Nevin Manimala

Eur Spine J. 2025 Nov 29. doi: 10.1007/s00586-025-09644-9. Online ahead of print.

ABSTRACT

PURPOSE: Upper lumbar disc herniations (L1-2, L2-3) present unique anatomical challenges due to narrow interlaminar windows and facet joint proximity. This pilot feasibility study aimed to evaluate the safety and short-term efficacy of a novel minimally invasive tubular trans-isthmus oblique approach for upper lumbar disc herniation, prior to a planned prospective trial.

METHODS: Twenty patients (13 males, 7 females; mean age 50.8 years) with imaging-confirmed L1-2 or L2-3 paracentral disc herniation and unilateral leg pain unresponsive to conservative management were enrolled between January 2022 and January 2024. All underwent decompression using the novel tubular trans-isthmus oblique approach designed to preserve the medial facet cortex. Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for leg pain were assessed preoperatively and at 1, 3, 6, and 12 months. Modified Macnab criteria were recorded at 12 months. Dynamic radiographs and postoperative CT (in selected cases) assessed stability and facet preservation. Statistical analysis was performed using JASP v0.18 with Wilcoxon Signed Rank Test and Friedman test.

RESULTS: Median preoperative ODI was 83%, improving to 5% at 3 months (p < 0.001). VAS leg pain scores improved from a mean of 8.24 to 1, 0, and 0 at 1, 3, and 12 months respectively (p < 0.01). Seventeen patients had excellent outcomes, 2 good, and 1 fair per Macnab criteria. No recurrence or radiological instability was observed. One dural tear and one transient L2 dysesthesia resolved without sequelae.

CONCLUSION: To the best of our knowledge, this is the first clinical study to describe and evaluate a minimally invasive tubular trans-isthmus oblique approach for upper lumbar disc herniation. The technique appears technically feasible and safe. These encouraging results support the need for larger prospective trials to confirm long-term outcomes and reproducibility.

PMID:41318870 | DOI:10.1007/s00586-025-09644-9

Sci Rep. 2025 Nov 29. doi: 10.1038/s41598-025-30695-x. Online ahead of print.

ABSTRACT

The brown bear Ursus arctos, Eurasian lynx Lynx lynx, and gray wolf Canis lupus are Europe’s threatened large carnivores. The analyses were conducted using data on the abundance of these species in Poland, collected by the Polish Central Statistical Office (bear 1965-2023, wolf 1995-2023, and lynx 1996-2023). For the years 2000-2023, data were also available by region. We subjected these data to statistical analysis: chi-square tests, segmented regression, and principal component analysis. Biplots, charts of population dynamics, and distribution maps were created to visualize the results. In Poland in the analyzed time period, an increase in the population of all three studied carnivores was observed along with the westward expansion of the territorial range of lynx and wolf, while bear range remained unchanged. The most mean population increase was exhibited by the gray wolf (7.01%), followed by the brown bear (4.78%) and, finally, the Eurasian lynx (2.94%). The population dynamics of the carnivores showed trends over time, with a notable increase in the last decade. The use of multi-year data in modelling enables a better understanding of the mechanisms governing the abundance and distribution of populations of endangered species. This, in turn, facilitates the planning of more effective conservation measures.

PMID:41318866 | DOI:10.1038/s41598-025-30695-x

Inflammopharmacology. 2025 Nov 29. doi: 10.1007/s10787-025-02059-4. Online ahead of print.

ABSTRACT

BACKGROUND: Urarthritis is an inflammatory disorder triggered by monosodium urate (MSU) crystal deposition, and its pathogenesis involves interaction between oxidative stress (OS) and inflammation. Diacerein, an agent endowed with anti-inflammatory and antioxidant properties, has not yet been fully characterized in acute urarthritis. This study was designed to evaluate the therapeutic efficacy of diacerein in acute urarthritis and to elucidate its regulatory effects on the Nrf-2/HO-1 and NF-κB pathways.

METHODS: The Wistar rat model of acute urarthritis was established, and 50 rats were randomly divided into 5 groups (10 rats per group): normal control group (AG, gavage with 0.5% sodium carboxymethyl cellulose), model group (BG, gavage with 0.5% sodium carboxymethyl cellulose), low-dose diacerein group (CG, gavage with 50 mg/kg diacerein), medium-dose diacerein group (DG, gavage with 100 mg/kg diacerein), high-dose diacerein group (EG, gavage with 200 mg/kg diacerein), and positive control group (FG, gavage with 5 mg/kg indomethacin). After continuous administration for 7 days, the ankle joint swelling degree, mechanical pain threshold, serum inflammatory factors (IL-1β, TNF-α, IL-6) levels, renal function indicators (blood urea nitrogen BUN, creatinine Cr, uric acid UA, kidney index) of rats in each group were detected, and the expression of Nrf-2/HO-1 and NF-κB pathway-related proteins in ankle joint synovial tissue was analyzed by Western blot.

RESULTS: Compared with the BG, diacerein groups and the FG significantly reduced the percentage of ankle swelling (P < 0.001) and increased the mechanical pain threshold (P < 0.001): At 24 h after modeling, there was no statistical difference in the swelling percentage between the EG and the FG (P > 0.05); At 7 days after modeling, the mechanical pain threshold in the EG was similar to that in the FG (P > 0.05). The serum levels of IL-1β, TNF-α, and IL-6 in the intervention groups were reduced in a dose-dependent manner (P < 0.001), and the inhibition rate of IL-1β in the EG exceeded 73%, which was comparable to that in the FG (P > 0.05); Renal function indicators were significantly improved (P < 0.001), and there was no significant difference in the UA level between the EG and the FG (P > 0.05). Mechanistically, diacerein dose-dependently up-regulated the expression of Nrf-2 and HO-1 proteins (P < 0.001) and down-regulated the expression of NF-κB p65 and p-IκBα proteins (P < 0.001); The FG only significantly down-regulated the expression of NF-κB p65 and p-IκBα proteins (P < 0.001), with no significant effect on the expression of Nrf-2 and HO-1 proteins (P > 0.05). The ratios of Nrf-2/GAPDH and HO-1/GAPDH in the EG were significantly higher than those in the FG (P < 0.001).

CONCLUSION: The anti-inflammatory, analgesic, and renal protective effects of high-dose diacerein are comparable to those of indomethacin, and its oral administration is convenient, which provides experimental references for the subsequent clinical transformation research of diacerein in acute urarthritis and the development of multi-target anti-gout drugs.

PMID:41318857 | DOI:10.1007/s10787-025-02059-4

Clin Rheumatol. 2025 Nov 29. doi: 10.1007/s10067-025-07830-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To prospectively compare the efficacy of glucocorticoid(GC)-free maintenance therapy versus low-dose GC regimens and evaluate short-term safety in complete or partial remission lupus nephritis patients.

METHOD: This study is a prospective, open-label, randomized controlled trial that enrolled lupus nephritis patients who achieved remission within one year prior to screening and maintained stable immunosuppressive therapy. Ninety-three subjects were randomized to a GC-free group (n = 47, tapering off GC over 3 months) and a low-dose GC group (n = 46, prednisone dosage 2.5-10 mg/day), with basic immunosuppressants continued in both groups. Primary endpoints were total flare rate and time to flare, while secondary endpoints included renal or extrarenal flare, immunological changes of parameters, and subgroup analyses stratified by remission status (complete vs. partial) and different maintenance regimen types.

RESULTS: There were 91 patients who were analyzed. The low-dose GC group demonstrated a numerically lower flare rate compared to the GC-free group(4.5%vs. 17.0%, p = 0.065). Among patients experiencing flares, the median time to flare was significantly shorter in the GC-free group (9.4 months) compared with the low-dose group (39.32 months; HR 0.37, 95% CI 0.14-0.99, p = 0.044). Kaplan-Meier analysis revealed significantly higher cumulative flare rates in the GC-free group (log-rank p = 0.031). Notably, the GC-free group exhibited a 14.9% extrarenal flare incidence versus 0% in the low-dose group (absolute risk difference 14.9%, 95% CI 3.2-26.6; p = 0.017).

CONCLUSION: In this pilot study, the flare rate was numerically lower, and the time to flare was significantly longer in the low-dose GC group compared to the GC-free group. These preliminary findings suggest a potential benefit of low-dose GC maintenance therapy but still need large sample size trials to confirm. Key Points • In patients with SLE in remission, glucocorticoid-free therapy significantly increases flare risk and shortens time to flare. • Future biomarker-driven decision-making criteria should be uncovered to replace empirical withdrawal of individual decisions.

PMID:41318847 | DOI:10.1007/s10067-025-07830-0

Odontology. 2025 Nov 29. doi: 10.1007/s10266-025-01263-6. Online ahead of print.

ABSTRACT

To investigate the fracture and apparent flexural strength at fracture of three-unit implant-supported bridge restorations at different connector cross-sectional areas according to material type, produced on ti-base abutments using the CAD-CAM system. A total of 42 three-unit implant-supported bridge restorations were designed digitally (maxillary canine and second premolar as abutment and 1st premolar as a pontic). Two main groups (N = 21) were created to be manufactured from monolithic zirconia and lithium disilicate. Then, each group was divided into three subgroups (n = 7) according to the connector cross-sectional area (9 mm², 12 mm², 15 mm² for monolithic zirconia; 12 mm², 16 mm², 20 mm² for lithium disilicate). The samples were subjected to a fracture test on a universal testing machine and the values obtained were formulated to calculate the apparent flexural strength at fracture. In terms of fracture strength, there were statistically significant differences for both monolithic zirconia and lithium disilicate (p < 0.001, p < 0.001, respectively). In terms of apparent flexural strength at fracture, there were statistically significant differences for both monolithic zirconia and lithium disilicate (p = 0.012, p = 0.007, respectively). When monolithic zirconia and lithium disilicate samples with a common connector cross-sectional area (12 mm²) were compared, it was found that monolithic zirconia was statistically significantly stronger (p = 0.002). Under the present static test conditions, monolithic zirconia can be used as three-unit bridges safely in the premolar region. Lithium disilicate can also be used as three-unit bridges in the premolar region; in cases where there is sufficient connector area and the patient does not have parafunctional habits. As a result, increasing the connector cross-sectional area increases the strength significantly (p < 0.05).

PMID:41318837 | DOI:10.1007/s10266-025-01263-6

Naunyn Schmiedebergs Arch Pharmacol. 2025 Nov 29. doi: 10.1007/s00210-025-04856-8. Online ahead of print.

ABSTRACT

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain a major global health burden, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Despite advancements in vaccination and antiviral therapies, viral persistence, immune evasion, and disease progression continue to challenge global elimination goals. Recent evidence suggests that the gut-liver-virus axis, involving microbiota dysbiosis, immunometabolic reprogramming, and exosome mediated signaling, plays a central role in HBV and HCV related pathogenesis. A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar from January 2000 to August 2025. Studies were screened according to the PICO framework, focusing on HBV/HCV persistence, gut microbiota dysbiosis, immunometabolic changes, exosome-mediated communication, and therapeutic interventions. A total of 100 eligible studies, including clinical, preclinical, and mechanistic investigations, were synthesized. The analysis revealed that HBV and HCV infections remodel the gut liver axis through depletion of short-chain fatty acid (SCFA) producing taxa, enrichment of pro-inflammatory bacteria, and dysregulated bile acid and lipopolysaccharide metabolism. Viral persistence is sustained by immunometabolic rewiring, including glycolysis upregulation, lipid accumulation, and tryptophan kynurenine pathway activation, leading to T-cell exhaustion and immune suppression. Exosomes derived from infected hepatocytes and tumors facilitate viral spread, immune evasion, and oncogenesis while emerging as potential biomarkers and therapeutic nanocarriers. Collectively, these interconnected mechanisms drive inflammation, fibrosis, cirrhosis, and progression to HCC. The progression of HBV/HCV infections is governed by a complex interplay of viral persistence, gut microbiota alterations, metabolic reprogramming, and exosome-mediated communication. Targeting these pathways through microbiota-directed therapies, metabolic modulators, and exosome-based interventions offers promising opportunities for precision medicine. Future studies employing multi-omics integration, validated models, and longitudinal cohorts are required to establish causality and translate mechanistic insights into effective clinical strategies for preventing HBV/HCV associated cirrhosis and cancer.

PMID:41318835 | DOI:10.1007/s00210-025-04856-8

Int Urol Nephrol. 2025 Nov 29. doi: 10.1007/s11255-025-04922-3. Online ahead of print.

ABSTRACT

BACKGROUND: Urethral stricture disease remains a challenging condition in urology, particularly in cases with recurrent anterior urethral narrowing following prior endoscopic treatments. Traditional options such as dilation and direct vision internal urethrotomy (DVIU) are limited by high failure rates. The Optilume^® drug-coated balloon (DCB) delivers mechanical dilation combined with localized paclitaxel delivery, aiming to reduce restenosis and improve durability.

OBJECTIVE: To evaluate the short-term functional outcomes and safety of Optilume^® DCB in patients with recurrent urethral strictures.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective single-center study including 35 male patients with anterior urethral strictures ≤ 3 cm and at least one prior endoscopic treatment. Outcomes were assessed at 1, 3, and 6 months post-procedure.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes included changes in Qmax (uroflowmetry), post-void residual (PVR), IPSS, and erectile function (IIEF-5). Recurrence was defined as symptomatic deterioration, Qmax < 10 mL/s, or need for retreatment. Paired t-tests were used for pre- and post-treatment comparisons, with p < 0.05 considered statistically significant. As this was an exploratory pilot study, no formal sample size calculation was performed; analyses were descriptive and hypothesis-generating.

RESULTS AND LIMITATIONS: Mean Qmax improved from 10.2 ± 4.9 to 21.6 ± 3.1 mL/s (p < 0.001), and PVR decreased from 74.6 ± 36.3 to 24.8 ± 16.0 mL (p < 0.001). IPSS improved from 21.8 ± 4.8 to 8.7 ± 2.0 (p < 0.0001), and IIEF-5 scores increased from 13.7 ± 7.7 to 18.5 ± 7.6 (p = 0.012). The recurrence rate at 6 months was 8.6% (3/35). Minor adverse events included transient hematuria and dysuria. No Clavien-Dindo grade ≥ 2 complications were recorded. Study limitations include its single-arm, non-randomized design and relatively short follow-up, limiting direct comparison with DVIU, urethroplasty, or emerging minimally invasive surgical therapies (MISTs).

CONCLUSIONS: Optilume^® DCB treatment demonstrated significant improvements in urinary flow and symptoms with a low recurrence and complication rate at 6 months. It may serve as a minimally invasive alternative for patients unsuitable or unwilling to undergo urethroplasty. Further prospective evaluation is warranted, including its potential role in bladder neck sclerosis and benign prostatic obstruction.

PMID:41318833 | DOI:10.1007/s11255-025-04922-3

Environ Monit Assess. 2025 Nov 29;197(12):1386. doi: 10.1007/s10661-025-14836-3.

ABSTRACT

Accurately classifying forest successional stages remains a major challenge in applied ecology due to the continuum of succession, ecological heterogeneity, and limited interpretability of many machine learning (ML) approaches. Prevailing models typically rely on black-box algorithms that, while accurate, often lack ecological transparency, limiting their practical use in restoration and regulatory contexts. Here, we introduce and evaluate an ecology-informed symbolic machine learning (EISy-ML) framework that integrates symbolic regression with adaptive ecological constraints, specifically monotonic biomass trajectories and structural complexity proxies, derived from allometric functions. Using field data from 467 plots in the Subtropical Atlantic Forest, Brazil, EISy-ML generated interpretable and biologically plausible equations for successional classification. Performance was benchmarked against eight standard ML classifiers using balanced accuracy, macro F1, Cohen’s kappa, and Matthews correlation coefficient. EISy-ML achieved the highest test accuracy (0.899), F1 (0.905), Kappa (0.829), and MCC (0.803), with no statistically significant difference compared to the next best models. The symbolic framework offers substantial improvements in transparency, reproducibility, and ecological coherence over conventional approaches, enabling direct application in restoration monitoring and environmental auditing. These results validate the hypothesis that symbolic ML integrated with ecological constraints produces models that are both robust and operationally interpretable. Future research should extend EISy-ML validation to other biomes, incorporate temporal and functional trait data, and explore uncertainty-aware or fuzzy logic extensions for handling transitional successional states.

PMID:41318828 | DOI:10.1007/s10661-025-14836-3

Sci Rep. 2025 Nov 30. doi: 10.1038/s41598-025-29071-6. Online ahead of print.

ABSTRACT

This study aims to compare the effects of posture education and corrective games on the alignment of the thoracic and cervical spine, as well as the daily habits in children. This is a three-armed individual-randomized trial design of three groups in blinded evaluators. The statistical population of this study was formed by elementary students with malalignments in the thoracic and cervical spine of Baharestan city (Iran). A total of 60 participants were assigned to this study and using a simple random method with computer-generated random numbers divided into posture education group (PE, n = 20) corrective games group (CG, n = 20) and control group (CON, n = 20) groups. Kyphosis angle, forward head posture and forward shoulder posture measured with a flexible ruler, goniometer, and double square, respectively. Also, daily habits measured with students’ daily functional activities questioner. A repeated measures ANOVA analysis of variance (3 × 3, Group×Time) was utilized to analyze data. Significance was set at p ≤ 0.05. Both the PE and CG showed significant improvements in kyphosis (p = 0.01 for PE, p = 0.02 for CG), forward head posture (p = 0.02 for PE, p = 0.04 for CG), forward shoulder posture (p = 0.001 for PE, p = 0.02 for CG), and daily habits (p = 0.02 for PE, p = 0.03 for CG) after an 8-week training intervention compared to the CON group. Also, after the training period, the analysis revealed no statistically significant differences in the dependent variables between the PE group and the CG, with a p-value greater than 0.05. However, after a 3-month detraining period, the changes in both the PE and CG were found to be statistically insignificant (p > 0.05). The interventions effectively enhanced participants’ posture and daily activity patterns, with no significant differences between the PE and CG groups. The sustainability of these improvements indicates that participants developed lasting skills and habits that promote spinal health. This study highlights the importance of integrating educational and engaging physical activities into curricula to support children’s musculoskeletal well-being.Trial registration: IRCT registration number: IRCT20250316065103N1, Registration date: 2025-03-25 (Retrospectively registered), Trial Id: 82539.

PMID:41318818 | DOI:10.1038/s41598-025-29071-6

Sci Rep. 2025 Nov 29. doi: 10.1038/s41598-025-30747-2. Online ahead of print.

ABSTRACT

Phenotypic age (PhenoAge) is a biological aging clock that estimates an individual’s biological age. However, the effect of PhenoAge acceleration (PhenoAgeAccel) on cancer is unclear. This study investigates the relationship between PhenoAgeAccel and cancer survivors. Data for this cohort study were sourced from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018. The relationship between PhenoAgeAccel and cancer prevalence was evaluated using weighted multivariate logistic regression. Kaplan-Meier analyses and weighted multivariate-adjusted Cox analyses were conducted to examine the association between PhenoAgeAccel and all-cause as well as cancer-specific mortality in cancer survivors. Restricted cubic spline (RCS) analysis was utilized to assess nonlinear associations. Subgroup and sensitivity analyses were also performed to confirm the robustness of the findings. A total of 34,246 participants were included in our study, of which 3067 were cancer survivors (8.95% prevalence). With a median follow-up of 117 months (interquartile range: 50-155 months), there were 1161 deaths, including 351 from cancer. Weighted multivariate regression analysis revealed a significant positive association between higher PhenoAgeAccel and cancer prevalence (P for trend < 0.001). Multivariable-adjusted Cox regression analyses showed that elevated PhenoAgeAccel was significantly associated with increased all-cause and cancer-specific mortality among cancer survivors (P for trend < 0.001). RCS regression indicated no nonlinear relationship between PhenoAgeAccel and mortality outcomes (P for nonlinear relationship > 0.05). Kaplan-Meier analyses indicated a poorer prognosis with higher PhenoAgeAccel. Subgroup analyses based on tumor classification highlighted the differential prognostic impact of PhenoAgeAccel across various tumor types. Our findings reveal a significant linear correlation between PhenoAgeAccel and both all-cause and cancer-specific mortality in cancer survivors.

PMID:41318813 | DOI:10.1038/s41598-025-30747-2