Nevin Manimala

Pharmacoeconomics. 2025 Feb 20. doi: 10.1007/s40273-025-01469-0. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to assess the cost effectiveness of nirsevimab, a recently authorized monoclonal antibody (mAb) for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV), in comparison with the standard practice involving palivizumab for high-risk infants during their first RSV season in the Netherlands.

METHODS: A static cost-effectiveness model was populated for the Netherlands to evaluate different immunization strategies for nirsevimab over a single RSV season from a societal perspective. The model considered the most recently published RSV incidence data (average incidence from 2006 to2018), costs (adjusted to the 2023 price year), and associated health effects. Extensive scenario analyses were conducted to explore various strategies, and sensitivity analysis was performed to assess the model’s robustness.

RESULTS: In the base-case scenario, all-infant protection-a strategy of in-season with catch-up immunization for all infants-nirsevimab has the potential to prevent numerous RSV-related cases, including 2333 hospitalizations and 150 intensive-care admissions, in the overall population compared with the standard of care. Nirsevimab appears to be cost effective under this strategy with an economically justifiable acquisition price for nirsevimab of €220 at a willingness-to-pay threshold of €50,000 per quality-adjusted life-year. Sensitivity analyses indicate a 52% probability that nirsevimab is cost effective at this threshold. Comparison of different vaccination strategies revealed that the all-infant protection approach was the one that prevented the higher number of cases.

CONCLUSIONS: This study indicates that universal infant immunization with nirsevimab has the potential to be cost effective and significantly reduces the burden of RSV among Dutch infants. These findings underscore the importance of implementing effective protective measures against RSV-LRTD, reducing the pressure on the healthcare system during the RSV season.

PMID:39976899 | DOI:10.1007/s40273-025-01469-0

Discov Oncol. 2025 Feb 20;16(1):213. doi: 10.1007/s12672-025-01977-7.

ABSTRACT

This study analyzes the research landscape of nanomaterials in treating hepatocellular carcinoma (HCC) and examines publication trends in this field by conducting a comprehensive bibliometric analysis within the Web of Science Core Collection (WoSCC) database. Articles published from 2000 to September 16, 2024 were retrieved using a structured search formula targeting studies on nanomaterials in HCC, including nanoparticles, nanodots, nanorods, nanosheets, and nanomedicine. Only English full-text articles and reviews relevant to nanomaterial applications in HCC were considered, excluding conference abstracts and non-research items. The analysis encompasses annual publication trends, country-wise publication distribution, prominent institutions, and key journals in the field. Statistical and graphical analyses were performed using GraphPad Prism (v8.0.2) to illustrate publication trends. CiteSpace (6.2.4R) and VOSviewer (1.6.18) software were used to visualize co-citation and keyword networks, highlighting scientific knowledge structures and research hotspots. Notable advancements have emerged as a promising strategy, enabling hepatocyte-specific drug delivery to enhance therapeutic precision and minimize off-target effects. This analysis provides a comprehensive understanding of the evolution of HCC nanomaterials research, key contributing countries, major research institutions, and frequently cited keywords. The findings offer valuable insights into the field’s knowledge base, emerging trends, and future directions in HCC treatment with nanomaterials.

PMID:39976894 | DOI:10.1007/s12672-025-01977-7

Biochem Genet. 2025 Feb 20. doi: 10.1007/s10528-025-11051-0. Online ahead of print.

ABSTRACT

Breast cancer is one of the most prevalent cancers globally and remains a significant cause of cancer-related mortality among women despite advancements in early detection and treatment. The heterogeneity of breast cancer arises from a complex interplay of genetic and environmental factors. Early-stage breast cancer is often asymptomatic, with initial signs including subtle changes in breast morphology and localized swelling, emphasizing the need for reliable diagnostic tools for early detection. Recent research has highlighted the potential of molecular biomarkers, particularly non-coding RNAs such as circular RNAs (circRNAs), in cancer diagnosis. CircRNAs, a unique subset of non-coding RNAs, are characterized by their covalently closed-loop structure, which confers exceptional stability and resistance to exonuclease degradation. They are present in various body fluids and have demonstrated regulatory roles in transcription, translation, and as microRNA sponges, making them promising candidates for cancer diagnostics and prognostics. This study focuses on evaluating the diagnostic potential of two circRNAs, hsa_circ_0001666 and hsa_circ_0003227, by examining their expression in normal, tumor, and metastatic breast cancer cell lines. Breast cancer cell lines representing normal (MCF-10A), tumor (MCF-7), and metastatic (BT-20) stages were cultured for analysis. Total RNA was extracted using a column-based RNA extraction kit, and RNA quality was assessed through NanoDrop spectrophotometry and agarose gel electrophoresis. Complementary DNA (cDNA) synthesis was performed using random hexamers, and the expression levels of hsa_circ_0001666 and hsa_circ_0003227 were quantified using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR), with beta-actin serving as the internal control. Statistical analyses were conducted using SPSS software to evaluate differences in expression levels across cell lines. A significant downregulation of hsa_circ_0001666 and hsa_circ_0003227 was observed in tumor and metastatic cell lines compared to normal breast cell lines (P < 0.05). These results suggest that the expression of these circRNAs correlates with the progression of breast cancer, with decreased levels observed as cells transition from normal to tumorigenic and metastatic stages. The findings of this study indicate that hsa_circ_0001666 and hsa_circ_0003227 have potential utility as diagnostic biomarkers for breast cancer. Their significant expression changes across different stages of breast cancer highlight their relevance in early detection and disease monitoring. This study reinforces the potential of RNA-based biomarkers, particularly circRNAs, in cancer diagnosis and treatment. However, in vitro findings require validation in clinical samples and larger cohorts. Future research should explore their roles in breast cancer progression and integration into non-invasive diagnostics.

PMID:39976889 | DOI:10.1007/s10528-025-11051-0

J Robot Surg. 2025 Feb 20;19(1):76. doi: 10.1007/s11701-025-02237-0.

ABSTRACT

This meta-analysis examines and compares the perioperative results (such as complications, recovery, and other surgical outcomes) in obese patients who undergo either robotic-assisted partial nephrectomy (RPN) or open partial nephrectomy (OPN). Essentially, the study is looking at how these two types of surgeries perform in obese patients, specifically focusing on outcomes related to the surgery process itself. We conducted a comprehensive search of major databases, including PubMed, Cochrane Library, and Web of Science, focusing on English studies, up to November 2024. Review articles, research protocols without published data, conference abstracts, and irrelevant studies were excluded. We performed data analysis using the Cochran-Mantel-Haenszel method and random-effects models, followed by mean differences, inverse variance, and 95% confidence intervals (CIs). The results were presented as odds ratios (ORs) and 95% CIs, and data with p values less than 0.05 were identified. This meta-analysis included three cohort studies with a total of 604 patients. Compared to OPN, RPN was associated with significantly shorter hospital stays (WMD – 2.27, 95% CI – 3.67 to – 0.87; p = 0.002), lower overall complication rates (OR 0.50, 95% CI 0.34-0.73; p = 0.0004), and reduced estimated blood loss (WMD – 125.12, 95% CI – 198.02 to – 52.22; p = 0.0008). No significant differences were found between the two groups in transfusion rates, major complications, renal ischemia times, or operative times. RPN offers a safe and feasible option for obese patients compared to OPN, with advantages such as shorter hospital stays, reduced blood loss, and fewer overall complications.

PMID:39976852 | DOI:10.1007/s11701-025-02237-0

Community Ment Health J. 2025 Feb 20. doi: 10.1007/s10597-024-01417-w. Online ahead of print.

ABSTRACT

People living with psychosis live up to 20 years less compared to the general population. Cardiometabolic ill-health and barriers to health-related behaviour are significant contributors. This is a cross-sectional descriptive study of cardiometabolic health and health behaviours of consumers attending a public community mental health service in an Australian city. One hundred and fourteen consumers currently living with psychosis participated. Standard measures of cardiometabolic health, quality of life and, health-related behaviours were utilised. Data were analysed using descriptive statistics. The cohort reported higher fruit intake and physical activity, and lower excess alcohol use compared to previous studies. Health-related behaviours including smoking and vegetable intake were poorer than previously reported. Participants had low levels of cardiometabolic health (e.g. abnormal lipids). Physical and mental quality of life was also lower than for general populations. Improved efforts to address physical health for people with mental health conditions are urgently needed.

PMID:39976847 | DOI:10.1007/s10597-024-01417-w

Endocr Metab Immune Disord Drug Targets. 2025 Feb 19. doi: 10.2174/0118715303329277250120104421. Online ahead of print.

ABSTRACT

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate insecticide that is mostly used in agriculture for pest control.

AIM: This investigation aimed to evaluate the possible protective role of chrysin nanocrystals on thyroid gland hormones and histology in male rats after exposure to a high dose of chlorpyrifos.

METHOD: Rats were randomly divided into 6 groups (6 rats in each group): 1. healthy control group, 2. treated with chrysin nanocrystal (5 mg/kg), 3. treated with chrysin nanocrystal (10 mg/kg), 4. treated with chrysin nanocrystal (5 mg/kg) + chlorpyrifos, 5. treated with chrysin nanocrystal (10 mg/kg) + chlorpyrifos, and 6. treated with chlorpyrifos (30 mg/kg). After 15 days of intervention, rats were anesthetized, and blood samples were taken from the heart to measure thyroid hormones. Then, the thyroid gland was isolated and stored in 10% formalin for histopathological studies. Thyroid samples were also stored at -80 ° C for measuring oxidative stress parameters.

RESULT: A significant reduction was observed in the serum concentrations of T3 and T4 in all treated groups compared with the control group (p < 0.01). In addition, hormone level examination revealed no statistically significant (p ˃ 0.05) changes in plasma TSH concentration in any of the groups. The treatment with CPF and chrysin nanocrystal did not affect the levels of oxidative biomarkers (MDA, GSH, and NO) in thyroid glands. Photomicrographs of a histological section of the thyroid gland showed vacuolar degenerated follicle epithelium and missing colloids in the histological section of the thyroid gland of all groups.

CONCLUSION: Our findings demonstrated that the oral administration of chrysin nanocrystals could not inhibit the toxic effect of a high dose of CPF on the thyroid gland in the rats.

PMID:39976093 | DOI:10.2174/0118715303329277250120104421

Curr Med Chem. 2025 Feb 18. doi: 10.2174/0109298673359149250212073143. Online ahead of print.

ABSTRACT

BACKGROUND: The precise function of DDX59 Antisense RNA 1 (DDX59- AS1) in lung adenocarcinoma (LUAD) has yet to be fully elucidated.

OBJECTIVE: This study uses bioinformatics analysis and experimental validation to investigate the association between DDX59-AS1 and LUAD.

METHODS: This study uses statistical analysis and database interrogation to investigate the potential association between DDX59-AS1 expression and various clinical characteristics, prognostic factors, regulatory networks, and immune infiltration in LUAD. The quantification of DDX59-AS1 expression in LUAD cell lines is conducted through the use of quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: DDX59-AS1 showed significantly elevated levels of expression in patients with LUAD. High levels of DDX59-AS1 expression were found to be significantly associated with poorer overall survival (OS) in patients with LUAD (p = 0.024). Furthermore, an independent correlation was observed between high DDX59-AS1 expression (p = 0.037) and OS in LUAD patients. DDX59-AS1 was found to be involved in various pathways, including glutathione metabolism, proteasome function, and the cytosolic DNA sensing pathway, among others. A significant correlation was observed between the expression levels of DDX59-AS1 and immune cell infiltration in the context of LUAD. Notably, elevated expression of DDX59-AS1 was observed in LUAD cell lines compared to the non-cancerous Beas-2B cell line.

CONCLUSION: A significant correlation was observed between elevated DDX59-AS1 expression in patients with LUAD and adverse prognosis, alongside increased immune infiltration. These results indicate that DDX59-AS1 may function as a prognostic marker for LUAD and a potential predictor of immunotherapy response.

PMID:39976021 | DOI:10.2174/0109298673359149250212073143

Blood Coagul Fibrinolysis. 2025 Jan 23. doi: 10.1097/MBC.0000000000001342. Online ahead of print.

ABSTRACT

OBJECTIVES: Concomitant use of cytochrome P-450 and P-glycoprotein (CYP 3A4/P-gp) inducing antiseizure medications and direct oral anticoagulants (DOAC) may result in reduced DOAC effectiveness, but study results are inconsistent and of variable quality. The purpose of this study was to assess the safety of concomitant CYP 3A4/P-gp inducing antiseizure medications and DOAC use.

METHODS: This was a retrospective cohort study of adult patients who were newly, concomitantly receiving a DOAC (apixaban, dabigatran, or rivaroxaban) and either a CYP 3A4/P-gp inducer (carbamazepine, phenytoin, phenobarbital, or primidone) or noninducer (gabapentin). The primary outcome was the occurrence of a thromboembolic complication, defined as the composite of ischemic stroke and systemic embolism (S/SE) and venous thromboembolism (VTE). Secondary outcomes included the components of the primary composite as well as all-cause mortality and clinically relevant bleeding. Adjusted multivariate proportional hazards modeling was used to compare outcomes for each DOAC individually in the inducer and noninducer groups.

RESULTS: There were 1843 and 14 647 patients who received a DOAC plus a CYP3A4/P-gp inducer and noninducer, respectively. Overall, patients were primarily older, white, had atrial fibrillation, and were dispensed dabigatran. After adjustment, there were no statistically significant differences in the primary outcome between the groups (P > 0.05); however, concomitant inducer and DOAC use was associated with an increased risk of all-cause mortality (P < 0.05).

CONCLUSIONS: No excess risk of thrombosis during concomitant use of DOACs with CYP3A4/P-gp inducing antiseizure medications compared to use with gabapentin was identified. Further research is needed to confirm an association with excess all-cause mortality.

PMID:39976008 | DOI:10.1097/MBC.0000000000001342

Eur J Gastroenterol Hepatol. 2025 Feb 21. doi: 10.1097/MEG.0000000000002949. Online ahead of print.

ABSTRACT

BACKGROUND: Excessive alcohol consumption is a major risk factor for liver disease, with significant variations in its impact across populations. BMI has been identified as a potential mediator in alcohol-related liver damage. This study aimed to examine the association between alcohol consumption and liver function and to explore the mediating role of BMI in a population from India, where both are rising public health concerns.

MATERIALS AND METHODS: A cross-sectional study was conducted using data from adult participants. Liver function was assessed using serum levels of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Alcohol consumption was self-reported, and BMI was calculated AST from height and weight measurements. Multiple linear regression models were used to evaluate the relationship between alcohol consumption and liver enzymes while adjusting for BMI as a mediator. Statistical significance was set at P < 0.05.

RESULTS: The results indicated that higher alcohol consumption was significantly associated with elevated levels of GGT, ALT, and AST. BMI was found to mediate this relationship, with individuals having higher BMI showing a greater increase in liver enzyme levels in response to alcohol consumption. However, no significant association was observed for ALP. BMI also independently correlated with higher levels of GGT, ALT, and AST.

CONCLUSION: This study highlights the mediating role of BMI in alcohol-induced liver dysfunction in the Indian population. Public health interventions focusing on both reducing alcohol intake and managing obesity may help mitigate the risk of liver disease in this high-risk population.

PMID:39975998 | DOI:10.1097/MEG.0000000000002949

Neuroreport. 2025 Jan 14. doi: 10.1097/WNR.0000000000002138. Online ahead of print.

ABSTRACT

Cannabinoid type 1 receptors (CB1Rs) play important roles in regulating neurotransmitter release, synaptic plasticity, cell differentiation, and survival. CB1R is coupled via pertussis toxin (PTX)-sensitive Gαi/o proteins to the activation of extracellular regulated kinase (ERK) signaling. However, there are multiple Gαi/o isoforms, and it is unknown which of these isoforms is responsible for CB1R-induced phosphorylation of ERK. The purpose of this study was to determine which Gαi/o isoform(s) couple CB1R to ERK phosphorylation. HEK293 cells stably expressing the mouse CB1R (CB1R-HEK cells) were transfected with either pcDNA3.1 or pcDNA3.1 encoding PTX-insensitive mutants of Gαo, Gαi1, Gαi2, or Gαi3. PTX was used to inactivate endogenous Gαi/o isoforms before cells were treated with vehicle, delta-9-tetrahydrocannabinol (∆9-THC), or CP55940 and ERK phosphorylation was measured by western blotting. CP55940 induced robust phosphorylation of ERK in cells transfected with vector alone. This effect was completely abolished by PTX treatment. CP55940-induced ERK phosphorylation was rescued by expression of PTX-insensitive forms of Gαo, Gαi1, Gαi2, or Gαi3, indicating that the CB1 receptor can couple to ERK phosphorylation through each of these Gαi/o isoforms. Consistent with its actions as a partial agonist, ∆9-THC induced nominal (two to four-fold) increases in ERK phosphorylation that did not reach statistical significance except in cells transfected with PTX-insensitive Gαi3. These data demonstrate that CB1R can couple to ERK phosphorylation through Gαo, Gαi1, Gαi2, or Gαi3 when stimulated with CP55940 (full agonist). However, ∆9-THC (partial agonist)-induced ERK activation might require high levels of Gαi3 expression.

PMID:39975996 | DOI:10.1097/WNR.0000000000002138