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Current investigation conducted to evaluate the associated fungal endophyte interactions of a Cd hyper-accumulator Solanum nigrum Korean ecotype under varying concentrations of Cd. Two indole-3-acetic acid (IAA) producing fungal strains, RSF-4L and RSF-6L, isolated from the leaves of S. nigrum, were initially screened for Cd tolerance and accumulation potential. In terms of dry biomass production, the strain RSF-6L showed higher tolerance and accumulation capacity for Cd toxicity in comparison to RSF-4L. Therefore, RSF-6L was applied in vivo to S. nigrum and grown for six weeks under Cd concentrations of 0, 10, and 30mgKg-1 of dry sand. The effect of fungal inoculation assessed by plant physiological responses, endogenous biochemical regulations, and Cd profile in different tissues. Significant increase were observed in plant growth attributes such as shoot length, root length, dry biomass, leaf area, and chlorophyll contents in inoculated RSF-6L plants in comparison to non-inoculated plants with or without Cd contamination. RSF-6L inoculation decreased uptake of Cd in roots and above ground parts, as evidenced by a low bio-concentration factor (BCF) and improved tolerance index (TI). However, Cd concentration in the leaves remained the same for inoculated and non-inoculated plants under Cd spiking. Fungal inoculation protected the host plants, as evidenced by low peroxidase (POD) and polyphenol peroxidase (PPO) activities and high catalase (CAT) activity. Application of appropriate fungal inoculation that can improve tolerance mechanisms of hyper-accumulators and reduce Cd uptake can be recommended for phyto-stabilisation/immobilisation of heavy metals in crop fields.
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Cadmio/metabolismo , Endófitos/fisiología , Hongos/fisiología , Contaminantes del Suelo/metabolismo , Solanum nigrum/metabolismo , Solanum nigrum/microbiología , Biodegradación Ambiental , Inactivación Metabólica , Solanum nigrum/efectos de los fármacos , Solanum nigrum/crecimiento & desarrolloRESUMEN
Most of the commercial nighttime pedestrian detection (PD) methods reported previously utilized the histogram of oriented gradient (HOG) or the local binary pattern (LBP) as the feature and the support vector machine (SVM) as the classifier using thermal camera images. In this paper, we propose a new feature called the thermal-position-intensity-histogram of oriented gradient (TPIHOG or T π HOG) and developed a new combination of the T π HOG and the additive kernel SVM (AKSVM) for efficient nighttime pedestrian detection. The proposed T π HOG includes detailed information on gradient location; therefore, it has more distinctive power than the HOG. The AKSVM performs better than the linear SVM in terms of detection performance, while it is much faster than other kernel SVMs. The combined T π HOG-AKSVM showed effective nighttime PD performance with fast computational time. The proposed method was experimentally tested with the KAIST pedestrian dataset and showed better performance compared with other conventional methods.
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A series of novel STAT3 inhibitors consisting of Michael acceptor has been identified through assays of the focused in-house library. In addition, their mode of action and structural feature responsible for the STAT3 inhibition were investigated. In particular, analog 6 revealed promising STAT3 inhibitory activity in HeLa cell lines. The analog also exhibited selective inhibition of STAT3 phosphorylation without affecting STAT1 phosphorylation and cytostatic effect in human breast epithelial cells (MCF10A-ras), which supports cancer cell-specific inhibitory properties.
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Factor de Transcripción STAT3/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Células HeLa , Humanos , Immunoblotting , Fosforilación/efectos de los fármacosRESUMEN
Fungal endophytes have been characterized as producers of phytohormones and potent promoters of plant growth. In this study, two fungal endophytes, Fusarium tricinctum RSF-4L and Alternaria alternata RSF-6L, were isolated from the leaves of Solanum nigrum. Culture filtrates (CFs) from each isolate were initially screened for indole compounds, and assayed for their ability to promote the growth of Dongjin rice plants. Nearly all plant growth attributes examined (i.e., chlorophyll content, root-shoot length, and biomass production) were significantly enhanced upon treatment with fungal CFs. Subsequently, gas chromatography/mass spectrometry analyses were utilized to confirm the presence of phytohormones in the CF of each fungal endophytic isolate. These analyses revealed that RSF-4L and RSF-6L produced 54 and 30 µg/mL indole acetic acid, respectively, within their respective cultures. These findings suggest that the endophytes isolated in this study synthesize bioactive compounds that could play important roles in promoting plant growth.
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Alternaria/aislamiento & purificación , Fusarium/aislamiento & purificación , Reguladores del Crecimiento de las Plantas/metabolismo , Solanum nigrum/crecimiento & desarrollo , Alternaria/química , Endófitos/química , Endófitos/aislamiento & purificación , Fusarium/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Oryza/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/microbiología , Solanum nigrum/microbiologíaRESUMEN
The present study demonstrates cloning, expression, and characterization of hyperthermostable L-asparaginase from Thermococcus kodakarensis KOD1 in Escherichia coli BLR(DE3). The recombinant 6× His-tagged protein L-asparaginase from T. kodakarensis (TkAsn), was purified to homogeneity by heat treatment followed by affinity chromatography using a nickel-nitrilotriacetic acid (Ni-NTA) column. The molecular mass of the purified enzyme was found to be approximately 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzymatic properties, such as optimum temperature and pH, were 90 °C and 8.0, respectively. Its appearent Km , Vmax , and Kcat values were 2.6 mM, 1121 µmol min(-1) mg(-1) , and 694 S(-1) , respectively. The enzyme displayed high thermal stability at optimum temperature with an insignificant loss in enzymatic activity, retaining almost 90% of its activity over a time period of 32 h. The relative activity of the enzyme was significantly inhibited by the supplementation of Cu(2+) and Ni(2+) ions, while moderately inhibited by other ions. In contrast, Mg(2+) ions enhanced the relative activity compared to the control. The acrylamide contents in baked dough were reduced to sixty percent after treatment with recombinant TkAsn as compared to the untreated control. Results of the present study revealed that the enzyme was highly active at broader range of temperatures and pH, which reflect the potential of recombinant TkAsn in the food processing industry. In addition, the high thermal stability of the enzyme may facilitates its handling, storage, and transportation.
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Asparaginasa/metabolismo , Thermococcus/enzimología , Secuencia de Aminoácidos , Asparaginasa/química , Asparaginasa/genética , Clonación Molecular , Electroforesis en Gel de Poliacrilamida , Activadores de Enzimas/análisis , Inhibidores Enzimáticos/análisis , Estabilidad de Enzimas , Escherichia coli/genética , Expresión Génica , Concentración de Iones de Hidrógeno , Cinética , Metales/metabolismo , Datos de Secuencia Molecular , Peso Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Temperatura , Thermococcus/genéticaRESUMEN
OBJECTIVES: To use clinical, radiographic, and CT radiomics features to develop and validate a preoperative prediction model for the early recurrence of pancreatic cancer. METHODS: We retrospectively analyzed 190 patients (150 and 40 in the development and test cohort from different centers) with pancreatic cancer who underwent pancreatectomy between January 2018 and June 2021. Radiomics, clinical-radiologic (CR), and clinical-radiologic-radiomics (CRR) models were developed for the prediction of recurrence within 12 months after surgery. Performance was evaluated using the area under the curve (AUC), Brier score, sensitivity, and specificity. RESULTS: Early recurrence occurred in 36.7% and 42.5% of the development and test cohorts, respectively (P = 0.62). The features for the CR model included carbohydrate antigen 19-9 > 500 U/mL (odds ratio [OR], 3.60; P = 0.01), abutment to the portal and/or superior mesenteric vein (OR, 2.54; P = 0.054), and adjacent organ invasion (OR, 2.91; P = 0.03). The CRR model demonstrated significantly higher AUCs than the radiomics model in the internal (0.77 vs. 0.73; P = 0.048) and external (0.83 vs. 0.69; P = 0.038) validations. Although we found no significant difference between AUCs of the CR and CRR models (0.83 vs. 0.76; P = 0.17), CRR models showed more balanced sensitivity and specificity (0.65 and 0.87) than CR model (0.41 and 0.91) in the test cohort. CONCLUSIONS: The CRR model outperformed the radiomics and CR models in predicting the early recurrence of pancreatic cancer, providing valuable information for risk stratification and treatment guidance.
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Neoplasias Pancreáticas , Radiómica , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Área Bajo la Curva , Tomografía Computarizada por Rayos XRESUMEN
Bacterial leaf blight of carrots caused by Xanthomonas hortorum pv. carotae (Xhc) is an important worldwide seed-borne disease. In 2012 and 2013, symptoms similar to bacterial leaf blight were found in carrot farms in Jeju Island, Korea. The phenotypic characteristics of the Korean isolation strains were similar to the type strain of Xhc. Pathogenicity showed symptoms on the 14th day after inoculation on carrot plants. Identification by genetic method was multi-position sequencing of the isolated strain JJ2001 was performed using four genes (danK, gyrB, fyuA, and rpoD). The isolated strain was confirmed to be most similar to Xhc M081. Furthermore, in order to analyze the genetic characteristics of the isolated strain, whole genome analysis was performed through the next-generation sequencing method. The draft genome size of JJ2001 is 5,443,372 bp, which contains 63.57% of G + C and has 4,547 open reading frames. Specifically, the classification of pathovar can be confirmed to be similar to that of the host lineage. Plant pathogenic factors and determinants of the majority of the secretion system are conserved in strain JJ2001. This genetic information enables detailed comparative analysis in the pathovar stage of pathogenic bacteria. Furthermore, these findings provide basic data for the distribution and diagnosis of Xanthomonas hortorum pv. carotae, a major plant pathogen that infects carrots in Korea.
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Malnutrition might play a key role in the prognosis of patients with Crohn's disease (CD). The aim of this study was to explore the impact of weight loss from diagnosis of CD to one-year post-diagnosis on disease prognosis in terms of surgery. Patients who were diagnosed with CD at Samsung Medical Center between 1995 to 2020 were included in this study. The study defined the "group with weight loss" as patients with weight loss in one year after diagnosis and the "group without body weight loss" as patients without weight loss in one year after diagnosis. Their data such as demographics, laboratory findings, and medical interventions were collected retrospectively. The primary outcome was confirmation of the difference in the incidence of surgery associated with CD between the group with weight loss and the group without body weight loss. We further analyzed factors associated with surgery outcomes. A total of 165 patients were analyzed in this study. Forty-one patients (24.8%) had body weight loss whereas 124 patients (75.2%) had no body weight loss. Body change at one year showed no significant association with direct surgical incidence. However, the patients with weight loss tended to undergo surgery earlier than patients without body weight loss. Among factors associated with outcomes of Crohn's surgery, the albumin was the only significant factor. Patients with weight loss had no statistically significant increase in the risk of surgery than patients without weight loss, although they tended to undergo surgery earlier than patients without body weight loss. A prospective study is needed to determine serial body weight changes during follow-up for patients with CD.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Estudios Retrospectivos , Pérdida de Peso , Pronóstico , Estudios ProspectivosRESUMEN
Recently, metal halide perovskite-based top cells have shown significant potential for use in inexpensive and high-performance tandem solar cells. In state-of-the-art p-i-n perovskite/Si tandem devices, atomic-layer-deposited SnO2 has been widely used as a buffer layer in the top cells because it enables conformal, pinhole-free, and highly transparent buffer layer formation. In this work, the effects of various electrical properties of SnO2 and C60 layers on the carrier transport characteristics and the performance of the final devices were investigated using a numerical simulation method, which was established based on real experimental data to increase the validity of the model. It was found that the band alignment at the SnO2/C60 interface does, indeed, have a significant impact on the electron transport. In addition, as a general design rule, it was suggested that at first, the conduction band offset (CBO) between C60 and SnO2 should be chosen so as not to be too negative. However, even in a case in which this CBO condition is not met, we would still have the means to improve the electron transport characteristics by increasing the doping density of at least one of the two layers of C60 and/or SnO2, which would enhance the built-in potential across the perovskite layer and the electron extraction at the C60/SnO2 interface.
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OBJECTIVES: The outlook of artificial intelligence for healthcare (AI4H) is promising. However, no studies have yet discussed the issues from the perspective of stakeholders in Korea. This research aimed to identify stakeholders' requirements for AI4H to accelerate the business and research of AI4H. METHODS: We identified research funding trends from the Korean National Science and Technology Knowledge Information Service (NTIS) from 2015 and 2019 using "healthcare AI" and related keywords. Furthermore, we conducted an online survey with members of the Korean Society of Artificial Intelligence in Medicine to identify experts' opinions regarding the development of AI4H. Finally, expert interviews were conducted with 13 experts in three areas (hospitals, industry, and academia). RESULTS: We found 160 related projects from the NTIS. The major data type was radiology images (59.4%). Dermatology-related diseases received the most funding, followed by pulmonary diseases. Based on the survey responses, radiology images (23.9%) were the most demanding data type. Over half of the solutions were related to diagnosis (33.3%) or prognosis prediction (31%). In the expert interviews, all experts mentioned healthcare data for AI solutions as a major issue. Experts in the industrial field mainly mentioned regulations, practical efficacy evaluation, and data accessibility. CONCLUSIONS: We identified technology, regulatory, and data issues for practical AI4H applications from the perspectives of stakeholders in hospitals, industry, and academia in Korea. We found issues and requirements, including regulations, data utilization, reimbursement, and human resource development, that should be addressed to promote further research in AI4H.
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Fine control of structural and morphological features in electrochromic materials is of paramount importance for realizing practical electrochromic devices (ECDs), which can dynamically adjust indoor light and temperature of buildings. To this end, herein we investigate impacts of two variants such as Ti-doping amount and the annealing temperature on physical and chemical properties of sol-gel derived electrochromic WO3 films. We use a wide range of titanium coupling agents (TCAs) as Ti-dopants ranging from 0 wt% to 20 wt% and vary the annealing temperature between 200 °C and 400 °C with 50 °C interval. Both variants greatly influence the physical properties of the resulting WO3 films, resulting in different crystallinities and morphologies. Through complementary analytical techniques, we find that the WO3 film featuring an amorphous phase with nano-porous morphology enhances the electrochemical and electrochromic performances. The specific TCA used in this study helps stabilize the amorphous WO3 structure and generate the nano-pores during the following thermal treatment via its thermal decomposition. As a result, the WO3 film having an optimal 8 wt% TCA annealed at 300 °C shows a high optical density of 73.78% in visible light (400-780 nm), rapid switching speed (t c = 5.12 s and t b = 4.74 s), and high coloration efficiency of 52.58 cm2 C-1 along with a superior cyclic stability. Thus, understanding a structure-property relationship is of paramount importance in engineering the advanced electrochromic WO3 for use in practical ECDs and other optoelectronic applications.
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BACKGROUND AND OBJECTIVE: The axillary vein is another option for central venous catheterisation, with less chance of accidental arterial puncture as there is a greater distance between artery and vein, and from vein to rib cage, compared with other sites. Better success, lower complication rates and faster access can be achieved with ultrasound guidance which is becoming the established technique for central venous catheterisation. We measured two key factors for successful infraclavicular axillary venous catheterisation: depth and diameter of the infraclavicular axillary vein in its medial part using ultrasound. METHODS: We recruited 98 patients, classified according to sex, age and BMI. Groups were divided according to BMI as follows: group 1 (≤20 kg m⻲), group 2 (20.01-25.00 kg m⻲) and group 3 (>25 kg m⻲); and these were further subdivided according to age: 20-39 years, 40-59 years and 60-80 years. The depth and diameter of the infraclavicular axillary vein was measured at a point between the medial third and midpoint of the clavicle. RESULTS: Vein diameter was significantly different between men and women (P = 0.005), whereas depth showed no significant difference. In the BMI subgroups, there was a significant difference in depth (P < 0.001), and a trend to significant difference in diameter (P = 0.056). However, age-specific differences in depth and diameter were not observed. CONCLUSION: During catheterisation of infraclavicular axillary vein, real-time visualisation of the needle tip when using ultrasound to gauge vein depth and diameter may diminish major complications such as pneumothorax and artery puncture.
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Vena Axilar/diagnóstico por imagen , Cateterismo Venoso Central/métodos , Ultrasonografía Intervencional/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Vena Axilar/anatomía & histología , Índice de Masa Corporal , Cateterismo Venoso Central/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Sexuales , Adulto JovenRESUMEN
Morphine is widely used in pain management although the risk of side effects is significant. The use of biased agonists to the G protein of µ-opioid receptors has been suggested as a potential solution, although oliceridine and PZM21 have previously failed to demonstrate benefits in clinical studies. An amplification-induced confusion in the process of comparing G protein and beta-arrestin pathways may account for previously biased agonist misidentification. Here, we have devised a strategy to discover biased agonists with intrinsic efficacy. We computationally simulated 430â¯000 molecular dockings to the µ-opioid receptor to construct a compound library. Hits were then verified experimentally. Using the verified compounds, we performed simulations to build a second library with a common scaffold and selected compounds that showed a bias to µ- and δ-opioid receptors in a cell-based assay. Three compounds (ID110460001, ID110460002, and ID110460003) with a dual-biased agonistic effect for µ- and δ-opioid receptors were identified. These candidates are full agonists for the µ-opioid receptor and show specific binding modes. On the basis of our findings, we expect our novel compounds to act as more biased agonists compared to existing drugs, including oliceridine.
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We investigated the clinical relevance of urinary cytokines/chemokines reflecting intrarenal immunologic micromilieu as prognostic markers and the optimal measurement timing after living donor kidney transplantation (LDKT). This prospective cohort study included 77 LDKT patients who were followed for ≥ 5 years. Patients were divided into control (n = 42) or acute rejection (AR, n = 35) group. Early AR was defined as AR occurring within 3 months. Serum and urine cytokines/chemokines were measured serially as follows: intraoperative, 8/24/72 h, 1 week, 3 months, and 1 year after LDKT. Intrarenal total leukocytes, T cells, and B cells were analyzed with immunohistochemistry followed by tissueFAXS. Urinary MCP-1 and fractalkine were also analyzed in a validation cohort. Urinary MCP-1 after one week was higher in the AR group. Urinary MCP-1, fractalkine, TNF-α, RANTES, and IL-6 after one week were significantly higher in the early AR group. Intrarenal total leukocytes and T cells were elevated in the AR group compared with the control group. Urinary fractalkine, MCP-1, and IL-10 showed positive correlation with intrarenal leukocyte infiltration. Post-KT 1 week urinary MCP-1 showed predictive value in the validation cohort. One-week post-KT urinary MCP-1 may be used as a noninvasive diagnostic marker for predicting AR after LDKT.
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Quimiocina CCL2/orina , Rechazo de Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Adulto , Biomarcadores/orina , Quimiocinas/sangre , Citocinas/sangre , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/orina , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios ProspectivosRESUMEN
BACKGROUND: The prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group. METHODS: We identified patients with pN0-1, HR+/HER2- breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score. RESULTS: A total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged >50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05-1.56; P = 0.015), as well as those aged >50 years. CONCLUSION: The BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2- early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.
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BACKGROUND: A timely decision in the initial stages for patients with an acute illness is important. However, only a few studies have determined the prognosis of patients based on insufficient laboratory data during the initial stages of treatment. OBJECTIVE: This study aimed to develop and validate time adaptive prediction models to predict the severity of illness in the emergency department (ED) using highly sparse laboratory test data (test order status and test results) and a machine learning approach. METHODS: This retrospective study used ED data from a tertiary academic hospital in Seoul, Korea. Two different models were developed based on laboratory test data: order status only (OSO) and order status and results (OSR) models. A binary composite adverse outcome was used, including mortality or hospitalization in the intensive care unit. Both models were evaluated using various performance criteria, including the area under the receiver operating characteristic curve (AUC) and balanced accuracy (BA). Clinical usefulness was examined by determining the positive likelihood ratio (PLR) and negative likelihood ratio (NLR). RESULTS: Of 9491 eligible patients in the ED (mean age, 55.2 years, SD 17.7 years; 4839/9491, 51.0% women), the model development cohort and validation cohort included 6645 and 2846 patients, respectively. The OSR model generally exhibited better performance (AUC=0.88, BA=0.81) than the OSO model (AUC=0.80, BA=0.74). The OSR model was more informative than the OSO model to predict patients at low or high risk of adverse outcomes (P<.001 for differences in both PLR and NLR). CONCLUSIONS: Early-stage adverse outcomes for febrile patients could be predicted using machine learning models of highly sparse data including test order status and laboratory test results. This prediction tool could help medical professionals who are simultaneously treating the same patient share information, lead dynamic communication, and consequently prevent medical errors.
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BACKGROUND: The development and application of clinical prediction models using machine learning in clinical decision support systems is attracting increasing attention. OBJECTIVE: The aims of this study were to develop a prediction model for cardiac arrest in the emergency department (ED) using machine learning and sequential characteristics and to validate its clinical usefulness. METHODS: This retrospective study was conducted with ED patients at a tertiary academic hospital who suffered cardiac arrest. To resolve the class imbalance problem, sampling was performed using propensity score matching. The data set was chronologically allocated to a development cohort (years 2013 to 2016) and a validation cohort (year 2017). We trained three machine learning algorithms with repeated 10-fold cross-validation. RESULTS: The main performance parameters were the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). The random forest algorithm (AUROC 0.97; AUPRC 0.86) outperformed the recurrent neural network (AUROC 0.95; AUPRC 0.82) and the logistic regression algorithm (AUROC 0.92; AUPRC=0.72). The performance of the model was maintained over time, with the AUROC remaining at least 80% across the monitored time points during the 24 hours before event occurrence. CONCLUSIONS: We developed a prediction model of cardiac arrest in the ED using machine learning and sequential characteristics. The model was validated for clinical usefulness by chronological visualization focused on clinical usability.
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We report a facile, but robust approach to fabricate structurally stable giant unilamellar vesicles (GUVs), on which a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membrane was made rigid by introducing amphiphilic block polymers. Particularly, we found that lateral co-assembly of an amphiphilic triblock copolymer (ATC) structured with a hydrophobic middle block and long molecular weight (20â¯Kâ¯g/mol) hydrophilic end blocks remarkably enhanced the stretching modulus (k) of GUVs. When the membrane composition was optimized, the k value of ATC-hybridized GUVs increased to 6.2â¯×â¯108â¯Pa, which was approximately 10-fold higher than that of DPPC GUVs, thus leading to a much longer half-life. Moreover, we demonstrated that our ATC-hybridized GUVs enabled development of a fascinating vesicular model, which shows great potential as a structurally stable cell membrane mimic.
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1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Membrana Dobles de Lípidos/química , Liposomas/química , Polímeros/química , Liposomas Unilamelares/química , 1,2-Dipalmitoilfosfatidilcolina/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signals that are often constitutively activated in many cancerous or transformed cells and some stromal cells in the tumor microenvironment. Persistent STAT3 activation in malignant cells stimulates proliferation, survival, angiogenesis, invasion, and tumor-promoting inflammation. STAT3 undergoes activation through phosphorylation on tyrosine 705, which facilitates its dimerization. Dimeric STAT3 translocates to the nucleus, where it regulates the transcription of genes involved in cell proliferation, survival, etc. In the present study, a synthetic deguelin analogue SH48, discovered by virtual screening, inhibited the phosphorylation, nuclear translocation, and transcriptional activity of STAT3 in H-ras transformed human mammary epithelial MCF-10A cells (MCF10A-ras). We speculated that SH48 bearing an α,ß-unsaturated carbonyl group could interact with a thiol residue of STAT3, thereby inactivating this transcription factor. Non-electrophilic analogues of SH48 failed to inhibit STAT3 activation, lending support to the above supposition. By utilizing a biotinylated SH48, we were able to demonstrate the complex formation between SH48 and STAT3. SH48 treatment to MCF10A-ras cells induced autophagy, which was verified by staining with a fluorescent acidotropic probe, LysoTracker Red, as well as upregulating the expression of LC3II and p62. In conclusion, the electrophilic analogue of deguelin interacts with STAT3 and inhibits its activation in MCF10A-ras cells, which may account for its induction of autophagic death.
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Quorum sensing (QS) enables bacteria to organize gene expression programs, thereby coordinating collective behaviors. It involves the production, release, and population-wide detection of extracellular signaling molecules. The cellular processes regulated by QS in bacteria are diverse and may be used in mutualistic coordination or in response to changing environmental conditions. Here, we focused on the influence of the QS-dependent genes of our model bacterial strain Serratia fonticola GS2 on potential plant growth promoting (PGP) activities including indole-3-acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, and biofilm formation. Based on genomic and phenotypic experimental data we identified and investigated the function of QS genes in the genome of the model strain. Our gene deletion study confirmed the biological functionality of the QS auto-inducer (gloI) and receptor (gloR) on potential PGP activities of GS2. A transcriptomic approach was also undertaken to understand the role of QS genes in regulation of genes primarily involved in PGP activities (IAA, ACC deaminase activity, and biofilm formation). Both transcriptomic and phenotypic data revealed that the QS-deletion mutants had considerably less PGP activities, as compared to the wild type. In addition, in vivo plant experiments showed that plants treated with GS2 had significantly higher growth rates than plants treated with the QS-deletion mutants. Overall, our results showed how QS-dependent genes regulate the potential PGP activities of GS2. This information may be helpful in understanding the relationship between QS-dependent genes and the PGP activity of bacteria, which aid in the production of practical bio-fertilizers for plant growth promotion.