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1.
Proc Natl Acad Sci U S A ; 121(22): e2404007121, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38768347

ABSTRACT

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.


Subject(s)
Touch , Virtual Reality , Wireless Technology , Humans , Wireless Technology/instrumentation , Touch/physiology , Skin , Robotics/instrumentation , Robotics/methods
2.
Proc Natl Acad Sci U S A ; 120(6): e2217828120, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36716364

ABSTRACT

Thermal sensations contribute to our ability to perceive and explore the physical world. Reproducing these sensations in a spatiotemporally programmable manner through wireless computer control could enhance virtual experiences beyond those supported by video, audio and, increasingly, haptic inputs. Flexible, lightweight and thin devices that deliver patterns of thermal stimulation across large areas of the skin at any location of the body are of great interest in this context. Applications range from those in gaming and remote socioemotional communications, to medical therapies and physical rehabilitation. Here, we present a set of ideas that form the foundations of a skin-integrated technology for power-efficient generation of thermal sensations across the skin, with real-time, closed-loop control. The systems exploit passive cooling mechanisms, actively switchable thermal barrier interfaces, thin resistive heaters and flexible electronics configured in a pixelated layout with wireless interfaces to portable devices, the internet and cloud data infrastructure. Systematic experimental studies and simulation results explore the essential mechanisms and guide the selection of optimized choices in design. Demonstration examples with human subjects feature active thermoregulation, virtual social interactions, and sensory expansion.


Subject(s)
Skin , Virtual Reality , Humans , Electronics , Thermosensing , Communication
3.
BMC Plant Biol ; 24(1): 215, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532331

ABSTRACT

BACKGROUND: Seed dormancy is a biological mechanism that prevents germination until favorable conditions for the subsequent generation of plants are encountered. Therefore, this mechanism must be effectively established during seed maturation. Studies investigating the transcriptome and miRNAome of rice embryos and endosperms at various maturation stages to evaluate seed dormancy are limited. This study aimed to compare the transcriptome and miRNAome of rice seeds during seed maturation. RESULTS: Oryza sativa L. cv. Nipponbare seeds were sampled for embryos and endosperms at three maturation stages: 30, 45, and 60 days after heading (DAH). The pre-harvest sprouting (PHS) assay was conducted to assess the level of dormancy in the seeds at each maturation stage. At 60 DAH, the PHS rate was significantly increased compared to those at 30 and 45 DAH, indicating that the dormancy is broken during the later maturation stage (45 DAH to 60 DAH). However, the largest number of differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were identified between 30 and 60 DAH in the embryo and endosperm, implying that the gradual changes in genes and miRNAs from 30 to 60 DAH may play a significant role in breaking seed dormancy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses confirmed that DEGs related to plant hormones were most abundant in the embryo during 45 DAH to 60 DAH and 30 DAH to 60 DAH transitions. Alternatively, most of the DEGs in the endosperm were related to energy and abiotic stress. MapMan analysis and quantitative real-time polymerase chain reaction identified four newly profiled auxin-related genes (OsSAUR6/12/23/25) and one ethylene-related gene (OsERF087), which may be involved in seed dormancy during maturation. Additionally, miRNA target prediction (psRNATarget) and degradome dataset (TarDB) indicated a potential association between osa-miR531b and ethylene biosynthesis gene (OsACO4), along with osa-miR390-5p and the abscisic acid (ABA) exporter-related gene (OsMATE19) as factors involved in seed dormancy. CONCLUSIONS: Analysis of the transcriptome and miRNAome of rice embryos and endosperms during seed maturation provided new insights into seed dormancy, particularly its relationship with plant hormones such as ABA, auxin, and ethylene.


Subject(s)
MicroRNAs , Oryza , Plant Dormancy/genetics , Oryza/genetics , Transcriptome , Plant Growth Regulators/metabolism , Germination/genetics , Seeds/genetics , Abscisic Acid/metabolism , Ethylenes/metabolism , Indoleacetic Acids/metabolism , MicroRNAs/metabolism , Gene Expression Regulation, Plant
4.
Brief Bioinform ; 23(4)2022 07 18.
Article in English | MEDLINE | ID: mdl-35709752

ABSTRACT

Unintended inhibition of the human ether-à-go-go-related gene (hERG) ion channel by small molecules leads to severe cardiotoxicity. Thus, hERG channel blockage is a significant concern in the development of new drugs. Several computational models have been developed to predict hERG channel blockage, including deep learning models; however, they lack robustness, reliability and interpretability. Here, we developed a graph-based Bayesian deep learning model for hERG channel blocker prediction, named BayeshERG, which has robust predictive power, high reliability and high resolution of interpretability. First, we applied transfer learning with 300 000 large data in initial pre-training to increase the predictive performance. Second, we implemented a Bayesian neural network with Monte Carlo dropout to calibrate the uncertainty of the prediction. Third, we utilized global multihead attentive pooling to augment the high resolution of structural interpretability for the hERG channel blockers and nonblockers. We conducted both internal and external validations for stringent evaluation; in particular, we benchmarked most of the publicly available hERG channel blocker prediction models. We showed that our proposed model outperformed predictive performance and uncertainty calibration performance. Furthermore, we found that our model learned to focus on the essential substructures of hERG channel blockers via an attention mechanism. Finally, we validated the prediction results of our model by conducting in vitro experiments and confirmed its high validity. In summary, BayeshERG could serve as a versatile tool for discovering hERG channel blockers and helping maximize the possibility of successful drug discovery. The data and source code are available at our GitHub repository (https://github.com/GIST-CSBL/BayeshERG).


Subject(s)
Deep Learning , Ether-A-Go-Go Potassium Channels , Bayes Theorem , Ether-A-Go-Go Potassium Channels/chemistry , Ether-A-Go-Go Potassium Channels/genetics , Humans , Potassium Channel Blockers/chemistry , Potassium Channel Blockers/pharmacology , Reproducibility of Results
5.
Cell Mol Life Sci ; 80(5): 132, 2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37185776

ABSTRACT

We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Focal Adhesion Protein-Tyrosine Kinases , Triple Negative Breast Neoplasms/metabolism , Cell Line, Tumor , Mitogen-Activated Protein Kinase Kinases , Cell Proliferation
6.
J Am Chem Soc ; 145(8): 4647-4658, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36745678

ABSTRACT

Cancer stem cells (CSCs) are associated with the invasion and metastatic relapse of various cancers. However, current cancer therapies are limited to targeting the bulk of primary tumor cells while remaining the CSCs untouched. Here, we report a new proton (H+) modulation approach to selectively eradicate CSCs via cutting off the H+ leaks on the inner mitochondrial membrane (IMM). Based on the fruit extract of Gardenia jasminoides, a multimodal molecule channel blocker with high biosafety, namely, Bo-Mt-Ge, is developed. Importantly, in this study, we successfully identify that mitochondrial uncoupling protein UCP2 is closely correlated with the stemness of CSCs, which may offer a new perspective for selective CSC drug discovery. Mechanistic studies show that Bo-Mt-Ge can specifically inhibit the UCP2 activities, decrease the H+ influx in the matrix, regulate the electrochemical gradient, and deplete the endogenous GSH, which synergistically constitute a unique MoA to active apoptotic CSC death. Intriguingly, Bo-Mt-Ge also counteracts the therapeutic resistance via a two-pronged tactic: drug efflux pump P-glycoprotein downregulation and antiapoptotic factor (e.g., Bcl-2) inhibition. With these merits, Bo-Mt-Ge proved to be one of the safest and most efficacious anti-CSC agents, with ca. 100-fold more potent than genipin alone in vitro and in vivo. This study offers new insights and promising solutions for future CSC therapies in the clinic.


Subject(s)
Mitochondrial Membranes , Neoplasms , Humans , Mitochondrial Membranes/metabolism , Protons , Neoplasms/pathology , Neoplastic Stem Cells/metabolism
7.
Mol Cell Biochem ; 478(1): 39-45, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35710684

ABSTRACT

TyG (triglyceride and glucose) index using triglyceride and fasting blood glucose is recommended as a useful marker for insulin resistance. To clarify whether the TyG index is a marker for predicting metabolic syndrome (MetS) and to investigate the importance of single-nucleotide polymorphisms (SNPs) in MetS diagnosis. From 2001 to 2014, a longitudinal prospective cohort study of 3580 adults aged 40-70 years was conducted. The area under the receiver operating characteristic curves (AUROC) and Youden index (YI) was calculated to assess the diagnostic value. During the 14-year follow-up, 1270 subjects developed MetS. Five SNPs in four genes (BUD13 rs10790162, ZPR1 rs2075290, APOA5 rs2266788, APOA5 rs2075291, and MKL1 rs4507196) significantly correlated with susceptibility to MetS (p < 0.00005). The areas under the curve of TyG index and HOMA-IR were 0.854 (95% confidence interval [CI], 0.841-0.867) and 0.702 (95% CI, 0.684-0.721), respectively. Despite no statistical significance, AUROC and YI were increased when MetS was diagnosed using TyG index and the five SNPs. TyG index might be useful for identifying individuals at high risk of developing MetS. The combination of TyG index and SNPs showed better diagnostic accuracy than TyG index alone, indicating the potential value of novel SNPs for MetS diagnosis.


Subject(s)
Insulin Resistance , Metabolic Syndrome , Adult , Humans , Biomarkers , Blood Glucose , Insulin Resistance/genetics , Metabolic Syndrome/diagnosis , Metabolic Syndrome/genetics , Polymorphism, Single Nucleotide , Prospective Studies , Triglycerides , Middle Aged , Aged
8.
J Biomed Inform ; 137: 104268, 2023 01.
Article in English | MEDLINE | ID: mdl-36513332

ABSTRACT

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.


Subject(s)
Deep Learning , Neoplasms , Neutropenia , Humans , Child , Neutrophils , Neutropenia/chemically induced , Neoplasms/drug therapy
9.
Am J Kidney Dis ; 79(2): 175-184.e1, 2022 02.
Article in English | MEDLINE | ID: mdl-34419516

ABSTRACT

RATIONALE & OBJECTIVE: Although existing studies have reported adverse health outcomes after kidney donation, its socioeconomic impact on living donors requires further study. STUDY DESIGN: A retrospective observational cohort study including a matched comparison group. SETTING & PARTICIPANTS: 1,285 living kidney donors from 7 tertiary hospitals between 2003 and 2016, and a matched comparison group consisting of the same number of health screening examinees with similar baseline clinical characteristics and socioeconomic status. All participants were receiving Korean national health insurance. EXPOSURE: Kidney donation as reflected in the Korean National Health Insurance System (NHIS) database. OUTCOME: Changes in household economic status estimated by Korean national health insurance fees and changes in employment status reflected in the NHIS database. ANALYTICAL APPROACH: The outcomes of the donor group and matched control group were compared annually using multivariable logistic regression analyses adjusted for clinical and demographic characteristics. RESULTS: The median ages of the donors and matched controls were 45 and 46 years, respectively; 44.6% of both groups were male. Compared to the comparison group, living donors were at higher risk of being unemployed or losing employment during the first 2 years after donation (eg, first-year loss of employment: odds ratio (OR), 2.27 [95% CI, 1.55-3.33]); however, this association did not persist. Donors also had a significantly lower odds of improvement in economic status (OR, 0.57 [95% CI, 0.47-0.71]) and a higher odds of deterioration in financial status (OR, 1.54 [95% CI, 1.23-1.93]) in the first year after transplantation and subsequently. LIMITATIONS: Unmeasured differences between donors and matched controls creating residual selection bias and confounding. CONCLUSIONS: Living kidney donors may suffer loss of employment and poor economic status after their voluntary donation. The socioeconomic impact on these donors should be considered in conjunction with the potential long-term adverse health outcomes after donation.


Subject(s)
Kidney Transplantation , Living Donors , Cohort Studies , Humans , Kidney , Male , Middle Aged , Nephrectomy , Republic of Korea/epidemiology , Retrospective Studies
10.
Cancer Cell Int ; 22(1): 289, 2022 Sep 20.
Article in English | MEDLINE | ID: mdl-36127671

ABSTRACT

BACKGROUND: The emergence of de novo or intrinsic trastuzumab resistance is exceedingly high in breast cancer that is HER2 positive and correlates with an abundant cancer stem cell (CSC)-like population. We sought to examine the capacity of ß-escin, an anti-inflammatory drug, to address trastuzumab resistance in HER2-positive breast cancer cells. METHODS: The effect of ß-escin on trastuzumab-resistant and -sensitive cell lines in vitro was evaluated for apoptosis, expression of HER2 family members, and impact on CSC-like properties. An in vivo model of trastuzumab-resistant JIMT-1 was used to examine the efficacy and toxicity of ß-escin. RESULTS: ß-escin induced mitochondrial-mediated apoptosis accompanied by reactive oxygen species (ROS) production and increased active p18Bax fragmentation, leading to caspase-3/-7 activation. Attenuation of CSC-related features by ß-escin challenge was accompanied by marked reductions in CD44high/CD24low stem-like cells and aldehyde dehydrogenase 1 (ALDH1) activity as well as hindrance of mammosphere formation. ß-escin administration also significantly retarded tumor growth and angiogenesis in a trastuzumab-resistant JIMT-1 xenograft model via downregulation of CSC-associated markers and intracellular domain HER2. Importantly, ß-escin selectively inhibited malignant cells and was less toxic to normal mammary cells, and no toxic effects were found in liver and kidney function in animals. CONCLUSIONS: Taken together, our findings highlight ß-escin as a promising candidate for the treatment of trastuzumab-resistant HER2-positive breast cancers.

11.
Medicina (Kaunas) ; 58(5)2022 May 20.
Article in English | MEDLINE | ID: mdl-35630098

ABSTRACT

Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein-protein interaction network. Results: Finally, we identified 137 differentially expressed genes (59 upregulated genes and 16 downregulated genes). AKAP12, AMOT, C3AR1, LY96, PIK3AP1, PLCD4, PLCG2, TENM2, TLR2, and TSPAN5 were filtrated by the hub genes related to the development of post-transplant AKI from the Protein-Protein Interaction (PPI) network. Conclusions: This may provide important evidence of the diagnostic and therapeutic biomarker of AKI.


Subject(s)
Acute Kidney Injury , Kidney Transplantation , Acute Kidney Injury/genetics , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Humans , Kidney Transplantation/adverse effects
12.
Ann Surg Oncol ; 28(12): 7742-7758, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33969463

ABSTRACT

BACKGROUND: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. METHODS: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. RESULTS: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. CONCLUSION: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Minimally Invasive Surgical Procedures , Neuroendocrine Tumors/surgery , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Propensity Score , Retrospective Studies , Treatment Outcome
13.
J Korean Med Sci ; 36(10): e71, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33724738

ABSTRACT

BACKGROUND: For the 2018-2019 season, the national influenza immunization program expanded to cover children aged from 6 months to 12 years in Korea. This study aimed to analyze vaccine effectiveness (VE) against influenza in children visiting the pediatric emergency room at a tertiary hospital during the 2018-2019 season. METHODS: Patients tested for influenza antigens from October 1st 2018 to May 31st 2019 at the pediatric emergency room of Samsung Medical Center were included. Patients' influenza antigen test results, influenza vaccination history, and underlying medical conditions were reviewed retrospectively. VE was estimated from the test-negative design study. RESULTS: Among the 2,901 visits with influenza test results 1,692 visits of 1,417 patients were included for analysis. Among these 1,417 patients, 285 (20.1%) were positive (influenza A, n = 211, 74.0%; influenza B, n = 74, 26.0%). The VE in all patients was 36.4% (95% confidence interval [CI], 13.9 to 53.1). The VE for influenza A was 37.6% (95% CI, 12.6 to 55.5) and VE for influenza B was 24.0% (?38.5 to 58.3). The VE in the age group 6 months to 12 years was significant with a value of 35.6% (95% CI, 10.5 to 53.7); it was not statistically significant in the age group 13 to 18 years. In a multivariate logistic regression model, patients who received an influenza vaccination were less likely to get influenza infection (OR, 0.6; 95% CI, 0.4 to 0.8; P = 0.001), with significant confounding factors such as age group 13 to 18 years (OR, 0.5; 95% CI, 0.3 to 0.8; P = 0.003) and underlying hematology-oncology disease (OR, 0.3; 95% CI, 0.1 to 0.6; P = 0.002). CONCLUSION: We report moderate effectiveness of influenza vaccination in previously healthy children aged from 6 months to 12 years in the 2018-2019 season.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Immunization Programs/organization & administration , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Vaccination/statistics & numerical data , Adolescent , Child , Female , Hospitalization/statistics & numerical data , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Influenza Vaccines/immunology , Influenza, Human/epidemiology , Influenza, Human/virology , Male , Republic of Korea/epidemiology , Retrospective Studies , Seasons
14.
Medicina (Kaunas) ; 57(9)2021 Sep 05.
Article in English | MEDLINE | ID: mdl-34577859

ABSTRACT

Background and Objectives: this study aimed to clarify the relationship between inflammation-based parameters and prognosis in patients with acute kidney injury (AKI). Materials and Methods: We analyzed the prospectively collected data of patients with AKI, who were admitted through the emergency department between March 2020 and April 2021. Their clinical characteristics, inflammation-based parameters, resolving/non-resolving AKI pattern, and major adverse kidney event (MAKE) rates were analyzed. Results: Among 177 patients, 129 (72.9%) had a resolving AKI pattern and 48 (27.1%) had a non-resolving AKI pattern. The outcome of MAKE occurred in 30 (16.9%) participants. Multivariate analyses showed that the neutrophil-to-monocyte ratio was an independent predictor of resolving AKI, and that the neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios were independent predictors of MAKE occurrence. Conclusions: we demonstrated that inflammation-based parameters are valuable predictors of early recovery and MAKE occurrence in patients with AKI.


Subject(s)
Acute Kidney Injury , Acute Kidney Injury/epidemiology , Humans , Inflammation , Lymphocytes , Neutrophils , Prognosis , Retrospective Studies , Risk Factors
15.
Mol Cancer ; 19(1): 161, 2020 11 20.
Article in English | MEDLINE | ID: mdl-33218356

ABSTRACT

Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/- 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24low/CD44high subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/drug effects , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Trastuzumab/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents, Immunological/pharmacology , Apoptosis , Biomarkers, Tumor/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation , Female , Humans , Mice , Neoplastic Stem Cells , Protein Domains , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
16.
Clin Exp Allergy ; 50(5): 585-596, 2020 05.
Article in English | MEDLINE | ID: mdl-32053269

ABSTRACT

BACKGROUND: Immunologic function in innate and adaptive immunity changes with the ageing process. Thus, age-related cytokine profiles in chronic rhinosinusitis (CRS) need to be investigated for precision medicine. OBJECTIVE: The objective of this study was to characterize age-related changes in immunologic profiles according to CRS subtypes. METHODS: Subjects in control (n = 29), CRS without nasal polyps (CRSsNP, n = 86), and CRS with nasal polyps (eosinophilic NP: ENP, n = 81; non-eosinophilic NP: NENP, n = 113) were enrolled in this study. Twenty markers for type 1/2/3 inflammation and other inflammatory processes were measured in homogenates of sinonasal tissues and statistically analysed. RESULTS: In control tissues, type 2/3 and proinflammatory mediators showed an inverse correlation with age. CRSsNP and NENP showed an age-related increase in type 2 cytokines and a decline in type 3 cytokines. Interestingly, the age-related decrease in type 3 mediators was associated with those of CT scores in NENP. ENP showed an age-related increase in type 3 cytokines with type 2 mediators sustained at high levels. Smokers with ENP demonstrated age-associated increases in type 1/2/3 mediators as well as CT scores. These age-related patterns in each CRS were confirmed by statistically adjusting atopy status, smoking history, and disease duration. CONCLUSION: Age-associated cytokine changes differed among CRS subtypes and control tissues. CRSsNP and NENP demonstrated a decline in type 3 mediators and increase in type 2 mediators, whereas type 3 mediators increased with age in ENP.


Subject(s)
Aging , Cytokines/metabolism , Nasal Polyps , Rhinitis , Sinusitis , Adolescent , Adult , Aged , Aging/metabolism , Aging/pathology , Biomarkers/metabolism , Female , Humans , Male , Middle Aged , Nasal Polyps/metabolism , Nasal Polyps/pathology , Rhinitis/metabolism , Rhinitis/pathology , Sinusitis/metabolism , Sinusitis/pathology
17.
Opt Lett ; 45(11): 3009-3012, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32479445

ABSTRACT

Photodetectors with internal gain are of great interest for imaging applications, since internal gain reduces the effective noise of readout electronics. High-gain photodetectors have been demonstrated, but only individually rather than as a full array in a camera. Consequently, there has been little investigation of the interaction between camera complementary metal oxide semiconductor (CMOS) electronics and the slow response time that high-gain photodetectors often exhibit. Here we show that this interaction filters shot noise and causes noise statistics to differ from the common Poisson distribution. As an example, we investigate a 320×256 array of InGaAs/InP high-gain phototransistors bonded to a CMOS readout chip. We demonstrate the filtering effects and discuss their consequences, including new (to the best of our knowledge) methods for extracting gain and increasing dynamic range.

18.
Biotechnol Bioprocess Eng ; 25(6): 895-930, 2020.
Article in English | MEDLINE | ID: mdl-33437151

ABSTRACT

As expenditure on drug development increases exponentially, the overall drug discovery process requires a sustainable revolution. Since artificial intelligence (AI) is leading the fourth industrial revolution, AI can be considered as a viable solution for unstable drug research and development. Generally, AI is applied to fields with sufficient data such as computer vision and natural language processing, but there are many efforts to revolutionize the existing drug discovery process by applying AI. This review provides a comprehensive, organized summary of the recent research trends in AI-guided drug discovery process including target identification, hit identification, ADMET prediction, lead optimization, and drug repositioning. The main data sources in each field are also summarized in this review. In addition, an in-depth analysis of the remaining challenges and limitations will be provided, and proposals for promising future directions in each of the aforementioned areas.

19.
J Pediatr ; 208: 243-250.e3, 2019 05.
Article in English | MEDLINE | ID: mdl-30871796

ABSTRACT

OBJECTIVE: To analyze the incidence of acute kidney injury (AKI) in the first year after cancer diagnosis in children and to evaluate the short-term and long-term effects on renal function and proteinuria. STUDY DESIGN: Retrospective review of medical records was done on children who were diagnosed and treated for cancer at Seoul National University Hospital between 2004 and 2013. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria. Impaired renal function of estimated glomerular filtration rate less than 90 mL/minute/1.73 m2 and development of proteinuria of cancer survivors were also assessed. RESULTS: This study included 1868 patients who were diagnosed with cancer at a median age of 7.9 years. During the course of treatment, 983 patients (52.6%) developed 1864 episodes of AKI, and the cumulative incidence at 2 weeks, 3 months, and 1 year after diagnosis was 28.9%, 39.6%, and 53.6%, respectively. The 1-year cumulative incidence was the highest in patients with acute myeloid leukemias (88.4%). In all, 6.1% of patients had more than 4 episodes of AKI and 11.8% of patients had stage 3 AKI. Among the 1096 childhood cancer survivors, 22.6% were found to have impaired renal function. A greater number of AKI episodes (≥4 times) and nephrectomy were independent risk factors of impaired renal function. Also, 8.2% of the survivors developed proteinuria among 742 childhood cancer survivors. CONCLUSIONS: A large percentage of children with cancer experience AKI during the course of treatment, and AKI is associated with impaired long-term renal function.


Subject(s)
Acute Kidney Injury/complications , Brain Neoplasms/complications , Leukemia, Myeloid, Acute/complications , Acute Kidney Injury/epidemiology , Brain Neoplasms/epidemiology , Cancer Survivors , Child , Child, Preschool , Female , Glomerular Filtration Rate , Humans , Incidence , Infant , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/epidemiology , Lymphoma/complications , Male , Nephrectomy , Proteinuria/complications , Proteinuria/epidemiology , Republic of Korea , Retrospective Studies , Risk Factors , Treatment Outcome
20.
Medicina (Kaunas) ; 55(6)2019 May 29.
Article in English | MEDLINE | ID: mdl-31146497

ABSTRACT

Background and objectives: To compare the first pass success (FPS) rate of the C-MAC video laryngoscope (C-MAC) and conventional Macintosh-type direct laryngoscopy (DL) during cardiopulmonary resuscitation (CPR) in the emergency department (ED). Materials and Methods: This study was a single-center, retrospective study conducted from April 2014 to July 2018. Patients were categorized into either the C-MAC or DL group, according to the device used on the first endotracheal intubation (ETI) attempt. The primary outcome was the FPS rate. A multiple logistic regression model was developed to identify factors related to the FPS. Results: A total of 573 ETIs were performed. Of the eligible cases, 263 and 310 patients were assigned to the C-MAC and DL group, respectively. The overall FPS rate was 75% (n = 431/573). The FPS rate was higher in the C-MAC group than in the DL group, but there was no statistically significant difference (total n = 431, 79% compared to 72%, p = 0.075). In the multiple logistic regression analysis, the C-MAC use had higher FPS rate (adjusted odds ratio: 1.80; 95% CI, 1.17-2.77; p = 0.007) than that of the DL use. Conclusions: The C-MAC use on the first ETI attempt during cardiopulmonary resuscitation in the emergency department had a higher FPS rate than that of the DL use.


Subject(s)
Intubation, Intratracheal/instrumentation , Laryngoscopes/standards , Resuscitation/instrumentation , Aged , Airway Management , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Intubation, Intratracheal/methods , Laryngoscopes/adverse effects , Male , Middle Aged , Outcome Assessment, Health Care/standards , Outcome Assessment, Health Care/statistics & numerical data , Resuscitation/methods , Retrospective Studies
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