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Nevin Manimala Statistics

A Novel Demography-Based Approach to Define Patient-Specific Outflow Boundary Conditions in CT-Based FFR Computations

Ann Biomed Eng. 2026 Mar 3. doi: 10.1007/s10439-026-04002-2. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Computed tomography-based fractional flow reserve computation (CT-FFR) is widely used in clinical practice, based on its efficacy demonstrated in many studies. However, major assumptions remain with the outflow boundary conditions (BCs) representing coronary microvasculature, especially in hyperaemia. We here propose a novel method to estimate patient-specific microvascular response to hyperaemia for CT-FFR calculations, based on patients’ routinely available demographic data.

METHODS: A statistical model to predict microvascular flow response (MFR) from routinely collected patient demographic parameters was derived using PET-based perfusion data of 101 patients with coronary artery disease. CT-FFR computations were then conducted with patient-specific anatomical models and outflow BCs derived from various MFR models including the proposed approach. The FFR values were calculated for an independent test cohort of 10 patients who had undergone CT coronary angiography, CT perfusion imaging and invasive FFR measurement. Computed FFR values were compared against invasive FFR and other CT-FFR algorithms.

RESULTS: A multivariate regression model predicting patient-specific MFR was derived as a function of sex, diabetes and smoking status of the patient. FFR values computed using our model agreed well with the invasive FFR (0.76 ± 0.09 vs. 0.75 ± 0.10, P = 0.217). The FFRs predicted with our model were also comparable to those calculated using outflow BC tuned with patient-specific perfusion data (FFR: 0.74 ± 0.10, P = 0.233 vs. invasive FFR) and showed marked improvement over the conventional approach (FFR: 0.68 ± 0.11, P = 0.004 vs. invasive FFR). Diagnostic accuracy vs. invasive FFR were 100, 91 and 82% for CT-FFR with CTP-based MFR, demography-based MFR, and conventional approach, respectively.

DISCUSSION: The proposed demography-based MFR model significantly improves FFR computation accuracy compared with a typical conventional model that assumes constant, healthy and population average MFR. Although its diagnostic accuracy is slightly lower than that of CT-FFR calibrated with patient-specific perfusion imaging data (91 vs. 100%), the demography-based model offers a substantial practical advantage by not requiring additional non-standard data acquisition, such as perfusion imaging. Consequently, it shows strong potential as a practical enhancement to conventional CT-FFR algorithms.

PMID:41774380 | DOI:10.1007/s10439-026-04002-2

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Nevin Manimala Statistics

Improving In Silico Cardiac Safety Prediction by Consensus Averaging of Transmural Ventricular Cell Models

Ann Biomed Eng. 2026 Mar 3. doi: 10.1007/s10439-026-04028-6. Online ahead of print.

ABSTRACT

PURPOSE: Established in silico frameworks for assessing Torsade de Pointes (TdP) risk primarily rely on single-cell electrophysiological biomarkers, which have demonstrated strong predictive capabilities. However, ventricular transmural electrophysiological heterogeneity is known to influence repolarization dynamics and arrhythmogenic mechanisms. Explicitly incorporating endocardium, epicardium, and mid-myocardium representations may enhance physiological interpretability, but direct integration of multi-cell features can introduce severe multicollinearity and compromise model stability. To address this challenge, we propose an ordinal logistic regression (OLR) framework that integrates multi-cell qNet information through probability averaging, preserving physiological context while maintaining robust statistical behavior.

METHODS: I C 50 values and Hill coefficients for 28 CiPA drugs were implemented in two ventricular cell models, the CiPAORdV1.0 and the ORd in silico models. qNet was computed independently for endocardium, epicardium, and mid-myocardium cells. Cell-specific OLR models produced class probabilities that were then averaged to generate the final prediction. Performance was compared against single-cell and direct multi-cell implementations across Manual and ChanTest datasets.

RESULTS: For CiPA-ORd v1.0 using the ChanTest dataset, qNet achieved substantial performance, with AUCs for ROC1 and ROC2 of 1.000 and 0.958, respectively, and also meeting seven “excellent” classification criteria. In the ORd model, probability averaging consistently improved performance for both the Manual and ChanTest datasets relative to single-cell and direct multi-cell approaches.

CONCLUSION: Probability-averaged integration of multi-cell qNet predictions mitigates multicollinearity while preserving physiological relevance, yielding more stable and accurate in silico TdP risk classification and supporting broader applicability to preclinical safety assessment.

PMID:41774378 | DOI:10.1007/s10439-026-04028-6

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Nevin Manimala Statistics

Infective endocarditis treated surgically: correlation between imaging, and surgical findings

Int J Cardiovasc Imaging. 2026 Mar 3. doi: 10.1007/s10554-026-03676-y. Online ahead of print.

ABSTRACT

Echocardiography is crucial in the diagnosis of infectious endocarditis (IE). We assessed the correlation between transesophageal echocardiography (TEE) and surgical findings. A retrospective study of IE patients who underwent surgery. Discrepancies between TEE and surgical findings were defined as ≥ 1 infected valves, vegetations and abscess, and vegetations size ≥5 mm. Descriptive statistics and regression analysis were performed. Eighty patients were included. Mean age was 55.03 years, 26.3% had prosthetic valves. S. aureus and S. viridans spp were identified in 22.5% and 20% of cases, respectfully. On TEE, 84% had vegetations, and 31.2% had abscesses. Mitral and aortic valves were affected in 51%, and 40%, respectfully. TEE and surgical findings highly correlated regarding abscess count, valve involvement, and vegetation size. Significantly, more vegetations were observed during surgery compared to TEE (19% vs. 11%). In 46 patients (57.5%) (Group 1) no discrepancies were found. In 34 patients (42.5%) ≥ 1 discrepancy was found (Group 2). Patients in Group 1 vs. 2 presented with significantly more weakness (80.4% vs. 52.9%) and confusion (21.2% vs. 2.9%). Mitral valve involvement [21 (45.7%) and 24 (70.6%)], and larger vegetations on TEE (15.17 mm vs. 20 mm) were significantly more common in Group 2. S. viridans was linked to more discrepancies (p = 0.07). In a multivariate model Charlson index and vegetation size were associated with discordant findings. Discrepancies were observed between TEE and surgical findings, especially in patients with S. viridans IE or mitral valve involvement. These differences did not affect surgery appropriateness.

PMID:41774377 | DOI:10.1007/s10554-026-03676-y

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Nevin Manimala Statistics

Hyaluronan and Associated Biomarkers: A Longitudinal Cohort Study in Patients with Obesity Following Gastric Bypass Surgery

Obes Surg. 2026 Mar 3. doi: 10.1007/s11695-026-08564-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Roux-en-Y Gastric Bypass (RYGB) is a common treatment option for obesity. After RYGB, loss of both adipose tissue and lean body mass is seen. In this study, we have investigated the dynamic metabolic changes of hyaluronan (HA) and associated biomarkers reflecting the extracellular matrix after RYGB.

MATERIALS AND METHODS: In this exploratory cohort study, a total of 306 serum samples were collected at 5 different times from 96 RYGB patients, preoperatively until 6 months after surgery, where 44/96 (46%) contributed samples at 6 months. HA and the cell-surface receptor CD44 were studied by enzyme-linked immunosorbent assay (ELISA), while Luminex Multiplex assays were used for MMP-2, MMP-9, TNF-α, IL-1β, IL-6 and IL-10.

RESULTS: Preoperatively, an elevated HA-concentration (> 120 ng/ml) was seen in 39.6% of the study population. From baseline to day of surgery, we found a statistically significant decrease (p < 0.05) in HA (Δ-21.4ng/mL [-42.6, -0.27]), CD44 (Δ-26.7ng/mL [-46.4, -6.9]), MMP-2 (Δ-32.4 ng/mL [-41.4 -23.4]) and MMP-9 (Δ-138.2 ng/mL [-188.0, -88.4]), TNF-α(Δ-3.1 pg/mL [-5.4, -0.8]), IL-1β (Δ-14.4 pg/mL [-22.2, -6.6]) and IL-6 (Δ-2.0 pg/mL [-3.1, -0.9]). At one month postoperatively, a subsequent increase was seen. Although the mean concentration of HA was unchanged at 6 months, patients with baseline HA ≥ 120 ng/mL demonstrated a decrease, (Δ-37.1 [-55.8 to -14.7] p < 0.01; exploratory analysis) CONCLUSION: Although mean HA levels returned to baseline at 6 months, a significant transient decrease was observed immediately postoperatively, and patients with elevated preoperative HA (> 120ng/ml) showed a sustained reduction. The postoperative increase of MMP-2 suggests a continuous remodeling of the extracellular matrix.

PMID:41774373 | DOI:10.1007/s11695-026-08564-x

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Nevin Manimala Statistics

Evaluation of Clinical Outcomes and Graft Patency Following Venous Resection and Vascular Reconstruction Using a Recanalized Ligamentum Teres Hepatis Graft in Pancreaticoduodenectomy

Ann Surg Oncol. 2026 Mar 3. doi: 10.1245/s10434-026-19379-6. Online ahead of print.

ABSTRACT

PURPOSE: Our objective was to evaluate clinical outcomes and vascular graft patency following portal vein/superior mesenteric vein (PV/SMV) reconstruction using recanalized autologous ligamentum teres hepatis (LTH) grafts.

METHODS: This study enrolled 387 patients, stratified into three groups: (1) pancreaticoduodenectomy alone, (2) pancreaticoduodenectomy with vascular resection and reconstruction via end-to-end anastomoses or lateral venorrhaphy, and (3) pancreaticoduodenectomy with PV/SMV resection and reconstruction using autologous LTH grafts. This retrospective study compared operative time, intraoperative blood loss, postoperative complication rates, mortality, and length of postoperative hospital stay across these groups.

RESULTS: The study included 336 patients who underwent pancreaticoduodenectomy, 23 who underwent pancreaticoduodenectomy with vascular resection and reconstruction via end-to-end anastomosis or lateral venorrhaphy, and 28 who underwent pancreaticoduodenectomy with PV/SMV resection and reconstruction using autologous LTH grafts. The group using autologous LTH grafts exhibited an operative time of 484.86 ± 103.77 (285-685) min; intraoperative blood loss of 236.79 ± 141.95 (80-800) mL; a postoperative complication rate of 42.86%; 30-day mortality rate of 7.14%; and postoperative hospital stay of 20.82 ± 8.25 (9-49) days. Statistical analysis revealed a significantly longer operative time in the autologous LTH grafts group than in the other groups (p < 0.001), with no significant intergroup differences in blood loss, postoperative complication rates, mortality, or hospitalization. Partial thrombosis involving ≤50% of vessel diameter without obstruction was observed in four cases involving autologous LTH grafts. All reconstructed vessels maintained 100% patency throughout the follow-up period.

CONCLUSIONS: Using autologous LTH grafts for PV/SMV reconstruction during pancreaticoduodenectomy was safe and feasible, demonstrating favorable vascular graft patency rates and supporting its role as a viable alternative conduit for vascular restoration.

PMID:41774366 | DOI:10.1245/s10434-026-19379-6

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Nevin Manimala Statistics

An evaluation of flipped classroom-based anatomy teaching in medical students

Ir J Med Sci. 2026 Mar 3. doi: 10.1007/s11845-026-04284-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Anatomy education forms a cornerstone of medical curricula, integrating theoretical knowledge with practical understanding. The flipped classroom model, an innovative and interactive pedagogical strategy, has gained increasing attention for promoting active learning, engagement, and long-term knowledge retention. This study aimed to evaluate the impact of the flipped classroom model on learning performance, student engagement, and perceptions of digital learning tools in anatomy education.

METHODS: A total of 194 second- and third-year medical students participated during the 2024-2025 academic year (94 second-year and 100 third-year students). Flipped classroom sessions focused on the cerebral hemispheres (second year) and the pelvis and perineum (third year). Preparatory materials were provided via Moodle at least 15 days before the sessions. Student performance was assessed through a 20-question formative quiz graded out of 10 marks and related items in the final committee examination. Post-session perceptions were gathered using a 14-item Likert-scale questionnaire. Statistical analyses were performed using the Mann-Whitney U and Wilcoxon Signed-Rank tests.

RESULTS: Average quiz scores were 8.4 for second-year and 8.3 for third-year students, while committee exam accuracy was 78% and 70.06%, respectively. Over 75% of students reported that the flipped classroom enhanced their understanding and engagement. Significant differences were observed between year groups in enjoyment (p = 0.004) and perceived support for independent learning (p = 0.004). More than 70% agreed that digital anatomy resources improved comprehension and confidence.

CONCLUSION: The flipped classroom model enhances engagement, independent learning, and comprehension in anatomy education. This digitally supported, student-centred approach promotes deeper cognitive involvement and supports the integration of hybrid learning models into future curricula.

PMID:41774341 | DOI:10.1007/s11845-026-04284-4

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Nevin Manimala Statistics

Geoenvironmental evaluation of leachate and soil pollution potential of an open dumpsite

Environ Monit Assess. 2026 Mar 3;198(3):272. doi: 10.1007/s10661-026-15037-2.

ABSTRACT

This study assessed leachate and soil contamination at the Igbatoro dumpsite, Akure, Nigeria. Leachate samples were analyzed for heavy metals, BOD, and other physicochemical parameters. Soil samples were collected at depths of 0.5, 1.0, and 1.5 m to evaluate twenty-five (25) parameters, including pH, TDS, DO, COD, and heavy metals. Statistical analyses, including two-way ANOVA and correlation analysis, were performed. Leachate Pollution Index (LPI), revised LPI (r-LPI), Geo-accumulation Index (Igeo), Metal Pollution Index (MPI), Pollution Load Index (PLI), Degree of Contamination (Cdeg), and Potential Ecological Risk Factor (RI) were used to evaluate contamination levels of Igbatoro dumpsite. Results showed that Leachate pH ranged from 5.44 to 6.45 (mean 6.01), and metals like As and Cu exceeded the Federal Environmental Protection Agency (FEPA) limits. Strong negative correlations were observed between pH and most parameters, while temperature showed positive correlations with nitrate and Ni. An LPI of 13.65 and r-LPI of 40.39 exceeded pollution thresholds, indicating significant contamination. Soil analysis revealed elevated metal concentrations compared to the control, with Cd showing the highest Igeo value (-0.60). Location 6 recorded the highest MPI values for Cu and Cr, while most heavy metals fell within pollution classes, reflecting severe contamination. The potential ecological risk factor (RI) value of 174.70 indicates moderate ecological risk, with Cd posing a particularly high risk (Eir = 98.34). Overall, the study highlights considerable environmental and public health risks, underscoring the urgent need for remediation and adoption of sustainable waste management practices.

PMID:41774287 | DOI:10.1007/s10661-026-15037-2

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Therapeutic effects of Chelidonium majus on ocular surface ınflammation and tear film homeostasis in a benzalkonium chloride-ınduced rat model of dry eye disease

Int Ophthalmol. 2026 Mar 3;46(1):142. doi: 10.1007/s10792-026-04021-x.

ABSTRACT

PURPOSE: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and chronic inflammation. Natural compounds with anti-inflammatory activity have therefore attracted increasing interest. Chelidonium majus (C. majus) latex contains bioactive alkaloids with proven anti-inflammatory properties; however, its potential role in DED has not yet been investigated.

METHODS: Forty-six Wistar rats were randomized into six groups: Control, DED, Loteprednol etabonate (LE), and three C. majus latex dilutions (1/1, 1/10, 1/100). DED was induced by twice-daily instillation of 0.2% benzalkonium chloride (BAC) for 14 days. Following induction, LE or C. majus latex was administered according to group allocation; controls received vehicle. Tear volume (phenol red thread test), fluorescein corneal staining score (CSS), and Cochet-Bonnet esthesiometry were measured on days 0, 14, 21, and 28. On day 29, corneal tissues were analyzed by ELISA for TNF-α, IL-1β, IFN-γ, NF-κB, MMP-2, MMP-9, TIMP-2, AQP1, and AQP5, and underwent histopathological evaluation (H&E). Latex composition was characterized using LC-QTOF-MS. Statistical analysis included ANOVA with post hoc Tukey testing; p < 0.05 was considered significant.

RESULTS: At week 2, the DED groups demonstrated reduced tear volume (2.13 ± 0.83 mm) and increased corneal staining scores (CSS) (4.63 ± 1.06). By week 4, tear secretion improved in the LE (4.38 ± 0.52 mm) and in the C. majus 1/1 (4.56 ± 0.56 mm), 1/10 (4.88 ± 0.52 mm), and 1/100 (4.56 ± 0.50 mm) groups, approaching values observed in the control group. CSS decreased markedly in the C. majus 1/10 (0.38 ± 0.52) and LE (1.13 ± 0.83) groups, whereas the DED group remained elevated (2.38 ± 0.52). Corneal sensitivity improved in the LE and C. majus 1/1 (3.44 ± 0.42 mm), 1/10 (3.75 ± 0.27 mm), and 1/100 (3.50 ± 0.46 mm) groups. Inflammatory cytokines and MMP-2/9 levels decreased significantly across treatment groups, with the most pronounced reductions observed in the C. majus 1/10 group. Histopathological analysis revealed better preservation of stromal architecture and reduced inflammatory infiltration in treated groups compared with the DED group.

CONCLUSIONS: Chelidonium majus latex demonstrated significant anti-inflammatory and tissue-protective effects in this experimental model, supporting further investigation as a potential adjunctive approach in inflammatory DED.

PMID:41774285 | DOI:10.1007/s10792-026-04021-x

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Nevin Manimala Statistics

Modified clear cell likelihood score and a new CAT score in the assessment of indeterminate small renal masses

J Cancer Res Clin Oncol. 2026 Mar 3;152(3):56. doi: 10.1007/s00432-026-06424-w.

ABSTRACT

PURPOSE: In recent decades, small renal masses (SRMs) have become common incidental findings in cross-sectional studies; however, a widely implemented approach for the characterization of SRMs is still lacking. Thus, in this study, we aimed to explore the diagnostic performance of existing algorithms and to propose – as a conceptual framework rather than a clinically verified tool – a new simple radiological scale for estimating the probability of malignancy in SRMs.

METHODS: Patients with indeterminate solid SRMs (N = 50), discovered using magnetic resonance imaging (MRI) between 2012 and 2023 were included. In 38 cases, the final diagnosis was based on histopathology, while in 12 cases it relied on regression or lack of progression during follow-up. Modified versions of the clear cell likelihood score (ccLS) were calculated, and its diagnostic performance was assessed. Moreover, we analyzed the newly created score, which consisted of selected MRI and clinical features. All of our modified scales used a Likert score for the likelihood of clear cell renal cell carcinoma (ccRCC).

RESULTS: Based on the results of our statistical analyses, we modified the ccLS by adding T1 SI ratio < 0.73, arterial to delayed ratio (ADER) > 0.99, and smoking as independent predictors of ccRCC. We created a new scale, the CAT score, which combined hyperintensity in the Corticomedullary phase, ADER > 0.99, and TI SI ratio < 0.73 (with 1 point being assigned to each of the above-mentioned MRI parameters). In our results, the best diagnostic accuracy was observed for a CAT score ≥ 2, with a sensitivity of 73.9% (51.6-89.8%), a specificity of 77.8% (57.7-91.4%), and an accuracy of 76.0% (61.8-86.9%). Univariate logistic regression analyses demonstrated that all scales created by our group were significant predictors of ccRCC. Importantly, they showed a better predictive ability than the standard ccLS score.

CONCLUSIONS: The CAT score appears to improve the prediction of ccRCC compared with both standard and modified versions of the ccLS and may serve as a potential aid in the routine assessment of indeterminate SRMs. Nonetheless, this study should be regarded as a preliminary, proof-of-concept analysis rather than a definitive model-development study. The main limitation of our study is its small, single-center cohort, which limits the statistical power and robustness of model development. Moreover, a substantial proportion of benign diagnoses based only on radiological follow-up rather than histopathology. Therefore, before clinical implementation, the CAT score requires prospective validation in larger, independent, multicenter cohorts.

PMID:41774259 | DOI:10.1007/s00432-026-06424-w

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Synthetic accessibility score as a filter for virtual chemical structures in polymer materials design

J Mol Model. 2026 Mar 3;32(4):89. doi: 10.1007/s00894-026-06670-2.

ABSTRACT

CONTEXT: Computer-aided design of polymers with specific properties often encounters excessive computational demands due to the vast number of potential chemical structures. Reducing the number of candidates is critical for efficient virtual screening. A promising approach to overcome this challenge is the use of the synthetic accessibility score (SAscore), originally proposed by Ertl and Schüffenhauer (2009). It relies on decomposing chemical structures into molecular fragments and leveraging statistical analyses of fragment frequencies from large chemical databases. The initial implementation of the SAscore algorithm was not suitable for polymers. In this study, we demonstrate that our previously developed polymer-adapted approach can be used to filter polymer structures. We analyzed the impact of using fragments obtained by decomposing chemical compounds from different databases on SAscore calculation results. We showed that, in most cases, the differences fall within the error range. However, structures containing fragments with limited database presence may exhibit notable SAscore fluctuations across fragment sources.

METHOD: The Ertl and Schüffenhauer SAscore algorithm was adapted to account for the specific structural features of polymeric structures. We implemented our algorithm in a program that decomposes large databases of chemical structures into fragments and calculates their frequency of occurrence. The decomposition of polymers into fragments considers the ambiguity of the smallest repeating unit (SRU) specification and the possibility of specifying a polymer structure with multiple SRUs. This ensures identical calculated SAscore values for polymers specified in different ways. For SAscore calculations, we used PubChem Compounds (115 million records as of August 2023) and Aurora Fine Chemicals (116 million records) as sources of molecular fragments. The resulting database of molecular fragments is publicly accessible. A test database of virtually generated polymers with calculated SAscore values (MCKintech, 2.2 million records) is also freely available.

PMID:41774247 | DOI:10.1007/s00894-026-06670-2