Risk of vitiligo in patients with SARS-CoV-2 vaccination or infection: a nationwide cohort study.

As recent sporadic case reports of newly developed vitiligo after SARS-CoV-2 infection or vaccination have been -published, a convincing large-scale study addressing this association is warranted. To investigate the association between SARS-CoV-2 infection or vaccination and vitiligo using the Korean National Health Insurance Service database. SARS-CoV-2-positive patients and those vaccinated against SARS-CoV-2 were recruited. In studies 1 and 2, control groups were selected based on 1:1 propensity score matching with vaccinated and SARS-CoV-2-positive patients, respectively. The occurrence of vitiligo was the main outcome. Each individual was monitored for six months. The hazard ratio (HR) for vitiligo was calculated using the Cox proportional hazards model. In study 1, the incidence of vitiligo in the vaccination group was 2.22-fold higher than that in the non-vaccination group (adjusted HR [aHR]: 2.22; 95% confidence interval [CI]: 1.54-3.19). Rheumatoid arthritis was a risk factor for vitiligo (aHR: 1.99; 95% CI: 1.12-3.54). Conversely, two factors associated with decreased incidence of vitiligo were male sex (aHR: 0.58; 95% CI: 0.40-0.82) and rural residency (aHR: 0.68; 95% CI: 0.49-0.96). In study 2, the incidence of newly-diagnosed vitiligo was not significantly different between SARS-CoV-2-positive patients and uninfected controls (aHR: 0.95; 95% CI: 0.51-1.78). SARS-CoV-2 vaccination may increase the risk of developing vitiligo in South Korea, although additional studies in other countries or with extended periods are needed. Clinicians should be aware of the impact of SARS-CoV-2 infection and vaccination on autoimmune skin diseases, including vitiligo.

Risk of Alopecia Areata After COVID-19.

This cohort study examines the incidence, prevalence, and risk of alopecia areata after COVID-19.

Accelerating the Search for New Solid Electrolytes: Exploring Vast Chemical Space with Machine Learning-Enabled Computational Calculations.

Discovering new solid electrolytes (SEs) is essential to achieving higher safety and better energy density for all-solid-state lithium batteries. In this work, we report machine learning (ML)-assisted high-throughput virtual screening (HTVS) results to identify new SE materials. This approach expands the chemical space to explore by substituting elements of prototype structures and accelerates an evaluation of properties by applying various ML models. The screening results in a few candidate materials, which are validated by density functional theory calculations and ab initio molecular dynamics simulations. The shortlisted oxysulfide materials satisfy key properties to be successful SEs. The advanced screening method presented in this work will accelerate the discovery of energy materials for related applications.

Geometric Tuning of Single-Atom FeN4 Sites via Edge-Generation Enhances Multi-Enzymatic Properties.

Single-atom nanozymes (SAzymes) are considered promising alternatives to natural enzymes. The catalytic performance of SAzymes featuring homogeneous, well-defined active structures can be enhanced through elucidating structure-activity relationship and tailoring physicochemical properties. However, manipulating enzymatic properties through structural variation is an underdeveloped approach. Herein, the synthesis of edge-rich Fe single-atom nanozymes (FeNC-edge) via an H2 O2 -mediated edge generation is reported. By controlling the number of edge sites, the peroxidase (POD)- and oxidase (OXD)-like performance is significantly enhanced. The activity enhancement results from the presence of abundant edges, which provide new anchoring sites to mononuclear Fe. Experimental results combined with density functional theory (DFT) calculations reveal that FeN4 moieties in the edge sites display high electron density of Fe atoms and open N atoms. Finally, it is demonstrated that FeNC-edge nanozyme effectively inhibits tumor growth both in vitro and in vivo, suggesting that edge-tailoring is an efficient strategy for developing artificial enzymes as novel catalytic therapeutics.

Analysis of Cause-of-Death Mortality in Children and Young Adults with Diabetes: A Nationwide 10-Year Follow-Up Cohort Study.

We examined the associations of clinical characteristics and cause-of-death patterns with mortality in children and young adults (<30 years) with diabetes. We analyzed a nationwide cohort sample from the KNHIS database using propensity score matching from a sample of 1 million people from 2002 to 2013. There were 10,006 individuals in the diabetes mellitus (DM) group and 10,006 in the control (no DM) group. The numbers of deaths were 77 in the DM group and 20 in the control group. The deaths of patients in the DM Group were 3.74 (95% confidence interval (CI) = 2.25-6.21) times higher than in the control group. Type 1 DM, type 2 DM and unspecified DM were 4.52 (95% CI = 1.89-10.82) times, 3.25 (95% CI = 1.95-5.43) times and 10.20 (95% CI = 5.24-20.18) times higher, respectively. Mental disorders were 2.08 times higher in the risk of death (95% CI = 1.27-3.40). Mortality rates have increased in children and young adults with diabetes alone. Therefore, in the future, it is necessary to identify the cause of the increased mortality rate among young diabetic people and select vulnerable groups among them so that early prevention can be achieved.

Catalytic activity trends of pyrite transition metal dichalcogenides for oxygen reduction and evolution.

Transition metal dichalcogenides (TMDs) have been considered as promising materials for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalysis. While there have been numerous studies focusing on layered TMDs, the ORR and OER catalytic activity trends of various cubic pyrite TMDs have not been systematically explored yet. Herein, we investigated 12 earth abundant element-based pyrite TMDs (MX2, where M = Mn, Fe, Co, Ni and X = S, Se, Te) using density functional theory (DFT) calculations. We initially constructed surface Pourbaix diagrams to determine the most stable surface coverages under the reaction conditions and found that the oxidized surfaces are most energetically preferred in all cases. We then calculated the binding free energies of reaction intermediates (O*, OH* and OOH*) and established their scaling relations. The electrochemical ORR and OER performances were then displayed on two-dimensional volcano plots, which suggest MnS2, FeS2, NiTe2 and CoSe2 to be ORR active, and CoTe2 and CoSe2 to be OER active. In addition, we built multivariate linear regression models to predict ΔGO* and ΔGOH* using only atomic and bulk properties to readily estimate the catalytic activities of pyrite TMDs and to explore correlations between those properties. Particularly, we found that the electron affinity and bulk Bader charges of metal atoms are critical in determining the ORR and OER catalytic activities, which could be used as a guidance for future catalyst design.

Accuracy of Dental Implant Placement by a Novel In-House Model-Free and Zero-Setup Fully Guided Surgical Template Made of a Light-Cured Composite Resin (VARO Guide®): A Comparative In Vitro Study.

BACKGROUND: This in vitro study mainly aimed to compare VARO Guide® to the surgical guide fabricated by CAD/CAM (NAVI Guide®) in terms of accuracy and efficacy of the implant surgery held in the dentiform model. METHODS: Twenty surgeons, 10 dentists in the beginner group and 10 dentists in the expert group, participated in the study. Each surgeon conducted fully guided surgery in dentiform models twice, once with VARO Guide® (VG surgery) and the other time with a conventional type of templates, NAVI Guide® (NG surgery). Based on the superimposition of presurgical and postsurgical STL files, the positional deviations between the virtually planned and actually placed implants and the time spent on presurgical preparation and surgical procedures were estimated and compared. RESULTS: All dimensional deviations were similar between the two groups (p > 0.05), and there was no significant difference between the expert and beginner groups regardless of the guide system. The total procedure time (mean (median)) of the VG surgery (26.33 (28.58) min) was significantly shorter than that of the NG surgery (378.83 (379.35) min; p < 0.05). While the time spent only for the fully guided implant surgery (from the start of the surgical guide sitting onto the dentiform model to the final installation of the implant fixture) was comparable (p > 0.05), the presurgical preparation time spent on virtual implant planning and surgical guide fabrication in the VG surgery (19.63 (20.93) min) was significantly shorter compared to the NG surgery (372.93 (372.95) min; p < 0.05). CONCLUSIONS: Regardless of experience, both VG and NG surgery showed reliable positional accuracy; however, the total procedure time and the preparation time were much shorter in the VG surgery compared to the NG surgery.

Clinical and biological significance of EZH2 expression in endometrial cancer.

The objective of this study was to examine the clinical significance of EZH2 expression and the therapeutic efficacy of its silencing in endometrial cancer. EZH2 expression in clinical samples was evaluated using a tissue microarray and correlated with clinical outcomes. The biological roles of EZH2 were assayed in vitro and in vivo. Gene expression was examined to reveal the molecular mechanism underlying the roles of EZH2 in endometrial cancer. We found that EZH2 overexpression was significantly correlated with disease-free and overall survival of patients with endometrial cancer. EZH2 silencing resulted in decreased cell viability and invasiveness, and increased apoptosis. In addition, EZH2 silencing enhanced the cytotoxicity of taxanes and cisplatin in Hec-1A and Ishikawa endometrial cancer cells. EZH2 silencing using small-interfering RNA (siRNA) incorporated into chitosan nanoparticles (siRNA/CN) induced a significant anti-tumor effect compared with that observed in controls (66.6% reduction in Hec-1A cells and 63.2% reduction in Ishikawa cells, p < .05 for both). Moreover, EZH2 siRNA/CN in combination with taxanes produced more robust anti-tumor effects versus those induced by monotherapies (77.0% for Hec-1A cells and 57.7% for Ishikawa cells, p < .05 for both). These results were associated with decreased angiogenesis and cell proliferation, and enhanced apoptosis. Genomic analyses revealed that EZH2 silencing decreased the expression levels of many genes associated with tumor growth, including PRDX6. Collectively, these results support EZH2 as an attractive target for the therapeutic management of endometrial cancer.

Type-Specific Viral Load and Physical State of HPV Type 16, 18, and 58 as Diagnostic Biomarkers for High-Grade Squamous Intraepithelial Lesions or Cervical Cancer.

PURPOSE: High rate of false-positive tests is a major obstacle to use human papillomavirus (HPV) detection as a diagnostic tool for high-grade squamous intraepithelial lesions or cervical cancer (HSIL+). We investigated whether type-specific viral load or physical state of HPV 16, 18, and 58 are useful biomarkers for HSIL+. MATERIALS AND METHODS: Type-specific viral loads of E6 and E2 genes in cervical cells from 240, 83, and 79 HPV 16-, 18-, and 58-infected women, respectively, were determined using real-time polymerase chain reaction. Viral loads were normalized to cellular DNA (copy/cell). Total and integrated viral loads and physical state were compared between HSIL+ and controls, and diagnostic value was determined using receiver operating characteristic analysis. RESULTS: Viral loads of HPV 16, 18, and 58 were significantly different in lesions in the same pathologic grade. High type-specific total viral loads were significantly associated with HSIL+ (odds ratio [OR], 14.065, 39.472, and 7.103 for HPV 16, 18, and 58, respectively). High integrated viral load was related to HSIL+ in women with HPV 16 (OR, 8.242), and integrated state was associated with HSIL+ in women with HPV 18 (OR, 9.443). Type-specific total viral load was significantly associated with HSIL+ (area under curve, 0.914, 0.937, and 0.971 for HPV 16, 18, and 58, respectively), indicating an excellent performance in detecting HSIL+. CONCLUSION: Type-specific total viral load may be a powerful diagnostic marker for HSIL+ in HPV 16-, 18-, and 58-infected HSIL+ lesions. If demonstrated in all other high-risk HPV types, this method can lead to a paradigm shift in the strategy of equivocal cytologic abnormalities.

Human papillomavirus genotypes and cofactors causing cervical intraepithelial neoplasia and cervical cancer in Korean women.

OBJECTIVE: Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, but the risk associated with the various viral types and related cofactors have not been adequately assessed in Korean women. This study aimed to investigate the genotype distribution of HPV and cofactors related to cervical carcinogenesis in Korean women. MATERIALS AND METHODS: We conducted a hospital-based case-control study in 215 women with histologically confirmed cervical neoplasia (111 cases of cervical intraepithelial neoplasia [CIN] and 104 cases of invasive cervical cancer [ICC]) and 1214 healthy control women. Polymerase chain reaction-based dot blot assays were used for detection of 16 high-risk HPV types. To clarify the cofactors, we administered questionnaires evaluating smoking, drinking, and sexual and reproductive history from women infected with HPV. RESULTS: Human papillomavirus was detected in 86.5% of the women with CIN and 96.2% of the women with ICC compared to 14.6% of the control women. The most common HPV types were, in descending order of frequency, types 16, 58, 18, 33, and 66 for CIN, and types 16, 18, 31, and 33 for ICC. Among the control women, HPV 16, 66, 33, 58, 18, and 31 were the most common types. Smoking and higher number of births (≥3) were associated with CIN (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.21-5.15, and OR, 2.67; 95% CI, 1.36-5.28, respectively). This relationship was also found in the women with ICC (OR, 3.42; 95% CI, 1.59-7.38, and OR, 2.17; 95% CI, 1.08-4.38, respectively) compared to controls. In addition, the circumcision of sexual partner and the sexual habit of condom use were protective factors for ICC (OR, 0.47; 95% CI, 0.24-0.90, and OR, 0.19; 95% CI, 0.06-0.57, respectively). CONCLUSION: Human papillomavirus types 16, 18, 31, 33, and 58 are the major causative genotypes for cervical carcinogenesis in Korean women. Smoking and multiparity seem to be the most significant cofactors.

Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.

AIMS: Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes. METHODS: Unsupervised hierarchical clustering analysis was applied to gene expression data from 177 patients with colorectal cancer to determine a prognostic gene expression signature. Validation of the signature was sought in two independent patient groups. The association between the signature and prognosis of patients was assessed by Kaplan-Meier plots, log-rank tests and the Cox model. RESULTS: The authors identified a gene signature that was associated with overall survival and disease-free survival in 177 patients and validated in two independent cohorts of 213 patients. In multivariate analysis, the signature was an independent risk factor (HR 3.08; 95% CI 1.33 to 7.14; p=0.008 for overall survival). Subset analysis of patients with AJCC (American Joint Committee on Cancer) stage III cancer revealed that the signature can also identify the patients who have better outcome with adjuvant chemotherapy (CTX). Adjuvant chemotherapy significantly affected disease-free survival in patients in subtype B (3-year rate, 71.2% (CTX) vs 41.9% (no CTX); p=0.004). However, such benefit of adjuvant chemotherapy was not significant for patients in subtype A. CONCLUSION: The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.

P53 codon 72 and p21 codon 31 polymorphisms and susceptibility to cervical adenocarcinoma in Korean women.

The aims of this study were to evaluate the genotype frequencies of p53 codon 72 and p21 codon 31 in cervical adenocarcinoma patients and controls, and the association between the specific genotype or genotype combination of these polymorphisms and the risk of cervical adenocarcinoma in Korean women. Genotyping was performed using DNA from cervical biopsy specimens collected from 53 patients with cervical adenocarcinoma, of whom 34 were HPV 16 or 18 positive, and from the cervical exfoliated cells from 286 control women, of whom 48 were positive for HPV 16 or 18. For the determination of p53 polymorphisms genomic DNA was examined by PCR amplification of the specific allele assay, and for the determination of p21 polymorphisms DNA was examined by the PCR-RFLP assay using BsmAI. We found significant differences in genotype frequencies of both genes between the two groups (p < 0.001). The p53 genotypes containing the Pro allele were significantly associated with cervical adenocarcinoma with an OR of 2.89 (95% CI 1.54-5.42). Also, homozygous carriers of the p21 Ser allele showed a substantially increased risk of developing cervical adenocarcinoma (OR 2.07; 95% CI 1.13-3.79) compared to genotypes containing the Arg allele. In addition, the combination of the Pro allele containing genotypes of p53 and the Ser homozygous genotype of p21 posed a remarkably increased risk (OR 5.22; 95% CI 2.24-12.16), although the interaction of the two genes could not be found. These significant differences were intensified in groups with high-risk HPV infection (types 16 or 18).

Precipitation characteristics of uranyl ions at different pHs depending on the presence of carbonate ions and hydrogen peroxide.

This work studied the dissolution of uranium dioxide and precipitation characteristics of uranyl ions in alkaline and acidic solutions depending on the presence of carbonate ions and H2O2 in the solutions at different pHs controlled by adding HNO3 or NaOH in the solution. The chemical structures of the precipitates generated in different conditions were evaluated and compared by using XRD, SEM, TG-DT, and IR analyses together. The sizes and forms of the precipitates in the solutions were evaluated, as well. The uranyl ions were precipitated in the various forms, depending on the solution pH and the presences of hydrogen peroxide and carbonate ions in the solution. In a 0.5 M Na2CO3 solution with H2O2, where the uranyl ions formed mixed uranyl peroxy-carbonato complexes, the uranyl ions were precipitated as a uranium peroxide of UO4(H20)4 at pH 3-4, and precipitated as a clarkeite of Na2U2Ox(OH)y(H2O)z above pH 13. In the same carbonate solution without H2O2, where the uranyl ions formed uranyl tris-carbonato complex, the uranyl ions were observed to be precipitated as a different form of clarkeite above pH 13. The precipitate of uranyl ions in a nitrate solution without carbonate ions and H2O2 at a high pH were studied together to compare the precipitate forms in the carbonate solutions.

Design, synthesis, and evaluation of peptidyl fluorescent probe for Zn2+ in aqueous solution.

A new fluorescent peptide probe for the detection of Zn(2+) was synthesized on the basis of zinc binding ligands in zinc enzymes. The peptide that has a unique amino acid sequence displayed a great selectivity for Zn(2+) in the presence of several transition metal ions in aqueous solution. The reversibility, binding stoichiometry, binding affinity, and pH sensitivity of the sensor were studied. Further, on-bead application of the peptide as chemosensors was demonstrated.