Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model.

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1ß (IL-1ß) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1ß induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.

A Sub-20 nm Organic/Inorganic Hybrid Dielectric for Ultralow-Power Organic Thin-Film Transistor (OTFT) With Enhanced Operational Stability.

Organic/inorganic hybrid materials are utilized extensively as gate dielectric layers in organic thin-film transistors (OTFTs). However, inherently low dielectric constant of organic materials and lack of a reliable deposition process for organic layers hamper the broad application of hybrid dielectric materials. Here, a universal strategy to synthesize high-k hybrid dielectric materials by incorporating a high-k polymer layer on top of various inorganic layers generated by different fabrication methods, including AlOx and HfOx , is presented. Those hybrid dielectrics commonly exhibit high capacitance (>300 nF·cm-2 ) as well as excellent insulating properties. A vapor-phase deposition method is employed for precise control of the polymer film thickness. The ultralow-voltage (<3 V) OTFTs are demonstrated based on the hybrid dielectric layer with 100% yield and uniform electrical characteristics. Moreover, the exceptionally high stability of OTFTs for long-term operation (current change less than 5% even under 30 h of voltage stress at 2.0 MV·cm-1 ) is achieved. The hybrid dielectric is fully compatible with various substrates, which allows for the demonstration of intrinsically flexible OTFTs on the plastic substrate. It is believed that this approach for fabricating hybrid dielectrics by introducing the high-k organic material can be a promising strategy for future low-power, flexible electronics.

Effects of a psychological first aid simulated training for pregnant flood victims on disaster relief worker's knowledge, competence, and self-efficacy.

AIMS: To develop a simulation-based psychological first aid (PFA) education program for disaster relief workers and verify its impact on their PFA knowledge, PFA performance competence, and self-efficacy. BACKGROUND: Relief workers should be provided with systematic education on their required knowledge and skills; however, PFA training for relief workers is lacking, which results in ineffective mental health support during disaster situations. METHODS: This study adopted a non-equivalent control group pre-posttest quasi-experimental design. Thirty relief workers from mental health welfare centers in Seoul and Gyeonggi Province participated. The experimental group received a PFA lecture, a simulation-based PFA education program, and access to the Psychological Life Support (PLS) mobile application, which provides information on disaster situations and PFA techniques. The comparison group received a PFA lecture. The control group was provided with self-learning PFA materials. RESULTS: Among the three groups, the experimental group showed the greatest improvement in PFA knowledge, PFA performance competence, and self-efficacy from pretest to posttest, which was statistically significant. CONCLUSIONS: This study demonstrated the effectiveness of the simulation-based PFA education program combined with a PFA lecture and the PLS mobile app as complementary methods to assist relief workers in applying PFA in disaster situations.

DT-Diaphorase as a Bifunctional Enzyme Label That Allows Rapid Enzymatic Amplification and Electrochemical Redox Cycling.

The most common enzyme labels in enzyme-linked immunosorbent assays are alkaline phosphatase and horseradish peroxidase, which, however, have some limitations for use in electrochemical immunosensors. This Article reports that the small and thermostable DT-diaphorase (DT-D) and electrochemically inactive 4-nitroso-1-naphthol (4-NO-1-N) can be used as a bifunctional enzyme label and a rapidly reacting substrate, respectively, for electrochemical immunosensors. This enzyme-substrate combination allows high signal amplification via rapid enzymatic amplification and electrochemical redox cycling. DT-D can convert an electrochemically inactive nitroso or nitro compound into an electrochemically active amine compound, which can then be involved in electrochemical-chemical (EC) and electrochemical-enzymatic (EN) redox cycling. Six nitroso and nitro compounds are tested in terms of signal-to-background ratio. Among them, 4-NO-1-N exhibits the highest signal-to-background ratio. The electrochemical immunosensor using DT-D and 4-NO-1-N detects parathyroid hormone (PTH) in phosphate-buffered saline containing bovine serum albumin over a wide range of concentrations with a low detection limit of 2 pg/mL. When the PTH concentration in clinical serum samples is measured using the developed immunosensor, the calculated concentrations are in good agreement with the concentrations obtained using a commercial instrument. Thus, the use of DT-D as an enzyme label is highly promising for sensitive electrochemical detection and point-of-care testing.

A comparative study on eating habits and mental health of Korean middle school students according to their bedtime across regions: using data from the 2020-2022 Korea Youth Risk Behavior Survey.

BACKGROUND/OBJECTIVES: The objective of this study was to compare dietary habits and mental health among middle school students in urban and rural areas based on bedtime, and to provide evidence supporting appropriate bedtime for Korean middle school students in relation to their healthy dietary habits and mental well-being. SUBJECTS/METHODS: The study population consisted of 25,681 second-year middle school students who participated in the Korea Youth Risk Behavior Survey in 2020-2022. Participants were asked about their bedtime and wake-up time during the past 7 days and were classified into five categories. The study compared the general characteristics, academic factors, dietary habits, and mental health of urban and rural students based on their bedtime. RESULTS: Bedtime was found to be later in the following order: urban female students, rural female students, urban male students, and rural male students. As bedtime got later, the rates of smoking and alcohol consumption increased. Students who went to bed before 11 p.m. had lower academic performance, while rural male students who went to bed after 2 a.m. had lower academic performance. Later bedtime was associated with increased smartphone usage, skipping breakfast, consuming fast food, and drinking carbonated beverages. Later bedtime was also associated with higher perceived stress levels, particularly among students who went to bed after 2 a.m., higher rates of suicidal ideation, experiencing sadness and despair, as well as the prevalence of clinically significant anxiety disorders. CONCLUSION: These results suggest that middle school students who go to bed too late have higher rates of smoking and alcohol drinking, as well as unhealthy eating habits, stress, suicidal ideation, sadness, and anxiety. Therefore, it is necessary to provide educational and social institutional support to promote adequate sleep for the health of adolescents.

Photochemically Inert Broad-Spectrum Sunscreen by Metal-Phenolic Network Coatings of Titanium Oxide Nanoparticles.

Titanium dioxide (TiO2) nanoparticles are extensively used as a sunscreen filter due to their long-active ultraviolet (UV)-blocking performance. However, their practical use is being challenged by high photochemical activities and limited absorption spectrum. Current solutions include the coating of TiO2 with synthetic polymers and formulating a sunscreen product with additional organic UV filters. Unfortunately, these approaches are no longer considered effective because of recent environmental and public health issues. Herein, TiO2-metal-phenolic network hybrid nanoparticles (TiO2-MPN NPs) are developed as the sole active ingredient for sunscreen products through photochemical suppression and absorption spectrum widening. The MPNs are generated by the complexation of tannic acid with multivalent metal ions, forming a robust coating shell. The TiO2-MPN hybridization extends the absorption region to the high-energy-visible (HEV) light range via a new ligand-to-metal charge transfer photoexcitation pathway, boosting both the sun protection factor and ultraviolet-A protection factor about 4-fold. The TiO2-MPN NPs suppressed the photoinduced reactive oxygen species by 99.9% for 6 h under simulated solar irradiation. Accordingly, they substantially alleviated UV- and HEV-induced cytotoxicity of fibroblasts. This work outlines a new tactic for the eco-friendly and biocompatible design of sunscreen agents by selectively inhibiting the photocatalytic activities of semiconductor nanoparticles while broadening their optical spectrum.

The Effect of Alkyl Chain Length in Organic Semiconductor and Surface Polarity of Polymer Dielectrics in Organic Thin-Film Transistors (OTFTs).

The interface between dielectric and organic semiconductor is critically important in determining organic thin-film transistor (OTFT) performance. Surface polarity of the dielectric layer can hinder charge transport characteristics, which has restricted utilization of polymeric dielectric materials containing polar functional groups. Herein, the electrical characteristics of OTFTs are analyzed depending on the alkyl chain length of organic semiconductors and surface polarity of polymer dielectrics. High-performance dibenzothiopheno[6,5-b:6',5'-f]thieno[3,2-b]thiophene (DBTTT) and newly synthesized its alkylated derivatives (C6-DBTTT and C10-DBTTT) are utilized as organic semiconductors. As dielectric layers, non-polar poly(1,3,5-trimethyl-1,3,5-trivinylcyclitrisiloxane) (pV3D3) and poly(2-cyanoethyl acrylate-co-diethylene glycol divinyl ether) [p(CEA-co-DEGDVE)] with polar cyanide functionality are utilized. The fabricated OTFTs with pV3D3 commonly exhibit the excellent charge transport characteristics. In addition, the OTFT performance is improved with lengthening the alkyl chain in organic semiconductors, which can be attributed to the molecular orientation of semiconductors. On the other hand, non-alkylated DBTTT OTFTs with polar p(CEA-co-DEGDVE) show relatively poor electrical characteristics, while their performance is drastically enhanced with the alkylated DBTTTs. The ultraviolet photoelectron spectroscopy (UPS) reveals that surface polarity of the dielectric layer can be abated with alkyl chain in organic semiconductors. It is believed that this study can provide a useful insight to optimize dielectric/semiconductor interface to achieve high-performance OTFTs.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort.

BACKGROUND: To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD. METHODS: Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients. RESULTS: Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412). CONCLUSIONS: Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

Effect of Surgical Findings on Prediction of Postoperative Ovarian Reserve in Patients with Ovarian Endometrioma.

Objective: Revised American Society for Reproductive Medicine (rASRM) classification for endometriosis is considered to have limited ability to predict fertility after surgery. This study evaluated the effect of surgical findings described by the rASRM classification on postoperative change in serum Anti-Müllerian hormone (AMH) in endometriosis. Study Design: We retrospectively analyzed 112 patients with endometrioma who underwent laparoscopic ovarian cystectomy. The ovarian score was defined as the sum of the endometrioma score from the size and depth of endometrioma and the adhesion score from the extent and types of ovarian adhesion described in the rASRM classification. The ovarian score was correlated with the AMH levels before surgery (AMH0), 3 (AMH3), and 6 months (AMH6) after surgery. To design a model for predicting AMH6, using ovarian score and AMH0, we calculated the unstandardized predictive value of AMH6/AMH0 (UPV) by linear regression analysis. The predicted AMH6 (pAMH6) could be calculated by multiplying the UPV by AMH0. When AMH6 is less than 1.0 ng/mL, it was defined as a poor ovarian reserve group (PORG), and the accuracy of the predictive model was validated. Results: The level of AMH declined more in rASRM stage IV compared to stage III after surgery. The ovarian score had a significant variable in the linear regression analysis with the ratio of AMH6/AMH0 (p = 0.001). The UPV was correlated with ovarian score negatively. The pAMH6 correlated with AMH6 positively and with age negatively. The pAMH6 showed sensitivity 0.564, specificity 0.909, positive predictive rate 0.786, and negative predictive rate 0.800 in the prediction of PORG (p < 0.001). Conclusion: The pAMH6 predicted the PORG at 6 months after surgery. Based on the results of our study, the surgical findings, including the size and depth of the endometrioma and extent and types of adhesion could be useful indicators for ovarian reserve after surgery.

Prediction of radiographic progression pattern in patients with ankylosing spondylitis using group-based trajectory modeling and decision trees.

Objective: This study aimed to identify trajectories of radiographic progression of the spine over time and use them, along with associated clinical factors, to develop a prediction model for patients with ankylosing spondylitis (AS). Methods: Data from the medical records of patients diagnosed with AS in a single center were extracted between 2001 and 2018. Modified Stoke Ankylosing Spondylitis Spinal Scores (mSASSS) were estimated from cervical and lumbar radiographs. Group-based trajectory modeling classified patients into trajectory subgroups using longitudinal mSASSS data. In multivariate analysis, significant clinical factors associated with trajectories were selected and used to develop a decision tree for prediction of radiographic progression. The most appropriate group for each patient was then predicted using decision tree analysis. Results: We identified three trajectory classes: class 1 had a uniformly increasing slope of mSASSS, class 2 showed sustained low mSASSS, and class 3 showed little change in the slope of mSASSS but highest mSASSS from time of diagnosis to after progression. In multivariate analysis for predictive factors, female sex, younger age at diagnosis, lack of eye involvement, presence of peripheral joint involvement, and low baseline erythrocyte sedimentation rate (log) were significantly associated with class 2. Class 3 was significantly associated with male sex, older age at diagnosis, presence of ocular involvement, and lack of peripheral joint involvement when compared with class 1. Six clinical factors from multivariate analysis were used for the decision tree for classifying patients into three trajectories of radiographic progression. Conclusion: We identified three patterns of radiographic progression over time and developed a decision tree based on clinical factors to classify patients according to their trajectories of radiographic progression. Clinically, this model holds promise for predicting prognosis in patients with AS.

Fetal intracranial hemorrhage and maternal vitamin K deficiency induced by total parenteral nutrition: A case report.

RATIONALE: Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause. PATIENT CONCERNS: We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation. DIAGNOSIS: After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed. INTERVENTIONS: After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring. OUTCOMES: The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed. LESSONS: This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.

Hyponatremia Associated with Pulmonary Arterial Hypertension: Syndrome of Inappropriate Antidiuresis Versus Right Heart Failure.

Because it is associated with mortality, hyponatremia is an important feature of pulmonary arterial hypertension. Its mechanisms remain unclear, although right heart failure resulting from pulmonary arterial hypertension may lead to systemic congestion and arterial underfilling. However, most patients with pulmonary arterial hypertension are clinically euvolemic and have no peripheral edema. Unlike patients with underlying heart disease, neurohumoral activation is not demonstrated in hyponatremic patients with pulmonary arterial hypertension, who show features of congestive heart failure only at later stages in their disease. Here, a case vignette is introduced, and the pathophysiology of hyponatremia in pulmonary arterial hypertension will be discussed. Syndrome of inappropriate antidiuresis (SIAD) appears to underlie hyponatremia in the initial phase of pulmonary arterial hypertension. The mechanisms by which various lung diseases can lead to SIAD remain an enigma.

Risk of malignancy in Korean patients with primary Sjögren's syndrome.

OBJECTIVES: To evaluate the risks of overall and site-specific malignancies in Korean patients with primary Sjögren's syndrome (pSS). METHODS: Using the Korean nationwide healthcare claims database, we constructed a retrospective cohort for prevalent pSS aged over 50 years. After enrollment between January 2012 and December 2014, patients were followed until the development of any malignancy, or until December 2015. Crude incidence rates of malignancies of pSS patients were calculated, and their standardized incidence ratios (SIRs) for malignancies were calculated compared to those in knee osteoarthritis (OA) patients. RESULTS: A total of 6,359 pSS and 5,476,302 knee OA patients were included in this study. During follow-up (19,474 person-years [PYs]), 310 cases of solid malignancy (158.8/10,000 PYs) and 47 cases of hematologic malignancies (23.5/10,000 PYs) were observed in pSS patients. The risks of overall (SIR 1.30, 95% CI 1.16-1.43), solid (SIR 1.16, 95% CI 1.03-1.29), and hematologic malignancies (SIR 4.80, 95% CI 3.43-6.17) were increased in pSS patients. There was an elevated risk of site-specific malignancy in non-Hodgkin's lymphoma (NHL, SIR 6.45, 95% CI 4.05-8.83), multiple myeloma (SIR 4.88, 95% CI 2.00-7.76), and oropharynx (SIR 4.16, 95% CI 1.90-6.42). The risk of lung cancer was increased only in male pSS patients (2.50, 95% CI 1.02-3.99), while the risk of thyroid cancer was increased in female patients (1.44, 95% CI 1.04, 1.84). CONCLUSION: In patients with pSS over age 50, the risk of solid cancers such as oropharynx, thyroid, and lung cancers is also increased in addition to NHL.

Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood. METHODS: In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients. RESULTS: In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro. CONCLUSIONS: Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

Identifying damage clusters in patients with systemic lupus erythematosus.

AIM: Systemic lupus erythematosus (SLE) causes irreversible damage to organ systems. Recently, evidence has been obtained for subphenotypes of SLE. This study aimed to identify damage clusters and compare the associated clinical manifestations, SLE disease activity, mortality, and genetic risk scores (GRS). METHODS: The study was conducted on the Hanyang BAE lupus cohort. Patients with disease duration <5 years were excluded to minimize confounding effects of disease duration. They were grouped into 3 clusters based on the Systemic Lupus International Collaborating Clinics Damage Index using k-means cluster analysis. RESULTS: Among the 1130 analyzed patients, musculoskeletal damage was most prevalent (20.2%), followed by ocular (11.4%), renal (10.5%), and neuropsychiatric damage (10.2%). Three significantly different damage clusters were identified. Patients in cluster 1 (n = 824) showed the least damage. Cluster 2 (n = 195) was characterized by frequent renal (55.4%) and ocular (58.0%) damage, and cluster 3 (n = 111) was dominated by neuropsychiatric (100%) and musculoskeletal damage (35.1%). Cluster 2 had the highest adjusted mean AMS (adjusted mean SLE Disease Activity Index score; mean ± SD: 5.4 ± 2.9), while cluster 3 had the highest mortality (14.4%). Weighted GRS did not differ significantly between the clusters. CONCLUSION: Patients in prevalent renal and ocular damage cluster had the highest AMS scores, while the cluster with frequent neuropsychiatric damage had the highest mortality.

Conformal 3D Nanopatterning by Block Copolymer Lithography with Vapor-Phase Deposited Neutral Adlayer.

Block copolymer (BCP) lithography is an effective nanopatterning methodology exploiting nanoscale self-assembled periodic patterns in BCP thin films. This approach has a critical limitation for nonplanar substrate geometry arising from the reflow and modification of BCP films upon the thermal or solvent annealing process, which is inevitable to induce the mobility of BCP chains for the self-assembly process. Herein, reflow-free, 3D BCP nanopatterning is demonstrated by introducing a conformally grown adlayer by the initiated chemical vapor deposition (iCVD) process. A highly cross-linked poly(divinylbenzene) layer was deposited directly onto the BCP thin film surface by iCVD, which effectively prevented the reflow of BCP thin film during an annealing process. BCP nanopatterns could be stabilized on various substrate geometry, including a nonplanar deformed polymer substrate, a pyramid shape substrate, and a graphene fiber surface. A fiber-type hydrogen evolution reaction (HER) catalyst is suggested by stabilizing lamellar Pt nanopatterns on severely rough graphene fiber surfaces.

Deletion at 2q14.3 is associated with worse response to TNF-α blockers in patients with rheumatoid arthritis.

BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment. RESULTS: The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10- 5 ≤ P ≤ 4.07 × 10- 4) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK. CONCLUSIONS: This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers.