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Nevin Manimala Statistics

Non-Coding Regulatory Variants in Autoimmune Disease: Biological Mechanisms, Immune Context, and Integrative Multi-Omics Interpretation

Biology (Basel). 2026 Feb 28;15(5):407. doi: 10.3390/biology15050407.

ABSTRACT

Autoimmune diseases arise from complex interactions between genetic susceptibility, immune regulation, and tissue-specific inflammatory processes, yet most risk variants identified by genome-wide association studies occur in non-coding regions with poorly defined biological functions. This review addresses the challenge of interpreting non-coding regulatory variants in autoimmunity by synthesizing emerging analytical frameworks that integrate functional genomics, single-cell profiling, spatial transcriptomics, and multi-omics data. We describe stepwise strategies that refine statistical associations through regulatory annotation, immune cell-state resolution, and perturbational evidence, highlighting complementary approaches such as massively parallel reporter assays, transcriptome-wide association studies, and single-cell expression quantitative trait locus mapping. These methods demonstrate that many autoimmune risk variants exert context-dependent effects that emerge only in specific immune cell states, activation trajectories, or tissue microenvironments. Advances in spatial and chromatin-informed technologies further clarify how regulatory variation shapes immune circuits in diseases such as systemic lupus erythematosus and rheumatoid arthritis. Finally, we discuss how machine learning-enabled multi-omics integration supports molecular endotyping and therapeutic inference while emphasizing interpretability and reproducibility. Collectively, this review highlights a shift from static variant annotation toward dynamic, context-aware analytical frameworks that enable mechanism-informed interpretation of genetic risk in autoimmune disease.

PMID:41823835 | DOI:10.3390/biology15050407

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Nevin Manimala Statistics

Spatio-Temporal Variability Description of the Rare Species Lilium martagon L. in Different Habitat Conditions

Biology (Basel). 2026 Feb 28;15(5):398. doi: 10.3390/biology15050398.

ABSTRACT

Martagon Lily, Lilium martagon, belongs to geophytes inhabiting mainly forest communities in temperate regions of Europe and Asia and it is considered as a rare and endangered species in many regions. The presented investigations were conducted in three populations, occurring in forest habitats in Southern Poland: Wolski Forest (population 1), Mount Chełm (population 2), and Hrabeński Forest (population 3). At each site, 10 phytosociological relevés covering an area of 100 m2 were taken. For each phytosociological relevé, the Shannon-Wiener, Pielou, and Simpson indices, as well as the number of species, were calculated. The detailed field studies were conducted in permanent study patches measuring 20 m × 20 m. The measurements of habitat conditions (e.g., number of species, soil moisture, light intensity at ground level, height of plant cover) were carried out in 2018. The observations of the abundance and developmental structure of stems, as well as selected traits (e.g., height, number and dimensions of leaves, number of flowers) were conducted in 2018-2023. The analysis of phytosociological relevés showed that the study sites in Wolski Forest and Mount Chełm were located in the Tilio cordatae-Carpinetum betuli oak-hornbeam forest association, while the study site in Hrabeński Forest was situated in the Dentario glandulosae-Fagetum mountain beech forest association. The statistical analysis confirmed that the greatest Shannon and Simpson index values, number of species, soil humidity, light intensity at ground level, and height of plant cover were recorded in Hrabeński forest. The greatest number of Lilium martagon stems and a lack of juvenile stems was found in population 3, while in less abundant populations-1 and 2-juvenile, immature, virginile, and generative stems were found. The statistical analysis showed that the highest immature and virginile stems with the greatest number of whorl leaves, as well as the substantial height of generative stems and number of whorl leaves observed in population 3, might be the result of growing in conditions of lateral shading provided by adjacent plants. The lowest height of immature and virginile stems recorded in population 1 and generative stems noticed in population 2 might be caused by them being overshaded by the canopy of surrounding trees. Moreover, the obtained results suggest the favourable impact of weather conditions during the meteorological spring and summer of 2019 on the growth of Lilium martagon stems. Nevertheless, the lack of a unified trend in the studied populations indicates the occurrence of site-specific temporal variability of individual traits. Considering the obtained results, it can be concluded that population 3 presents a much better state and prospects for persistence in the occupied site than populations 1 and 2. At the same time, it should be pointed out that further long-term observations of populations of Lilium martagon located in different habitat conditions are still strongly desired.

PMID:41823826 | DOI:10.3390/biology15050398

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Nevin Manimala Statistics

Effective Community Consultation for Prehospital EFIC Research: Lessons from a 20-Site Pediatric Trial

Prehosp Emerg Care. 2026 Mar 13:1-18. doi: 10.1080/10903127.2026.2639473. Online ahead of print.

ABSTRACT

OBJECTIVES: Research in the prehospital setting is frequently conducted with federal Exception from Informed Consent (EFIC). An EFIC requires community consultation (CC) and public disclosure (PD) to inform community members about research plans and create opportunities for community feedback and study modification prior to approval. There is limited research on the relative effectiveness of varying CC and PD strategies, particularly with increasing utilization of social media. We sought to characterize the frequency of use and reach of specific CC/PD strategies in the Pediatric Dose Optimization for Seizure in EMS (PediDOSE) trial, assess their relative effectiveness, and offer guidance to future EFIC studies on optimal strategies and potential pitfalls in conducting CC/PD.

METHODS: We completed a retrospective review of the CC/PD plans and summary reports from all 20 sites in the PediDOSE trial. We used descriptive statistics to determine the frequency and reported reach of specific CC/PD strategies. We also described sites’ modifications of their initial CC/PD plans.

RESULTS: All sites completed the required CC/PD activities, which began in October 2021. Sites conducted 52 CC meetings; meeting with community groups had the lowest attendance (median 9, IQR 2-11) and were the most frequently cancelled. Most sites (16/20) utilized social media for CC/PD; however, only 4 sites use paid social media advertisements. Paid advertising had greater reach on Facebook than posts to existing institutional followers (median reach 13992 paid vs 2504 free) at reasonable cost. All sites created PD materials and conducted CC surveys in Spanish; a majority of sites (11/20) reported actively recruiting minoritized populations for inclusion in CC/PD activities with variable success.

CONCLUSIONS: Based on our experience we recommend the following: EFIC studies should utilized paid social media for PD. Studies should establish standardized metrics for success of social media campaigns before beginning CC/PD activities. community meetings for CC should be conducted with inclusion of all relevant stakeholder groups, and sites should consider using social media to augment CC activities. Investigators of EFIC studies involving children should develop explicit plans to engage children and minoritized populations in CC/PD.

PMID:41823798 | DOI:10.1080/10903127.2026.2639473

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Nevin Manimala Statistics

The Transition from Strain Softening to Strain Hardening in Metallic Glasses

Nanomaterials (Basel). 2026 Mar 3;16(5):319. doi: 10.3390/nano16050319.

ABSTRACT

Despite their excellent mechanical properties, metallic glasses (MGs) are significantly hindered by poor plasticity and toughness, which are essential for structural applications. The brittleness arises from the rapid propagation of shear bands (SBs), leading to strain softening and catastrophic failure. Recent advancements in microstructural engineering, particularly boundary engineering, such as nano-glass, focus on the utilization of heterogeneous structures to promote the proliferation and delocalization of SBs. Various attempts have been made experimentally to address these issues, but with very limited improvement in tensile strength and toughness. Under tensile loading, micro- or nano-pillar samples exhibit strain softening and continue to undergo plastic deformation after reaching yield or peak stress, especially the nano-glass micro-pillar. Reports on tensile strain-hardening in MG micro-pillars are rare. In this finite element simulation study, we optimize appropriate statistical and spatial distributions of free volume within the microsamples. Both the post-yield strength and the mean tangent modulus increase with progressive gradient structural modifications, thereby inducing a transition from strain-softening to strain-hardening behavior, as well as a concurrent transition from plastic fracture to brittle fracture. We systematically investigate the deformation mechanisms and transition mechanisms of fracture modes, which are closely associated with heterogeneous microstructures and their evolution in MGs. These insights into the transition mechanism could significantly facilitate the design and optimization of MGs to achieve enhanced toughness and strain hardening.

PMID:41823771 | DOI:10.3390/nano16050319

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Nevin Manimala Statistics

Efficacy of Low-dose Aspirin in Preventing Hypertensive Disorders of Pregnancy in Women with Systemic Lupus Erythematosus: A Single-Center Retrospective Cohort Study

Mod Rheumatol. 2026 Mar 13:roag028. doi: 10.1093/mr/roag028. Online ahead of print.

ABSTRACT

OBJECTIVES: Low-dose aspirin (LDA) is widely recommended to prevent hypertensive disorders of pregnancy (HDP). However, the evidence of its effectiveness in pregnancies with systemic lupus erythematosus (SLE) remains limited. This study evaluated the efficacy of LDA in preventing HDP in women with SLE.

METHODS: We conducted a retrospective cohort study of 124 pregnancies with SLE managed at our hospital. Pregnancy outcomes were compared between women treated with LDA and those not treated, using propensity score and inverse probability weighting analyses to adjust for confounders.

RESULTS: LDA was used in 65 pregnancies and not used in 59. HDP occurred in 7/65 (10.8%) and 8/59 (13.6%), respectively. After adjusting for potential confounders, including antiphospholipid antibodies, lupus nephritis, chronic hypertension, chronic kidney disease, history of HDP, and hydroxychloroquine use, the risk ratio for HDP with LDA was 0.76 (95% confidence interval: 0.25-2.33; p=0.64). Sensitivity analysis was consistent.

CONCLUSIONS: LDA did not significantly reduce the incidence of HDP in women with SLE. This lack of effect may reflect the low event rate in a well-controlled cohort. These findings underscore the need for individualized risk assessment and careful monitoring, beyond reliance on LDA alone, in the management of pregnancies with SLE.

PMID:41823715 | DOI:10.1093/mr/roag028

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Nevin Manimala Statistics

Scientists built the hardest AI test ever and the results are surprising

As AI systems began acing traditional tests, researchers realized those benchmarks were no longer tough enough. In response, nearly 1,000 experts created Humanity’s Last Exam, a massive 2,500-question challenge covering highly specialized topics across many fields. The exam was engineered so that any question solvable by current AI models was removed. Early results show even the most advanced systems still struggle — revealing a surprisingly large gap between AI performance and true expert-level knowledge.
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Nevin Manimala Statistics

Process hygiene criteria for Salmonella in pig carcasses: comparing food business operator self-monitoring and official sampling in an Italian high-throughput slaughterhouse

Ital J Food Saf. 2026 Mar 12. doi: 10.4081/ijfs.2026.14646. Online ahead of print.

ABSTRACT

This study compares Salmonella monitoring data obtained from food business operator (FBO) self-monitoring and competent authority (CA) official sampling on pig carcasses in a high-throughput Italian slaughterhouse over ten years (2012-2021 for FBO; 2014-2021 for CA). A total of 1560 FBO and 377 CA samples were analyzed. Salmonella prevalence was 3.46% [95% confidence interval (CI): 2.6-4.5] for FBO and 10.34% (95% CI: 7.3-13.5) for CA, with statistically significant yearly differences in 2015, 2017, 2018, and 2020 (p<0.05). Derby was the predominant serovar (22.6%); however, 20.4% of the FBO isolates were classified only as ‘No Typhimurium and Enteritidis’, highlighting gaps in serotyping protocols. Discrepancies likely reflect differences in sampling frequencies, carcass origins, and the use of different accredited laboratories by FBO and CA (private and official ones, respectively). The study identifies regulatory ambiguities, including a mistranslation in the Italian Ministerial Note, and recommends enhanced farm-level controls and harmonized surveillance.

PMID:41823068 | DOI:10.4081/ijfs.2026.14646

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Nevin Manimala Statistics

Efficient design of partially nested randomized trials: A maximin approach

Stat Methods Med Res. 2026 Mar 13:9622802251409388. doi: 10.1177/09622802251409388. Online ahead of print.

ABSTRACT

For two-treatment randomized trials with clustering in one of the treatment arms and a continuous outcome, designs are presented that minimize the number of subjects or the amount of research budget, when aiming for a desired power level. These designs optimize the treatment-to-control allocation ratio of study participants but also optimize the choice between the number of clusters (such as therapy groups) versus the number of persons per cluster (therapy group) in the arm with clustering. Optimal designs require prior knowledge of parameters from the analysis model, which are unknown during the design stage. We present maximin designs which address this by ensuring a pre-specified power level for plausible ranges of the unknown parameters, while maximizing the power for worst-case values of these parameters. Maximin designs are also derived when the number of clusters, or the cluster size is fixed due to practical constraints. An empirical example illustrates how to calculate sample sizes for such practical designs and shows how much these maximin designs can reduce the required research budgets compared to designs with equal subject numbers in treatment and control. A user-friendly R Shiny app facilitates these sample size calculations.

PMID:41823059 | DOI:10.1177/09622802251409388

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Nevin Manimala Statistics

Comparative Investigation of Seasonal (Summer and Winter) and Sex-Related Differences in Tear Production and Intraocular Pressure in Sakız, Çine Çaparı, and Karya Sheep

Vet Ophthalmol. 2026 Mar;29(2):e70159. doi: 10.1111/vop.70159.

ABSTRACT

OBJECTIVE: This study investigated the seasonal (summer and winter) and sex-related variations in intraocular pressure (IOP) and tear production among Sakız, Çine Çaparı, and Karya sheep reared under similar environmental conditions in the same region.

MATERIALS AND METHODS: A total of 180 healthy sheep (30 males and 30 females per breed; Sakız, Çine Çaparı, Karya), ~2 years old, were examined. Schirmer tear test (STT-I) and IOP were measured in June (summer; 30°C) and January (winter; 10°C). Data were analyzed using IBM SPSS Statistics 22 with parametric or non-parametric tests.

RESULTS: STT-I values were higher in summer across all breeds (p < 0.05). Across breeds, Sakız consistently showed greater STT-I than Çine Çaparı and Karya in both summer and winter. Within-breed seasonal shifts were pronounced for STT-I but small for IOP. Sex effects were generally absent, except in Sakız during winter, where females had higher STT-I (17.64 ± 3.98 vs. 15.61 ± 3.51 mm/min) and IOP (18.78 ± 4.03 vs. 16.87 ± 2.74 mmHg) than males (p < 0.05). IOP remained stable in most breeds and seasons, and significant differences were confined to specific subgroups, including winter increases in Sakız and Karya females, with interbreed IOP variations limited to particular cases such as higher summer values in Karya males.

CONCLUSION: Seasonal variation significantly affects tear production, whereas intraocular pressure remains largely stable, with minor sex-related differences observed in some breeds.

PMID:41823045 | DOI:10.1111/vop.70159

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Nevin Manimala Statistics

Nano-Enabled Herbal Therapeutics for Diabetic Foot Ulcers: Translating Ethnopharmacological Bioactives into Advanced Wound Care

Chem Biodivers. 2026 Mar;23(3):e03644. doi: 10.1002/cbdv.202503644.

ABSTRACT

Diabetic foot ulcer (DFU) is a common and serious complication in individuals with diabetes, representing a leading cause of hospitalization and frequently resulting in severe outcomes such as amputations, increased morbidity, and mortality. The development of diabetic foot infection (DFI) is typically attributed to a combination of factors, including persistent hyperglycemia, impaired immune function, peripheral neuropathy, and vascular insufficiency. Early diagnosis and prompt treatment are crucial for favorable outcomes; however, the growing prevalence of antibiotic-resistant pathogens presents a significant challenge, placing additional strain on healthcare systems. Considering these concerns, there is an increasing interest in herbal therapies with antimicrobial, anti-inflammatory, and wound-healing properties-such as garlic (Allium sativum), turmeric (Curcuma longa), and neem (Azadirachta indica)-as potential adjunct or alternative treatments. This review explores key aspects of DFI, including its pathophysiology, global prevalence, statistical data, risk factors, diagnostic approaches, current and potential herbal treatments, associated challenges, and future directions.

PMID:41823036 | DOI:10.1002/cbdv.202503644