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18 pages, 2830 KB  
Article
Domain-Knowledge-Guided Precursor Descriptors Enable Low-Characterization Prediction of Sodium Storage in Sulfur-Containing Biomass-Derived Hard Carbons
by Chenghao Yu, Junxiao Li, Yanghao Jin, Shitao Wen, Senqiang Qin, Ao Wang, Mengmeng Fan, Kang Sun and Shule Wang
Appl. Sci. 2026, 16(8), 3706; https://doi.org/10.3390/app16083706 (registering DOI) - 10 Apr 2026
Abstract
Biomass-derived sulfur-containing hard carbons are promising anode candidates for sodium-ion batteries, but cross-study optimization remains difficult because reported electrochemical performance reflects both synthesis history and incomplete or non-uniform structural characterization. Here, we assembled a focused literature-derived dataset of 101 records from 16 journal [...] Read more.
Biomass-derived sulfur-containing hard carbons are promising anode candidates for sodium-ion batteries, but cross-study optimization remains difficult because reported electrochemical performance reflects both synthesis history and incomplete or non-uniform structural characterization. Here, we assembled a focused literature-derived dataset of 101 records from 16 journal articles and compared the predictive value of three information sources: precursor descriptors, process variables, and measured structural descriptors. We further introduced domain-knowledge-guided precursor descriptors to encode interpretable aspects of precursor chemistry and architecture, including lignin-related richness, polysaccharide contribution, volatile tendency, precursor-component coupling, and post-treatment category. In controlled feature-set comparisons, the model combining precursor and process descriptors achieved an R2 of 0.59, outperforming the conventional combination of process and structural descriptors (R2 = 0.57) and remaining close to the full-information setting (R2 ≈ 0.61). Model interpretation further showed that, when structural descriptors were removed, predictive reliance shifted toward precursor and process variables, indicating that accessible upstream descriptors retain a meaningful fraction of the formation-pathway information relevant to sodium storage. These results should be interpreted within this curated sulfur-containing literature space rather than as a universal predictor, but they demonstrate that domain-knowledge-guided precursor encoding can support low-characterization, screening-oriented prediction and experimental prioritization. Full article
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16 pages, 4359 KB  
Article
Diversity and Pathogenicity of Neopestalotiopsis Species Associated with Strawberry Leaf Spot and Fruit Rot in Nova Scotia
by Sajid Rehman and Shawkat Ali
J. Fungi 2026, 12(4), 275; https://doi.org/10.3390/jof12040275 (registering DOI) - 10 Apr 2026
Abstract
We reported the first isolation and characterization of Neopestalotiopsis spp. from symptomatic strawberry plants in Nova Scotia, Canada. Morphological and multilocus sequence analyses confirmed that these isolates were closely related to previously identified aggressive Neopestalotiopsis spp. strains from strawberry and blueberry in the [...] Read more.
We reported the first isolation and characterization of Neopestalotiopsis spp. from symptomatic strawberry plants in Nova Scotia, Canada. Morphological and multilocus sequence analyses confirmed that these isolates were closely related to previously identified aggressive Neopestalotiopsis spp. strains from strawberry and blueberry in the southeastern United States and other countries. Five representative isolates were evaluated for pathogenicity on detached leaves, whole plants, and fruits of multiple strawberry cultivars. The results revealed significant variation in virulence, with isolate NS-1 causing the most severe necrosis across all tissue types. Statistical analysis revealed significant effects of isolate, cultivar, and their interaction on disease severity, indicating differential cultivar responses to the tested isolates. Notably, tissue-specific differences were observed, with some isolates being aggressive on leaves but less virulent on fruit or whole plants, reinforcing the importance of multi-organ phenotyping in resistance screening. Phylogenetic analysis clustered the Nova Scotia isolates within the same clade as Neopestalotiopsis isolate 17–43 L from strawberry and isolates from blueberry, suggesting a potential epidemiological link. The shared nursery propagation system of strawberries and blueberries raises the risk of cross-infection, posing a substantial challenge to disease management strategies in both crops. Collectively, these findings underscore the urgent need for continued surveillance, population-level pathogen analysis, and the development of resistant cultivars to mitigate the spread of this emerging and rapidly evolving pathogen. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
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24 pages, 1262 KB  
Article
Combined Factors Influencing the Severity of Elderly-Pedestrian Crashes in Local Areas of Korea Using Classification and Regression Trees and Sensitivity Analysis
by Dong-youn Lee and Ho-jun Yoo
Standards 2026, 6(2), 15; https://doi.org/10.3390/standards6020015 (registering DOI) - 10 Apr 2026
Abstract
This study investigated injury severity in 18,528 police-reported vehicle-to-pedestrian crashes involving elderly pedestrians in legally classified local areas of South Korea during 2012–2021. Injury severity was coded into four ordered categories: fatal, serious, minor, and reported injury. To stabilize scenario extraction from a [...] Read more.
This study investigated injury severity in 18,528 police-reported vehicle-to-pedestrian crashes involving elderly pedestrians in legally classified local areas of South Korea during 2012–2021. Injury severity was coded into four ordered categories: fatal, serious, minor, and reported injury. To stabilize scenario extraction from a categorical crash database, an integrated screening workflow was applied, including near-zero-variance filtering, redundancy control among overlapping roadway encodings, representative-variable selection within redundant groups, and chi-square association checks. Classification and regression tree (CART) modeling was then used to identify rule-based combinations of environmental, roadway, driver, pedestrian, and vehicle factors associated with elevated severity, while tree complexity was controlled through cost-complexity pruning and 10-fold cross-validation. A scenario-based sensitivity analysis was further conducted to evaluate counterfactual shifts in severity distributions under targeted control of key conditions within representative high-risk scenarios. The results showed that severe outcomes were concentrated in stacked-risk combinations rather than in single factors alone. A dominant pathway involved nighttime conditions combined with maneuver-related driving contexts and speeding-related violations. High-fatality scenarios persisted even when speed-related predictors were excluded, underscoring the roles of nighttime exposure, visibility limitations, conflict-prone roadway settings, heavy-vehicle involvement, and pedestrian exposure behaviors. The proposed framework translates administrative crash records into concise, operationally interpretable scenarios and intervention-relevant evidence for local-area safety. Full article
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32 pages, 1193 KB  
Review
Modelling Skin Pigmentation Using the Monte Carlo Technique: A Review
by Raghda Al-Halawani, Meha Qassem and Panicos A. Kyriacou
Sensors 2026, 26(8), 2337; https://doi.org/10.3390/s26082337 (registering DOI) - 10 Apr 2026
Abstract
The impact of skin pigmentation on the accuracy of optical biomedical devices has gained increased attention since the COVID-19 pandemic, particularly following evidence of oximetry measurement bias in dark-skinned individuals. Meanwhile, many computational models utilising the Monte Carlo (MC) technique have been developed [...] Read more.
The impact of skin pigmentation on the accuracy of optical biomedical devices has gained increased attention since the COVID-19 pandemic, particularly following evidence of oximetry measurement bias in dark-skinned individuals. Meanwhile, many computational models utilising the Monte Carlo (MC) technique have been developed as a cost-effective and scalable method for investigating these effects. Hence, this review explores the application of the MC technique in modelling skin pigmentation, focusing specifically on how melanin in the epidermis is represented across different studies. First, the biological mechanisms of pigmentation and current stratification methods are outlined to contextualise the variability in skin tone, followed by the principles of MC modelling, including photon scattering, absorption, reflection, and detection. Following a screening and exclusion process, 50 studies were evaluated in terms of how melanin concentration and distribution are incorporated into MC models and their applications, revealing a range of approaches that include analytical equations, experimental optical property measurements, or hybrid methods. The benefits and limitations of each approach is discussed, in addition to emerging advancements such as heterogeneous melanin distribution and the relation between optical properties and skin colour classification scales. Overall, the review outlines the current methodological approaches utilised for skin pigmentation modelling and offers a reference framework for researchers seeking to improve the representation of skin pigmentation in MC-based optical simulations. Full article
(This article belongs to the Special Issue Feature Papers in Biosensors Section 2026)
15 pages, 1293 KB  
Article
A Flexible Wearable Glucose Sensor for Noninvasive Diabetes Screening: Functional Equivalence and Model Interpretability
by Wenhan Xie, Jinqi Wang, Hao Liu, Shuo Chen, Peng Wang, Yumei Han, Xianxiang Chen, Zhen Fang, Zhan Zhao, Guohong Zhang and Xiuhua Guo
Biosensors 2026, 16(4), 214; https://doi.org/10.3390/bios16040214 (registering DOI) - 10 Apr 2026
Abstract
Real-world evidence for wearable noninvasive glucose monitoring (NIGM) remains limited. To evaluate the functional equivalence of a wearable NIGM device and explore its utility for T2DM and prediabetes screening. In this multicenter study, 12-h daytime glucose profiles obtained by a flexible reverse iontophoresis-based [...] Read more.
Real-world evidence for wearable noninvasive glucose monitoring (NIGM) remains limited. To evaluate the functional equivalence of a wearable NIGM device and explore its utility for T2DM and prediabetes screening. In this multicenter study, 12-h daytime glucose profiles obtained by a flexible reverse iontophoresis-based electrochemical sensor were compared with capillary glucose using functional equivalence. Subgroup analyses were conducted. Screening models of T2DM and prediabetes were developed using elastic net and Logistic regression. A total of 135 participants (mean age 35.3 years; 60.0% female) were included, and no serious device-related adverse events were reported. Compared to the capillary measurements, functional equivalence was confirmed (T = −6.537 < threshold = −2.081) in the general population but not in older adults or T2DM patients. The T2DM noninvasive screening model demonstrated discrimination and reclassification performance comparable to those of the capillary-based model (AUC: 0.906 vs. 0.850, NRI: 0.044, IDI: −0.078, p > 0.05). Functional principal component scores facilitated the identification of prediabetes (AUC = 0.760). The device demonstrated acceptable accuracy and functional equivalence with reference methods. Its capability to detect T2DM and early glycemic anomalies supports its feasibility as a wearable, interpretative adjunct tool for large-scale screening in free-living populations. Full article
(This article belongs to the Section Biosensors and Healthcare)
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36 pages, 2635 KB  
Review
The Spectrum of Cutaneous Manifestations in Dermatomyositis: A Comprehensive Review
by Magdalena Kutwin, Paulina Karp, Marcelina Kądziela, Alicja Siennicka and Agnieszka Żebrowska
J. Clin. Med. 2026, 15(8), 2874; https://doi.org/10.3390/jcm15082874 (registering DOI) - 10 Apr 2026
Abstract
Dermatomyositis (DM) is a rare, autoimmune inflammatory myopathy characterized by a heterogeneous clinical course and complex etiopathogenesis. Although classically defined by the coexistence of muscle inflammation and distinctive skin lesions, DM frequently presents as a systemic disease, and, in some patients, cutaneous manifestations [...] Read more.
Dermatomyositis (DM) is a rare, autoimmune inflammatory myopathy characterized by a heterogeneous clinical course and complex etiopathogenesis. Although classically defined by the coexistence of muscle inflammation and distinctive skin lesions, DM frequently presents as a systemic disease, and, in some patients, cutaneous manifestations may precede muscle involvement or represent the sole clinical feature. The spectrum of skin lesions in DM is broad and includes pathognomonic, characteristic, rare, or atypical manifestations, ranging from classic Gottron’s sign and heliotrope rash to uncommon subtypes such as vesiculobullous dermatomyositis, Wong-type dermatomyositis, or flagellate dermatitis. Particular cutaneous phenotypes often correlate with distinct clinical subtypes, autoantibody profiles, systemic involvement, and prognosis. The diversity of dermatological presentations and their resemblance to other dermatoses may delay accurate diagnosis, especially in amyopathic and hypomyopathic forms of the disease. The aim of this review is to comprehensively discuss the wide spectrum of cutaneous manifestations of dermatomyositis, emphasize less recognized and rare dermatological clinical presentations, and highlight their diagnostic and prognostic significance. However, histopathological examination may support the diagnostic process in challenging cases. Early identification of characteristic skin lesions remains crucial for prompt diagnosis, appropriate screening for systemic complications and malignancy, and optimal management. Close interdisciplinary cooperation among dermatologists, rheumatologists, and other specialists is essential to ensure accurate diagnosis and improve outcomes in patients with dermatomyositis. Full article
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14 pages, 1515 KB  
Article
Development of a New FT-Raman Method for the Investigation of Cinnamon Authenticity
by Konstantinos Chatzipanagis and Ana Boix Sanfeliu
Foods 2026, 15(8), 1311; https://doi.org/10.3390/foods15081311 (registering DOI) - 10 Apr 2026
Abstract
The price of Cinnamomum verum (Ceylon cinnamon) is higher than that of other cinnamon varieties known as cassia cinnamon and/or Cinnamon camphora, which can trigger fraudsters to perform partial or total substitution of the former by the latter types, especially [...] Read more.
The price of Cinnamomum verum (Ceylon cinnamon) is higher than that of other cinnamon varieties known as cassia cinnamon and/or Cinnamon camphora, which can trigger fraudsters to perform partial or total substitution of the former by the latter types, especially in ground cinnamon products. In addition, substitution of cinnamon bark by different parts of the plant (e.g., root, leaves) and/or introduction of inorganic matter in any cinnamon variety can also occur, increasing the overall risk of fraud related to spices, which are among the most vulnerable food commodities. This work reports the development of a novel Fourier transform (FT) Raman spectroscopic method combined with principal component analysis (PCA) applied to ground cinnamon, as an analytical tool to detect suspicious samples related to the aforementioned fraudulent practices. The findings of this new analytical approach were supported by published results from experiments on these samples using confirmatory techniques, such as X-Ray Fluorescence (XRF) and Gas Chromatography–Mass Spectrometry (GC-MS), cited in this paper. Full article
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22 pages, 8790 KB  
Article
Ex Vivo Characterization Studies Identify Candidate Therapies for the Individualized Care of NF2-Related Schwannomatosis
by Ethan W. Hass, Anna Nagel, Alexandra J. Scott, Robert Allaway, Haley M. Hardin, Hollie M. Hayes, Lenna Huelbes, Alexander W. Sutton, Sofia A. Oliveira, Michelle Pei, Fred F. Telischi, John Ragheb, McKay McKinnon, Ziad Khatib, Mislen Bauer, Christine T. Dinh and Cristina Fernandez-Valle
Cancers 2026, 18(8), 1209; https://doi.org/10.3390/cancers18081209 (registering DOI) - 10 Apr 2026
Abstract
Background/Objectives: NF2-related schwannomatosis (NF2-SWN) is a genetic tumor predisposition syndrome of the nervous system caused by pathogenic variants in NF2 encoding the merlin tumor suppressor. Truncating variants in NF2 cause severe phenotypes with higher tumor burden, early mortality, and [...] Read more.
Background/Objectives: NF2-related schwannomatosis (NF2-SWN) is a genetic tumor predisposition syndrome of the nervous system caused by pathogenic variants in NF2 encoding the merlin tumor suppressor. Truncating variants in NF2 cause severe phenotypes with higher tumor burden, early mortality, and a lifetime need for multiple surgeries due to lack of medications that control schwannoma growth. Methods: We developed a functional precision medicine (FPM)-inspired workflow to identify drug sensitivities in cells isolated from a pediatric severe NF2-SWN patient’s spinal and peripheral schwannomas. Transcriptomic profiling, high-content drug sensitivity assays, tissue and isolated cell immunostaining, flow cytometry, and capillary-based immunoblotting were used to study the available tissues. Results: Aberrant merlin-dependent pathway expression was conserved between the spinal schwannoma and its cultured primary cells. Drug sensitivity screens in 2- and 3-dimensional formats revealed cytotoxic effects of fimepinostat in primary cells; dasatinib with brigatinib was the most effective cytostatic combination. Ineffective therapies attempted in the patient were also ineffective ex vivo. Conclusions: These data support the idea of using the FPM workflow to improve and individualize the standard of care for severe NF2-SWN patients using surgical samples. Full article
(This article belongs to the Special Issue Targeted Therapies for Pediatric Nervous System Tumors)
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27 pages, 1243 KB  
Review
The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease
by Anna Kotlyarova, Aleksandra Iskrina and Stanislav Kotlyarov
Int. J. Mol. Sci. 2026, 27(8), 3399; https://doi.org/10.3390/ijms27083399 - 10 Apr 2026
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article
(This article belongs to the Special Issue Molecular Insights into Chronic Liver Disease and Liver Failure)
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18 pages, 2946 KB  
Article
The RUS1 (ROOT UVB SENSITIVE 1) Protein Is Required for Cold Resistance in Chlamydomonas reinhardtii
by Yulong Wang, Du Cao, Kangning Guo, Tingting You, Penghao Yang and Xiaobo Li
Cells 2026, 15(8), 670; https://doi.org/10.3390/cells15080670 (registering DOI) - 10 Apr 2026
Abstract
Low temperature critically influences cellular metabolism by impairing processes such as membrane fluidity, enzyme activity, and protein folding. However, the comprehensive genetic landscape and regulatory mechanisms governing cold acclimation remain poorly understood. Here, we performed high-throughput, pooled genetic screening in the model alga [...] Read more.
Low temperature critically influences cellular metabolism by impairing processes such as membrane fluidity, enzyme activity, and protein folding. However, the comprehensive genetic landscape and regulatory mechanisms governing cold acclimation remain poorly understood. Here, we performed high-throughput, pooled genetic screening in the model alga Chlamydomonas reinhardtii (C. reinhardtii) to identify genes essential for cold acclimation. Our screening revealed numerous candidate genes implicated not only in early cold response pathways but also in core cellular processes, including DNA dynamics, protein homeostasis, metabolic regulation, and substrate transport. Notably, we identified a member of the RUS (ROOT UVB SENSITIVE) family, encoding a conserved DUF647 domain protein, designated CrRUS1. CRISPR-generated rus1 mutant alleles in C. reinhardtii display a phenotype consistent with our screening: the mutants did not exhibit any visible growth defects, but show severe growth defects at low temperature. Interestingly, the cold-induced phenotypic changes in rus1 can be reversed by dark conditions, suggesting that CrRUS1 likely promotes cold acclimation in C. reinhardtii through a light-dependent pathway. Our work provides novel genetic resources and mechanistic insights into cold acclimation in C. reinhardtii, with potential translational relevance for enhancing cold tolerance in crop species. Full article
(This article belongs to the Section Plant, Algae and Fungi Cell Biology)
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17 pages, 263 KB  
Article
“It Was Traumatizing, Because It Makes You Feel Like You Are Not Right”: 2S/LGBTQIA+ Survivors’ Experiences Accessing Care for Intimate Partner Violence-Caused Brain Injury
by Emily Chisholm and Tori N. Stranges
Healthcare 2026, 14(8), 997; https://doi.org/10.3390/healthcare14080997 (registering DOI) - 10 Apr 2026
Abstract
2S/LGBTQIA+ survivors of intimate partner violence (IPV) face multiple, intersecting barriers to accessing care, yet little is known about how these barriers are shaped by IPV-caused brain injury (IPV-BI). Background/Objectives: This study aimed to explore how stigma and institutional trust influence 2S/LGBTQIA+ survivors’ [...] Read more.
2S/LGBTQIA+ survivors of intimate partner violence (IPV) face multiple, intersecting barriers to accessing care, yet little is known about how these barriers are shaped by IPV-caused brain injury (IPV-BI). Background/Objectives: This study aimed to explore how stigma and institutional trust influence 2S/LGBTQIA+ survivors’ experiences of help-seeking following IPV-BI. Guided by a Community Advisory Board, four semi-structured focus groups were conducted with 29 2S/LGBTQIA+ IPV-BI survivors. Methods: Reflexive thematic analysis was used to examine participants’ help-seeking accounts, with attention to minority stress and intersecting stigmas related to IPV, BI, and 2S/LGBTQIA+ identity. Results: The findings indicate that survivors navigated compounded stigmas that limited access to safe, affirming services and heightened vulnerability during help-seeking. Institutional trust was central to participants’ decisions to disclose sensitive information and engage in care, with confidentiality emerging as a critical determinant of perceived safety. Participants described negotiating disclosure, anticipating discrimination, and avoiding services when systems were perceived as unsafe or unresponsive. Conclusions: These findings highlight the need for service systems to integrate IPV-BI into screening and support protocols, provide training on the intersections of IPV, BI, and 2S/LGBTQIA+ identities, and centre confidentiality as a condition for trust and access, ultimately fostering safer, more responsive systems of care. Full article
12 pages, 533 KB  
Article
Flooding-Induced Mobilization of Heavy Metals in Surface Soils and Associated Carcinogenic and Non-Carcinogenic Health Risks: A Screening-Level Risk Assessment
by Nicole Montes Pérez and Tia Warrick
Int. J. Environ. Med. 2026, 1(2), 6; https://doi.org/10.3390/ijem1020006 (registering DOI) - 10 Apr 2026
Abstract
Flooding is an increasingly frequent climate hazard with the potential to mobilize environmental contaminants and elevate human health risks. In this study, we assessed heavy metals and metalloids across five sites arranged along a flood-risk gradient from low to high. Six replicate samples [...] Read more.
Flooding is an increasingly frequent climate hazard with the potential to mobilize environmental contaminants and elevate human health risks. In this study, we assessed heavy metals and metalloids across five sites arranged along a flood-risk gradient from low to high. Six replicate samples per site (n = 30 per contaminant) were collected in a single sampling event. Contaminants were evaluated using the US Environmental Protection Agency (EPA) risk assessment framework to calculate chronic daily intake (CDI), hazard quotients (HQs), and lifetime cancer risk. Arsenic, chromium, and nickel emerged as the most concerning cancer drivers, with nickel cancer risk consistently exceeding 1 × 10−3 (equivalent to one additional cancer case per 1000 exposed individuals) and arsenic at 4.4 × 10−4 (about 1 in 2250). Lead posed non-cancer risks (HQ = 0.912, near the threshold of concern), while cobalt demonstrated a significant decreasing gradient with increasing flood-risk (p = 0.018). Arsenic and thallium more than doubled in concentration at high-flood sites relative to low-flood sites, while cadmium, cobalt, and nickel decreased. These findings suggest flooding may mobilize arsenic, lead, and thallium, while diluting or displacing other metals such as cadmium, cobalt, and nickel. Organs of concern include the liver and kidneys for arsenic, cadmium, nickel, and cobalt, the brain and bones for lead, and the lungs and liver for chromium. Although statistical significance was limited by the small sample size, effect sizes and fold-changes indicate meaningful flood-related differences. This study highlights the importance of considering flood-risk in contaminant hazard assessments and the need for flood-adaptive risk management strategies in vulnerable communities. Full article
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14 pages, 1526 KB  
Article
Effectiveness of an Oral Supplementation of Phycocyanin and Palmitoylethanolamide for a Short-Term Prophylaxis of Menstrual Migraine: A Retrospective Observational Study
by Gianni Allais, Massimo Autunno, Florindo D’Onofrio, Luisa Fofi, Maria Gabriella Saracco, Fabiola Bergandi, Chiara Benedetto, Francesca Silvagno and Loredana Bergandi
Biomedicines 2026, 14(4), 865; https://doi.org/10.3390/biomedicines14040865 (registering DOI) - 10 Apr 2026
Abstract
Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation [...] Read more.
Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. Full article
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