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Nevin Manimala Statistics

Intraoral tomosynthesis accuracy for cone length measurement is comparable to physical measurement of gutta-percha

Oral Surg Oral Med Oral Pathol Oral Radiol. 2026 Jul 7:S2212-4403(26)00345-7. doi: 10.1016/j.oooo.2026.06.024. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy of cone fit measurements of digital periapical (PA) and stationary intraoral tomosynthesis (s-IOT) images and compare them to the physical measurement of gutta-percha (gold standard).

STUDY DESIGN: Images of 40 extracted teeth with gutta-percha in their prepared root canals were acquired using digital PA and 3D s-IOT devices (Portray system), while the physical cone length of the gutta-percha was measured using a digital vernier caliper. Digital PA cone length was measured using MiPACS Dental Enterprise Viewer Software with a polyline measurement tool. Cone length in the s-IOT images was measured by scrolling through synthetic images taken at different angle disparities. All measurements were recorded and subjected to statistical analysis.

RESULTS: Interclass correlation coefficient (ICC) test showed statistical significance. The gold standard vs s-IOT measurements had the highest reliability across all groups, often exceeding 0.9. Comparisons involving PA (PA vs gold standard and PA vs s-IOT) tend to have lower reliability, with several confidence intervals including 0. Statistically significant P-values across all comparisons suggest these ICCs are meaningful, but confidence intervals highlight potential issues with data variability.

CONCLUSIONS: While both modalities differed from the gold standard, s-IOT demonstrated a clear advantage in measurement accuracy and reliability.

PMID:42603742 | DOI:10.1016/j.oooo.2026.06.024

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Phoenixin-14 May Be a Potential Limiting Neuropeptide for Exaggerated Inflammation in Familial Mediterranean Fever and Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis Syndrome: A Comparative Study

J Rheumatol. 2026 Aug 15:jrheum.2026-0178. doi: 10.3899/jrheum.2026-0178. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate serum Phoenixin-14 (PNX-14) levels in Familial Mediterranean Fever (FMF) and Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) patients during both attack and attack-free periods to investigate its potential biomarker value.

METHODS: A total of 140 children were included in this cross-sectional study: 46 FMF, 48 PFAPA, and 46 healthy children. Blood samples were collected during both febrile and attack-free periods in the FMF and PFAPA patients, whereas samples from healthy controls were collected at a single time point. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), fibrinogen, and serum PNX-14 levels were evaluated. Serum PNX-14 levels were measured using ELISA. SPSS 25 was used for statistical analyses.

RESULTS: PNX-14 levels were significantly higher during attack periods in FMF and PFAPA patients compared to attack-free periods and healthy controls (p < 0.001). PNX-14 levels during attack-free periods were also higher in both patient groups than in healthy controls (p < 0.001). While a positive correlation was observed between PNX-14 levels and CRP (rho = 0.222, p = 0.04), no significant correlation was observed with ESR, SAA, or fibrinogen. No significant associations were observed between PNX-14 levels and disease severity (PRAS), colchicine treatment duration, or daily colchicine dose in the FMF group.

CONCLUSION: PNX-14 may be part of a neuroimmune response aimed at resolving inflammation in autoinflammatory processes and could be a potential immunomodulatory biomarker. PNX-14 may be a complementary indicator reflecting inflammatory burden or the healing process.

PMID:42603718 | DOI:10.3899/jrheum.2026-0178

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Cone beam computed tomography integration in clear aligner therapy in the treatment planning of Class II division 2 malocclusion

Angle Orthod. 2026 Aug 13:e022126-156.1. doi: 10.2319/022126-156.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the impact of cone-beam computed tomography (CBCT) integration on clear aligner therapy (CAT) digital treatment planning for maxillary incisors in patients with Class II division 2 malocclusion.

MATERIALS AND METHODS: Digital treatment plans were developed for patients using Spark Approver software (Ormco, Orange, CA, USA), with and without CBCT integration. Planned lingual root torque (LRT) and lingual root movement (LRM) were recorded from the tooth movement table for maxillary incisors that satisfied selection criteria. Predicted lingual dehiscence (PLD) and clinical parameters including number of aligners, prescribed interproximal reduction (IPR), and number of intermediate and challenging tooth movements were recorded. Inferential statistics were used to compare treatment plans developed with and without CBCT.

RESULTS: 56 maxillary incisors from 18 patients were assessed. With CBCT integration, planned LRT and LRM were significantly reduced by 51.5% and 42.4%, respectively. PLD per tooth significantly decreased from 3.7 mm (SD: 3.5) without CBCT, to 0.8 mm (SD: 1.3) with CBCT. Although no significant differences were observed in the number of aligners, prescribed IPR, or planned intermediate tooth movements, significantly fewer challenging movements were planned when CBCT was utilized.

CONCLUSIONS: CBCT integration into CAT digital treatment planning significantly alters planned root movements, minimizes PLD, and limits challenging tooth movements. Clinicians must carefully review digital treatment plans to identify and modify planned movements that may exceed anatomical limits to ensure alveolar boundaries are respected.

PMID:42603708 | DOI:10.2319/022126-156.1

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Prophylactic Fingolimod Administration Prevents the Development of Proliferative Vitreoretinopathy in an Experimental Rat Model

Exp Eye Res. 2026 Aug 15:111203. doi: 10.1016/j.exer.2026.111203. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to evaluate the prophylactic potential of fingolimod, an FDA-approved sphingosine-1-phosphate receptor modulator, in preventing proliferative vitreoretinopathy (PVR) in an experimental rat model induced by intravitreal platelet-rich plasma (PRP) injection.

METHODS: Thirty-two male Wistar albino rats were randomly assigned to four groups (n = 8 per group): Control, Fingolimod, PVR, and PVR+Fingolimod. PVR was induced by intravitreal injection of autologous PRP in the PVR and PVR+Fingolimod groups. Fingolimod (0.3 mg/kg/day) was administered by oral gavage for 21 days to the rats in the Fingolimod and PVR+Fingolimod groups. Histopathological evaluation included grading of retinal folds, epiretinal membrane (ERM) scoring, staging of retinal detachment and assessments of overall PVR severity, vessel count, retinal thickness, vitreoretinal traction membrane presence, and retinal-layer disruption. Body weight was monitored at baseline and at euthanasia. A complete blood count was also performed.

RESULTS: Prophylactic fingolimod administration significantly reduced the indicators of PVR severity. The PVR+Fingolimod group showed significantly lower retinal fold grades (1.12 ± 0.99 vs. 3.25 ± 1.04, p < 0.001), ERM grades (1.25 ± 0.46 vs. 3.12 ± 0.99, p < 0.001), and retinal detachment grades (1.38 ± 0.52 vs. 2.75 ± 0.71, p < 0.001) than the PVR group. Neovascularization was significantly lower in the PVR+Fingolimod group (6.50 ± 1.31 vs. 10.50 ± 3.96 vessels, p < 0.001). Vitreoretinal traction membrane was present in 75% of eyes showing PVR but completely absent in the PVR+Fingolimod group (p < 0.05). Prophylactic fingolimod administration also significantly reduced white blood cell (3.75 ± 1.52 vs. 8.70 ± 2.39 × 103/μL, p < 0.001) and lymphocyte (1.90 ± 0.90 vs. 6.86 ± 1.91 × 103/μL, p < 0.001) counts. Post-hoc power analysis indicated statistical power > 0.80 for most primary endpoints. Body weight monitoring showed no overt systemic toxicity or weight loss.

CONCLUSIONS: To the best of our knowledge, this proof-of-concept study provides the first preclinical evidence that prophylactic fingolimod administration effectively prevents PVR development, consistent with anti-inflammatory and immunomodulatory mechanisms. Thus, Fingolimod represents a promising prophylactic candidate for PVR prevention, warranting further clinical investigation.

PMID:42603669 | DOI:10.1016/j.exer.2026.111203

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Statistical and procedural interpretation of randomized emergency cervical cerclage strategies (Reply to Letter-to-the-Editor)

Am J Obstet Gynecol. 2026 Aug 15:S0002-9378(26)00417-5. doi: 10.1016/j.ajog.2026.08.014. Online ahead of print.

NO ABSTRACT

PMID:42603659 | DOI:10.1016/j.ajog.2026.08.014

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Clastogenicity of the food constituent higenamine in cultured V79 cells

Toxicol Lett. 2026 Aug 15:113179. doi: 10.1016/j.toxlet.2026.113179. Online ahead of print.

ABSTRACT

Higenamine is a catecholic benzyltetrahydroisoquinoline alkaloid occurring in plant-derived foods and food supplements, the latter potentially resulting in substantially higher exposure levels than conventional foods. Because of its catechol and alkylphenol structures, oxidative conversion to electrophilic quinone or quinone methide intermediates is plausible, raising concern about a potential genotoxic hazard. However, experimental data on the genotoxic potential of higenamine are lacking. The present study, therefore, investigated its potential to induce gene mutations and chromosomal damage in cultured V79 cells. Gene mutations were examined at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus after 24hours treatment without metabolic activation and after 4hours in the absence or presence of rat liver S9-mix. Clastogenicity and aneugenicity were assessed using in vitro micronucleus assay with CREST staining after 4hours of treatment, followed by compound-free postincubation periods of 16 and 24hours. Proliferation and mitotic activity were monitored, and higenamine stability was analyzed by HPLC-UV. Higenamine caused a statistically significant increase in the frequency of micronuclei at 300-510µM, reaching maxima of 51 and 73 micronucleated cells per 1,000 cells without and with metabolic activation, respectively. Micronuclei mainly contained chromosomal fragments, indicating a prevalent clastogenic mode of action, although a smaller increase in micronuclei containing whole chromosomes was also observed. Mutant frequencies in the HPRT assay were not significantly increased under any condition tested, despite concentration-dependent cytotoxicity. During incubation, higenamine concentrations decreased while only minor formation of O-methylated metabolites was detected, suggesting conversion into additional reactive products. Overall, these findings provide the first experimental evidence that higenamine exhibits clastogenic potential in vitro and support the hypothesis that oxidative activation of its catechol and/or alkylphenol moiety to electrophilic intermediates capable of reacting with cellular nucleophiles might contribute to its genotoxic activity.

PMID:42603655 | DOI:10.1016/j.toxlet.2026.113179

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The Role of Circulating Tumor Cell Dynamics in the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis

Crit Rev Oncol Hematol. 2026 Aug 15:105547. doi: 10.1016/j.critrevonc.2026.105547. Online ahead of print.

ABSTRACT

OBJECTIVE: The prognostic value of circulating tumor cells (CTCs) in colorectal cancer (CRC) remains debated. This meta-analysis evaluates their role in monitoring treatment response and predicting survival.

METHODS: We systematically searched multiple databases up to November 2025. Inclusion criteria comprised cohort studies involving CRC patients that assessed peripheral blood CTCs and reported outcomes such as CTC positivity/levels before and after treatment, progression-free survival (PFS), and overall survival (OS). Two reviewers independently extracted data and assessed the risk of bias using the Newcastle-Ottawa Scale. The meta-analysis was performed using Stata 18.0, with pooled odds ratios (ORs), standardized mean differences (SMDs), and hazard ratios (HRs) calculated using fixed- or random-effects models based on heterogeneity assessed by the I² statistic. This study was registered in PROSPERO.

RESULTS: A total of 18 studies involving 2,838 CRC patients were included. The meta-analysis demonstrated a significant decrease in both the CTC-positive rate (OR=0.52, 95% CI 0.31-0.87) and CTC count (SMD=-0.32, 95% CI -0.42 to -0.21) following therapy. Compared to patients without CTC reduction, those with reduced CTCs exhibited significantly better progression-free survival (HR=2.41, 95% CI 1.75-3.31) and overall survival (HR=3.29, 95% CI 1.99-5.45). Furthermore, CTC-positive status, both before and after treatment, was consistently associated with inferior PFS and OS (all p < 0.0001).

CONCLUSIONS: CTCs can serve as a biomarker for monitoring CRC therapeutic efficacy, predicting prognosis, and guiding subsequent treatment.

PMID:42603643 | DOI:10.1016/j.critrevonc.2026.105547

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Degenerative Histopathology in Ascending Aortic Aneurysms: Comparative Analysis by Aneurysm Location

Cardiovasc Pathol. 2026 Aug 15:107854. doi: 10.1016/j.carpath.2026.107854. Online ahead of print.

ABSTRACT

Aortic aneurysms have traditionally been studied as a single pathological entity, with emphasis on valve morphology. While histopathological differences between bicuspid (BAV) and tricuspid (TAV) aortopathy are well documented, less is known about how these mechanisms interact with aneurysm location within the ascending aorta. This gap complicates risk assessment and surgical planning beyond diameter-based criteria. We aimed to evaluate histopathological features of ascending aortic aneurysms across three topographical subgroups-root, tubular, and combined involvement-and assess modification by valve cuspidity. Using systematic criteria from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology consensus statement, the analysis focused on medial degeneration, adventitial alterations and atherosclerosis in patients undergoing ascending aortic surgery at a Finnish tertiary care center. The cohort comprised 296 patients with aneurysms located in the sinus of Valsalva (n = 122), tubular part (n = 130), and both regions (n = 44). Medial degeneration was present in all samples and predominantly moderate, with comparable median severity score of 2 (range 1-3, P = 0.829) across groups. In the overall cohort, no statistically significant differences were observed between topographical groups. Among TAV patients, tubular aneurysms demonstrated significantly higher histopathological scores for medial degeneration, elastic fiber fragmentation and loss, elastic fiber disorganisation, smooth muscle cell disorganization and nuclei loss, laminar medial collapse, medial fibrosis, adventitial fibrosis and atherosclerosis (all P < 0.05). In BAV patients, no statistical differences were found. Tubular aneurysms are characterized by more extensive wall remodeling and adventitial changes compared to root aneurysms, particularly in TAV patients. Notably, female sex emerged as a strong independent predictor of advanced medial and adventitial pathology. These findings underscore the importance of considering anatomical location, valve morphology, and sex in risk stratification and may inform surgical decision-making beyond diameter-based criteria.

PMID:42603640 | DOI:10.1016/j.carpath.2026.107854

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Preoperative stereotactic body radiotherapy for early-stage luminal breast cancer: a systematic review and meta-analysis (PRELUMEN)

Radiother Oncol. 2026 Aug 15:111743. doi: 10.1016/j.radonc.2026.111743. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Preoperative stereotactic body radiotherapy (SBRT) has emerged as a precision locoregional strategy for early luminal breast cancer, yet no quantitative meta-analysis exists in this subtype. We aimed to estimate the pooled pathological complete response (pCR) rate, identify its predictors through meta-regression, and characterise safety and cosmetic outcomes.

MATERIALS AND METHODS: A systematic review and meta-analysis of prospective trials of preoperative SBRT in patients with clinical stage T1-T2 N0-N1 luminal (ER-positive, HER2-negative) breast cancer was conducted following PRISMA 2020 guidelines. Random-effects models with REML estimation were fitted on logit-transformed proportions. Univariable meta-regression analyses examined absorbed dose (BED_4), irradiation-to-surgery interval, fractionation, technique, and biological tumor characteristics as covariates.

RESULTS: Eleven prospective studies (428 patients) were included. Eight trials (N = 277) reported pCR data, yielding a pooled pCR rate of 21.4 % (95 % CI: 12.1-35.1 %; I2 = 77.0 %). The irradiation-to-surgery interval was the sole statistically significant predictor of pCR (β = +0.045 per week; p < 0.001; R2 = 98.9 %), whilst BED_4, fractionation, and technique showed no independent association. Pooled late grade ≥ 3 toxicity was 5.9 % (95 % CI: 3.7-9.1 %) and excellent or good cosmesis was achieved in 88.3 % of patients (95 % CI: 79.4-93.6 %).

CONCLUSION: Preoperative SBRT achieves a clinically meaningful pCR rate in early luminal breast cancer, with acceptable toxicity and preserved cosmesis. The irradiation-to-surgery interval is the dominant modifiable predictor of pathological response. Randomized trials prospectively optimizing this interval in the luminal subtype are warranted.

PMID:42603618 | DOI:10.1016/j.radonc.2026.111743

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“LAPAGE Index In Differentiating Tuberculous Pleurisy and Malignant Pleural Effusion”

Am J Med Sci. 2026 Aug 15:S0002-9629(26)00313-7. doi: 10.1016/j.amjms.2026.08.005. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVE: Malignant pleural effusion and tuberculous pleurisy may both present with elevated levels, making their differential diagnosis challenging. Although an ADA level ≥ 40 U/L increases the likelihood of both conditions, additional biomarkers are needed for better discrimination. Therefore, we aimed to evaluate clinical and biochemical markers that could aid in differentiating these two conditions in patients with high ADA levels.

MATERIALS AND METHODS: This retrospective cohort study included patients with pleural effusion and pleural fluid ADA levels ≥ 40 U/L who were evaluated between 2014 and 2024. The cancer ratio (serum LDH/pleural ADA) and the pleural LDH/ADA ratio, previously described in the literature, were calculated. Multivariable regression analysis was performed to identify independent predictors of malignant pleural effusion.

RESULTS: A total of 294 patients constituted the study cohort. In multivariable regression analysis, cancer ratio was not statistically significant in differentiating malignant pleural effusion from tuberculous pleurisy. In contrast, the pleural LDH/ADA ratio, pleural protein level and age were identified as independent predictors of malignant pleural effusion. The LAPAGE index, derived from these variables [(pleural LDH / ADA) × age / pleural protein], demonstrated superior diagnostic performance in predicting malignant pleural effusion compared with individual parameters.

CONCLUSION: In patients with pleural effusion and ADA levels ≥ 40 U/L, neither the cancer ratio nor the pleural LDH/ADA ratio alone provided sufficient discriminatory power between malignant pleural effusion and tuberculous pleurisy. The LAPAGE index may serve as a useful adjunctive tool in the differential diagnosis of tuberculosis and malignancy in pleural effusions with high ADA levels.

PMID:42603615 | DOI:10.1016/j.amjms.2026.08.005