Nevin Manimala

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

Biomed Environ Sci. 2025 Jul 20;38(7):885-890. doi: 10.3967/bes2025.073.

NO ABSTRACT

PMID:40820257 | DOI:10.3967/bes2025.073

Sci Rep. 2025 Aug 17;15(1):30121. doi: 10.1038/s41598-025-14436-8.

ABSTRACT

Potato leafroll disease, caused by potato leafroll virus (PLRV), is one of the most devastating diseases, resulting in significant losses to the potato crop. Research on comprehensive studies examining the prediction of mutations in PLRV genes for this viral disease is limited. This study aims to quantify and characterize the accumulation of these genetic mutations by predicting SNPs for PLRV RNA-dependent RNA polymerase (RdRP) using computational approaches. We utilized advanced online protein prediction tools to explore the impact of DNA mutations on protein function and structure. These tools enabled us to assess the potential level and location of disorder within proteins, providing crucial insights into their behavior. In our study, the polymerase chain reaction (PCR) yielded a product corresponding to the PLRV-RdRp gene, measuring 450 base pairs (bp). This sequence has been documented in GenBank under the access number MT576073 and is cataloged in the UniProt database with the ID A0A8E6I3S8. The phylogenetic analysis of the PLRV-RdRp sequence involved a comparative study with reference sequences in the NCBI database. We focused on two notable predicted inversion mutations located at positions 93 (A93T) and 117 (K117G). Remarkably, the (Lys/Gly) mutation at position 117 exhibited a substantial disorder percentage of 61%, significantly higher than the reference sequence’s 13.4%. These single nucleotide polymorphisms (SNPs) are not just statistical anomalies; they have real implications. They alter RdRp protein stability and physicochemical properties, altering pocket residues and influencing the protein’s interaction with natural compounds. In conclusion, our findings provide a solid foundation for future research and development efforts focused at the rapid diagnosis and sustainable management of PLRV.

PMID:40820237 | DOI:10.1038/s41598-025-14436-8

Gut Liver. 2025 Aug 18. doi: 10.5009/gnl250164. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The relationship between Helicobacter pylori (HP) eradication and osteoporosis development remains inadequately elucidated. This study aimed to ascertain whether HP eradication therapy confers protective effects against osteoporosis progression.

METHODS: Subjects without osteoporosis who underwent esophagogastroduodenoscopy with concurrent HP testing were prospectively recruited between May 2003 and February 2023 at Seoul National University Bundang Hospital. Participants were stratified into two cohorts: those with successful HP eradication and those without. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry, and the risk of osteoporosis was assessed using Cox proportional hazards regression analysis.

RESULTS: The successfully eradicated cohort comprised 730 individuals (mean age, 56.4 years; 67.5% female), compared with 116 individuals (mean age, 56.2 years; 74.1% female) in the non-eradicated cohort. Osteoporosis occurred in 179 subjects (24.5%) in the eradicated group and in 40 subjects (34.5%) in the non-eradicated group. Significant risk factors for osteoporosis included female sex (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.93 to 5.05; p<0.001), advanced age (HR, 1.08; 95% CI, 1.06 to 1.10 per year; p<0.001), and persistent HP infection (HR, 1.60; 95% CI, 1.13 to 2.28; p=0.009). In subgroup analyses according to sex and age, HP eradication demonstrated a significant reduction in osteoporosis risk in females (p=0.005) than in males, especially among females aged ≥50 years (p=0.003). However, this change was not pronounced in males.

CONCLUSIONS: HP eradication may serve as a preventive intervention against osteoporosis development, particularly among female subjects (ClinicalTrials.gov: NCT06818591).

PMID:40820207 | DOI:10.5009/gnl250164

Trop Dis Travel Med Vaccines. 2025 Aug 18;11(1):29. doi: 10.1186/s40794-025-00265-0.

ABSTRACT

BACKGROUND: Malaria is a major health problem around the world. Plasmodium falciparum (P. falciparum) is the species that is most commonly associated with the severe and complicated forms of malaria, especially in tropical and subtropical areas, including Ethiopia. One of the complications of malaria is its impact on kidney and electrolyte levels. The objectives of the study were to assess the kidney function and serum electrolyte levels among untreated malaria patients infected with P. falciparum.

METHODOLOGY: A case-control study that enrolled a total of 108 participants (54 with confirmed untreated P. falciparum malaria as a case and 54 were non-malaria as a control). Participants in the study were included based on systematic random sampling technique. Data were collected using questionnaires administered by interviewers. 5 ml of blood samples were collected to investigate kidney function such as creatinine and urea, as well as serum electrolytes such as sodium ion (Na⁺) and potassium ion (K⁺), using a chemistry automated analyzer. Data were analyzed using the statistical package for social science (SPSS) version 27. P < 0.05 was considered statistically significant at a 95% confidence interval (CI).

RESULT: The study subjects were comprised of 52 (48.1%) men and 56 (51.9%) women. The mean age for the case group and the control group was 26.85 ± 8 and 27.17 ± 7.17 years old, respectively. The result showed a statistically significant (P < 0.05) increase in serum creatinine and urea level in the case group (1.32 ± 0.29 mg/dL and 39.8 ± 8.34 mg/dL) compared with the control group (0.92 ± 0.32 mg/dL and 25.78 ± 7.97 mg/dL), respectively. The serum levels of Na⁺ and K⁺ were significantly (P < 0.05) decreased in the case group (132.15 ± 3.96 mmol/L and 3.44 ± 0.40 mmol/L) as compared to the control group (137.11 ± 3.11 mmol/L and 3.94 ± 0.39 mmol/L), respectively.

CONCLUSION: Malaria has a significant impact on kidney function (creatinine and urea) and serum electrolytes (Na⁺ and K⁺). This may indicate that malaria is the determinant factor for developing kidney dysfunction and serum electrolyte imbalance. Hence, we recommend routine evaluation of these parameters in malaria-infected individuals.

PMID:40820204 | DOI:10.1186/s40794-025-00265-0

Sci Rep. 2025 Aug 17;15(1):30103. doi: 10.1038/s41598-025-14108-7.

ABSTRACT

Antimicrobial resistance (AMR), associated with irrational antimicrobial use (AMU) poses a significant health threat to both humans and animals. Thus, our research determined AMU patterns and their associated factors in Bangladeshi chicken farms. We conducted a cross-sectional study in 340 commercial chicken farms comprising broilers (109), layers (109), and Sonali (122) farms in seven districts of Bangladesh from September to October 2021. Data were collected using in-person interviews with a pre-tested semi-structured questionnaire. Statistical analyses were performed, including descriptive statistics to understand farmer demographics and AMU practices, a Chi-square test to evaluate farmers’ knowledge, attitudes and practices (KAP), and logistic regression analysis to determine the factors associated with AMU. The findings indicated that 93.2% (317/340) farms administered at least one antimicrobial (AM) to chickens during the production cycle, with 67.0% of farmers used antimicrobials (AMs) in the 14 days before data collection. The usage of AMs was higher in meat-type chickens, such as broiler (78.0%) and Sonali (67.2%), in contrast to egg-type chickens, like layer (41.3%). The AMU practices were significantly associated with multiple factors, such as farming experience, poultry production type, knowledge gaps in proper AMU practices, the person managing the farm, reuse of left-over AMs, and compliance with veterinarians’ recommendations. We highlight the indiscriminate use of AMs that is occurring in poultry industry in Bangladesh, which could result in AM residues and resistance, posing detrimental consequences for public health. Farmers training on increasing their KAP regarding AMU to protect animal health, human health, and the ecosystem, is urgently needed.

PMID:40820200 | DOI:10.1038/s41598-025-14108-7

Adv Ther. 2025 Aug 18. doi: 10.1007/s12325-025-03318-0. Online ahead of print.

ABSTRACT

BACKGROUND: Tobacco smoking remains a global public health challenge, contributing to preventable mortality and morbidity and imposing substantial burdens on health care costs. We investigated whether direct health care costs differ substantially between self-reported tobacco smokers and non-smokers.

METHODS: This systematic literature review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Medline PubMed, Embase, PubMed Central, and Scopus were searched to identify studies of direct health care costs between smokers and non-smokers for participants aged ≥18 years. All observational, prospective, retrospective, and non-randomized comparative studies were considered. Data extraction included mean annual health care costs (± SD) for both groups. Mean differences (MD) in annual health care costs between smokers and non-smokers, expressed in 2025 US dollars, were compared and adjusted for a 12-month period and inflated to 2025 using consumer price indices.

RESULTS: Of 873 studies identified, 11 were included in quantitative synthesis, which compared 19,759,529 smokers with 206,913,108 non-smokers for direct health care costs. Mean age ranged from 34.5-60.6 years for smokers and 34.3-65.1 years for non-smokers. Mean annual health care costs ranged from $65,640-$1297.1 for smokers and $54,564-$724.4 for non-smokers. Annual incremental direct health care costs for smokers versus non-smokers ranged from -$458 (95% CI [confidence interval]: -2011.0 to 1,095.0) to $11,076 (95% CI: 10,211.9 to 11,940.1) in 2025 US dollars. Meta-analysis revealed smoking generally incurred greater health care costs than non-smoking, with a mean annual incremental cost of $1916.5 (95% CI: -439.9 to 4,272.9). The result was not statistically significant (MD = 1,916.5; p = 0.111). Substantial heterogeneity was observed (I² = 99.9%). Sensitivity analysis excluding studies of chronic disease yielded a reduced incremental cost for the general population, with a statistically significant difference (MD = 583.9, p = 0.02), although heterogeneity remained high (I² = 98.0%).

CONCLUSION: This meta-analysis supports the assertion that smoking substantially increases direct health care costs compared with non-smoking, particularly for the general population.

PMID:40820188 | DOI:10.1007/s12325-025-03318-0