Tag: pubmed

Front Microbiol. 2024 Dec 12;15:1504742. doi: 10.3389/fmicb.2024.1504742. eCollection 2024.

ABSTRACT

This study aimed to screen native methionine gamma-lyase (L-methioninase) producing bacteria from soil samples and optimize the culture media for enhanced enzyme production using statistical design. Three bacteria, Pseudomonas mosselii, Ralstonia solanacearum, and Cytobacillus kochii, were identified as novel L-methioninase producers, which alternative source of L-methioninase for cancer treatment could be utilized alongside other therapeutic agents. The bacteria were isolated from various garden soils and cultured on a modified M9 medium and screened by Nessler reagent. According to Bergey’s manual of systematic bacteriology, identification tests determined the morphological, physiological, and biochemical characterizations. Further identification was performed using the analysis of the 16 s rDNA gene sequences using PCR and universal bacterial primers. The optimization of medium constituents for L-methioninase production was performed in two steps using Response Surface Methodology (RSM). The first step used the “one factor at a time” method to screen and identify critical medium components for L-methioninase production. The second step used the Box-Behnken design to assess quadratic effects and two-way interactions between variables and determine the response’s nonlinear nature. The study found that three isolates produced L-methioninase, namely Pseudomonas mosselii spp.MN02 (GenBank PP431975), Ralstonia solanacearum spp.MN02 (GenBank PP431636), and Cytobacillus kochii spp.MN02 (GenBank PP432622). Among these, Pseudomonas mosselii spp.MN02 produced the highest amount of L-methioninase and was therefore chosen for enzyme production optimization process. The maximum L-methioninase production of 1.5 ± 0.1 U/mL was obtained at a pH 6, and the best nitrogen source was yeast extract (1% concentration). The influence of different carbon sources revealed that glucose was the best carbon source for L-methioninase production (3.25 ± 0.1 U/mL). The optimization experiments using the Box-Behnken design predicted that L-methioninase would have an activity of 12.56 U/mL under optimal conditions, including 2% glucose, 2% yeast extract, pH 6, and temperature at 30°C. In conclusion, this study presents a promising new methods for identifying potential L-methioninase producers and optimizing the culture medium for more enzyme production by microbial fermentation. This could pave the way for developing a drug that assists in human cancers treatment.

PMID:39726960 | PMC:PMC11669666 | DOI:10.3389/fmicb.2024.1504742

Front Microbiol. 2024 Dec 11;15:1491551. doi: 10.3389/fmicb.2024.1491551. eCollection 2024.

ABSTRACT

Yak (Bos grunniens) is a large ruminant endemic to the Tibetan plateau. The addition of enzyme complexes to feed can significantly improve their growth performance. Therefore, studying the effects of ruminant compound enzyme preparations dosage on yak rumen microorganisms and production performance is crucial to promoting the development of the yak industry. This study aimed to determine the effects of feeding yaks with different doses of ruminant enzyme compounds on the performance, meat quality, and rumen microorganisms of yaks. Three kinds of experimental diets with doses of 0.5 g/kg (LE group), 1 g/kg (ME group), and 2 g/kg (HE group) were selected to determine the growth index, meat quality, serum biochemical indexes, rumen fluid pH and other indexes of the three experimental groups. Metagenomics studies were used to investigate the differences in rumen microbial composition and function among yak groups, and transcriptome sequencing of the longest dorsal muscle was performed to reveal the expression of differential genes among different groups. It was determined that the levels of dietary enzyme complexes significantly affected growth performance, rumen fluid pH, and serum biochemical indices. At the phylum level, the dominant phylum in all three treatment groups was Bacteroidota, Bacillota, Kiritimatiellota, and Pseudomonadota. At the genus level, Prevotella, Methanobrevibacter, Oscillibacter. Fibrobacter showed statistically significant differences in abundance (p < 0.05). CAZymes family analysis revealed significant differences in GHs, CTs, and CEs among the three groups. Genome-wide differential gene expression in the longest muscle of the yak back was analyzed by RNA-seq between the three experimental groups. Some DEGs were found to be enriched in the ECM, PI3K-Akt, PPAR, and protein digestion and absorption receptor pathways. Combined metagenomics and transcriptomics analyses revealed that some microorganisms were significantly associated with the genes COL11A1, POSTN, and PTHLH, which are involved in growth metabolism. In summary, this study investigated the effects and interrelationships of ruminant complex enzymes on yak performance, meat quality, and rumen environment. The results of this study provide a scientific basis for adding ruminant enzymes to yaks.

PMID:39726957 | PMC:PMC11670318 | DOI:10.3389/fmicb.2024.1491551

Front Genet. 2024 Dec 12;15:1488425. doi: 10.3389/fgene.2024.1488425. eCollection 2024.

ABSTRACT

BACKGROUND: Noonan syndrome (NS) is a rare group of autosomal genetic disorders. In recent years, with the exploration and development of molecular diagnostic techniques, more and more researchers have begun to pay attention to NS. However, there is still a lack of reports on the bibliometric analysis of NS worldwide. This study aims to assess the current research status and development trend of NS, to explore the research hotspots and emerging topics, and to point out the direction for future scientific research.

METHODS: Web of Science Core Collection was selected as the search database for bibliometric analysis of NS-related publications from 1998 to 2023. Statistical and visual analysis of the number of publications, countries, institutions, authors, journals, keywords, and references were analyzed using Citespace, VOSviewer, Scimago Graphica, and BibliometrixR.

RESULTS: A total of 2041 articles were included in this study. The United States had the highest number of publications, and Istituto Superiore di Sanità, Italy, was the institution with the highest number of publications. TARTAGLIA M was the scientist with the highest number of publications and citations. Among the journals, AMERICAN JOURNAL OF MEDICAL GENETICS PART A has the highest output, and Nature Genetics is the most frequently cited. The reference with the highest outburst intensity is Roberts AE, LANCET, 2013. the cluster diagram divides all the keywords into seven categories, with the most vigorous outburst being “of function mutations.”

CONCLUSION: Research hotspots in the field of NS focus on the correspondence between NS genotype and phenotype and the precise diagnosis of NS. Future research efforts will explore more deeply from the perspective of long-term intervention strategies for NS. There is an urgent need to rely on significant research countries, institutions, journals, and authors to lead the construction of a more robust global collaborative network that will enhance research efficacy.

PMID:39726952 | PMC:PMC11669677 | DOI:10.3389/fgene.2024.1488425

Front Cardiovasc Med. 2024 Dec 12;11:1475483. doi: 10.3389/fcvm.2024.1475483. eCollection 2024.

ABSTRACT

BACKGROUND AND OBJECTIVES: The optimal timing for complete revascularization (CR) in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) remain uncertain.

METHODS: This post-hoc analysis of the FRAME-AMI trial included AMI patients with MVD (n = 549). They were classified into immediate (n = 329) and staged CR (n = 220) groups. All percutaneous coronary interventions were performed during inex hospitalization. The primary endpoint was a composite of all-cause death, acute myocardial infarction, and repeated revascularization. Secondary endpoints included each component of the primary endpoint. Additional comparisons for the outcomes in ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were also performed.

RESULTS: The incidence of the primary endpoint was not significantly different in any of the AMI patients [12.7% [immediate CR] vs. 17.4% [staged CR], p = 0.905, adjusted hazard ratio [HR] of staged CR = 0.81, 95% confidence interval = 0.43-1.53, p = 0.528]. Other secondary endpoints were also not significantly different. Analyses of STEMI and Neither the primary or secondary endpoints of NSTEMI patients were significantly different.

CONCLUSIONS: In this post-hoc analysis of the FRAME-AMI trial, no significant difference in clinical outcomes was observed between the immediate and staged CR strategies for AMI with MVD and the subgroups, such as STEMI or NSTEMI. However, the results should be interpreted carefully because of the many limitations, including a limited sample size and a lack of statistical power. Trial Registration: FRAME-AMI clinicaltrials.gov, identifier (NCT02715518).

PMID:39726942 | PMC:PMC11669547 | DOI:10.3389/fcvm.2024.1475483

J Sci Comput. 2024 Jul;100(1):17. doi: 10.1007/s10915-024-02535-z. Epub 2024 Jun 3.

ABSTRACT

The numerical solution of differential equations using machine learning-based approaches has gained significant popularity. Neural network-based discretization has emerged as a powerful tool for solving differential equations by parameterizing a set of functions. Various approaches, such as the deep Ritz method and physics-informed neural networks, have been developed for numerical solutions. Training algorithms, including gradient descent and greedy algorithms, have been proposed to solve the resulting optimization problems. In this paper, we focus on the variational formulation of the problem and propose a Gauss-Newton method for computing the numerical solution. We provide a comprehensive analysis of the superlinear convergence properties of this method, along with a discussion on semi-regular zeros of the vanishing gradient. Numerical examples are presented to demonstrate the efficiency of the proposed Gauss-Newton method.

PMID:39726935 | PMC:PMC11671159 | DOI:10.1007/s10915-024-02535-z

World J Clin Cases. 2024 Dec 26;12(36):6916-6925. doi: 10.12998/wjcc.v12.i36.6916.

ABSTRACT

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are frequent co-occurring disorders that affect regular metabolic functions. Obesity has also been linked to an increased risk of developing diabetes. Obesity and diabetes are on the rise, increasing healthcare costs and raising mortality rates. Research has revealed that the expression profile of microRNAs (miRNAs) changes as diabetes progresses. Furthermore, vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index (BMI). Low vitamin D levels do not solely cause obesity, which could be a factor in the etiology of T2DM.

AIM: To evaluate miRNA-200a and miRNA-200b expression, and vitamin-D levels in obese and obese T2DM individuals.

METHODS: This study included 210 participants, of which, 82 were obese (BMI > 30 kg/m²) without T2DM, 28 were obese with T2DM, and 100 were healthy controls. BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM. Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes, and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique. All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.

RESULTS: Overall, a 2.20- and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls. MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold, respectively, while in obese T2DM participants these values were 2.67-fold, and 5.78-fold, respectively, and these differences were found to be statistically significant (P = 0.02) (P < 0.0001). Obese participants showed a vitamin D level of 34.27 ng/mL, while in obese-T2DM participants vitamin D level was 22.21 ng/mL (P < 0.0001). Vitamin D was negatively correlated with miRNA-200a (r = -0.22, P = 0.01) and miRNA-200b (r = -0.19, P = 0.04). MiRNA-200a sensitivity was 75%, and specificity was 57%, with a cutoff value of 2.07-fold. MiRNA-200b sensitivity was 75%, and specificity was 71% with a cutoff value of 4.12-fold, suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07- and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.

CONCLUSION: MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants, and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.

PMID:39726924 | PMC:PMC11531979 | DOI:10.12998/wjcc.v12.i36.6916

MedEdPORTAL. 2024 Dec 26;20:11473. doi: 10.15766/mep_2374-8265.11473. eCollection 2024.

ABSTRACT

INTRODUCTION: A physician’s first patient harm event oftentimes occurs during the intern year. Residents encounter and are responsible for medical errors, yet little training is offered in how to properly cope with these events. Earlier and more in-depth education about how to process patient harm events is needed.

METHODS: We developed a 110-minute workshop focused on coping strategies for patient harm events and delivered it to a cohort of fourth-year medical students during a transition-to-residency course just before graduation. The workshop emphasized interns’ increasing exposure to medical errors, how to personally process them, and how to debrief near-peers in processing them.

RESULTS: A total of 190 students participated in the workshop. Our survey response rate was 88%. Students’ confidence in defining second casualty after the workshop grew from eight responding very or extremely confident (7%) to 95 responses (87%). Comfort utilizing positive coping mechanisms improved from 14 very or extremely confident responses (12%) to 73 responses (67%). Confidence utilizing first responder structure grew from three very or extremely confident responses (3%) to 61 responses (56%). Comfort helping colleagues cope with patient harm events grew from 16 very or extremely confident responses (14%) to 78 responses (72%).

DISCUSSION: This workshop fills an important gap in UME by preparing senior-level students to resolve emotional conflict related to patient harm events. Our findings illustrate that a short-term intervention on this topic can impact students’ confidence. We believe discussion around how patient harm events emotionally impact trainees should be expanded.

PMID:39726898 | PMC:PMC11669734 | DOI:10.15766/mep_2374-8265.11473

Front Nutr. 2024 Dec 12;11:1504946. doi: 10.3389/fnut.2024.1504946. eCollection 2024.

ABSTRACT

OBJECTIVE: Inflammation and nutritional status are closely associated with the mortality risk of survivors of cardio-cerebrovascular events. This study aims to evaluate the relationship between inflammation and nutritional indices and mortality among, identifying the most predictive indices.

METHODS: This study included cohort data of the survivors of major adverse cardiovascular and cerebrovascular events (MACCE) from the National Health and Nutrition Examination Survey (NHANES) in 1999-2010. MACCE is defined as a composite of myocardial infarction, heart failure and stroke, and at least one of the three events occurs. The main outcomes were all-cause mortality and cardiovascular mortality. Kaplan-Meier analysis and receiver operating characteristic curves were used to compare the correlation between seven inflammatory nutritional indices (such as Advanced Lung Cancer Inflammation Index, ALI) and mortality among the survivors. A multivariable-adjusted Cox regression and restricted cubic splines analysis identified the most predictive index, with the optimal number of nodes determined by the Akaike information criterion. Subgroup and sensitivity analyses were conducted to assess model stability.

RESULTS: A total of 2,045 MACCE survivors were included. The higher levels of ALI and serum albumin were significantly associated with lower risks of all-cause and cardiovascular mortality among these individuals. Increases in C-reactive protein to Lymphocyte Ratio, Neutrophil to Serum Albumin Ratio, Neutrophil-to-Lymphocyte Ratio, Systemic Immune-Inflammation Index (SII), and C-reactive protein were similarly correlated with higher mortality risk. ALI outperformed other indices, displaying a distinct L-shaped nonlinear relationship with both all-cause and cardiovascular mortality among MACCE survivors, with an inflection point at 90 indicating the lowest risk. To the left of this inflection, each unit increase in ALI was associated with a 1.3% decrease in all-cause and cardiovascular mortality risk among MACCE patients. To the right, the risk might increase by 0.2%, although the change was not statistically significant. Subgroup analyses and sensitivity analyses showed that the association between ALI and risk of mortality remained stable in most MACCE survivor populations.

CONCLUSION: Routine and dynamic monitoring of ALI is helpful for clinicians to assess the mortality risk among MACCE survivors. Anti-inflammatory therapies and appropriate nutritional support are crucial for reducing mortality in these individuals.

PMID:39726875 | PMC:PMC11669911 | DOI:10.3389/fnut.2024.1504946

Front Nutr. 2024 Dec 12;11:1454286. doi: 10.3389/fnut.2024.1454286. eCollection 2024.

ABSTRACT

BACKGROUND: This systematic review and meta-analysis examine the effects of okra consumption on cardiometabolic risk factors in individuals with prediabetes and diabetes. Okra is a widely consumed vegetable with potential health benefits, and understanding its impact on metabolic parameters in these populations is important.

METHODS: A comprehensive search of the literature was conducted up to May 2024 in PubMed/Medline, Scopus, and Web of Science to find relevant randomized clinical trials (RCTs) by using following keyword: (“okra” OR “okras” OR “abelmoschus esculentus“) AND (“intervention” OR “controlled trial” OR “randomized” OR “randomized” OR “randomly” OR “clinical trial” OR “trial” OR “randomized controlled trial” OR “randomized clinical trial” OR “RCT” OR “blinded” OR “placebo” OR “Cross-Over” OR “parallel”). The selected trials were subjected to heterogeneity tests using the I² statistic. Random effects models were examined based on the heterogeneity tests, and the pooled data were calculated as weighted mean differences (WMD) with a 95% confidence interval (CI). In this meta-analysis, all the analyses were performed by using the STATA version 17 software.

RESULTS: Of the 1,339 papers, nine eligible RCTs were included in the present meta-analysis. Our findings indicated that okra consumption significantly reduced total cholesterol (TC) levels (WMD: -14.40 mg/dL; (95% CI: -20.94 to -7.86); p < 0.001), low-density lipoprotein (LDL) (WMD: -7.90 mg/dL; (95% CI: -13.30 to -2.48); p = 0.004), fasting blood glucose (FBG) (WMD: -39.58 mg/dL; (95% CI: -61.60 to -17.56); p < 0.001), and hemoglobin A1C (HbA1c) (WMD: -0.46 mg/dL; (95% CI: -0.79 to -0.13); p = 0.005). Overall effect size showed that okra intake failed to change triglycerides (TG), high-density lipoprotein (HDL), Insulin, homeostatic model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight, and body Mass Index (BMI) significantly.

CONCLUSION: Okra decreased TC, LDL, FBG, and HbA1c levels in the intervention compared to the control group. A dose ≤3,000 mg/day caused a significant decrease in TG, TC, LDL, HbA1c, and a significant increase in HDL. More study is needed to determine the optimum dose and duration of intervention.

PMID:39726865 | PMC:PMC11670074 | DOI:10.3389/fnut.2024.1454286

Pain Rep. 2024 Dec 24;10(1):e1218. doi: 10.1097/PR9.0000000000001218. eCollection 2025 Feb.

ABSTRACT

INTRODUCTION: Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.

OBJECTIVES: We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.

METHODS: Using phenotypes and imputed genotypes from the UK Biobank 500k dataset, we generated a multi-trait phenotype by combining 3 BP-related phenotypes: chronic BP, dorsalgia, and intervertebral disk disorders. We performed gene-based association analysis for 3 BP-related phenotypes and multi-trait phenotype. Conditional analysis was applied to account for the effects of genetic variants outside the gene. Finally, we replicated significantly associated genes using the FinnGen database.

RESULTS: We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported. Several new genes are known to be associated with traits genetically correlated with BP or to be involved in pathways associated with BP.

CONCLUSION: Using new powerful methods of association analysis, we identified 7 novel genes associated with BP. Our results provide new insights into the genetics of back pain.

PMID:39726856 | PMC:PMC11671072 | DOI:10.1097/PR9.0000000000001218