Category: Statistics

Planta. 2025 Dec 22;263(1):33. doi: 10.1007/s00425-025-04898-5.

ABSTRACT

To elucidate the phytobiochemical mechanisms underlying differentiation among wild populations of Tithonia diversifolia (Helms) A. Gray and establish how soil parameters regulate metabolic pathways.

METHODS: 90 individuals from three populations (Ixtaczoquitlán, Orizaba, Rafael Delgado; Veracruz, Mexico) were analyzed. A multi-analytical approach included lipid profiling by gas chromatography-mass spectrometry (GC-MS), identification of secondary metabolites via HPTLC, quantitative bromatological analyses, photosynthetic pigment quantification, and comprehensive edaphoclimatic characterization. Statistical modeling integrated soil chemistry, climatic dynamics, and phytobiochemical responses.

RESULTS: Populations exhibited distinct metabolic phenotypes shaped by edaphic stress. Plants from Rafael Delgado expressed a classical hormetic response under moderate stress (neutral pH, high EC and CEC, low organic matter, clayey soil), with upregulation of biosynthetic pathways resulting in higher protein content (27.25 ± 1.12% DW) and a diverse fatty acid profile (seven compounds). In contrast, Ixtaczoquitlán and Orizaba populations, under more favorable soils, maintained homeostatic regulation prioritizing primary metabolism, with higher chlorophyll accumulation (1.96 ± 0.10 mg g^-1) but reduced synthesis of defensive compounds. Foliar pH remained stable (6.7 ± 0.3) across sites, suggesting a robust self-regulation capacity despite edaphoclimatic variability.

CONCLUSIONS: Stress-induced metabolic switching emerges as a key adaptive mechanism in this non-model species, highlighting how environmental gradients reprogram biosynthetic pathways. Hormesis-driven enhancement of bioactive compounds positions T. diversifolia as a promising system for biotechnology aimed at stress-induced biocompound production. These findings advance the state of the art in plant metabolic plasticity and support the sustainable exploitation of renewable ethnobotanical resources.

PMID:41428232 | DOI:10.1007/s00425-025-04898-5

Langenbecks Arch Surg. 2025 Dec 22. doi: 10.1007/s00423-025-03950-y. Online ahead of print.

ABSTRACT

PURPOSE: The indication for surgical treatment of rectus diastasis (RD) without a coexisting hernia remains controversial. Although guidelines exist, the lack of robust data allows only weak recommendations. This study aimed to provide comprehensive nationwide data on the surgical management of RD without hernia.

METHODS: This retrospective observational multicenter study analyzed anonymous data from the German nationwide hospital discharge dataset (2010-2023). Patients with coexisting hernia or under 18 years were excluded. The primary endpoint was the annual number of RD surgeries without hernia. Secondary endpoints included trends over 13 years, patient demographics, mesh use, and early postoperative complications.

RESULTS: A total of 2,768 cases were identified (mean age 46.2 ± 13.2 years; 76.2% female). The annual case number ranged from 120 to 253, with no consistent trend. A mesh was used in 28.0% (n = 775), while 72.0% underwent reconstruction without documented mesh. Data on surgical approach (open vs. minimally invasive) were not available. The overall early complication rate was 6.9%, with bleeding and wound infections most common. Male patients had significantly higher complication rates. Major limitations include potential coding bias, underreporting, and missing data on surgical technique.

CONCLUSION: This is the first real-world big data analysis of RD repair without hernia in Germany. On average, 198 procedures are performed annually with a low complication rate. The findings support surgical treatment in selected symptomatic cases and emphasize the need for standardized coding and prospective registry data.

PMID:41428229 | DOI:10.1007/s00423-025-03950-y

Eur J Clin Pharmacol. 2025 Dec 22;82(1):14. doi: 10.1007/s00228-025-03959-8.

ABSTRACT

PURPOSE: This systematic review aimed at consolidating evidence regarding vancomycin dosing regimens, therapeutic drug monitoring (TDM) practices, clinical efficacy, and toxicity profiles in neonates admitted to neonatal intensive care units (NICUs). The primary research question focused on identifying the most effective and safe vancomycin protocols for this vulnerable population.

METHODS: Following PRISMA guidelines, a comprehensive search was conducted in six databases: PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Lilacs. Eligible studies included observational cohorts and randomized clinical trials involving neonates receiving intravenous vancomycin with reported dosing and TDM data. Data extraction encompassed study design, dosing regimens, serum concentration targets, efficacy outcomes, and toxicity reports.

RESULTS: Thirty-two studies met inclusion criteria, revealing substantial heterogeneity in vancomycin dosing strategies, target trough concentrations, and evaluation methods for efficacy and toxicity. Target serum concentrations varied widely (5-30 mg/L), and dosing regimens ranged from 10 to 61 mg/kg/day. Only three studies assessed clinical efficacy, and eleven evaluated nephrotoxicity risk, with reported nephrotoxicity rates between 1.1% and 14%. Variability in methods limited the comparability across studies.

CONCLUSIONS: Vancomycin use in neonates lacks standardized dosing and monitoring practices, making it challenging to define an optimal therapeutic protocol. Greater consistency in clinical approaches and further high-quality studies are urgently needed to establish safe and effective vancomycin management strategies for neonatal patients.

PMID:41428193 | DOI:10.1007/s00228-025-03959-8

Adv Ther. 2025 Dec 22. doi: 10.1007/s12325-025-03441-y. Online ahead of print.

ABSTRACT

INTRODUCTION: PTEN hamartoma tumor syndrome (PHTS) is a rare genetic disorder caused by germline pathogenic variants in the PTEN tumor suppressor gene. Everolimus, an oral mTORC1 inhibitor, is approved for the treatment of tuberous sclerosis complex-related tumors; however, evidence for its efficacy in PHTS remains limited. A recent randomized controlled trial (RCT) reported safety and efficacy findings, but the composite primary efficacy endpoint did not reach statistical significance.

METHODS: We conducted a sensitivity analysis of this RCT to further evaluate the efficacy of everolimus in PHTS. Five statistical approaches were applied: analysis of covariance and four linear mixed-effects models. Outcomes included the composite neurocognitive score as a primary endpoint and multiple secondary neurocognitive and behavioral measures.

RESULTS: Across all analysis approaches, everolimus did not significantly improve the composite neurocognitive score compared with placebo. However, several secondary outcomes showed consistent benefits. Fine motor function assessed by the Purdue Pegboard Test (left hand) demonstrated sustained improvement over placebo across models. Social functioning, assessed by the total score (higher values indicating better functioning) of the reverse-coded Social Responsiveness Scale, second edition, improved over time, with significant differences observed at 6 months in the everolimus group. Several additional secondary endpoints showed consistent trends favoring everolimus.

CONCLUSION: Although the composite primary endpoint did not demonstrate significant improvement, sensitivity analyses identified potential benefits of everolimus in motor and social domains in individuals with PHTS. These results are consistent with the original trial findings and provide further support for investigating everolimus as a therapeutic option in this population.

PMID:41428178 | DOI:10.1007/s12325-025-03441-y

Curr Med Sci. 2025 Dec 22. doi: 10.1007/s11596-025-00146-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the associations of the triglyceride-glucose (TyG) index with kidney function decline, cardiovascular disease (CVD) events, and all-cause mortality across different glucose tolerance statuses.

METHODS: We analyzed 8,434 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. The primary outcomes were kidney function decline, CVD events, and all-cause mortality. Associations between the TyG index and outcomes were evaluated using binary logistic regression models.

RESULTS: During a 5-year follow-up, 150 participants (1.80%) developed kidney function decline, 357 (4.30%) experienced CVD events, and 335 (4.00%) died from all causes. An elevated TyG index was associated with increased risks of kidney function decline, nonfatal CVD events, and all-cause mortality in the overall population and among participants with diabetes (quartile 4 [Q4] vs. quartile 1 [Q1]: hazard ratio [HR] [95% confidence interval, P-value] = 4.97 [1.41-31.71, P = 0.034], 4.63 [1.25-30.19, P = 0.047], and 4.54 [1.70-15.88, P = 0.007], respectively). These associations were not statistically significant in participants with normal glucose tolerance or prediabetes. Notably, an elevated TyG index was significantly associated with increased risk of fatal CVD events in the overall population and across all glucose tolerance subgroups, with the strongest association observed in participants with prediabetes rather than diabetes.

CONCLUSIONS: The TyG index is significantly associated with the risks of kidney function decline, CVD events, and all-cause mortality, and these associations differ by glucose tolerance status.

PMID:41428156 | DOI:10.1007/s11596-025-00146-9

Eur J Clin Pharmacol. 2025 Dec 22;82(1):13. doi: 10.1007/s00228-025-03954-z.

ABSTRACT

PURPOSE: We conducted a comprehensive analysis of esketamine-related adverse events (AE) on the FDA Adverse Event Reporting System (FAERS) database, taking into account for the first time drug-drug interaction signals.

METHODS: We conducted a retrospective case/non-case study of esketamine-related AEs reported in the FAERS database up to the last quarter (Q4) of 2024. Potential signals were detected using the reporting odds ratio (ROR) and confidence intervals (CI), while drug-drug interactions were studied using different metrics such as lift, conviction and the combination risk ratio detection algorithm. An analysis of sex differences was also performed using the relative ROR and CI.

RESULTS: The analysis of 7,790 reports in which esketamine was a primary or secondary suspect identified potential safety signals for 173 AEs. Novel signals include homicidal ideation (ROR = 5.30, 95% CI: 2.38-11.82) and substance use disorder (ROR = 6.12, 95% CI: 2.54-14.73). Women showed a longer time to onset than men (p = 0.003). In addition, we detected sex differences in 23 AEs, seven of which were more likely to be reported in women, while 16 in men. Among these, four were significant exclusively in women (oxygen saturation decreased, abnormal behaviour, unresponsive to stimuli and aggression) and two in men (vision blurred and bradycardia). Potential signals of additive and multiplicative drug-drug interactions were detected for antidepressants (venlafaxine for”dizziness” and bupropion for “agitation”) and antipsychotics (risperidone for “vertigo”).

CONCLUSIONS: Our results increase knowledge on potential risks related to esketamine AEs and potential drug-drug interaction signals in a real-world setting.

PMID:41428148 | DOI:10.1007/s00228-025-03954-z

J Neurol. 2025 Dec 22;273(1):37. doi: 10.1007/s00415-025-13574-3.

ABSTRACT

BACKGROUND: Structural MRI studies have shown hypothalamic atrophy and altered white matter (WM) connectivity in amyotrophic lateral sclerosis (ALS), as a possible substrate of hypermetabolism in this condition. However, hypothalamic functional connectivity and its association with clinical features in ALS remain unclear. This study explored hypothalamic resting-state functional connectivity (RS-FC) in ALS patients compared to controls and its relationship with disease severity defined by the ALS Functional Rating Scale (ALSFRS-r), body mass index (BMI), disease duration, progression rate, survival, hypothalamic volume, and WM integrity.

METHODS: Seventy-one ALS patients and 39 healthy controls underwent structural and RS functional MRI. The bilateral hypothalamus was segmented, and a seed-based RS-FC analysis was performed. Group differences in hypothalamic RS-FC and their correlations with ALSFRS-r scores, BMI, disease duration, progression rate, survival, hypothalamic volume, and WM integrity were assessed. Tract-based spatial statistics was performed to estimate the correlation between WM damage in ALS and hypothalamic RS-FC.

RESULTS: ALS patients showed increased hypothalamic RS-FC with caudate nuclei compared to controls. Additionally, greater disease severity correlated with increased hypothalamic RS-FC with the caudate nuclei and orbitofrontal cortex. Hypothalamic RS-FC mean values also associated with FA in the genu of corpus callosum and forceps minor and disease progression rate. No significant correlations were observed with other clinical features.

CONCLUSIONS: These findings support hypothalamic alterations in ALS. Early detection of hypothalamic changes could be useful in prognostic stratification and evaluating intervention effects.

PMID:41428120 | DOI:10.1007/s00415-025-13574-3

Neuromolecular Med. 2025 Dec 22;28(1):1. doi: 10.1007/s12017-025-08900-x.

ABSTRACT

Lactylation has been identified as a novel epigenetic modification involved in neuroinflammation, mitochondrial dysfunction, and tau pathology. Although its relevance has been suggested in Alzheimer’s disease (AD), its causal contribution to distinct dementia subtypes remains unclear. We conducted a two-sample Mendelian randomization (MR) study to investigate whether the genetically predicted expression of 15 lactylation-related genes is causally associated with the risk of five dementia subtypes: Alzheimer’s disease (AD), Parkinson’s disease with dementia (PDD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and vascular dementia (VaD). Gene expression instruments were selected from whole-blood eQTL data (n = 31,684), and outcome data were derived from large-scale GWASs. The inverse-variance weighted (IVW) method served as the primary analytical approach, with Bonferroni correction (α = 0.05/15) applied for multiple testing. After correction, six gene-dementia associations remained statistically significant. Increased expression of EP300 and PFKP was associated with higher AD risk, while SIRT1 and LDHC showed protective effects against PDD. NUP50 was associated with increased FTD risk, and STMN1 with reduced risk of DLB. No significant associations were detected for VaD. All findings were robust in sensitivity analyses and supported by brain expression evidence from GTEx. Genetic evidence was provided for a causal relationship between lactylation-related gene expression and dementia subtype risk, offering potential mechanistic insights and therapeutic targets.

PMID:41428114 | DOI:10.1007/s12017-025-08900-x

Environ Monit Assess. 2025 Dec 22;198(1):63. doi: 10.1007/s10661-025-14910-w.

ABSTRACT

Climate change can affect the dispersion of air pollutants, and it is important to investigate how the emission sources would contribute to air pollution in the context of future climate scenarios. The main objective of this study is to examine the impact of climate-induced changes on dispersion and concentration of local air pollutants related with aircraft operations in airport. The dispersion modelling was implemented considering current and future climate conditions (Copernicus data for 2050). The emission inventory for NO₂ from aircraft was compiled for winter and summer periods using current publicly available flight-tracking data and emission factors provided by the European Environment Agency. The methodology is applied to Lisbon International Airport allowing quantification of climate-induced changes on local air pollution near the airport. Although the highest NO₂ levels related to aircraft activities occur in winter, the most pronounced difference between the two climate scenarios is obtained for summer, with an increase up to 73% in the daily average concentration under future climate conditions. The area exceeding the EU daily average limit value expands by 59% in summer, while a slight 4% decrease is obtained for winter. Additionally, the data were analysed considering modelling receptor point co-located with the current measurements and showing that at some hours the airport may contribute up to 25% of NO₂ observed in densely populated area. This study highlights the importance of climate change in shaping future airport-related air pollution, emphasizing the need for effective air quality management strategies in the context of climate change.

PMID:41428112 | DOI:10.1007/s10661-025-14910-w

J Robot Surg. 2025 Dec 22;20(1):104. doi: 10.1007/s11701-025-03075-w.

ABSTRACT

Even though robotic surgery is well described in simple vesico-ureteral reflux (VUR), few studies explore its role in complex uretero-vesical junction (UVJ) anomalies or redo surgery. This study assesses the role of different robotic surgical procedures and clinical features that can impact the result of complex robotic ureteral reimplantation in children. Retrospective, multicenter cohort of pediatric patients who underwent robotic reimplantation between 2017 and 2023 in case of redo surgery or complex UVJ anatomy. Reimplantation techniques included: dismembered and non-dismembered Lich-Gregoire(D-RALUR, ND-RALUR), Dismembered Extravesical Cross-Trigonal reimplantation(RADECUR). Major criteria of resolution: no symptoms and/or reintervention with a minimum follow-up of 6 months. The study included 6 centers, 134 patients, median age 4 years (IQR 2.1-6.6; range: 0.5-17.4), median weight 15.2 Kg(IQR 13.1-22.0; range: 6.7-80.0). Redo surgery(48, 35.8%), duplex systems(38, 28.4%), obstructive megaureter(29, 21.6%) and others(27, 20.1%). D-RALUR 65 (48.5%), ND-RALUR 56(41.8%), RADECUR 13(9.7%). Early post-operative complication rate was 17.9%(including Clavien I-IIIb, with major complications, grade IIIb in 4.5% of patients – 2 incisional hernia, 4 UVJ stenosis). At a median follow-up of 21.2 months (IQR 11.7-33.3; range 6.0-80.1) the resolution was 82.2%. The comparative analysis found no significant difference in resolution respect to pathology (p = 0.179), technique (p = 0.331), age (p = 0.937) and weight (p = 0-495). There was no statistical difference in resolution rate when stratifying on weight ≤ 10Kg (p = 0.633) and ≤ 15 kg (p = 0.586). Within patients who experienced treatment failure we recorded 9 UVJ obstruction: 5(9%)D-RALUR, 4(8%)ND-RALUR; 11 VUR: 2(15%)RADECUR, 7(12%) D-RALUR, 2 (4%)ND-RALUR and 1 recurrent febrile UTI without VUR or obstruction: 1(D-RALUR). Robotic reimplantation is a valid option in case of complex pediatric UVJ pathologies, with good results also in children with a < 10 kg body weight.

PMID:41428111 | DOI:10.1007/s11701-025-03075-w