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Multi-omics profiling characterizes cancer biology and supports biomarker discovery for prognosis and therapy selection. Although numerous computational multi-omics biomarker identification methods have been proposed, their ability to identify clinically relevant biomarkers has not been systematically evaluated, leaving it unclear whether the resulting biomarker nominations are reliable for downstream validation. Here, we systematically benchmark 20 representative statistical, machine learning and deep learning methods using curated gold-standard prognostic and therapeutic biomarkers across five real-world datasets. We evaluate performance in terms of both biomarker identification accuracy and stability. Overall, DeePathNet and DeepKEGG achieve the best performance. Across methods, effective biomarker recovery is associated with the integration of biological knowledge, global feature interactions, multivariate feature attribution, and effective regularization. Analysis of omics type contributions reveals method- and modality-specific biases, highlighting the importance of broader omics integration. We further evaluate methods on simulated datasets to probe sensitivity with controlled signal and noise. By aggregating results from top-performing methods, we construct consensus biomarker panels that nominate candidates for potential investigations. Finally, we provide user-friendly interfaces to allow researchers to benchmark new methods against the 20 baselines or apply selected methods for biomarker identification on custom multi-omics datasets. Our benchmark is publicly available at https://github.com/athanzli/CancerMOBI-Bench.

A bruise or haematoma in a non-mobile infant is a red flag prompting concern for non-accidental injury. Bruising does not always signify trauma however and may occur spontaneously due to an underlying medical cause. This case report describes a 3-month-old infant presenting with unexplained faint bruising to the axilla and an associated lump. Point of care ultrasound revealed a chest wall haematoma without any other evidence of trauma prompting blood tests, which demonstrated severely deranged coagulation and conjugated hyperbilirubinaemia. The child was subsequently diagnosed with Alagille Syndrome. Point of care ultrasound is a useful clinical adjunct for providing greater detail to the examination of unusual lumps or swellings which in this case prompted further investigations leading to a rare diagnosis.

This study investigated the neural mechanisms underlying feedback-based learning of novel-object-novel-word associations, focusing on how feedback-locked event-related potentials acquired during learning relate to subsequent memory performance and acquired association strength. Specifically, we examined whether amplitudes of the feedback-related negativity (FRN) and N170 components after immediate or delayed feedback predicted not only free recall and recognition performance, but also N400 priming effects exerted by the novel objects on the novel words as a neural correlate of the strength of the associations acquired through feedback-based learning. Sixty-six healthy young adults learned novel associations receiving either immediate or delayed deterministic feedback, followed by free recall tests and a newly introduced primed recognition task to measure N400 priming effects. Results showed that FRN amplitudes during learning were associated with recognition performance and predicted frontal N400 priming effects, suggesting a link to procedural, automatically retrieved memories. In contrast, N170 amplitudes were related not only to recognition, but also free recall and to general facilitation of semantic retrieval and integration processes, reflected in reduced N400 amplitudes, indicating a role in declarative memory and familiarity-driven processing facilitation. Overall, feedback-based learning elicited robust N400 priming effects, reflecting successful associative integration. However, no consistent effects of feedback timing or valence were observed, likely due to learning strategies adopted based on the deterministic nature of feedback and the anticipation of the memory tasks after learning. These findings highlight distinct contributions of feedback-related ERP components to different forms of memory representations, linking general mechanisms of feedback-based learning to the resulting representations.

Muscle dysfunction is a critical construct in dysphagia. Despite the availability of diverse techniques to evaluate muscle function, a comprehensive synthesis of measurement items and their properties is lacking. A systematic review of studies examining the measurement techniques used to directly evaluate oropharyngeal muscle function was performed. Studies investigating the use of surface electromyography, tongue dynamometry, ultrasound, high-resolution pharyngeal manometry, magnetic resonance imaging and computed tomography and reporting measurement properties in line with the COnsensus-based Standards for the selection of health Measurement InstrumeNts (COSMIN) were included. Measurement outcomes derived from these techniques were operationalised as single-item measures. Methodological quality was evaluated using the QualSyst tool. From the 6279 records, 125 eligible studies were identified. The breakdown of techniques was surface electromyography (n = 33), tongue dynamometry (n = 34), ultrasound (n = 17), high-resolution pharyngeal manometry (n = 15), magnetic resonance imaging (n = 5), computed tomography (n = 4) and combined techniques (n = 17). Single-item measures were heterogenous, covering a range of domains including muscle activation, coordination, strength, endurance, composition, thickness, and kinematics. Studies focused predominantly on oral rather than pharyngeal musculature. Validity (n = 117) was widely reported, primarily via known-group validity or hypothesis testing. Fewer studies examined reliability (n = 20) and responsiveness (n = 25); however, where reported, results indicated excellent intra- and inter-rater reliability and responsiveness to therapeutic interventions. A diverse range of single-item measures were identified across included measurement techniques. Measurement properties were sparsely reported. Future research should focus on rigorous measurement instrument design and standardisation to comprehensively evaluate the underlying mechanisms of dysphagia.

Epilepsy is frequently accompanied by psychiatric comorbidities, whereas functional gastrointestinal disorders are often overlooked. This study investigated the prevalence of functional gastrointestinal disorders in adult patients with epilepsy (PWE) and their associations with psychological symptoms, chronotype, and seizure characteristics. In this cross-sectional case-control study, 100 adult PWE and 100 age- and sex-matched healthy controls (HC) were evaluated. Functional gastrointestinal disorders were assessed using Rome IV criteria and stool form with the Bristol Stool Form Scale. Depression and anxiety were measured with the Beck inventories, and chronotype with the Morningness-Eveningness Questionnaire. Clinical epilepsy variables and antiseizure medication profiles were recorded. Functional gastrointestinal disorders were significantly more prevalent in PWE than in HCs. Irritable bowel syndrome and functional constipation occurred more frequently in the PWE, and constipation-predominant stool patterns were markedly increased. Patients with epilepsy showed higher rates of moderate-to-severe depression and anxiety and a predominance of intermediate chronotype. Within the PWE, functional gastrointestinal disorders and constipation-predominant stool patterns were associated with higher psychological symptom burden, polytherapy, and ongoing seizures, but not with epilepsy subtype, electroencephalography, or magnetic resonance imaging findings. Adults with epilepsy exhibit a substantially increased burden of functional gastrointestinal disorders accompanied by elevated psychological symptoms and altered chronotype distribution. Gastrointestinal symptoms were largely unreported clinically, despite their association with greater disease complexity. Systematic screening for functional gastrointestinal disorders, mood symptoms, and chronotype may facilitate a more comprehensive and integrated approach to epilepsy care. These findings underscore the need for multidisciplinary assessment in practice.

Surgical procedures in critical care settings are often associated with prolonged postoperative pain, which remains a significant clinical challenge. Conventional analgesic strategies typically rely on injection-based delivery, which is invasive, requires trained personnel, and carries risks such as infection and tissue damage. To address these limitations, this study developed a minimally invasive transdermal delivery system for the local anaesthetic ropivacaine (ROP) using hydrogel-forming microneedles (HFMNs) combined with drug reservoir tablets. Two HFMN formulations were prepared using Gantrez® S-97 (MN1) and PVA-PVP (MN2), each paired with reservoirs fabricated by direct compression (DCT) or lyophilisation (LYO). Insertion capability study demonstrated that MN2 exhibited superior skin penetration compared with MN1. In vitro permeation studies showed that MN2-DCT achieved the highest transdermal delivery of ROP (> 12 mg across dermatomed porcine skin). However, when both permeated and deposited drug (within skin and HFMNs) were considered, LYO reservoirs paired with either MN1 or MN2 resulted in higher total drug delivery over 24 h. This is attributed to the porous structure of LYO tablets, which enhances fluid uptake and rapid dissolution. The retained drug within the skin and HFMN matrix may serve as a depot for sustained release. In vivo evaluation in a postoperative pain mouse model demonstrated that MN2-LYO provided rapid and sustained analgesia, achieving > 50% maximum possible effect (%MPE) within 1 h and maintaining efficacy for up to 72 h, whereas MN1-LYO showed limited analgesic response. Furthermore, both MN1-LYO and MN2-LYO significantly reduced inflammatory cytokines (IL-6 and TNF-α), with the greatest reduction observed for MN2-LYO (~ 50% decrease compared with negative control and subcutaneous ROP groups). Overall, these findings highlight the potential of HFMN-based delivery systems combined with LYO reservoirs as a minimally invasive, patient-friendly alternative to injectable anaesthetics for prolonged postoperative pain management.

Only 6% of UK memory services meet Alzheimer's disease (AD) biomarker access guidelines, limiting psychiatrists' experience. Emerging AD blood biomarker (BBM) tests will potentially expand access. Exploring implementation barriers and enablers a priori can inform rollout strategies. This study examined current clinical practises, barriers and enablers to implementation and potential interventions to support implementation. In November 2024, Royal College of Psychiatrists Old Age Psychiatry Faculty members (n&#x2009;=&#x2009;172) participated in an online survey and four focus groups (n&#x2009;=&#x2009;16 participants), informed by the Theoretical Domains Framework (TDF) and Behaviour Change Wheel. Demographic data were summarised descriptively. Mean (SD) belief statement scores for TDF domains and percentage agreement were calculated. Multiple linear regression examined associations between TDF domains and intention to use BBMs. Respondents were mainly consultants in England; <33% had used biomarkers. Key barriers to use were: 'Knowledge,' 'Environmental Context and Resources' and 'Goals.' Enablers included: 'Behavioural Regulation,' 'Social Influences' and 'Intention.' Mixed enablers/barriers included: 'Beliefs about Consequences', 'Optimism' and 'Social/Professional Role & Identity'. In regression analyses, 'Memory, Attention and Decision Processes' (B&#x2009;=&#x2009;0.44, 95%CI 0.20-0.68), 'Beliefs about Consequences'(B&#x2009;=&#x2009;0.45, 95%CI 0.11-0.78), and 'Social Influences' (B&#x2009;=&#x2009;0.24, 95%CI 0.04-0.44) were positively associated with intention, while 'Optimism' (B&#x2009;=&#x2009;-0.31,95% CI-0.58 to-0.04) and 'Emotion' (B&#x2009;=&#x2009;-0.33, 95%CI -0.60 to-0.06) were negatively associated. Key interventions were 'Guidelines' (e.g. appropriate use criteria) and 'Environmental Restructuring' to expand resources and re-organise pathways. A complex interplay of barriers and enablers influences AD BBM implementation. Interventions targeting clinician, service and policy levels are required to support their introduction.

We present the complete genome sequence of Debaryomyces hansenii DSM 3428, assembled using long- and short-read sequencing data. This genome provides a valuable reference for investigating the genetic basis of stress tolerance and biotechnologically relevant traits in this yeast.

Arsenic accumulation and biotransformation in fungi remain poorly understood, particularly in mushrooms. This study investigated arsenic distribution, speciation, and detoxification mechanisms in three mushroom species of the genus Hebeloma: H. bulbiferum, H. sinapizans, and H. mesophaeum. Wild collected fruit bodies and laboratory mycelial cultures were analysed using size-exclusion chromatography (SEC) and ion-pair reversed-phase ICP-MS to determine total arsenic concentrations and speciation patterns. H. bulbiferum exhibited the highest arsenic accumulation in fruit bodies (up to 563&#xa0;mg kg&#x207b;&#xb9; dry mass), predominantly as dimethylarsenate, whereas H. sinapizans accumulated less total As (up to 41.2&#xa0;mg kg&#x207b;&#xb9; dry mass), comprising mainly arsenobetaine and dimethylarsenate, and H. mesophaeum (up to 4.2&#xa0;mg kg&#x207b;&#xb9; dry mass) was dominated by inorganic arsenic and arsenocholine. SEC revealed that arsenic was present as low-molecular-weight fractions, although a minor protein-associated peak was observed in H. sinapizans, suggesting a possible presence of an arsenic-binding protein. Mycelial cultures demonstrated species-specific tolerance to arsenate and the ability to transform inorganic arsenic into organic arsenicals, with varying degrees of arsenate reduction, arsenite efflux, and methylation. In particular, H. sinapizans and H. mesophaeum exhibited a higher degree of As(III) efflux than H. bulbiferum, indicating a more efficient As reduction and export. Notably, some organoarsenicals, dimethylarsenate and trimethylarsine oxide, were actively excreted into the growth medium, indicating a role for mushroom mycelia in environmental arsenic cycling. These findings highlight distinct arsenic detoxification strategies in Hebeloma species, reveal fungal de novo arsenobetaine synthesis, and provide insights into arsenic transformation and sequestration in ectomycorrhizal mushrooms.

The relationship between craniofacial pattern and upper airway function remains incompletely understood. This study investigated differences in upper pharyngeal airway morphology and airflow characteristics among young adults with skeletal Classes I, II, and III according to the ANB angle. Three-dimensional (3D) models were reconstructed from CBCT images. Morphological parameters, including total airway volume and minimum cross-sectional area (mCSA), were measured. Computational fluid dynamics simulations were performed to evaluate airflow velocity and maximum pressure within the human upper airway (HUA). Class II subjects exhibited significantly reduced airway volume and mCSA, compared with Class I and Class III subjects. These anatomical differences were associated with higher airflow velocity and increased airway suggesting greater airflow resistance. In contrast, individuals with Class III demonstrated larger airway spaces with lower airflow velocity and pressure. Skeletal pattern significantly influences both airway morphology and airflow behavior. Class II individuals exhibit narrower airways and higher resistance, whereas Class III individuals present more favourable airway characteristics.

Quantitative ultrasound (QUS) techniques provide tissue characterization and have applications in precision diagnostics and therapy monitoring. A common QUS approach estimates backscatter coefficients (BSCs) using the external reference phantom method, which does not adequately address attenuation and transmission losses. To address this issue, we previously utilized a 2&#x2009;mm titanium bead as an in situ calibration reference with conventional focused wave (FW) imaging. Plane wave compounding (PWC), which transmits multiple angled plane waves, enables rapid image acquisition while maintaining quality, making it widely useful in Doppler and elastographic imaging. However, its role in BSC estimation with an in situ bead had not been investigated. We hypothesized that PWC would outperform FW, as diffraction effects vary more slowly away from the bead depth when using PWC. We tested this hypothesis by comparing BSC estimation in phantoms and in vivo rabbit mammary tumors. Results indicated that PWC with in situ calibration better compensated for attenuation loss and reduced variability in scatterer property estimates compared to FW. Specifically, the scatterer diameter variance was 15.2 &#x3bc;m2 when using PWC versus 45.4 &#x3bc;m2 when using FW where the focus was offset from the bead depth. These findings demonstrate the superiority of using PWC with an in situ calibration target for accurate, efficient BSC estimation.

Sugars are essential nutrients for the growth, development, and reproduction of insects. To enhance the reproductive and pest control potential of Trichogramma pintoi, this study investigated the effects of supplementing different concentrations (10%, 15%, 20%, and 25%) of nutrients, sucrose, glucose, fructose, maltose, trehalose, honey, and water (control), on the longevity, fecundity, flight capacity, and gustatory response of T. pintoi adults. The results showed that T. pintoi took the shortest time to locate 20% concentrations of the different nutrients and exhibited the longest feeding duration. Supplementing fructose (female 19.53 d, male 11 d) and sucrose (female 17.67 d, male 9 d) resulted in the longest adult longevity of T. pintoi, with the highest fecundity (131.73 eggs/female, and 137.4 eggs/female, respectively). While, T. pintoi fed on water had a shortest longevity (Female: 1.47 d, Male: 1.27 d), and a lowest fecundity (12.93 eggs/female). Additionally, supplementing with different sugar solutions significantly enhanced the flight capability of T. pintoi. Among them, honey produced the highest proportion of L4 (flight capability with Level 4), reaching 78.67%. This study demonstrated that supplementing with 20% fructose and sucrose can significantly prolong the longevity and fecundity of T. pintoi, while honey can significantly enhance their flight capacity. These findings provide a reference standard for improving the mass rearing capacity and application effcacy of T. pintoi pest control.

Genetic myopathies encompass a heterogeneous spectrum of neuromuscular disorders whose diagnosis remains challenging despite major technological advances. Traditional methods such as clinical evaluation, creatine kinase measurement, electromyography, and muscle histopathology remain valuable tools for recognizing disease patterns and, when clinically indicated, for complementing and guiding molecular investigations. However, genetically complex or atypical cases still lack an appropriate approach for assertive diagnosis. Aiming to shed light on emerging integrative molecular approaches, this review will discuss the evolving diagnostic landscape of myopathies, highlighting the integration of next-generation molecular tools with conventional methodologies for assertive diagnosis. Long-read sequencing and optical genome mapping have markedly increased diagnostic yield by enabling comprehensive detection of structural variants and complex genomic rearrangements in different myopathies. Complementary proteomic and transcriptomic analyses provide functional insight into how genetic variants alter protein expression and cellular pathways, supporting biomarker discovery and therapeutic development. Together, these omics approaches bridge the gap between genetic alterations and their functional and clinical manifestations in myopathies. They improve the interpretation of variants of uncertain significance, facilitate the identification of biomarkers linked with disease severity or therapeutic response, and support the development of personalized therapeutic strategies, advancing precision medicine in neuromuscular disorders.

Background. Our recent findings indicate that the rough form of the Mycobacterium abscessus complex (MABC) is associated with worse clinical outcomes compared to the smooth variant. The glycopeptidolipid (GPL) locus has been considered vital for this transition; however, this has only been shown during in vitro selection. Thus, we aimed to investigate genetic differences between the morphotypes among clinical isolates.Methods. Whole-genome sequencing (WGS) by Oxford Nanopore was applied to rough and smooth clinical MABC strains (n=10), including laboratory strains and in vitro exposure to nitric oxide (NO). Comparative genomic analysis, methylation and pangenome analysis were used to investigate the orthologs and unique protein clusters in relation to morphotype.Results. WGS analysis showed high average nucleotide sequence identity (>98%), but genetic variants compared to the reference genome ranged from 1,433 to 27,025, and these differences did not correlate with morphotype. Among clinical isolates, smooth MABC clustered and were separated from the rough isolates. In both rough and smooth phenotypes, random genetic variations that could not separate the morphotypes were detected mainly in the nrps of the GPL loci. The major protein-cluster differences between smooth (n=123) and rough (n=22) clinical isolates were observed in key genes outside the GPL locus, such as fabH, pks15, fadD29, otaA, mabA, lysX and acdA, primarily involved in fatty acid biosynthesis and transporter systems. Repeated NO exposure, serving as a proxy for host-related stress, induced a rough phenotype by altering the acyl desaturase DesA1 protein, which is involved in fatty acid synthesis.Conclusion. By analysing clinical MABC isolates, we show that morphotype variation cannot be explained by the GPL locus only. Unique genes involved in fatty acid biosynthesis were identified, informing further investigation into mechanisms distinguishing smooth and rough morphotypes of clinical MABC isolates.

Intermuscular coherence (IMC), especially in the beta band, has been widely used as a non-invasive approach to estimate the strength of corticospinal connectivity. The corticospinal tract is frequently damaged as a result of stroke, which may impair the strength of corticospinal connectivity, particularly that contributing to manual dexterity. Here we investigated acute adaptations in IMC and manual dexterity in fifteen chronic stroke survivors and seven age-matched healthy controls who performed exercise to task-failure with their non-paretic hand (or dominant hand for healthy controls). Dexterity (measured by Box-and-Blocks Test, BBT) and IMC were tested at baseline, following exercise to task-failure, and every 45&#x2005;min until 4&#x2005;h after task-failure (7 times in total). At baseline, paretic hand beta and gamma band IMC were significantly reduced in stroke survivors (P's&#x2009;=&#x2009;0.006). Additionally, at baseline paretic hand (or non-dominant hand for healthy controls) BBT performance and gamma band IMC revealed significant positive correlations in both stroke survivors (R2&#x2009;=&#x2009;0.40, P&#x2009;=&#x2009;0.010) and the whole sample (R2&#x2009;=&#x2009;0.33, P&#x2009;=&#x2009;0.005). Paretic hand BBT performance increased immediately and at 225&#x2005;min after task-failure compared with baseline (P's&#x2009;=&#x2009;0.017 and 0.014, respectively). Paretic hand beta band IMC increased immediately and remained significantly elevated at 45&#x2005;min after task-failure (P&#x2009;=&#x2009;0.045 and 0.005, respectively) while paretic hand gamma band IMC was increased at 135&#x2005;min after task-failure (P&#x2009;=&#x2009;0.051). Taken together, our results suggest increased strength of corticospinal connectivity to the paretic hand as an acute adaptation to non-paretic hand exercise to task-failure. Concurrent facilitation of paretic hand manual dexterity and strengthened ipsilesional corticospinal connectivity suggests this approach should be explored as a strategy to promote recovery of corticospinal connectivity and paretic hand motor function in neurorehabilitation.

Bacteroides spp. are a key immune-programming microbe in healthy individuals-these bacteria have been shown to be reduced in abundance across a variety of disease states. Our study investigated the systemic and region-specific responses to Bacteroides colonization in the gut, including sex-related differences, in mice. Utilizing C57BL/6 mice, we administered Bacteroides to conventional, antibiotic-treated mice, then assessed this microbe's influence on the gut microbiota composition and inflammatory responses following an airway lipopolysaccharide challenge to assess effects on the gut-lung axis. We found that Bacteroides successfully colonizes the intestinal tract of antibiotic-treated mice, particularly the colon lumen of the large intestine, as evidenced by 16S rRNA amplicon gene sequencing and culturing. Differential gene expression analysis using NanoString technology revealed significant immune response variations across the gut regions, with notable differences in adaptive immune response genes. A striking sex-dependent outcome was noted in the regulation of atg12 in the cecum, potentially enhancing autophagic function, particularly in female mice. Additionally, Bacteroides intestinal colonization was associated with altered expression of macrophage markers such as cd163, cd84, and ms4a4a, which may reflect shifts in the macrophage profile within the cecum. These findings pave the way for novel therapeutic approaches that leverage microbial impacts on gut and systemic health, offering a deeper understanding of Bacteroides' role in human health and disease. Our study highlights the necessity for further research to elucidate the intricate relationships between gut microbiota, host immunity, biological sex, and their interplay. This research marks an investigation into how specific microbiota, like Bacteroides, regulate host responses across different gut regions to influence systemic health. By dissecting the impact of Bacteroides across multiple regions of the intestinal tract, this study offers new insights into the localized and whole-body effects of this important immune-programming microbe. Such an understanding is crucial as it helps in unraveling the complex interplay between gut microbes and the host's immune system. This research helps bridge the gap between local intestinal ecology and overall systemic health, addresses important questions relevant to the gut-lung axis, and helps pave the way for innovative therapies.

In this study, the potential protective effects of syringic acid (SA) on gastric tissue were investigated in an indomethacin (INDO)-induced gastric ulcer model. A total of 84 male Sprague-Dawley rats were randomly divided into seven groups. In the in vivo experiments, rats were administered SA at doses of 5, 50, and 100 mg/kg and omeprazole (OMP) at a dose of 5 mg/kg intragastrically (i.g.) for 14 days, and indomethacin (100&#xa0;mg/kg, i.g.) was administered on the final day. Following INDO administration, the rats were sacrificed under anesthesia, and gastric tissues were carefully excised for further analyses. The collected gastric tissues were subjected to biochemical, histopathological, and immunofluorescence analyses. In addition, in silico analyses were performed to support the INDO-induced gastric ulcer model. Using the licensed Schr&#xf6;dinger Maestro 2025/1 software, the binding properties of INDO to the COX-1 receptor were evaluated through molecular docking, MM-GBSA, and pharmacophore matching analyses. INDO administration was associated with oxidative stress, inflammation, apoptosis, and histopathological damage in gastric tissue. SA treatment appeared to alleviate INDO-induced gastric injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. SA treatment ameliorated histopathological alterations in ulcerated areas, particularly at doses of 50 and 100&#xa0;mg/kg, whereas the 5&#xa0;mg/kg dose did not show a significant protective effect. In addition, in silico analyses suggested that INDO may contribute to ulcer formation by inhibiting COX-1, thereby reducing prostaglandin production in the gastric mucosa. Overall, the findings of this study suggest that SA may reduce oxidative stress, suppress inflammatory responses, and inhibit apoptosis, thereby contributing to the protection of gastric tissue against INDO-induced injury. These results indicate that SA may have therapeutic potential for the prevention of NSAID-induced gastric injury; however, further experimental and clinical studies are needed to confirm these effects and clarify the underlying mechanisms.

Recent studies indicate that both sprayed and condensed water droplets can spontaneously generate hydroxyl radicals (&#x2022;OH) via interfacial reactions and contact electrification, leading to the formation of hydrogen peroxide (H2O2). However, their behavior under natural conditions, such as in tiny rain droplets, remains poorly understood. Here, we performed on-site electroanalysis of single rain droplets (5 &#x3bc;L) and demonstrated the spontaneous, catalyst-free formation of detectable H2O2 levels within tiny droplets on natural leaf surfaces. Notably, the amount of H2O2 is influenced by leaf surface topography and hydrophobicity (Rosa vs Buxus leaves as model systems), sunlight exposure versus shade&#x2500;likely due to temperature rather than UV effects&#x2500;and the pH of rain droplets. Using a combined electrode (&#x2248;1.2 mm diameter), we achieved direct electrochemical detection of H2O2 in single droplets with a detection limit of 0.27 ppm (&#x223c;8 &#x3bc;M), complemented by parallel colorimetric assays for validation. Controls excluded UV or photosynthetic interference, and repeated analyses on artificial plastic surfaces and behind glass (blocking UV radiation) confirmed that H2O2 formation originates solely from the droplet interface (&#x223c;5 &#x3bc;L), consistent with previous studies of artificial droplet studies. In contrast, bulk rainwater (0.5 mL) or large droplets showed no detectable oxidants. Importantly, this study focuses not on H2O2 sensing but on revealing natural phenomena and their regulating factors on leaves, as probed by miniaturized sensors and optical kits. These findings reveal previously hidden interfacial chemistry, demonstrating that tiny rain droplets can act not only as cleansing agents but also as natural oxidants, potentially providing protection against microbial contamination and localized biocorrosion, although further studies on natural rain droplets are needed. The results further suggest that similar processes may occur in aerosols, dew, and fog, highlighting the need for further investigation of spontaneous reactive oxygen species formation in natural droplets.

Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for &#x2265;&#x2009;48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was <&#x2009;10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was &#x2265;&#x2009;10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n&#x2009;=&#x2009;85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.