Sparse ordinal discriminant analysis.

Ordinal class labels are frequently observed in classification studies across various fields. In medical science, patients' responses to a drug can be arranged in the natural order, reflecting their recovery postdrug administration. The severity of the disease is often recorded using an ordinal scale, such as cancer grades or tumor stages. We propose a method based on the linear discriminant analysis (LDA) that generates a sparse, low-dimensional discriminant subspace reflecting the class orders. Unlike existing approaches that focus on predictors marginally associated with ordinal labels, our proposed method selects variables that collectively contribute to the ordinal labels. We employ the optimal scoring approach for LDA as a regularization framework, applying an ordinality penalty to the optimal scores and a sparsity penalty to the coefficients for the predictors. We demonstrate the effectiveness of our approach using a glioma dataset, where we predict cancer grades based on gene expression. A simulation study with various settings validates the competitiveness of our classification performance and demonstrates the advantages of our approach in terms of the interpretability of the estimated classifier with respect to the ordinal class labels.

Risk factors for scabies in hospital: a systematic review.

BACKGROUND: Annually, 175.4 million people are infected with scabies worldwide. Although parasitic infections are important nosocomial infections, they are unrecognized compared to bacterial, fungal, and viral infections. In particular, nonspecific cutaneous manifestations of scabies lead to delayed diagnosis and frequent nosocomial transmission. Hospital-based studies on the risk factors for scabies have yet to be systematically reviewed. METHODS: The study followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42023363278). Literature searches were conducted in three international (PubMed, Embase, and CINAHL) and four Korean (DBpia, KISS, RISS, and Science ON) databases. We included hospital-based studies with risk estimates calculated with 95% confidence intervals for risk factors for scabies infection. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tools. Two authors independently performed the screening and assessed the quality of the studies. RESULTS: A total of 12 studies were included. Personal characteristics were categorized into demographic, economic, residential, and behavioral factors. The identified risk factors were low economic status and unhygienic behavioral practices. Being a patient in a long-term care facility or institution was an important factor. Frequent patient contact and lack of personal protective equipment were identified as risk factors. For clinical characteristics, factors were categorized as personal health and hospital environment. People who had contact with itchy others were at higher risk of developing scabies. Patients with higher severity and those with a large number of catheters are also at increased risk for scabies infection. CONCLUSIONS: Factors contributing to scabies in hospitals range from personal to clinical. We emphasize the importance of performing a full skin examination when patients present with scabies symptoms and are transferred from settings such as nursing homes and assisted-living facilities, to reduce the transmission of scabies. In addition, patient education to prevent scabies and infection control systems for healthcare workers, such as wearing personal protective equipment, are needed.

Ventriculoperitoneal shunt infection and malfunction in adult patients: incidence, risk factors, and long-term follow-up of single institution experience.

Ventriculoperitoneal shunt surgery was developed to manage excessive cerebrospinal fluid (CSF) in the brain's ventricles and is considered a mainstream treatment. Despite the development of the shunt device system, various complications still occur. In this study, we reported 307 cases and a long-term follow-up of at least five years of adult patients who underwent VP shunt surgery and analyzed various factors that may affect revision surgery. A retrospective study was conducted at Asan Medical Center, Korea, a tertiary medical center. We reviewed 307 cases from January 2012 to December 2018. The patients' neurological status, predisposing medical conditions, laboratory findings, and other operation-related factors were reviewed using electrical medical records. The normal function group comprised 272 cases (88.6%), and the overall incidence of revision group comprised 35 cases (11.4%). Of the 35 revision surgery cases, 30 (85.71%) were due to shunt malfunctions, such as obstruction, overdrainage, and valve-related errors while 5 (14.29%) were due to shunt infection. Patient demographics, mental status, and operation time did not influence revision as risk factors. Serum laboratory findings showed no statistical difference between the two groups. The white blood cell (WBC) count in the CSF profile differed significantly between the two groups. The Hakim Programmable valve (Codman, USA) is mainly used in our center. In addition, various shunt systems were used, including Strata Regulatory valve (Medtronic, USA), proGAV (Aesculap, USA), and Accu-Flo (Codman, USA). This study analyzed the factors affecting long-term outcomes. Based on these findings, efforts are needed to achieve more favorable outcomes in the future.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Comparative study of lumbar bone mineral content using DXA and CT Hounsfield unit values in chest CT.

BACKGROUND: Bone mineral content (BMC) values in certain bones and changes in BMC over time are key features for diagnosing osteoporosis. This study examined those features using morphometric texture analysis in chest computational tomography (CT) by comparing a dual-energy X-ray absorptiometry (DXA)-based BMC. An accessible approach for screening osteoporosis was suggested by accessing BMC using only Hounsfield units (HU). METHODOLOGY: The study included a total of 510 cases (255 patients) acquired between May 6, 2012, and June 30, 2020, at a single institution. Two cases were associated with two chest CT scans from one patient with a scan interval of over two years, and each scan was followed soon after by a DXA scan. Axial cuts of the first lumbar vertebra in CT and DXA-based L1 BMC values were corrected for each case. The maximum trabecular area was selected from the L1 spine body, and 45 texture features were extracted from the region using gray-level co-occurrence matrices. A regression model was employed to estimate the absolute BMC value in each case using 45 features. Also, an additional regression model was used to estimate the change in BMC between two scans for each patient using 90 features from the corresponding cases. RESULTS: The correlation coefficient (CC) and mean absolute error (MAE) between estimates and DXA references were obtained for the evaluation of regressors. In the case of the BMC estimation, CC and MAE were 0.754 and 1.641 (g). In the case of the estimation of change in BMC, CC and MAE were 0.680 and 0.528 (g). CONCLUSION: The modality using morphometric texture analysis with CT HUs can indirectly help screening osteoporosis because it provides estimates of BMC and BMC change that show moderate positive correlations with DXA measures.

All-Graphene-Contact Electrically Pumped On-Demand Transferrable Nanowire Source.

On-demand NW light sources in a photonic integrated circuit (PIC) have faced several practical challenges. Here, we report on an all-graphene-contact, electrically pumped, on-demand transferrable NW source that is fabricated by implementing an all-graphene-contact approach in combination with a highly accurate microtransfer printing technique. A vertically p-i-n-doped top-down-fabricated semiconductor NW with optical gain structures is electrically pumped through the patterned multilayered graphene contacts. Electroluminescence (EL) spectroscopy results reveal that the electrically driven NW device exhibits strong EL emission between the contacts and displays waveguiding properties. Further, a single NW device is precisely integrated into an existing photonic waveguide to perform light coupling and waveguiding experiments. Three-dimensional numerical simulation results show a good agreement with experimental observations. We believe that our all-graphene-contact approach is readily applicable to various micro/nanostructures and devices, which facilitates stable electrical operation and thus extends their practical applicability in compact integrated circuits.

Monolithically Programmed Stretchable Conductor by Laser-Induced Entanglement of Liquid Metal and Metallic Nanowire Backbone.

Owing to its low mechanical compliance, liquid metal is intrinsically suitable for stretchable electronics and future wearable devices. However, its invariable strain-resistance behavior according to the strain-induced geometrical deformation and the difficulty of circuit patterning limit the extensive use of liquid metal, especially for strain-insensitive wiring purposes. To overcome these limitations, herein, novel liquid-metal-based electrodes of fragmented eutectic gallium-indium alloy (EGaIn) and Ag nanowire (NW) backbone of which their entanglement is controlled by the laser-induced photothermal reaction to enable immediate and direct patterning of the stretchable electrode with spatially programmed strain-resistance characteristics are developed. The coexistence of fragmented EGaIn and AgNW backbone, that is, a biphasic metallic composite (BMC), primarily supports the uniform and durable formation of target layers on stretchable substrates. The laser-induced photothermal reaction not only promotes the adhesion between the BMC layer and substrates but also alters the structure of laser-irradiated BMC. By controlling the degree of entanglement between fragmented EGaIn and AgNW, the initial conductivity and local gauge factor are regulated and the electrode becomes effectively insensitive to applied strain. As the configuration developed in this study is compatible with both regimes of electrodes, it can open new routes for the rapid creation of complex stretchable circuitry through a single process.

The impact of obesity on the accuracy of DXA BMD for DXA-equivalent BMD estimation.

INTRODUCTION: As the radiomics technique using texture features in CT is adopted for accessing DXA-equivalent bone mineral density (BMD), this study aims to compare BMD by DXA and predicted BMD to investigate the impact of obesity and central obesity in general patients. MATERIALS AND METHODS: A total of 710 cases (621 patients) obtained from May 6, 2012, to June 30, 2021, were used in the study. We focused both their abdomen & pelvis CT's first lumbar vertebrae axial cuts to predict estimated BMD and bone mineral content (BMC). In each patient's CT, we extracted the largest trabecular region of the L1 vertebral body as a region of interest (ROI) using the gray-level co-occurrence matrices (GLCM) technique, and linear regression was applied to predict the indices. Cases were divided by central obesity/overall obesity and normal group by body mass index (BMI), waist circumference (WC), or index of central obesity (ICO) standard. RESULTS: The coefficients were all above 0.73, respectively. P-values from ICO were over 0.05 when the measures were Hip BMD and Hip BMC. In contrast, those from ICO were 0.0131 and 0.0351 when the measures were L1 BMD and L1 BMC, respectively, which show a difference between the two groups. CONCLUSIONS: The CT HU texture analysis method was an effective and economical method for measuring estimated BMD and BMC and evaluating the impact of obesity. We found that central obesity especially exerted an effect on the disturbance of the clinical BMD measurements since groups were significantly different under the ICO standard.

Nanoconfining solution-processed organic semiconductors for emerging optoelectronics.

Solution-processable organic materials for emerging electronics can generally be divided into two classes of semiconductors, organic small molecules and polymers. The theoretical thermodynamic limits of device performance are largely determined by the molecular structure of these compounds, and advances in synthetic routes have led to significant progress in charge mobilities and light conversion and light emission efficiencies over the past several decades. Still, the uncontrolled formation of out-of-equilibrium film microstructures and unfavorable polymorphs during rapid solution processing remains a critical bottleneck facing the commercialization of these materials. This tutorial review provides an overview of the use of nanoconfining scaffolds to impose order onto solution-processed semiconducting films to overcome this limitation. For organic semiconducting small molecules and polymers, which typically exhibit strong crystal growth and charge transport anisotropy along different crystallographic directions, nanoconfining crystallization within nanopores and nanogrooves can preferentially orient the fast charge transport direction of crystals with the direction of current flow in devices. Nanoconfinement can also stabilize high-performance metastable polymorphs by shifting their relative Gibbs free energies via increasing the surface area-to-volume ratio. Promisingly, such nanoconfinement-induced improvements in film and crystal structures have been demonstrated to enhance the performance and stability of emerging optoelectronics that will enable large-scale manufacturing of flexible, lightweight displays and solar cells.

Feature Selection Method Using Multi-Agent Reinforcement Learning Based on Guide Agents.

In this study, we propose a method to automatically find features from a dataset that are effective for classification or prediction, using a new method called multi-agent reinforcement learning and a guide agent. Each feature of the dataset has one of the main and guide agents, and these agents decide whether to select a feature. Main agents select the optimal features, and guide agents present the criteria for judging the main agents' actions. After obtaining the main and guide rewards for the features selected by the agents, the main agent that behaves differently from the guide agent updates their Q-values by calculating the learning reward delivered to the main agents. The behavior comparison helps the main agent decide whether its own behavior is correct, without using other algorithms. After performing this process for each episode, the features are finally selected. The feature selection method proposed in this study uses multiple agents, reducing the number of actions each agent can perform and finding optimal features effectively and quickly. Finally, comparative experimental results on multiple datasets show that the proposed method can select effective features for classification and increase classification accuracy.

Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments.

tRNA-derived RNA fragments (tRFs) have emerged as a new class of functional RNAs implicated in cancer, metabolic and neurological disorders, and viral infection. Yet our understanding of their biogenesis and functions remains limited. In the present study, through analysis of small RNA profile we have identified a distinct set of tRFs derived from pre-tRNA 3' trailers in the hepatocellular carcinoma cell line Huh7. Among those tRFs, tRF_U3_1, which is a 19-nucleotide-long chr10.tRNA2-Ser(TGA)-derived trailer, was expressed most abundantly in both Huh7 and cancerous liver tissues, being present primarily in the cytoplasm. We show that genetic loss of tRF_U3_1 does not affect cell growth and it is not involved in Ago2-mediated gene silencing. Using La/SSB knockout Huh7 cell lines, we demonstrate that this nuclear-cytoplasmic shuttling protein directly binds to the 3' U-tail of tRF_U3_1 and other abundantly expressed trailers and plays a critical role in their stable cytoplasmic accumulation. The pre-tRNA trailer-derived tRFs capable of sequestering the limiting amounts of La/SSB in the cytoplasm rendered cells resistant to various RNA viruses, which usurp La/SSB with RNA chaperone activity for their gene expression. Collectively, our results establish the trailer-derived tRF-La/SSB interface, regulating viral gene expression.

Ultrafast Infrared Photoresponse from Heavily Hydrogen-Doped VO2 Single Crystalline Nanoparticles.

Infrared photodetectors are sought for diverse applications and their performance relies on photoactive materials and photocurrent generation mechanisms. Here, we fabricate IR photodetectors with heavily hydrogen-doped VO2 (i.e., HVO2) single-crystalline nanoparticles which show two orders greater resistivities than pure VO2. The I-V plots obtained under IR light irradiation are expressed by space charge limited current mechanism and the increase in photocurrent occurs due to the increase in the number of photoinduced trap sites. This phenomenon remarkably improves the key parameters at λ = 780 nm of high responsivity of 35280 A/W, high detectivity of 1.12 × 1013 Jones, and strikingly fast response times of 0.6-2.5 ns, that is, 3 orders of magnitude faster than the best records of two-dimensional structures and heterostructures. Density functional theory calculations illustrate that the generation of photoinduced trap sites is attributed to the movement of hydrogen atoms to less stable interstitial sites in VO2 under light exposure.

N-Phenyl Cinnamamide Derivatives Protect Hepatocytes against Oxidative Stress by Inducing Cellular Glutathione Synthesis via Nuclear Factor (Erythroid-Derived 2)-Like 2 Activation.

Substituted N-phenyl cinnamamide derivatives were designed and synthesized to confirm activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway by the electronic effect on beta-position of Michael acceptor according to introducing the R1 and R2 group. Compounds were screened using the Nrf2/antioxidant response element (ARE)-driven luciferase reporter assay. Compound 1g showed desirable luciferase activity in HepG2 cells without cell toxicity. mRNA and protein expression of Nrf2/ARE target genes such as NAD(P)H quinone oxidoreductase 1, hemeoxygenase-1, and glutamate-cysteine ligase catalytic subunit (GCLC) were upregulated by compound 1g in a concentration-dependent manner. Treatment with 1g resulted in increased endogenous antioxidant glutathione, showing strong correlation with enhanced GCLC expression for synthesis of glutathione. In addition, tert-butyl hydroperoxide (t-BHP)-generated reactive oxygen species were significantly removed by 1g, and the results of a cell survival assay in a t-BHP-induced oxidative cell injury model showed a cytoprotective effect of 1g in a concentration dependent manner. In conclusion, the novel compound 1g can be utilized as an Nrf2/ARE activator in antioxidative therapy.

Reversible Polymorphic Transition and Hysteresis-Driven Phase Selectivity in Single-Crystalline C8-BTBT Rods.

Organic semiconductors (OSCs) are highly susceptible to the formation of metastable polymorphs that are often transformed by external stimuli. However, thermally reversible transformations in OSCs with stability have not been achieved due to weak van der Waals forces, and poor phase homogeneity and crystallinity. Here, a polymorph of a single crystalline 2,7-dioctyl[1] benzothieno[3,2-b][1]benzothio-phene rod on a low molecular weight poly(methyl methacrylate) (≈120k) that limits crystal coarsening during solvent vapor annealing is fabricated. Molecules in the polymorph lie down slightly toward the substrate compared to the equilibrium state, inducing an order of greater resistivity. During thermal cycling, the polymorph exhibits a reversible change in resistivity by 5.5 orders with hysteresis; this transition is stable toward bias and thermal cycling. Remarkably, varying cycling temperatures leads to diverse resistivities near room temperature, important for nonvolatile multivalue memories. These trends persist in the carrier mobility and on/off ratio of the polymorph field-effect transistor. A combination of in situ grazing incident wide angle X-ray scattering analyses, visualization for electronic and structural analysis simulations, and density functional theory calculations reveals that molecular tilt governs the charge transport characteristics; the polymorph transforms as molecules tilt, and thereby, only a homogeneous single-crystalline phase appears at each temperature.

Drop impact on hot plates: contact times, lift-off and the lamella rupture.

When a liquid drop impacts on a heated substrate, it can remain deposited, or violently boil in contact, or lift off with or without ever touching the surface. The latter is known as the Leidenfrost effect. The duration and area of the liquid-substrate contact are highly relevant for the heat transfer, as well as other effects such as corrosion. However, most experimental studies rely on side view imaging to determine contact times, and those are often mixed with the time until the drop lifts off from the substrate. Here, we develop and validate a reliable method of contact time determination using high-speed X-ray imaging and total internal reflection imaging. We exemplarily compare contact and lift-off times on flat silicon and sapphire substrates. We show that drops can rebound even without formation of a complete vapor layer, with a wide range of lift-off times. On sapphire, we find a local minimum of lift-off times that is much shorter than expected from capillary rebound in the comparatively low-temperature regime of transition boiling/thermal atomization. We elucidate the underlying mechanism related to spontaneous rupture of the lamella and receding of the contact area.

Recoverable Electrical Breakdown Strength and Dielectric Constant in Ultralow-k Nanolattice Capacitors.

The dielectric reliability of low-k materials during mechanical deformation attracts tremendous attention, owing to the increasing demand for thin electronics to meet the ever-shrinking form factor of consumer products. However, the strong coupling between dielectric/electric and mechanical properties limits the use of low-k dielectrics in industrial applications. We report the leakage current and dielectric properties of a nanolattice capacitor during compressive stress cycling. Electrical breakdown measurements during the stress cycling, combined with a theoretical model and in situ mechanical experiments, provide insights to key breakdown mechanisms. Electrical breakdown occurs at nearly 50% strain, featuring a switch-like binary character, correlated with a transition from beam bending and buckling to collapse. Breakdown strength appears to recover after each cycle, concomitant with nanolattice's shape recovery. The compressive displacement at breakdown decreases with cycling due to permanently buckled beams, transforming the conduction mechanism from Schottky to Poole-Frankel emission. Remarkably, our capacitor with 99% porosity, k ∼ 1.09, is operative up to 200 V, whereas devices with 17% porous alumina films breakdown upon biasing based on a percolation model. Similarly with electrical breakdown, the dielectric constant of the capacitor is recoverable with five strain cycles and is stable under 25% compression. These outstanding capabilities of the nanolattice are essential for revolutionizing future flexible electronics.

Comparison of the Treatment Outcome of Oral Tofacitinib with Other Conventional Therapies in Refractory Alopecia Totalis and Universalis: A Retrospective Study.

Treatment of alopecia totalis and alopecia universalis is often challenging and unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The aim of this study is to compare the efficacy and tolerability of oral tofacitinib and conventional modalities for treating refractory alopecia totalis/universalis. A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional oral treatment (steroid ± cyclosporine), and 30 treated with diphenylcyclopropenone) were included in the study. The patients' medical records were reviewed retrospectively. After 6 months, 44.4% of patients in the tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in the diphenylcyclopropenone group achieved 50% improvements in the Severity of Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group, 73.1% in the conventional oral treatment group, and 10% in the diphenylcyclopropenone group experienced adverse drug reactions. In conclusion, oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and more tolerable than conventional oral treatment after 6 months of treatment.

IMU Sensor-Based Hand Gesture Recognition for Human-Machine Interfaces.

We propose an efficient hand gesture recognition (HGR) algorithm, which can cope with time-dependent data from an inertial measurement unit (IMU) sensor and support real-time learning for various human-machine interface (HMI) applications. Although the data extracted from IMU sensors are time-dependent, most existing HGR algorithms do not consider this characteristic, which results in the degradation of recognition performance. Because the dynamic time warping (DTW) technique considers the time-dependent characteristic of IMU sensor data, the recognition performance of DTW-based algorithms is better than that of others. However, the DTW technique requires a very complex learning algorithm, which makes it difficult to support real-time learning. To solve this issue, the proposed HGR algorithm is based on a restricted column energy (RCE) neural network, which has a very simple learning scheme in which neurons are activated when necessary. By replacing the metric calculation of the RCE neural network with DTW distance, the proposed algorithm exhibits superior recognition performance for time-dependent sensor data while supporting real-time learning. Our verification results on a field-programmable gate array (FPGA)-based test platform show that the proposed HGR algorithm can achieve a recognition accuracy of 98.6% and supports real-time learning and recognition at an operating frequency of 150 MHz.

Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2.

The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase. The decrease in miR-122 expression resulted in the dysregulation of the known functions of miR-122, including its proviral activity for HCV. By high-throughput sequencing of small RNAs from human liver biopsies, we found that the 22-nucleotide (nt) prototype miR-122 is modified at its 3' end by 3'-terminal non-templated and templated nucleotide additions. Remarkably, the proportion of miR-122 isomers bearing a single nucleotide tail of any ribonucleotide decreased in liver specimens from patients with HCV. We found that these single-nucleotide-tailed miR-122 isomers display increased miRNA activity and stability over the 22-nt prototype miR-122 and that the 3'-terminal extension is catalyzed by the unique terminal nucleotidyl transferase activity of GLD-2, which is capable of adding any single ribonucleotide without preference of adenylate to the miR-122 3' end. The HCV core protein specifically inhibited GLD-2, and its interaction with GLD-2 in the cytoplasm was found to be responsible for miR-122 downregulation. Collectively, our results provide new insights into the regulatory role of the HCV core protein in controlling viral RNA abundance and miR-122 functions through miR-122 stability modulation.

Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.