Category: Nevin Manimala

Discov Oncol. 2025 Aug 18;16(1):1579. doi: 10.1007/s12672-025-03215-6.

ABSTRACT

BACKGROUND: Mitochondrial dynamics, particularly the balance between fission and fusion, play a crucial role in cancer progression, including prostate cancer, by influencing cellular metabolism and survival. MTFP1 and MTFP2 are key regulators of mitochondrial fission, and their roles in prostate cancer warrant further investigation.

METHODS: We conducted a comprehensive bioinformatics analysis using RNA-seq data from The Cancer Genome Atlas (TCGA) and SNP data from the UK Biobank (ukb-b-13348) GWAS dataset. Differential gene expression analysis was performed using the limma package, and pathway enrichment analysis was conducted using clusterProfiler. Hub genes were ranked using the CytoHubba algorithms. MCC was prioritized due to its robustness in identifying fully connected subgraphs. Mendelian Randomization (MR) analysis was performed using the TwoSampleMR package to assess the causal relationships between identified hub genes and prostate cancer.

RESULTS: The analysis revealed significant differential expression of MTFP1 and MTFP2 between tumor and adjacent normal tissues, with MTFP2 showing a highly significant upregulation (p-value = 7.06e-06) and an AUC of 0.698, suggesting its potential as a biomarker. In the MR analysis, several hub genes, including ANLN, CDC45, CDCA2, and KIF15, were identified as having a significant causal relationship with prostate cancer, with effect estimates ranging from – 0.03 to 0.15 and statistically significant p-values. These findings suggest that mitochondrial dynamics and related pathways play a critical role in prostate cancer pathogenesis.

CONCLUSION: The study highlights the potential diagnostic and prognostic value of mitochondrial fission-related genes, particularly MTFP2, in prostate cancer and underscores the importance of further investigating these pathways as therapeutic targets.

PMID:40824549 | DOI:10.1007/s12672-025-03215-6

Eur Heart J. 2025 Aug 18:ehaf465. doi: 10.1093/eurheartj/ehaf465. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Dementia is a leading cause of death and disability that shares risk factors with atherosclerotic cardiovascular disease (ASCVD). High lipoprotein(a) is a causal risk factor for ASCVD while results for dementia are conflicting. With lipoprotein(a) lowering drugs in clinical trials, it was tested whether lipoprotein(a) levels are associated with the risk of Alzheimer’s disease and/or vascular-related dementia.

METHODS: Lipoprotein(a) measurements were available in 539 478 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the UK Biobank. Individuals were followed for up to 30.2 years, during which 6404 developed Alzheimer’s disease and 7866 vascular-related dementia. LPA kringle IV type 2 (KIV-2) number of repeats, which determines lipoprotein(a) isoform size and correlates inversely with lipoprotein(a) levels, were available in 117 029 individuals from the Copenhagen studies. Statistical analyses accounted for competing risk of death, important for studies of dementia occurring late in life.

RESULTS: On continuous scales, lipoprotein(a) levels were not associated with the risk of Alzheimer’s disease or vascular-related dementia. When accounting for competing risk of death, absolute risks of vascular-related dementia increased with higher lipoprotein(a) levels in the UK Biobank (n = 452 989; events = 5132; P = .01), but not in the Copenhagen studies (n = 80 313; events = 2734; P = .42). In the Copenhagen studies, LPA KIV-2 number of repeats ≤5th vs > 50th percentiles associated with a subdistribution hazard ratio for Alzheimer’s disease of 1.25 (95% confidence interval, 1.06-1.46).

CONCLUSIONS: Low lipoprotein(a) levels were not associated with the risk of Alzheimer’s disease or vascular-related dementia. It cannot be excluded that very high lipoprotein(a) or small isoform size increases the risk of dementia.

PMID:40824531 | DOI:10.1093/eurheartj/ehaf465

Int J Comput Assist Radiol Surg. 2025 Aug 18. doi: 10.1007/s11548-025-03500-3. Online ahead of print.

ABSTRACT

PURPOSE: Computed tomography perfusion (CTP) imaging for acute ischemic stroke relies on accurately identifying hypoperfused brain tissue to guide treatment decisions. However, deconvolution-based methods often suffer from variability in perfusion parameters and lesion volumes across different software. This study evaluated the feasibility of temporal fractal analysis, specifically, time series-derived fractal dimension (FD) using the Higuchi method, as a biomarker for detecting hypoperfused brain tissue.

METHODS: Fractal analysis was applied to voxel-wise time-series data from both simulated phantom datasets and 149 CTP images from the publicly available Ischemic Stroke Lesion Segmentation (ISLES) 2024 dataset. FD was calculated using optimized parameters determined through the phantom study. In the patient study, the ischemic core was defined by follow-up MRI, and the penumbra was defined as tissue with Tmax > 6 s. FD values were statistically compared between core, penumbra, and normal tissue. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis.

RESULTS: In the phantom study, FD showed a strong correlation (ρ > 0.9) with true cerebral blood flow (CBF) across all cerebral blood volume (CBV) values when the tuning parameter k_max was optimized based on the number of CTP frames. In the patient study, FD differed significantly across tissue types (p < 0.001). For penumbra versus normal classification, FD achieved an AUC of 0.732, outperforming CBF and CBV (p < 0.001). In core versus penumbra classification, FD showed the highest AUC of 0.641 among all metrics.

CONCLUSION: Time series-derived FD offers a promising approach to characterizing perfusion abnormalities in stroke, with potential as a complementary metric to conventional CTP parameters.

PMID:40824507 | DOI:10.1007/s11548-025-03500-3

J Cancer Educ. 2025 Aug 18. doi: 10.1007/s13187-025-02709-9. Online ahead of print.

ABSTRACT

Patient-reported outcomes (PROs) and caregiver-reported outcomes (CROs) are tools for evaluating behavioral medicine interventions and for bringing the patient voice into observational research. This study aimed to identify barriers to using PROs/CROs in behavioral cancer research and to equitably address those barriers. Forty-nine members of a cancer special interest group from a research society completed surveys in early 2023 about needs related to the use of PROs and CROs. Descriptive statistics were used to summarize results. Most participants used PROs (n = 34, 69%) but few frequently used CROs (n = 12, 24%). More than 80% of the sample were familiar with common PRO/CRO properties such as reliability and validity. Participants reported considering a wide variety of population characteristics when using PROs and CROs, including language (n = 31, 70%) and education level (n = 31, 70%). The most common barriers to using PROs/CROs in research were time, funding, and technology with many reflecting potential reasons for inequitable representation of certain groups in research. Webinars were the most preferred educational format (n = 38, 78%) for resources related to PROs/CROs. Many participants encountered barriers to using PROs in research. Creation and dissemination of educational resources to promote equitable use of PROs/CROs across underrepresented groups and overcome common barriers to use of these measurement tools are warranted.

PMID:40824476 | DOI:10.1007/s13187-025-02709-9

Blood Res. 2025 Aug 18;60(1):46. doi: 10.1007/s44313-025-00094-2.

ABSTRACT

BACKGROUND: Inflammation indices are emerging predictors of diseases. Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous state and chronic inflammation may drive MGUS progression. This study aimed to evaluate the association between inflammatory markers and MGUS.

METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) III and 1999-2004 were collected from 6,383 participants. MGUS subtypes were identified using immunofixation electrophoresis. Seven inflammatory indices [lymphocyte count (LC), neutrophil count (NC), platelet-neutrophil product (PPN), systemic immune inflammation index (SII), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP)] were calculated. Weighted multivariate regression and subgroup analyses assessed the relationships, reported as odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Of the 6383 patients included in the study, 157 (2.45%) underwent MGUS. There was a significant correlation trend between ln PPN level and the development of MGUS, especially at low levels (OR: 2.62, 95% CI: 1.54-4.75, p-trend = 0.001), while the correlation between PLR level and MGUS was not obvious. In the subgroup analysis, a significant association between PPN level and MGUS was mainly found in the overall population, female sex, non-Hispanic black, non-hypercholesterolemia, non-type 2 diabetes (T2D), high school education or above, and divorced or widowed; however, there was no significant interaction between PPN level and MGUS in each subgroup.

CONCLUSION: PPN levels were significantly associated with MGUS development. Our study identified PPN as a novel and convenient inflammatory marker with potential clinical relevance. Although preliminary, the observed associations highlight the need for validation through longitudinal studies before considering their clinical applications.

PMID:40824475 | DOI:10.1007/s44313-025-00094-2

J Robot Surg. 2025 Aug 18;19(1):492. doi: 10.1007/s11701-025-02679-6.

ABSTRACT

The relative benefits of single-port (SP) versus multi-port (MP) robot-assisted radical prostatectomy (RARP) for prostate cancer remain uncertain, with conflicting evidence reported in the literature. This systematic review aimed to compare perioperative outcome metrics, oncologic efficacy, and functional recovery outcomes between SP-RARP and MP-RARP. A thorough literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library to locate English-language research published until June 2025. All statistical analyses, encompassing meta-analyses, were performed utilizing R software (version 4.3.1). Weighted mean differences (WMDs) and 95% CIs were used to summarize continuous outcomes, while odds ratios (ORs) with 95% CIs were computed for dichotomous variables. Statistical significance was established at P < 0.05. The review protocol was registered prospectively in PROSPERO (CRD420251114408). A total of 15 studies involving 3,116 patients (SP-RARP: 1,525; MP-RARP: 1,591) were included. Patients undergoing SP-RARP experienced significantly lower estimated blood loss (WMD -41.36 (-68.79, -13.94); P = 0.003), shorter hospital stays (SMD -0.95 (-1.77, -0.13); P = 0.02), and earlier urinary catheter removal (WMD -1.77 (-2.88, -0.66); P = 0.002) compared with those receiving MP-RARP. SP-RARP was also associated with lower pain scores on the day of surgery (WMD -0.88 (-1.29, -0.48); P < 0.001) and reduced opioid use during hospitalization (OR 0.35 (0.22, 0.54); P < 0.001) and at discharge (OR 0.03 (0.01, 0.10); P < 0.001). Nonetheless, for functional outcomes related to potency and continence, along with perioperative complications, positive surgical margins, biochemical recurrence, and duration of surgery, no statistically significant differences were seen between the groups. SP-RARP offers advantages in reducing intraoperative blood loss, accelerating recovery, and improving postoperative pain control compared to MP-RARP. Although operative time is longer, both approaches provide comparable oncological and functional outcomes.

PMID:40824469 | DOI:10.1007/s11701-025-02679-6

Cancer Chemother Pharmacol. 2025 Aug 18;95(1):81. doi: 10.1007/s00280-025-04804-6.

ABSTRACT

PURPOSE: Inherited dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for severe 5-fluorouracil toxicity. We report a phenotyping approach (thymine challenge test) to prospectively determine DPD activity and the association with severe adverse events.

METHODS: The primary aim of this prospective study was to determine whether a thymine challenge test could prospectively identify patients at risk of severe toxicity from treatment with 5-fluorouracil/capecitabine in combination chemotherapy schedules or monotherapy. The focus was prediction of those at risk of ≥ grade 3 gastrointestinal toxicity. DPD activity was determined from the thymine/dihydrothymine (THY/DHT) ratio measured in a urine sample after a thymine test dose (250 mg, oral).

RESULTS: Of the 166 patients, 11.7% had severe diarrhoea/mucositis. The THY/DHT ratio was not significantly different in these individuals compared to those with minimal toxicity. However, post hoc analysis found decreased DPD activity in those who had non-gastrointestinal toxicity, most notably grade ≥ 2 Hand-Foot syndrome (p = 0.001).

CONCLUSION: The data do not support our primary hypothesis that this phenotyping approach would discriminate those at risk of severe/life-threatening gastrointestinal toxicity. The clinical factors which influence gastrointestinal toxicity, particularly in patients receiving CAPOX require further investigation.

CLINICAL TRIAL REGISTRATION: ACTRN 12,617,001,109,392 registered 28/07/2017.

PMID:40824448 | DOI:10.1007/s00280-025-04804-6

AMB Express. 2025 Aug 18;15(1):119. doi: 10.1186/s13568-025-01930-5.

ABSTRACT

Evidence from observational studies and clinical trials has reported that gut microbiota (GM) was associated with chronic lung diseases (CLDs). However, the causal relationships between GM and CLDs have yet to be fully ascertained. The Mendelian randomization (MR) based causal analysis was performed using the genome-wide association study (GWAS) summary statistics from the MiBioGen and FinnGen consortium. GM served as exposure, and CLDs were taken for outcomes. Inverse variance weighted, MR-Egger, and weighted median methods were utilized to examine the causal association between GM and CLDs. The sensitivity analyses were then conducted to validate the robustness of the results. Further, the reverse MR analysis was performed to evaluate the possibility of reverse causation. Finally, the in-silico in-situ microbiota resequencing (ISSMR) of high-throughput sequencing data was utilized as a supplement to dissect the role of microbiota spatial distribution disturbance on the onset of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). This study revealed that GM had causal associations with CLDs. Conversely, reverse MR analysis suggested that the presence of COPD and IPF may causally influence the abundance of specific GM. And ISSMR further provided clues to the interaction of intra-tissue as well as gut microbe disturbance in IPF and COPD from synergistic or independent perspectives. In short, the MR analysis revealed a causal relationship between GM and CLDs from a host genetic perspective, and ISSMR extended the host-microbe regulatory modality from a microbe genetic perspective, thus together providing novel insights into the gut microbiota-mediated development mechanism of CLDs.

PMID:40824435 | DOI:10.1186/s13568-025-01930-5

Head Neck Pathol. 2025 Aug 18;19(1):104. doi: 10.1007/s12105-025-01834-7.

ABSTRACT

AIM: The present study aimed to contribute to the biological characterization of odontogenic ghost cell lesions (OGCL).

MATERIALS AND METHODS: Sixty-nine OGCL consisting of 60 calcifying odontogenic cysts (COC) and nine dentinogenic ghost cell tumors (DGCT) were collected from a single center over a period of 63 years. The clinical, radiographic, and histopathological features were re-evaluated. Histochemical and immunohistochemical studies were performed in 37 COC and three DGCT. Molecular studies were performed in 17 COC to identify possible CTNNB1 gene mutations.

RESULTS: COC was more frequent in women, in the second decade of life, involved the anterior region of both jaws, and manifested mainly as a unilocular radiolucency. DGCT was more frequent in women, in the ninth decade of life, involved the anterior region of mandible, and manifested as irregular mixed lesions. The ameloblastic/ameloblastomatous epithelium and ghost cells stained positive for AE1-AE3 (40/40), amelogenin (40/40), β-catenin (40/40), E-cadherin (40/40), S100 (22/40), and vimentin (15/40) in both the studied entities. TOM-20 (40/40), BCL-2 (40/40), BRAF V600E (4/40), and p63 (1/40) were only positive in the ameloblastic/ameloblastomatous epithelium, and lysozyme (40/40) and CD68 (35/40) were positive in the ghost cells. No single-nucleotide variants were detected in CTNNB1, except for a change at codon 38.

CONCLUSIONS: The protein immuno-expression observed in ghost cells confirms an epithelial origin and suggests that these cells result from a degenerative process involving an increase in lysosomes and accumulation of proteins. Immuno-expression of β-catenin in the absence of CTNNB1 mutations suggests the presence of mutations in other genes associated with the WNT/β-catenin pathway.

PMID:40824428 | DOI:10.1007/s12105-025-01834-7

Br J Math Stat Psychol. 2025 Aug 18. doi: 10.1111/bmsp.70007. Online ahead of print.

ABSTRACT

The use of exponential random graph models (ERGMs) is becoming prevalent in psychology due to their ability to explain and predict the formation of edges between vertices in a network. Valid inference with ERGMs requires correctly specifying endogenous and exogenous effects as network statistics, guided by theory, to represent the network-generating process while ensuring key effects shaping network topology are not omitted. However, specifying a comprehensive model is challenging, particularly when relying on a single model. Despite this, most applied research continues to use a single ERGM, raising two concerns: Selecting misspecified models compromises valid statistical inference, and single-model inference ignores uncertainty in model selection. One approach to addressing these issues is Bayesian model averaging (BMA), which evaluates multiple candidate models, accounts for uncertainty in parameter estimation and model selection, and is more robust to model misspecification than single-model inference. This tutorial provides a guide to implementing BMA for ERGMs. We illustrate its application using data from a college friendship network, with a supplementary example based on the Florentine marriage network; both focus on averaging exogenous covariate effects. We demonstrate how BMA incorporates theoretical considerations and addresses modelling challenges in ERGMs, with annotated R code provided for replication and extension.

PMID:40820875 | DOI:10.1111/bmsp.70007