Category: Nevin Manimala

Metabol Open. 2024 Oct 18;24:100325. doi: 10.1016/j.metop.2024.100325. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25 % of the global population, presenting a significant health challenge. It is often asymptomatic but linked to severe conditions like cirrhosis and liver cancer. Previous research indicates that people often underestimate MASLD risks. This study examines MASLD prevalence and awareness among medical students in an academic health care institute in India.

MATERIAL AND METHODS: This cross-sectional study at SRM Medical College Hospital, Chennai, involved 80 medical and paramedical students aged 18-25. Exclusion criteria included history of alcohol use, neurological disorders, thyroid issues, diabetes, and hypertension. After obtaining informed consent, anthropometric data and blood samples were collected. Biochemical parameters including fasting plasma glucose, triglycerides, HDL-C, and GGT were measured. The Fatty Liver Index (FLI) was used to assess liver steatosis, with an FLI ≥60 indicating NAFLD. Data were analysed using SPSS Version 22.0, with statistical significance set at p < 0.05.

RESULTS: Among 80 participants, the mean age and BMI were 20.2 ± 1.03 years and 23.16 ± 4.55 kg/m². The mean Fatty Liver Index (FLI) score was 15.11 ± 19.68. MASLD prevalence was 7.5 % (n = 6). Significant positive correlations were found between FLI and BMI, waist circumference, fasting plasma glucose, triglycerides, and GGT, while HDL-C showed a non-significant negative correlation. Most participants were aware of MASLD and its risk factors but showed varied adherence to preventive measures.

CONCLUSION: Health Sciences undergraduates had a 7.5 % MASLD prevalence, highlighting a gap in understanding and testing. Addressing this requires better guidelines, awareness, and healthcare system enhancements.

PMID:39507991 | PMC:PMC11539341 | DOI:10.1016/j.metop.2024.100325

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Sep 20;55(5):1316-1321. doi: 10.12182/20240960402.

ABSTRACT

OBJECTIVE: To establish a viable bacteria assay for Helicobacter pylori (H. pylori) by assessing the cgt gene expression, and to develop accordingly a rapid and novel testing method for clinical precision treatment.

METHODS: Viable bacteria count was determined in bacterial cultures. The transcriptional expression level of cgt (hp0421), the conserved gene that encodes cholesterol-α-glucosyltransferase (CGT) in H. pylori, was measured by RT-PCR. The correlation between the number of colonies and cgt gene transcription expression was analyzed and the regression model was constructed. The linear range, sensitivity, and specificity of the new method were examined accordingly. The bactericidal action of clarithromycin was assessed using this method to verify the performance of the method in determining clinical bacterial drug resistance.

RESULTS: The Ct values of cgt for H. pylori colony counts of 10², 10⁴, 10⁶, and 10⁸ CFU/mL were 29.67±0.14, 23.37±0.36, 17.65±0.37, and 11.38±0.39, respectively. In the range of 10¹-10⁸ CFU/mL, the regression equation for cgt gene expression and viable bacterial counts determined by RT-qPCR was y=-0.3501x+12.49, with the correlation coefficient being R ²=0.9992 and the sensitivity being 10¹ CFU/mL, showing no cross-reaction with 13 other bacteria. The lg values of live H. pylori bacteria treated with clarithromycin at 0, 5, 10, 20, and 40 μg/mL for 12 h were 2.57±0.02, 2.45±0.01, 2.19±0.02, 1.91±0.07, and 1.33±0.05, respectively. The corresponding cgt gene Ct values were 27.76±0.09, 28.37±0.24, 29.51±0.14, 30.11±0.12, and 31.66±0.11. By applying the cgt gene expression in the equation, the estimated counts of viable bacteria were found to be 2.73±0.03, 2.52±0.08, 2.11±0.05, 1.89±0.02, and 1.33±0.04, showing no significant difference in statistical analysis (P>0.05).

CONCLUSION: The method for assessing viable bacteria account by evaluating cgt gene expression in H. pylori was successfully established, significantly reducing the time required to determine viable bacteria count and providing a new method for clinical viable bacteria testing.

PMID:39507989 | PMC:PMC11536244 | DOI:10.12182/20240960402

Bone Marrow Transplant. 2024 Nov 6. doi: 10.1038/s41409-024-02447-4. Online ahead of print.

ABSTRACT

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR reporting site between 2013 and 2019. No statistically significant post-transplant differences were observed between those testing IDH1m positive (n = 53, 36%) and negative pre-transplant (overall survival (OS): p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

PMID:39506075 | DOI:10.1038/s41409-024-02447-4

Sci Rep. 2024 Nov 6;14(1):26957. doi: 10.1038/s41598-024-78358-7.

ABSTRACT

This study examined the effectiveness of various electrical stimulation methods in alleviating symptoms and enhancing the quality of life for women with urinary incontinence. We conducted a systematic search of PubMed, Cochrane Library, PEDro, EMBASE, and ClinicalTrials.gov from inception to August 2024. Randomized controlled trials (RCTs) that meet following criteria were included, urinary continence in women, using various electric stimulation treatments and evaluated outcomes related to symptoms, quality of life. Thirty RCTs were subjected to risk of bias assessment, certainty of evidence, and network meta-analysis. Statistical analysis was performed using a random-effects model, with continuous variables expressed as standardized mean difference (SMD) and 95% confidence interval (CI). Percutaneous tibial stimulation (SMD – 1.86, 95% CI – 2.77 to – 0.96) and intravaginal stimulation (SMD – 0.97, 95% CI – 1.55 to – 0.38) significantly reduced symptom severity. Additionally, percutaneous tibial, intravaginal, transcutaneous tibial, and trans-sacral stimulations improved quality of life. Percutaneous tibial stimulation was the most effective, followed by intravaginal stimulation. Despite moderate to low confidence in the evidence, large-scale RCTs are needed to evaluate long-term benefits of these treatment.

PMID:39506061 | DOI:10.1038/s41598-024-78358-7

Sci Rep. 2024 Nov 6;14(1):26926. doi: 10.1038/s41598-024-78442-y.

ABSTRACT

Acquired or de novo resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) is a major challenge to ovarian cancer treatment. Therefore, strategies to overcome PARPi resistance are critical to improve prognosis. The purpose of this study is to evaluate whether inhibition of ADAM17 sensitizes ovarian cancer to treatment with olaparib, a PARPi, thereby bypassing resistance mechanisms and improving treatment response. Thus, we analyzed the effect of olaparib in combination with the ADAM17 inhibitor GW280264X in ovarian cancer using a 2D monolayer and a 3D spheroid model followed by a multicontent readout (viability, caspase activation and cytotoxicity). To emphasize the translational aspect of our work, we performed corresponding experiments on primary cells derived from ovarian cancer patients initially screened for their mutation status of the breast cancer gene (BRCA 1/2). In 2D, we observed a significant reduction in cell viability and a subsequent increase in apoptosis of the combined treatment (olaparib + GW280264X) compared with olaparib mono-treatment. The combined treatment allows a substantial dose reduction of olaparib rendering a strong synergistic effect. Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response.

PMID:39506058 | DOI:10.1038/s41598-024-78442-y

Sci Rep. 2024 Nov 7;14(1):27026. doi: 10.1038/s41598-024-77914-5.

ABSTRACT

DNA methylation is a molecular process that mediates gene-environment interactions. Epigenome-wide association studies (EWAS) using the Illumina Human Methylation BeadChip are powerful tools for quantifying the relationship between DNA methylation and phenotypes. Recently, the Illumina Methylation EPICv2 BeadChip (EPICv2) was released, which includes new features, such as duplicated probes and changed probe names. Several published algorithms have been updated to address these features in EPICv2. However, appropriate EPICv2 preprocessing and integration with previous microarray versions remain complex. Therefore, MethylCallR, an open-source R package designed to provide standard procedures for performing EWAS using Illumina methylation microarrays including EPICv2, was developed. MethylCallR can be used to control duplicated probes in EPICv2, by using pre-set data implemented in MethylCallR or new customized data. MethylCallR includes a straightforward conversion function between different types of Illumina Human Methylation BeadChips. Using MethylCallR, potential outlier sample detection and statistical power estimation were conducted and used to select meaningful probes. Publicly available data was analyzed using MethylCallR and the findings were compared to that of a previous study.

PMID:39506033 | DOI:10.1038/s41598-024-77914-5

Sci Rep. 2024 Nov 6;14(1):26905. doi: 10.1038/s41598-024-78661-3.

ABSTRACT

Underreporting of adverse events in healthcare systems is a global concern. This study aims to address the underreporting of adverse events (AE) by implementing a TRIZ-based model to identify and overcome barriers to reporting, thus filling gaps in current reporting practices and improving incident recognition. A TRIZ (Theory of Inventive Problem Solving) approach was adopted, integrating with SERVQUAL methodologies to design interventions. Preintervention and postintervention surveys were conducted to evaluate changes in the recognition of adverse events and barriers to reporting. Statistical analyses were performed to assess the effectiveness of the interventions. Recognition improved and barriers to reporting AEs significantly decreased. Monthly reported cases rose from 33.7 to 50.3 (p = 0.000), demonstrating the effectiveness of the TRIZ-based interventions. Implementing a TRIZ-based model significantly improved adverse event reporting by enhancing the recognition of reportable events and overcoming identified barriers. Future research should explore the long-term sustainability of these interventions and their broader applicability in diverse healthcare settings.

PMID:39506028 | DOI:10.1038/s41598-024-78661-3

Sci Rep. 2024 Nov 7;14(1):27033. doi: 10.1038/s41598-024-77041-1.

ABSTRACT

This study is an investigation of the impact of volatile phenols (VPs) released from burning wood during wildfires on grape composition and the resulting wines. Baseline levels of VPs in grapes and sensory differences between smoke-impacted wines and non-smoke-impacted wines were determined. The differences were related to different levels of smoke taint marker compounds in different wine matrices, using modified descriptive analysis (DA), multivariate statistics, gas chromatography mass spectrometry (GC-MS) and liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS) of the free and total VPs, and individual bound glycosides, respectively. Across two DA panels, Cabernet Sauvignon, Cabernet Franc, Petite Verdot, Merlot, Syrah, Malbec, and Zinfandel wines made from grape originating from different areas in California were evaluated. The results show sensory differences between highly smoke-impacted and non-impacted wines with wines made from highly smoke-impacted grapes characterized as smoky, barbeque, medicinal, and having a retro-nasal ashtray character. Low smoke-impact wines based on free and total VP concentrations were not significantly different from the non-impacted wines when rated through descriptive analysis. The amount of smoke exposure was the largest contributor to smoke impact determined by sensory evaluation, but the different wine matrices from different locations and varietals also played an important role in determining the level of perceived smoke impact. The results of this study will contribute to our understanding of smoke impact and how it influences wine characteristics by relating smoke marker indicator compounds to wine sensory attributes.

PMID:39506001 | DOI:10.1038/s41598-024-77041-1

Sci Rep. 2024 Nov 6;14(1):26972. doi: 10.1038/s41598-024-76424-8.

ABSTRACT

Procedural coding presents a taxing challenge for clinicians. However, recent advances in natural language processing offer a promising avenue for developing applications that assist clinicians, thereby alleviating their administrative burdens. This study seeks to create an application capable of predicting procedure codes by analysing clinicians’ operative notes, aiming to streamline their workflow and enhance efficiency. We downstreamed an existing and a native German medical BERT model in a secondary use scenario, utilizing already coded surgery notes to model the coding procedure as a multi-label classification task. In comparison to the transformer-based architecture, we were levering the non-contextual model fastText, a convolutional neural network, a support vector machine and logistic regression for a comparative analysis of possible coding performance. About 350,000 notes were used for model adaption. By considering the top five suggested procedure codes from medBERT.de, surgeryBERT.at, fastText, a convolutional neural network, a support vector machine and a logistic regression, the mean average precision achieved was 0.880, 0.867, 0.870, 0.851, 0.870 and 0.805 respectively. Support vector machines performed better for surgery reports with a sequence length greater than 512, achieving a mean average precision of 0.872 in comparison to 0.840 for fastText, 0.837 for medBERT.de and 0.820 for surgeryBERT.at. A prototypical front-end application for coding support was additionally implemented. The problem of predicting procedure codes from a given operative report can be successfully modelled as a multi-label classification task, with a promising performance. Support vector machines as a classical machine learning method outperformed the non-contextual fastText approach. FastText with less demanding hardware resources has reached a similar performance to BERT-based models and has shown to be more suitable for explaining the predictions efficiently.

PMID:39505974 | DOI:10.1038/s41598-024-76424-8

Sci Rep. 2024 Nov 6;14(1):26935. doi: 10.1038/s41598-024-78432-0.

ABSTRACT

Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 – ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6A_NUC vs. ER r = 0.2373 and KAT6B_NUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.

PMID:39505971 | DOI:10.1038/s41598-024-78432-0