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Nevin Manimala Statistics

A Novel Neutrophil Extracellular Trap Signature Predicts Patient Chemotherapy Resistance and Prognosis in Lung Adenocarcinoma

Mol Biotechnol. 2024 May 11. doi: 10.1007/s12033-024-01170-1. Online ahead of print.

ABSTRACT

Chemoresistance is a key obstacle in the long-term survival of patients with locally and advanced lung adenocarcinoma (LUAD). This study used bioinformatic analysis to reveal the chemoresistance of gene-neutrophil extracellular traps (NETs) associated with LUAD. RNA sequencing data and LUAD expression patterns were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. The GeneCards database was used to identify NETosis-related genes (NRGs). To identify hub genes with significant and consistent expression, differential analysis was performed using the TCGA-LUAD and GEO datasets. LUAD subtypes were determined based on these hub genes, followed by prognostic analysis. Immunological scoring and infiltration analysis were conducted using NETosis scores (N-scores) derived from the TCGA-LUAD dataset. A clinical prognostic model was established and analyzed, and its clinical applications explored. Twenty-two hub genes were identified, and consensus clustering was used to identify two subgroups based on their expression levels. The Kaplan-Meier (KM) curves demonstrated statistically significant differences in prognosis between the two LUAD subtypes. Based on the median score, patients were further divided into high and low N-score groups, and KM curves showed that the N-scores were more precise at predicting the prognosis of patients with LUAD for overall survival (OS). Immunological infiltration analysis revealed significant differences in the abundances of 10 immune cell infiltrates between the high and low N-score groups. Risk scores indicated significant differences in prognosis between the two extreme score groups. The risk scores for the prognostic model also indicated significant differences between the two groups. The results provide new insights into NETosis-related differentially expressed genes (NRDEGs) associated with chemotherapy resistance in patients with LUAD. The established prognostic model is promising and could help with clinical applications to evaluate patient survival and therapeutic efficiency.

PMID:38734842 | DOI:10.1007/s12033-024-01170-1

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Nevin Manimala Statistics

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

Metabolomics. 2024 May 11;20(3):54. doi: 10.1007/s11306-024-02127-w.

ABSTRACT

INTRODUCTION: The prevalence of type 2 diabetes has surged to epidemic proportions and despite treatment administration/adherence, some individuals experience poorly controlled diabetes. While existing literature explores metabolic changes in type 2 diabetes, understanding metabolic derangement in poorly controlled cases remains limited.

OBJECTIVE: This investigation aimed to characterize the urine metabolome of poorly controlled type 2 diabetes in a South African cohort.

METHOD: Using an untargeted proton nuclear magnetic resonance metabolomics approach, urine samples from 15 poorly controlled type 2 diabetes patients and 25 healthy controls were analyzed and statistically compared to identify differentiating metabolites.

RESULTS: The poorly controlled type 2 diabetes patients were characterized by elevated concentrations of various metabolites associated with changes to the macro-fuel pathways (including carbohydrate metabolism, ketogenesis, proteolysis, and the tricarboxylic acid cycle), autophagy and/or apoptosis, an uncontrolled diet, and kidney and liver damage.

CONCLUSION: These results indicate that inhibited cellular glucose uptake in poorly controlled type 2 diabetes significantly affects energy-producing pathways, leading to apoptosis and/or autophagy, ultimately contributing to kidney and mild liver damage. The study also suggests poor dietary compliance as a cause of the patient’s uncontrolled glycemic state. Collectively these findings offer a first-time comprehensive overview of urine metabolic changes in poorly controlled type 2 diabetes and its association with secondary diseases, offering potential insights for more targeted treatment strategies to prevent disease progression, treatment efficacy, and diet/treatment compliance.

PMID:38734832 | DOI:10.1007/s11306-024-02127-w

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Nevin Manimala Statistics

Variants of the P3 event-related potential operate as indicators of distinct mechanisms contributing to problematic alcohol use

Neuropsychopharmacology. 2024 May 11. doi: 10.1038/s41386-024-01874-7. Online ahead of print.

ABSTRACT

Considerable research has linked relative reduction in the amplitude of the P3 event-related potential (ERP) during cognitive task performance (i.e., Target-P3) with increased risk of alcohol-related problems. A separate literature indicates that a relative increase in the amplitude of the P3 elicited by cues signaling alcohol availability (i.e., ACR-P3) also is associated with alcohol use and problems. To date, no research has integrated these seemingly discrepant findings. Here, we aimed to demonstrate that P3 amplitudes elicited in different task contexts reflect distinct domains of functioning relevant to problematic alcohol involvement (PAI), and therefore can inform heterogeneity in the etiology of PAI. 156 emerging adults (61% women; 88% White/Non-Hispanic) completed a mental rotation task and a picture-viewing task while ERPs were recorded. Participants also completed questionnaire measures of trait disinhibition, alcohol use, and alcohol-related problems. Findings from regression analyses indicated that (a) Target-P3 was negatively associated and ACR-P3 was positively associated with a PAI latent variable; (b) the two P3s accounted for unique variance in PAI, beyond that accounted for by recent drinking; and (c) the association between Target-P3 and PAI-but not ACR-P3 and PAI-was statistically mediated by trait disinhibition. The present findings highlight the unique contributions of distinct functional domains associated with disinhibition and incentive salience in the etiology of PAI. Moreover, findings are consistent with a nuanced understanding of the P3 ERP, whereby its specific meaning varies according to the task context in which it is elicited.

PMID:38734817 | DOI:10.1038/s41386-024-01874-7

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Nevin Manimala Statistics

Neonatal outcomes of preterm infants with pulmonary hypertension: clustering based on prenatal risk factors

Pediatr Res. 2024 May 11. doi: 10.1038/s41390-024-03232-1. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate association of prenatal risk factors and neonatal outcomes of preterm infants with pulmonary hypertension (PH).

METHODS: A prospective cohort study of very-low-birth-weight infants born at 22-29 weeks’ gestation who received PH-specific treatment during hospitalization. Infants were classified using a two-step cluster analysis based on gestational age (GA), small-for-gestational-age (SGA), exposure to antenatal corticosteroids (ACS), histologic chorioamnionitis (HCA), and oligohydramnios.

RESULTS: Among 910 infants, six clusters were identified: cluster A (HCA, n = 240), cluster B (oligohydramnios, n = 79), cluster C (SGA, n = 74), cluster D (no-ACS, n = 109), cluster E (no dominant parameter, n = 287), and cluster F (HCA and oligohydroamnios, n = 121). Cluster A was used as a reference group for comparisons among clusters. Compared to cluster A, cluster C (aHR: 1.63 [95% CI: 1.17-2.26]) had higher risk of overall in-hospital mortality. Clusters B (aHR: 1.52 [95% CI: 1.09-2.11]), D (aHR: 1.71 [95% CI: 1.28-2.30]), and F (aHR: 1.51 [95% CI: 1.12-2.03]) had higher risks of receiving PH-specific treatment within the first week of birth compared to cluster A.

CONCLUSION: These findings may provide a better understanding of prenatal risk factors contributing to the development of PH.

IMPACT: Pulmonary hypertension (PH), presenting as hypoxic respiratory failure, has complex etiologies in preterm infants. Although multifactorial risks for the development of PH in preterm infants are known, few studies have classified infants with similar etiologies for PH. Each cluster has distinct patterns of prenatal condition and neonatal outcome.

PMID:38734814 | DOI:10.1038/s41390-024-03232-1

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Nevin Manimala Statistics

Examining the association of non-melanoma skin cancer with immunomodulatory conditions: a cross-sectional analysis of the All of Us database

Arch Dermatol Res. 2024 May 11;316(5):161. doi: 10.1007/s00403-024-02921-5.

NO ABSTRACT

PMID:38734810 | DOI:10.1007/s00403-024-02921-5

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Nevin Manimala Statistics

Vaccination in twin pregnancies: comparison between immunization before conception and during pregnancy

Sci Rep. 2024 May 11;14(1):10813. doi: 10.1038/s41598-024-61504-6.

ABSTRACT

To evaluate the development of neutralizing Anti-Spike Protein IgG (Anti-S-IgG) during twin pregnancies before conception vs. during pregnancy. In this prospective study, three blood samples were collected from pregnant women and subjected to anti-S-IgG immunodiagnostics. The patient’s medical records, including vaccination and PCR test results, were collected from the hospital’s electronic database. Age-matched non-pregnant women were used as a control group. We enrolled 83 women with twin pregnancies. 49 women were vaccinated before conception, 21 women were vaccinated during pregnancy, and 13 were not vaccinated. Of the 13 women who weren’t vaccinated, three became positive during pregnancy, and all three were severely ill. By contrast, in women who were vaccinated during or before pregnancy, COVID-19 infection during pregnancy caused only mild symptoms. A ten-fold lower level of neutralizing Anti-S-IgG in the 3rd trimester was observed in healthy women who were vaccinated before conception and remained healthy until discharge from the hospital after delivery 1605 (IQR: 763-2410) compared to the healthy women who were vaccinated during pregnancy 152 AU/mL (IQR: 54-360). This difference was higher among women who were infected by COVID-19 (as verified by a positive PCR test). The third-trimester level of neutralizing Ant-S-IgG in the infected group was 4770 AU/mL (4760-6100) in infected women vaccinated before conception compared to those vaccinated during pregnancy who had 70 AU/mL (IQR: 20-170) (p < 0.001). In women vaccinated at 13-16 weeks gestation, neutralizing Anti-S-IgG at 20-22 weeks went up to 372 AU/mL (IQR: 120-1598) but rapidly dropped to 112 AU/mL (IQR: 54-357) at 28-30 weeks, (p < 0.001), a faster decline than in women vaccinated at a median 22 weeks before conception. Being infected by COVID-19 before conception was linked to having low Anti-S-IgG levels during pregnancy, whereas being infected by COVID-19 during pregnancy led to a very high response in the 3rd trimester. In twin pregnancies, significantly lower neutralizing Anti-S-IgG levels were observed in women vaccinated during pregnancy compared to those vaccinated before conception, whether infected or not infected by COVID-19. A full course of vaccination before conception is recommended.Trial registration. ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: October 4, 2021. https://clinicaltrials.gov/ ID: NCT04595214.

PMID:38734805 | DOI:10.1038/s41598-024-61504-6

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Nevin Manimala Statistics

Racial and ethnic disparities in basal cell carcinoma treated by Mohs micrographic surgery: the Columbia experience

Arch Dermatol Res. 2024 May 11;316(5):151. doi: 10.1007/s00403-024-02858-9.

NO ABSTRACT

PMID:38734798 | DOI:10.1007/s00403-024-02858-9

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Nevin Manimala Statistics

MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume

Abdom Radiol (NY). 2024 May 11. doi: 10.1007/s00261-024-04349-x. Online ahead of print.

ABSTRACT

BACKGROUND: Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning.

METHODS: This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, “raw” and bladder-normalized T2 signal intensity, as well as SV volume, were obtained.

RESULTS: Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01).

CONCLUSION: While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

PMID:38734785 | DOI:10.1007/s00261-024-04349-x

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Nevin Manimala Statistics

Understanding linguistic diversity in the dermatology workforce and requirements to provide medical care in a non-english language: a survey

Arch Dermatol Res. 2024 May 11;316(5):160. doi: 10.1007/s00403-024-02883-8.

NO ABSTRACT

PMID:38734784 | DOI:10.1007/s00403-024-02883-8

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Nevin Manimala Statistics

Occupational association with melanoma: a US ecological county-level analysis

Arch Dermatol Res. 2024 May 11;316(5):165. doi: 10.1007/s00403-024-02922-4.

NO ABSTRACT

PMID:38734782 | DOI:10.1007/s00403-024-02922-4