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Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

The HEALthy Brain and Child Development (HBCD) study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The study plans enrolling over 7000 families across 27 sites. This manuscript presents the measures from the Neurocognition and Language Workgroup. Constructs were selected for their importance in normative development, evidence for altered trajectories associated with environmental influences, and predictive validity for child outcomes. Evaluation of measures considered psychometric properties, brevity, and developmental and cultural appropriateness. Both performance measures and caregiver report were used wherever possible. A balance of norm-referenced global measures of development (e.g., Bayley Scales of Infant Development-4) and more specific laboratory measures (e.g., deferred imitation) are included in the HBCD study battery. Domains of assessment include sensory processing, visual-spatial reasoning, expressive and receptive language, executive function, memory, numeracy, adaptive behavior, and neuromotor. Strategies for staff training and quality control procedures, as well as anticipated measures to be added as the cohort ages, are reviewed. The HBCD study presents a unique opportunity to examine early brain and neurodevelopment in young children through a lens that accounts for prenatal exposures, health and socio-economic disparities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pulmonary fibrosis is a progressive lung condition characterized by the excessive activation of myofibroblasts. Transforming growth factor beta 1 (TGFβ1) plays a crucial role in the differentiation of fibroblasts into myofibroblasts. In addition, toll-like receptor 2 (TLR2), known for its role in immune responses, contributes to pulmonary fibrosis by promoting myofibroblast differentiation. However, the interplay between TGFβ1 and TLR2 signaling pathways in myofibroblast differentiation has remained elusive. In the present study, we investigated the involvement of TLR2 in TGFβ1-induced fibroblast differentiation into myofibroblasts using IMR-90 human pulmonary fibroblasts as a model cell line. We found that TLR2 activation induced myofibroblast differentiation by enhancing the expression of early growth response 1 (EGR1) via the mitogen-activated protein kinase (MAPK) signaling pathway. Elevated EGR1 levels were detected in the lung tissues of a bleomycin (BLM)-induced mouse model of pulmonary fibrosis. Moreover, the administration of tomaralimab, an antagonistic anti-TLR2 antibody, reduced the EGR1 expression and collagen deposition. Altogether, targeting the TLR2-EGR1 pathway could be a promising therapeutic approach for pulmonary fibrosis by blocking TGFβ1-induced myofibroblast differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pulmonary fibrosis is a severe and progressive lung disease characterized by lung tissue scarring. Transforming growth factor beta 1 (TGFβ1) is crucial in causing pulmonary fibrosis by promoting the activation of fibroblasts and their differentiation into myofibroblasts, which are responsible for excessive extracellular matrix deposition. This study aimed to identify genes activated by TGFβ1 that promote fibrosis and to understand the regulatory pathway controlling myofibroblast. Endothelin-1 (ET-1) was identified as the top-ranking gene in the fibrosis-related gene set using quantitative PCR array analysis. TGFβ1 upregulated EGR1 expression through the ERK1/2 and JNK1/2 MAPK pathways. EGR1 and p-SMAD2 proteins interacted with the ET-1 gene promoter region to regulate TGFβ1-induced ET-1 expression in IMR-90 pulmonary fibroblasts. Mice lacking the Egr1 gene showed reduced ET-1 levels in a model of pulmonary fibrosis induced by intratracheal administration of bleomycin. These findings suggest that targeting EGR1 is a promising approach for treating pulmonary fibrosis, especially idiopathic pulmonary fibrosis, by affecting ET-1 expression and profibrotic reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epidermal hyperinnervation is a critical feature of pruritus during skin inflammation. However, the mechanisms underlying epidermal hyperinnervation are unclear. This study investigates the role of the transcription factor EGR1 in epidermal innervation by utilizing wild-type (Egr1 +/+ ) and Egr1-null (Egr1 ‒/‒ ) mice topically applied Dermatophagoides farinae extract from dust mite. Our findings revealed that Egr1 ‒/‒ mice exhibited reduced scratching behaviors and decreased density of epidermal innervation compared with Egr1 +/+ mice. Furthermore, we identified artemin, a neurotrophic factor, as an EGR1 target responsible for Dermatophagoides farinae extract-induced hyperinnervation. It has been demonstrated that Dermatophagoides farinae extract stimulates toll-like receptors in keratinocytes. To elucidate the cellular mechanism, we stimulated keratinocytes with Pam3CSK4, a toll-like receptor 1/2 ligand. Pam3CSK4 triggered a toll-like receptor 1/2-mediated signaling cascade involving IRAK4, IκB kinase, MAPKs, ELK1, EGR1, and artemin, leading to increased neurite outgrowth and neuronal migration. In addition, increased expression of EGR1 and artemin was observed in the skin tissues of patients with atopic dermatitis. These findings highlight the significance of the EGR1-artemin axis in keratinocytes, promoting the process of epidermal innervation and suggesting it as a potential therapeutic target for alleviating itch and pain associated with house dust mite-induced skin inflammation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Corticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients., Methods: Patients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models., Results: During the median follow-up period of 7.22±3.85 years, 357 (0.62 %) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95 % CI: 1.25-1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk., Conclusion: AVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use., Competing Interests: Conflict of interest None, (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication., Objectives: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry., Methods: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes., Results: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients., Conclusions: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful., Condensed Abstract: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high., Competing Interests: Declaration of competing interest A. Aminian is a consultant and proctor for Boston Scientific and Abbott. I. Akin received lecture and proctoring fees from Boston Scientific for the Watchman Okkluder. J. Lund discloses a clinical advisor (proctor) role in LAAC (Abbott) and lecture fees (Abbott, Boston scientific). E. Guerios serves as proctor for LAA closure for Abbott and Lifetech Scientific. N. Amabile has received proctoring and consulting fees from Abbott Vascular and Boston Scientific. C. Skurk has received proctor honoraria from Boston Scientific and speaker fees from Boston Scientific and Lifetech Scientific. J. Harvey is proctor for Abiomed, Boston Scientific and Medtronic and part of the Speaker's bureau for Abiomed, Boston Scientific and Medtronic. He also is part of the advisory board for Avail, Boston Scientific and Medtronic. H. Sievert has received study honoraria to institution, travel expenses and consulting fees from 4tech Cardio, Abbott, Ablative Solutions, Adona Medical, Akura Medical, Ancora Heart, Append Medical, Axon, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Cardiac Dimensions, Cardiac Success, Cardimed, Cardionovum, Celonova, Contego, Coramaze, Croivalve, CSL Behring LLC, CVRx, Dinova, Edwards, Endobar, Endologix, Endomatic, Esperion Therapeutics, Inc., Hangzhou Nuomao Medtech, Holistick Medical, Intershunt, Intervene, K2, Laminar, Lifetech, Magenta, Maquet Getinge Group, Metavention, Mitralix, Mokita, Neurotronic, NXT Biomedical, Occlutech, Recor, Renal Guard, Shifamed, Terumo, Trisol, Vascular Dynamics, Vectorious Medtech, Venus, Venock, Vivasure Medical, Vvital Biomed and Whiteswell. M. Kühne received personal fees from Bayer, Böhringer Ingelheim, Pfizer BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson & Johnson, and F. Hoffmann-La Roche Ltd., as well as grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo. S. Sabir is part of the Boston Scientific WATCHMAN advisory board. J. Kim has received proctoring fees from Abbott Vascular. M. Montorfano received consultant fees from Abbott, Boston Scientific, Kardia. M. Ancona received consultant fees from Abbott. Relevant research funding went to Vanderbilt University Medical Center from Boston Scientific, Boehringer-Ingelheim, Medtronic and Atricure, where C. Ellis is practicing. He also reseves a consultant and advisor fee from Abbott Medical, Atricure, Boston Scientific, Medtronic. L. Nombela-Franco is proctor for Abbott Vascular and has received lectures fees from Boston Scientific. A. Natale has received speaker honoraria from Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic. He also is a consultant for Biosense Webster, St. Jude Medical, and Janssen. All other authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Emergency departments (ED) nurses experience high mental workloads because of unpredictable work environments; however, research evaluating ED nursing workload using a tool incorporating nurses' perception is lacking. Quantify ED nursing subjective workload and explore the impact of work experience on perceived workload., Methods: Thirty-two ED nurses at a tertiary academic hospital in the Republic of Korea were surveyed to assess their subjective workload for ED procedures using the National Aeronautics and Space Administration Task Load Index (NASA-TLX). Nonparametric statistical analysis was performed to describe the data, and linear regression analysis was conducted to estimate the impact of work experience on perceived workload., Results: Cardiopulmonary resuscitation (CPR) had the highest median workload, followed by interruption from a patient and their family members. Although inexperienced nurses perceived the 'special care' procedures (CPR and defibrillation) as more challenging compared with other categories, analysis revealed that nurses with more than 107 months of experience reported a significantly higher workload than those with less than 36 months of experience., Conclusion: Addressing interruptions and customizing training can alleviate ED nursing workload. Quantified perceived workload is useful for identifying acceptable thresholds to maintain optimal workload, which ultimately contributes to predicting nursing staffing needs and ED crowding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination., Methods: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay., Results: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups., Discussion: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: There is limited research into the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic for non-COVID-19 pneumonia in older adults, as well as their quality of care or outcomes. This study aims to assess the process and outcome quality of care for hospitalized older adult patients with pneumonia before and after the pandemic., Methods: A retrospective cohort of older adult patients (age ≥ 65) hospitalized for non-COVID pneumonia were recruited from five Korean hospitals (January 20, 2019, to January 19, 2021). The quality of care before and after the COVID-19 pandemic was evaluated., Results: A total of 7356 hospitalization episodes of older adult pneumonia were identified, and 978 cases (552 pre-pandemic and 426 during the pandemic) were analyzed. The pneumonia severity score was higher during the pandemic, and the waiting time from the emergency room to admission was also longer. Furthermore, the pneumonia mortality rate during the pandemic was higher than that in the pre-pandemic period (in-hospital mortality: 10.1% vs. 18.1%; 90-day mortality: 11.6% vs. 22.3%). A significantly higher mortality risk was observed during the pandemic than in the period prior (adjusted odds ratio: 1.74, 95% confidence interval: 1.14-2.63)., Conclusions: While the quality of care for hospitalized pneumonia has been maintained during the pandemic, there has been an increase in mortality rates. Further investigations are needed to understand the underlying causes of this increase., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study assessed the changes in color stability and biocompatibility of computer-aided design and computer-aided manufacturing (CAD-CAM) glass-ceramics after ultraviolet weathering (UW) aging., Methods: A total of 300 plate-shaped specimens (12.0 × 14.0 × 1.5 mm 3 ) were prepared using a leucite-reinforced glass-ceramic (IPS Empress CAD; E), a lithium disilicate (IPS e.max CAD; M), and two zirconia-reinforced lithium silicate (Celtra Duo; C, Vita Suprinity; V) glass-ceramics. Specimens were divided into three groups (n = 25, each), subjected to water storage at 37 °C for 24 h (control group), or UW aging at 150 kJ/m 2 (first-aged group) or 300 kJ/m 2 (second-aged group). The color stability, mechanical and surface properties, and biocompatibility of the CAD-CAM glass-ceramics were investigated experimentally, followed by statistical analysis., Results: The brightness and redness or greenness were reduced in all groups after aging. After the first aging, V exhibited the largest color change and E exhibited the smallest color change. After the second aging, E exhibited the highest nanoindentation hardness and Young's modulus. The surface roughness was the highest for V after the first aging. Furthermore, the hydrophilicity of the materials increased after aging process. The cell proliferation/viability of human gingival fibroblasts was the highest in E before and after aging. Almost all cells survived for all groups based on a live/dead assay., Conclusions: Leucite-reinforced glass-ceramic exhibit the highest color stability and biocompatibility after aging. The color stability and biocompatibility of CAD-CAM glass-ceramics depend on the aging process and material type., Clinical Significance: Various CAD-CAM glass-ceramics exhibit adequate color stability after UW aging. The leucite-reinforced glass-ceramics exhibit the highest color stability, cell proliferation, and viability after aging. The color stability, mechanical and surface properties, and biocompatibility of the glass-ceramics depend on the aging process and material type., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This study aimed to develop a new symmetric-end antimicrobial peptide (AMP) with cell selectivity, antibiofilm, and anti-inflammatory activities. Two symmetric-end AMPs, Lf6-pP and Lf6-GG, were designed based on the sequence RRWQWRzzRWQWRR, which contains two symmetric repeat sequences connected by a β-turn-promoting sequence (zz) that can be a rigid turn by D-Pro-Pro (pP) or a flexible turn by Gly-Gly (GG). Both Lf6-pP and Lf6-GG exhibited potent antibacterial activity without causing hemolysis, but Lf6-pP exhibited better cell selectivity, likely due to the more significant impact of the rigid pP turn. Compared to Lf6-GG, Lf6-pP demonstrated approximately three times higher antimicrobial activity against drug-resistant bacteria, had a low incidence of drug resistance, and maintained its activity in the presence of physiological salts and human serum. Additionally, Lf6-pP was more effective than Lf6-GG in inhibiting biofilm formation and eradicating mature biofilms. The BODIPY-cadaverine assay indicated that the potent anti-inflammatory activity of Lf6-pP may be attributed to its direct interaction with LPS, resulting in decreased TNF-α and IL-6 levels in LPS-stimulated macrophages. Mechanistic studies, including membrane depolarization, outer/inner membrane permeation, and membrane integrity change, demonstrated that Lf6-pP exerts its antibacterial action through an intracellular-target mechanism. Overall, we propose that Lf6-pP has potential as a novel antibacterial, antibiofilm, and anti-inflammatory agent against drug-resistant bacterial infections., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Neutropenia and its complications are major adverse effects of cytotoxic chemotherapy. The time to recovery from neutropenia varies from patient to patient, and cannot be easily predicted even by experts. Therefore, we trained a deep learning model using data from 525 pediatric patients with solid tumors to predict the day when patients recover from severe neutropenia after high-dose chemotherapy. We validated the model with data from 99 patients and compared its performance to those of clinicians. The accuracy of the model at predicting the recovery day, with a 1-day error, was 76%; its performance was better than those of the specialist group (58.59%) and the resident group (32.33%). In addition, 80% of clinicians changed their initial predictions at least once after the model's prediction was conveyed to them. In total, 86 prediction changes (90.53%) improved the recovery day estimate., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MHS, SYS, and HC have a pending patent application on some of the material reported in this manuscript. The remaining authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

PER2 is a core circadian clock gene that regulates circadian rhythms. IL-4 plays a critical role in the pathogenesis of skin inflammation, including atopic dermatitis. IL-4 enhances PER2 expression, suggesting a relationship between inflammation and the circadian clock. However, little is known about the molecular and cellular mechanisms regulating PER2 expression by inflammatory cytokines. This study showed that transcription factor EGR1 interacted with the PER2 promoter and promoted IL-4‒induced transcriptional activation of the PER2, as revealed by promoter‒reporter assay, electrophoretic mobility shift assay, DNA affinity precipitation assay, and chromatin immunoprecipitation analysis. We also found that IL-4 can use both MAPK and Jak signaling pathways to induce EGR1-mediated PER2 expression, and c-Jun N-terminal kinase 1/2 can augment IL-4‒induced activation of the Jak‒signal transducer and activator of transcription 3 pathway. Consistently, Per2 expression was reduced in dinitrochlorobenzene-induced atopic dermatitis‒like skin lesions in Egr1 ‒/‒ mice compared with that in Egr1 +/+ mice. In addition, using a real-time bioluminescence assay, we observed that EGR1 is required for rhythmic oscillation of PER2 expression under IL-4 exposure. These findings provide further insight into the role of EGR1 in regulating PER2 expression in impaired circadian rhythm in skin inflammation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs., Design: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset., Participants: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants)., Methods: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students., Main Outcome Measures: Mean squared error (MSE)., Results: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC., Conclusions: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet., (Copyright © 2022. Published by Elsevier Inc.)

Novel (Z)-3-((4,6-diphenylpyrimidin-2-ylamino)methylene)-2,3-dihydrochromen-4-one derivatives were designed and synthesized to find chemotherapeutic agents. Derivative 9 was selected based on its clonogenicity against cancer cells and synthetic yield for further biological experiments. It showed decreases in aurora kinase A, B, and C phosphorylation from western blot analysis. Derivative 9 upregulated the expression of G1 cell cycle inhibitory proteins including p21 and p27, and G1 progressive cyclin D1, and downregulated G1-to-S progressive cyclins, resulting in cell cycle arrest at the G1/S boundary. It stimulated the cleavage of caspase-9, -3, -7, and poly (ADP-ribose) polymerase, resulting in triggering apoptosis through a caspase-dependent pathway. In addition, derivative 9 inhibited in vivo tumor growth in a syngeneic tumor implantation mouse model. The findings of this study suggest that derivative 9 can be considered as a lead compound for chemotherapeutic agents., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Amniotic mesenchymal stromal cells (AMSCs) can be obtained from the mesoderm of human amniotic membrane. AMSCs derived from term baby show increased expression of genes associated with apoptosis and senescence. The objective of this study was to examine gene expression profiles of AMSCs derived from preterm (preterm AMSCs) and term labors (term AMSCs) and analyze common and different mechanisms., Materials and Methods: We isolated and cultured AMSCs from 43 placentas: 27 from term labor and 16 from preterm labor. Microarray analysis and gene network analysis were performed to compare gene expression profile (GEP) of preterm (n = 6) with term AMSCs (n = 10). Senescence-associated gene (CDKN2A and CDKN2B) expression was also measured by reverse transcription quantitative PCR., Results: GEP demonstrated that preterm AMSCs showed upregulation of nicotinamide adenine dinucleotide biosynthetic process and downregulation of extracellular matrix, cholesterol import and transport, lipid storage, and maintenance of location. CDKN2A and CDKN2B genes showed similar expression levels between term and preterm AMSCs. CDKN2A gene expression was correlated with CDKN2B expression and population doubling time. Compared to term AMSCs, preterm AMSCs showed significantly different expression of genes associated with inflammatory response which could be one of the major players in labor events., Conclusion: Increased CDKN2A expression in AMSCs is associated with placental membrane aging which participates in both preterm and term labor. To the best of our knowledge, this is the first report to demonstrate the association of AMSCs with labor., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine peptidase that plays a crucial role in regulating skin desquamation. KLK7 expression is highly upregulated in atopic dermatitis (AD) skin lesions in both humans and mice. Th2-lymphocyte-derived cytokines, including interleukin (IL)-4 and IL-13, have been shown to promote KLK7 expression in keratinocytes in patients with AD. However, the molecular mechanism underlying KLK7 expression remains poorly understood. Here, we demonstrated that the EGR-1-binding sequence (EBS) in the promoter region of KLK7 played a crucial role in IL-13-induced KLK7 transcription. Disruption of the EBS induced by a point mutation inhibited IL-13-induced KLK7 promoter activity. EGR-1 was shown to directly bind to the EBS, and EGR1 knockdown with shRNA abrogated IL-13-induced KLK7 expression. Using Egr1 knockout mice, we showed that Egr-1 was necessary for KLK7 expression in AD-like lesions induced by the repeated topical application of 2,4-dinitrobenzene on the dorsal skin of mice. We also demonstrated that the ERK1/2 mitogen-activated protein kinase (MAPK) pathway was responsible for EGR-1-dependent KLK7 transcription in response to IL-13 stimulation. Our findings delineate a signaling pathway that contributes to the regulation of KLK7 expression through the IL13-ERK MAPK-EGR1 signaling axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: We aimed to compare the antiviral effect of hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) in patients with COVID-19., Methods: Nationwide retrospective case-control study was conducted to compare the effect of HCQ and LPV/r on viral shedding duration among patients with mild-to-moderate COVID-19 using the reimbursement data of National Health Insurance Service. After propensity score matching (PSM), multivariate analysis was conducted to determine statistically significant risk factors associated with prolonged viral shedding., Results: Overall, 4197 patients with mild-to-moderate COVID-19 were included. Patients were categorized into three groups: LPV/r (n = 1268), HCQ (n = 801), and standard care without HCQ or LPV/r (controls, n = 2128). The median viral shedding duration was 23 (IQR 17-32), 23 (IQR 16-32), and 18 (IQR 12-25) days in the LPV/r, HCQ, and control groups, respectively. Even after PSM, the viral shedding duration was not significantly different between LPV/r and HCQ groups: 23 (IQR, 17-32) days versus 23 (IQR, 16-32) days. On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were statistically significant risk factors for prolonged viral shedding., Conclusion: The viral shedding duration was similar between HCQ and LPV/r treatment groups. There was no benefit in improving viral clearance compared to the control group., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Proadrenomedullin N-terminal 20 peptide (PAMP) is a regulatory peptide that is found in various cell types. It is involved in many biological activities and is rich in basic and hydrophobic amino acids, a common feature of antimicrobial peptides (AMPs). In this study, the cell selectivity and antimicrobial mechanism of PAMP and its C-terminal peptide, PAMP(9-20), were investigated. PAMP and PAMP(9-20) displayed potent antimicrobial activity (minimum inhibitory concentration: 4-32 μM) against standard bacterial strains, but showed no hemolytic activity even at the highest tested concentration of 256 μM. PAMP(9-20) showed 2- to 4-fold increase in antimicrobial activity against gram-negative bacteria compared to PAMP. Cytoplasmic membrane depolarization, leakage of calcein dye from membrane mimic liposomes, SYTOX Green uptake, membrane permeabilization, and flow cytometry studies indicated that the major target of PAMP and PAMP(9-20) is not the microbial cell membrane. Interestingly, laser-scanning confocal microscopy demonstrated that FITC-labeled PAMP and PAMP(9-20) enter the cytoplasm of Escherichia coli similar to buforin-2, and gel retardation assay indicated that PAMP and PAMP(9-20) effectively bind to bacterial DNA. These results suggest that the intracellular target mechanism is responsible for the antimicrobial action of PAMP and PAMP(9-20). Collectively, PAMP and PAMP(9-20) could be considered promising candidates for the development of new antimicrobial agents., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We propose a novel deep learning based system for vessel segmentation. Existing methods using CNNs have mostly relied on local appearances learned on the regular image grid, without consideration of the graphical structure of vessel shape. Effective use of the strong relationship that exists between vessel neighborhoods can help improve the vessel segmentation accuracy. To this end, we incorporate a graph neural network into a unified CNN architecture to jointly exploit both local appearances and global vessel structures. We extensively perform comparative evaluations on four retinal image datasets and a coronary artery X-ray angiography dataset, showing that the proposed method outperforms or is on par with current state-of-the-art methods in terms of the average precision and the area under the receiver operating characteristic curve. Statistical significance on the performance difference between the proposed method and each comparable method is suggested by conducting a paired t-test. In addition, ablation studies support the particular choices of algorithmic detail and hyperparameter values of the proposed method. The proposed architecture is widely applicable since it can be applied to expand any type of CNN-based vessel segmentation method to enhance the performance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Most bioinformatic tools for next generation sequencing (NGS) data are computationally intensive, requiring a large amount of computational power for processing and analysis. Here the utility of graphic processing units (GPUs) for NGS data computation is assessed., Method: In a previous study, we developed a probabilistic evolutionary algorithm with toggling for haplotyping (PEATH) method based on the estimation of distribution algorithm and toggling heuristic. Here, we parallelized the PEATH method (PEATH/G) using general-purpose computing on GPU (GPGPU)., Results: The PEATH/G runs approximately 46.8 times and 25.4 times faster than PEATH on the NA12878 fosmid-sequencing dataset and the HuRef dataset, respectively, with an NVIDIA GeForce GTX 1660Ti. Moreover, the PEATH/G is approximately 13.3 times faster on the fosmid-sequencing dataset, even with an inexpensive conventional GPGPU (NVIDIA GeForce GTX 950)., Conclusions: PEATH/G can be a practical single individual haplotyping tool in terms of both its accuracy and speed. GPGPU can help reduce the running time of NGS analysis tools., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A moderate elevation in reactive oxygen species (ROS) levels can generally be controlled in normal cells, but may lead to death of cancer cells as the ROS level in cancer cells is already elevated. Therefore, a ROS-generating compound can act as a selective chemotherapeutic agent for cancer cells that does not affect normal cells. In our previous study, a compound containing a Michael acceptor was selectively cytotoxic to cancer cells without affecting normal cells; therefore, we designed and synthesized 26 compounds containing a Michael acceptor. Their cytotoxicities against HCT116 human colon cancer cell lines were measured by using a clonogenic long-term survival assay. To derive the structural conditions required to obtain stronger cytotoxicity against cancer cells, the relationships between the half-maximal cell growth inhibitory concentration values of the synthesized compounds and their physicochemical properties were evaluated by Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis. It was confirmed that the compound with the best half-maximal cell growth inhibitory concentration triggered apoptosis through ROS generation, which then led to stimulation of the caspase pathway., (Copyright © 2018. Published by Elsevier Inc.)

2-Hydroxy-3',5,5'-trimethoxychalcone (named DK-139) is a synthetic chalcone derivative that has anti-inflammatory, anti-tumor, and endoplasmic reticulum-mediated apoptosis activities. However, the mode of action of DK-139 on reactive oxygen species (ROS)-induced apoptosis remains unknown. In this study, we found that DK-139 activated DNA damage responses, as was revealed by the accumulation of the tumor suppressor p53 and the phosphorylation of histone H2AX at Ser139 (called γ-H2AX), which are hallmarks of DNA damage responses. The occurrence of DK-139-induced DNA damage was confirmed through single-cell gel electrophoresis (comet tail assay). Interestingly, using p53-null HCT116 cells revealed that p53 was not involved in DK-139-induced apoptosis. Instead, we found that DK-139 increased the production of ROS, which led to the processing of caspase-2, BH3 interacting-domain death agonist (BID), caspase-9, and caspase-7. Pretreatment with the ROS scavenger N-acetyl cysteine reduced the frequency of DK-139-induced γ-H2AX formation, demonstrating that DK-139 triggered DNA damage through ROS production. In addition, NAC pretreatment prevented DK-139-induced processing of caspase-2, BID, caspase-9, caspase-7, and poly(ADP-ribose) polymerase. These results suggest that DK-139 triggers apoptosis through ROS-mediated DNA damage and activation of the caspase-2 cascade in A549 human lung cancer cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

CXCL14 is a CXC chemokine family that exhibits antimicrobial activity and contains an amphipathic cationic α-helical region in the C-terminus, a characteristic structure of antimicrobial peptides (AMPs). In this study, we designed three analogs of CXCL14 59-75 (named CXCL14-C17) corresponding to the C-terminal α-helix of CXCL14, which displayed potential antimicrobial activity against a wide variety of gram-negative and gram-positive bacteria with minimum inhibitory concentrations of 4-16 μM without mammalian cell toxicity. Furthermore, two CXCL14-C17 analogs (CXCL14-C17-a1 and CXCL14-C17-a3) with improved cell selectivity were engineered by introducing Lys, Arg, or Trp in CXCL14-C17. Additionally, CXCL14-C17 analogs showed much greater synergistic effect (FICI: 0.3125-0.375) with chloramphenicol and ciprofloxacin against multidrug-resistant Pseudomonas aeruginosa (MDRPA) than LL-37 did (FICI: 0.75-1.125). CXCL14-C17 analogs were more active against antibiotic-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA), MDRPA, and vancomycin-resistant Enterococcus faecium (VREF) than LL-37 and melittin. In particular, CXCL14-C17-a2 and CXCL14-C17-a3 completely inhibited the biofilm formation at sub-MIC and all of the peptides were able to eliminate pre-formed biofilm as well. Membrane depolarization, flow cytometry, sytox green uptake, ONPG hydrolysis and confocal microscopy revealed the possible target of the native peptide (CXCL14-C17) to likely be intracellular, and the amphipathic designed analogs targeted the bacterial membrane. CXCL14-C17 also showed DNA binding characteristic activity similar to buforin-2. Interestingly, CXCL14-C17-a2 and CXCL14-C17-a3 effectively inhibited the production and expression of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 from lipopolysaccharide (LPS)-stimulated RAW264.7 cells, suggesting that these peptides could be promising anti-inflammatory and antimicrobial agents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to understand the concept of innovative behavior and its theoretical and practical implications for nursing., Methods: Eight-step modification of Wilson's classic concept analysis procedure (1963) by Walker and Avant's (2005) was used to explore the antecedents, attributes, and consequences of innovative behavior in the literature. Electronic searches were conducted in PubMed, Google Scholar, OVID Medline, Science Direct, and ERIC databases using "innovative behavior" or "innovative work behavior", "innovativeness", "innovation", "leadership", "healthcare", and "nursing" as keywords, with no limitation on publication date., Results: Organizing the framework based on the method of concept analysis by Walker and Avant , defining attributes to innovative behavior were opportunity exploration, idea generation, idea search, idea communication, promotion of idea, idea championing, application, and overcoming obstacles. Antecedents to innovative behavior are categorized into three groups: organizational characteristics, work environmental characteristics, and individual characteristics. Consequences of innovative behavior included job productivity, lower levels of job burnout, job satisfaction, solving the organizational problems, organizational commitment, organizational efficiency, and effectiveness., Conclusion: Eight dimensions including opportunity exploration, idea generation, idea search, idea communication, idea promotion, championing, application, and overcoming obstacles were analyzed. We suggest promoting innovative behavior through leadership and management in nursing. Future research should focus on developing instruments and conducting empirical studies on innovative behavior in nursing research and practice., (Copyright © 2018. Published by Elsevier B.V.)

Atrial fibrillation (AF) is a common and progressive heart rhythm disorder that causes structural, functional, and electrical remodelling of the heart. Although we do not fully understand AF yet, this arrhythmia is one clinical feature of a syndrome that is represented by irregularly irregular atrial rhythm accompanied by progressive atrial structural and functional remodelling. Although ischemic stroke, the most feared complication of AF, can be prevented by anticoagulation, the asymptomatic or paroxysmal nature of AF makes timely diagnosis of AF difficult. Thus, appropriate screening method for AF is necessary. In this review, we will discuss the importance and future perspectives of population screening for AF., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Given the increased interest in public hygiene due to outbreaks of food poisoning, increased emphasis has been placed on developing novel monitoring systems for point-of-care testing (POCT) to evaluate pathogens causing foodborne illnesses. Here, we demonstrate a pathogen evaluation system utilizing simple film-based microfluidics, featuring simultaneous gene amplification, solution mixing, and electrochemical detection. To minimize and integrate the various functionalities into a single chip, patterned polyimide and polyester films were mainly used on a polycarbonate housing chip, allowing simple fabrication and alignment, in contrast to conventional polymerase chain reaction, which requires a complex biosensing system at a bench-top scale. The individual integrated sensing chip could be manually fabricated in 10 min. Using the developed film-based integrated biosensing chip, the genes from the pathogens causing foodborne illnesses were simultaneously amplified based on multiple designed microfluidic chambers and Hoechst 33258, which intercalates into double-stranded DNA, to generate the electrochemical signal. The target pathogen gene was accurately analyzed by square wave voltammetry (SWV) within the 25 s, while the gel electrophoresis required about 30 min. Based on the developed integrated biosensing chip, the 1.0 × 10 1 and 1.0 × 10 2  colony-forming unit (CFU) of Staphylococcus aureus and Escherichia coli were sensitively detected with high reproducibility in the 25 s. On the basis of the significant features of the film-based molecular analysis platform, we expect that the developed sensor could be applied to the screening of various pathogens as a POCT device., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study evaluated the influence of different factors on pork hams cooked by sous-vide method. The quality and structural and microbiological properties of the treated samples were compared with those of controls. Samples were subjected to treatment at different combinations of temperature (61 °C or 71 °C), time (45 or 90 min), and vacuum degree (98.81% or 96.58%). The control sample was air packaged and boiled for 45 min in boiling water. Temperature and vacuum degree affected quality properties, while the effect of time was limited. Samples cooked at 61 °C showed higher moisture content, redness, and pink color of the meat juice, whereas samples cooked at 71 °C showed higher cooking loss rate, lightness, and volatile basic nitrogen values. Texture analysis indicated tenderer meat for the treatment group than the control. No microbial growth was detected in any treatment groups. Meat cooked at 61 °C and 98.81% vacuum showed more spacious arrangement of meat fiber., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mycobacterium avium complex (MAC) is the most common etiologic organisms of nontuberculous mycobacteria (NTM) lung disease. In this study, we aimed to retrospectively investigate the differences in drug susceptibility patterns of two major MAC species; Mycobacterium avium and Mycobacterium intracellulare. A total of 1883 major two MAC isolates (1060 M. avium and 823 M. intracellulare) from respiratory specimens were included in this study during the period 2011─2016. The minimum inhibitory concentrations (MICs) were determined by broth microdilution method and MIC 50 /MIC 90 values were derived from MIC distribution. M. intracellulare had generally low susceptible rates than M. avium for almost all tested antimicrobials except ethambutol and amikacin. The susceptible rate to clarithromycin was >94% of the MAC without significant differences between the two species. The MIC 50 values of ciprofloxacin, clarithromycin, linezolid, moxifloxacin, and rifampicin were higher in M. intracellulare than in M. avium, contrary to the results of ethambutol with a higher MIC 50 in M. avium. In general, M. intracellulare showed a higher resistance rate and higher MIC 50 values than M. avium. Differences between this study and previous reports suggest regional differences in drug susceptibility profile of MAC species., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Maintaining the quality of medical images and videos is an essential part of the e-services provided by the healthcare sector. The convergence of modern communication systems and the healthcare industry necessitates the provision of better quality of service and experience by the service provider. Recent inclusion and standardization of the high efficiency video coder (HEVC) has made it possible for medical data to be compressed and transmitted over wireless networks with minimal compromise of the quality. Quality evaluation and assessment of these medical videos transmitted over wireless networks is another important research area that requires further exploration and attention. In this paper, we have conducted an in-depth study of video quality assessment for compressed wireless capsule endoscopy (WCE) videos. Our study includes the performance evaluation of several state-of-the-art objective video quality metrics in terms of determining the quality of compressed WCE videos. Subjective video quality experiments were conducted with the assistance of experts and non-experts in order to predict the diagnostic and visual quality of these medical videos, respectively. The evaluation of the metrics is based on three major performance metrics that include, correlation between the subjective and objective scores, relative statistical performance and computation time. Results show that the metrics information fidelity criterion (IFC), visual information fidelity-(VIF) and especially pixel based VIF stand out as best performing metrics. Furthermore, our paper reports the performance of HEVC compression on medical videos and according to the results, it performs optimally in preserving the diagnostic and visual quality of WCE videos at Quantization Parameter (QP) values of up to 35 and 37 respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although the human-derived antimicrobial peptide (AMP) LL-37 has potent antimicrobial and anti-inflammatory activities, its therapeutic application is limited by its low cell selectivity and high production cost due to its large size. To overcome these problems, we tried to develop novel LL-37-derived short α-helical AMPs with improved cell selectivity and without a significant loss of anti-inflammatory activity relative to that of parental LL-37. Using amino acid substitution, we designed and synthesized a series of FK13 analogs based on the sequence of the 13-meric short FK13 peptide (residues 17-29 of LL-37) that has been identified as the region responsible for the antimicrobial activity of LL-37. Among the designed FK13 analogs, FK-13-a1 and FK-13-a7 showed high cell selectivity and retained the anti-inflammatory activity. The therapeutic index (a measure of cell selectivity) of FK-13-a1 and FK-13-a7 was 6.3- and 2.3-fold that of parental LL-37, respectively. Furthermore, FK-13-a1 and FK-13-a7 displayed more potent antimicrobial activity against antibiotic-resistant bacteria including MRSA, MDRPA, and VREF, than did LL-37. In addition, FK-13-a1 and FK-13-a7 exhibited greater synergistic effects with chloramphenicol against MRSA and MDRPA and were more effective anti-biofilm agents against MDRPA than LL-37 was. Moreover, FK-13-a1 and FK-13-a7 maintained their activities in the presence of physiological salts and human serum. SYTOX green uptake, membrane depolarization and killing kinetics revealed that FK13-a1 and FK13-a7 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Taken together, our results suggest that FK13-a1 and FK13-a7 can be developed as novel antimicrobial/anti-inflammatory agents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Study Objective: To compare the clinical efficacy and safety of laparoscopic cornuotomy and cornual resection in the treatment of interstitial pregnancy., Design: Retrospective chart review between 2006 and 2014 (Canadian Task Force classification II-2)., Setting: Two academic tertiary care hospitals., Patients: Seventy-five patients with interstitial pregnancy treated by laparoscopy., Measurement and Main Results: In the 75 patients, 53 who underwent cornual resection and 22 who underwent cornuotomy, we evaluated operating time, changes in hemoglobin levels after surgery, the rate of major complications, and the incidence of persistent interstitial pregnancy. The mean operating time was significantly shorter for cornuotomy than for cornual resection (59.36 ± 19.32 minutes vs. 77.11 ± 23.97 minutes, respectively). Changes in hemoglobin level after the operation, rates of major complications, and the incidence of persistent interstitial pregnancy were not significantly different in the 2 surgery groups., Conclusion: Laparoscopic cornuotomy yielded clinical results comparable to those of cornual resection. Laparoscopic cornuotomy may reduce the time of operation, and had the same incidence of persistent interstitial pregnancy as cornual resection., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Cytogenetic analysis aides in risk stratification for patients with multiple myeloma (MM). Although several cytogenetic aberrations have been reported to be prognostic, less is known about the association between the presence of monosomies and prognosis. The present study evaluated the prevalence and prognostic implications of monosomies in patients with MM., Materials and Methods: Karyotypes were determined using conventional cytogenetics and fluorescence in situ hybridization (FISH). The prognostic effect of monosomies was evaluated by comparison with the clinical factors in MM patients with normal karyotypes., Results: Karyotypes were successfully determined in 167 of the 170 patients with MM. Of these 167 patients, 52 (31.1%) had abnormal karyotypes. Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14, and loss of X detected by metaphase analysis were each associated with reduced progression-free survival (P < .05 for each). Univariable analyses showed that a normal karyotype, hypodiploidy, monosomies of chromosomes 13 and 16, deletion or monosomy of 13q14 detected by metaphase analysis and FISH-determined RB1 (13q)/TP53 (17p) deletion were each associated with reduced overall survival (P < .05 for each). Multivariable analysis showed that hypodiploidy detected by metaphase analysis was independently prognostic of shorter progression-free survival (P < .05 for each) and that hypodiploidy, monosomy 16, and loss of Y chromosome and FISH-determined TP53 (17p) deletion were associated with reduced overall survival (P < .05 for each)., Conclusion: In addition to known cytogenetic abnormalities, such as monosomy 13, hypodiploidy, and TP53 (17p) deletion, monosomy 16 and loss of the Y chromosome have adverse prognostic implications in patients with MM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

(E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP) is a novel synthetic naphthal chalcone derivative. The aim of this study was to investigate the mode of action underlying the antitumor activity of HMP. We found that treatment with HMP potently inhibited the clonogenicity and triggered cell death in HCT116 colon cancer cells. Flow cytometry showed that HMP induced an increase in the population of sub-G 0 /G 1 -phase cells. Annexin V binding assay revealed that HMP triggered apoptotic cell death. Furthermore, HMP stimulated the cleavages of caspase-7 and its substrate poly (ADP-ribose) polymerase (PARP). HMP promoted γ-H2AX formation and the production of reactive oxygen species (ROS), and up-regulated expression of the tumor suppressor p53. Interestingly, HMP-induced caspase-7 processing was not completely abrogated in p53-null (p53 -/- ) HCT116 cells, suggesting that p53-dependent and -independent mechanisms are involved in HMP-induced apoptosis. Egr-1, a zinc finger transcription factor, was upregulated by HMP. Silencing of Egr-1 by shRNA significantly reduced HMP-induced caspase-7 and PARP cleavages, regardless of p53 status. These results suggest that HMP triggers caspase-mediated apoptosis through two distinct mechanisms involving p53-dependent and p53-independent, Egr-1-dependent pathways., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

LONG HYPOCOTYL5 (HY5) and STF1 (Soybean TGACG-motif binding Factor 1) are two related bZIP transcription factors that play a positive role in photomorphogenesis and hormonal signaling. In this study, we compared full length STF1 and truncated STF1 overexpression lines and found that the C-terminal 133 amino acids (194-306) possess all the HY5-like function in Arabidopsis. The STF1-DC1 mutant (1-306), with a 20 amino acid deletion at the carboxy terminus, failed to complement the hy5 mutant phenotype, which suggests an intact C-terminus is required for STF1 function. To understand the role of the C-terminal domain in photomorphogenesis we used a yeast two-hybrid screen to isolate proteins that bind to the STF1 C-terminus. We isolated three soybean cDNAs encoding the zinc-finger proteins GmSTO, GmSTH, and GmSTH2, which interact with STF1. These proteins belong to a family of B-box zinc finger proteins that include Arabidopsis SALT TOLERANCE (STO) and STO HOMOLOG (STH) and STH2, which play a role in light-dependent development and gene expression. The C-terminal 63 amino acids of STF1, containing a leucine zipper and the two N-terminal B-boxes, contains the domain involved in interactions between STF1 and GmSTO. In addition, we identified an interaction between soybean COP1 (GmCOP1) and GmSTO and GmSTH, as well as STF1, which strongly suggests the presence of a similar regulatory circuit for light signaling in soybean as in Arabidopsis. This study shows that photomorphogenic control requires complex molecular interactions among several different classes of transcription factors such as bZIP, B-box factors, and COP1, a ubiquitin ligase., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Alpha-synuclein (α-Syn), a small (14 kDa) protein associated with Parkinson's disease, is abundant in human neural tissues. α-Syn plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals; however, the mechanism by which it performs this function are not well understood. In addition, there is a correlation between α-Syn over-expression and upregulation of an innate immune response. Given the growing body of literature surrounding antimicrobial peptides (AMPs) in the brain, and the similarities between α-Syn and a previously characterized AMP, Amyloid-β, we set out to investigate if α-Syn shares AMP-like properties. Here we demonstrate that α-Syn exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, we demonstrate a role for α-Syn in inhibiting various pathogenic fungal strains such as Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani. We also analyzed localizations of recombinant α-Syn protein in E. coli and Candida albicans. These results suggest that in addition to α-Syn's role in neurotransmitter release, it appears to be a natural AMP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Brassinosteroids (BRs) are plant-specific steroids that are involved in plant growth and defense responses. However, the exact roles of BR in plant defense are unclear. We used the bes1-D gain-of-function mutant to define the underlying relationship between plant growth and defense through BR signaling and innate immunity. In bes1-D, further downstream component BES1 transcription factor is stabilized, leading to the activation of BR signaling. Previous reports on BES1 target genes showed that approximately 10% are related to biotic stress responses. Therefore, the bes1-D PTI responses were examined. The bes1-D mutant was specifically susceptible to Alternaria brassicicola, a necrotrophic fungus, which successfully produced spore, resulting in considerable cell death. However, it was not affected by a biotrophic pathogen, Pseudomonas syringae pv. tomato (Pst) DC3000. Instead of a ROS burst, a representative initial PTI responses, higher ROS accumulation was sustained in bes1-D than in the wild type plant. PDF1.2 expression was not induced in response to fungal pathogen infection in bes1-D. These results suggest that BES1 is also involved in JA-related defense responses, especially in response to necrotrophic pathogens., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Overexpression of AtNTRC (AtNTRC(OE)) in Arabidopsis thaliana led to a freezing and cold stress tolerance, whereas a knockout mutant (atntrc) showed a stress-sensitive phenotype. Biochemical analyses showed that the recombinant AtNTRC proteins exhibited a cryoprotective activity for malate dehydrogenase and lactic dehydrogenase. Furthermore, conclusive evidence of its interaction with nucleic acids in vitro is provided here on the basis of gel shift and electron microscopy analysis. Recombinant AtNTRC efficiently protected RNA and DNA from RNase A and metal catalyzed oxidation damage, respectively. The C-terminal thioredoxin domain is required for the nucleic acid-protein complex formation. From these results, it can be hypothesized that AtNTRC, which is known to be an electron donor of peroxiredoxin, contributes the stability of macromolecules under cold stress., (Copyright © 2015 Elsevier Inc. All rights reserved.)