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Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.
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BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metástase Linfática , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Idoso , Seguimentos , Prognóstico , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Idoso de 80 Anos ou mais , Excisão de Linfonodo , Pneumonectomia , RadiômicaRESUMO
BACKGROUND: Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. METHODS: This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. RESULTS: In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781-0.961) and 0.883 (range: 0.798-0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862-0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837-0.966) and 0.922 (range: 0.872-0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886-0.968). CONCLUSIONS: The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metástase Linfática , Aprendizado de Máquina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Pescoço/diagnóstico por imagem , Radiômica , Estudos Retrospectivos , Ultrassonografia/métodosRESUMO
Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.
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Doença de Alzheimer , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Modelos Animais de Doenças , Canais de Potencial de Receptor Transitório , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Autofagia/efeitos dos fármacos , Camundongos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Humanos , Camundongos Transgênicos , Peptídeos beta-Amiloides/metabolismo , Camundongos Endogâmicos C57BL , Serina-Treonina Quinases TOR/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Transdução de Sinais/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genéticaRESUMO
Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth.
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Proteínas de Ancoragem à Quinase A/metabolismo , Autofagia , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Células HCT116 , Células HEK293 , Células HeLa , Humanos , CamundongosRESUMO
BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa/estatística & dados numéricos , Epidemias , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adolescente , Adulto , Idoso , Betacoronavirus/genética , COVID-19 , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/virologia , Transmissão de Doença Infecciosa/prevenção & controle , Epidemias/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , SARS-CoV-2 , Adulto JovemRESUMO
This paper presents a new remote sensing (RS) algorithm for retrieving instantaneous sea surface solar irradiance (SR) by using the XGBoost (XGB) package in RStudio and available remote sensing data along with ground-truth solar irradiance data. By means of XGB, the new RS algorithm, called LSU model, was structurally built with nine key RS parameters, including photosynthetically available radiation (PAR); instantaneous PAR (iPAR); water leaving reflectance Rrs at wavelengths 412, 443, 469, and 488 nm; angstrom; aerosol optical thickness (aot_869); and latitude that represent major sources and sinks of solar irradiance, as model input variables. Among the nine parameters, the most important four parameters are PAR, iPAR, latitude, and aot_869. It was found that the sea surface SR is highly affected by conditions in both the atmosphere and the seawater. The aot_869 is by far the most important factor describing the effects of the atmospheric absorption and scattering of SR before reaching the sea surface. The most important factors describing the effects of seawater characteristics on solar irradiance are PAR, iPAR, and latitude. Comparisons with existing SR models indicate that LSU model is scientifically sound due to the use of major source and sink factors of SR as model input variables. LSU model is also technically accurate due to its fine resolution (1×1 km) and overall best performance in predicting instantaneous SR. More importantly, LSU model is globally applicable as it can be utilized to obtain global-scale SR data for any day, any time, and anywhere in the world.
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Monitoramento Ambiental , Tecnologia de Sensoriamento Remoto , Luz Solar , Algoritmos , Água do MarRESUMO
BACKGROUND: Closed reduction and percutaneous pinning (CRPP) is a promising treatment for pediatric lateral condyle humerus fractures (LCHFs) displaced >4 mm. However, few studies discussed roles of fracture types on success of CRPP in LCHFs. This study aimed to analyze the impacts of types of LCHFs displaced >4 mm on the success rate of CRPP. METHODS: We retrospectively reviewed 66 consecutive pediatric LCHFs attempted CRPP at our center. Song, Milch, Jakob, and Weiss classification were used to classify LCHFs. The fracture gap ≤2 mm and step of articular surface ≤2 mm were deemed as a successful CRPP. Otherwise, open reduction and internal fixation (ORIF) would be performed. Different fracture types and preoperative displacement were analyzed for their roles on success rate of CRPP in treating LCHFs displaced >4 mm. RESULTS: Fifty patients met the inclusion criteria were finally included in this study. Results showed that Milch type II LCHFs had a higher success rate of CRPP than type I LCHFs (P=0.03, <0.05). Correlation was found between Milch types and success rate of CRPP displaced >4 mm. No difference was found between Song stage 4 and 5 LCHFs displaced >4 mm in success rate of CRPP (P=0.90, >0.05), also no difference was found in pre-operative displacement between CRPP group and ORIF group. CONCLUSIONS: Milch classification is more important than Song classification in the success rate of CRPP when treating LCHFs displaced >4 mm. Milch type II LCHFs are recommended to be treated with CRPP, while Milch type I LCHFs are recommended to be treated with ORIF. The current study confirm Song's initial report that closed reduction can be successful and should be attempted for fractures with such displacement rather than going directly to ORIF. LEVEL OF EVIDENCE: Level III.
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Fixação Intramedular de Fraturas , Fraturas do Úmero , Criança , Fixação Interna de Fraturas/métodos , Fixação Intramedular de Fraturas/métodos , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Vibrio parahaemolyticus (V.p) is a marine pathogenic bacterium that poses a high risk to human health and shellfish industry, yet an effective regional-scale nowcasting model for managing the risk remains lacking. This study presents the first regional-scale model for nowcasting the level of V.p in oysters in the marine environment by developing an ensemble modeling approach. The ensemble modeling approach involves the integration of genetic programming (GP) and deep artificial neural networks (DNN)-based modeling. The new approach was demonstrated by developing three GP-DNN ensemble models for predicting the V.p level in North Carolina, New Hampshire, and the combined region. Specifically, GP was employed to establish nonlinear functions between the V.p level and antecedent conditions of environmental variables. The nonlinear GP functions and current conditions of individual environmental variables were then utilized as inputs into a DNN model, forming a GP-DNN ensemble model. Modeling results indicated that the GP-DNN ensemble models were capable of predicting the V.p level with the correlation coefficient of 0.91, 0.90, and 0.80 for North Carolina, New Hampshire, and the combined region, respectively, demonstrating the impact of distinct environmental conditions in the local areas on accuracy of the combined regional-scale model. Sensitivity analysis results showed that sea surface temperature and sea surface salinity are the two most important environmental predictors for the abundance of V.p in oysters, followed by water level, pH, chlorophyll-a, and turbidity. The findings suggested that the GP-DNN ensemble models could be utilized as effective predictive tools for mitigating the V.p risk.
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Aprendizado Profundo , Ostreidae , Vibrio parahaemolyticus , Animais , Humanos , Monitoramento Ambiental , Ostreidae/microbiologia , Frutos do Mar/análiseRESUMO
This paper presents a hybrid model for predicting oyster norovirus outbreaks by combining the Artificial Neural Networks (ANNs) and Principal Component Analysis (PCA) methods and using the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite remote-sensing data. Specifically, 10 years (2007-2016) of cloud-free MODIS Aqua data for water leaving reflectance and environmental data were extracted from the center of each oyster harvest area. Then, the PCA was utilized to compress the size of the MODIS Aqua data. An ANN model was trained using the first 4 years of the data from 2007 to 2010 and validated using the additional 6 years of independent datasets collected from 2011 to 2016. Results indicated that the hybrid PCA-ANN model was capable of reproducing the 10 years of historical oyster norovirus outbreaks along the Northern Gulf of Mexico coast with a sensitivity of 72.7% and specificity of 99.9%, respectively, demonstrating the efficacy of the hybrid model.
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Norovirus , Ostreidae , Animais , Surtos de Doenças , Monitoramento Ambiental , Redes Neurais de Computação , Imagens de SatélitesRESUMO
BACKGROUND: The optimal treatment for pediatric supracondylar humeral fractures accompanied with a pink pulseless hand is controversial. Some clinicians recommend close observation after closed reduction and percutaneous pinning of the fractures, while some recommend surgical exploration if the radial pulse is unpalpable. The present study aimed to analyze the benefits and outcomes of close observation for treating pediatric supracondylar humeral fractures with a pink pulseless hand. METHODS: Thirteen consecutive children presenting with a pink pulseless hand following supracondylar humeral fracture were enrolled in this study. Preoperative and postoperative color-flow Duplex ultrasound detection was used to assess brachial artery compromise in most cases. Urgent closed reduction and percutaneous pinning of the fractures were attempted first. Close observation was carried out when the hand was pink and pulseless with an absent radial pulse. RESULTS: Preoperative color-flow Duplex ultrasound showed no disruption of the brachial artery in cases detected. Compression of the artery by the proximal fragment was observed in most cases, with one case of entrapment of the artery between fragments, and thrombus considered in two cases. All cases underwent urgent surgery, after which nine experienced immediate return of the radial pulse. The remaining four without a palpable pulse were managed with close observation and no deterioration of the vascular status was observed; therefore, no surgical exploration was performed. Postoperative color-flow Duplex ultrasound revealed continuity of the artery and rich collateral circulation. Patients completed an average of 4.5 years of follow-up, during which no major complications occurred. All patients achieved excellent limb function. CONCLUSIONS: Our study demonstrates that close observation after urgent closed reduction and percutaneous pinning is a sufficient approach for the treatment of pediatric supracondylar humeral fractures accompanied with a pink pulseless hand. Surgical exploration is not necessary as long as the hand is warm and well perfused. Color-flow Duplex ultrasound is beneficial for assessing vascular compromise and determining treatment strategies.
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Fraturas do Úmero , Criança , Mãos/diagnóstico por imagem , Humanos , Fraturas do Úmero/complicações , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Pulso Arterial , Resultado do TratamentoRESUMO
BACKGROUND: Although open reduction and internal fixation (ORIF) is recommended for lateral condylar humerus fractures (LCHFs) displaced by > 4 mm, several studies have reported the use of closed reduction and percutaneous pinning (CRPP) to treat LCHFs with significant displacement. However, little is known about the clinical differences between these two surgical techniques. This study aimed to compare the therapeutic effects of CRPP and ORIF in treating LCHFs displaced by > 4 mm. METHODS: We retrospectively reviewed pediatric LCHFs displaced by > 4 mm treated with either CRPP or ORIF at our center from June 2019 to October 2020. Song and Milch fracture classifications were used. Variables such as age at injury, sex, side injured, fracture displacement, fracture type, operating time, postoperative treatment, and complications were compared between the two techniques. RESULTS: One hundred twenty LCHFs met inclusion criteria. There were 36 Milch type I and 84 type II LCHFs, and 69 Song stage 4 and 51 stage 5 LCHFs. CRPP was performed in 45 cases and ORIF in 75 cases. No differences were found in age, sex, side injured, preoperative displacement, postoperative displacement, and length of immobilization between the CRPP and ORIF groups. There was a difference between operation time and pin duration. The CRPP group had shorter operation times and pin duration, and required no additional operations to remove internal pins. The average follow-up duration was 13.9 months. All patients achieved fracture union, and no complications such as infection, nonunion, delayed union, osteonecrosis, fishtail deformity, cubitus varus or valgus, or pain were recorded during follow-up. Bone spurs, lateral prominences, and decreased carrying angle were common complications in all groups. No obvious cubitus varus was observed. Unaesthetic scars were only observed in the ORIF groups. No differences in range of motion or elbow function was found among the different therapies. CONCLUSIONS: Both CRPP and ORIF can achieve satisfactory clinical outcomes in treating LCHFs displaced by > 4 mm. No differences were found in complications or prognoses between the two groups. However, CRPP shows some advantages over ORIF, like less invasive surgery, no obvious scarring, and no need for secondary surgery with anesthesia for pin removal.
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Fraturas do Úmero , Estudos Transversais , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Lateral condylar humerus fractures (LCHFs) are the second most common pediatric distal humerus fractures. Open reduction and internal fixation is recommended for fractures displaced by more than 2 mm. Few studies described using closed reduction and percutaneous pinning (CRPP) for treating fractures with greater displacements. This study aims to explore the feasibility of CRPP in treating displaced LCHFs. METHODS: All patients underwent attempted CRPP first. Once a satisfying reduction was obtained, as determined using fluoroscopy based on the relative anatomical position of the fragments, an intraoperative arthrogram was performed to further confirm the congruence of the articular surface of the distal humerus. Open reduction is necessary to ensure adequate reduction if the fracture gap is more than 2.0 mm on either anteroposterior view or oblique internal rotational view by fluoroscopy after CRPP. All included fractures were treated by a single pediatric surgeon. RESULTS: Forty-six patients were included, 29 boys and 17 girls, with an average age of 5.2 years. Of these, 22/28 (78%) Jakob type II fractures and 14/18 (78%) Jakob type III fractures were treated with CRPP. All cases in Song stages II and III, 19/25 (76%) cases in Song stage IV, and 14/18 (78%) cases of Song stage V were treated with CRPP. The remaining converted to open reduction with internal fixation. Overall, 36 of the 46 patients (78%) were treated with CRPP. The average pre-op displacement was 7.2 mm, and the average post-op displacement was 1.1 mm on the anteroposterior or oblique internal rotational radiograph in cases treated with CRPP. CRPP was performed in an average of 37 min. The average casting period was 4 weeks and the average time of pin removal was 6 weeks postoperatively. The average time of follow-up was 4 months. All patients achieved union, regardless of closed or open reduction. No infection, delayed union, cubitus varus or valgus, osteonecrosis of the trochlea or capitellum, or pain were recorded during follow-up. CONCLUSIONS: Closed reduction and percutaneous pinning effectively treats LCHFs with displacement more than 4 mm. More than 3/4 of Song stage V or Jakob type III patients can avoid an incision.
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Fixação Intramedular de Fraturas , Fraturas do Úmero , Pinos Ortopédicos , Criança , Pré-Escolar , Feminino , Fixação Interna de Fraturas , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A Minisci-type δ-selective C(sp3)-H heteroarylation of sulfonyl-protected primary aliphatic amines with N-heteroarenes under photoredox-catalyzed conditions was developed. The reaction typically uses a slight excess of amine reactant. The use of benziodoxole acetate (BI-OAc) oxidant and hexafluoroisopropanol solvent is critical to achieve high yield. Besides methylene C-H bonds, heteroarylation reactions of δ methyl C-H bonds also worked under more forced conditions. The reactions show a broad scope for both amine and N-heteroarene substrates, offering a straightforward method for synthesis of complex δ-heteroarylalkylmines from simple precursors.
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A Pd-catalyzed amide-directed enantioselective hydrocarbofunctionalization of unactivated alkenes with C-H nucleophiles has been developed using a chiral monodentate oxazoline (MOXin) ligand. Various indoles react at C3 position with aminoquinoline-coupled 3-alkenamides to give γ addition products in good to excellent yield and enantioselectivity. This study represents an important advance of the development of chiral monodentate oxazoline ligands, which have been underexplored for asymmetric catalysis.
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Live poultry markets (LPM) are one of the most important sources of human infection with avian influenza virus (AIV). During our routine surveillance of AIV, we identified an H9N6 virus (JX-H9N6) in a LPM in Nanchang city, Jiangxi Province, China. Using Bayesian coalescent analysis, it was predicted that JX-H9N6 had originated from a reassortment event between H9N2 and H6N6 AIVs in early 2014, instead of being derived from an H9N6 virus reported previously. Mutations in HA, PB1, PA, M, and NS protein, which could increase mammalian transmission and virulence, were also detected. Currently, both H9N2 and H6N6 AIVs are widely distributed in poultry and contribute to the generation of novel reassortant viruses causing human infection. Our findings highlight the importance of enhanced surveillance in birds for early prediction of human infections.
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Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Aves Domésticas/virologia , Vírus Reordenados/classificação , Vírus Reordenados/isolamento & purificação , Animais , China , Evolução Molecular , Vírus da Influenza A/genética , Mutação , Vírus Reordenados/genética , Proteínas Virais/genéticaRESUMO
The RNA component of human telomerase (hTR) localizes to Cajal bodies, and it has been proposed that Cajal bodies play a role in the assembly of telomerase holoenzyme and telomerase trafficking. Here, the role of Cajal bodies was examined in Human cells deficient of coilin (i.e. coilin-knockout (KO) cells), in which no Cajal bodies are detected. In coilin-KO cells, a normal level of telomerase activity is detected and interactions between core factors of holoenzyme are preserved, indicating that telomerase assembly occurs in the absence of Cajal bodies. Moreover, dispersed hTR aggregates and forms foci specifically during S and G2 phase in coilin-KO cells. Colocalization of these hTR foci with telomeres implies proper telomerase trafficking, independent of Cajal bodies. Therefore, telomerase adds similar numbers of TTAGGG repeats to telomeres in coilin-KO and controls cells. Overexpression of TPP1-OB-fold blocks cell cycle-dependent formation of hTR foci and inhibits telomere extension. These findings suggest that telomerase assembly, trafficking and extension occur with normal efficiency in Cajal bodies deficient human cells. Thus, Cajal bodies, as such, are not essential in these processes, although it remains possible that non-coilin components of Cajal bodies and/or telomere binding proteins (e.g. TPP1) do play roles in telomerase biogenesis and telomere homeostasis.
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Corpos Enovelados/fisiologia , Proteínas Nucleares/fisiologia , Telomerase/metabolismo , Homeostase do Telômero , Humanos , Chaperonas Moleculares , Mutagênese , Proteínas Nucleares/genética , Fase S/genética , Complexo Shelterina , Telômero/enzimologia , Proteínas de Ligação a Telômeros/metabolismoRESUMO
Norovirus is the most common cause of outbreaks of non-bacterial gastroenteritis in human. While the winter seasonality of norovirus outbreaks has been widely reported, the association between norovirus outbreak epidemics and environmental factors remains not fully understood. This literature review is intended to improve understanding of environmental factors governing norovirus outbreaks and how the factors affect norovirus transmission. To that end, a large number of studies (67) from countries around the world were critically reviewed and discussed. Results of the literature review show that temperature, humidity, and rainfall are the most important environmental variables governing the norovirus epidemic cycle. It was found that low temperature between -6.6 and 20 °C, relative humidity between 10 and 66 %, and rainfall from 1 day to 3 months before an outbreak are effective ranges of the environmental factors, which favor the prevalence of norovirus. Some other environmental factors might have an association with the cycle of norovirus epidemics. However, further investigations are needed to understand effects of the other factors on norovirus incidence. The findings of this literature review improve our understanding of the relationship between norovirus outbreaks and environmental factors and provide the direction for future research on norovirus outbreaks.
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Surtos de Doenças , Gastroenterite/epidemiologia , Norovirus/fisiologia , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Meio Ambiente , Gastroenterite/virologia , Humanos , IncidênciaRESUMO
A new algorithm was developed for retrieving sea surface temperature (SST) in coastal waters using satellite remote sensing data from Moderate Resolution Imaging Spectroradiometer (MODIS) aboard Aqua platform. The new SST algorithm was trained using the Artificial Neural Network (ANN) method and tested using 8 years of remote sensing data from MODIS Aqua sensor and in situ sensing data from the US coastal waters in Louisiana, Texas, Florida, California, and New Jersey. The ANN algorithm could be utilized to map SST in both deep offshore and particularly shallow nearshore waters at the high spatial resolution of 1 km, greatly expanding the coverage of remote sensing-based SST data from offshore waters to nearshore waters. Applications of the ANN algorithm require only the remotely sensed reflectance values from the two MODIS Aqua thermal bands 31 and 32 as input data. Application results indicated that the ANN algorithm was able to explaining 82-90% variations in observed SST in US coastal waters. While the algorithm is generally applicable to the retrieval of SST, it works best for nearshore waters where important coastal resources are located and existing algorithms are either not applicable or do not work well, making the new ANN-based SST algorithm unique and particularly useful to coastal resource management.
Assuntos
Algoritmos , Monitoramento Ambiental/métodos , Imagens de Satélites , Água do Mar/química , Temperatura , California , Florida , Louisiana , Redes Neurais de Computação , New Jersey , Texas , ÁguaRESUMO
How to address public health priorities after COVID-19 is becoming a critical task. To this end, we conducted wastewater surveillance for six leading pathogens, namely, SARS-CoV-2, norovirus, rotavirus, influenza A virus (IAV), enteroviruses and respiratory syncytial virus (RSV), in Nanchang city from January to April 2023. Metaviromic sequencing was conducted at the 1st, 4th, 7th, 9th, 12th and 14th weeks to reveal the dynamics of viral pathogens that were not covered by qPCR. Amplicon sequencing of the conserved region of norovirus GI and GII and the rotavirus and region encoding nonstructural protein of RSV was also conducted weekly. The results showed that after a rapid decrease in SARS-CoV-2 sewage concentrations occurred in January 2023, surges of norovirus, rotavirus, IAV and RSV started at the 6th, 7th, 8th and 11th weeks, respectively. The dynamics of the sewage concentrations of norovirus, rotavirus, IAV and RSV were consistent with the off-season resurgence of the above infectious diseases. Notably, peak sewage concentrations of norovirus GI, GII, rotavirus, IAV and RSV were found at the 6th, 3rd, 7th, 7th and 8th weeks, respectively. Astroviruses also resurge after the 7th week, as revealed by metaviromic data, suggesting that wastewater surveillance together with metaviromic data provides an essential early warning tool for revealing patterns of infectious disease resurgence.