Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.

Receptor tyrosine kinase (RTK)-mediated activation of downstream effector pathways such as the RAS GTPase/MAP kinase (MAPK) signaling cascade is thought to occur exclusively from lipid membrane compartments in mammalian cells. Here, we uncover a membraneless, protein granule-based subcellular structure that can organize RTK/RAS/MAPK signaling in cancer. Chimeric (fusion) oncoproteins involving certain RTKs including ALK and RET undergo de novo higher-order assembly into membraneless cytoplasmic protein granules that actively signal. These pathogenic biomolecular condensates locally concentrate the RAS activating complex GRB2/SOS1 and activate RAS in a lipid membrane-independent manner. RTK protein granule formation is critical for oncogenic RAS/MAPK signaling output in these cells. We identify a set of protein granule components and establish structural rules that define the formation of membraneless protein granules by RTK oncoproteins. Our findings reveal membraneless, higher-order cytoplasmic protein assembly as a distinct subcellular platform for organizing oncogenic RTK and RAS signaling.

Polypeptide organic radical batteries.

In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles1, with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous disposal of batteries2. Only a small fraction of lithium-ion batteries are recycled, further exacerbating global material supply of strategic elements3-5. A potential alternative is to use organic-based redox-active materials6-8 to develop rechargeable batteries that originate from ethically sourced, sustainable materials and enable on-demand deconstruction and reconstruction. Making such batteries is challenging because the active materials must be stable during operation but degradable at end of life. Further, the degradation products should be either environmentally benign or recyclable for reconstruction into a new battery. Here we demonstrate a metal-free, polypeptide-based battery, in which viologens and nitroxide radicals are incorporated as redox-active groups along polypeptide backbones to function as anode and cathode materials, respectively. These redox-active polypeptides perform as active materials that are stable during battery operation and subsequently degrade on demand in acidic conditions to generate amino acids, other building blocks and degradation products. Such a polypeptide-based battery is a first step to addressing the need for alternative chemistries for green and sustainable batteries in a future circular economy.

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition.

Double-stranded RNA (dsRNA) is a common by-product of viral infections and acts as a potent trigger of antiviral immunity. In the nematode C. elegans, sid-1 encodes a dsRNA transporter that is highly conserved throughout animal evolution, but the physiological role of SID-1 and its orthologs remains unclear. Here, we show that the mammalian SID-1 ortholog, SIDT2, is required to transport internalized extracellular dsRNA from endocytic compartments into the cytoplasm for immune activation. Sidt2-deficient mice exposed to extracellular dsRNA, encephalomyocarditis virus (EMCV), and herpes simplex virus 1 (HSV-1) show impaired production of antiviral cytokines and-in the case of EMCV and HSV-1-reduced survival. Thus, SIDT2 has retained the dsRNA transport activity of its C. elegans ortholog, and this transport is important for antiviral immunity.

Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Posttranslational Modification as a Critical Determinant of Cytoplasmic Innate Immune Recognition.

Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm. This concept is critical to establish the "guard hypothesis" whereby otherwise homeostatic pathways that keep innate immune sensors at bay are released in response to alterations in their posttranslational modification status. Originally identified in plants, evidence that a similar guardlike mechanism exists in humans has recently been identified, whereby a mutation that prevents phosphorylation of the innate immune sensor pyrin triggers a dominantly inherited autoinflammatory disease. It is also noteworthy that even when a cytoplasmic innate immune sensor has a direct ligand, such as bacterial peptidoglycan (NOD1 or NOD2), RNA (RIG-I or MDA5), or DNA (cGAS or IFI16), it can still be influenced by posttranslational modification to dramatically alter its response. Therefore, due to their existence in the cytoplasmic milieu, posttranslational modification is a key determinant of intracellular innate immune receptor functionality.

Fcg-Former: Identification of Functional Groups in FTIR Spectra Using Enhanced Transformer-Based Model.

Deep learning (DL) is becoming more popular as a useful tool in various scientific domains, especially in chemistry applications. In the infrared spectroscopy field, where identifying functional groups in unknown compounds poses a significant challenge, there is a growing need for innovative approaches to streamline and enhance analysis processes. This study introduces a transformative approach leveraging a DL methodology based on transformer attention models. With a data set containing approximately 8677 spectra, our model utilizes self-attention mechanisms to capture complex spectral features and precisely predict 17 functional groups, outperforming conventional architectures in both functional group prediction accuracy and compound-level precision. The success of our approach underscores the potential of transformer-based methodologies in enhancing spectral analysis techniques.

Storage and Distribution of Organic Carbon and Nutrients in Acidic Soils Developed on Sulfidic Sediments: The Roles of Reactive Iron and Macropores.

In a boreal acidic sulfate-rich subsoil (pH 3-4) developing on sulfidic and organic-rich sediments over the past 70 years, extensive brownish-to-yellowish layers have formed on macropores. Our data reveal that these layers ("macropore surfaces") are strongly enriched in 1 M HCl-extractable reactive iron (2-7% dry weight), largely bound to schwertmannite and 2-line ferrihydrite. These reactive iron phases trap large pools of labile organic matter (OM) and HCl-extractable phosphorus, possibly derived from the cultivated layer. Within soil aggregates, the OM is of a different nature from that on the macropore surfaces but similar to that in the underlying sulfidic sediments (C-horizon). This provides evidence that the sedimentary OM in the bulk subsoil has been largely preserved without significant decomposition and/or fractionation, likely due to physiochemical stabilization by the reactive iron phases that also existed abundantly within the aggregates. These findings not only highlight the important yet underappreciated roles of iron oxyhydroxysulfates in OM/nutrient storage and distribution in acidic sulfate-rich and other similar environments but also suggest that boreal acidic sulfate-rich subsoils and other similar soil systems (existing widely on coastal plains worldwide and being increasingly formed in thawing permafrost) may act as global sinks for OM and nutrients in the short run.

Leadership, regulatory approaches and policy to re-orientate health services towards health promotion.

Globally, oral conditions remain the most prevalent of all non-communicable diseases. Among the broad range of target goals and recommendations for action by the World Health Organization's Global Oral Health Strategy, we call out three specific actions that provide an enabling environment to improve population oral health including: (i) enabling population oral health reform through leadership, (ii) enabling innovative oral health workforce models, (iii) enabling universal health coverage that includes oral health. The aim of the article is to outline how leadership, regulatory approaches and policy in Australia can strengthen health promotion practice and can inform global efforts to tackle the complex wicked problems associated with population oral health. Examples in Australia show that effective leadership, regulatory approaches and well-designed policies can address the growing burden of non-communicable diseases, and are made possible through public health advocacy, collaboration and research.

A policy option towards improving efficiencies in Victorian public oral healthcare.

BACKGROUND: International oral health policy directions led by the World Health Organisation call for the inclusion of oral health within universal health coverage. The aim of this study is to perform a budget impact analysis of a policy option for a more cost-efficient oral health workforce skill-mix (dentists and oral health therapists) to provide public oral healthcare in Victoria, Australia. METHODS: Two hypothetical standard care pathways were developed. A dynamic population Markov model in TreeAge software, with a time horizon of 6 years. Two scenarios were modelled to determine: (1) base-case scenario: the threshold the dentist workforce could reduce per year, while achieving the same service delivery outputs, and (2) alternative scenario: the potential cost-savings for utilising an optimally cost-efficient oral health workforce skill-mix. RESULTS: The threshold analysis showed a minimum reduction of 13% of the dentist workforce being replaced with oral health therapists can occur without having any impact on the same service delivery outputs. Under the alternative scenario, the potential cost-savings would be AUD$1,425,037 (standard deviation 58,954). CONCLUSIONS: Governments and policy-decision makers should consider strategies in training, attracting, and retaining oral health therapists to achieve an optimally cost-efficient oral health workforce skill-mix when delivering public oral healthcare.

A user-friendly deep learning application for accurate lung cancer diagnosis.

BACKGROUND: Accurate diagnosis and subsequent delineated treatment planning require the experience of clinicians in the handling of their case numbers. However, applying deep learning in image processing is useful in creating tools that promise faster high-quality diagnoses, but the accuracy and precision of 3-D image processing from 2-D data may be limited by factors such as superposition of organs, distortion and magnification, and detection of new pathologies. The purpose of this research is to use radiomics and deep learning to develop a tool for lung cancer diagnosis. METHODS: This study applies radiomics and deep learning in the diagnosis of lung cancer to help clinicians accurately analyze the images and thereby provide the appropriate treatment planning. 86 patients were recruited from Bach Mai Hospital, and 1012 patients were collected from an open-source database. First, deep learning has been applied in the process of segmentation by U-NET and cancer classification via the use of the DenseNet model. Second, the radiomics were applied for measuring and calculating diameter, surface area, and volume. Finally, the hardware also was designed by connecting between Arduino Nano and MFRC522 module for reading data from the tag. In addition, the displayed interface was created on a web platform using Python through Streamlit. RESULTS: The applied segmentation model yielded a validation loss of 0.498, a train loss of 0.27, a cancer classification validation loss of 0.78, and a training accuracy of 0.98. The outcomes of the diagnostic capabilities of lung cancer (recognition and classification of lung cancer from chest CT scans) were quite successful. CONCLUSIONS: The model provided means for storing and updating patients' data directly on the interface which allowed the results to be readily available for the health care providers. The developed system will improve clinical communication and information exchange. Moreover, it can manage efforts by generating correlated and coherent summaries of cancer diagnoses.

The Association between Red Blood Cell Distribution Width and Mortality Risk after Hip Fracture: A Meta-Analysis.

Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.

Is smoking a risk factor for complications following total ankle arthroplasty? A meta-analysis.

BACKGROUND: Smoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management. METHODS: A comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO. RESULTS: The analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13-4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12-5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77-1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10-14.13; P = .90) following TAA. CONCLUSIONS: Smoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications.

12th Japan-US Seminar in Plant Pathology Meeting Report.

The 12th iteration of the Japan-US Seminar in Plant Pathology was held in Ithaca, New York at Cornell University in the fall of 2022. Presentations covered a range of topics under the theme "Remodeling of the Plant-Microbe Environment During Disease, Defense, and Mutualism," and the meeting included a panel discussion of best practices in science communication. This report presents highlights of the meeting, from the perspective of early career participants of the seminar. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Burden of Postinfectious Symptoms after Acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.

Monkeypox Virus Infection in 2 Female Travelers Returning to Vietnam from Dubai, United Arab Emirates, 2022.

Mpox was diagnosed in 2 women returning to Vietnam from the United Arab Emirates. The monkeypox viruses belonged to an emerging sublineage, A.2.1, distinct from B.1, which is responsible for the ongoing multicountry outbreak. Women could contribute to mpox transmission, and enhanced genomic surveillance is needed to clarify pathogen evolution.

DECO: a framework for jointly analyzing de novo and rare case/control variants, and biological pathways.

MOTIVATION: Rare variant-based analyses are beginning to identify risk genes for neuropsychiatric disorders and other diseases. However, the identified genes only account for a fraction of predicted causal genes. Recent studies have shown that rare damaging variants are significantly enriched in specific gene-sets. Methods which are able to jointly model rare variants and gene-sets to identify enriched gene-sets and use these enriched gene-sets to prioritize additional risk genes could improve understanding of the genetic architecture of diseases. RESULTS: We propose DECO (Integrated analysis of de novo mutations, rare case/control variants and omics information via gene-sets), an integrated method for rare-variant and gene-set analysis. The method can (i) test the enrichment of gene-sets directly within the statistical model, and (ii) use enriched gene-sets to rank existing genes and prioritize additional risk genes for tested disorders. In simulations, DECO performs better than a homologous method that uses only variant data. To demonstrate the application of the proposed protocol, we have applied this approach to rare-variant datasets of schizophrenia. Compared with a method which only uses variant information, DECO is able to prioritize additional risk genes. AVAILABILITY: DECO can be used to analyze rare-variants and biological pathways or cell types for any disease. The package is available on Github https://github.com/hoangtn/DECO.

Relationship between polygenic risk scores and symptom dimensions of schizophrenia and schizotypy in multiplex families with schizophrenia.

BACKGROUND: Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders. AIMS: To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia. METHOD: The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum. RESULTS: Schizophrenia PRS is significantly associated with the negative/disorganised symptom dimension in participants with a history of a psychotic episode (P = 2.31 × 10-4) and negative dimension in participants without a history of a psychotic episode (P = 1.42 × 10-3). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (P = 3.70 × 10-4). No association with major depressive disorder PRS was observed. CONCLUSIONS: Polygenic liability to schizophrenia is associated with higher negative/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.

Investigation of the functional role of UNC93B1 in Nile tilapia (Oreochromis niloticus): mRNA expression, subcellular localization, and physical interaction with fish-specific TLRs.

Nile tilapia (Oreochromis niloticus) is one of the major food fish worldwide. The farming business, on the other hand, has faced considerable obstacles, such as disease infestations. Toll-like receptors (TLRs) play an important function in the activation of the innate immune system in response to infections. Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing TLRs. Here the UNC93B1 gene, which was cloned from Nile tilapia tissue for this investigation, had the same genetic structure as a homologous gene in humans and mice. Phylogenetic analysis revealed that Nile tilapia UNC93B1 clustered with UNC93B1 from other species and separately from the UNC93A clade. The gene structure of the Nile tilapia UNC93B1 was found to be identical to that of human UNC93B1. Our gene expression studies revealed that Nile tilapia UNC93B1 was highly expressed in the spleen, followed by other immune-related tissues such as the head kidney, gills, and intestine. Moreover, Nile tilapia UNC93B1 mRNA transcripts were up-regulated in vivo in the head kidney and spleen tissues from poly I:C and Streptococcus agalactiae injected Nile tilapia, as well as in vitro in LPS stimulated Tilapia head kidney (THK) cells. The Nile tilapia UNC93B1-GFP protein signal was detected in the cytosol of THK cells and was co-localized with endoplasmic reticulum and lysosome but not with mitochondria. Moreover, the results of a co-immunoprecipitation and immunostaining analysis showed that Nile tilapia UNC93B1 can be pulled down with fish-specific TLRs such as TLR18 and TLR25 from Nile tilapia, and was found to be co-localized with these fish-specific TLRs in the THK cells. Overall, our findings highlight the potential role of UNC93B1 as an accessory protein in fish-specific TLR signaling.

Modeled health economic and equity impact on dental caries and health outcomes from a 20% sugar sweetened beverages tax in Australia.

Dental caries is the most prevalent oral disease across the life course. This study modeled the population health and economic impact of a 20% sugar sweetened beverages tax (SSB) for preventing dental caries compared to no intervention (societal and healthcare perspective). A cost-effectiveness analysis according to quintiles of area-level socioeconomic disadvantage was performed for the 2020 Australian population (0-100 years old) using a closed cohort Markov model. A qualitative assessment of implementation considerations (e.g., acceptability, equity, sustainability) was undertaken. Health outcomes were modeled as decayed teeth prevented and disability-adjusted life years (DALYs) averted. The 10-year and lifetime scenarios were modeled with probabilistic sensitivity analysis (Monte Carlo simulation, 2000 cycles). The 10-year scenario from a societal perspective yielded cost-savings of AUD$63.5M, healthcare cost-savings of AUD$42.2M, 510,977 decayed teeth averted and 98.1 DALYs averted. The lifetime scenario resulted in societal cost savings of AUD$176.6M, healthcare cost-savings of AUD$122.5M, 1,309,211 decayed teeth averted and 254.9 DALYs averted. Modeling indicated 71.5% and 74.5% cost-effectiveness for the 10-year and lifetime scenarios, respectively. A three-fold health benefit for the least advantaged was found compared to the most advantaged. A 20% SSB tax in Australia is cost-effective and promotes health equity.

Associations between pediatric asthma and age at menarche: evidence from the Indonesian Family Life Survey.

OBJECTIVE: To examine the association between pediatric asthma and age at menarche, and to assess whether early life factors modify the association. METHODS: This is a retrospective cross-sectional study using the Indonesian Family Life Survey Fifth Wave which had a total of 11 822 females aged 15-57 years to evaluate whether those with pediatric asthma were associated with earlier menarche, compared to females without asthma. We performed a weighted linear regression model adjusting for age, urbanicity, parental smoking, infectious disease history during childhood, childhood socioeconomic status, and health status during childhood. We also performed analyses by age at asthma diagnosis, interval length between asthma diagnosis and menarche, urbanicity, parental smoking, and infectious disease history during childhood. RESULTS: In the adjusted model, females with pediatric asthma had an earlier average age at menarche by 5.2 months and those diagnosed with asthma at 5-8 years of age had the fastest acceleration by 14.9 months. The significant association persisted among those with 0-5 years interval between asthma diagnosis and menarche, who resided in urban areas, and those without infectious disease history during childhood. CONCLUSIONS: Our findings showed that females with pediatric asthma were associated with an earlier age at menarche, and some early life factors modified the association. Better asthma management with more targeted strategies at those at risk of earlier menarche may improve the reproductive and future health of children with asthma. Future studies to elucidate the mechanisms between pediatric asthma and age at menarche are warranted.