Atto-Scale Noise Near-Infrared Organic Photodetectors Enabled by Controlling Interfacial Energetic Offset through Enhanced Anchoring Ability.

The near-infrared (NIR) sensor technology is crucial for various applications such as autonomous driving and biometric tracking. Silicon photodetectors (SiPDs) are widely used in NIR applications; however, their scalability is limited by their crystalline properties. Organic photodetectors (OPDs) have attracted attention for NIR applications owing to their scalability, low-temperature processing, and notably low dark current density (JD), which is similar to that of SiPDs. However, the still high JD (at NIR band) and few measurements of noise equivalent powers (NEPs) pose challenges for accurate performance comparisons. This study addresses these issues by quantitatively characterizing the performance matrix and JD generation mechanism using electron-blocking layers (EBLs) in OPDs. The energy offset at an EBL/photosensitive layer interface determines the thermal activation energy and directly affects JD. A newly synthesized EBL (3PAFBr) substantially enhances the interfacial energy barrier by forming a homogeneous contact owing to the improved anchoring ability of 3PAFBr. As a result, the OPD with 3PAFBr yields a noise current of 852 aA (JD = 12.3 fA cm⁻2 at V → -0.1 V) and several femtowatt-scale NEPs. As far as it is known, this is an ultralow of JD in NIR OPDs. This emphasizes the necessity for quantitative performance characterization.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22-09.

BACKGROUND: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. METHODS: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. DISCUSSION: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. TRIAL REGISTRATION: NCT05525858.

A MOF-Templated Double-Shelled Co3O4/NiCo2O4 Nanocomposite for Electrochemical Detection of Alfuzosin.

We developed a novel electrochemical sensor for the detection of alfuzosin (AFZ), a drug used to treat benign prostatic hyperplasia, using a double-shelled Co3O4/NiCo2O4 nanocomposite-modified electrode. The nanocomposites were synthesized using a template-assisted approach, with zeolitic imidazole framework-67 (ZIF-67) as the sacrificial template, involving the formation of uniform ZIF-67/Ni-Co layered double hydroxide (LDH) hollow structures followed by calcination to achieve the final nanocomposite. The nanocomposite was characterized by various techniques and showed high porosity, large surface area, and good conductivity. The nanocomposite-modified electrode exhibited excellent electrocatalytic activity towards AFZ oxidation, with a wide linear range of 5-180 µM and a low limit of detection of 1.37 µM. The sensor also demonstrated good repeatability, reproducibility, and stability selectivity in the presence of common interfering substances. The sensor was successfully applied to determine the AFZ in pharmaceutical tablets and human serum samples, with satisfactory recoveries. Our results suggest that the double-shelled Co3O4/NiCo2O4 nanocomposite is a promising material for the fabrication of electrochemical sensors for AFZ detection.

Cytosine-Rich Oligonucleotide and Electrochemically Reduced Graphene Oxide Nanocomposite for Ultrasensitive Electrochemical Ag+ Sensing.

Silver ions (Ag+) are crucial in various fields, but pose environmental and health risks at high concentrations. This study presents a straightforward approach for the ultra-trace detection of Ag+, utilizing a composite of a cytosine-rich oligonucleotide (CRO) and an electrochemically reduced graphene oxide (ERGO). Initially, ERGO was synthesized on a glassy carbon electrode (GCE) through the reduction of graphene oxide (GO) via cyclic voltammetry. A methylene blue-tagged CRO (MB-CRO) was then anchored to the ERGO surface through π-π interactions, resulting in the formation of an MB-CRO-modified ERGO electrode (MB-CRO/ERGO-GCE). The interaction with Ag+ ions induced the formation of silver-mediated C-Ag+-C coordination, prompting the MB-CRO to adopt a hairpin structure. This conformational change led to the desorption of the MB-CRO from the ERGO-GCE, causing a variation in the redox current of the methylene blue associated with the MB-CRO. Electrochemical assays revealed that the sensor exhibits extraordinary sensitivity to Ag+ ions, with a linear detection range from 1 femtomolar (fM) to 100 nanomolars (nM) and a detection limit of 0.83 fM. Moreover, the sensor demonstrated high selectivity for Ag+ ions and several other benefits, including stability, reproducibility, and straightforward fabrication and operational procedures. Additionally, real sample analyses were performed using the modified electrode to detect Ag+ in tap and pond water samples, yielding satisfactory recovery rates.

Laser-Printed Photoanode: Femtosecond Laser-Induced Crystalline Phase Transformation of WO3 Nanorods for Space-Efficient and Flexible Thin-Film Solar Water-Splitting Cells.

Despite its potential for clean hydrogen harvesting, photoelectrochemical (PEC) water-splitting cells face challenges in commercialization, particularly related its harvesting performance and productivity at an industrial scale. Herein, a facile fabrication method of flexible thin-film photoanode for PEC water-splitting to overcome these limitations, based on laser processing technologies, is proposed. Laser-induced graphene, a carbon structure produced through direct laser writing carbonization (DLWC), plays a dual role: a flexible and stable current collector and a substrate for the hydrothermal synthesis of tungsten trioxide (WO3) nanorods (NRs). To facilitate water-splitting, a femtosecond-pulsed laser (fs laser) is focused on the WO3 NRs, converting their crystalline phase from pristine orthorhombic to monoclinic structure without thermal damage. With NiFe layered double hydroxide (LDH) catalyst, the flexible thin-film photoanode exhibits good PEC performance (1.46 mA cm-2 at 1.23 VRHE) and retains ≈90% of its performance after 3000 bending cycles. With its excellent mechanical properties, the flexible photoanode can be operated in various shapes with different curvatures, enabling space-efficient PEC water-splitting by loading larger photoanode within a given space. This study is expected to contribute to the advancement of large-scale solar water-splitting cells, introducing a new approach to enhance H2/O2 production and expand its application range.

Distribution of 35 Polycyclic Aromatic Hydrocarbons in Pine Needle Samples from Selected Locations in the Republic of Korea.

Polycyclic aromatic hydrocarbons (PAHs), dust, and wax were measured in pine needles, and PAHs were also measured in surface soil. Pearson correlation analysis was performed between the analytical values. The main compounds responsible for the increase in total PAHs were non-carcinogenic phenanthrene and fluoranthene. Therefore, the % content of carcinogenic PAHs decreased with a slope = -0.037 (r = 0.47, p < 0.01), as the total PAH concentration in pine needles increased. Correlations between individual PAHs in pine needles and surface soil were very high when only low-number ring PAHs (2R- and 3R-PAHs) were statistically analyzed and significant when only high-number ring PAHs were statistically analyzed. Low-number ring PAH mainly moves in the gas phase and diffuses into the wax layer, so it was found to be statistically significant with the wax content of pine needles. High-number ring PAHs showed a high correlation with the amount of dust in pine needles because they mainly attached to dust particles and accumulated on the surface of pine needles. The ratios of fluoranthene/pyrene and methylphenanthrene/phenanthrene for predicting the origin of atmospheric PAHs have also been proven valid for pine needles.

Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways-JAK/STAT, MAPK, and NF-kappa B signaling-suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Anti-chitinase-3-like 1 antibody attenuated atopic dermatitis-like skin inflammation through inhibition of STAT3-dependent CXCL8 expression.

BACKGROUND AND PURPOSE: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1ß, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.

Resveratrol facilitates bone formation in high-glucose conditions.

Periodontitis is known to be affected by high-glucose conditions, which poses a challenge to periodontal tissue regeneration, particularly in bone formation. In this study, the potential effects of resveratrol (3,5,4'-trihydroxystilbene, RSV) in facilitating bone formation under high-glucose conditions after periodontitis has been investigated. We focused on the analysis of osteoblasts and periodontal ligament cells, which are essential for bone formation including cell proliferation and differentiation. And we aimed to investigate the impact of RSV on bone healing, employed diabetic mouse model induced by streptozotocin and confirmed through histological observation. High-glucose conditions adversely affected cell proliferation and ALP activity in both MC3T3-E1 and hPDLF in vitro, with more significant impact on MC3T3-E1 cells. RSV under high-glucose conditions had positive effects on both, showing early-stage effects for MC3T3-E1 cells and later-stage effects for hPDLF cells. RSV seemed to have a more pronounced rescuing role in MC3T3-E1 cells. Increased ALP activity was observed and the expression levels of significant genes, such as Col 1, TGF-ß1, ALP, and OC, in osteogenic differentiation were exhibited stage-specific expression patterns. Upregulated Col 1 and TGF-ß1 were detected in the early stage, and then ALP and OC expressions became more pronounced in the later stages. Similarly, stronger positive reactions against RUNX2 were detected in the RSV-treated group compared to the control. Furthermore, in in vivo experiment, RSV stimulates the growth and differentiation of osteoblasts, thereby promoting bone formation. High-glucose levels have the potential to impair cellular functions and the regenerative capacity to facilitate bone formation with MC3T3-E1 rather than hPDLF cells. Resveratrol appears to facilitate the inherent abilities of MC3T3-E1 cells compared with hPDLF cells, indicating its potential capacity to restore functionality during periodontal regeneration.

Ginsenosides for the treatment of insulin resistance and diabetes: Therapeutic perspectives and mechanistic insights.

Diabetes mellitus (DM) is a systemic disorder of energy metabolism characterized by a sustained elevation of blood glucose in conjunction with impaired insulin action in multiple peripheral tissues (i.e., insulin resistance). Although extensive research has been conducted to identify therapeutic targets for the treatment of DM, its global prevalence and associated mortailty rates are still increasing, possibly because of challenges related to long-term adherence, limited efficacy, and undesirable side effects of currently available medications, implying an urgent need to develop effective and safe pharmacotherapies for DM. Phytochemicals have recently drawn attention as novel pharmacotherapies for DM based on their clinical relevance, therapeutic efficacy, and safety. Ginsenosides, pharmacologically active ingredients primarily found in ginseng, have long been used as adjuvants to traditional medications in Asian countries and have been reported to exert promising therapeutic efficacy in various metabolic diseases, including hyperglycemia and diabetes. This review summarizes the current pharmacological effects of ginsenosides and their mechanistic insights for the treatment of insulin resistance and DM, providing comprehensive perspectives for the development of novel strategies to treat DM and related metabolic complications.

Toxic effects of fragmented polyethylene terephthalate particles on the marine rotifer Brachionus koreanus: Based on ingestion and egestion assay, in vivo toxicity test, and multi-omics analysis.

Microplastics (MPs) are a major concern in marine ecosystem because MPs are persistent and ubiquitous in oceans and are easily consumed by marine biota. Although many studies have reported the toxicity of MPs to marine biota, the toxicity of environmentally relevant types of MPs is little understood. We investigated the toxic effects of fragmented polyethylene terephthalate (PET) MP, one of the most abundant MPs in the ocean, on the marine rotifer Brachionus koreanus at the individual and molecular level. No significant rotifer mortality was observed after exposure to PET MPs for 24 and 48 h. The ingestion and egestion assays showed that rotifers readily ingested PET MPs in the absence of food but not when food was supplied; thus, there were also no chronic effects of PET MPs. In contrast, intracellular reactive oxygen species levels and glutathione S-transferase activity in rotifers were significantly increased by PET MPs. Transcriptomic and metabolomic analyses revealed that genes and metabolites related to energy metabolism and immune processes were significantly affected by PET MPs in a concentration-dependent manner. Although acute toxicity of PET MPs was not observed, PET MPs are potentially toxic to the antioxidant system, immune system, and energy metabolism in rotifers.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A retrospective observational study.

PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable RNFL thickness (RNFLT) measurements were performed using optical coherence tomography. Factors associated with the rate of thinning of the unaffected eyes of unilateral NTG patients were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: RNFLT decreased significantly in both the unaffected eyes of unilateral NTG patients and the healthy eyes (both P<0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral NTG patients than in the healthy eyes (P<0.001), specifically in the temporal-inferior sector (P=0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral NTG patients were thicker baseline RNFL of the unaffected eyes (P=0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P=0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P=0.007). CONCLUSIONS: The unaffected eyes of unilateral NTG patients showed faster RNFL thinning than healthy control eyes, more obviously in the temporal-inferior sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral NTG patients, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma.

Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy.

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil-lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20-0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27-0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC.

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

Upadacitinib in Active Non-radiographic Axial Spondyloarthritis: 1-Year Data From a Double-Blind, Randomized, Placebo-Controlled, Phase 3 Trial.

OBJECTIVE: Upadacitinib improved the signs and symptoms of non-radiographic axial spondyloarthritis (nr-axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT-AXIS 2 nr-axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr-axSpA in SELECT-AXIS 2. METHODS: Patients aged at least 18 years diagnosed with nr-axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52-week double-blind period. Efficacy was assessed using non-responder imputation incorporating multiple imputation (NRI-MI) and as-observed analyses for binary endpoints, and mixed-effects model repeated measures for continuous endpoints. RESULTS: Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI-MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI-MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. CONCLUSION: Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit-risk profile of upadacitinib treatment for nr-axSpA.

A Simple Tube Escape Assay to Test Learning and Memory in Zebrafish with Minimized Habituation.

Various methods have been used in rodents to evaluate learning and memory. Although much less frequently used, the zebrafish emerges as an alternative model organism in this context. For example, it allows assessing potential behavioral deficits because of neurodevelopmental disorders or environmental neurotoxins. A variety of learning tasks have been employed in previous studies that required extensive habituation and training sessions. Here, we introduce a simpler and faster method to evaluate learning and memory of zebrafish with minimum habituation. A new apparatus, a transparent L-shaped tube, was developed in which we trained each zebrafish to swim through a long arm and measured the time to swim through this arm. We demonstrate that in this task, zebrafish could acquire both short-term (1 h) and long-term memory (4 days). We also studied learning and memory of a gene knockout (KO) zebrafish that showed social impairments related to autism. We found KO mutant zebrafish to show a quantitative impairment in habituation, learning, and memory performance compared with wild-type control fish. In conclusion, we established a novel learning apparatus and sensitive paradigm that allowed us to evaluate learning and memory of adult zebrafish that required only a brief habituation period and minimal training.

Lutimonas zeaxanthinifaciens sp. nov., a zeaxanthin-producing marine bacterium isolated from coastal sediment.

A Gram-stain-negative, yellow-pigmented, strictly aerobic, non-flagellated, motile by gliding, rod-shaped bacterium, designated strain YSD2104T, was isolated from a coastal sediment sample collected from the southeastern part of the Yellow Sea. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain YSD2104T was closely related to three type strains, Lutimonas vermicola IMCC1616T (97.4 %), Lutimonas saemankumensis SMK-142T (96.9 %), and Lutimonas halocynthiae RSS3-C1T (96.8 %). Strain YSD2104T has a single circular chromosome of 3.54 Mbp with a DNA G+C content of 38.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain YSD2104T and the three type strains (L. vermicola IMCC1616 T, L. saemankumensis SMK-142T, and L. halocynthiae RSS3-C1T) were 74.0, 86.2 and 73.6 %, and 17.9, 30.3 and 17.8 %, respectively. Growth was observed at 20-30 °C (optimum, 30 °C), at pH 6.5-8.5 (optimum, pH 7.0), and with NaCl concentrations of 1.5-3.5 % (optimum, 2.5 %). The major carotenoid was zeaxanthin, and flexirubin-type pigment was not produced. The major respiratory quinone was menaquinone-6. The major fatty acids (>10 %) were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), and summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl C16 : 0). The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, two unidentified aminolipids, and eight unidentified lipids. Conclusively, based on this polyphasic approach, we classified strain YSD2104T (=KCTC 102008T=JCM 36287T) as representing a novel species of the genus Lutimonas and proposed the name Lutimonas zeaxanthinifaciens sp. nov.