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Nevin Manimala Statistics

Optimal treatment strategies for unresectable stage III EGFR-mutated non-small cell lung cancer: a systematic review and Bayesian network meta-analysis

Front Oncol. 2026 Jun 26;16:1852617. doi: 10.3389/fonc.2026.1852617. eCollection 2026.

ABSTRACT

BACKGROUND: The PACIFIC regimen (consolidation durvalumab following chemoradiotherapy) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). With the publication of data from the phase III LAURA trial and the emergence of real-world evidence regarding sequential toxicity, concurrent chemoradiotherapy followed by sequential targeted therapy with EGFR tyrosine kinase inhibitors (TKIs) is recommended for patients with EGFR mutations. However, the optimal combination regimen remains to be determined.

METHODS: We systematically searched the PubMed, Embase, Cochrane Library, and Web of Science databases to identify randomized controlled trials (RCTs) and high-quality retrospective studies comparing various therapeutic strategies for unresectable stage III EGFR-mutated NSCLC. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary endpoints included the objective response rate (ORR) and safety profiles. A network meta-analysis (NMA) was performed using a Bayesian random-effects model. Hazard ratios (HRs), odds ratios (ORs), and their corresponding 95% credible intervals (CrIs) were calculated.

RESULTS: A total of 12 studies involving 1,529 patients were analyzed to compare six therapeutic strategies: consolidation durvalumab following chemoradiotherapy (CRT+Durva), CRT alone, consolidation EGFR-TKIs after CRT (CRT+EGFR-TKI), EGFR-TKI monotherapy, EGFR-TKI in combination with chemotherapy (EGFR-TKI+Chemo), and EGFR-TKI integrated with radiotherapy (EGFR-TKI+RT) via induction, concurrent, or consolidation sequencing. NMA revealed that CRT+EGFR-TKI was the only strategy to demonstrate a statistically significant improvement in OS compared to CRT alone (HR = 0.63, 95% CrI: 0.41-0.94), while also achieving the highest ORR. EGFR-TKI+RT (chemotherapy-free regimen) ranked first for PFS (HR = 0.14, 95% CrI: 0.06-0.33) and exhibited a favorable safety profile, associated with the lowest risk of severe radiation pneumonitis (RP). Notably, CRT+Durva failed to yield a survival benefit (PFS: HR = 0.75; OS: HR = 0.82) and was characterized by higher toxicity. An RCT-only sensitivity analysis demonstrated consistent PFS benefits and a comparable OS trend (HR = 0.68, 95% CrI: 0.33-1.4), validating the integration of real-world data to maintain adequate statistical power.

CONCLUSIONS: For unresectable stage III EGFR-mutated NSCLC, CRT+EGFR-TKI represents the optimal strategy for extending OS. Conversely, the EGFR-TKI+RT (chemotherapy-free regimen) approach provides a superior balance between prolonged PFS and clinical tolerability.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261285935.

PMID:42434745 | PMC:PMC13349829 | DOI:10.3389/fonc.2026.1852617

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Intravoxel incoherent motion combined with conventional MRI for the differentiation of benign, intermediate, and malignant fibrous soft-tissue tumors

Front Oncol. 2026 Jun 26;16:1863609. doi: 10.3389/fonc.2026.1863609. eCollection 2026.

ABSTRACT

BACKGROUND: Fibroblastic/myofibroblastic tumors are among the most common soft-tissue tumors (STTs) encountered clinically. Several magnetic resonance imaging (MRI) features associated with malignant tumors overlap with benign tumors, making differential diagnosis challenging. Intravoxel incoherent motion (IVIM) is a valuable MRI technique for differentiating various tumors. This study aims to evaluate the abilities of conventional MRI and IVIM in differentiating benign, intermediate, and malignant fibrous STTs.

METHODS: Fifty-five patients with fibrous STTs were prospectively enrolled, comprising 18 benign, 18 intermediate, and 19 malignant cases. All the patients underwent MRI examinations including IVIM. Conventional MRI signs and standard-apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were recorded. Statistical analyses were performed using Kruskal-Wallis H test, Chi-square test,post hoc test with Bonferroni correction, receiver operating characteristic (ROC) curves, and DeLong test. p < 0.05 indicated statistical significance.

RESULTS: Malignant tumors had higher heterogeneity on T2WI (p = 0.020 and 0.009) and contrast enhancement T1WI (p = 0.013 and 0.029), and were more prone to necrosis (p < 0.001 andp = 0.001) compared with benign and intermediate tumors, respectively. Tail-like pattern (p = 0.034 and 0.009) and invasiveness (p = 0.018 and 0.033) were more frequently observed in intermediate and malignant tumors than in benign tumors, respectively. Standard-ADCmean, standard-ADCmin, Dmean, and Dmin values decreased from benign to intermediate and malignant fibrous STTs. Malignant STTs displayed higher fmean and fmin values than benign tumors (p = 0.002 and 0.013, respectively). Standard-ADCmean showed the highest AUC (0.894) in differentiating intermediate from benign STTs. Dmean showed the highest AUC (0.961 and 0.905) in differentiating malignancies from benign and intermediate STTs, respectively. For discriminating between benign and non-benign fibrous STTs, the combination of conventional MRI signs and IVIM parameters yielded the highest AUC of 0.971.

CONCLUSION: IVIM diffusion parameters differentiated benign, intermediate, and malignant fibrous STTs and can complement conventional MRI signs.

PMID:42434743 | PMC:PMC13349916 | DOI:10.3389/fonc.2026.1863609

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Comparative effectiveness and safety of adjuvant trastuzumab plus pertuzumab versus trastuzumab emtansine in HER2-positive breast cancer with residual disease after neoadjuvant therapy: a real-world retrospective study

Front Oncol. 2026 Jun 26;16:1852055. doi: 10.3389/fonc.2026.1852055. eCollection 2026.

ABSTRACT

PURPOSE: To compare the effectiveness, safety, and tolerability of adjuvant trastuzumab plus pertuzumab (HP) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with residual invasive disease after neoadjuvant therapy, and to perform exploratory analyses of outcomes in clinically favorable subgroups.

MATERIALS AND METHODS: Patients with HER2-positive breast cancer and residual invasive disease after NAT, enrolled between 2020 and 2024, were included. Propensity score matching (1:1) was applied to adjust for baseline characteristic differences. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare survival outcomes (iDFS, RFS, OS) between the two groups. Additionally, the incidence of adverse events and treatment adherence were compared.

RESULTS: A total of 272 patients were analyzed, with 134 remaining after propensity score matching. After a median follow-up of 37.7 months, no statistically significant differences in short-term survival outcomes were detected between the two groups. Grade 3 or higher adverse events occurred more frequently in the T-DM1 group, particularly thrombocytopenia. Treatment interruption or regimen modification occurred in 22.7% of patients in the T-DM1 group and 2.2% in the HP group.

CONCLUSION: In HER2-positive breast cancer patients with residual invasive disease after NAT, no statistically significant difference in short-term recurrence or survival outcomes was detected between adjuvant HP and T-DM1, while HP was associated with a more favorable safety and tolerability profile. These findings should be interpreted as complementary real-world evidence in the contemporary dual-blockade era and as hypothesis-generating support for future risk-adapted adjuvant strategies.

PMID:42434737 | PMC:PMC13349879 | DOI:10.3389/fonc.2026.1852055

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Postoperative complications after cataract surgery with and without concurrent minimally invasive glaucoma surgery in patients with primary open angle glaucoma: a comparative risk analysis

Front Ophthalmol (Lausanne). 2026 Jun 26;6:1830822. doi: 10.3389/fopht.2026.1830822. eCollection 2026.

ABSTRACT

BACKGROUND: Primary open-angle glaucoma (POAG) is the most common form of glaucoma and a leading cause of irreversible blindness worldwide. Treatment focuses on lowering intraocular pressure (IOP), often through cataract extraction with intraocular lens implantation (CE/IOL) alone or combined with minimally invasive glaucoma surgery (MIGS). However, comparative postoperative complication risks between these approaches remain unclear.

METHODS: This retrospective cohort study utilized the TriNetX US Collaborative Network to identify all adults (ages ≥18 years) with a diagnosis of POAG who underwent CE/IOL with or without concurrent MIGS between 2006 and 2026. The cumulative postoperative incidence of hyphema, cystoid macular edema (CME), retinal detachment (RD), and endophthalmitis were evaluated at four time intervals up to 90 days postoperatively. Propensity score matching was used to balance baseline characteristics and reduce confounding. Outcomes were compared using relative risks with 95% confidence intervals, and P-values were calculated using chi-square tests.

RESULTS: After propensity score matching, each routine cataract surgery cohort (with and without MIGS) comprised 7, 998 patients. Patients undergoing CE/IOL with MIGS had a significantly higher rate of hyphema compared with patients undergoing CE/IOL alone at all reported postoperative time points, with a cumulative incidence of 1.19% versus 0.15% at 1-90 days after surgery, respectively (P<0.0001). Conversely, the cumulative incidence of CME (2.585% vs 2.376%, P = 0.3993), RD (0.215% vs 0.139%, P = 0.2566) and endophthalmitis (0.276% vs 0.15%, P = 0.0862) at 1-90 days postoperatively at 1-90 days postoperatively were not statistically different between groups. Similar associations were observed among patients undergoing routine or complex CE/IOL combined with MIGS compared with those undergoing routine or complex CE/IOL alone with respect to hyphema, CME, and RD.

CONCLUSIONS: In this large retrospective cohort study, combined CE/IOL with MIGS was associated with a significantly increased risk of postoperative hyphema, while rates of CME, RD, and endophthalmitis remained comparable to CE/IOL alone.

PMID:42434709 | PMC:PMC13349877 | DOI:10.3389/fopht.2026.1830822

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Effects of age on the genetic and clinical characteristics of retinitis pigmentosa

Front Ophthalmol (Lausanne). 2026 Jun 26;6:1776570. doi: 10.3389/fopht.2026.1776570. eCollection 2026.

ABSTRACT

PURPOSE: This study aimed to investigate how age affects the genetic and clinical characteristics of retinitis pigmentosa (RP), focusing on the detectability of causative genes and the age at disease onset.

METHODS: We conducted a single-center study of 506 patients with RP who underwent comprehensive genetic testing through targeted resequencing of 83 known RP-associated genes using next-generation sequencing. Patients were stratified by age at study entry into six groups: <40 years (20-39), 40s (40-49), 50s (50-59), 60s (60-69), 70s (70-79), and ≥80 years. Detection rates of causative genes were calculated and compared across age groups using the Cochran-Armitage trend test. Genetically solved cases included 42 with EYS, 19 with USH2A, 9 with RP1, 14 with RHO, and 7 with RPGR. Clinical data were collected retrospectively. Age at onset was defined as the age when the patient first noticed night blindness, visual field constriction, or decreased best corrected visual acuity. Age at onset was compared across causative genes using an one-way analysis of variance (ANOVA). For pairwise comparisons, the Wilcoxon rank-sum test was applied with Bonferroni correction to adjust for multiple testing.

RESULTS: The mean age of participants was 58.8 years, and our sample included 235 males and 271 females. Case numbers by age group were as follows: <40 years, 58; 40s, 92; 50s, 94; 60s, 125; 70s, 104; and ≥80 years, 33. Detection rates of causative genes declined steadily with age: 39.7% (<40), 41.3% (40s), 36.2% (50s), 27.2% (60s), 19.2% (70s), and 3.0% (≥80), showing a statistically significant trend (p = 8.22 × 10-7, Cochran-Armitage trend test). In subset analysis, mean onset ages were RPGR (5.2 years), EYS (19.5 years), RHO (24.3 years), RP1 (25.2 years), and USH2A (34.1 years), indicating a significant difference among genes (p < 0.001). Pairwise comparisons showed significantly earlier onset in the RPGR group relative to USH2A (p = 0.004).

CONCLUSIONS: The detection rate of known causative genes of RP was lower in the elderly patients, potentially reflecting factors associated with a late-onset phenotype.

PMID:42434706 | PMC:PMC13349749 | DOI:10.3389/fopht.2026.1776570

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Unsupervised OCT Image Interpolation Using Deformable Registration and generative models

Med Image Comput Comput Assist Interv. 2026;15963:661-671. doi: 10.1007/978-3-032-04965-0_62. Epub 2025 Sep 19.

ABSTRACT

Optical coherence tomography (OCT) images are often acquired as highly anisotropic volumes, where the scanning step is dense along the fast axis but sparse along the slow axis. This affects image analysis, such as image registration for longitudinal alignment. To create more isotropic volumes, bicubic interpolation can be used along the slow axis, but it generally produces blurry features. Registration-based interpolation can reduce blurriness, but often fails to generate realistic OCT images. Deep generative models can sample realistic images, but lack the structural consistency constraints required for interpolation. In this paper, we propose an unsupervised image interpolation method that combines registration-based interpolation with a deep generative model to overcome their individual limitations and improve the structural accuracy and realism of interpolated OCT images. We compare the proposed method with both bicubic and registration-based interpolation on real OCT datasets, and show that it achieves the best interpolation performance.

PMID:42434689 | PMC:PMC13352931 | DOI:10.1007/978-3-032-04965-0_62

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Behavioral phenotypes in aging: structured exploratory computational analysis of multi-assay behavioral data

Front Behav Neurosci. 2026 Jun 19;20:1861841. doi: 10.3389/fnbeh.2026.1861841. eCollection 2026.

ABSTRACT

BACKGROUND: Aging is associated with progressive alterations in behavioral function, yet majority of the studies interpret behavioral outcomes on an assay-by-assay basis, limiting understanding of how behavioral domains are organized. Our previously published study used a mouse cohort to report assay-specific behavioral effects. In this study, we examined whether aging-related behavioral signals remain localized to individual assays or can be summarized as coordinated domain-level patterns.

METHODS: A structured rule-based workflow was implemented for feature engineering, direction harmonization, z-score standardization, and domain-level composite construction across locomotion/exploration, anxiety/avoidance, depression/passive coping, cognition/learning, memory, and sociability domains. Outcomes were analyzed using parametric or non-parametric models following assumption screening, with effect sizes reported.

RESULTS: Domain-level composite scores did not show significant age- or sex-related effects, indicating limited broad behavioral separation. In contrast, refined feature-level analysis identified modest locomotor differences (core locomotion distance; Kruskal-Wallis p = 0.048) and the clearest age-related signal in Barnes Maze performance, particularly the Barnes Maze efficiency index (F = 10.815, p < 0.001), with reduced performance in older animals. Repeated-measures analyses further confirmed training-related improvements in latency across days. Several additional measures showed a trend but did not reach statistical significance and hence are reported descriptively only.

CONCLUSION: Aging-related behavioral changes in this dataset were concentrated in specific assay-level measures rather than broadly distributed across domains. Domain-level aggregation reduced separation of effects, indicating that the present composites should be interpreted as heuristic summaries rather than validated behavioral dimensions. The main added value of this reanalysis is therefore interpretive, showing that the strongest signals remain most evident in selected measures, particularly Barnes Maze outcomes.

PMID:42434686 | PMC:PMC13351101 | DOI:10.3389/fnbeh.2026.1861841

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Implementing the Eat, Sleep, Console (ESC) Model in a Small Safety-Net Hospital: A Phased Quality Improvement Initiative

Cureus. 2026 Jun 9;18(6):e110557. doi: 10.7759/cureus.110557. eCollection 2026 Jun.

ABSTRACT

BACKGROUND AND OBJECTIVE: The rising prevalence of opioid use during pregnancy has contributed to increasing rates of neonatal opioid withdrawal syndrome (NOWS). Traditional management using the Finnegan Neonatal Abstinence Scoring System (FNASS) is associated with prolonged hospitalization, increased neonatal intensive care unit (NICU) utilization, and reduced maternal‑infant bonding. Function‑based models such as Eat, Sleep, Console (ESC) emphasize non‑pharmacologic care and may improve outcomes. This project aimed to transition from FNASS to ESC within a small safety‑net hospital and evaluate associated clinical outcomes.

METHODS: We conducted a single‑center quality improvement initiative using a phased implementation strategy over 2.5 years. Eligible neonates were >36 weeks gestation or >2000 grams with prenatal opioid exposure. Clinical outcomes were compared between infants managed with FNASS (n=24) and ESC (n=12). Due to the small sample size and skewed distributions, continuous variables were analyzed using Mann-Whitney U tests and reported as medians with interquartile ranges.

RESULTS: ESC implementation was associated with shorter median length of stay (3.5 vs. 16.5 days; p<0.001), fewer days on pharmacologic treatment (0 vs. 11.5 days; p=0.008), and fewer days in the NICU (0 vs. 13.5 days; p<0.001). Infants in the ESC group spent a higher percentage of hospitalization bonding with their mothers (100% vs. 14.6%; p=0.002), although the total number of bonding days did not differ significantly (p=0.199). Pharmacologic treatment use was lower in the ESC group (0% vs. 54.2%; p=0.002).

CONCLUSIONS: Transitioning to ESC was associated with reduced pharmacologic treatment, shorter hospitalization, decreased NICU utilization, and improved maternal‑infant bonding. These findings support the feasibility of ESC implementation in resource‑limited safety‑net settings and highlight a scalable framework for equitable NOWS care.

PMID:42434680 | PMC:PMC13349960 | DOI:10.7759/cureus.110557

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A Cross-Sectional Study on the Knowledge, Awareness, Myths, and Acceptability of Menstrual Cups Among Adolescent Girls in Nagamangala Taluk

Cureus. 2026 Jun 10;18(6):e110582. doi: 10.7759/cureus.110582. eCollection 2026 Jun.

ABSTRACT

Introduction Menstrual cups are a safe, cost-effective, and sustainable menstrual hygiene product; however, their awareness and acceptability among adolescents remain low due to socio-cultural barriers and misconceptions. The study aimed to assess the knowledge, awareness, myths, and acceptability of menstrual cups among adolescent girls and to evaluate factors influencing their willingness to use them. Materials and methods A community-based cross-sectional study was conducted among 812 adolescent girls aged 13-19 years in Nagamangala taluk, Karnataka, from February to April 2026. Data were collected using a pre-tested semi-structured questionnaire. Knowledge was categorized as adequate when >50% responses were correct. Associations were analyzed using the chi-squared test, with p < 0.05 considered statistically significant. Results Awareness of menstrual cups was observed in 308 (37.9%) participants. Adequate knowledge was present in 342 (42.1%), while myths and misconceptions were reported by 498 (61.3%). The most common misconception was fear of pain during insertion 362 (44.6%). Overall, 548 (67.5%) participants expressed willingness to use menstrual cups. Awareness increased significantly with age (χ² = 9.82, p = 0.002). Willingness was significantly higher among those aware, 220 (71.4%), compared to those not aware, 328 (65.1%) (χ² = 4.21, p = 0.040). Adequate knowledge was associated with higher acceptability (χ² = 14.7, p < 0.001), while the presence of myths was associated with lower willingness (χ² = 41.6, p < 0.001). Conclusion Despite low awareness and prevalent misconceptions, the acceptability of menstrual cups was relatively high, particularly after exposure to appropriate information. Strengthening menstrual health education and addressing myths may improve the adoption of menstrual cups among adolescents.

PMID:42434676 | PMC:PMC13352334 | DOI:10.7759/cureus.110582

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Top-Cited Articles on Dysphagia and Cognitive Impairment: A Scopus-Based Bibliometric Analysis of Publications Retrieved Through October 2025

Cureus. 2026 Jun 10;18(6):e110620. doi: 10.7759/cureus.110620. eCollection 2026 Jun.

ABSTRACT

Deglutition disorders and cognitive impairment co-occur frequently in older adults and in patients with neurodegenerative or cerebrovascular disease, yet the intellectual structure and collaborative patterns at this clinical interface have not been mapped. We performed a bibliometric analysis, with scoping-review-style charting, of publications indexed in the Scopus database through the search date of 10 October 2025; we retrieved 1,190 records and retained the 100 most-cited articles for in-depth analysis. Because the most recent publications (2023-2025) have not yet accrued sufficient citations, the resulting top-100 corpus spans 2009-2022. Articles were stratified into three citation tiers: Hyperclassics (≥500 citations, n = 11), Top-Class (250-499 citations, n = 20), and Classics (100-249 citations, n = 69). Performance analysis and science mapping were conducted in R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria) using the bibliometrix and biblioshiny packages (open-source; https://www.bibliometrix.org/). Continuous variables were compared using the Kruskal-Wallis test followed by post hoc Mann-Whitney U tests; categorical variables with the chi-squared test and Cramér’s V; and correlations among journal indicators with Spearman’s rho and 95% confidence intervals derived via Fisher’s z-transformation. The corpus accumulated 30,872 total citations (range 112-4,312). Stroke was the leading venue (6 articles; 7,909 citations; 25.6% of the corpus), and the United States contributed 32 articles representing 47% of all citations, followed by the United Kingdom, Italy, Canada, and Germany. Hyperclassics significantly out-cited Classics in both total citations and citations per year (both p<0.0001) but not in author count or active years. Inter-metric correlations among Journal Impact Factor (JIF), CiteScore, SCImago Journal Rank (SJR), and Source Normalized Impact per Paper (SNIP) were uniformly strong (ρ>+0.84; all p<0.001), whereas correlations between these journal-level indicators and article-level citations were weak (ρ +0.22 to +0.29; all p<0.05). Keyword co-occurrence resolved three thematic clusters-stroke, dementia, and dysphagia (clinical burden and nutrition); Parkinson’s disease and movement disorders; and neurological symptoms, cognition, and diagnostic imaging-while a complementary thematic-evolution analysis traced eight finer research streams. The field is dominated by stroke-related research and Anglo-American academic medicine, with a small set of influential guidelines driving disproportionate citation weight. Within this most-cited corpus, articles centred explicitly on the dysphagia-cognition interface were comparatively few (14% of the corpus), whereas disease-context and guideline records predominated; sensitivity analyses excluding peripheral records preserved the thematic and geographic structure. Estimating under-representation relative to clinical burden would require a field-normalised denominator and is proposed as future work. Future work should prioritize mechanistic neuroimaging in cognitively impaired patients, validated screening instruments adapted for dementia and parkinsonism, and comparative-effectiveness trials of dysphagia interventions across diagnostic categories.

PMID:42434674 | PMC:PMC13354282 | DOI:10.7759/cureus.110620