Fracturing flowback plays a vital role in coalbed methane (CBM) reservoir development, but field flowback rates are still commonly selected based on operational experience and are therefore difficult to generalize across wells. To move beyond a field-application description, this study develops a mechanics-based and parameterized framework for estimating the allowable flowback-rate window after hydraulic fracturing. The model incorporates the post-break viscosity of the fracturing fluid and formulates the critical particle-mobilization condition from the force balance acting on coal fines and proppant before and after fracture closure. Instead of calibrating an empirical correlation for a single block, the method uses measurable or literature-constrained inputs, including particle size and density, fluid density and viscosity, fracture pressure differential, wetting-phase saturation, and contact-mechanics coefficients. Field parameters from two CBM wells are used as demonstrative cases to implement the workflow and to examine whether the calculated operating window is consistent with realistic field flowback-rate magnitudes. The calculated critical proppant flowback velocity ranges from 3.6 to 498 m³/day before fracture closure and 36-890 m³/day after closure, while the minimum velocity required to mobilize coal fines increases with particle size. Sensitivity analysis identifies particle radius, post-closure pressure differential, particle density, fluid viscosity, and wetting-phase saturation as the dominant controlling factors. Larger and denser particles increase the required flowback velocity, whereas higher fluid viscosity reduces it by enhancing drag. Capillary forces promote particle mobilization, while friction becomes the primary resisting force after fracture closure. Because no new laboratory flowback experiment is conducted in this work, the model is not claimed to be fully experimentally validated; instead, its reliability is supported by transparent parameterization, literature-constrained coefficients, order-of-magnitude comparison with reported flowback rates, and systematic sensitivity analysis. The proposed workflow provides a transferable screening tool for selecting flowback rates that balance early cleanup efficiency and long-term fracture conductivity in CBM and other propped-fracture operations.
Atypical chemokine receptors (ACKRs) indirectly mediate cell migration through chemokine scavenging, which generally requires phosphorylation by G protein-coupled receptor kinases (GRKs) to efficiently control chemokine levels. Despite not coupling to G proteins, ACKR4 is preferentially modified by GRK3, a kinase dependent on active G protein subunits for membrane translocation and phosphorylation activity. How ACKR4 circumvents G protein dependency to engage GRK3 is unclear. To resolve the underlying mechanism, we used live-cell bioluminescence resonance energy transfer assays to measure GRK3 and phosphorylation-dependent arrestin recruitment and tracked the impact of fluorescent chemokine uptake by flow cytometry. We demonstrate that ACKR4 engages arrestin preferentially downstream of GRK2/3 phosphorylation fully independent of G protein coordination. Instead, the kinases are recruited directly to the atypical receptor via a unique acidic-rich motif in the proximal receptor C terminus. Mutations in this region severely impaired kinase and arrestin recruitment, as well as chemokine scavenging. Productive phosphorylation also plays a substantial role in G protein-independent GRK3 translocation to ACKR4, and recruitment of kinase-dead GRK3 is severely impaired. Together, these findings suggest that ACKR4 directly coordinates GRK3 coupling, highlighting a uniquely evolved atypical mechanism to use GRK2/3 while bypassing G protein activation and thereby supporting efficient chemokine scavenging by the atypical receptor. SIGNIFICANCE STATEMENT: Cell migration and positioning is efficiently regulated by atypical chemokine receptors (ACKR) through chemokine scavenging, often upon GRK phosphorylation. GRK3 dominates the phosphorylation of ACKR4, despite ACKR4 not activating G proteins needed to promote the kinase activity. This study resolved that ACKR4 is directly modified by GRK3 without G protein involvement. Instead, specific acidic residues coordinate the phosphorylation reaction. While seemingly unique to ACKR4, similar mechanisms for GRK2/3 action may contribute to kinase modification of other atypical and canonical GPCRs.
Clinical equipoise-genuine uncertainty within the expert community regarding the relative merits of competing treatments-forms the ethical and scientific foundation of randomized controlled trials. The growing adoption of thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection (uTBAD) has increasingly challenged the principle of clinical equipoise in the treatment algorithm of uTBAD. Optimal medical therapy remains the accepted standard in the treatment of uTBAD. However, the expanding role of TEVAR has led some clinicians and institutions to view early intervention as beneficial, despite the lack of definitive comparative data. Randomized controlled trials, such as INSTEAD, INSTEAD-XL, and ADSORB, have demonstrated that TEVAR promotes false-lumen thrombosis and remodeling, but have not shown a clear survival benefit over optimal medical therapy. Retrospective studies frequently suggest favorable aortic remodeling and improved survival with TEVAR, yet these associative findings cannot establish causality and fall short of the evidentiary strength required to resolve treatment uncertainty. Contemporary guidelines reflect this ambiguity by endorsing aggressive medical therapy with selective TEVAR for anatomically high-risk patients. In the absence of definitive data, practice patterns have been shaped by institutional culture. Persistent uncertainties underscore the need for a definitive randomized trial. These unresolved questions underscore the persistence of clinical equipoise and the ethical necessity for a definitive randomized trial. Equipoise is challenged by institutional culture, specialty bias, referral patterns, patient expectations, and device marketing. Clinical equipoise in uTBAD will be resolved by adequately powered trials demonstrating improvement in patient-centered outcomes. Surrogate measures of aortic remodeling are insufficient.
Noncommunicable diseases (NCDs) account for over 70% of global deaths, with hypertension and diabetes serving as major contributors. The COVID-19 pandemic disrupted traditional health care services for NCDs and highlighted telehealth as a crucial alternative. Telehealth-encompassing synchronous and asynchronous electronic communication to deliver clinical services remotely-can overcome geographical barriers and enhance patient engagement. However, telehealth usability among health care professionals (HCPs) remains under-studied across low-, middle-, and high-income countries. This study aimed to examine which telehealth engagement patterns, technical infrastructure factors, and user profiles were most strongly associated with usability among HCPs and to descriptively compare these across 4 diverse countries: Brazil (high- to middle-income country), Ghana (low- to middle-income country), Honduras (low- to middle-income country), and the United Kingdom (high-income country). A multinational cross-sectional survey was conducted with 290 HCPs across 4 countries. Participants completed the System Usability Scale and provided data on telehealth engagement (eg, frequency, duration, and number of systems used), technical infrastructure (connection stability and support satisfaction), and their user profile (demographics, job role, and training received). Descriptive statistics summarized these patterns and usability scores. Multiple linear regression with bootstrap-based sensitivity analyses identified factors associated with telehealth usability. Given the nonprobability design, no formal inferential comparisons were made between countries. Instead, observed patterns were reported descriptively. Higher telehealth usability scores were associated with greater connection stability (b=5.06, 95% CI 3.06-7.05), higher satisfaction with online support information (b=5.02, 95% CI 3.27-6.75), more frequent use (b=3.05, 95% CI 1.36-4.73), longer duration of use (b=1.59, 95% CI 0.49-2.68), and being a physician by profession (b=3.82, 95% CI 0.23-7.40). Average usability scores were highest among users in Ghana (mean 79.75, SD 14.19) and the United Kingdom (mean 79.00, SD 14.71), followed by Brazil (mean 72.01, SD 14.62) and Honduras (mean 63.09, SD 15.57). According to System Usability Scale guidelines, scores corresponded to "good" usability for users in Ghana, the United Kingdom, and Brazil and were below the "good" threshold for users in Honduras. While most users in Ghana (97/111, 87.4%), Honduras (31/38, 81.6%), and Brazil (57/80, 70.4%) reported using only 1 telehealth system, two-thirds of UK users (40/60, 66.7%) reported using 2 or more systems. User profiles also varied; prepandemic use was highest in Ghana (84/111, 75.7%) and lowest in Honduras (7/38, 18.4%). Other engagement patterns across countries were reported. Telehealth usability is driven by technical infrastructure reliability, a robust online support infrastructure, and an "experience effect" from frequent and long-term engagement. Descriptive differences in engagement patterns and infrastructure highlight the need for tailored strategies to address setting-specific challenges. These are essential to optimize telehealth integration and improve health care outcomes for patients with NCDs worldwide.
Agricultural waste materials can serve as functional constituents in cement-based composites through three pathways: (i) organic bio-aggregates that lower density and alter thermal behavior, (ii) lignocellulosic fibers that control cracking and improve post-cracking resistance, and (iii) agro-ash supplementary cementitious materials (SCMs) that densify pore structure and reduce permeability when ash quality and curing are controlled. This review draws on 98 papers, with coconut shell aggregate and coir/coconut fibers as the core focus; agro-ash SCMs (notably palm oil fuel ash, POFA, and rice husk ash, RHA) enter where they clarify mechanisms or inform hybrid design. Rather than cataloging compressive-strength data, the synthesis is organized around controllable process inputs (feedstock conditioning, mix design, curing) and the interface-governed mechanisms that determine performance: interfacial transition zone (ITZ) character and pore connectivity. In coconut shell systems, density reductions come at a cost: elastic modulus drops and moisture sensitivity rises unless shell conditioning, particle packing, and matrix refinement are managed. In fiber systems, gains in toughness and residual capacity are bounded by mixing workability and by the long-term stability of the fiber-matrix bond under alkaline and wet-dry exposure. A mix must first meet strength, serviceability, and transport requirements before its embodied impact is compared with conventional alternatives. The contribution is to reframe these systems around controllable processing and interface mechanisms instead of tabulated strength values; preparation, treatment, and characterization data are consolidated into bounded design windows, an explicit core versus supporting evidence convention is applied, and sustainability is judged under functional equivalency rather than per-volume carbon.
Lysine β-hydroxybutyrylation (Kbhb) is a β-hydroxybutyrate-derived lysine acylation that connects ketone-body metabolism with chromatin regulation and non-histone protein function. Initially described as a fasting-responsive histone mark, Kbhb is now implicated in immune memory, metabolic adaptation, cancer metabolism and neuroprotection. This Review reframes Kbhb as a context-dependent metabolic acylation system. We discuss the metabolic origin of β-hydroxybutyryl-CoA, the writer, reader and eraser machinery of Kbhb, its crosstalk with acetylation, lactylation and crotonylation, and the evidence standards required to distinguish Kbhb-driven mechanisms from broader β-hydroxybutyrate biology. Recent studies have identified p300/CBP as a Kbhb writer, HDACs and sirtuins as erasers, and ENL as an H3K9bhb reader. Kbhb has also been linked to CD8+ T-cell memory, fasting-responsive chromatin remodeling, tumor metabolic rewiring and non-histone protein regulation. However, shared enzymes, overlapping acylation programs and pleiotropic BHB signaling complicate causal attribution. Kbhb should not be viewed as uniformly beneficial or pathological. Instead, its effects depend on donor availability, site specificity, reader engagement, tissue context, disease stage and competing acylations. Future work should prioritize site-resolved mass spectrometry, validated chromatin profiling, parallel acylome analysis, functional perturbation and clinically interpretable biomarkers to define which Kbhb events are causal and therapeutically actionable.
Oxalate​​ is widely distributed and serves various functional roles in plants. However, its biosynthetic pathway and regulatory mechanisms ​​remain​​ poorly defined. In this study, we further investigated the mechanism of oxalate accumulation using rice (Oryza sativa) CRISPR-Cas9-generated nitrate reductase (NR)​​ and ​​nitrite reductase (NiR)​​ mutants, combined with different treatments. Both NR and NiR mutants exhibited significantly reduced oxalate levels. The reduced oxalate in NR and NiR mutants was restored by nitrite and nitrate, respectively, whereas ammonium had no effect​​, indicating that both nitrate and nitrite reduction, rather than the subsequent ammonium assimilation, are involved in modulating oxalate accumulation in rice. Furthermore, various organic acids, ​​including​​ glycolate, glyoxylate, glycerate, and oxaloacetate, markedly stimulated oxalate content. Transcriptomic and metabolomic analyses revealed that oxalate levels were closely and positively associated with the expression of glycolytic and tricarboxylic acid (TCA) cycle genes and the content of their intermediate metabolites. Treatment with glycolytic intermediates (phosphoenolpyruvate (PEP) and 3-phosphoglycerate (3PGA)) and inhibitors (iodoacetate (IOA)and 3-bromopyruvate (BrPA)) further confirmed that glycolysis drives oxalate synthesis in rice. Nicotinamide (NAM), a NAD precursor, also restored the oxalate content, suggesting that NAD/NADH may play a mediatory role in oxalate regulation through both nitrate and nitrite reduction. Collectively, our results demonstrate that oxalate accumulation is intimately associated with glycolysis in rice, rather than with photorespiration, which instead regulates oxalate accumulation indirectly via the glycerate-mediated​​ impact on glycolysis.​​.
Cell-free DNA can be used for early cancer detection, minimal residual disease monitoring, and post-treatment risk stratification. However, current assays are often designed for a single purpose and rely on deep or broad sequencing panels that capture only a small fraction of tumor-derived signals, limiting transferability, increasing cost, and reducing scalability. Fragmentia-AI is an artificial intelligence language model that learns fragment-level sequence patterns in tumor-derived cell-free DNA. Instead of focusing on mutations, it uses the structure of cell-free DNA to detect cancer signals in a partially panel-agnostic manner from ultra-low sequencing input, approximately 0.1%-1% of conventional depth. The model performs well across cancer types and clinical settings, including monitoring after surgery or immunotherapy, and in samples with low variant allele frequencies or no detected mutations. Fragment-level analyses identify shorter fragments and tumor-derived sequence patterns across panels of different sizes and ultra-low-pass whole-genome sequencing in multiple cohorts.
Course-based Undergraduate Research Experiences (CUREs) provide an accessible, scalable platform for scientific discovery. Here, we present the WormFood CURE, which mines environmental bacterial isolates for bioactive secondary metabolites using Caenorhabditis elegans phenotype suppression as a functional readout. Utilizing the multivulva (Muv) phenotype, our pilot cohort interrogated 41 wild bacterial isolates for suppression of Ras/MAPK signaling. We identified one Bacillus safensis isolate BAC-08 and one Bacillus altitudinis isolate BAC-44 that significantly inhibited ectopic vulval precursor cell (VPC) induction in Muv strains when fed as a live food source. BAC-08 and BAC-44 also significantly affected wild-type nematode development and growth. Metabolic pathway reconstruction from annotated genome assemblies did not support nutritional deficiency as the potential mechanism; instead, we observed that methanol-soluble intracellular extracts from BAC-44 were sufficient to inhibit pseudovulvae growth. We concluded that the observed Muv suppression is likely driven by a secondary metabolite effect. Comparative genomic analysis further identified unique biosynthetic gene clusters (BGCs) present in both BAC-08 and BAC-44 isolates compared to the other isolated Bacillus species. Altogether, our study demonstrates that the WormFood CURE model successfully identifies novel bacterial-genetic interactions, providing a scalable platform for discovery of new natural microbial products that modulate conserved eukaryotic signaling pathways.
Depth of invasion (DOI) is a well-established prognostic factor in oral cavity squamous cell carcinoma (OSCC). Incorporating DOI into the OSCC staging system has substantially refined T-classification and now informs key management decisions in patients with early-stage (T1-T2) disease. In contrast, the prognostic significance of DOI in oropharyngeal squamous cell carcinoma (OPSCC) remains relatively unclear. The aim of this study was to evaluate the prognostic value of DOI in T1-2 OPSCC. A population-based cohort representative of 1033 head and neck squamous cell carcinoma patients was used to identify T1-2 OPSCC patients treated with a curative intent and a tumor sample available for DOI measurement. In this retrospective cohort study of 74 patients, of whom 63.8% (n = 44) were p16-positive, 71.6% (n = 53) had a DOI ≥ 5 mm. While high DOI correlated with heavy alcohol consumption, it did not predict survival outcomes (5-year disease-specific survival HR 1.06; 95% CI 0.94-1.20; p = 0.315) or locoregional metastasis (HR 1.54; 95% CI 0.51-4.63; p = 0.444) in T1-2 tumors of the oropharynx. Instead, within the p16-negative cohort, increased DOI (≥ 5 mm) was associated with an observable tendency toward poorer survival. DOI was not a prognostic factor in p16-positive T1-2 OPSCC. Nevertheless, DOI may hold prognostic relevance for p16-negative disease. The patterns of local invasion and locoregional spread in OPSCC may reflect distinct biological mechanisms compared to those in other head and neck subsites.
The cellular cytosol is a crowded environment. Biomolecular Förster resonance energy transfer (FRET) sensors have been developed to measure crowding in cytosol mimics composed of synthetic polymers such as polyethylene glycol (PEG) and Ficoll that impart an excluded volume effect. We investigate the PEG-driven phase separation of a protein crowding sensor, AcGFP1/mCherry-FRET crowding helix 2 (CrH2), into fluorescent puncta compared to a DNA-based crowding sensor (CrD) with an Alexa488/Cy5 FRET pair that did not form observable puncta under the same crowding conditions of 100-400 mg/mL 8 kDa PEG. Using fluorescence recovery after photobleaching imaging, we uncover the liquid-like physical properties of the PEG-induced puncta. Two-color fluorescence microscopy imaging reveals crowder-induced inhomogeneity, concentration variations, and partition coefficients across the dilute and dense phases of the liquid puncta, which remain largely underexplored in bulk fluorometry measurements. Thus, the average crowding sensor response may originate from an aqueous biphasic system, reporting an erroneous average response instead of distinct levels of crowdedness. A comparison of excluded volume effects conferred by Ficoll and PEGs of various molecular weights shows the influence of size, concentration, excluded volume, and chemical composition on the CrH2 sensor response. We demonstrate that ≥18% PEG (w/v) was sufficient to enable the phase separation of CrH2 and alter sensor response through a mechanism that may be driven by polymer interactions with the flexible hinge region. We also show that CrD can form fluorescence puncta upon charge-neutralization with poly-l-lysine. Thus, our study emphasizes the need to probe crowding environments with orthogonal sensors.
Aging does not occur uniformly throughout an organism but is instead differentially regulated across distinct physiological systems. In particular, reproductive aging is often temporally distinct from somatic aging and exhibits species-specific trajectories, suggesting that different physiological functions may age independently. Here we show that mutation of inx-20, an innexin family gene encoding a gap junction component, markedly extends reproductive span, with only a minor increase in overall lifespan. Furthermore, this extension of reproductive span persists in a feminized genetic background, thereby precluding the possibility that it is driven by altered sperm dynamics. inx-20 is expressed in a specific subset of cells within the alimentary tract, and its expression is selectively repressed in a fraction of these cells during dauer diapause, suggesting a role in nutrient responses. Genetic analyses suggest that inx-20 operates via a distinct mechanism that does not intersect with the TGF-beta and IIS-FOXO pathways, which are established regulators of reproductive span. Collectively, our results suggest that gap junctions in the alimentary tract are a selective determinant of reproductive span, capable of extending it substantially without a commensurate effect on lifespan.
We report an effective nonlinear readout body-coupled modulation strategy that enables electrical amplification of sensitivity in a single p-channel metal-oxide semiconductor (PMOS) field-effect transistor (FET). The threshold voltage exhibits a quadratic dependence on the body potential (VB) by dynamically biasing the body terminal instead of the gate, thus providing an extra electrical amplification from the intrinsic electrochemical surface potential changes. Implemented on a commercial PMOS with a TiN extended electrode here, this architecture achieves apparent VB-amplified sensitivity up to 1200 mV/pH, over twentyfold enhancement, without any additional circuit or process complexity. The p-channel configuration is crucial, as its less body-effect coupling and hole-dominated conduction enhance the interfacial response far beyond its n-type counterpart. The same body-coupled response also amplifies biomolecular recognition signals such as DNA hybridization, suggesting a transistor-level electrical amplification mechanism for chemical and biological sensing possibilities. This work introduces a minimalistic yet powerful approach that transforms conventional p-channel FETs into ultra-sensitive electrochemical transducers, establishing a scalable pathway toward high performance sensors. This is an ultra-low-cost route to achieving controllable high sensitivity, which offers an efficient amplification strategy over conventional approaches in field-effect sensors.
The role of social media in in shaping the public perception of health crises is growing, yet we know little about the contribution of platforms such as YouTube in shaping knowledge regarding child undernutrition. We aimed to explore the digital discussion of and sentiment around YouTube content on child undernutrition in Pakistan, where at least 38% of children are stunted (as per global rankings). We compiled a dataset of 1847 videos and 42 963 comments YouTube users that were uploaded between January 2010 and March 2024. We used Latent Dirichlet Allocation (LDA) topic modelling to analyse this data and identify narrative frames present in the content. We also used the Valence Aware Dictionary for sEntiment Reasoning (VADER) to analyses sentiment in the comments. The analysis reveals six dominant narrative frames, where 'policy failure' made up 32% of the discourse, while just 5% addressed 'solution-focused actions'. The VADER sentiment analysis supports this with a compound score of -0.72, suggesting an overall negative and highlighting considerable public concern about institutional responses. The data further suggests specific engagement patterns that point to a clear break between crisis-oriented and solution-oriented information. Algorithms on digital platforms amplify the narratives that serve as digital determinants of health, shaping public perceptions and reinforcing public distrust in institutional policy responses. It will not be enough to simply 'get the message right' if we seek to create effective health communication - we must, instead, be prepared to actively challenge harmful discourses, champion fair and locally relevant narratives, and engage for algorithmic transparency and public health-centred content curation from these platforms. These results provide an important evidence base for the reframing of nutrition communication initiatives in Pakistan and beyond.
Anti-amyloid monoclonal antibodies have emerged as disease-modifying therapies for Alzheimer's disease. However, their broader clinical adoption is limited by amyloid-related imaging abnormalities, a key safety concern. Traditionally viewed as an unavoidable and dose-dependent adverse effect, amyloid-related imaging abnormalities often lead to treatment interruption or the exclusion of high-risk patients from therapy. Emerging evidence now suggests that amyloid-related imaging abnormalities may instead reflect a transient modifiable cerebrovascular response, primarily influenced by the kinetics of amyloid clearance rather than the absolute magnitude of amyloid removal. Recent data from titration-based dosing strategies demonstrate that gradual amyloid mobilization can significantly reduce the incidence of amyloid-related imaging abnormalities without compromising amyloid positron emission tomography responses or downstream biomarkers. This kinetic perspective may support a more nuanced re-evaluation of patient groups previously deemed unsuitable for therapy, including APOE ε4 carriers, individuals with cerebral microbleeds, and patients on antithrombotic treatment. In this Current Opinion, we propose a pragmatic clinical framework that integrates amyloid clearance kinetics, magnetic resonance imaging-based risk stratification, and individualized protocols for treatment interruption and re-challenge. By reframing amyloid-related imaging abnormalities as a modifiable clinical decision-making challenge rather than an inherent toxicity, anti-amyloid therapies may be optimized for safer use; however, whether such approaches can enable broader and more inclusive treatment strategies remains to be established in prospective studies, particularly in high-risk populations.
Human body form reveals cumulative effects of ecological and socio-cultural factors. China's provides an exceptional context for investigating these multifactorial influences, not only because of its extensive geographic and cultural diversity, but also because recent decades have been marked by rapid economic development, urbanisation, migration, and the population-level trauma of the Great Famine. Using anthropometric data from > 90,000 adults across 213 geo-referenced groups from mid-late-20th and early-21st centuries, we applied Bayesian hierarchical models to assess the roles of climate, altitude, urban-rural status, linguistic affiliation, and time in shaping stature, body mass, relative sitting height, and body breadth. Substantial secular increases in body size, particularly body mass, were associated with recent economic development and urbanisation. Males and females responded similarly across environmental and temporal gradients, indicating limited sex-based differentiation. Northern groups remained taller and heavier than their southern counterparts. Notably, maximum precipitation, not temperature, emerged as the strongest climatic correlate, likely reflecting indirect effects of subsistence and disease burden. Relative sitting height increased modestly over time, while relative body breadth showed a stable east-west gradient, potentially shaped by population history. Regional exceptions, including highland Tibetan and Sherpa populations and northeastern groups, along with widening divergence among linguistic subgroups, underscore the persistent roles of migration, developmental constraints and potential high-altitude adaptation. These findings show that recent changes in human body form in China cannot be understood as simple outcomes of modernisation alone, but instead reflect layered interactions among ecology, population history, socio-economic transformation, and cohort-specific historical experience.
Particulate matter (PM) pollution remains a critical environmental and health issue. This study applies seven classical probability distribution functions (PDFs) alongside Gaussian mixture models (GMMs) to hourly PM10 concentration data collected in 2021 at an urban-traffic site (RasteKuche) and an industrial site (Rahahan). Model fitting using maximum likelihood estimation and evaluation via the Kolmogorov - Smirnov test and Akaike information criterion highlight distinct site-specific behaviours. At the urban site, seasonal variability is well captured by Gumbel, log-normal, and gamma distributions, with winter exhibiting the highest PM10 exceedance probability (0.51) and a short average return period of 1.94 hours, indicating frequent exceedance of the WHO interim target of 50 μg/m3. Achieving compliance during winter would necessitate emission reductions over 64%. In contrast, the industrial site exhibits complex, multimodal PM10 distributions poorly represented by classical PDFs; instead, 4- to 5-component GMMs capture these patterns effectively. Seasonal exceedance probabilities at this site peak in spring (0.23) and summer (0.22), requiring moderate emission reductions (up to 37%). These findings emphasize the urgency of seasonally tailored emission control strategies and demonstrate the utility of GMMs for risk assessment in heterogeneous industrial environments. This integrated probabilistic framework provides robust, locally calibrated benchmarks for air quality management in Tabriz.
Real-time binaural beat synthesis in dynamic acoustic environments is challenged by carrier non-stationarity, interaural phase discontinuities, and processing delay in conventional digital signal processing pipelines. This study proposes a predictive dual-stage neural framework for phase-coherent auditory synthesis under non-stationary acoustic conditions. The framework decouples real-time carrier estimation from phase-coherent signal generation through two specialized modules. An intelligent acoustic sensing module (AI-1) estimates time-varying carrier information across harmonic, fluctuating, and broadband acoustic profiles using a causal neural front-end with an adaptive confidence-driven strategy. A predictive phase-coherent generator (AI-2) then forecasts short-horizon carrier trajectories and drives a discrete-time phase accumulator to maintain continuous phase evolution during binaural beat embedding. Objective evaluation under multiple acoustic profiles and noise conditions shows that the proposed framework maintains strong phase continuity, with a Phase Coherence Factor greater than 0.91, and low artifact levels, with a Signal-to-Artifact Ratio greater than 39.8 dB, under the evaluated conditions. Additional comparisons with conventional DSP baselines, stronger classical F0 estimators, a lightweight neural F0 tracker, and component-wise ablation variants further demonstrate that the performance improvement arises from the combination of adaptive carrier estimation and predictive phase-coherent actuation, rather than from carrier estimation alone. Hardware profiling shows a combined INT8 inference time of 2.4 ms per frame on a resource-constrained Raspberry Pi Zero 2W-class edge device. Importantly, this inference time and the sub-millisecond phase-accumulator resolution should not be interpreted as sub-millisecond end-to-end physical audio latency. The complete system still includes buffering, framing, neural inference, and output processing delay; the proposed method instead reduces effective phase-boundary misalignment through short-horizon predictive compensation. These results support the proposed framework as a lightweight engineering solution for real-time phase-continuous auditory synthesis in dynamic listening environments. The reported PCF and SAR values should be interpreted as signal-level indicators of phase continuity and artifact suppression, rather than as evidence of listener comfort, perceptual preference, or neurophysiological efficacy.
Array Gm-APD LiDAR is highly vulnerable to strong backscattering caused by dynamic smoke. Conventional depth imaging methods cannot rapidly identify the smoke occlusion state, which greatly reduces the target recovery quality of the reconstructed depth image. To solve this problem, this paper presents a non-parametric algorithm for rapid smoke detection and depth imaging for array Gm-APD LiDAR. The proposed method does not rely on parameter estimation of the echo model. Instead, it determines the presence of smoke occlusion by calculating the Pearson correlation coefficient between the echo signal obtained from the superposition of all array pixels and the instrument response function. In this way, the method rapidly identifies smoke interference in a single depth image, performs fast denoising, and reconstructs the depth image. In a dynamic smoke environment with an average attenuation length of no more than 5.1, the proposed algorithm achieves 100% accuracy in occlusion discrimination based on 250 frames of array data. When the smoke occlusion rate reaches 96% and the average attenuation length is 2.29, the method obtains a target recovery of 0.71, which is 86.8% higher than that of the conventional algorithm. These results indicate that the proposed method has strong practical value for array Gm-APD LiDAR, especially for high-speed depth imaging in harsh atmospheric environments with severe obscuration.
Celiac disease (CeD) requires lifelong adherence to a strict gluten-free (GF) diet. During the COVID-19 pandemic, the prevailing clinical assumption was that food supply disruptions and dietary management difficulties would be the primary sources of patient distress. This exploratory cross-sectional study directly tested this assumption in an Italian CeD cohort. COVIMPACT is an exploratory observational, web-based study conducted in Italy (data collected: July-September 2024; participants retrospectively reported their experiences during the COVID-19 pandemic period 2020-2022). Participants with a confirmed CeD diagnosis were recruited through patient associations and online networks. A structured 26-item questionnaire addressed socio-demographic, nutritional, psychological, and healthcare-access domains. Descriptive statistics, chi-square bivariate analyses (Cramér's V as effect size), and binary logistic regression were performed using R (v4.1) and Python. Among 118 participants (78% female; median age 36 years; IQR 12-42), 27% reported self-perceived psychological distress. Against expectation, difficulties in accessing GF products and changes in gluten consumption showed no clear associations with distress. Instead, social exclusion showed the strongest association (Firth OR = 5.55, 95% CI: 1.80-17.09, p = 0.003), while reduced physical activity (Firth OR = 5.28, 95% CI: 1.86-14.99, p = 0.002, full model; Firth OR = 5.54, p = 0.001, reduced model) and negative economic impact (Firth OR = 3.77, 95% CI: 0.89-15.97, p = 0.071, trend) were additional associated factors. Female sex showed a non-significant trend (Firth OR = 4.21, p = 0.082). All estimates carry wide confidence intervals (EPV = 4.1) and should be treated as hypothesis-generating. These preliminary findings suggest that social exclusion and physical inactivity may be more strongly associated with self-perceived distress than dietary challenges in contexts where GF food access is structurally protected. Results are exploratory, hypothesis-generating, and should not be generalised beyond this selected Italian cohort.