Browse Articles

Impact of antibiotics, iron oxide, and sodium sulfate on microbial community composition in laboratory-built municipal solid waste microcosms

Municipal solid waste (MSW) landfills represent underexplored microbial ecosystems. Landfills contain variable amounts of antibiotic and construction and demolition (C&D) wastes, which have the potential to alter microbial metabolism due to biocidal or redox active components, and these effects are largely underexplored. To circumvent the challenge of MSW heterogeneity, we conducted a 65-day time series study on simulated MSW microcosms to assess microbiome changes using 16S rRNA sequencing in response to 1) Fe(OH)3 and 2) Na2SO4 to represent redox active components of C&D waste as well as 3) antibiotics. The addition of Fe(OH)3 altered the overall community composition and increased Shannon diversity and Chao1 richness. The addition of a mixture of seven antibiotics (1000 ng/L each) altered the community composition without affecting diversity metrics. Sulfate addition had little effect on microbial community composition or diversity. These results suggest that the microbial community composition in fresh MSW may be significantly impacted by influxes of iron waste and a single application of antibiotics.

Publisher's note: “Phase tailoring of silver oxide thin films for improved antimicrobial activity” [J. Appl. Phys. 136, 235301 (2024)]

Automating alloy design and discovery with physics-aware multimodal multiagent AI

The design of new alloys is a multiscale problem that requires a holistic approach that involves retrieving relevant knowledge, applying advanced computational methods, conducting experimental validations, and analyzing the results, a process that is typically slow and reserved for human experts. Machine learning can help accelerate this process, for instance, through the use of deep surrogate models that connect structural and chemical features to material properties, or vice versa. However, existing data-driven models often target specific material objectives, offering limited flexibility to integrate out-of-domain knowledge and cannot adapt to new, unforeseen challenges. Here, we overcome these limitations by leveraging the distinct capabilities of multiple AI agents that collaborate autonomously within a dynamic environment to solve complex materials design tasks. The proposed physics-aware generative AI platform, AtomAgents, synergizes the intelligence of large language models (LLMs) and the dynamic collaboration among AI agents with expertise in various domains, including knowledge retrieval, multimodal data integration, physics-based simulations, and comprehensive results analysis across modalities. The concerted effort of the multiagent system allows for addressing complex materials design problems, as demonstrated by examples that include autonomously designing metallic alloys with enhanced properties compared to their pure counterparts. Our results enable accurate prediction of key characteristics across alloys and highlight the crucial role of solid solution alloying to steer the development of advanced metallic alloys. Our framework enhances the efficiency of complex multiobjective design tasks and opens avenues in fields such as biomedical materials engineering, renewable energy, and environmental sustainability.

Climate change heterogeneity: A new quantitative approach

Climate change is a spatial and temporarily non-uniform phenomenon that requires understanding its evolution to better evaluate its potential societal and economic impact. The value added of this paper lies in introducing a quantitative methodology grounded in the trend analysis of temperature distribution quantiles to analyze climate change heterogeneity (CCH). By converting these quantiles into time series objects, the methodology empowers the definition and measurement of various relevant concepts in climate change analysis (warming, warming typology, warming amplification and warming acceleration) in a straightforward and robust testable linear regression format. It also facilitates the introduction of new testable concepts like warming dominance to compare (globally or partially) the warming process experienced by different regions. Furthermore, the methodology holds the added significance of concurrently encompassing both temporal and spatial dimensions in temperature analysis, owing to the close alignment between unconditional quantiles and latitude measures. Applying our quantitative methodology for the period 1950-2019 to the Globe (2192 stations) and Spain (30 stations) as a benchmark region, we find that both experience a distributional warming process (beyond the standard average) but of very different types. While the Globe experiences a stronger warming in the lower temperatures than in the upper ones, Spain evolves from equal warming in the whole distribution toward a stronger warming in the upper quantiles (similar to the warming process experienced in the African continent). In the two cases, the warming process accelerates (non-linear behavior) over time and is asymmetrically amplified. Overall, although both the Globe and Spain suffer an equivalent warming process in the median (mean) temperature, Spain’s warming dominates the Globe in the upper quantiles and is dominated in the lower tail of the global temperature distribution that corresponds to the Arctic region. Our climate change heterogeneity results open the door to the need for a non-uniform causal-effect climate analysis that goes beyond the standard causality in mean and for a more efficient design of the mitigation-adaptation policies. In particular, the heterogeneity found suggests these policies should contain a common global component and a clear local-regional idiosyncratic element. The latter is usually more straightforward to implement.

Resistive switching and synaptic characteristics in ZnO@β-SiC composite-based RRAM for neuromorphic computing

The advancement of neuromorphic computing in resistive random-access memory (RRAM) is crucial for the rapid expansion of artificial intelligence. Conventional metal oxide-based RRAM faces challenges in mimicking synaptic activity, leading to the exploration of new resistive switching (RS) materials. This study introduces a ZnO@β-SiC composite-based RRAM device that exhibits biological synapse-like functionality. The device shows self-compliance and forming-free RS at ∼0.8 V, where it also mimics synaptic responses such as potentiation, depression, and paired-pulse facilitation at low voltage stimuli (∼0.6 V, 40 ms) with learning and forgetting behavior. Moreover, the synaptic plasticity is analyzed through spike rate dependent plasticity, spike number dependent plasticity, and spike time dependent plasticity. Further, the transition from short-term plasticity to long-term plasticity is observed under more training pulses and lower interval stimuli. The observed RS mechanism and synaptic functionalities are explained by the electric field-driven formation and dissolution of conducting filaments of oxygen vacancies. The chemical properties and local electronic structure have been examined by x-ray photoelectron spectroscopy and x-ray absorption spectroscopy. To elucidate the atomistic memristive behavior and the contribution of different electrical parameters in RRAM, detailed conductive atomic-force microscopy and impedance analysis have been carried out.

Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells

Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.

Publisher's note: “A design technique for transforming statically designed phononic crystals and metamaterials into multifunctional, programmable active acoustic meta-devices” [J. Appl. Phys. 137, 033105 (2025)]

3D ophthalmic ultrasonography at the slit lamp using existing ultrasound systems

Purpose This study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp. Significance Despite ultrasound’s long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp. Methods A custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the system’s applicability. Results The system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the system’s potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the system’s capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions. Conclusions The introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The device’s modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the system’s performance and validate its clinical utility.

Growth and structure of alpha-Ta films for quantum circuit integration

Tantalum films incorporated into superconducting circuits have exhibited low surface losses, resulting in long-lived qubit states. The remaining loss pathways originate in microscopic defects that manifest as two level systems (TLSs) at low temperatures. These defects limit performance, so careful attention to tantalum film structures is critical for optimal use in quantum devices. In this work, we investigate the growth of tantalum using magnetron sputtering on sapphire, Si, and photoresist substrates. In the case of sapphire, we present procedures for the growth of fully-oriented films with α-Ta [1 1 1]//Al2O3 [0 0 0 1] and α-Ta [1 −1 0]//Al2O3 [1 0 −1 0] orientational relationships and having residual resistivity ratio (RRR) ∼ 60 for 220 nm thick films. On Si, we find a complex grain texturing with Ta [1 1 0] normal to the substrate and RRR ∼ 30. We further demonstrate airbridge fabrication using Nb to nucleate α-Ta on photoresist surfaces. For the films on sapphire, resonators show TLS-limited quality factors of 1.3 ± 0.3 × 106 at 10 mK (for a waveguide gap and conductor width of 3 and 6 μm, respectively). Structural characterization using scanning electron microscopy, x-ray diffraction, low temperature transport, secondary ion mass spectrometry, and transmission electron microscopy reveal the dependence of residual impurities and screw dislocation density on processing conditions. The results provide practical insights into the fabrication of advanced superconducting devices including qubit arrays and guide future works on crystallographically deterministic qubit fabrication.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four pathogenic variants of SOX9 identified in a cohort of patients with congenital vertebral malformations. We report a pathogenic missense variant in the transactivation middle (TAM) domain of SOX9 associated with mild skeletal dysplasia and scoliosis. We isolated a Sox9 mutant mouse with an in-frame microdeletion in the TAM domain ( Sox9 Asp272del ), which exhibits skeletal dysplasia including kinked tails, rib cage anomalies, and scoliosis in homozygous mutants. We find that both the human missense and the mouse microdeletion mutations resulted in reduced SOX9 protein stability in cell culture, while Sox9 Asp272del mutant mice show decreased SOX9 expression in the growth plate and annulus fibrosus tissues of the spine. This reduction in SOX9 expression was correlated with the reduction of extracellular matrix components, such as tenascin-X and the Adhesion G-protein coupled receptor ADGRG6. In summary, our work identified and modeled a pathologic variant of SOX9 within the TAM domain and demonstrated its importance for SOX9 protein stability. Our work demonstrates that SOX9 stability is important for the regulation of ADGRG6 expression, which is a known regulator of postnatal spine homeostasis, underscoring the essential role of SOX9 dosage in a spectrum of axial skeleton dysplasia in humans.

Impact of exercise with blood flow restriction on muscle hypertrophy and performance outcomes in men and women

Blood flow restriction training (BFRT) has been previously studied as an alternative form of resistance training to gain lean mass and improve performance outcomes. However, in all exercise studies of BFRT, the proportion of female participants represents only 17–29% of all research participants. This highlights a strong underrepresentation of females and the need for more knowledge on the impact of BFRT and sex differences. The primary objective was to compare the impact of 6-week BFRT on lean mass, strength, and performance outcomes between males and females. A total of 38 adults [age, 25.3 ±  3.1 years; female, n = 19 (50%)] performed whole-body resistance training program with blood flow restriction three times per week. Exercises were performed at 30% of 1-repetition maximum (1-RM) and blood flow restriction cuffs were set to 60% of each individual’s limb occlusion pressure. Body composition was assessed via dual-energy x-ray absorptiometry and strength was measured using 1-RM. A significant increase in lean mass was observed in males (p = 0.009) and females (p = 0.023) with no difference in the change between groups (p = 0.279). Both males and females increased 1-RM for upper- and lower-body exercises, with significant interaction effects (time x sex) for chest press (p = 0.003), seated row (p = 0.038), knee flexion (p = 0.043), and knee extension (p = 0.035), suggesting males increased 1-RM more for these exercises. Furthermore, peak power was improved in males (p < 0.001) and females (p = 0.002) during a vertical squat jump, but a significant interaction (time x sex) effect was observed (p = 0.039), suggesting males increased to a greater extent. Males and females significantly increased lean body mass, to a similar degree, following six weeks of resistance training in combination with blood flow restriction. Likewise, both males and females improved muscle strength following 6-week BFRT, however males may improve strength to a greater extent than females.

Exploring magnetic anisotropy in garnet films at low temperatures using ferromagnetic resonance

Ferromagnetic resonance is widely acknowledged as a robust tool for characterizing magnetic materials and studying physical phenomena. Low-temperature magnonics has recently garnered substantial attention; however, it lacks convenient methods for acquiring key magnetic material characteristics. In this study, we introduce a rapid and universal method to determine the temperature dependence of magnetic anisotropy constants of (111)-oriented garnet films using ferromagnetic resonance measurements, demonstrated specifically on the bismuth-substituted iron garnet film grown on a diamagnetic substrate. Our observations reveal a competitive interplay of different anisotropy types as temperature decreases. Notably, the uniaxial magnetic anisotropy constant Ku undergoes a sign change from negative to positive around 120 K, while the anisotropy type remains consistent.

Diffusive topology preserving manifold distances for single-cell data analysis

Manifold learning techniques have emerged as crucial tools for uncovering latent patterns in high-dimensional single-cell data. However, most existing dimensionality reduction methods primarily rely on 2D visualization, which can distort true data relationships and fail to extract reliable biological information. Here, we present DTNE (diffusive topology neighbor embedding), a dimensionality reduction framework that faithfully approximates manifold distance to enhance cellular relationships and dynamics. DTNE constructs a manifold distance matrix using a modified personalized PageRank algorithm, thereby preserving topological structure while enabling diverse single-cell analyses. This approach facilitates distribution-based cellular relationship analysis, pseudotime inference, and clustering within a unified framework. Extensive benchmarking against mainstream algorithms on diverse datasets demonstrates DTNE’s superior performance in maintaining geodesic distances and revealing significant biological patterns. Our results establish DTNE as a powerful tool for high-dimensional data analysis in uncovering meaningful biological insights.

Impact of media coverage on the transmission dynamics of TB with vaccines and treatment

Tuberculosis (TB) is one of the deadly infectious diseases affecting millions of individuals throughout the world. The main objective of this study is to investigate the impact of media coverage on the transmission dynamics of TB with vaccine and treatment strategy using mathematical model analysis. In the qualitative analysis of the proposed model we proved the existence, uniqueness, positivity, and boundedness of the model solutions, investigated both the disease-free and endemic equilibrium points, computed the basic and effective reproduction numbers using next generation matrix approach, analyzed the stability analysis of the equilibrium points, the backward bifurcation using the Castillo-Chavez and Song theorem and we re-formulated the corresponding optimal control problem and analyzed by applying the Pontryagin’s Minimum Principle. In the model quantitative (numerical) analysis part, we performed the model parameters sensitivity analysis and carried out numerical simulation to verify the qualitative analysis results. The findings of the study indicate that if the reproduction number is less than one, the solution converges to the disease-free state, signifying the asymptotic stability of the TB-free steady state. Moreover, the existence of a backward bifurcation shows that the disease-free equilibrium coexists with one or more endemic equilibria, even when the basic reproduction number is less than 1. Furthermore, it is found that as media efficacy increases, the disease infection rate decreases, which consequently leads to an increase in prevention and treatment control strategies.

Magnetocaloric effect in La1−<i>z</i>Ce<i>z</i>(Fe0.88−<i>y</i>Mn<i>y</i>Si0.12)13 with tunable, low transition temperature in high magnetic fields

Cryogenic magnetic refrigeration becomes more and more important nowadays, especially for the liquefaction of gases such as hydrogen. In this study, we have synthesized La1−zCez(Fe0.88−yMnySi0.12)13 samples and investigated their magnetic and magnetocaloric properties in order to assess their potential for cryogenic applications. By adjusting the Mn and Ce content and adding excess rare-earth elements, the first-order ferromagnetic transition was lowered from 200 to 40 K and the adiabatic temperature change of the samples was measured directly using pulsed magnetic fields. The sample with the lowest transition temperature still showed a significant adiabatic temperature change in magnetic fields up to 10 T, with an increasingly stronger first-order transition observed in samples with higher Ce substitution. In addition, we synthesized spherical powder with diameters between 20 and 120 μm using ultrasonic atomization while maintaining the magnetic transition, which is a promising starting material for future additive manufacturing of magnetocaloric materials.

Representational geometry explains puzzling error distributions in behavioral tasks

Measuring and interpreting errors in behavioral tasks is critical for understanding cognition. Conventional wisdom assumes that encoding/decoding errors for continuous variables in behavioral tasks should naturally have Gaussian distributions, so that deviations from normality in the empirical data indicate the presence of more complex sources of noise. This line of reasoning has been central for prior research on working memory. Here, we reassess this assumption and find that even in ideal observer models with Gaussian encoding noise, the error distribution is generally non-Gaussian, contrary to the commonly held belief. Critically, we find that the shape of the error distribution is determined by the geometrical structure of the encoding manifold via a simple rule. In the case of a high-dimensional geometry, the error distributions naturally exhibit flat tails. Using this insight, we apply our theory to visual short-term memory tasks, and find that it can account for a large array of experimental data with only two free parameters. Our results challenge the dominant view in the mechanisms and capacity constraints of working memory systems. They instead suggest that the Bayesian framework, which explains various aspects of perceptual behavior, also provides an excellent account of working memory. Overall, our results establish a direct connection between neural manifold geometry and behavior, and call attention to the geometry of the representation as a critically important, yet underappreciated factor in determining the character of errors in human behavior.

The importance of method selection when estimating diet composition with quantitative fatty acid signature analysis

Quantitative fatty acid signature analysis (QFASA) is a common method of estimating the composition of prey species in the diets of consumers from polar and temperate ecosystems in which lipids are an important source of energy. A key characteristic of QFASA is that the large number of fatty acids that typically comprise lipids permits the dietary contributions of a correspondingly large number of prey types to be estimated. Several modifications to the original QFASA methods have been suggested in the literature and a significant extension of the original model published in 2017 allows simultaneous estimation of both diet proportions and calibration coefficients, which are metabolic constants in the model whose values must otherwise be estimated in independent feeding experiments. However, comparisons of diet estimates obtained using different estimation options have been limited. QFASA has been used to estimate the diet composition of several polar bear (Ursus maritimus) subpopulations, including the Southern Beaufort Sea (SBS) subpopulation. Prior QFASA estimates of SBS polar bear diet composition have most often been obtained using variations of the original QFASA model. We investigated the influence of variations in QFASA analytical methods on diet estimates by re-estimating the diet composition of polar bears from the Alaska portion of the SBS using three different methods and found that differences among the three sets of estimates were substantial. Our results illustrate how important the careful and deliberate selection of QFASA methods can be and we provide some guidance on techniques one might use to evaluate options.

Cryogenic behavior of high-permittivity gate dielectrics: The impact of atomic layer deposition temperature and the lithographic patterning method

Dielectrics featuring a high relative permittivity, i.e., high-k dielectrics, have become the standard insulators in gate architectures, enhancing the electrical performance of both room temperature and cryogenic electronics. This study delves into the cryogenic (3 K) performance of high-k dielectrics commonly used as gate insulators. We fabricated Al2O3 and HfO2 layers via atomic layer deposition (ALD) and extrapolated relative permittivity (k) and dielectric strength (EBD) from AC (100 Hz–100 kHz) and DC measurements on metal–insulator–metal capacitors. Our findings reveal a strong dependence of HfO2 cryogenic performance on ALD growth temperature, while the latter shows a negligible impact on Al2O3. We estimated ∼9% and ∼14% reductions in the relative permittivities of HfO2 and Al2O3, respectively, at temperatures from 300 to 3 K. Additionally, we designed and fabricated Al2O3/HfO2 bilayers and checked their properties at cryogenic temperatures. The study also investigates the impact of the patterning method, namely, UV or electron-beam lithography (acceleration voltage of 10, 20, or 30 kV), on the high-k dielectric properties.

The <i>Pseudomonas</i> ligninolytic catalytic network reveals the importance of auxiliary enzymes in lignin biocatalysts

Lignin degradation by biocatalysts is a key strategy to develop a plant-based sustainable carbon economy and thus alleviate global climate change. This process involves synergy between ligninases and auxiliary enzymes. However, auxiliary enzymes within secretomes, which are composed of thousands of enzymes, remain enigmatic, although several ligninolytic enzymes have been well characterized. Moreover, it is a challenge to understand synergistic lignin degradation via a diverse array of enzymes, especially in bacterial systems. In this study, the coexpression network of the periplasmic proteome uncovers potential accessory enzymes for B-type dye-decolorizing peroxidases (DypBs) in Pseudomonas putida A514. The catalytic network of the DypBs-based multienzyme complex is characterized. DypBs couple with quinone reductases and nitroreductase to participate in quinone redox cycling. They work with superoxide dismutase to induce Fenton reaction for lignin oxidation. A synthetic enzyme cocktail (SEC), recruiting 15 enzymes, was consequently designed with four functions. It overcomes the limitation of lignin repolymerization, exhibiting a capacity comparable to that of the native periplasmic secretome. Importantly, we reveal the synergistic mechanism of a SEC-A514 cell system, which incorporates the advantages of in vitro enzyme catalysis and in vivo microbial catabolism. Chemical analysis shows that this system significantly reduces the molecular weight of lignin, substantially extends the degradation spectra for lignin functional groups, and efficiently metabolizes lignin derivatives. As a result, 25% of lignin is utilized, and its average molecular weight is reduced by 27%. Our study advances the knowledge of bacterial lignin-degrading multienzymes and provides a viable lignin degradation strategy.

Association between chiropractic spinal manipulation for sciatica and opioid-related adverse events: A retrospective cohort study

Background Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM. Methods We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.) of more than 216 million patients, yielding data ranging from 2009 to 2024. We included patients aged ≥18 years with sciatica, excluding those post-spine surgery, prior anesthesia, serious pathology, high risk of ORADEs, and an ORADE ≤ 1-year prior. Patients were divided into two cohorts: (1) CSM and (2) usual medical care. We used propensity score matching to control for confounding variables associated with ORADEs. Comparative outcomes were analyzed by calculating risk ratios (RRs) and 95% confidence intervals (CIs) for the incidence of ORADEs and oral opioid prescription between cohorts. Results 372,471 patients per cohort remained after matching. The incidence of ORADEs over 1-year follow-up was less in the CSM cohort compared to the usual medical care cohort (CSM: 0.09%; usual medical care: 0.30%), yielding an RR of 0.29 (95% CI: 0.25–0.32; P &lt; .00001). CSM patients had a lower risk of receiving an oral opioid prescription (RR of 0.68 [95% CI: 0.68–0.69; P &lt; .00001]). Conclusions This study found that adults with sciatica who initially received CSM had a lower risk of an ORADE compared to matched controls not initially receiving CSM, likely explained by a lower probability of opioid prescription. These findings corroborate existing practice guidelines which recommend adding CSM to the management of sciatica when appropriately indicated.