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Nevin Manimala Statistics

Novel Distance Regression for Repeated Outcomes With Missing Data: Applications to Longitudinal and Crossover Studies of Microbiome Beta-Diversity

Stat Med. 2026 Jul;45(15-17):e70654. doi: 10.1002/sim.70654.

ABSTRACT

The human microbiome plays a crucial role in health, but understanding its dynamic relationship with the host requires regular monitoring. Beyond challenges such as high dimensionality and sparsity, additional complexities arise, particularly within-cluster correlation from repeated measures and pervasive missing data. To address these issues, we develop Edger, a novel distance regression method for modeling community-level beta-diversity dynamics and their interactions with treatment or host physiology. By focusing on beta-diversity, a distance metric between microbial profiles, Edger (Ensembled semiparametric distance-based generalized estimation for repeated outcomes) directly models these distances as repeated outcomes, yielding interpretable coefficients and enabling a covariate batching strategy to mitigate omitted variable bias. Our semiparametric inference framework eliminates the need for time-consuming permutation tests, distinguishes between-cluster heterogeneity from within-cluster fluctuations, and allows flexible specification of working correlation structures. To handle missing data, we assume a missing-at-random (MAR) mechanism and incorporate a between-subject propensity score in the repeated distance regression to provide seamless joint inference, ensuring robust variance estimation without casewise deletion. Additionally, we introduce an algorithm to generate synthetic data from real-world microbial counts while preserving their zero-inflated and correlated nature. Edger demonstrates superior inferential power and computational efficiency through our numerical studies and real-world applications, making it a valuable tool for uncovering microbiome-host interactions and advancing multi-omics data integration.

PMID:42393392 | DOI:10.1002/sim.70654

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Nevin Manimala Statistics

Composite desirability-based multi-objective optimization of textile-dye biodegradation by novel Brevundimonas sp. AJZ05: mechanistic and phytotoxicity insights

Environ Geochem Health. 2026 Jul 2;48(10):430. doi: 10.1007/s10653-026-03332-3.

ABSTRACT

Improper discharge of untreated textile effluents comprising synthetic azo-dyes which are characterised by azo bond (-N = N-), poses severe environmental and public health concern due to persistence, toxicity and resistance towards conventional treatment techniques. This has created pressing need for low-cost, eco-friendly alternatives where microbial degradation shows effective remediation compared to chemical and physicochemical treatment methods, which are often costly, energy-intensive, and generate secondary pollutants. In this study, novel azoreductase-producing bacterium, Brevundimonas sp. AJZ05, was isolated from textile effluent and exhibited initial Direct Blue-6 decolorization efficiency of 85.24% and azoreductase activity of 0.172 U/mL. Plackett Burman design identified dye concentration, yeast extract, inoculum level as key variables influencing decolorization efficiency, while glucose, yeast extract, and inoculum level significantly affected azoreductase activity. Multi-response optimization via Response Surface Methodology with desirability functional approach determined optimal conditions: dye concentration (101.76 mg/L), glucose (5.19 g/L), yeast extract (5.87 g/L), and inoculum level (5.45%), achieving maximum decolorization efficiency (98.50%) and azoreductase activity (0.761 U/mL), corresponding to 1.1-fold and 2.83-fold increases, respectively. The optimized process remained effective in the presence of metal ions (Cu2+, Mg2+, Mn2+, Zn2+, Fe2+ at 0.5-1 mM), indicating its robustness under effluent condition. UV-Vis spectroscopy, FTIR, GC-MS and phytotoxicity analysis using Vigna radiata confirmed complete breakdown of DB-6 into less/non-toxic intermediates. Overall, Brevundimonas sp. AJZ05 exhibits strong potential for azo-dye bioremediation and toxicity reduction, showing significant promise towards environmental sustainability.

PMID:42393388 | DOI:10.1007/s10653-026-03332-3

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Nevin Manimala Statistics

Large-Scale Monitoring and Risk Assessment of Metal Contamination from Urban Areas in the Amazon River Basin

Arch Environ Contam Toxicol. 2026 Jul 2;91(1):8. doi: 10.1007/s00244-026-01206-4.

ABSTRACT

In this study we provide a comprehensive assessment of metal contamination in the Amazon River and its main tributaries, with a focus on urban contamination hotspots. A monitoring campaign was conducted across 40 sampling sites, analysing water concentrations of As, Cd, Cu, Cr, Fe, Mn, Pb, Ni, and Zn. Metal concentrations were evaluated against national and international water quality standards and compared between urbanized and less impacted regions to delineate pollution patterns. Additionally, an ecological risk assessment was conducted for individual metals and for metal mixtures using Species Sensitivity Distributions (SSDs). The results of this study show that Fe levels in the Amazon River were exceptionally high, with potential implications for aquatic species distribution across the basin. Exceedances of water quality standards were identified for four metals (Fe, Pb, Mn, Cu), with metal enrichment observed particularly in Manaus, Macapá, and Belém. Acute multi-substance potentially affected fraction (msPAF) of species in the Amazon River and its tributaries indicated insignificant risks, while chronic values ranged from 3% to 33%. In urban areas, acute msPAF values were generally low, with the exception of two samples taken in Manaus that exhibited values of 11% and 16%. Chronic riskvalues, however, were consistently high in these urban locations, reaching up to 72% of species potentially affected and reflecting sustained ecotoxicological stress. Cu, Zn and Mn were identified as the primary contributors to chronic toxicity, with Cu and Zn dominating in Manaus, and Mn in Macapá. These findings underscore the need for stricter industrial discharge regulations and improved wastewater treatment systems to preserve Amazonian freshwater ecosystems.

PMID:42393378 | DOI:10.1007/s00244-026-01206-4

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Nevin Manimala Statistics

Feasibility and preliminary effects of outdoor versus indoor cognitive-motor therapy in women with Alzheimer’s disease: A randomized single-blind pilot study

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-60446-5. Online ahead of print.

ABSTRACT

Alzheimer’s disease is associated with progressive cognitive, functional and social decline. Non-pharmacological interventions that combine cognitive and motor stimulation are increasingly used in long-term care, but less is known about the feasibility and preliminary effects of delivering such programmes in outdoor rather than indoor settings. This exploratory randomized single-blind pilot study compared outdoor and indoor cognitive-motor therapy in institutionalized older women with Alzheimer’s disease, focusing on global cognitive performance, selected functional outcomes, attendance and practical implementation. Fifty women aged 66.1-70.2 years with late-onset Alzheimer’s disease were randomized to a seven-month outdoor cognitive-motor programme (n = 25) or an indoor cognitive-motor programme (n = 25). Sessions were delivered five times weekly for 45 min. Outcome assessors and data analysts were blinded to group allocation; therapists and participants could not be blinded because of the intervention setting. Global cognition was assessed with the Mini-Mental State Examination (MMSE). Functional outcomes were assessed using modified FIM-based indicators for daily tasks, mobility and social adaptability. Attendance and adverse events were recorded as feasibility outcomes. All randomized participants completed the study. Mean attendance was 91% in the outdoor group and 89% in the indoor group, and no intervention-related adverse events were recorded. Both groups improved on the MMSE, with a median increase of approximately two points. The outdoor group showed statistically significant within-group improvements in all three FIM-based indicators (daily tasks, mobility and social adaptability), whereas the indoor group did not show statistically significant functional change. However, these broader gains were observed in the context of baseline functional imbalance, including lower outdoor-group mobility and social-adaptability scores, and the small female-only sample and partial non-equivalence of intervention content limit between-group causal interpretation. A seven-month cognitive-motor programme was feasible in participating long-term care facilities. The findings suggest that outdoor delivery may be associated with broader functional gains than indoor delivery, but the results should be interpreted as preliminary and in light of the baseline functional imbalance. A fully powered, prospectively registered trial with more equivalent intervention arms, repeated measurement points, standardized functional outcomes and detailed monitoring of comorbidities and medication changes is warranted.

PMID:42393367 | DOI:10.1038/s41598-026-60446-5

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Nevin Manimala Statistics

Impact of conventional versus retropubic TOT procedures on female sexual function

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-59783-2. Online ahead of print.

ABSTRACT

Urinary incontinence, coital incontinence, dyspareunia, and sexual dysfunction are clinical conditions that can result from this condition. Treatment options include conservative and surgical approaches. The gold standard in surgery is mid-urethral sling procedures. The aim of this study is to compare the effects of the commonly used conventional transobturator tape (TOT) and retropubic transobturator tape (TOTRP) techniques on female sexual function and to evaluate possible differences, particularly regarding dyspareunia. A total of 108 sexually active women with stress urinary incontinence who underwent conventional TOT (n = 54) or TOTRP (n = 54) surgery between January 2023 and January 2025 were included in the study. Women aged 18-60 years who presented to the clinic for stress urinary incontinence between January 2023 and January 2025, were sexually active, underwent TOT or TOTRP surgery, and had a minimum of 6 months postoperatively were included in the study. The FSFI questionnaire data and demographic characteristics of patients in this group, as routinely collected in our practice, were retrieved from the hospital database and patient files. Data analysis and statistics were performed using jamovi software (version 2.6.44). No significant differences were found between the demographic and clinical characteristics of the two groups included in the study. A significant increase in postoperative FSFI scores was observed in both groups compared to the preoperative period. No significant difference was found between TOT and TOTRP in terms of total FSFI scores. However, when FSFI subscales were examined, a significant improvement in dyspareunia scores was observed only in the TOTRP group in the postoperative period (p < 0.001). No significant change in dyspareunia was observed in the conventional TOT group. Postoperative coital incontinence decreased significantly in both groups. Conventional TOT and TOTRP techniques provide a general improvement in female sexual function after SUI surgery. Although there is no significant superiority between the techniques in terms of total sexual function scores, improvement in dyspareunia scores was observed in the TOTRP group; however, direct superiority over conventional TOT could not be established. Prospective, randomized, long-term follow-up studies are needed to confirm these findings.

PMID:42393323 | DOI:10.1038/s41598-026-59783-2

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Nevin Manimala Statistics

Gamma knife radiosurgery for renal cell carcinoma brain metastases across systemic therapy eras: survival, intracranial failure, and lesion-level predictors

J Neurooncol. 2026 Jul 3;178(3):87. doi: 10.1007/s11060-026-05692-3.

ABSTRACT

BACKGROUND: Brain metastases from renal cell carcinoma (RCC) are uncommon but clinically consequential. We evaluated survival, intracranial failure, lesion-level local failure, and MRI volumetric response after Gamma Knife radiosurgery (GKRS), including associations with systemic therapy exposure.

METHODS: We retrospectively identified patients treated with GKRS for intracranial RCC metastases (2001-2025). Systemic therapy exposure (TKI and/or immunotherapy) was captured time-agnostically. Overall survival (OS) and patient-level intracranial treatment failure were analyzed using Kaplan-Meier/Cox models. Lesion-level treatment failure was analyzed using clustered generalized estimating equations (GEE). Six-month volumetric response was assessed using an epsilon-stabilized log volume ratio ln{(V6m+ϵ)/(VGKRS+ϵ)}, ε = 0.01.

RESULTS: Thirty-four patients (87 lesions) were treated; 22 deaths occurred. Overall survival was numerically longer among patients who received systemic therapy compared with those who did not, although this did not reach statistical significance (log-rank p = 0.058). In a parsimonious adjusted Cox model, TKI exposure was associated with improved OS (aHR 0.191; 95% CI 0.062-0.593; p = 0.004), as was higher KPS (HR 0.37 per 10-point increase; 95% CI 0.21-0.63; p < 0.001). Ten patient-level intracranial treatment failure events occurred, without significant differences by systemic therapy exposure. At the lesion level, 15/87 lesions failed; postoperative cavities had higher failure than intact lesions (71.4% vs. 12.5%; p = 0.001) and remained associated with failure after clustered adjustment (OR 9.92; 95% CI 1.44-68.27; p = 0.020). Dmax was not correlated with 6-month log volume ratio (ρ=-0.075; p = 0.535), but poorer 6-month volumetric response was associated with subsequent lesion failure (p = 0.0023; clustered OR 2.84; 95% CI 1.16-6.96; p = 0.023).

CONCLUSIONS: In RCC brain metastases treated with GKRS, postoperative cavities showed a higher observed rate of local failure than intact lesions, although this finding should be interpreted cautiously given the small number of cavity targets. While Dmax was not associated with early volumetric change, early 6-month volumetric trajectory was associated with subsequent local failure, suggesting a pragmatic imaging marker for risk-adapted surveillance and salvage planning. Systemic therapy exposure, particularly TKIs, was associated with OS in adjusted analysis, whereas intracranial treatment failure did not differ by systemic exposure in this cohort.

PMID:42393321 | DOI:10.1007/s11060-026-05692-3

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Nevin Manimala Statistics

Exploring the Relationship Between Cerebral Blood Flow and Oral Exercise Using Head-Mounted Near-Infrared Spectroscopy

Dysphagia. 2026 Jul 3. doi: 10.1007/s00455-026-10975-y. Online ahead of print.

ABSTRACT

Swallowing activities have been increasingly recognized as relevant to cognitive function, yet the physiological pathways linking these functions to the brain remain incompletely understood. One proposed mechanism involves changes in cerebral blood flow. This study examined whether a standardized oral exercise program could alter prefrontal cerebral blood flow, measured by near-infrared spectroscopy. This single-center prospective study enrolled 52 healthy adults (mean age 33.1 ± 10.4 years; 67.3% female). Participants performed a 12-min exercise protocol consisting of 15 guided tasks classified into neck and shoulder relaxation, swallowing muscle strengthening, and vocalization practice. Cerebral hemodynamic responses were recorded continuously with a head-mounted dual-wavelength spectrophotometer. Hemoglobin difference (HbD), defined as oxygenated minus deoxygenated hemoglobin (HbO₂ – HbR), was used as a surrogate marker of blood flow, and task-related changes (ΔHbD) were calculated relative to baseline. Category-level effects were evaluated with Bonferroni correction, and task-wise comparisons were treated as exploratory and adjusted using Benjamini-Hochberg false discovery rate correction. Swallowing muscle strengthening tasks demonstrated a significant category-level increase in ΔHbD (0.34 ± 0.96 µM; p = 0.01), whereas the other exercise categories did not show significant overall effects after correction. In exploratory task-wise analyses, tongue protrusion (p = 0.0098, q = 0.049), lateral tongue movements (p = 0.0003, q = 0.0045), and chewing and swallowing action (p = 0.0095, q = 0.049) remained statistically significant after false discovery rate adjustment. No differences were observed by age or sex. In summary, swallowing-related oral exercises were associated with acute increases in prefrontal cerebral blood flow. These results suggest a possible physiological link between oral motor activity and cerebral perfusion, which warrants further investigation in larger and more diverse populations.

PMID:42393301 | DOI:10.1007/s00455-026-10975-y

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Nevin Manimala Statistics

Prevalence of and risk factors for diabetic retinopathy: The Thessaloniki Eye Study

Eye (Lond). 2026 Jul 2. doi: 10.1038/s41433-026-04698-5. Online ahead of print.

ABSTRACT

OBJECTIVE: To estimate DR prevalence, risk factors, and undiagnosed disease in the Thessaloniki Eye Study.

DESIGN: Cross-sectional, population-based study.

SETTING: Community examinations and home visits in Thessaloniki, Greece.

PARTICIPANTS: Adults aged 60 years or older; 2468 with gradable fundus data or fundus examination were analysed.

EXPOSURES: Self-reported diabetes mellitus (DM), demographics, ocular/systemic history, and lifestyle factors.

MAIN OUTCOMES AND MEASURES: DR prevalence/severity graded from fundus photographs using a modified Airlie House system; clinically significant macular oedema (CSMO), vision-threatening retinopathy (VTR), and DR risk factors.

RESULTS: Among 2468 participants, DR prevalence was 6.9% (170/2468; 95% CI, 6.0%-8.0%). Among 352 participants with self-reported diabetes, 31.0% (109/352; 95% CI, 26.4%-36.0%) had DR; mild, moderate, severe non-proliferative DR, and proliferative DR were observed in 13.6%, 7.1%, 7.4%, and 2.8%, respectively. CSMO and VTR were present in 6.5% and 11.9%, respectively. Increased DR risk was associated with male gender (OR = 2.64), insulin therapy (OR = 4.87), and longer antihyperglycaemic treatment duration (OR = 1.05/year). Lower DR risk was associated with older age (OR = 0.87/year), regular alcohol intake (OR = 0.39), and migraines with aura (OR = 0.11). Among participants with DR, 73.9% were unaware of their diagnosis.

CONCLUSIONS: DR affected nearly one-third of participants with diabetes, and most DR cases were undiagnosed. These findings support improved DR screening and education in older Greek adults.

PMID:42393291 | DOI:10.1038/s41433-026-04698-5

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Nevin Manimala Statistics

Analysis of dose reconstruction techniques in pre-treatment QA of large-field RapidArc technique with a 2D detector array

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-60065-0. Online ahead of print.

ABSTRACT

This study aims to evaluate the impact of two dose reconstruction techniques, standard and composite, on gamma passing rates (GPRs) during pre-treatment quality assurance of large-field pelvic RapidArc plans using the Octavius 4D system with a 1500 2D ionization chamber array. The investigation focuses on quantifying the effect of reconstruction methodology across varying gamma criteria and normalization modes. Ten large-field pelvic RapidArc verification plans for pelvic radiotherapy cases were analysed using both standard reconstructions based on a single measurement and composite reconstructions generated by merging two longitudinally shifted measurements in the Octavius 4D system. Measurements were performed on a Varian TrueBeam linac using 6 MV beams, and dose comparisons were conducted in verisoft software. The composite reconstruction was generated by merging two longitudinally shifted measurements to extend the detector’s effective field of view. Gamma analyses were performed under both global and local normalization at multiple criteria (1 mm/2%, 2 mm/2%, 2 mm/3%, 3 mm/2%, and 3 mm/3%). Statistical significance between reconstruction methods was assessed using paired tests (p < 0.05). Under global normalization, 3D GPRs exceeded 95% for all criteria, with negligible differences (< ±2%) between standard and composite reconstructions (p > 0.05). Local normalization exhibited greater sensitivity, showing up to -11.6% lower GPRs for the composite method at the most stringent criterion (1 mm/2%), though these differences diminished (<2%) at 3 mm/3%. Composite reconstructions consistently produced volumetric and transverse-plane GPRs that were comparable to or higher than those from single-plane analyses, confirming stable dose agreement across planes. The composite reconstruction method provides dosimetric accuracy equivalent to the standard approach while enabling full-field verification for large field pelvic RapidArc fields. Its use significantly enhances QA efficiency without compromising clinical reliability. For standard practice, composite reconstruction combined with global normalization and 3 mm/3% gamma criteria offers an optimal balance between accuracy and practicality in large-field pre-treatment QA.

PMID:42393290 | DOI:10.1038/s41598-026-60065-0

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Nevin Manimala Statistics

Evaluation of surgical outcomes and associated factors in cataracts secondary to blunt trauma

Int Ophthalmol. 2026 Jul 2;46(1):275. doi: 10.1007/s10792-026-04151-2.

ABSTRACT

PURPOSE: To evaluate the postoperative visual and refractive outcomes of cataract surgery following blunt ocular trauma over a ten-year period and to investigate the impact of timing of surgical intervention, and preoperative clinical findings on the final visual prognosis.

METHODS: This study included 92 patients who underwent cataract surgery secondary to blunt ocular trauma at a single-center tertiary care hospital between January 2015 and January 2025. Demographic characteristics, cataract types, lens status, timing of surgery, preoperative and postoperative best-corrected visual acuity (BCVA), spherical equivalent (SE), associated ocular findings, surgical complications, and same-session intraocular lens (IOL) implantation were analyzed.

RESULTS: The mean age of the patients was 54.7 ± 18.4 years, and 66.3% were male. The most common cataract types were mature cataract (50%) and cortical cataract (28.3%). Mean preoperative BCVA improved significantly to a mean best-achieved postoperative BCVA of 0.39 ± 0.50 logMAR. The mean postoperative spherical equivalent was – 1.11 ± 2.02 D. Complications were observed in 29.3% of patients intraoperatively and 35.9% postoperatively. No statistically significant associations were found between postoperative BCVA, SE, or astigmatism and lens status, cataract type, iris integrity, or timing of IOL implantation (p > 0.05).

CONCLUSION: Cataract surgery secondary to blunt ocular trauma can result in significant visual improvement when appropriately managed; however, the risk of intraoperative and postoperative complications remains considerable. Therefore, individualized surgical planning is essential for optimizing outcomes in these patients.

PMID:42393286 | DOI:10.1007/s10792-026-04151-2