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Physiologically based ferritin thresholds to redefine early pregnancy iron screening: a cross-sectional study

Abstract Iron deficiency in early pregnancy is common yet frequently missed because current screening strategies rely on ferritin cutoffs designed to detect iron deficiency anemia. We aimed to establish physiologically based ferritin functional reference limits (FRLs) in healthy, non-anemic pregnant women, specifically to model early iron insufficiency prior to the onset of anemia, where screening strategies are most clinically actionable. The study was conducted at a maternity hospital in Ho Chi Minh City, Vietnam, enrolling first-trimester pregnant women. Participants were included if they had hemoglobin ≥ 11 g/dL, no evidence of infection, body-mass index (BMI) < 30 kg/m², and no confirmed hemoglobinopathies or unexplained microcytosis/hypochromia. The primary outcome was the ferritin FRLs, defined using restricted cubic spline modelling of standalone erythrocyte indices (MCV, MCH, HGB, and RDW). Diagnostic performance was assessed against TSAT. A total of 452 participants had complete data for validation. The final suggested ferritin FRL is 59 ng/mL, which identified more women with non-anemic iron deficiency compared with traditional cutoffs. Validation against TSAT showed excellent rule-out performance with a negative predictive value of 95.8%. A four-zone classification for iron deficiency emerged, including absolute deficiency (< 15 ng/mL), early-stage deficiency (15–26 ng/mL), transitional state (26–59 ng/mL), and physiologic sufficiency (≥ 59 ng/mL). Physiologically derived ferritin thresholds identify early iron deficiency more effectively than conventional cutoffs and provide a grounded framework for screening in the first trimester.

FGFR1–ETV1–CXCL1 signaling in dermal fibroblast orchestrates fibroblast-associated itch

Fibroblasts are a heterogeneous group of mesenchymal cells essential for tissue homeostasis maintenance and pathological responses. However, the mechanistic contributions of fibroblast plasticity to somatosensory dysfunction, particularly pathological pruritus, remain poorly characterized. Here, we developed fibroblast-associated itch models via acute incision and chronic bleomycin treatment. In Pdgfra CreER mice, chemogenetic activation of dermal fibroblasts using Gq-coupled designer receptors activated by designer drugs (DREADDs) evokes scratching behaviors, whereas inhibition with Gi-coupled DREADDs suppresses fibroblast-associated itch. Integrated in vitro and in vivo experimental evidence establishes a previously unrecognized pruritogenic signaling axis centered on fibroblast growth factor receptor 1 (FGFR1), transcription factor ETS variant 1 (ETV1), and chemokine ligand 1 (CXCL1) in fibroblast-associated itch. Moreover, ETV1 nuclear translocation during dermal fibroblast activation is coordinated by the enzyme poly-ADP-ribose polymerase 1. Finally, conditional knockout of ETV1 in Pdgfra CreER ;ETV1 flox mice verify the essential role of the signaling in fibroblast-associated itch. Collectively, FGFR1–ETV1–CXCL1 axis in dermal fibroblasts functions as a pivotal itch signaling, establishing a conceptual framework that links fibroblast dynamics to somatosensory disorders.

Vision-Language Models for automated quality control: a benchmarking framework and comprehensive study

Molecular de-extinction looks to the past to find the molecules of the future

Retraction: HGLER: A hierarchical heterogeneous graph networks for enhanced multimodal emotion recognition in conversations

Young adults with PIMD Polyhandicap in pediatric settings a situation more complex than problematic

Correction to Supporting Information for Liu et al., Efficient quantum algorithm for dissipative nonlinear differential equations

Cohort profile: Mothers who use substances and their children in British Columbia, Canada

Introduction Perinatal substance use is a growing public health challenge in the province of BC. A population-based cohort was established using linked health administrative data to underpin three research studies that will evaluate: 1) the effectiveness of specialized acute care for pregnant people who use substances; 2) the comparative effectiveness of different medication regimens for the treatment of perinatal opioid use disorder (OUD); and 3) the longitudinal association between maternal substance use and child health outcomes. Methods The population-based cohort includes all individuals in British Columbia (BC), Canada, who delivered an infant from April 1, 2000–March 31, 2022, and who had an indication of substance use in their health administrative records between one year prior to the first pregnancy-related healthcare contact and time of delivery. Individual-level data for mothers and children were linked across ten population-level databases, which include information on demographics, healthcare utilization, drug dispensations, incarceration in provincial prisons, maternal and newborn health outcomes, receipt of housing and income assistance, and deaths and underlying causes. Results We identified 38,670 mothers with substance use disorders and their children (n = 45,823), with a median of 9 (interquartile range: 5–15) years of follow-up available. At the time of delivery, mothers ranged from <19–45 years of age. High levels of morbidity and mortality were documented among both mothers and their children. Discussion The growing population of mothers with substance use disorder represent a critical need for the province of British Columbia. This population-based retrospective cohort will be used to inform service design and otherwise advocate for client needs.

Self-defending 6G networks through AI-driven adaptive decoy generation at the edge

TGFb signaling instructs a conserved fibrosis-associated cell state marked by LRRC15

Fibroblasts are key potentiators of chronic disease pathophysiology. Despite their established roles in promoting pathological inflammation and tissue remodeling, activated myofibroblasts are generally characterized as a single, homogeneous cell population, obscuring critical functional distinctions. Defining the cell states, their molecular regulators, and restricted markers is critical to developing effective therapies for the treatment of fibrosis. Here, using a human lung stromal cell atlas of idiopathic pulmonary fibrosis, we identify two myofibroblast transcriptional states associated with distinct predicted biological function, regulation, and cell surface marker expression. We identify fibroblast-specific TGFb signaling as the key regulator of the mechanistic switch from a wound healing–associated and proliferative to a profibrotic myofibroblast. Further, we elucidate conserved TGFb-dependent and suppressed gene expression programs that define these states. Our findings reveal that LRRC15 is highly restricted to myofibroblasts that primarily express an extracellular matrix-remodeling gene program and illuminate that this key cell state can differentiate in the absence of an obligate inflammatory precursor intermediate. Last, we apply machine learning using a human single-cell foundation model to demonstrate broad applicability of the biology described herein to human chronic disease.

Prevalence and severity of anxiety, depression, and stress among optometry students in Nigeria: A cross-sectional study

Purpose To assess the prevalence and severity of anxiety, depression, and stress among optometry students in Nigeria, and to identify demographic factors associated with mental distress. Methods A cross-sectional, web-based survey was administered to optometry students from 10 Nigerian universities between 16 April and 18 November 2024, with an estimated sample size of 427. Mental health status was evaluated using the Depression, Anxiety, and Stress Scale-21 items (DASS-21). Collected data included age, gender, year of study, marital status, and DASS-21 scores. Descriptive statistics summarized demographic characteristics and the prevalence of symptoms. Binary logistic regression was used to identify associations between demographic variables and mental health outcomes, with significance set at p < 0.05. Results A total of 474 students participated (mean age: 23 ± 3 years; 54.6% female; 94.1% unmarried). Overall, 51.1% experienced depressive symptoms, with 14.6% reporting severe or extremely severe symptoms. Severe anxiety was reported by 36.5%, and 25.1% experienced concurrent symptoms of anxiety, depression, and stress. Nearly half (49.2%) had at least two coexisting mental health conditions, indicating a significant emotional burden and potential impact on academic performance. Female students had significantly higher odds of experiencing depression (OR: 1.66; 95% CI:1.15–2.39) and overall mental distress (OR: 1.58; 95% CI: 1.03–2.43) compared to males. Conclusion This study revealed a high prevalence of mental health conditions among Nigerian optometry students, with one in four experiencing a comorbid of all three conditions. Female students were more likely to report adverse mental health outcomes. These findings underscore the urgent need for structured mental health support and preventive interventions within optometry training programs in Nigeria.

Coastal land uplift and intensified land-use influence seagrass carbon and nitrogen sink capacity over millennial timescales

Abstract Seagrass meadows store sedimentary carbon and nitrogen and thus play an important role in climate change mitigation and nutrient retention globally. Here we reconstruct the impact of land-use and coastal land uplift on millennial–scale seagrass ( Zostera marina ) blue carbon and nitrogen accumulation in the Baltic Sea based on a multiproxy paleoreconstruction approach. We show that increased landscape clearance resulted in higher terrestrial runoff and increased accumulation of carbon and nitrogen, whereas land uplift led to hydrodynamically sheltered environments facilitating seagrass colonization, occurring 1700 and > 4000 years ago. The establishment of the seagrass meadows resulted in enhancement of the quality of carbon and nitrogen stocks with increased lignin contents. Seagrass establishment also likely supported export of organic matter to surrounding unvegetated areas and thereby contributed to carbon and nitrogen accumulation beyond habitat boundaries. The findings show that the long-term carbon and nitrogen accumulation rates and permanence are shaped by land cultivation and geomorphological changes and highlights the importance of seagrass conservation for maintaining thousands of years of sedimentary carbon and nitrogen storage.

NRF2 activation by myeloid cell–derived oxidative stress induces SNAI-driven features of EMT in breast cancer

Metastasis is facilitated by epithelial-to-mesenchymal transition (EMT), a process in which epithelial cancer cells, including breast cancer cells, acquire mesenchymal-like phenotypes. Production of reactive oxygen species (ROS) by NADPH oxidase 2 (NOX2) is a principal inflammatory and antimicrobial feature of myeloid cells. Inflammation has been linked to EMT, but the role of ROS released from tumor-infiltrating myeloid cells in EMT is unknown. In coculture experiments with human or murine myeloid cells and breast cancer cells, we observed that NOX2-derived ROS induced EMT-like changes in MCF-7, T-47D, 4T1, and EO771 cells via activation of SNAI transcription factors, mediated by the ROS-sensitive transcription factor NRF2. Intratumoral administration of the NOX2/ROS-activating peptide WKYMVm to mice carrying orthotopically implanted 4T1 or EO771 tumors increased primary tumor growth, augmented tumor cell expression of EMT markers and aggravated distant metastasis. Effects of ROS released from myeloid cells were mimicked by exogenous hydrogen peroxide (H 2 O 2 ) and reversed by a ROS scavenger or a NOX2 inhibitor. In accordance, myeloid cells from Nox2 -deficient mice were less prone to induce EMT in breast cancer cells in vitro or in vivo. Analysis of publicly available human breast cancer datasets showed correlations between NOX2 and EMT-related gene expression within the tumor microenvironment. Additionally, high expression of NOX2 subunit genes and SNAI1 associated with reduced metastasis-free survival. These findings imply that myeloid cell–derived ROS initiate partial EMT in breast cancer cells to promote dissemination and that strategies to target myeloid cell–derived ROS may be explored to limit metastasis.

A hybrid machine learning and explainable AI framework for optimizing risk-based authentication

As online platforms continue to grow, the need for strong authentication mechanisms becomes increasingly important to protect sensitive information and networks. Risk-Based Authentication (RBA) is an adaptive approach that dynamically adjusts authentication decisions based on user behavior and contextual information, thereby improving both security and user experience. This study proposes a hybrid RBA framework that integrates machine learning ensemble techniques, fuzzy logic, clustering, and optimization to enhance account takeover detection and dynamic risk assessment. The ensemble classifier, combining Gradient Boosting, SVM, and XGBoost, predicts the probability of account compromise based on login behavior, device attributes, and network information. K-Means clustering is used to generate initial risk thresholds (low, medium, and high), which are further refined using a fuzzy logic system to map probabilities to risk levels. The L-BFGS-B optimization algorithm is employed to fine-tune fuzzy membership boundaries and improve threshold consistency. Experimental results demonstrate strong performance, achieving 97.77% accuracy, 99.41% precision, 98.04% recall, 98.72% F1-score, and an EER of 0.0303. On large-scale datasets ranging from 2M to 30M records, the proposed framework demonstrates consistent improvement in authentication decisions. For the 2M dataset, Allow Login actions increase from 349,432–349,923, while Deny Login actions decrease from 1,462–1,228, along with a slight reduction in additional authentication prompts. Furthermore, the use of Explainable AI techniques, particularly SHAP, enhances the transparency and interpretability of the model, supporting more informed decision-making. Overall, the proposed framework is accurate, adaptive, and suitable for real-world risk-based authentication applications.

Reduced predator avoidance follows ocular and lateral line pathology in minnow species after diesel exposure

Abstract Petroleum chemicals reach freshwater habitats and can elicit acute toxic effects on ecosystem members. 1 Until recently standardized acute toxicology experiments and water quality standards (also referred to as Maximum Allowable Concentrations in some jurisdictions) focused on mortality of aquatic organisms after 96 h of toxicant exposure 2,3 , but in nature sublethal effects can manifest into mortality and in lotic environments (streams and rivers) exposure times can be far shorter (< 24 h). Here we show that Plains Minnow ( Hybognathus placitus ), Fathead Minnow ( Pimephales promelas ), and Flathead Chub ( Platygobio gracilis ) (Family Leuciscidae) exposed to sublethal concentrations of diesel fuel for 24 h experienced sublethal injuries which render them susceptible to death by predation. Diesel-exposed prey represented 77% of predated fish across all predation events. Decreased predator avoidance likely arose from sensory impairment. Diesel-exposed Fathead Minnow had significantly decreased lateral line neuromast counts and severe ophthalmic pathology. Standardized toxicity experiments would have missed these key effects. Sublethal petroleum exposures have global implications for the conservation of fish species and derivations of water quality standards intended to protect fish from petrochemical pollution need to include sublethal endpoints with the potential to manifest into population loss.

Hydraulic geometry hypothesis allows reverse engineering of 3D quasi-equilibrium landscapes from 2D channel networks: Earth, Mars, Titan

The 2D dendritic structure of stream networks within fluvial catchments has not previously been linked to reach-scale channel processes. Existing extensions of 2D network models to 3D landscapes yield only pixelized landscapes, without resolving channels or their properties. At-a-point relations for hydraulic geometry alone provide no insight into how fluvial processes sculpt 3D landscapes in which channels are embedded. We provide this insight by reverse-engineering generic fluvial landscapes with scalable dimensions for all attributes. We do this by coupling a) a 2D network generator, b) dimensionless, physically grounded relations for gravel-bed river hydraulic geometry, and c) a simplified hillslope model. Catchment hypsometric curve and relief, as well as relations between local channel properties and basin structure, cannot be predicted with just one of these components. Our model predicts in specific, dimensioned terms not only how attributes such as hypsometric curve change with changing bed grain size, precipitation and catchment area, but also why, because each model element can be interrogated individually or jointly. Our method offers a tool for studying the effect of varied mean annual precipitation and intensity on catchment structure. Our central application is to tectonically inactive, quasi-equilibrium, low-relief montane landscapes on Earth. We underline the insight provided by our formulation through application to analogous planetary fluvial landscapes. We implement this for Mars and Titan using appropriate values for gravitational acceleration and sediment submerged specific gravity, both freely variable in our model. Our reverse-engineering methodology indicates why and how an analogous class of landscapes should differ in different planetary settings.

MAPUNet: Multi-scale attention for InSAR phase unwrapping in mining areas

Due to the large deformation gradient caused by large-scale and high-intensity mining in the mining area, severe incoherence is prone to occur during the radar interferometry processing. The traditional phase PU method cannot obtain the correct phase unwrapping (PU) results, resulting in inaccurate monitoring results. To achieve precise monitoring of large gradient deformations in mining areas, a multi-scale phase PU method for mining area based on PUNet with multi-attention mechanism (named MAPUNet) was proposed in this paper. Firstly, the atrous spatial pyramid pooling (ASPP) is added to the original dilated block, and combined with dual attention network (DA-Net), which is used to extract the interferogram feature information at multiple scales. Then, an efficient channel attention network (ECA-Net) optimized residual module is designed to enable the network to extract important interferogram features at both branches and suppress phase noise. Three simulated interferograms with different signal-to-noise ratios (SNR) were selected for the experiment. Under conditions of large phase gradients changes and high noise (SNR = 1), compared with the optimal PUGAN method, SSIM increased by 0.0176, compared with the original PUNet model, SSIM increased by 0.298. The model in this paper has higher accuracy and better robustness, and achieves rewrapped results that are closer to the real situation in the real mining area interferogram. Finally, based on the MAPUNet model, the deformation inversion of the certain mining area in Shanxi has been achieved. The maximum settlement in this area within one month can reach −9.3 cm. Our method effectively solves the problems existing when large-scale subsidence in the mining area, providing a new technical reference for more accurate monitoring of surface deformation.

Single-cell transcriptomics and mouse model phenotyping for biomarker screen of peripheral blood in Huntington’s disease

Abstract Transcriptional dysregulation is among the most prominent molecular alterations in Huntington’s disease (HD). It is not confined to the brain but also extends to peripheral tissues and cells, enabling minimally invasive screening strategies to identify transcriptional surrogates of the health status in HD mutation carriers. Nonetheless, transcriptomics approaches have failed to identify consistent candidates from peripheral blood, probably due to the low impact of the HD mutation in the transcriptional profiles of circulating cells, which can be masked by the high cellular complexity of this biofluid. In this study, we applied for the first time single-cell RNA-seq to peripheral blood mononuclear cells (PBMCs) to determine which cells accumulate the most prominent gene expression changes, and therefore, represent potential sources of reliable biomarkers. We observed common transcriptional alterations across different blood cell subtypes, which were partially validated in published bulk transcriptomics datasets. To relate these gene expression patterns with disease progression in the absence of a large cohort of patients, we examined selected candidates in a phenotypically characterized cohort of transgenic R6/1 mice. Among the tested genes, only the variations in the interferon related gene Irf7 in blood were mildly correlated with motor coordination performance in mutant mice. Notably, striatal Irf7 expression did not show such phenotypical correlation in the same individuals. Overall, transcriptional-based changes in peripheral blood can be linked to HD but they are mild and not apparently confined to particular cellular subpopulations. In conclusion, dissection of individual blood cells in combination with subsequent validation in mouse models emphasizes the challenges in obtaining clinically relevant biomarkers in HD.

Chinmo defines the region-specific oncogenic competence in the <i>Drosophila</i> central nervous system

While genetic mutations can promote hyperplastic growth, they do not always result in oncogenic outcomes. We and others have previously identified the transcription factors Nerfin-1 and Lola as inhibitors of dedifferentiation. Here, we investigate how the oncogenic potential of dedifferentiation varies across different neural lineages in the Drosophila central nervous system. We found that Nerfin-1 inactivation causes tumorigenic phenotypes in the central brain and the ventral nerve cord but not the optic lobes (OLs). In contrast, Lola inactivation leads to tumor overgrowth specifically in the OLs. We identify Chinmo, a temporal transcription factor, and its regulation by ecdysone signaling as key determinants of the oncogenic competence in different regions of the brain, influencing the tumorigenic outcome of dedifferentiation. This study provides a fundamental framework to understand how oncogenic competence arises beyond genetic mutations.

Determinants of secondary prophylaxis for childhood rheumatic heart disease in Ethiopia: A qualitative study of children and caregivers

Background Rheumatic heart disease (RHD) remains a major public health challenge in Ethiopia, particularly among children. Monthly intramuscular benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis, yet adherence and delivery are suboptimal. This study explores the lived experiences of children and adolescents with RHD, capturing their direct voices and those of their caregivers to understand determinants of secondary prophylaxis uptake. Methods A qualitative descriptive study was conducted from May to July 2022 in four Ethiopian public hospitals providing RHD care. Focus group discussions were held with children living with RHD (C-RHD) and their caregivers to explore barriers and facilitators of BPG delivery. Audio recordings were transcribed, translated, and thematically analysed using the framework method, with findings mapped onto the Capability, Opportunity, Motivation, Behaviour (COM-B) model. Results Forty-two participants (30 C-RHD, 12 caregivers) identified five interrelated determinants of BPG delivery: structural barriers (geographic inaccessibility, transport costs, limited policies), organizational challenges (drug shortages, inadequate follow-up and counselling), therapeutic issues (painful injections, needle blockages, limited alternatives), provider-related concerns (fear of adverse reactions), and individual factors (misconceptions, psychological distress, adherence behaviours). Despite a preference for injectable BPG, some children received less effective oral antibiotics due to poor access. Participants emphasized the need for reliable BPG supply, dedicated providers, and strengthened patient support programs. Conclusions Strengthening patient/carer education, improving BPG formulations and access, and addressing resource gaps within healthcare systems are critical to enhancing adherence, preventing ARF/RHD, and improving patient outcomes.