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Nevin Manimala Statistics

NIR spectroscopy-CNN-enabled chemometrics for multianalyte monitoring in microbial fermentation

Biotechnol Bioeng. 2024 Feb 23. doi: 10.1002/bit.28681. Online ahead of print.

ABSTRACT

As the biopharmaceutical industry looks to implement Industry 4.0, the need for rapid and robust analytical characterization of analytes has become a pressing priority. Spectroscopic tools, like near-infrared (NIR) spectroscopy, are finding increasing use for real-time quantitative analysis. Yet detection of multiple low-concentration analytes in microbial and mammalian cell cultures remains an ongoing challenge, requiring the selection of carefully calibrated, resilient chemometrics for each analyte. The convolutional neural network (CNN) is a puissant tool for processing complex data and making it a potential approach for automatic multivariate spectral processing. This work proposes an inception module-based two-dimensional (2D) CNN approach (I-CNN) for calibrating multiple analytes using NIR spectral data. The I-CNN model, coupled with orthogonal partial least squares (PLS) preprocessing, converts the NIR spectral data into a 2D data matrix, after which the critical features are extracted, leading to model development for multiple analytes. Escherichia coli fermentation broth was taken as a case study, where calibration models were developed for 23 analytes, including 20 amino acids, glucose, lactose, and acetate. The I-CNN model result statistics depicted an average R2 values of prediction 0.90, external validation data set 0.86 and significantly lower root mean square error of prediction values ∼0.52 compared to conventional regression models like PLS. Preprocessing steps were applied to I-CNN models to evaluate any augmentation in prediction performance. Finally, the model reliability was assessed via real-time process monitoring and comparison with offline analytics. The proposed I-CNN method is systematic and novel in extracting distinctive spectral features from a multianalyte bioprocess data set and could be adapted to other complex cell culture systems requiring rapid quantification using spectroscopy.

PMID:38390805 | DOI:10.1002/bit.28681

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Nevin Manimala Statistics

Distinguishing Clinical from Statistical Significances in Contemporary Comparative Effectiveness Research

Ann Surg. 2024 Feb 23. doi: 10.1097/SLA.0000000000006250. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER).

BACKGROUND: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase healthcare costs and treatment toxicity.

METHODS: CER studies from 2022 issues of Annals of Surgery, Journal of the American Medical Association, Journal of Clinical Oncology, Journal of Surgical Research, and Journal of the American College of Surgeons were systematically reviewed by two different investigators. The primary outcome of interest was whether authors specified what they considered to be a clinically significant difference in the Methods.

RESULTS: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size (r=-0.30, P=0.038).

CONCLUSION: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical-decision making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards.

PMID:38390761 | DOI:10.1097/SLA.0000000000006250

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Oxidative stress, microparticles, and E-selectin do not depend on HIV suppression

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024 Feb 23. doi: 10.5507/bp.2024.002. Online ahead of print.

ABSTRACT

BACKGROUND: Oxidative stress and inflammation are considered predictors of diseases associated with aging. Markers of oxidative stress, inflammation, and endothelial activation were investigated in people with HIV on antiretroviral treatment to determine whether they had an immunosenescent phenotype that might predispose to the development of premature age-related diseases.

PATIENTS AND METHODS: This study was conducted on 213 subjects with HIV. The control groups consisted of healthy HIV-negative adults. The level of oxidative stress was measured by assessing the production of malondialdehyde levels, which were detected by thiobarbituric acid reactive substance (TBARS) assay. The level of microparticles indicated the presence of inflammation and endothelial activation was measured by E-selectin levels. Significant differences were determined by appropriate statistical tests, depending on the distribution of variables. Relationships between continuous variables were quantified using Spearman’s rank correlation coefficient.

RESULTS: TBARS, and microparticle and E-selectin levels were significantly higher in untreated and treated subjects with HIV compared with HIV-negative controls (P<0.001). The levels of the investigated markers were not significantly different between untreated and treated patients and no significant correlation of these markers was found with CD4+ count, CD4+/CD8+ ratio, and the number of HIV-1 RNA copies.

CONCLUSIONS: Elevated markers of oxidative stress, inflammatory and endothelial activation were independent of the virologic and immunologic status of people with HIV. These results support the hypothesis that residual viremia in cellular reservoirs of various tissues is a key factor related to the premature aging of the immune system and predisposition to the premature development of diseases associated with aging.

PMID:38390755 | DOI:10.5507/bp.2024.002

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Multiomics Approach Reveals Serum Biomarker Candidates for Congenital Zika Syndrome

J Proteome Res. 2024 Feb 23. doi: 10.1021/acs.jproteome.3c00677. Online ahead of print.

ABSTRACT

The Zika virus (ZIKV) can be vertically transmitted, causing congenital Zika syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances of developing CZS. This syndrome involves several pathologies with a complex diagnosis. In this work, we aim to identify biological processes and molecular pathways related to CZS and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. We analyzed serum samples of healthy pregnant women and ZIKV-infected pregnant women bearing nonmicrocephalic and microcephalic fetuses. A total of 1090 proteins and 512 metabolites were identified by bottom-up proteomics and untargeted metabolomics, respectively. Univariate and multivariate statistical approaches were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as CZS signatures. Five proteins and four metabolites were selected as CZS biomarker candidates. Serum multiomics analysis led us to propose nine putative biomarkers for CZS prognosis with high sensitivity and specificity.

PMID:38390744 | DOI:10.1021/acs.jproteome.3c00677

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Evaluation of the Relationship Between Mobile Phone Usage and miRNA-574-5p and miRNA-30C-5p Levels in Thyroid Cancer Patients

Mol Imaging Radionucl Ther. 2024 Feb 22;33(1):19-27. doi: 10.4274/mirt.galenos.2023.04880.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the relationship between mobile phone usage and miRNA-574-5p and miRNA-30C-5p levels in patients diagnosed with differentiated thyroid cancer (DTC).

METHODS: Fifty patients diagnosed with DTC and 50 healthy volunteers were included in the study. miRNA-574-5p and miRNA-30C-5p gene expression levels in the blood of all subjects were analyzed by real time-polymerase chain reaction, and a questionnaire including various questions was administered to both groups.

RESULTS: Although there was a 7.60-fold increase in miRNA-30C-5p gene expression levels in the patient group compared with the control group, it was not found to be statistically significant. Considering the miRNA-574-5p gene expression levels, although there was a 2.96-fold increase in the patient group compared with the control group, no significant relationship was found. In our study, 85% of our patients were using mobile phones with internet access, whereas 98% of our healthy volunteers were using mobile phones (p<0.05). While 53.5% of the patients had their mobile phones with them while they were sleeping, this rate was 83.7% in healthy volunteers (p<0.05). However, 93.9% of the healthy volunteers did not have a Wi-Fi device in their bedrooms, and this rate was 75% in the patient group (p<0.05).

CONCLUSION: Although miRNA-30C-5p and miRNA-574-5p gene expression levels were higher in patients than in healthy volunteers, the differences were not statistically significant. Although there was no significant difference in miRNA levels, we believe that due to the higher rate of Wi-Fi device presence in bedrooms in patients compared with healthy volunteers, the effects of electromagnetic radiation on the thyroid can be reduced by paying attention to this simple change.

PMID:38390734 | DOI:10.4274/mirt.galenos.2023.04880

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Role of 18F-FCH PET/CT in Detecting Recurrences of Prostate Cancer After Curative Treatments

Mol Imaging Radionucl Ther. 2024 Feb 22;33(1):1-10. doi: 10.4274/mirt.galenos.2023.26122.

ABSTRACT

OBJECTIVES: To evaluate the role of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) in prostate cancer (PC) patients with biochemical recurrence who were submitted to different curative treatments.

METHODS: Seventy-five patients with PC who underwent 18F-FCH PET/CT for biochemical recurrence were retrospectively analyzed to distinguish patients who were submitted only to prostatectomy (PR group), only to radiotherapy (RT) on prostate with curative intent (RT group), and to both (PR + RT group). Correlations between 18F-FCH PET/CT and outcome and between prostate-specific antigen (PSA) values and sites and the number of metastases were analyzed. The performance of 18F-FCH PET/CT in relation to the PSA value and of maximum standardized uptake value (SUVmax) value in relation to patient outcome were assessed by receiver operating characteristic (ROC) curves.

RESULTS: 18F-FCH PET/CT relapses mostly involved lymph nodes, bones, and prostate bed. K-cohen test showed moderate agreement with the outcome in the whole population and in the PR group, whereas in the RT group it was perfect and in PR + RT fair. A statistically significant difference in PSA values was observed in the presence of lymph node metastases and with multiple metastases. ROC curves showed PSA cut-off values of 1.96 ng/dL, 1.95, 1.81, and 2.96, respectively, in the whole population, PR, RT and PR + RT group. SUVmax cut-off values of 3.75, 3.45, and 4.7 were described in the whole population, PR group, and PR + RT group.

CONCLUSION: The study confirms that 18F-FCH PET/CT is still valid in PC patients with suspected biochemical recurrence. Therefore, we can affirm that it still makes sense to perform it both with high PSA values and with lower values when prostate-specific membrane antigen tracers are not available.

PMID:38390705 | DOI:10.4274/mirt.galenos.2023.26122

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A study on immunohistochemical expression of HER2/Neu and p63 and its association with grade and invasiveness in case of bladder carcinoma

Urologia. 2024 Feb 23:3915603241229764. doi: 10.1177/03915603241229764. Online ahead of print.

ABSTRACT

INTRODUCTION: Bladder cancer is a global disease, ranks as the fourth most prevalent cancer. The incidence and prevalence increase with age. Grade and aggressiveness have been found to be related with different genetic expression and mutation.

AIMS: To evaluate any relation of grade and invasiveness of urothelial cancer with varied expression of immune histochemical marker p63 and her2/neu.

MATERIALS AND METHODS: The present study was a hospital based prospective cross-sectional study. This Study was conducted from July 2021 to April 2023 in the Urology department of a tertiary care hospital. Total 90 patients undergoing trans urethral resection of bladder tumour (TURBT) were included in this study.

RESULT: It was found that, patients who had decreased p63 expression had high grade in tumours (93.1%) compared to patients who were expressing normal p63 (32.8%) and this was statistically significant (p < 0.0001). Tumours with decreased p63 also appeared to be more invasive, 62.1% were found to be muscle invasive. Tumours with her2 neu expression found to be more aggressive in nature, 85.7% had high grade features and 53.6% were muscle invasive.

CONCLUSION: Our findings suggest that immunohistochemical expression of HER2/neu positive and decreased p63 expression were associated with high grade and invasiveness in case of bladder carcinoma.

PMID:38390685 | DOI:10.1177/03915603241229764

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Synthesis and antifungal properties of triazole Schiff base agent based on 3D-QSAR model

Chem Biodivers. 2024 Feb 23:e202302064. doi: 10.1002/cbdv.202302064. Online ahead of print.

ABSTRACT

Based on our previous research, a 3D-QSAR model (q2=0.51, ONC=5, r2=0.982, F=271.887, SEE=0.052) was established to predict the inhibitory effects of triazole Schiff base compounds on Fusarium graminearum, and its predictive ability was also confirmed through the statistical parameters. According to the results of the model design, 30 compounds with superior bioactivity compared to the template molecule 4 were obtained. Seven of these compounds (DES2-6, DES9-10) with improved biological activity and readily available raw materials were successfully synthesized. Their structures were confirmed through HRMS, NMR, and single crystal X-ray diffraction analysis (DES-5). The bioactivity of the final products was investigated through an in vitro antifungal assay. There was little difference in the EC50 values between the experimental and predicted values of the model, demonstrating the reliability of the model. Especially, DES-3 (EC50=9.915 mg/L) and DES-5 (EC50=9.384 mg/L) exhibited better inhibitory effects on Fusarium graminearum compared to the standard drug (SD) triadimenol (EC50=10.820 mg/L). These compounds could serve as potential new fungicides for future research. The interaction between the final products and isocitrate lyase (ICL) was investigated through molecular docking. Compounds with R groups that have a higher electron-donating capacity were found to be biologically active.

PMID:38390665 | DOI:10.1002/cbdv.202302064

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The psychopathology among the offspring of schizophrenia and bipolar I disorder patients in an Egyptian sample: A comparative study

Int J Soc Psychiatry. 2024 Feb 23:207640231216354. doi: 10.1177/00207640231216354. Online ahead of print.

ABSTRACT

BACKGROUND: A variety of psychiatric illnesses can develop in children of parents who suffer from bipolar affective disorder.

AIMS: The purpose of the research was to investigate, among the offsprings of patients diagnosed with schizophrenia and bipolar disorder type I, the prevalence of a variety of psychiatric diseases as well as a range of behavioral abnormalities.

METHOD: This was a cross-sectional observational comparative study. The outpatient psychiatric clinics at Shebin Elkom Mental Health Hospital, Menofia Governorate, Egypt 500 offspring (there were 250 offspring of parents both diagnosed with schizophrenia and 250 offsprings born to parents with bipolar affective disorder).

RESULTS: Statistically significant association of male gender with somatic complaints, social problems, and attention problems in the bipolar offspring group. In addition, there was a statistically significant association between female gender and anxiety or depression in the bipolar offspring group. Moreover, there was a statistically significant association between male gender and thought problems and aggressive behavior in the schizophrenia group. Assessment of psychiatric symptoms using K-SADS in relation to gender revealed a statistically significant association of male gender with affective disorder, behavioral disorder, and substance use disorder in the bipolar offspring group. Moreover, there was a statistically significant association between female gender and psychotic disorder in the schizophrenia group.

CONCLUSION: We concluded that offspring with bipolar illness had a significant association with somatic symptoms, anxiety/depressive disorder, social issues, attention problems, and aggressive behavior. Schizophrenia offspring were strongly related to thought issues.

PMID:38390657 | DOI:10.1177/00207640231216354

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Undernutrition among exclusive breastfeeding mothers and its associated factors in Southwest Ethiopia: A community-based study

Womens Health (Lond). 2024 Jan-Dec;20:17455057241231478. doi: 10.1177/17455057241231478.

ABSTRACT

BACKGROUND: An exclusive breastfeeding period is a time when the infant’s feeding depends on only breast milk. Inadequate maternal nutrition during this period could lead to insufficient infant feeding, which can further lead to childhood undernutrition and developmental restrictions. Evidently, the burden of maternal undernutrition was higher in resource-limited countries, including Ethiopia.

OBJECTIVES: This study aimed to assess the proportion of undernutrition among exclusive breastfeeding mothers and its associated factors in Southwest Ethiopia.

DESIGN: The study used a community-based cross-sectional design.

METHODS: The study was conducted among 442 nursing mothers from 10 to 30 June 2022. The participants were selected using multistage sampling techniques. An interviewer-administered structured questionnaire was used to collect information. Statistical software EpiData version 3.1 and SPSS version 20 were used for data entry and analysis, respectively. The factors associated with undernutrition were identified using a binary logistic regression analysis. In the bivariable analysis, a p-value of less than 0.25 was used to include the variable in the multivariable analysis, whereas p-value less than 0.05 was an odds ratio used to declare an independent association at a 95% confidence interval.

RESULTS: The proportion of undernutrition among the participants was found to be 24.8% in the study area. Poor intake of extra meals (adjusted odds ratio = 2.104; 95% confidence interval: 1.208, 3.664), poor dietary diversity habits (adjusted odds ratio = 3.605; 95% confidence interval: 2.112, 6.153), a lack of nutrition information (adjusted odds ratio = 1.853; 95% confidence interval: 1.070, 3.212), and household food insecurity (adjusted odds ratio = 4.424; 95% confidence interval: 2.639, 7.417) were identified as factors enhancing undernutrition among exclusive breastfeeding mothers in the area.

CONCLUSION: A quarter of exclusive breastfeeding mothers were undernourished in the area. Poor dietary diversity habits, poor intake of extra meals, a lack of nutrition information, and household food insecurity were found to be the factors determining undernutrition. Hence, it is important to reinforce nutrition intervention programs, including maternal nutrition education and counseling.

PMID:38390653 | DOI:10.1177/17455057241231478