeed in revealing a ‘true’ transmission history remains unclear. In this study, we compared the transmission trees obtained through contact tracing investigations and various inference methods to identify the contribution and value of each approach. We studied eighty-six sequenced cases reported in Guinea between March and November 2015. Contact tracing investigations classified these cases into eight independent transmission chains. We inferred the transmission history from the genetic sequences of the cases (phylogenetic approach), their onset date (epidemiological approach), and a combination of both (combined approach). The inferred transmission trees were then compared to those from the contact tracing investigations. Inference methods using individual data sources (i.e. the phylogenetic analysis and the epidemiological approach) were insufficiently informative to accurately reconstruct the transmission trees and the direction of transmission. The combined approach was able to identify a reduced pool of infectors for each case and highlight likely connections among chains classified as independent by the contact tracing investigations. Overall, the transmissions identified by the contact tracing investigations agreed with the evolutionary history of the viral genomes, even though some cases appeared to be misclassified. Therefore, collecting genetic sequences during outbreak is key to supplement the information contained in contact tracing investigations. Although none of the methods we used could identify one unique infector per case, the combined approach highlighted the added value of mixing epidemiological and genetic information to reconstruct who infected whom.

PMID:36926449 | PMC:PMC10013732 | DOI:10.1093/ve/vead007

Adv Biomed Res. 2023 Jan 27;12:8. doi: 10.4103/abr.abr_353_21. eCollection 2023.

ABSTRACT

BACKGROUND: This study investigated the feasibility of channelized hoteling observer (CHO) model in computed tomography (CT) protocol optimization regarding the image quality and patient exposure. While the utility of using model observers such as to optimize the clinical protocol is evident, the pitfalls associated with the use of this method in practice require investigation.

MATERIALS AND METHODS: This study was performed using variable tube current and adaptive statistical iterative reconstruction (ASIR) level (ASIR 10% to ASIR 100%). Various criteria including noise, high-contrast spatial resolution, CHOs model were used to compare image quality at different captured levels. For the implementation of CHO, we first tuned the model in a restricted dataset and then it to the evaluation of a large dataset of images obtained with different reconstruction ASIR and filtered back projection (FBP) levels.

RESULTS: The results were promising in terms of CHO use for the stated purposes. Comparisons of the noise of reconstructed images with 30% ASIR and higher levels of noise in rebuilding images using the FBP approach showed a significant difference (P < 0.05). The spatial resolution obtained using various ASIR levels and tube currents were 0.8 pairs of lines per millimeter, which did not differ significantly from the FBP method (P > 0.05).

CONCLUSIONS: Based on the results, using 80% ASIR can reduce the radiation dose on lungs, abdomen, and pelvis CT scans while maintaining image quality. Furthermore using ASIR 60% only for the reconstruction of lungs, abdomen, and pelvis images at standard radiation dose leads to optimal image quality.

PMID:36926443 | PMC:PMC10012030 | DOI:10.4103/abr.abr_353_21

Adv Biomed Res. 2023 Jan 27;12:12. doi: 10.4103/abr.abr_295_21. eCollection 2023.

ABSTRACT

BACKGROUND: Despite recognizing the traditional coronary artery disease (CAD) risk factors, some secondary factors, such as opioid substance abuse, have to be considered. We aimed to assess the relationship between opioid consumption and emergency percutaneous coronary intervention (PCI) revascularization results, according to Thrombolysis in Myocardial Infarction (TIMI) flow and in-hospital survival outcomes in ST-elevation myocardial infarction (STEMI) patients.

MATERIALS AND METHODS: This case-control study was conducted on 186 patients (93 patients in each group) with acute STEMI, who were referred to Chamran Heart Center, Isfahan, Iran. Opioid addiction was diagnosed by patients’ records and confirmed by conducting an interview based on the Diagnostic and Statistical Manual of Mental Disorders, 4^th Edition (DSM-IV) criteria. Patients in both groups were evaluated and compared for angioplasty results based on the TIMI flow grade and in-hospital cardiovascular events and complications.

RESULTS: Ninety-one patients (97.84%) of each group were male, and opioid-addicted patients were younger than the non-opioid users (52.95 9.91 vs. 57.90 12.17, P = 0.003). Among the CAD risk factors, prevalence of dyslipidemia was significantly higher in non-opioid users, whereas cigarette smoking was higher in opioid-addicted patients (P < 0.050). There was no significant difference between the two groups regarding pre- and post-procedural myocardial infarction complications as well as mortality rate (P > 0.050). Also, there were no significant differences between the opioid and non-opioid users regarding TIMI flow grading, and successful PCI rate based on achieving TIMI III was 60.21% versus 59.1% in opiate-dependent and non-opioid users, respectively (P = 0.621).

CONCLUSION: Opioid addiction has no effects on post-PCI angiographic results and in-hospital survival outcomes in STEMI patients which undergoing emergency PCI.

PMID:36926439 | PMC:PMC10012017 | DOI:10.4103/abr.abr_295_21

Adv Biomed Res. 2023 Jan 27;12:10. doi: 10.4103/abr.abr_219_21. eCollection 2023.

ABSTRACT

BACKGROUND: Preeclampsia, a pregnancy-specific complication, has been associated with cytomegalovirus (CMV) infection in observational studies. CMV-specific T cell response plays a major role in viremia clearance. We explored whether CMV-specific cell-mediated immunity (CMI) status is associated with preeclampsia in pregnant women.

MATERIALS AND METHODS: CMV-specific CMI was assessed using CMV-QuantiFERON (QF-CMV) assay in plasma serum of 35 women with preeclampsia as well as 35 normal pregnant controls, retrospectively. Participants were matched for gestational age in a 1:1 ratio. The proportion of reactive results, the mean value of interferon-gamma (IFN-γ) level produced in mitogen and antigen tubes were compared between the cases and controls through Chi-square and Wilcoxon rank-sum tests, respectively. The odds ratio and confidence interval were calculated as well.

RESULTS: No significant differences observed between demographic characteristics of the case and control groups. The QF-CMV assay turned reactive (QF-CMV [ + ]) Women with preeclampsia had lower mean IFN-γ levels in antigen tube compared with normal pregnant controls. There were no statistically significant differences in the value of mitogen tube between case and controls women with suppressed CMV-CMI were 6.3 times more likely to have preeclampsia. This result even strengthened after adjustment for age, gestational age, and gravidity.

CONCLUSIONS: Our findings support an association between suppressed CMV-specific CMI and preeclampsia.

PMID:36926438 | PMC:PMC10012023 | DOI:10.4103/abr.abr_219_21

Adv Biomed Res. 2023 Jan 27;12:16. doi: 10.4103/abr.abr_88_21. eCollection 2023.

ABSTRACT

BACKGROUND: Psoriasis (PSO) is a common chronic autoimmune skin disease with a significant psycho-socio-economic burden. Some antidepressants (ADs) such as fluoxetine and bupropion can induce or exacerbate PSO. This study aimed to investigate the correlation between ADs history before PSO onset, and the risk of PSO induction, in Isfahan province, Iran.

MATERIALS AND METHODS: In this case-control study, 80 patients with PSO were selected by non-probability sampling method, and 80 healthy individuals were selected using simple random sampling. They were interviewed and medical information was recorded. Chi-square, Mann-Whitney, and Kruskal-Wallis tests for dichotomous or categorical data, and independent-sample t test for continuous data were used. Statistical significance was taken as P ≤ 0.05.

RESULTS: In this case-control study, a total of 160 individuals, 80 participants in each group, were included. The mean age of the total samples was 44.8 ± 16 years. Forty-three percent of the individuals were women. PSO familial history in the cases was significantly higher than the control group (OR = 11.94, P = 0.001). It was revealed that use of ADs by patients before PSO induction, was greater than the controls (OR = 2.78, P = 0.058).

CONCLUSIONS: Past history of ADs in the cases before PSO onset, was higher than the controls, indicating a possible association between ADs and the risk of PSO induction. This study can be effective to pay more attention to the possible complications of ADs and PSO risk factors. Accurate knowledge of PSO risk factors will be useful for better management and morbidity reduction.

PMID:36926437 | PMC:PMC10012025 | DOI:10.4103/abr.abr_88_21

Adv Biomed Res. 2023 Jan 27;12:11. doi: 10.4103/abr.abr_292_21. eCollection 2023.

ABSTRACT

BACKGROUND: Magnesium oxide may be effective in renal insufficiency prevention after carboplatin therapy. We have evaluated magnesium oxide impression on the serum creatinine (Cr) and blood urea nitrogen (BUN) levels plus glomerular filtration rate (GFR) in cancerous children.

MATERIALS AND METHODS: A group of children with different cancers (n = 18) was treated with 250 mg/day magnesium oxide supplementation (MOS) and compared with a matched placebo-treated group (n = 18). After 2 weeks, carboplatin chemotherapy started. We compared serum Cr, BUN, and GFR values before and 3 and 7 days post intervention.

RESULTS: Serum Cr and BUN were increased significantly 3 and 7 days after intervention in both the groups. Serum Cr and BUN were not statistically different between the MOS and placebo groups before the intervention and 3 or 7 days after carboplatin administration (P > 0.05). Three days after the intervention, the GFR reduced from 101.38 ± 14.67 to 90.11 ± 10.52 mL/min/1.73 m² in the MOS group. Furthermore, in the placebo group, 3 days after the intervention, the GFR was reduced from 97.5 ± 9.71 to 92.33 ± 10.61 mL/min/1.73 m². Further, in the MOS group, after 7 days of the intervention, the GFR was reduced to 84.11 ± 12.47 mL/min/1.73 m². In the placebo group, after 7 days of the intervention, the GFR was diminished to 85.38 ± 10.66 mL/min/1.73 m² (P = 0.371).

CONCLUSION: The current study suggests that magnesium supplementation does not prevent carboplatin-induced nephrotoxicity in children with malignancies. Anyway, we propose magnesium oxide supplementation for this group of pediatrics because magnesium is an essential element for cell and tissue growth, maintenance, and metabolism.

PMID:36926429 | PMC:PMC10012022 | DOI:10.4103/abr.abr_292_21

Oral Surg Oral Med Oral Pathol Oral Radiol. 2023 Feb 1:S2212-4403(23)00010-X. doi: 10.1016/j.oooo.2023.01.010. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate and compare the immunohistochemical expression of connexin 43 (Cx43) in tooth germs (TGs), ameloblastic fibromas (AFs), ameloblastic fibro-odontomas (AFOs), and conventional ameloblastomas (AMs).

STUDY DESIGN: Nine TGs, 12 AFs, 12 AFOs, and 27 AMs were evaluated for Cx43 expression by immunohistochemistry.

RESULTS: Most of the TGs expressed Cx43 in the mesenchyme (77.6%) and in the late stages of odontogenesis. Cx43 was more highly expressed (P < .05) in the mesenchymal layer of all groups than in the epithelial layer except for the AFOs. When comparing the expression of Cx43 in the different layers of the analyzed groups, statistically significant differences were observed between AFO vs AM (*P = .0158) in the epithelial layer and between AF vs AFO (P** = .0046) in the mesenchymal layer.

CONCLUSIONS: The results obtained in this study showed that Cx43 is a protein with important expression in the mesenchymal layer of the embryonic and odontogenic tissues studied. It could be speculated that Cx43 participates in mineralization events based on the relationship of the expression of this protein between the epithelial and mesenchymal layers of odontogenic tissues.

PMID:36925450 | DOI:10.1016/j.oooo.2023.01.010

Vaccine. 2023 Mar 3:S0264-410X(23)00243-8. doi: 10.1016/j.vaccine.2023.02.081. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of the study is to understand the evolution of COVID-19 vaccine acceptance over the key 7-month vaccine campaign in Italy, a period in which the country moved from candidate vaccines to products administered to the public. The research focus points to evaluate COVID-19 vaccine attitudes in adults and their children, propension towards compulsory vaccination, past and present adherence to anti-flu and anti-pneumococcal vaccines, and the reasons for trust/mistrust of vaccines.

METHODS: Italian residents aged 16->65 years were invited to complete an online survey from September 2020 to April 2021. The survey contained 13 questions: 3 on demographic data; 8 on vaccine attitudes; and 2 open-ended questions about the reasons of vaccine confidence/refusal. A preliminary word frequency analysis has been conducted, as well as a statistical bivariate analysis.

RESULTS: Of 21.537 participants, the confidence of those in favor of the COVID-19 vaccine increases of 50 % and the number of people who wanted more information decreases by two-third. Willingness to vaccinate their children against COVID-19 also increased from 51 % to 66.5 %. Only one-third of the strong vaccine-hesitant participants, i.e. 10 %, remained hostile. Compulsory vaccination showed a large and increasing favor by participants up to 78 %, in a way similar to their propensity for children’s mandatory vaccination (70.6 %). Respondents’ past and present adherence to anti-flu and anti-pneumococcal vaccines does not predict their intentions to vaccinate against COVID-19. Finally, a semantic analysis of the reasons of acceptance/refusal of COVID-19 vaccination suggests a complex decision-making process revealed by the participants’ use of common words in pro-and-cons arguments.

CONCLUSION: The heterogeneity in the COVID-19 vaccine hesitancy, determinants and opinions detected at different ages, genders and pandemic phases suggests that health authorities should avoid one-size-fits-all vaccination campaigns. The results emphasize the long-term importance of reinforcing vaccine information, communication and education needs.

PMID:36925424 | DOI:10.1016/j.vaccine.2023.02.081

Vaccine. 2023 Mar 14:S0264-410X(23)00261-X. doi: 10.1016/j.vaccine.2023.03.014. Online ahead of print.

ABSTRACT

OBJECTIVE: Immune correlate analyses for vaccine trials have been applied to investigate associations of vaccine efficacy and surrogate markers such as vaccine-induced antibodies. However, the role of antibody as a surrogate marker in predicting the outcome can vary by time, and surrogate-outcome confounding may have resulted in bias even in randomized trials. We provide a framework for surrogate marker assessment to address the aforementioned issues.

STUDY DESIGN AND SETTING: We reanalyzed the vaccine randomized trial for influenza B. We conducted a mediation analysis that enables estimation of vaccine efficacy, mediation effects and proportion of mediation on disease probabilities at various follow-up times. We proposed instrumental variable (IV) analyses with randomized vaccination as an IV accounting for potential unmeasured confounding.

RESULTS: The mediation effect of vaccine efficacy by hemagglutination inhibition (HAI) titer was significantly protective at 181 days after vaccination: 63.2% [95% confidence interval, (CI) = (39.9%, 82.0%)], and HAI titer explained 61.1% [95% CI = (36.7%, 96.2%)] of the protective effect of vaccination.

CONCLUSIONS: Most of vaccine efficacy is mediated by HAI titer, particularly in children 10 years and older. Our contribution is to provide causal analytics for the role of surrogate marker with weaker assumptions regarding surrogate-disease causation.

PMID:36925423 | DOI:10.1016/j.vaccine.2023.03.014