Available Alternative Biologics and Disease Groups Influence Biologic Drug Survival in Patients with Psoriasis and Psoriatic Arthritis.

BACKGROUND: Factors other than efficacy and safety could influence the survival of biologics in patients with psoriasis. Little is known about whether different disease groups affect drug survival of biologics or not. OBJECTIVE: This study aimed to investigate whether the availability of alternative biologics and disease groups could influence drug survival of biologics approved for psoriasis and psoriasis arthritis (PsA). METHODS: A nationwide population-based retrospective cohort study was conducted using the Health Insurance and Review Assessment data in Korea between January 2009 and August 2019. RESULTS: The drug survival analysis included 5,634 biologic episodes. Ustekinumab was the most frequently prescribed drug (n=2,488, 44.2%). Multivariable time-dependent Cox regression analysis showed that higher age, female sex, no comorbidity, concomitant cyclosporine or acitretin use, biologic-experienced and use of tumor necrosis factor (TNF)-α inhibitors were predictors of drug discontinuation. PsA was a predictor of drug persistence, particularly for TNF-α inhibitors. Ustekinumab and adalimumab discontinuation significantly increased after introducing secukinumab and ustekinumab, respectively. CONCLUSION: The availability of alternative biologics and disease groups affect biologic drug survival in patients with psoriasis and PsA.

Association Between Short-Term PASI90 Achievement and Drug Survival of Biologics in Patients with Psoriasis.

Background: With accumulating evidence that achieving a 90% improvement in the Psoriasis Area and Severity Index score (PASI90) has better correlation with improved health-related quality of life as compared to PASI75 achievement, there has been demand for establishing new treatment goals for psoriasis. We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement. Objective: We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement. Methods: This single-center retrospective cohort study reviewed 180 treatment series in 128 patients with plaque psoriasis, who were treated with tumor necrosis factor-alpha inhibitors (n=12), ustekinumab (n=88), secukinumab (n=23), guselkumab (n=45), and ixekizumab (n=12). The first effectiveness assessment, usually performed within 12 to 20 weeks, was considered a short-term treatment response to biologics. Results: After adjustment for covariates, time-dependent Cox proportional hazards regression analysis showed that moderate responders (short-term achievement of ≥PASI75 but

Clinical and Histological Effects of Topical Epidermal Growth Factor on Acne and Acne Scars.

BACKGROUND: The inflammatory lesions of acne leave scars which greatly affect patients' quality of life. Treatment options targeting both acne and acne scars are still lacking. OBJECTIVES: To evaluate the clinical efficacy of epidermal growth factor ointment (EGFO) on acne and acne scars. METHODS: The study design was 12-week, prospective, split-face, single-blinded. The 36 patients with mild to moderate acne vulgaris applied EGFO on one side of the face and the vehicle ointment on the other side twice daily. The patients were assessed every 4 weeks by acne lesion and scar counts, investigator's global assessment for acne (IGA) and scar (SGA), and the ECCA scar grading scale. Biopsies were performed before and after treatment. RESULTS: Acne and acne scars were significantly improved on EGFO-treated sides, while control sides were not. Acne lesion and scar counts were significantly reduced after 4 weeks, while IGA, SGA, and ECCA grade significantly decreased after 8 weeks. Immunohistochemistry showed decreased expression of keratin 16, NF-κB p65, IL-1α, and IL-8, and increased expression of TGF-ß1, elastin, and collagen type 1, 3 after treatment. CONCLUSIONS: EGFO can be a treatment option targeting acne and acne scars.

Association of Rosacea With Cardiovascular Disease: A Retrospective Cohort Study.

Background There is emerging evidence that rosacea, a chronic cutaneous inflammatory disease, is associated with various systemic diseases. However, its association with cardiovascular disease (CVD) remains controversial. We aimed to investigate whether patients with rosacea are at increased risk of developing CVD. Methods and Results This retrospective cohort study from the Korean National Health Insurance Service-Health Screening Cohort included patients with newly diagnosed rosacea (n=2681) and age-, sex-, and index year-matched reference populations without rosacea (n=26 810) between 2003 and 2014. The primary outcome was subsequent CVD including coronary heart disease and stroke. Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios for subsequent CVD adjusted for major risk factors of CVD. Compared with the reference population (13 410 women; mean [SD] age, 57.7 [9.2] years), patients with rosacea (1341 women; mean [SD] age, 57.7 [9.2] years) displayed an increased risk for CVD (adjusted hazard ratios, 1.20; 95% CI, 1.03-1.40) and coronary heart disease (adjusted hazard ratios, 1.29; 95% CI, 1.05-1.60). The risk for stroke was not significantly elevated (adjusted hazard ratios, 1.12; 95% CI, 0.91-1.37). Conclusions This study suggests that patients with rosacea are more likely to develop subsequent CVD. Proper education for patients with rosacea to manage other modifiable risk factors of CVD along with rosacea is needed.

Quantitative determination of lithium depletion during rapid cycling in sulfide-based all-solid-state batteries.

We propose a promising electrochemical analysis tool based on the distribution of relaxation times (DRT) to quantify interfacial resistances towards a comprehensive understanding of complex solid-state interfacial phenomena in sulfide-based all-solid-state batteries (ASSBs). Using DRT-assisted impedance analysis, we identify a new resistance component in the range of 102-103 Hz of 3.5 and 0.9 Ω in the absence and presence of a LiNbO3 layer, respectively, at 1C-rate. Experimental and computational studies confirm that this interfacial resistance results from lithium depletion in sulfide solid electrolytes. Furthermore, we expect our approach to provide new insights into complex interfacial phenomena in ASSBs.

Clinical efficacy of herbal extracts in treatment of mild to moderate acne vulgaris: an 8-week, double-blinded, randomized, controlled trial.

BACKGROUND: Herbal extracts with fewer adverse effects can be an alternative to these drugs because they can target various molecular pathways of acne pathogenesis. OBJECTIVES: To evaluate the clinical efficacy of herbal extracts (mangosteen, Lithospermum officinale, Tribulus terrestris L., Houttuynia cordata Thunb) for the treatment of mild to moderate acne vulgaris. METHODS: Sixty patients were randomized in a 1:1 ratio to receive blinded treatment with herbal extracts or vehicle for 8 weeks. Inflammatory and non-inflammatory acne lesion counts, Investigator's Global Assessment, patient's satisfaction and safety profiles were assessed. We also performed skin biopsy at baseline and week 8 to confirm immunological changes with immunohistochemistry staining. RESULTS: By the end of the study period, both inflammatory and non-inflammatory acne lesion counts were significantly decreased in herbal extracts group (p< .05). In immunohistochemistry staining, expressions of IL-1α, IL-8, and keratin 16 were significantly decreased in herbal extracts group compared to vehicle group from baseline to week 8. There was no serious adverse events in both groups. CONCLUSIONS: This herbal extracts can be a new therapeutic option for patients with mild to moderate acne vulgaris who are reluctant to use drugs.

Effects of reflection and immediate feedback to improve clinical reasoning of medical students in the assessment of dermatologic conditions: a randomised controlled trial.

BACKGROUND: There are few studies that directly compared different interventions to improve medical students' clinical reasoning for dermatologic conditions. OBJECTIVE: To investigate the effectiveness of adding practice with reflection and immediate feedback on traditional dermatology electives in improving medical students' ability in evaluating skin lesions. METHODS: The participants were fourth-year medical students of Seoul National University College of Medicine, Korea, who were enrolled to take a 2-week dermatology elective course (n = 87). Students were assigned to one of the three educational interventions: 2-h training involving 10 written clinical cases (experimental); 1-h lecture and 1-h outpatient clinic (lecture); and 2-h outpatient clinic (no intervention). Before and at the end of rotation, diagnostic accuracy was estimated using 20 written clinical cases with photographs (10 novel cases presented in diagnostic training [training set], 10 cases with diagnoses not included in training [control set]). RESULTS: There was a significant interaction effect of intervention×set×time. A post hoc analysis indicated that the students in the experimental group outperformed students in the other two groups only in the training set of the final tests; after completing the 2-week rotation, for the training set, the mean score was higher in the experimental group (7.5 ± 1.3) than in the lecture (5.7 ± 1.6) and no intervention (5.6 ± 1.3) groups, producing an effect size of 1.2 standard deviation (SD) and 1.5 SD, respectively. CONCLUSION: Practicing written clinical cases with reflection and feedback is superior to a lecture-based approach and yields additional benefits to a dermatology elective, thereby enhancing medical students' ability to accurately diagnose skin lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03472001. Registered 21 March 2018.

Superionic Halogen-Rich Li-Argyrodites Using In Situ Nanocrystal Nucleation and Rapid Crystal Growth.

Although several crystalline materials have been developed as Li-ion conductors for use as solid electrolytes in all-solid-state batteries (ASSBs), producing materials with high Li-ion conductivities is time-consuming and cost-intensive. Herein, we introduce a superionic halogen-rich Li-argyrodite (HRLA) and demonstrate its innovative synthesis using ultimate-energy mechanical alloying (UMA) and rapid thermal annealing (RTA). UMA with a 49 G-force milling energy provides a one-pot process that includes mixing, glassification, and crystallization, to produce as-milled HRLA powder that is ∼70% crystallized; subsequent RTA using an infrared lamp increases this crystallinity to ∼82% within 25 min. Surprisingly, this HRLA exhibits the highest Li-ion conductivity among Li-argyrodites (10.2 mS cm-1 at 25 °C, cold-pressed powder compact) reported so far. Furthermore, we confirm that this superionic HRLA works well as a promising solid electrolyte without a decreased intrinsic electrochemical window in various electrode configurations and delivers impressive cell performance (114.2 mAh g-1 at 0.5 C).

Pervasive Misclassification and Misconception of Study Designs in Asian Dermatology Journals Listed in Science Citation Index-Expanded.

BACKGROUND: Misclassification of study designs of journals can hinder the readers from assessing the strengths and weaknesses of the study and evaluating the applicability of the study in the real-world setting. However, it seems that it is common for authors to neglect to classify the study design. OBJECTIVE: We aimed to evaluate the accuracy of the classification of study designs and examine the common errors. METHODS: This descriptive study analyzed four Asian dermatology journals listed in the science citation index expanded from January 2018 to December 2018. We investigated discrepancies between author-reported and actual study designs. Design Algorithm for Medical Literature on Intervention (DAMI) was used to determine the actual study design. RESULTS: Of the 177 papers analyzed, only 72 articles (40.7%) revealed their study design and among them, 23 articles (32.0%) showed discrepancies between the author-reported and the actual study designs. Case-control studies were the most commonly misclassified study designs by authors. CONCLUSION: There were considerable differences between the author-reported study design and the actual study design in Asian dermatology journals. Proper classification of study designs by the authors is essential to strengthen evidencebased medicine.

Functional surgery versus amputation for in situ or minimally invasive nail melanoma: A meta-analysis.

BACKGROUND: Evidence on whether functional surgery is not inferior to amputation for the treatment of in situ or minimally invasive (Breslow thickness ≤0.5 mm) nail melanoma is limited. OBJECTIVE: To investigate the difference in local recurrence between the 2 interventions for in situ or minimally invasive nail melanoma using available published studies. METHODS: We performed systematic search on PubMed, Embase, Cochrane Library, trial registers, and grey literature databases from inception to June 28, 2018. We included observational studies with at least 5 patients with in situ or minimally invasive nail melanoma. Main outcome was local recurrence. RESULTS: The odds ratio synthesized from 5 studies including 109 patients (88 functional operations and 21 amputations) was 1.57 (95% confidence interval, 0.31-8.00). LIMITATIONS: Small sample size and possible interstudy heterogeneity. CONCLUSIONS: Our meta-analysis revealed no difference in local recurrence between the 2 interventions. Considering the functional deficit after amputation, conservative surgery should be the treatment of choice for in situ or minimally invasive nail melanoma.

Electrochemical behaviors of Li-argyrodite-based all-solid-state batteries under deep-freezing conditions.

We probe the electrochemical performance of Li-argyrodite-based all-solid-state batteries under deep-freezing conditions (-30 °C) using electrochemical impedance spectroscopy. The performance deterioration is mainly caused by the increased interfacial resistances of electrolyte and active materials resulting from the slow kinetics of Li-ion transport in solid materials at low temperatures.

Thermally Induced S-Sublattice Transition of Li3PS4 for Fast Lithium-Ion Conduction.

The ion-transport phenomenon, determined by the interaction of strain and electrostatic energy, is one of the most important examples that confirms the effects of the polymorphism and atomic morphology. We investigated the correlation between the structural morphology and Li-ion conduction characteristics in α-Li3PS4, a high-temperature phase of the Li3PS4, using ab initio molecular dynamics (AIMD) calculations. We successfully reproduced the thermal disorder and partial occupancy observed at high temperatures by AIMD and confirmed the Li-ion sites and its migration pathways. The activation energy and Li-ion conductivity of α-Li3PS4 at room temperature were predicted to be about 0.18 eV and 80 mS cm-1, respectively, indicating that α-Li3PS4 is one of the fastest Li-ion conductors known so far. The fast Li-ion conduction in α-Li3PS4 is mainly caused by the BCC S-sublattice and tetrahedron-tetrahedron pathway with fully occupied Li-ion sites. Therefore, α-Li3PS4 having a BCC S-sublattice offers a promising structural morphology for effective Li-ion conduction.

Quantitative Analysis of Microstructures and Reaction Interfaces on Composite Cathodes in All-Solid-State Batteries Using a Three-Dimensional Reconstruction Technique.

The composite cathode of an all-solid-state battery composed of various solid-state components requires a dense microstructure and a highly percolated solid-state interface different from that of a conventional liquid-electrolyte-based Li-ion battery. Indeed, the preparation of such a system is particularly challenging. In this study, quantitative analyses of composite cathodes by three-dimensional reconstruction analysis were performed beyond the existing qualitative analysis, and their microstructures and reaction interfaces were successfully analyzed. Interestingly, various quantitative values of structure properties (such as the volume ratio, connectivity, tortuosity, and pore formation) associated with material optimization and process development were predicted, and they were found to result in limited electrochemical charge/discharge performances. We also verified that the effective two-phase boundaries were significantly suppressed to ∼23% of the total volume because of component dispersion and packing issues.

Collateral hydrogenation over proton-conducting Ni/BaZr0.85Y0.15O3-δ catalysts for promoting CO2 methanation.

Despite the importance of CO2 methanation for eco-friendly carbon-neutral fuel recycling, the current technologies, relying on catalytic hydrogenation over metal-based catalysts, face technological and economical limitations. Herein, we employ the steam hydrogenation capability of proton conductors to achieve collateral CO2 methanation over the Ni/BaZr0.85Y0.15O3-δ catalyst, which is shown to outperform its conventional Ni/Al2O3 counterpart in terms of CH4 yield (8% higher) and long-term stability (3% higher for 150 h) at 400 °C while exhibiting a CH4 selectivity above 98%. Moreover, infrared and X-ray photoelectron spectroscopy analyses reveal the appearance of distinct mobile proton-related OH bands during the methanation reaction.

Strain-Induced Tailoring of Oxygen-Ion Transport in Highly Doped CeO2 Electrolyte: Effects of Biaxial Extrinsic and Local Lattice Strain.

We explored oxygen-ion transport in highly doped CeO2 through density-functional theory calculations. By applying biaxial strain to 18.75 mol % CeO2:Gd, we predicted the average migration-barrier energy with six different pathways, with results in good agreement with those of experiments. Additionally, we found that the migration-barrier energy could be lowered by increasing the tetrahedron volume, including the space occupied by the oxygen vacancy. Our results indicate that the tetrahedron volume can be expanded by larger codopants, as well as biaxial tensile strain. Thus, the combination of thin-film structure and codoping could offer a new approach to accelerate oxygen-ion transport.

Catalytic behavior of metal catalysts in high-temperature RWGS reaction: In-situ FT-IR experiments and first-principles calculations.

High-temperature chemical reactions are ubiquitous in (electro) chemical applications designed to meet the growing demands of environmental and energy protection. However, the fundamental understanding and optimization of such reactions are great challenges because they are hampered by the spontaneous, dynamic, and high-temperature conditions. Here, we investigated the roles of metal catalysts (Pd, Ni, Cu, and Ag) in the high-temperature reverse water-gas shift (RWGS) reaction using in-situ surface analyses and density functional theory (DFT) calculations. Catalysts were prepared by the deposition-precipitation method with urea hydrolysis and freeze-drying. Most metals show a maximum catalytic activity during the RWGS reaction (reaching the thermodynamic conversion limit) with formate groups as an intermediate adsorbed species, while Ag metal has limited activity with the carbonate species on its surface. According to DFT calculations, such carbonate groups result from the suppressed dissociation and adsorption of hydrogen on the Ag surface, which is in good agreement with the experimental RWGS results.