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1.
Sci Rep ; 12(1): 1090, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058521

RESUMO

It is not clear whether mortality is associated with body temperature (BT) in older sepsis patients. This study aimed to evaluate the mortality rates in sepsis patients according to age and BT and identify the risk factors for mortality. We investigated the clusters using a machine learning method based on a combination of age and BT, and identified the mortality rates according to these clusters. This retrospective multicenter study was conducted at five hospitals in Korea. Data of sepsis patients aged ≥ 18 years who were admitted to the intensive care unit between January 1, 2011 and April 30, 2021 were collected. BT was divided into three groups (hypothermia < 36 °C, normothermia 36‒38 °C, and hyperthermia > 38 °C), and age groups were divided using a 75-year age threshold. Kaplan‒Meier analysis was performed to assess the cumulative mortality over 90 days. A K-means clustering algorithm using age and BT was used to characterize phenotypes. During the study period, 15,574 sepsis patients were enrolled. Overall, 90-day mortality was 20.5%. Kaplan‒Meier survival analyses demonstrated that 90-day mortality rates were 27.4%, 19.6%, and 11.9% in the hypothermia, normothermia, and hyperthermia groups, respectively, in those ≥ 75 years old (Log-rank p < 0.001). Cluster analysis demonstrated three groups: Cluster A (relatively older age and lower BT), Cluster B (relatively younger age and wide range of BT), and Cluster C (relatively higher BT than Cluster A). Kaplan‒Meier curve analysis showed that the 90-day mortality rates of Cluster A was significantly higher than those of Clusters B and C (24.2%, 17.1%, and 17.0%, respectively; Log-rank p < 0.001). The 90-day mortality rate correlated inversely with BT groups among sepsis patients in either age group (< 75 and ≥ 75 years). Clustering analysis revealed that the mortality rate was higher in the cluster of patients with relatively older age and lower BT.

2.
J Hazard Mater ; 422: 126919, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449340

RESUMO

The feasibility of preparing TiO2/g-CN heterojunction from Ti-incorporated dried dye wastewater sludge is explored in this study. Two reaction routes of composite formation were evaluated. In the initial approach, one-step calcination of dried sludge and melamine mixture @600 °C was carried out. Detailed morphological and chemical characterizations showed that the one-step calcination route did not create TiO2/g-CN composites; instead, only N-doped anatase TiO2 composites were formed. Moreover, due to the non-uniform composition of organic content in the dried sludge, it was not easy to control the N doping level by varying melamine content (0-100%) in the precursor mix. However, successful formation of anatase TiO2 and g-CN was observed when a two-step calcination route was followed, i.e., via synthesis of anatase TiO2 from dried sludge, and later development of heterojunction by calcining (@550 °C) the TiO2 and melamine mixture. X-ray diffraction along with infrared and X-ray photoelectron spectroscopy verified the effective heterojunction. In addition, maximum atmospheric NO removal under UV and visible light were observed for the prepared composite when the melamine content in the precursor mixture was 70%. After 1 h of UV and visible light irradiation, the best TiO2/g-CN composite removed 25.71% and 13.50% of NO, respectively. Optical characterization suggested that the enhanced NO oxidation under UV/visible light was due to the bandgap narrowing and diminished photogenerated electron-hole recombination.


Assuntos
Esgotos , Titânio , Catálise , Luz
3.
World J Surg Oncol ; 19(1): 339, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34872570

RESUMO

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a poorly studied, rare, soft tissue sarcoma. LGMS is characterized by a low malignancy potential, tendency for local recurrence, and low likelihood of distant metastases. However, no studies have reported on the surgical treatment method and its long-term outcomes. METHODS: We included all patients treated for LGMS at our institution between March 2010 and March 2021. Medical charts were retrospectively reviewed to collect demographic information, as well as information about the clinical course, tumor characteristics, and outcomes. Statistical analysis was performed to identify the factors associated with the recurrence rate. RESULTS: Fifteen patients who underwent surgical treatment were enrolled in this study. There were seven cases in the upper extremities, four in the trunk area, three in the lower extremities, and one in the head and neck area. There were no metastatic cases and two cases of local recurrence. CONCLUSIONS: The incidence of LGMS in the extremities or trunk may be higher than expected based on the current literature. Univariate analysis showed that local tissue invasion and surgical method could be associated with local recurrence. Although further large studies are needed to establish risk factors of local recurrence or extent of resection margins, based on our study, wide local excision under the proper diagnosis is the most important treatment.

4.
J Pers Med ; 11(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34945803

RESUMO

Headaches, especially migraines, have been associated with various vestibular symptoms and syndromes. Tinnitus and hearing loss have also been reported to be more prevalent among migraineurs. However, whether headaches, including migraine or non-migraine headaches (nMH), are associated with vestibular and cochlear disorders remains unclear. Thus, we sought to investigate possible associations between headache and vestibulocochlear disorders. We analyzed 10 years of data from the Smart Clinical Data Warehouse. In patients with migraines and nMH, meniere's disease (MD), BPPV, vestibular neuronitis (VN) and cochlear disorders, such as sensorineural hearing loss (SNHL) and tinnitus, were collected and compared to clinical data from controls who had health check-ups without headache. Participants included 15,128 with migraines, 76,773 patients with nMH and controls were identified based on propensity score matching (PSM). After PSM, the odds ratios (OR) in subjects with migraine versus controls were 2.59 for MD, 2.05 for BPPV, 2.98 for VN, 1.74 for SNHL, and 1.97 for tinnitus, respectively (p < 0.001). The OR for MD (1.77), BPPV (1.73), VN (2.05), SNHL (1.40), and tinnitus (1.70) in patients with nMH was also high after matching (p < 0.001). Our findings suggest that migraines and nMH are associated with an increased risk of cochlear disorders in addition to vestibular disorders.

5.
Biomed Res Int ; 2021: 4128827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754880

RESUMO

Background: Successful reconstruction of the feet and ankles remains challenging due to limited quantities of soft tissue and laxity. The free lateral arm flap (LAF) is an alternative to conventional flaps and has been widely used due to advancements in its flap characteristics. This study is aimed at utilizing the advantages of this flap to validate its increased applications for foot and ankle defects. Methods: Twenty patients with various LAF types between May 2011 and May 2020 were enrolled. Clinical data was retrospectively collected, and defect sites were classified according to the subunit principle. We utilized various LAF types, such as LAFs with sensate, extended, osteomyocutaneous, or myocutaneous flaps, as necessary. A two-point discrimination test was performed, and results were statistically compared between flaps. Results: Among the diverse etiologies of skin defects, chronic inflammation was the most common cause of defects. Various LAF types, including LAFs with fasciocutaneous, extended fasciocutaneous, musculocutaneous, and osteomyocutaneous flaps, were used. The versatility of free LAF helped successfully cover various defects in all cases. Results of the two-point discrimination test were statistically significant between groups. Conclusions: Free LAF is a unique soft tissue free flap that is more versatile than other flaps, allowing flaps to be continuously modified and applied to various foot and ankle defects under different clinical conditions.

6.
Viruses ; 13(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34696371

RESUMO

Neurological diseases in cattle can be caused by several infectious agents. Astroviruses are increasingly recognized as the causative agent of encephalitis in various animals, including humans. In this study, a neuroinvasive astrovirus (BoAstV 20B05) was discovered in the brain tissues of an 81-month-old Korean native cattle with neurological symptoms. Lymphocyte infiltration and multifocal perivascular cuffing were observed in the cerebrum and brain stem, and viral antigens were also detected in the meninges. In particular, the concentration of the astroviral genome was high in the brain tissues. Korean BoAstV 20B05 was classified into the CH13/NeuroS1 clade and was closely related to the Neuro-Uy and KagoshimaSR28-462 strains. Our evolutionary analysis showed that Korean BoAstV 20B05 belongs to the sub-lineage NeuroS1 and evolved independently of BoAstV KagoshimaSR28-462. These results suggest that neuroinvasive astroviruses were first introduced in Korea. However, analysis is limited by the lack of reference astrovirus sequences reported in various countries within Asia, and further analysis should be performed using more strains. In this study, we identified a neuroinvasive astrovirus infection with neurological symptoms for the first time in South Korea and confirmed that BoAstV 20B05 may have been introduced in South Korea a long time ago.

7.
J Craniofac Surg ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643597

RESUMO

INTRODUCTION: In case of zygomaticomaxillary fibrous dysplasia (FD), surgical treatment is often required due to visual disturbance, exophthalmos, and also necessary for cosmetic reasons. However, it is not easy to determine the timing and method of operation. The objective of our study is to define a new surgical option, for the treatment of FD of zygomaticomaxillary area. MATERIALS AND METHODS: Five patients affected by FD of their zygomaticomaxillary area who underwent surgery with a core extirpation were included in this study. A retrospective chart review and pre- and post-operative analysis of computed tomography scan were performed. RESULTS: All patients underwent core extirpation surgery and zygoma reduction was combined in 2 patients. All patients showed the cessation of the increase of external size postoperatively and results of the operation were well maintained over the follow-up period of 1 year. CONCLUSIONS: In this article, we present our experiences in the management of FD using the core extirpation with or without zygoma reduction, focusing on surgical indication, techniques, and results. Although there are limitations due to selective operative indication, the procedure can be usefully performed to prevent external growth and avoid repetitive surgery.

8.
Cells ; 10(10)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685725

RESUMO

Mature cardiomyocytes (CMs) obtained from human pluripotent stem cells (hPSCs) have been required for more accurate in vitro modeling of adult-onset cardiac disease and drug discovery. Here, we found that FGF4 and ascorbic acid (AA) induce differentiation of BG01 human embryonic stem cell-cardiogenic mesoderm cells (hESC-CMCs) into mature and ventricular CMs. Co-treatment of BG01 hESC-CMCs with FGF4+AA synergistically induced differentiation into mature and ventricular CMs. FGF4+AA-treated BG01 hESC-CMs robustly released acute myocardial infarction (AMI) biomarkers (cTnI, CK-MB, and myoglobin) into culture medium in response to hypoxic injury. Hypoxia-responsive genes and potential cardiac biomarkers proved in the diagnosis and prognosis of coronary artery diseases were induced in FGF4+AA-treated BG01 hESC-CMs in response to hypoxia based on transcriptome analyses. This study demonstrates that it is feasible to model hypoxic stress in vitro using hESC-CMs matured by soluble factors.

9.
Adv Mater ; : e2105485, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636092

RESUMO

Human behavior (e.g., the response to any incoming information) has very complex forms and is based on the response to consecutive external stimuli entering varied sensory receptors. Sensory adaptation is an elementary form of the sensory nervous system known to filter out irrelevant information for efficient information transfer from consecutive stimuli. As bioinspired neuromorphic electronic system is developed, the functionality of organs shall be emulated at a higher level than the cell. Because it is important for electronic devices to possess sensory adaptation in spiking neural networks, the authors demonstrate a dynamic, real-time, photoadaptation process to optical irradiation when repeated light stimuli are presented to the artificial photoreceptor. The filtered electrical signal generated by the light and the adapting signal produces a specific range of postsynaptic states through the neurotransistor, demonstrating changes in the response according to the environment, as normally perceived by the human brain. This successfully demonstrates plausible biological sensory adaptation. Further, the ability of this circuit design to accommodate changes in the intensity of bright or dark light by adjusting the sensitivity of the artificial photoreceptor is demonstrated. Thus, the proposed artificial photoreceptor circuits have the potential to advance neuromorphic device technology by providing sensory adaptation capabilities.

10.
J Craniofac Surg ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545055

RESUMO

ABSTRACT: Osteoma is a benign, slow growing lesion that consists of compact or cancellous bone. Three types of osteomas could be classified: the central osteoma arising from the endosteum, the peripheral osteoma from the periosteum, and the extraskeletal soft tissue osteoma. In the craniofacial region, peripheral osteomas of the zygoma are quite rare. A literature review identified 7 cases of zygomatic arch and 3 cases of zygomatic body. This is the first report of zygomatic osteoma that was endoscopically removed. This report presents a rare case of osteoma of the zygoma and its endoscopic approach. The authors were able to confirm that endoscopic approach of this zygomatic osteoma was safe and effective surgical choice.

11.
BMC Pediatr ; 21(1): 379, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479534

RESUMO

OBJECTIVE: A significant number of patients with KS have cleft palate (CP) or submucous cleft palate (SMCP) and show delayed speech development. However, few reports have discussed the characteristics of CP in KS and the outcomes of postoperative speech development. The purpose of this study was to investigate the characteristics and surgical outcomes of CP in patients with KS, and to discuss the importance of the diagnosis of CP or SMCP. METHODS: We conducted a retrospective study on patients with clinically diagnosed KS who underwent palatoplasty. Clinical and surgical data were collected from patients' medical records, and velopharyngeal function was evaluated using nasopharyngoscopy and speech analysis. RESULTS: In 11 cases, 5 patients had CP (45.5%) and 6 had SMCP (54.5%). Four patients who were genetically tested had a pathogenic variant of KMT2D. Seven of nine patients (77.8%) who underwent conventional palatoplasty showed velopharyngeal insufficiency and hypernasality. All patients who underwent pharyngeal flap surgery achieved velopharyngeal competency. Statistical analysis revealed a statistically significant difference in postoperative results between non-syndromic and KS patients. CONCLUSION: Patients with SMCP may be more common than previously reported. The results showed that it is difficult to produce optimal results with conventional palatoplasty; therefore, pharyngeal flap surgery should be considered as a treatment to obtain favorable results. Pharyngeal flap surgery in patients with KS should be carefully designed based on speech evaluation and nasopharyngoscopic findings.


Assuntos
Anormalidades Múltiplas , Fissura Palatina , Anormalidades Múltiplas/cirurgia , Fissura Palatina/diagnóstico , Fissura Palatina/cirurgia , Face/anormalidades , Doenças Hematológicas , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Doenças Vestibulares
12.
Biomed Res Int ; 2021: 4331250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485512

RESUMO

Excision is the gold standard for lipomas. Patients desire minimal scars, but minimal incisions can increase complications and produce hypertrophic scars. We propose an algorithmic method named the minimal one-third incision and four-step extraction method (MOTIF) for lipoma excision. This retrospective study analyzed lipomas surgically excised using the MOTIF method at our institution between January 2016 and December 2018. A total of 112 lipomas were included. The complication rates and Vancouver Scar Scale (VSS) for three different size groups (<3 cm, 3 ~ 6 cm, >6 cm) were compared. Complete excision of all palpable lipomas was achieved with this approach. There were two seromas, two hematomas, and one postoperative nerve injury. There was no difference in complication rates and VSS between the three size groups. The MOTIF method is a cost-effective, reliable, and cosmetically pleasing method that can be applied to all lipomas regardless of size and location.


Assuntos
Cicatriz Hipertrófica/patologia , Lipoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias/patologia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cicatriz Hipertrófica/etiologia , Feminino , Humanos , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Adulto Jovem
13.
J Clin Med ; 10(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34575335

RESUMO

In patients with intraoperative massive bleeding, the effects of fluid and blood volume on postoperative pulmonary edema are uncertain. Patients with intraoperative massive bleeding who had undergone a non-cardiac surgery in five hospitals were enrolled in this study. We evaluated the association of postoperative pulmonary edema risk and intra- and post-operatively administered fluid and blood volumes in patients with intraoperative massive bleeding. In total, 2090 patients were included in the postoperative pulmonary edema analysis, and 300 patients developed pulmonary edema within 72 h of the surgery. The postoperative pulmonary edema with hypoxemia analysis included 1660 patients, and the condition occurred in 161 patients. An increase in the amount of red blood cells transfused per hour after surgery increased the risk of pulmonary edema (hazard ratio: 1.03; 95% confidence interval: 1.01-1.05; p = 0.013) and the risk of pulmonary edema with hypoxemia (hazard ratio: 1.04; 95% confidence interval: 1.01-1.07; p = 0.024). An increase in the red blood cells transfused per hour after surgery increased the risk of developing pulmonary edema. This increase can be considered as a risk factor for pulmonary edema.

14.
J Am Chem Soc ; 143(36): 14635-14645, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34410692

RESUMO

Antibodies are recognition molecules that can bind to diverse targets ranging from pathogens to small analytes with high binding affinity and specificity, making them widely employed for sensing and therapy. However, antibodies have limitations of low stability, long production time, short shelf life, and high cost. Here, we report a facile approach for the design of luminescent artificial antibodies with nonbiological polymeric recognition phases for the sensitive detection, rapid identification, and effective inactivation of pathogenic bacteria. Transition-metal dichalcogenide (TMD) nanosheets with a neutral dextran phase at the interfaces selectively recognized S. aureus, whereas the nanosheets bearing a carboxymethylated dextran phase selectively recognized E. coli O157:H7 with high binding affinity. The bacterial binding sites recognized by the artificial antibodies were thoroughly identified by experiments and molecular dynamics simulations, revealing the significance of their multivalent interactions with the bacterial membrane components for selective recognition. The luminescent WS2 artificial antibodies could rapidly detect the bacteria at a single copy from human serum without any purification and amplification. Moreover, the MoSe2 artificial antibodies selectively killed the pathogenic bacteria in the wounds of infected mice under light irradiation, leading to effective wound healing. This work demonstrates the potential of TMD artificial antibodies as an alternative to antibodies for sensing and therapy.

15.
Biofabrication ; 13(4)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34404035

RESUMO

A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl-collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.


Assuntos
Infarto do Miocárdio , Telas Cirúrgicas , Animais , Gelatina , Hidrogéis , Infarto do Miocárdio/terapia , Miócitos Cardíacos , Impressão Tridimensional , Ratos , Engenharia Tecidual
16.
Braz J Anesthesiol ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252452

RESUMO

BACKGROUND: Both predictions and predictors of difficult laryngoscopy are controversial. Machine learning is an excellent alternative method for predicting difficult laryngoscopy. This study aimed to develop and validate practical predictive models for difficult laryngoscopy through machine learning. METHODS: Variables for the prediction of difficult laryngoscopy included age, Mallampati grade, body mass index, sternomental distance, and neck circumference. Difficult laryngoscopy was defined as grade 3 and 4 by the Cormack-Lehane classification. Pre-anesthesia and anesthesia data of 616 patients who had undergone anesthesia at a single center were included. The dataset was divided into a base training set (n = 492) and a base test set (n = 124), with equal distribution of difficult laryngoscopy. Training data sets were trained with six algorithms (multilayer perceptron, logistic regression, supportive vector machine, random forest, extreme gradient boosting, and light gradient boosting machine), and cross-validated. The model with the highest area under the receiver operating characteristic curve (AUROC) was chosen as the final model, which was validated with the test set. RESULTS: The results of cross-validation were best using the light gradient boosting machine algorithm with Mallampati score x age and sternomental distance as predictive model parameters. The predicted AUROC for the difficult laryngoscopy class was 0.71 (95% confidence interval, 0.59-0.83; p =  0.014), and the recall (sensitivity) was 0.85. CONCLUSION: Predicting difficult laryngoscopy is possible with three parameters. Severe damage resulting from failure to predict difficult laryngoscopy with high recall is small with the reported model. The model's performance can be further enhanced by additional data training.

17.
J Clin Med ; 10(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069799

RESUMO

Previous scoring models, such as the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, do not adequately predict the mortality of patients receiving mechanical ventilation in the intensive care unit. Therefore, this study aimed to apply machine learning algorithms to improve the prediction accuracy for 30-day mortality of mechanically ventilated patients. The data of 16,940 mechanically ventilated patients were divided into the training-validation (83%, n = 13,988) and test (17%, n = 2952) sets. Machine learning algorithms including balanced random forest, light gradient boosting machine, extreme gradient boost, multilayer perceptron, and logistic regression were used. We compared the area under the receiver operating characteristic curves (AUCs) of machine learning algorithms with those of the APACHE II and ProVent score results. The extreme gradient boost model showed the highest AUC (0.79 (0.77-0.80)) for the 30-day mortality prediction, followed by the balanced random forest model (0.78 (0.76-0.80)). The AUCs of these machine learning models as achieved by APACHE II and ProVent scores were higher than 0.67 (0.65-0.69), and 0.69 (0.67-0.71)), respectively. The most important variables in developing each machine learning model were APACHE II score, Charlson comorbidity index, and norepinephrine. The machine learning models have a higher AUC than conventional scoring systems, and can thus better predict the 30-day mortality of mechanically ventilated patients.

18.
Mater Sci Eng C Mater Biol Appl ; 126: 112174, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082975

RESUMO

Engineered muscle tissues can be used for the regeneration or substitution of irreversibly damaged or diseased muscles. Recently, graphene oxide (GO) has been shown to improve the adsorption of biomolecules through its biocompatibility and intrinsic π-π interactions. The possibility of producing various GO modifications may also provide additional functionality as substrates for cell culture. In particular, substrates fabricated from pristine GO have been shown to improve cellular functions and influence stem cell differentiation. In this study, we fabricated tunable GO substrates with various physical and chemical properties and demonstrated the ability of the substrate to support myogenic differentiation. Higher cellular adhesion affinity with unique microfilament anchorage was observed for GO substrates with increased GO concentrations. In addition, amino acid (AA)-conjugated GO (GO-AA) substrates were fabricated to modify GO chemical properties and study the effects of chemically modified GO substrates on myogenic differentiation. Our findings demonstrate that minor tuning of GO significantly influences myogenic differentiation.


Assuntos
Grafite , Diferenciação Celular , Desenvolvimento Muscular , Músculo Esquelético
19.
Bioorg Chem ; 113: 105022, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34098397

RESUMO

In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid ß (Aß) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure-activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aß aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aß and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aß42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.


Assuntos
Catecóis/química , Isoflavonas/química , Fármacos Neuroprotetores/química , Proteínas tau/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Desenho de Fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/metabolismo , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Proteínas tau/antagonistas & inibidores
20.
JMIR Med Inform ; 9(6): e29667, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34185005

RESUMO

BACKGROUND: The fact that medical terms require special expertise and are becoming increasingly complex makes it difficult to employ natural language processing techniques in medical informatics. Several human-validated reference standards for medical terms have been developed to evaluate word embedding models using the semantic similarity and relatedness of medical word pairs. However, there are very few reference standards in non-English languages. In addition, because the existing reference standards were developed a long time ago, there is a need to develop an updated standard to represent recent findings in medical sciences. OBJECTIVE: We propose a new Korean word pair reference set to verify embedding models. METHODS: From January 2010 to December 2020, 518 medical textbooks, 72,844 health information news, and 15,698 medical research articles were collected, and the top 10,000 medical terms were selected to develop medical word pairs. Attending physicians (n=16) participated in the verification of the developed set with 607 word pairs. RESULTS: The proportion of word pairs answered by all participants was 90.8% (551/607) for the similarity task and 86.5% (525/605) for the relatedness task. The similarity and relatedness of the word pair showed a high correlation (ρ=0.70, P<.001). The intraclass correlation coefficients to assess the interrater agreements of the word pair sets were 0.47 on the similarity task and 0.53 on the relatedness task. The final reference standard was 604 word pairs for the similarity task and 599 word pairs for relatedness, excluding word pairs with answers corresponding to outliers and word pairs that were answered by less than 50% of all the respondents. When FastText models were applied to the final reference standard word pair sets, the embedding models learning medical documents had a higher correlation between the calculated cosine similarity scores compared to human-judged similarity and relatedness scores (namu, ρ=0.12 vs with medical text for the similarity task, ρ=0.47; namu, ρ=0.02 vs with medical text for the relatedness task, ρ=0.30). CONCLUSIONS: Korean medical word pair reference standard sets for semantic similarity and relatedness were developed based on medical documents from the past 10 years. It is expected that our word pair reference sets will be actively utilized in the development of medical and multilingual natural language processing technology in the future.

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