Heterogeneous Characteristics of the CD90+ Progenitors in the Fibrocartilage of Different Joints.

OBJECTIVE: This study aimed to isolate and compare the mesenchymal stem cell characteristics of CD90+ cells from different fibrocartilage tissues in the temporomandibular joint (TMJ), the knee joint, and the intervertebral joint to further understand the similarities and differences of these 4 fibrocartilage tissues. METHODS: CD90+ cells were isolated from TMJ disc, condylar cartilage, meniscus, and intervertebral disc by using magnetic-activated cell sorting. Cellular assays including 4.5-ethynyl-2'-deoxyuridine labeling, multilineage differentiation, colony formation, and cell migration were conducted to compare their mesenchymal stem cell characteristics. Immunofluorescent staining was performed for observing the expression of actively proliferating CD90+ cells within the tissues. H&E staining and Safranine O staining were used to compare the histological features. RESULTS: The CD90+ cells derived from these 4 fibrocartilage tissues exhibited comparable cell proliferation abilities. However, the cells from the TMJ disc displayed limited multilineage differentiation potential, colony formation, and cell migration abilities in comparison with the cells from the other fibrocartilage tissues. In vivo, there was relatively more abundant expression of CD90+ cells in the TMJ disc during the early postnatal stage. The limited EDU+ cell numbers signified a low proliferation capacity of CD90+ cells in the TMJ disc. In addition, we observed a significant decrease in cell density and a restriction in the synthesis of extracellular proteoglycans in the TMJ disc. CONCLUSION: Our study highlights the spatial heterogeneity of CD90+ cells in the fibrocartilages of different joint tissues, which may contribute to the limited cartilage repair capacity in the TMJ disc.

Divergent chondro/osteogenic transduction laws of fibrocartilage stem cell drive temporomandibular joint osteoarthritis in growing mice.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER+; Tmfl/-mice and Sox9-CreER+;Tmfl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1+ FCSCs as well as osteogenic differentiation of Sox9+ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.

VEGF-modified PLA/HA nanocomposite fibrous membrane for cranial defect repair in rats.

A major obstacle to bone tissue repair is the difficulty in establishing a rapid blood supply areas of bone defects. Vascular endothelial growth factor (VEGF)-infused tissue-engineered scaffolds offer a possible therapeutic option for these types of injuries. Their role is to accelerate angiogenesis and improve bone healing. In this study, we used electrostatic spinning and biofactor binding to construct polylactic acid (PLA)/hydroxyapatite (HA)-VEGF scaffold materials and clarify their pro-vascular role in bone defect areas for efficient bone defect repair. PLA/HA nanocomposite fibrous membranes were manufactured by selecting suitable electrostatic spinning parameters. Heparin and VEGF were bound sequentially, and then the VEGF binding and release curves of the fiber membranes were calculated. A rat cranial defect model was constructed, and PLA/HA fiber membranes bound with VEGF and unbound with VEGF were placed for treatment. Finally, we compared bone volume recovery and vascular recovery in different fibrous membrane sites. A VEGF concentration of 2.5 µg/mL achieved the maximum binding and uniform distribution of PLA/HA fibrous membranes. Extended-release experiments showed that VEGF release essentially peaked at 14 days. In vivo studies showed that PLA/HA fibrous membranes bound with VEGF significantly increased the number of vessels at the site of cranial defects, bone mineral density, bone mineral content, bone bulk density, trabecular separation, trabecular thickness, and the number of trabeculae at the site of defects in rats compared with PLA/HA fibrous membranes not bound with VEGF. VEGF-bound PLA/HA fibrous membranes demonstrate the slow release of VEGF. The VEGF binding process does not disrupt the morphology and structure of the fibrous membranes. The fibrous membranes could stimulate both osteogenesis and angiogenesis. Taken together, this research provides a new strategy for critical-sized bone defects repairing.

A retrospective three-dimensional study of the mandibular growth during preoperative orthodontics in late adolescent patients with skeletal Class III malocclusion.

INTRODUCTION: The mandible's ongoing development presents a contraindication for combined orthodontic-orthognathic treatment. The aim of this study was to evaluate the mandibular stability before and after preoperative orthodontic treatment in late adolescent patients with skeletal Class III malocclusion and to investigate the most appropriate time to start preoperative orthodontic treatment. MATERIAL AND METHODS: The study population consisted of 58 adolescents, aged between 15 and 21 years, with skeletal Class III malocclusion; the adolescents underwent CT scans at the beginning (T1) and the end (T2) of preoperative orthodontic treatment. The CT data were analyzed using ITK-SNAP and 3D Slicer software, and the effects of age and gender on mandibular development were investigated. RESULTS: In these 58 patients, there were no significant local bone alterations in the condyle and anterior chin point between T1 and T2 and no significant changes in the mandibular branch height, mandibular body length, condylar distance, and mandibular angle distance (p>0.05). The mandibular growth at the angel of mandible was statistically significant (p<0.05), but it was not clinically significant because the mean value of the growth was small (right: 0.416±0.986 mm, left: 0.328±0.886 mm). No effect of age and gender on mandibular development was observed. CONCLUSION: The mandibular morphology was stable during preoperative orthodontic treatment in patients at the late adolescent stage. This study provides evidence for the possibility of early implementation of preoperative orthodontics.

Quality evaluation of metabolic and bariatric surgical guidelines.

Objective: To evaluate the quality of surgical guidelines on bariatric/metabolic surgery. Methods: Four independent reviewers used the AGREE II (The Appraisal of Guidelines for Research and Evaluation II) tool to assess the methodological quality of the included guidelines and conducted a comparative analysis of the main recommendations for surgical methods of these guidelines. Results: Nine surgical guidelines were included in this study. Five articles with AGREE II scores over 60% are worthy of clinical recommendation. The field of rigor of development was relatively low, with an average score of 50.82%. Among 15 key recommendations and the corresponding best evidence in the guidelines, only 4 key recommendations were grade A recommendations. Conclusions: The quality of metabolic and bariatric guidelines is uneven, and there is much room for improvement.

Igf1 Regulates Fibrocartilage Stem Cells, Cartilage Growth, and Homeostasis in the Temporomandibular Joint of Mice.

Temporomandibular joint (TMJ) growth requires orchestrated interactions between various cell types. Recent studies revealed that fibrocartilage stem cells (FCSCs) in the TMJ cartilage play critical roles as cell resources for joint development and repair. However, the detailed molecular network that influences FCSC fate during TMJ cartilage development remains to be elucidated. Here, we investigate the functional role of Igf1 in FCSCs for TMJ cartilage growth and homeostasis by lineage tracing using Gli1-CreER+ ; Tmflfl mice and conditional Igf1 deletion using Gli1-/Col2-CreER+ ; Igf1fl/fl mice. In Gli1-CreER+ ; Tmflfl mice, red fluorescence+ (RFP+ ) FCSCs show a favorable proliferative capacity. Igf1 deletion in Gli1+ /Col2+ cell lineages leads to distinct pathological changes in TMJ cartilage. More serious cartilage thickness and cell density reductions are found in the superficial layers in Gli1-CreER+ ; Igf1fl/fl mice. After long-term Igf1 deletion, a severe disordered cell arrangement is found in both groups. When Igf1 is conditionally deleted in vivo, the red fluorescent protein-labeled Gli1+ FCSC shows a significant disruption of chondrogenic differentiation, cell proliferation, and apoptosis leading to TMJ cartilage disarrangement and subchondral bone loss. Immunostaining shows that pAkt signaling is blocked in all cartilage layers after the Gli1+ -specific deletion of Igf1. In vitro, Igf1 deletion disrupts FCSC capacities, including proliferation and chondrogenesis. Moreover, the deletion of Igf1 in FCSCs significantly aggravates the joint osteoarthritis phenotype in the unilateral anterior crossbite mouse model, characterized by decreased cartilage thickness and cell numbers as well as a loss of extracellular matrix secretions. These findings uncover Igf1 as a regulator of TMJ cartilage growth and repair. The deletion of Igf1 disrupts the progenitor capacity of FCSCs, leading to a disordered cell distribution and exaggerating TMJ cartilage dysfunction. © 2023 American Society for Bone and Mineral Research (ASBMR).

A single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury.

The biological characteristics of the temporomandibular joint disc involve complex cellular network in cell identity and extracellular matrix composition to modulate jaw function. The lack of a detailed characterization of the network severely limits the development of targeted therapies for temporomandibular joint-related diseases. Here we profiled single-cell transcriptomes of disc cells from mice at different postnatal stages, finding that the fibroblast population could be divided into chondrogenic and non-chondrogenic clusters. We also find that the resident mural cell population is the source of disc progenitors, characterized by ubiquitously active expression of the NOTCH3 and THY1 pathways. Lineage tracing reveals that Myh11+ mural cells coordinate angiogenesis during disc injury but lost their progenitor characteristics and ultimately become Sfrp2+ non-chondrogenic fibroblasts instead of Chad+ chondrogenic fibroblasts. Overall, we reveal multiple insights into the coordinated development of disc cells and are the first to describe the resident mural cell progenitor during disc injury.

Random and aligned electrostatically spun PLLA nanofibrous membranes enhance bone repair in mouse femur midshaft defects.

Long-segment bone defects are a common clinical challenge and abstract biomaterials are a promising therapy. Poly-L-lactic acid (PLLA) nanofibrous membranes prepared by electrostatic spinning have a good bone repair potential. However, there are random and aligned surface morphologies of electrostatic spun PLLA nanofibrous membranes, which can affect the migration, proliferation, and differentiation ability of cells. The role of surface morphology in the repair of long bone defects in vivo is currently unknown. In this study, random and aligned electrostatically spun PLLA nanofibrous membranes were prepared, characterised, and implanted into a femur midshaft defect mouse model. The ability of electrostatically spun PLLA nanofibrous membranes to enhance bone repair was tested using X-ray photography, high-resolution micro-computed tomography (micro-CT), and pathological section specimens. The results showed that both random and aligned electrostatically spun PLLA nanofibrous membranes enhanced bone regeneration at bone defects, but the aligned ones exhibited superior results. These results provide a theoretical basis for engineering the surface morphology of bone repair materials.

Oscillatory Order-Disorder Transition during Layer-by-Layer Growth of Indium Selenide.

It is important to understand the polymorph transition and crystal-amorphous phase transition in In2Se3 to tap the potential of this material for resistive memory storage. By monitoring layer-by-layer growth of ß-In2Se3 during molecular beam epitaxy (MBE), we are able to identify a cyclical order-disorder transition characterized by a periodic alternation between a glassy-like metastable subunit cell film consisting of n < 5 sublayers (nth layers = the number of subunit cell layers), and a highly crystalline ß-In2Se3 at n = 5 layers. The glassy phase shows an odd-even alternation between the indium-cluster layer (n = 1, 3) and an In-Se solid solution (n = 2, 4), which suggests the ability of In and Se atoms to diffuse, aggregate, and intermix. These dynamic natures of In and Se atoms contribute to a defect-driven memory resistive behavior in current-voltage sweeps that is different from the ferroelectric switching of α-In2Se3.

Regulatory role of human fibrocartilage stem cells in condyle osteochondroma.

OBJECTIVE: Osteochondroma is a common benign skeletal disorder for which different molecular and histological features of long bones have been reported. We investigated cell-of-origin and molecular mechanisms of a rare condylar osteochondroma (CO). METHODS: Human fibrocartilage stem cells (hFCSCs) isolated from CO and normal condyle tissue were used for RNA sequencing, real-time PCR, Western Blotting, immunohistology, flowcytometry, as well as for chondrogenic differentiation, proliferation, and apoptosis detection assays. RESULTS: HFCSCs were fewer in number with weaker proliferative capacity and higher apoptosis ratio in the CO group. During the chondrogenic inducing process, hFCSCs from CO were prone to form more mature and hypertrophic cartilage. The result of RNA sequencing of hFCSCs from CO and normal condyle revealed a correlation between the PI3K/AKT signalling pathway and CO. Activated PI3K/AKT signalling might lead to functional changes in hFCSCs by enhancing cell apoptosis in the developmental process of CO. Increased expression of BCL2-like protein 11 (BIM) in CO tissue also supports this conclusion. Furthermore, the activation of the PI3K/AKT pathway in TMJ of mice induced histological disorder and increased apoptosis in condylar cartilage. CONCLUSION: We conclude that the activation of PI3K/AKT signalling in hFCSCs of CO suggests a new hypothesis for the cell-of-origin of human CO and another possible target to treat it.

Learning Optimal Time-Frequency-Spatial Features by the CiSSA-CSP Method for Motor Imagery EEG Classification.

The common spatial pattern (CSP) is a popular method in feature extraction for motor imagery (MI) electroencephalogram (EEG) classification in brain-computer interface (BCI) systems. However, combining temporal and spectral information in the CSP-based spatial features is still a challenging issue, which greatly affects the performance of MI-based BCI systems. Here, we propose a novel circulant singular spectrum analysis embedded CSP (CiSSA-CSP) method for learning the optimal time-frequency-spatial features to improve the MI classification accuracy. Specifically, raw EEG data are first segmented into multiple time segments and spectrum-specific sub-bands are further derived by CiSSA from each time segment in a set of non-overlapping filter bands. CSP features extracted from all time-frequency segments contain more sufficient time-frequency-spatial information. An experimental study was implemented on the publicly available EEG dataset (BCI Competition III dataset IVa) and a self-collected experimental EEG dataset to validate the effectiveness of the CiSSA-CSP method. Experimental results demonstrate that discriminative and robust features are extracted effectively. Compared with several state-of-the-art methods, the proposed method exhibited optimal accuracies of 96.6% and 95.2% on the public and experimental datasets, respectively, which confirms that it is a promising method for improving the performance of MI-based BCIs.

Giant g-factor in Self-Intercalated 2D TaS2.

Central to the application of spintronic devices is the ability to manipulate spins by electric and magnetic fields, which relies on a large Landé g-factor. The self-intercalation of layered transitional metal dichalcogenides with native metal atoms can serve as a new strategy to enhance the g-factor by inducing ferromagnetic instability in the system via interlayer charge transfer. Here, scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) are performed to extract the g-factor and characterize the electronic structure of the self-intercalated phase of 2H-TaS2 . In Ta7 S12 , a sharp density of states (DOS) peak due to the Ta intercalant appears at the Fermi level, which satisfies the Stoner criteria for spontaneous ferromagnetism, leading to spin split states. The DOS peak shows sensitivity to magnetic field up to 1.85 mV T-1 , equivalent to an effective g-factor of ≈77. This work establishes self-intercalation as an approach for tuning the g-factor.

Platelet-rich plasma contributes to chondroprotection by repairing mitochondrial function via AMPK/NF-κB signaling in osteoarthritic chondrocytes.

Osteoarthritis (OA), also known as degenerative osteoarthritis, has a complex etiology, and its pathogenesis remains unclear. Platelet-rich plasma (PRP) therapy has been widely used in medicine and other related professions since its clinical application was first reported in the 1980 s and the 1990 s. This study aimed to investigate the effects and potential mechanisms of PRP in OA. An in vitro model of osteoarthritis was constructed by lipopolysaccharide (LPS) stimulation, and the effect of PRP on LPS-induced chondrocytes was evaluated. The results indicated that although LPS inhibited chondrocyte proliferation and promoted inflammation and apoptosis, these effects were reversed by PRP. In addition, the LPS-suppressed expression of aggrecan, TGF-ß, PDGF, and COL2A1 was restored by PRP, whereas the LPS-enhanced expression of MMP3 was suppressed by PRP. Furthermore, PRP inhibited LPS-induced mitochondrial damage by suppressing reactive oxygen species production, mitochondrial permeability transition pore opening, Drp1 expression, and upregulating Mfn1 expression. In addition, PRP inhibited the phosphorylation of AMPK and NF-κB. Collectively, this study indicates that PRP might be a potential therapeutic candidate for the treatment of OA by repairing mitochondrial function through the activation of AMPK/NF-κB signaling.

Electroacupuncture regulates inflammation, collagen deposition and macrophage function in skeletal muscle through the TGF-ß1/Smad3/p38/ERK1/2 pathway.

Skeletal muscle injury is one of the most common sports injury, which accounts for ~40% of all sports-related injuries among the elderly. In addition, cases of full recovery from treatment are rare. Although electroacupuncture (EA) is an integral aspect of traditional Chinese medicine, the effects of EA on skeletal muscle fibrosis and the possible underlying mechanism remain unclear. To investigate the effect and potential mechanism of EA on skeletal inflammation, collagen deposition and macrophage function, a skeletal muscle injury model was established by injecting 100 µl cardiotoxin into the anterior tibial muscle of Sprague Dawley rats. The animals were randomly divided into the following three groups: Control, model and EA. The expression of inflammation-related factors (IL-6, IL-4, IL-33, IL-10 and TNF-α) were measured using ELISA. H&E staining, Masson's staining and immunohistochemistry (collagen II, Axin2 and ß-catenin) were performed to assess collagen deposition and fibrosis in the muscle tissues. Additionally, immunofluorescence was performed to measure the ratio of M1 to M2 macrophages. Western blotting was performed to examine the activity of the TGF-ß1/Smad3/p38/ERK1/2 pathway. Compared with that in the control rats, the mental state, such as the degree of activity and excitement, of the model rats deteriorated, with clear activity limitations. Compared with those in the model rats, EA-treated rats exhibited improved mental status and activity, reduced levels of IL-6, IL-4 and TNF-α, reduced collagen deposition and fibrosis, in addition to increased expression of IL-33 and IL-10. This improvement became increasingly evident with prolonged intervention time. EA also promoted the transformation of macrophages from the M1 into the M2 sub-type, where the M1/M2 ratio on day 7 was lower compared with that on day 14. Western blotting results showed that compared with that in the model rats, the expression of TGF-ß1, MMP-2, MMP-7 and the activation of Smad3 and p38 was decreased in EA-treated rats, whilst the activation of ERK1/2 was significantly elevated. In conclusion, EA can inhibit inflammation and collagen deposition whilst promoting the transformation of macrophages from the M1 into the M2 sub-type. The underlying mechanism was found to be associated with TGF-ß1/Smad3/p38/ERK1/2 signaling.

Iron Single Atom Catalyzed Quinoline Synthesis.

The production of high-value chemicals by single-atom catalysis is an attractive proposition for industry owing to its remarkable selectivity. Successful demonstrations to date are mostly based on gas-phase reactions, and reports on liquid-phase catalysis are relatively sparse owing to the insufficient activation of reactants by single-atom catalysts (SACs), as well as, their instability in solution. Here, mechanically strong, hierarchically porous carbon plates are developed for the immobilization of SACs to enhance catalytic activity and stability. The carbon-based SACs exhibit excellent activity and selectivity (≈68%) for the synthesis of substituted quinolines by a three-component oxidative cyclization, affording a wide assortment of quinolines (23 examples) from anilines and acetophenones feedstock in an efficient, atom-economical manner. Particularly, a Cavosonstat derivative can be synthesized through a one-step, Fe1 -catalyzed cyclization instead of traditional Suzuki coupling. The strategy is also applicable to the deuteration of quinolines at the fourth position, which is challenging by conventional methods. The synthetic utility of the carbon-based SAC, together with its reusability and scalability, renders it promising for industrial scale catalysis.

Atomic Imaging of Electrically Switchable Striped Domains in ß'-In2 Se3.

2D ferroelectricity in van-der-Waals-stacked materials such as indium selenide (In2 Se3 ) has attracted interests because the ferroelectricity is robust even in ultrathin layers, which is useful for the miniaturization of ferroelectric field effect transistors. To implement In2 Se3 in nanoscale ferroelectric devices, an understanding of the domain structure and switching dynamics in the 2D limit is essential. In this study, a biased scanning tunnelling microscopy (STM) tip is used to locally switch polarized domains in ß'-In2 Se3 , and the reconfiguration of these domains are directly visualized using STM. The room-temperature surface of ß'-In2 Se3 breaks into 1D nanostriped domains, which changes into a zig-zag striped domains of ß″ phase at low temperatures. These two types of domains can coexist, and by applying a tip-sample bias, they can be interchangeably switched locally, showing volatile or nonvolatile like behavior depending on the threshold voltage applied. An atomic model is proposed to explain the switching mechanism based on tip-induced flexoelectric effect and the ferroelastic switching between ß' and ß″ phases.

Structural characterization and immunomodulatory activity of a polysaccharide from Eurotium cristatum.

By combining DEAE-cellulose-52 and Sepharose-CL-6B chromatography, a heteropolysaccharide ECIP-1A with an average molecular weight of 24,336 Da was isolated from the hyphae of Eurotium cristatum. The main components of the monosaccharides of ECIP-1A were mannose, glucose and galactose, and their molar ratio is 4.003: 0.592: 4.58. Analysis of the immunomodulatory activity showed that ECIP-1A could significantly promote the proliferation of RAW264.7 cells and induce the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) by RAW264.7 cells. The results therefore suggested that ECIP-1A, as an immunomodulator, may have potential application prospects in the food and pharmaceutical industries.

Transformation of ginsenoside via deep eutectic solvents based on choline chloride as an enzymatic reaction medium.

Ginsenoside compound K (CK) with a wide range of pharmacological activities has been widely used in the healthcare product industry. However, the application of CK is limited by low productivity and difficult separation. The purpose of this study is to convert ginsenoside Rb1 into CK by improving conversion efficiency in novel "green" reaction medium-deep eutectic solvent (DES). Talaromyces purpureogenus was selected from ginseng rhizosphere soil to produce ß-glucosidase with high activity and purity to transform ginsenosides, and Mn2+ was found to be an enzyme promoter. Among the DES based on choline chloride as hydrogen-bond receptor, choline chloride:ethylene glycol (ChCl:EG = 2:1) was the most promising solvent in maintaining enzyme activity and stability. In the presence of 30% v/v ChCl:EG = 2:1, the half-life of ß-glucosidase was increased by 96%, the solubility of F2 was increased by 120%, and CK yield was increased by 54% compared with those in the buffer. Fourier transform infrared, circular dichroism, and fluorescence spectroscopy confirmed that DES did not destroy the structure and conformation of ß-glucosidase. In addition, 80.6% CK conversion was obtained at 60 °C, pH 4.5, 48 h and 8 mM Rb1, which provided a feasible method for efficiently producing CK.

DiscoRhythm: an easy-to-use web application and R package for discovering rhythmicity.

MOTIVATION: Biological rhythmicity is fundamental to almost all organisms on Earth and plays a key role in health and disease. Identification of oscillating signals could lead to novel biological insights, yet its investigation is impeded by the extensive computational and statistical knowledge required to perform such analysis. RESULTS: To address this issue, we present DiscoRhythm (Discovering Rhythmicity), a user-friendly application for characterizing rhythmicity in temporal biological data. DiscoRhythm is available as a web application or an R/Bioconductor package for estimating phase, amplitude, and statistical significance using four popular approaches to rhythm detection (Cosinor, JTK Cycle, ARSER, and Lomb-Scargle). We optimized these algorithms for speed, improving their execution times up to 30-fold to enable rapid analysis of -omic-scale datasets in real-time. Informative visualizations, interactive modules for quality control, dimensionality reduction, periodicity profiling, and incorporation of experimental replicates make DiscoRhythm a thorough toolkit for analyzing rhythmicity. AVAILABILITY AND IMPLEMENTATION: The DiscoRhythm R package is available on Bioconductor (https://bioconductor.org/packages/DiscoRhythm), with source code available on GitHub (https://github.com/matthewcarlucci/DiscoRhythm) under a GPL-3 license. The web application is securely deployed over HTTPS (https://disco.camh.ca) and is freely available for use worldwide. Local instances of the DiscoRhythm web application can be created using the R package or by deploying the publicly available Docker container (https://hub.docker.com/r/mcarlucci/discorhythm). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.