Tag: nevin manimala

Histochem Cell Biol. 2026 Jan 30;164(1):7. doi: 10.1007/s00418-026-02457-x.

ABSTRACT

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a lipid-metabolizing enzyme implicated in ferroptosis regulation and tumor aggressiveness. Although ACSL4 overexpression has been reported in various malignancies, its immunohistochemical profile in primary cutaneous melanoma has not been fully characterized. This study aimed to evaluate ACSL4 expression in melanoma compared with normal skin using quantitative digital image analysis. A total of 80 formalin-fixed paraffin-embedded samples were analyzed, including 50 primary cutaneous melanoma specimens and 30 control skin samples obtained from benign dermatologic excisions. Hematoxylin-eosin staining was used to assess histopathologic features, and ACSL4 immunostaining was performed using a standardized protocol. Quantitative evaluation was conducted with QuPath software by calculating the percentage of positive cells, mean intensity scores (0-3), and H-scores (0-300) in epidermal and dermal compartments. Group comparisons were performed using the independent t test, with p < 0.05 considered statistically significant. Control tissues exhibited minimal ACSL4 expression (epidermal H-score 12; dermal H-score 9), whereas melanoma specimens demonstrated markedly increased ACSL4 immunoreactivity. Dermal atypical melanocytic tumor cells showed the highest expression levels (mean intensity 2.10 ± 0.35; H-score 168; p < 0.001), while epidermal layers also exhibited moderately elevated staining (H-score 58; p < 0.001). Histopathologic evaluation revealed characteristic features of invasive melanoma, including atypical melanocytic nests, pagetoid spread, cytologic atypia, and architectural disorder. Overall, ACSL4 expression was significantly upregulated in primary cutaneous melanoma compared with normal skin, particularly within dermal atypical melanocytic tumor cells, suggesting that ACSL4 may contribute to melanoma biology through lipid metabolic pathways and may represent a potential biomarker of tumor aggressiveness, warranting further investigation into its diagnostic and prognostic relevance.

PMID:41615507 | DOI:10.1007/s00418-026-02457-x

Breast Cancer Res Treat. 2026 Jan 30;215(3):67. doi: 10.1007/s10549-026-07897-6.

ABSTRACT

PURPOSE: The study aims to develop and validate a predictive tool for assessing the risk of in-breast tumor recurrence (IBTR) in breast cancer patients considered candidates for intraoperative radiotherapy using electrons (IOERT).

METHODS: This study included 3397 breast cancer patients treated with IOERT at a single institution between 2000 and 2016. The primary endpoint was IBTR, with or without nodal or distant metastasis. Fine and Gray regression models were used to identify predictors of IBTR. A nomogram predicting the 5- and 10-year probability of IBTR was developed based on the multivariable model and was validated both internally and externally using data from the IOERT arm of the ELIOT phase III trial (585 patients).

RESULTS: With a median follow-up of 6.1 years (interquartile range 4.3-8.0), 265 IBTRs (7.8%) were observed, resulting in an IBTR cumulative incidence of 4.4% (95% CI 3.7-5.2) at 5 years and 13.5% (95% CI 11.7-15.5) at 10 years. Multivariable analysis revealed that age under 60, certain histologic subtypes, positive axillary nodes, and intermediate/high tumor grade were key risk factors for IBTR. The overall Harrell’s concordance statistic was 0.69 (95% CI 0.66-0.73) in the internal and 0.64 (95% CI 0.57-0.71) in the external validation.

CONCLUSION: The nomogram has demonstrated moderate discriminative ability in predicting IBTR in the internal validation set and may be a useful tool to support treatment decision-making in breast cancer patients eligible for IOERT.

PMID:41615490 | DOI:10.1007/s10549-026-07897-6

Eur Radiol. 2026 Jan 30. doi: 10.1007/s00330-026-12349-2. Online ahead of print.

NO ABSTRACT

PMID:41615471 | DOI:10.1007/s00330-026-12349-2

Eur Radiol. 2026 Jan 30. doi: 10.1007/s00330-026-12334-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the safety and diagnostic performance of CT-guided core needle biopsy (CNB) of focal pulmonary lesions with coexisting interstitial lung abnormalities (ILAs).

MATERIALS AND METHODS: This retrospective 1:1 matched case-control study included patients with ILAs and controls who underwent CT-guided CNB of a focal pulmonary lesion from February 2010 to December 2023. Complications, nondiagnostic specimens, and CNB diagnostic performance for malignancy were compared. Logistic regression was used to identify predictors of complications and nondiagnostic specimens. Resected cases were reviewed for histopathological changes in the nonneoplastic lung.

RESULTS: Seventy-three patients with ILAs and matched controls were included (both groups: median age, 73.0 years; 13 women). No significant difference was found in complications (overall: 21/73 [29%] vs 24/73 [33%], p = 0.72; major: 2/73 [3%] vs 3/73 [4%], p = 1.00; minor: 19/73 [26%] vs 21/73 [29%], p = 0.85), nondiagnostic specimens (12/73 [16%] vs 9/73 [12%], p = 0.20), or diagnostic performance (accuracy: 89% [65/73] vs 96% [70/73], p = 0.11; sensitivity: 88% [61/69] vs 95% [62/65], p = 0.13; specificity: 100% [4/4] vs 100% [8/8], p = 1.00). Needle traversal of ILAs (OR, 7.04; 95% CI: 2.07-26.28; p = 0.008) and multiple pleural passes (OR, 8.06; 95% CI: 1.26-70.46; p = 0.03) were associated with complications. Nonneoplastic lung in ILAs revealed more complex histology and increased fibrotic features than controls.

CONCLUSION: CT-guided CNB of focal pulmonary lesions with coexisting ILAs was as safe and accurate as in patients without ILAs. However, traversing ILAs and multiple pleural passes increased complication risk.

KEY POINTS: Question Whether CT-guided CNB of focal pulmonary lesions with coexisting ILAs is as safe and accurate as in those without ILAs. Findings CNB in patients with ILAs showed similar safety and diagnostic performance to controls; however, complications were more frequent when ILAs were traversed or multiple pleural passes were performed. Clinical relevance CNB is a safe and effective diagnostic tool in patients with ILAs. Avoiding ILA traversal and multiple pleural passes may help minimize the risk of complications.

PMID:41615470 | DOI:10.1007/s00330-026-12334-9

Anaesthesiologie. 2026 Jan 30. doi: 10.1007/s00101-026-01648-4. Online ahead of print.

ABSTRACT

BACKGROUND: A regression model to estimate the duration from the onset of resuscitation efforts to the return of spontaneous circulation (ROSC) could help improving both resuscitation care and the quality control of registries. This study aims to evaluate the prediction accuracy and to identify challenges for future model development.

METHOD: Regression models based on M5P, random forest (RF) algorithms and a linear regression (LR) modified using M5P were retrospectively developed using a Belgian cohort of 84 individuals in whom ROSC was achieved. Model performance was assessed using quality metrics, such as the correlation coefficient (CC), coefficient of determination (R²), and root mean square error (RMSE) in a cross-validation approach.

RESULTS: In the cohort 61.9% were male with a mean age of 65.7 years. A shockable rhythm was present in 27.7% of cases and the bystander cardiopulmonary resuscitation (CPR) rate was 48.2%. The no-flow time averaged 5.13 min. The mean time from CPR onset to first defibrillation was 7.81 min and to first medication administration 11.31 min. The ROSC occurred after an average of 16.8 min, the LR showed the highest correlation (0.73, 95% confidence interval, CI 0.72-0.74) and R² (0.53 [0.52-0.55]) along with the lowest RMSE (6.76 min [6.63-6.90]). The M5P yielded similar not significantly different values (CC 0.72 [0.70-0.73], R² 0.52 [0.50-0.53], RMSE 6.84 min [6.69-6.99]). In contrast, RF performed significantly worse (CC 0.62 [0.61-0.63], R² 0.38 [0.37-0.40], RMSE 7.89 min [7.82-7.96], all p < 0.01). Only LR showed no significant difference between predicted and actual values in terms of mean (p = 0.75) and variance (p = 0.15). The proportion of potentially prematurely terminated resuscitation attempts, defined as cases with actual ROSC occurring later than predicted ROSC plus RMSE, ranged from 13% (M5P) to 18% (LR).

CONCLUSION: The duration from the start of CPR to ROSC appears to be a process that is suitable for modelling with machine learning algorithms. At this early stage of development, the individual regression models did not demonstrate sufficient validity possibly due to low sample size and simplified data structure; however, the findings indicated potential for an application as a quality assurance tool to compare actual vs. predicted time to ROSC. Therefore, to increase the robustness the results require further evaluation in a larger cohort with additional variables and improved data quality based on the Utstein criteria.

PMID:41615433 | DOI:10.1007/s00101-026-01648-4

J Gerontol A Biol Sci Med Sci. 2026 Jan 30:glag019. doi: 10.1093/gerona/glag019. Online ahead of print.

ABSTRACT

BACKGROUND: Visual impairment is a potential risk factor for depression and other outcomes in older adults. In population-based studies, vision can be measured using self-report or performance-based visual acuity, but epidemiologic associations often depend on which measure is used.

METHODS: In this Research Practice article, we illustrate the use of propensity scores to harmonize analyses of self-reported and performance-based vision in older adults. Using 2021 data from the National Health and Aging Trends Study (NHATS; n = 2,447), we measured associations between self-reported visual difficulty, distance visual impairment (logMAR >0.3), and depression. To harmonize self-reported and performance-based measures of vision, we modeled distance visual impairment as a function of self-reported vision and covariates and calculated exposure misclassification overlap weights. External validation was conducted using the Canadian Longitudinal Study on Aging (CLSA) and the Longitudinal Aging Study in India (LASI).

RESULTS: Self-reported visual difficulty was associated with depression (adjusted OR 2.32, 95% CI: 1.46-3.69), but distance visual impairment was not (OR 1.41, 95% CI: 0.99-2.01). After exposure misclassification overlap weighting, self-reported vision was no longer associated with depression, and results mirrored the association between distance visual impairment and depression (OR 1.49, 95% CI: 0.93-2.36). Similar findings were observed in CLSA and LASI.

CONCLUSIONS: Associations between vision and depression in older adults differ according to how vision is measured. In studies that measure self-reported vision but not visual acuity, propensity score methods that leverage known relationships between the two can be used to approximate associations between reduced visual acuity and health outcomes.

PMID:41615430 | DOI:10.1093/gerona/glag019

Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70323. doi: 10.1002/pds.70323.

ABSTRACT

PURPOSE: This nationwide cohort study examined the effects of discontinuation versus continuation of renin-angiotensin system inhibitors (RASis) on major renal and cardiovascular outcomes after the estimated glomerular filtration rate (eGFR) decreased to below 45 mL/min/1.73 m² in patients with type 2 diabetes and treated with RASis.

METHODS: Using linked Taiwanese databases with claims and clinical data, we identified patients with type 2 diabetes who used RASis during 2016-2020, and either discontinued or continued RASis within 180 days when their eGFR fell below 45 mL/min/1.73 m². The outcomes of interest included end-stage renal disease (ESRD), myocardial infarction, stroke, heart failure, and all-cause mortality. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for RASi discontinuation versus RASi continuation using on-treatment and intention-to-treat analyses and inverse probability weighting to adjust for baseline and time-varying covariates.

RESULTS: We identified 251 853 eligible patients, of whom 37 108 (15%) discontinued RASis and 214 745 (85%) continued RASis. The on-treatment HR associated with RASi discontinuation was 2.52 (95% CI, 2.33-2.73) for ESRD, 1.18 (1.08-1.30) for myocardial infarction, 1.28 (1.19-1.37) for stroke, 1.18 (1.13-1.24) for heart failure, and 1.77 (1.70-1.84) for all-cause mortality. Results from the intention-to-treat analysis were similar, albeit more conservative. Findings remained consistent across eGFR strata (≥ 30 to < 45 and < 30 mL/min/1.73 m²), urine albumin-creatinine ratio categories (≥ 300 and < 300 mg/g), and patient subgroups with various baseline characteristics.

CONCLUSION: Our results support continuing RASi treatment even when the eGFR declines to below 45 mL/min/1.73 m² based on potential renal, cardiovascular, and survival benefits.

PMID:41614370 | DOI:10.1002/pds.70323

Bioinformatics. 2026 Jan 30:btag044. doi: 10.1093/bioinformatics/btag044. Online ahead of print.

ABSTRACT

MOTIVATION: Phylogenetic trees describe the evolutionary history among biological species based on their genomic data. Maximum Likelihood (ML) based phylogenetic inference tools search for the tree and evolutionary model that best explain the observed genomic data. Given the independence of likelihood score calculations between different genomic sites, parallel computation is commonly deployed. This is followed by a parallel summation over the per-site scores to obtain the overall likelihood score of the tree. However, basic arithmetic operations on IEEE 754 floating-point numbers, such as addition and multiplication, inherently introduce rounding errors. Consequently, the order by which floating-point operations are executed affects the exact resulting likelihood value since these operations are not associative. Moreover, parallel reduction algorithms in numerical codes re-associate operations as a function of the core count and cluster network topology, inducing different round-off errors. These low-level deviations can cause heuristic searches to diverge and induce high-level result discrepancies (e.g., yield topologically distinct phylogenies). This effect has also been observed in multiple scientific fields beyond phylogenetics.

RESULTS: We observe that varying the degree of parallelism results in diverging phylogenetic tree searches (high level results) for over 31% out of 10 179 empirical datasets. More importantly, 8% of these diverging datasets yield trees that are statistically significantly worse than the best known ML tree for the dataset (AU-test, p<0.05). To alleviate this, we develop a variant of the widely used phylogenetic inference tool RAxML-NG, which does yield bit-reproducible results under varying core-counts, with a slowdown of only 0 to 12.7% (median 0.8%) on up to 768 cores. For this, we introduce the ReproRed reduction algorithm, which yields bit-identical results under varying core-counts, by maintaining a fixed operation order that is independent of the communication pattern. ReproRed is thus applicable to all associative reduction operations-in contrast to competitors, which are confined to summation. Our ReproRed reduction algorithm only exchanges the theoretical minimum number of messages, overlaps communication with computation, and utilizes fast base-cases for local reductions. ReproRed is able to all-reduce (via a subsequent broadcast) 4.1×106 operands across 48 to 768 cores in 19.7 to 48.61 μs, thereby exhibiting a slowdown of 13 to 93% over a non-reproducible all-reduce algorithm. ReproRed outperforms the state-of-the-art reproducible all-reduction algorithm ReproBLAS (offers summation only) beyond 10 000 elements per core. In summary, we re-assess non-reproducibility in parallel phylogenetic inference, present the first bit-reproducible parallel phylogenetic inference tool, as well as introduce a general algorithm and open-source code for conducting reproducible associative parallel reduction operations.

AVAILABILITY AND IMPLEMENTATION: ReproRed: https://doi.org/10.5281/zenodo.15004918 (LGPL)-Reproducible RAxML-NG version https://doi.org/10.5281/zenodo.15017407 (GPL).

SUPPLEMENTARY INFORMATION: https://doi.org/10.5281/zenodo.15524754.

FUNDING: This project received funding from the Klaus Tschira Foundation, the European Union via European Research Council (ERC) Horizon 2020 research and innovation grant No. 882500, and via the EU ERA Chair (HORIZON-WIDERA-2022-TALENTS-01: 2023-2028) program grant No. 101087081 (Comp-Biodiv-GR). The authors gratefully acknowledge the Gauss Centre for Supercomputing e. V. (www.gauss-centre.eu) for funding this project by providing computing time on the GCS Supercomputer SuperMUC-NG at Leibniz Supercomputing Centre (www.lrz.de).

PMID:41614360 | DOI:10.1093/bioinformatics/btag044

Indian J Dent Res. 2026 Jan 29. doi: 10.4103/ijdr.ijdr_138_25. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate and compare chairside clinical time and acceptance of prefabricated and conventional band and loop space maintainers in children with premature loss of primary molars.

METHODS: Sixty children aged 4-8 years with premature loss of primary first or second molars requiring a space maintainer were randomized into two groups: group 1, conventional band and loop space maintainer (CBLSM), and group 2, prefabricated band and loop space maintainer (PBLSM). The clinical evaluation for patient acceptance was carried out at six months follow-up using a five-point Likert scale. Patient comfort during clinical procedure, chairside clinical time, space loss, gingival index and plaque index were also recorded and compared between the two groups.

RESULTS: After six months, both space maintainers were well accepted by the children, showing no statistically significant difference between the groups (P > 0.05). In group 1, 40% of children, and in group 2, 46.6% of them showed mild discomfort measured using the Sound, Eye, Motor (SEM) scale, while the others were comfortable during the clinical procedure. The mean chairside clinical time required was 14.12 ± 3.90 and 19.96 ± 5.55 min for group 1 and group 2, respectively, and there was a statistically significant difference between the two groups (P < 0.001). The plaque index, the gingival index and space loss after six months had no statistically significant differences between groups.

CONCLUSION: The CBLSM and PBLSM were comparable in terms of patient acceptance, comfort during clinical procedure and space loss after six months. However, the mean chairside clinical time required was significantly higher in PBLSM group.

PMID:41614351 | DOI:10.4103/ijdr.ijdr_138_25

Otolaryngol Head Neck Surg. 2026 Jan 30. doi: 10.1002/ohn.70132. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the diagnostic utility of asymmetrical tonsils in detecting tonsillar malignancy.

DATA SOURCES: PubMed, Embase, Scopus, and Cochrane Library; from inception until December 17, 2024.

REVIEW METHODS: We included observational studies of adult/pediatric patients undergoing excisional tonsillectomy or incisional tonsillar biopsy that reported at least one diagnostic accuracy outcome for tonsillar asymmetry in predicting malignancy. We pooled estimates using frequentist univariate random-effects generalized linear mixed models, examined and adjusted for publication bias via visual inspection, Egger’s test, and trim-and-fill, performed influence and cumulative meta-analyses, and used a Bayesian bivariate model as a sensitivity analysis. Outcome measures included the following: sensitivity, specificity, positive/negative likelihood ratio (LR+/LR-), and positive/negative predictive value (NPV/PPV) with 95% confidence interval (95% CI).

RESULTS: Twenty-nine studies (5178 participants) from 422 records were included. The risk of bias was low-moderate. The sensitivity and specificity of tonsillar asymmetry as a diagnostic marker for malignancy were 77.2% (95% CI: 68.6%-84.0%) and 96.4% (95% CI: 91.6%-98.6%), respectively. The LR- was 0.24 (0.17-0.34) and LR+ was 21.44 (8.05-57.0). The NPV and PPV were 99.8% (95% CI: 99.1%-99.9%) and 4.31% (95% CI: 1.83%-9.80%), without considering clinical risks. With concomitant high-risk clinical features such as lymphadenopathy, the PPV (probability of malignancy given asymmetrical tonsils) was 38.5% (30.3%-47.4%). Without other high-risk features, the PPV was 0.16% (0.15%-0.18%). The overall quality of evidence was high.

CONCLUSION: Tonsillar asymmetry has a high specificity and moderate sensitivity for tonsillar malignancy. Due to the low prevalence of malignancy, the probability of malignancy is less than 1% if no other suspicious clinical features are present.

PMID:41614350 | DOI:10.1002/ohn.70132