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Recognizing intolerance or resistance to hydroxyurea (HU), which is related to the high risk of a disease transformation and reduced survival in essential thrombocythemia (ET), is crucial to making a reasonable decision about second-line therapy. We assessed the prognostic impact of the modified European LeukemiaNet (mELN) criteria used in a recent MAJIC-ET trial by analyzing the incidence of resistance or intolerance to HU and the survival outcome compared with those of the ELN criteria.We retrospectively compared the development of HU resistance or intolerance according to the ELN and mELN criteria for 148 high-risk ET patients receiving HU between 2014 and 2018. The maximum tolerated dose for defining HU resistance was used in the mELN criteria.The median age of patients was 65 years (range, 36-87), with a median follow-up of 3.6 years (range, 1.1-6.4). Two thromboembolic events were observed during HU treatment. When applying the ELN criteria, 10 patients (6.9%) were resistant (n = 5 [3.4%]) or intolerant (n = 5 [3.4%]) to HU in comparison with 22 patients (15%, 14 [9.8%]) resistant and 8 [5.5%] intolerant when applying the mELN criteria. Transformation to myelofibrosis and acute myeloid leukemia occurred in 2 (1.4%) patients and 1 (0.7%) patient, respectively, as defined by the ELN criteria compared with 3 (2.1%) and 2 (1.4%) patients as defined by the mELN criteria. In multivariate analysis of transformation-free survival, HU resistance defined by the mELN criteria but not the ELN criteria was an independent prognostic factor. In addition, HU resistance as defined by both sets of criteria was an independent risk factor for inferior overall survival. Intolerance of HU did not have any prognostic impact on survival.The mELN criteria are useful for identifying high-risk ET patients who might be eligible for second-line therapy in practice, which should be validated in a prospective setting.

There are limited studies on the association of COVID-19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID-19 vaccination and the occurrence of NA.We explored unexpected safety signals for NA related to COVID-19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database.On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (information component [IC]A weak association was observed between NA and COVID-19 vaccines. However, the risk did not surpass that of influenza vaccines.

Actinidia polygama (silver vine) is considered a medical plant which has been used in oriental medicine. It has been used for the treatment of pain, gout, rheumatoid arthritis, and inflammation. Few studies reported on the effect of Actinidia polygama (silver vine) on skin photoaging.To evaluate the anti-photoaging effect of the ethanol and water extracts of A. polygama (APEE and APWE, respectively) in UVB-irradiated hairless mice.SKH-1 hairless mice were exposed to UVB irradiation (30-60 mJ/cmOral administration of APEE or APWE at 100 or 200 mg/kg in UVB-irradiated mice alleviated the symptoms of skin aging, such as wrinkling, epidermal hyperplasia, and water loss. In addition, the APEE or APWE oral administration increased skin elasticity by enhancing the production of type I collagen, elastin, and hyaluronic acid synthase and downregulating matrix metalloproteinase (1, 3, and 9) expression.Based on results for our study, APEE or APWE could protect the UVB-mediated skin wrinkle and is new target for the developing anti-wrinkle cosmetics.

An innovative foam formulation for the fixed-dose combination of calcipotriol and betamethasone dipropionate (Cal/BD) has recently become available for the treatment of psoriasis vulgaris. Observational studies of patients treated with Cal/BD foam in routine practice have been conducted in several Western countries, but there are limited data on outcomes in Asian patients. We performed a prospective, open-label, noncomparative, noninterventional study to investigate treatment outcomes and satisfaction in adult patients receiving Cal/BD foam for psoriasis vulgaris in dermatological centers and outpatient clinics in Korea. Data were collected at the time of enrollment (Visit 1) and at a routine clinic visit ~4 weeks later (Visit 2). In total, 218 patients were enrolled, of whom 175 were included in the safety analysis set (58.9% male; mean age ± standard deviation 46.7 ± 15.1 years; use of Cal/BD foam at least once daily 74.3%). Of the safety analysis set, 166 patients had at least mild psoriasis (Investigator Global Assessment [IGA] ≥ 2) and were analyzed for treatment outcomes and satisfaction. Of the 166 patients, 71.7% had mild psoriasis (IGA 2) at baseline. The majority (57.8%) achieved an IGA of 0/1 (clear/almost clear) at Visit 2. The Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) showed significant improvements from Visit 1 to Visit 2 (PASI -2.4 ± 3.0, DLQI -4.5 ± 5.2, both P 0.0001). Most of the patients were satisfied with the Cal/BD foam treatment; 77.0%, 60.0%, and 73.9% were satisfied in terms of effectiveness, ease of use, and global satisfaction, respectively. In the safety analysis set, adverse events were reported in 13 patients (7.4%). In conclusion, this first Korean real-world study of Cal/BD foam shows improvement of lesions and health-related quality of life after 4 weeks of treatment, with high global satisfaction and good overall tolerability and safety.

Wearing a face mask is one of the most effective personal protective strategies to diminish the spread of coronavirus disease 2019 (COVID-19). Several dermatological outcomes were reported because of the prolonged use of face masks, especially due to the constant mask-on policy, but the photoprotective effect of face masks has received less attention.The aim of this study was to provide guidance in the use of face masks by comparing the photoprotective effects of routinely used masks.A total of 12 frequently used face masks were tested, including certified respirators, Korea filter (KF)94, KF-anti-droplet (KF-AD), and KF80. The amount of light that penetrates each face mask was measured using a light sensor that can quantify Ultraviolet A (UVA), visible light (VL), and infrared A (IR-A) rays.Black-colored KF94 masks and surgical masks reduced penetration of UVA, VL, and IR-A by approximately 100%. The UVA penetration decreased on average by 95.51%, 90.97%, 85.06%, and 86.41% with white-colored KF94, KF-AD, KF80, and surgical masks, respectively. The VL and IR-A were blocked by approximately 75.58%, 66.16%, 59.18%, and 64.48% with white-colored KF94, KF-AD, KF80, and surgical masks, respectively.In conclusion, the different photoprotective effectiveness of face masks was mainly determined by colors, and therefore, black-colored, multi-layered respirators can be recommended in terms of photoprotection in the COVID-19 pandemic. The quantified comparative results will be helpful to the person with pre-existing photo-aggravated dermatosis, especially in the season of the high intensity of sunlight.

Infection is associated with the occurrence, recurrence, and progression of atrial fibrillation (AF), and is also closely related to poor prognosis. However, studies of the relationship between infectivity and severe complications of coronavirus infectious disease-19 (COVID-19) with a history of AF are limited. To estimate infectivity and severity of complications in COVID-19 patients with a history of AF, this study was done. From the Korean nationwide COVID-19 dataset, 212 678 participants with at least one severe acute respiratory syndrome coronavirus 2 (COVID-19) test were included between January 1 and June 4, 2020. AF was defined according to at least two outpatient hospital visits or one admission with an ICD-10 code of "I48" before the COVID-19 test. To investigate the association of AF with infectivity and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) was performed. Severe complications of COVID-19 were defined as a composite outcome of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. Among 212 678 participants who underwent the COVID-19 test, there were 7713 COVID-19 positive patients. After PSM, COVID-19 PCR positivity did not show a significant difference according to the presence of AF (odds ratio [OR]: 0.79, 95% confidence interval [CI]: [0.60-1.04]). Of 7713 COVID-19 patients, 62 (0.8%) had a history of AF and severe complications occurred in 444 (5.7%) patients. After PSM, AF was associated with the development of severe complications (OR: 2.04, 95% CI: [1.10-3.79]) and mortality (OR: 2.09, 95% CI: [1.01-4.31]) of COVID-19. We found that AF was associated with an increased risk of severe complications in COVID-19 infected patients.

We estimated volume changes in the posterior bony wall of the sphenoid sinus, as well as alterations in nasal function (including olfactory function and subjective symptoms), after sphenoid mucosal repositioning using the endoscopic endonasal transsphenoidal approach (EETSA).During 2010 and 2021, 13 patients underwent sphenoid mucosal repositioning during EETSA, while 24 patients (the control group) did not. Pre- and postoperative paranasal sinus computed tomography and the Mimics program were used to evaluate three-dimensional changes in the posterior wall of the sphenoid sinus. All patients underwent the Connecticut Chemosensory Clinical Research Center (CCCRC) test, the Cross-Cultural Smell Identification Test (CCSIT), Nasal Obstruction Symptoms Evaluation (NOSE), the Sino-Nasal Outcome Test-20 (SNOT-20), and visual analog scale (VAS) evaluation.The increase in the volume of the posterior wall of the sphenoid sinus after surgery was objectively smaller in the sphenoid mucosal repositioning group than in the control group (P = .046). However, this did not affect olfactory function (as revealed by the CCCRC test or the CCSIT) or subjective symptoms (as revealed by the NOSE, SNOT-20, and VAS scores) (all P .05).Surgical closure via sphenoid mucosal repositioning during EETSA reduces the volume of the posterior wall of the sphenoid sinus and facilitates re-operation. We suggest that sphenoid mucosal repositioning is appropriate during EETSA.4 Laryngoscope, 132:965-972, 2022.

The mechanical and physical properties of implant screw access opening deteriorate if composite resin is not polymerized properly. Therefore, this study aimed to analyze the effect of using composite resin in implant access opening on the degree of conversion (DC).Two prosthetic materials (Co-Cr and zirconia), two types of composite resin (low and high viscosity), two light-cured resin depths (2 and 3 mm), and two polymerization methods (max-mode 10 s and mid-mode 20 s: 16 and 22 J/cm2, respectively) were considered (n = 192). The DC of the polymerized composite resin was measured through Fourier-transform infrared (FTIR) spectroscopy. The top and bottom surfaces of the polymerized composite resin body were observed through scanning electron microscopy. Multiple linear regression analysis and analysis of variance (ANOVA) were used to identify significant differences in DC (α = .05).The DC was lower when the low-viscosity composite resin (β = -0.431), light-polymerized resin depth of 2 mm (β = -0.430), zirconia prosthesis (β = -0.191), and mid-mode polymerization method (β = -0.164) were used. The resin type, depth of resin to be light-cured, prosthesis material, and polymerization method had an effect on the DC.Low-viscosity composite resin should be polymerized at a low irradiance and long polymerization time (such that the light-cured resin depth does not exceed 2 mm) to ensure proper composite resin polymerization in implant screw access opening. This article is protected by copyright. All rights reserved.

Funder: New faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0049)., Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

Hypoxic‐ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin‐preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin‐preconditioned human Wharton's jelly‐derived mesenchymal stem cells (th‐hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th‐hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th‐hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague‐Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th‐hWJMSCs on the growth of newborn babies. Our results suggest that th‐hWJMSCs are non‐toxic and non‐tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.

We aimed to evaluate the performance of convolutional neural networks (CNNs) in the classification of coronavirus disease 2019 (COVID‐19) disease using normal, pneumonia, and COVID‐19 chest radiographs (CXRs). First, we collected 9194 CXRs from open datasets and 58 from the Korea University Anam Hospital (KUAH). The number of normal, pneumonia, and COVID‐19 CXRs were 4580, 3884, and 730, respectively. The CXRs obtained from the open dataset were randomly assigned to the training, tuning, and test sets in a 70:10:20 ratio. For external validation, the KUAH (20 normal, 20 pneumonia, and 18 COVID‐19) dataset, verified by radiologists using computed tomography, was used. Subsequently, transfer learning was conducted using DenseNet169, InceptionResNetV2, and Xception to identify COVID‐19 using open datasets (internal) and the KUAH dataset (external) with histogram matching. Gradient‐weighted class activation mapping was used for the visualization of abnormal patterns in CXRs. The average AUC and accuracy of the multiscale and mixed‐COVID‐19Net using three CNNs over five folds were (0.99 ± 0.01 and 92.94% ± 0.45%), (0.99 ± 0.01 and 93.12% ± 0.23%), and (0.99 ± 0.01 and 93.57% ± 0.29%), respectively, using the open datasets (internal). Furthermore, these values were (0.75 and 74.14%), (0.72 and 68.97%), and (0.77 and 68.97%), respectively, for the best model among the fivefold cross‐validation with the KUAH dataset (external) using domain adaptation. The various state‐of‐the‐art models trained on open datasets show satisfactory performance for clinical interpretation. Furthermore, the domain adaptation for external datasets was found to be important for detecting COVID‐19 as well as other diseases.

This study investigated the effect of the antioxidant dieckol, a component of Ecklonia cava, on maturation and developmental competence of porcine oocytes exposed to oxidative stress in vitro. Oocytes were matured in in vitro maturation (IVM) medium containing various concentrations of dieckol. The blastocyst formation rate was highest in the 0.5 μM dieckol-treated (0.5 DEK) group. The reactive oxygen species level was decreased, and the level of glutathione and expression of antioxidant genes (NFE2L, SOD1, and SOD2) at metaphase II were increased in the 0.5 DEK group. Abnormal spindle organization and chromosome misalignment were prevented in the 0.5 DEK group. Expression of maternal markers (CCNB1 and MOS) and activity of p44/42 mitogen-activated protein kinase were increased in the 0.5 DEK group. After parthenogenetic activation, the total number of cells per blastocyst was increased and the percentage of apoptotic cells was decreased in the 0.5 DEK group. Expression of development-related genes (CX45, CDX2, POU5F1, and NANOG), antiapoptotic genes (BCL2L1 and BIRC5), and a proapoptotic gene (CASP3) were altered in the 0.5 DEK group. These results indicate that the antioxidant dieckol improves IVM and subsequent development of porcine oocytes and can be used to improve the quality of oocytes under peroxidation experimental conditions.

Eosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL-1β overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro-autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy-enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL-1β production in ECRS pathogenesis.We investigated the therapeutic effects of trehalose and saccharin on macrophage IL-1β production and eosinophilia in the mouse model of ECRS with myeloid cell-specific autophagy-related gene 7 (Atg7) deletion. The mechanisms underlying their anti-inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors.Unexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy-independent effect was associated with reduced macrophage IL-1β expression. Various sugars recapitulated the anti-inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL-1β production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin.Our results revealed a previously unappreciated anti-inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment.

In flowering plants, double fertilization between male and female gametophytes, which are separated by distance, largely depends on the unique pattern of the male gametophyte (pollen): two non-motile sperm cells suspended within a tube-producing vegetative cell. A morphological screen to elucidate the genetic control governing the strategic patterning of pollen has led to the isolation of a sticky generative cell (sgc) mutant that dehisces abnormal pollen with the generative cell immobilized at the pollen wall. Analyses revealed that the sgc mutation is specifically detrimental to pollen development, causing ectopic callose deposition that impedes the timely internalization and differentiation of the generative cell. We found that the SGC gene encodes the highly conserved domain of unknown function 707 (DUF707) gene that is broadly expressed but is germline specific during pollen development. Additionally, transgenic plants co-expressing fluorescently fused SGC protein and known organelle markers showed that SGC localizes in the endoplasmic reticulum, Golgi apparatus and vacuoles in pollen. A yeast two-hybrid screen with an SGC bait identified a thaumatin-like protein that we named GCTLP1, some homologs of which bind and/or digest β-1,3-glucans, the main constituent of callose. GCTLP1 is expressed in a germline-specific manner and colocalizes with SGC during pollen development, indicating that GCTLP1 is a putative SGC interactor. Collectively, our results show that SGC suppresses callose deposition in the nascent generative cell, thereby allowing the generative cell to fully internalize into the vegetative cell and correctly differentiate as the germline progenitor, with the potential involvement of the GCTLP1 protein, during pollen development in Arabidopsis.

OBJECTIVE To determine the association between insufficient sleep in the prenatal period and postpartum depression (PPD), and whether changes in sleep patterns during pregnancy increase the risk of PPD. METHODS A prospective cohort study was conducted between March 2013 and November 2017. Participants completed a sleep questionnaire pre-pregnancy and at 12, 24 and 36 gestational weeks (GW). Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, and the cut-off score for PPD was 10 or more. RESULTS Of 2512 participants, 410 (16.3%) were identified as having PPD. Only insufficient sleep at 36 GW was significantly associated with PPD after adjusting for confounding factors (odds ratio 1.79, 95% confidence interval 1.40-2.27, P