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Nevin Manimala Statistics

Molecular Characterization of the Epstein-Barr Virus in Malignant Tumors of Different Origins: An Emphasis on EBER Promoter Value for EBV Classification

Front Biosci (Schol Ed). 2026 Mar 23;18(1):46442. doi: 10.31083/FBS46442.

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a well-known cause of infectious mononucleosisand it has also been linked to the development of various malignant tumors. EBV can be classified into two genotypes based on EBNA-2 and EBNA-3 polymorphisms, with further subclassification predominantly based on BNLF-1 and EBNA-1 variations. Currently, EBV subtyping has not been performed using EBER genes. Thus, this study aimed to determine EBV subtypes in various malignant tumors and to assess the potential of EBER polymorphisms for EBV classification.

METHODS: DNA was isolated from tissue samples of patients diagnosed with classical Hodgkin lymphoma (cHL), angioimmunoblastic T cell lymphoma (AITL), and nasopharyngeal carcinoma (NPC). Specific fragments of the BNLF-1, EBNA-1, EBNA-3C, and EBER genes were amplified, and population sequencing was conducted.

RESULTS: Based on EBNA-3C sequences, all tumor samples were genotype EBV-1, whereas the BNLF-1, EBNA-1, and EBER sequences indicated that the tumor tissues were infected with different EBV subtypes. The B95-8 subtype predominated in cHL, whereas North Carolina and P-ala were the most frequent subtypes in NPC. In addition, we propose a newly designed algorithm for EBER-based subclassification, which showed that the subtype Cro2 is more frequently present in cHL and AITL than in NPC.

CONCLUSION: The results of this study show characteristic pattern of EBV diversity based on the EBNA-3C, EBNA-1, and BNLF-1 gene sequences, as well as the EBER promoter sequence in AITL, NPC, and cHL cohorts specific for the Caucasian population of southeastern Europe; however, these results may not relate to the distribution of EBV variants in other geographic areas.

PMID:41914172 | DOI:10.31083/FBS46442

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Nevin Manimala Statistics

AAV9-Mediated Targeting of Defined Neuronal Populations in Spinal Cord Through Intrathecal Injection

Front Biosci (Elite Ed). 2026 Feb 9;18(1):44274. doi: 10.31083/FBE44274.

ABSTRACT

BACKGROUND: Adeno-associated viruses (AAVs) are established vectors for efficient gene delivery to the central nervous system (CNS). Increasingly, strategies aim to restrict transduction to specific neuronal subtypes defined by the associated functional properties, thereby enhancing precision and therapeutic potential.

METHODS: Recombinant AAV9 vectors carrying fluorescent reporters under the control of cytomegalovirus (CMV), human synapsin (hSyn), or homeobox 9 (Hb9) promoters were delivered intrathecally in Wistar rats. Transgene expression was evaluated 7 days post-injection by confocal microscopy. Neurons in laminae VII-X were quantified across cervical, thoracic, lumbar, and sacral spinal cord levels. Statistical analysis was performed using the Kruskal-Wallis test followed by Mann-Whitney U tests with Bonferroni correction.

RESULTS: In lamina VII, consistent neuronal expression was mediated by hSyn across all spinal levels, with significantly higher transduction at cervical compared to thoracic and lumbar regions (p < 0.01). CMV and Hb9 showed no detectable tropism for this lamina. In lamina VIII, CMV drove markedly higher expression than hSyn and Hb9, with a 2.8-fold difference at the lumbar level (p < 0.001). In lamina X, CMV expression exceeded hSyn at the lumbar and sacral levels (p < 0.05), while Hb9 showed no activity. In lamina IX, all promoters mediated motoneuron transduction, but only Hb9 restricted expression specifically to motoneuron somata. Notably, CMV induced off-target expression in glial cells.

CONCLUSIONS: AAV9-mediated expression patterns in the spinal cord are strongly shaped by promoter choice and segmental level. Hb9 provides high motoneuron specificity, hSyn supports broad neuronal activation across laminae VII-X, whereas CMV drives robust but non-specific expression with significant off-target activity. These findings highlight the importance of rational promoter selection for spinal cord gene therapy and strategies aimed at functional recovery in motor system disorders.

PMID:41914168 | DOI:10.31083/FBE44274

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Nevin Manimala Statistics

Biomechanical Differences in Young Patients With True Femoral Retrotorsion: Correlations Between Gait Deviations, Clinical Measurements, and Imaging Data

J Pediatr Orthop. 2026 Mar 31. doi: 10.1097/BPO.0000000000003241. Online ahead of print.

ABSTRACT

BACKGROUND: Torsional abnormalities of the femur, such as femoral retrotorsion, can significantly impact gait and joint biomechanics in children and adolescents. However, the resulting gait patterns as well as the relationship between static imaging measurements and dynamic gait deviations remain unclear. This study aimed to investigate biomechanical differences in gait between young individuals with true femoral retrotorsion and typically developing peers, examining correlations between gait deviations, clinical measurements, and imaging data.

METHODS: A multicenter retrospective study was conducted, including 31 patients with unilateral or bilateral femoral retrotorsion and a control group of typically developing children. Femoral torsion was assessed using MRI or CT, while 3D motion capture was used for gait analysis. Clinical hip rotation was measured, and statistical analyses, including correlation assessments, were performed to evaluate relationships between imaging, clinical, and gait parameters.

RESULTS: Patients exhibited significantly increased hip external rotation and out-toeing gait compared with controls. However, no correlation was found between femoral torsion measured by imaging and hip rotation during gait or foot progression angle. In contrast, the midpoint of clinical hip rotation correlated moderately with both hip rotation and foot progression angle during gait. In addition, patients had higher BMI and demonstrated compensatory knee valgus, despite no radiologic evidence of knee malalignment.

CONCLUSION: Children and adolescents with femoral retrotorsion exhibit distinct gait deviations, but static imaging alone does not reliably predict dynamic gait patterns. This emphasizes the need for dynamic assessment in clinical decision-making.

PMID:41914160 | DOI:10.1097/BPO.0000000000003241

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Nevin Manimala Statistics

Impact of Symptom Phenotype on Surgical Quality and Survival in Small-Bowel Neuroendocrine Tumours: A Quality Metrics Analysis

J Surg Oncol. 2026 Mar 30. doi: 10.1002/jso.70245. Online ahead of print.

ABSTRACT

BACKGROUND: There is debate regarding the optimal management of small-bowel neuroendocrine tumours (SBNETs), particularly concerning upfront resection in various clinical presentations. While symptom phenotypes are known to influence survival, their impact on technical surgical quality, especially in the emergency setting, remains poorly defined. This study evaluates whether symptom phenotype compromises the delivery of guideline-concordant surgical care.

METHODS: A retrospective analysis of 108 consecutive SBNET resections (2000-2023) at a specialized tertiary centre was performed. Patients were stratified into four phenotypes: obstructive/perforation (n = 54), carcinoid syndrome (22), asymptomatic/incidental (22), and other symptoms (9). Operative metrics, including lymph-node harvest (LNY) and margin status (R0/R1), were compared alongside overall survival (OS).

RESULTS: Symptom phenotype was a predictor of operative urgency and approach. Obstructive cases required emergency surgery in 50% of instances compared to ≤ 11% in all other groups (p < 0.001). Synchronous liver metastases were most prevalent in the carcinoid syndrome phenotype (50%) and lowest in the asymptomatic group (5%) (p = 0.002). Despite these disparities in presentation and urgency, technical quality markers were uniform across all groups: median LNY ranged from 10 to 13 (p = 0.426), R1/R2 margin rates were statistically similar (p = 0.290), and median length of stay was 8 days for all cohorts (p = 0.311). Multivariable analysis identified the asymptomatic phenotype as independently protective for OS (HR 0.42, p = 0.032), while liver metastasis was the strongest adverse prognostic factor (HR 3.25, p < 0.001).

CONCLUSIONS: Symptom phenotype dictates operative urgency and reflects disease burden but does not compromise the technical standards of surgery in a specialized unit. These findings suggest that high-quality, guideline-concordant lymphadenectomy is achievable even in emergency obstructive presentations, and correspondingly, access to specialized surgical oncology expertise may be sought even in obstructed patients to ensure technical quality is maintained.

PMID:41913096 | DOI:10.1002/jso.70245

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Nevin Manimala Statistics

Exploring White Matter Microstructural Abnormalities Using MRI in Women With Premenstrual Dysphoric Disorder via Brain Connectome

J Magn Reson Imaging. 2026 Mar 30. doi: 10.1002/jmri.70318. Online ahead of print.

ABSTRACT

BACKGROUND: The neurostructural underpinnings of premenstrual dysphoric disorder (PMDD), particularly integrated white matter and network alteration, remain unclear.

PURPOSE: To identify a core structural network in PMDD by integrating multiple diffusion tensor imaging (DTI)-derived metrics and to develop a predictive model.

STUDY TYPE: Prospective case-control study.

SUBJECTS: Forty-two PMDD patients (age: 23.86 ± 1.32 years), diagnosed according to the American Psychiatric Association DSM-5, and 42 healthy controls (age: 23.79 ± 1.72 years).

FIELD STRENGTH/SEQUENCE: 3.0 T, T1-weighted three-dimensional gradient-echo and echo planar imaging DTI sequences.

ASSESSMENT: Microstructural and connectivity features were extracted from DTI using tract-based spatial statistics (TBSS), network-based statistics (NBS), and graph theory analyses. A combined predictive model was constructed by integrating the most stable features from the three single-modality models via least absolute shrinkage and selection operator (LASSO) regression.

STATISTICAL TESTS: Group comparisons were performed using two-sample t-tests or Mann-Whitney U tests, with false discovery rate correction. Features were selected using LASSO and integrated to construct a combined model. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC) using leave-one-out cross-validation. p < 0.05 was considered significant.

RESULTS: PMDD patients exhibited widespread microstructural and connectivity alterations, including elevated axial diffusivity in the right posterior limb of the internal capsule, enhanced edge connectivity, and altered network topology. The combined model achieved significantly superior predictive performance (AUC = 0.855) compared with the TBSS-based model (AUC = 0.699) and the network-based model (AUC = 0.727), and a higher AUC than the graph-based model (AUC = 0.790). Key predictive features included two enhanced edges originating from the left inferior frontal gyrus and reduced degree centrality of the left inferior occipital gyrus and sulcus.

DATA CONCLUSION: Our DTI-based predictive model showed alterations in brain connections and network properties in the left inferior frontal and inferior occipital regions of PMDD patients.

TECHNICAL EFFICACY: Stage 2.

PMID:41913094 | DOI:10.1002/jmri.70318

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Nevin Manimala Statistics

Multi-Centre Reproducibility of DTI and NODDI in White Matter Tracts Segmented Using TractFinder Across Three MRI Scanners of the Same Model

Hum Brain Mapp. 2026 Apr 1;47(5):e70491. doi: 10.1002/hbm.70491.

ABSTRACT

Quantitative imaging biomarkers (QIBs) are objective measures derived from quantitative imaging that can differentiate pathological changes from healthy biological processes. Diffusion MRI parameters derived from Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) could serve as potential QIBs for studying both healthy neurodevelopment and various neurological conditions. However, quantitative neuroimaging studies often require large datasets collected across multiple scanners, which introduces variability. To ensure the reliability of multi-centre studies, the inter-centre reproducibility of DTI and NODDI parameters must be thoroughly assessed before data collection begins. Discrepancies between results reported by previous studies can be explained by other sources of variability. The inter-scanner reproducibility of diffusion parameters needs to be determined when the other sources of variability, such as differences in acquisition parameters, processing and ROI segmentation are controlled for. We assess the reproducibility of DTI and NODDI parameters in clinically relevant white matter (WM) tracts across three scanners of the same model, ensuring consistency in the acquisition scheme and pre-processing pipelines. WM tract regions of interest (ROIs) are automatically segmented to standardise the analysis. Additionally, we investigate ROI and signal-to-noise ratio differences to better understand the sources of variability in diffusion parameters. According to the Koo and Li classification system, our results demonstrate excellent reproducibility for fractional anisotropy and mean diffusivity across scanners of the same model (ICC ≥ 0.964) when using identical acquisition schemes, pre-processing pipelines and automated ROI segmentation. NODDI orientation dispersion index and neurite density index exhibit a similar level of reproducibility (ICC ≥ 0.942 and ICC ≥ 0.911, respectively), while free water fraction (FWF) has ICC ≥ 0.862. However, statistically significant variability was observed in the FWF, specifically within the left inferior fronto-occipital fasciculus (CoV 9.43%) and optic radiation (CoV 9.95%), even when scanning the same cohort across sites. If there is an error in the signal fraction in one compartment in the NODDI model, the signal fractions from other compartments may likely be misestimated. The reproducibility and variability of diffusion parameters reported in this study provide guidance for future QIB research involving datasets derived from multiple scanners. These findings can help determine whether observed changes in diffusion parameters reflect meaningful biological differences or are highly influenced by measurement variability.

PMID:41913049 | DOI:10.1002/hbm.70491

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Nevin Manimala Statistics

Combined supplementation of lysophospholipids, synthetic emulsifier and monoglycerides alleviates the adverse effects of energy- and amino acid-deficient diets on growth performance, nutrient utilization, and intestinal health in broilers

J Anim Sci. 2026 Mar 30:skag106. doi: 10.1093/jas/skag106. Online ahead of print.

ABSTRACT

Improving nutrient utilization in nutrient-restricted diets is an important strategy to reduce feed costs and maintain productivity in broiler production. Dietary emulsifiers are commonly used to improve lipid digestion and overall nutrient utilization in poultry diets. The objective of this study was to investigate the effects of a combination of lysophospholipids, synthetic emulsifier and monoglycerides (LEX) in energy- and amino acid-deficient broiler diets on growth performance, carcass traits, nutrient digestibility, and intestinal morphology from day 11 to 35. A total of 168 ten-day-old Ross 308 male broiler chicks were randomly assigned to one of three dietary treatments in a completely randomized design, with seven replicates and eight birds per cage. The dietary treatments were as follows: i) a positive control diet (PC) containing standard metabolizable energy and amino acid levels; ii) a negative control diet (NC) with 100 kcal/kg less metabolizable energy and 4.0% reduction in essential amino acids (lysine, methionine + cysteine, and threonine); iii) NC diet supplemented with 250 g/ton of LEX. Statistical analyses were conducted using the general linear model (GLM) procedure for one-way analysis of variance (ANOVA), with significance declared at P < 0.05. Broilers fed the LEX-supplemented NC diet exhibited improved (P < 0.001) growth performance, including body weight at day 35 (1737.14 to 1903.46 g), average daily gain (day 11-35; 58.49 to 64.95 g/day), and feed conversion ratio (1.60 to 1.41 g/g), compared to those fed the NC diet alone. Apparent digestibility of crude protein and crude fat in both the jejunum and ileum was higher (P < 0.001) in birds receiving the LEX-supplemented NC diet than in those on the NC diet. In addition, LEX improved intestinal morphology, evidenced by increased villus height (920.87 to 1086.84 µm), crypt depth (126.74 to 161.28 µm) on day 35 (P < 0.05). However, there were no significant differences (P > 0.05) in carcass yield parameters, including breast and leg muscle weights and abdominal fat content, among the dietary treatments. In conclusion, supplementation of 250 g/ton of LEX to a broiler diet deficient in energy and amino acids effectively improved growth performance and nutrient utilization by enhancing protein and fat digestibility and promoting intestinal development. These findings suggest that a combination product based on lysophospholipids, synthetic emulsifier, and monoglycerides can serve as a practical and effective nutritional strategy to optimize production efficiency under nutrient-restricted feeding conditions in commercial broiler production.

PMID:41913048 | DOI:10.1093/jas/skag106

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Nevin Manimala Statistics

Negative and nonlinear association between oxidative balance score and hyperuricemia: a cross-sectional analysis based on the NHANES database

Clin Rheumatol. 2026 Mar 30. doi: 10.1007/s10067-026-08083-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Hyperuricemia (HUA) is a prevalent metabolic disorder linked to substantial morbidity. Oxidative stress is a key pathogenic mechanism, yet the cumulative effect of dietary and lifestyle pro- and anti-oxidants remains unclear. The Oxidative Balance Score (OBS) offers a comprehensive metric of oxidative potential. This study aimed to investigate the association between OBS and HUA in a large, nationally representative US adult population.

METHODS: This cross-sectional study included 29,876 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The OBS was constructed from 16 dietary and 4 lifestyle components. HUA was defined as serum uric acid ≥ 7.0 mg/dL for men and ≥ 6.0 mg/dL for women. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between OBS quartiles and HUA. Restricted cubic splines (RCS) were employed to model non-linear relationships. Subgroup analyses were conducted by gender, age, and estimated glomerular filtration rate (eGFR).

RESULTS: The overall prevalence of HUA was 20.2%. A significant inverse association was observed between OBS and HUA. After adjusting for multiple confounders, participants in the highest OBS quartile (Q4, most anti-oxidant profile) had a 42% lower odds of HUA compared to those in the lowest quartile (Q1) (OR: 0.58, 95% CI: 0.51-0.66, P-trend < 0.001). This association was more pronounced for lifestyle OBS (OR for Q4 vs. Q1: 0.35, 95% CI: 0.29-0.42) than for dietary OBS (OR for Q4 vs. Q1: 0.70, 95% CI: 0.61-0.81). RCS analysis revealed a significant nonlinear relationship (P-nonlinearity < 0.001), with the protective effect of OBS plateauing at higher scores. The inverse association was consistent across gender and age subgroups but appeared stronger in individuals with normal renal function (eGFR ≥ 90 mL/min/1.73m2).

CONCLUSION: A higher OBS, reflecting a lifestyle and diet rich in antioxidants, is independently and non-linearly associated with a lower prevalence of hyperuricemia. These findings highlight the importance of a holistic approach targeting overall oxidative balance, particularly through modifiable lifestyle factors, for the primary prevention of hyperuricemia. Key Points • A higher Oxidative Balance Score is linked to lower hyperuricemia prevalence. • Lifestyle factors show a stronger protective association than dietary factors. • The relationship is nonlinear, with benefits plateauing at higher scores.

PMID:41913033 | DOI:10.1007/s10067-026-08083-1

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Retention of lithium disilicate and translucent zirconia veneers bonded with light-cured resin cements: a systematic review and meta-analysis

Saudi Dent J. 2026 Mar 30;38(4):42. doi: 10.1007/s44445-026-00156-w.

ABSTRACT

BACKGROUND: Light-cured resin cements are widely used for veneer cementation due to their color stability and extended working time. However, polymerization through ceramic materials may be influenced by ceramic composition, thickness, and bonding substrate, potentially affecting bond strength. A quantitative comparison between lithium disilicate and translucent zirconia veneers under light-cured protocols remains limited.

OBJECTIVE: To compare the bond strength of lithium disilicate and translucent zirconia veneers luted with light-cured resin cements and to evaluate the influence of substrate type and veneer thickness.

METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. Six in vitro studies (64 specimens) met inclusion criteria. Random-effects models using restricted maximum likelihood estimation with Hartung-Knapp adjustment were applied. Subgroup analyses were performed according to ceramic material and substrate. An exploratory meta-regression assessed the association between veneer thickness and bond strength.

RESULTS: The pooled mean bond strength across all studies was 15.9 MPa. Lithium disilicate veneers demonstrated higher pooled bond strength (25.4 MPa) than translucent zirconia (12.1 MPa). Enamel substrates showed higher bond strength (21.1 MPa) compared with composite cores (11.3 MPa). Considerable heterogeneity was observed (I2 = 98.2%). Meta-regression suggested an inverse trend between veneer thickness and bond strength; however, this finding was based on a limited dataset and should be interpreted cautiously.

CONCLUSION: Within the limitations of in vitro evidence, lithium disilicate and enamel bonding were associated with higher bond strength under light-cured cementation. Due to substantial heterogeneity and limited study numbers, these findings should be considered exploratory and not directly extrapolated to clinical performance.

PMID:41913027 | DOI:10.1007/s44445-026-00156-w

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Efficacy and Safety of Tranexamic Acid in Solid Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials with GRADE Assessment

Ann Surg Oncol. 2026 Mar 30. doi: 10.1245/s10434-026-19377-8. Online ahead of print.

ABSTRACT

BACKGROUND: There is a significant risk of blood loss and transfusion requirements during surgeries for different cancers, raising perioperative morbidity and mortality. The antifibrinolytic drug tranexamic acid (TXA) has been studied to address this issue, but the results remain conflicting. This systematic review and meta-analysis pools all available evidence regarding the use of this medication in cancer surgeries.

PATIENTS AND METHODS: The PubMed, Scopus, Web of Science, and Cochrane CENTRAL databases were used for data retrieval until 29 April 2025. Any randomized controlled trial involving surgical patients with cancer who received TXA as the intervention was included. The main addressed outcomes were perioperative blood loss, transfusion requirements, and complications. Study quality and evidence certainty were appraised with the Cochrane RoB 2.0 tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

RESULTS: A total of 16 RCTs with 1830 patients were analyzed. TXA markedly reduced total, intraoperative, and postoperative blood loss compared with control. Hemoglobin changes were also smaller in the TXA group. Intraoperative blood component and perioperative red blood cell transfusions were lower with TXA. TXA was also linked to a modest reduction in operative time. No significant differences were observed between the groups for perioperative complications, reoperation rate, in-hospital or 30-day mortality, and length of hospital stay. GRADE assessments for the outcomes were mainly moderate or low, except for two that had very low certainty.

CONCLUSIONS: TXA appears to statistically improve perioperative outcomes in cancer surgeries while maintaining a favorable safety profile.

PMID:41913008 | DOI:10.1245/s10434-026-19377-8