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1.
Life Sci ; : 119592, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33984363

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the common malignancies worldwide. Slit-Robo GTPase-activating proteins (SRGAPs) have been shown to regulate the occurrence and development of various tumors. However, their specific roles in HCC remain elusive. METHODS: The expression pattern, genetic alteration and prognostic value of SRGAPs in HCC are analyzed by bioinformatics tools. The biological functions of SRGAP2 in HCC cells are demonstrated by in vitro experiments. The high-throughput RNA sequencing is conducted to explore the underlying molecular mechanisms of SRGAP2 in HCC cells. RESULTS: The expression levels of SRGAP1 and SRGAP2 are significantly elevated in HCC tissues compared to the normal both in Oncomine and TCGA datasets, and SRGAP2 are dramatically upregulated both in mRNA and protein levels. Moreover, higher SRGAP2 is significantly related to the clinical stages of HCC. Meanwhile, SRGAP2 might be an independent prognostic indicator, as it correlates negatively with the clinical outcomes of HCC patients. Further SRGAP2-silencing experiments imply that SRGAP2 might remarkably promote the migration and invasion of HCC cells in an EMT-independent pattern. Based on the high-throughput RNA sequencing of SRGAP2-knockdown HCC cells, enrichment and network analyses demonstrate that SRGAP2 is closely associated with cellular metabolic signaling. CONCLUSIONS: Our study firstly illustrates the crucial role of SRGAP2 in the metastasis of HCC and explores its underlying molecular mechanisms. We identify SRGAP2 as a promising prognostic biomarker and a novel therapeutic target for HCC patients.

2.
Chem Commun (Camb) ; 57(37): 4588-4591, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33956028

RESUMO

We report a general palladium-catalyzed one-pot procedure for the synthesis of phosphonates, phosphinates and phosphine oxides from phenols mediated by sulfuryl fluoride. It features mild conditions, broad substrate scope, high functionality tolerance and water insensitivity. The utility of this procedure has been well demonstrated by gram-scale synthesis, sequential synthesis of click chemistry building blocks, late-stage decoration of drugs and natural products and on-DNA synthesis of phosphine oxide for a DNA-encoded library (DEL).

3.
Am J Dent ; 34(2): 97-100, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33940667

RESUMO

PURPOSE: This pilot study assessed the periodontal status and biomarkers of systemic inflammation in acute coronary syndrome (ACS) patients. METHODS: 15 ACS patients on statin (anti-cholesterol) therapy, were recruited into the study an average of 9 months after discharge from university hospital. Blood and mouthrinse samples were collected for analysis of inflammatory biomarkers including high sensitivity C-reactive protein (hsCRP), IL-6, IL-1ß, TNF-α, and MMP-9. Full-mouth periodontal examination, including pocket depth (PD), clinical attachment levels (CAL), bleeding on probing (BOP), and tooth mobility, was performed. RESULTS: When their periodontal status was assessed by CAL, 100% of these statin-treated ACS patients exhibited moderate (66.7%) to severe (33.3%) periodontal disease, which appears to be higher than the rate described for the general adult population (i.e., 47% for periodontitis). In addition, (1) their blood hsCRP levels ranged from 0.94 to 12.6 mg/L with a mean of 3.41 mg/L, which is considered high risk for cardiovascular disease (CVD) in spite of their statin therapy, and (2) the data demonstrated a positive correlation between severe periodontitis and elevated blood hsCRP levels (P< 0.05), consistent with systemic inflammation. CLINICAL SIGNIFICANCE: This pilot study provides preliminary data for future large-scale studies to define the relationship between ACS and chronic periodontitis, the underlying mechanisms, and the potential therapeutic efficacy of appropriate periodontal management to reduce the risk for cardiovascular disease.


Assuntos
Síndrome Coronariana Aguda , Periodontite Crônica , Síndrome Coronariana Aguda/tratamento farmacológico , Adulto , Proteína C-Reativa/análise , Humanos , Índice Periodontal , Projetos Piloto
4.
J Asthma ; : 1-7, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33827355

RESUMO

OBJECTIVE: Asthma and obesity are two of the most common chronic childhood illnesses. The purpose of this study was to better understand the relationship between co-morbid asthma and obesity in children aged 4-17 and whether it impacts the caregiver's perception of health and/or healthcare utilization. METHODS: This was a secondary analysis of the National Health and Nutrition Examination Surveys (NHANES) datasets from 2007 to 2018. Cumulative logistic regression models were used to analyze the caregiver's perception of health, received healthcare, and overnight hospital stay as dependent variables. Asthma and weight status were included as covariates, with adjustment for age, income, head of the household's education, gender, race, and insurance. RESULTS: The sample included 15,386 children. When looking at weight status in addition to asthma, compared to caregivers of children with current asthma and normal weight, caregivers of children with current asthma and with obesity are more likely to perceive their children as having worse health (OR = 1.73, 95%CI = [1.30, 2.32], p = 0.0003), and are more likely to have more frequent healthcare utilization but the results did not reach a statistical significance. CONCLUSIONS: Caregiver's perception of overall health was worse in caregivers of those with co-morbid obesity/asthma than in caregivers of children with asthma alone. This indicates that caregivers of children with co-morbid asthma and obesity have insight into their children's condition and may be primed for discussion and counseling in the healthcare setting.

5.
Int J Oral Maxillofac Implants ; 36(2): 322-326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909722

RESUMO

PURPOSE: Short implants are used in clinical conditions of insufficient vertical bone availability. This study aimed to compare the primary stability of short implants with different macrodesigns placed in different bone densities in vitro. MATERIALS AND METHODS: One hundred twenty short (6-mm) implants (20/group) were placed at the bone level in commercially available polyurethane blocks representing type I and IV bone quality. The groups were as follows: test A group (4.6-mm diameter with tapered body), test B group (4.8-mm diameter/cylindric microthreaded neck), and test C group (4.8-mm diameter, cylindric body with polished collar, three threads at the intraosseous portion). Implant primary stability was assessed using insertion torque and implant stability quotient (ISQ) values. A blinded calibrated clinician recorded all measurements. Statistical comparisons were completed using a one-way analysis of variance (ANOVA) and Bonferroni posttests. RESULTS: The insertion torque values (mean ± SD) for groups A, B, and C in type I bone were 52.50 ± 5.25, 49.00 ± 5.98, and 46.25 ± 3.93, and in type IV bone, the values were 14.00 ± 2.05, 15.50 ± 2.76, and 9.75 ± 1.11, respectively. Also, the ISQ values were 67.25 ± 2.760, 69.25 ± 1.67, and 61.80 ± 5.68 (type I bone); and 53.27 ± 1.99, 60.65 ± 2.11, and 51.97 ± 4.51 (type IV bone), respectively. The comparison showed statistical differences in ISQ (Bonferroni adjusted P < .0001) for the A and B groups but also for the A and C groups (type I bone), in soft bone between the A and B groups and between the B and C groups, and also for the insertion torque values for the A and C groups and between the B and C groups in type IV bone. CONCLUSION: Short implant macrogeometry defines primary stability. Short implants with 6-mm length and multiple threads can achieve good primary stability in vitro in type I and IV artificial bone.


Assuntos
Implantação Dentária Endo-Óssea , Implantes Dentários , Densidade Óssea , Osso e Ossos , Torque
6.
Artigo em Inglês | MEDLINE | ID: mdl-33930132

RESUMO

OBJECTIVE: The United States is experiencing an opioid epidemic. In recent years, there were more than 10 million opioid misusers aged 12 years or older annually. Identifying patients at high risk of opioid use disorder (OUD) can help to make early clinical interventions to reduce the risk of OUD. Our goal is to develop and evaluate models to predict OUD for patients on opioid medications using electronic health records and deep learning methods. The resulting models help us to better understand OUD, providing new insights on the opioid epidemic. Further, these models provide a foundation for clinical tools to predict OUD before it occurs, permitting early interventions. METHODS: Electronic health records of patients who have been prescribed with medications containing active opioid ingredients were extracted from Cerner's Health Facts database for encounters between January 1, 2008, and December 31, 2017. Long short-term memory models were applied to predict OUD risk based on five recent prior encounters before the target encounter and compared with logistic regression, random forest, decision tree, and dense neural network. Prediction performance was assessed using F1 score, precision, recall, and area under the receiver-operating characteristic curve. RESULTS: The long short-term memory (LSTM) model provided promising prediction results which outperformed other methods, with an F1 score of 0.8023 (about 0.016 higher than dense neural network (DNN)) and an area under the receiver-operating characteristic curve (AUROC) of 0.9369 (about 0.145 higher than DNN). CONCLUSIONS: LSTM-based sequential deep learning models can accurately predict OUD using a patient's history of electronic health records, with minimal prior domain knowledge. This tool has the potential to improve clinical decision support for early intervention and prevention to combat the opioid epidemic.

7.
J Surg Res ; 265: 86-94, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33894453

RESUMO

INTRODUCTION: Splenic injury is common in blunt trauma. We sought to evaluate the injury characteristics and outcomes of BSI admitted over a 10-y period to an academic trauma center. METHODS: A retrospective review of adult blunt splenic injury patients admitted between January 2009 and September 2018. RESULTS: The 423 patients meeting inclusion criteria were divided by management: Observational (OBS, n = 261), splenic surgery (n = 114 including 4 splenorrhaphy patients), SAE (n = 43), and multiple treatment modalities (3 had SAE followed by surgery and 2 OBS patients underwent splenic surgery at readmission). The most common mechanism of injury was motor vehicle collision (47.8%). The median ISS (OBS 17, SAE 22, Surgery 34) and spleen AIS (OBS 2, SAE 3, Surgery 4) were significantly different.  Complication rates (OBS 21.8%, SAE 9.3%, Surgery 45.6%) rates were significantly different, but mortality (OBS 7.3%, SAE 2.3%, Surgery 13.2%), discharge to home and readmission rates were not. Additional abdominal injuries were identified in 26.3% of the surgery group and 2.7% of OBS group. SAE rate increased from 3.0% to 28%; median spleen AIS remained 2-3. Thirty-five patients expired; 28 had severe head, chest, and/or extremity injuries (AIS ≥4). CONCLUSION: SAE rates increased over time. Splenorrhaphy rates were low. SAE was associated with relatively low rates of mortality and complications in appropriately selected patients.

8.
Environ Pollut ; 285: 117230, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33930821

RESUMO

Uranyl carbonate (UC(VI)) is a stable form of uranyl (U(VI)) that widely coexists with amorphous colloidal silica (ACSi) and humic acid (HA) in carbonate-rich U-contaminated areas. In this context, the cotransport behavior and mechanism of UC(VI) with ACSi (100 mg L-1) and HA colloids in saturated porous media were systematically investigated. It was found that the ACSi and strip-shaped HA have a strong adsorption capacity for UC(VI), and their adsorption distribution coefficient (Kd) is 4-5 orders of magnitude higher than that of quartz sand (QS). In the ternary system, UC(VI) was mainly existing in the colloid-associated form at low UC(VI) concentration (4.2 × 10-6 M). Compared with the individual transport of UC(VI), the presence of ACSi and strip-shaped HA in the binary system promotes the transport of low-concentration UC(VI) (4.2 × 10-6 M) but shows a hindering effect when UC(VI) = 2.1 × 10-5 M. When ionic strength (IS) increased from 0 to 100 mM, the individual transport of UC(VI) and ACSi was weakened owing to the masking effect and the compression of the electrical double layer, respectively; this weakening effect is more pronounced in the binary (UC(VI)-ACSi) system. Notably, the transport of UC(VI) and ACSi in the ternary system is independent of the changes in IS due to the surface charge homogeneity strengthening the electrostatic repulsion between HA and QS. The Derjaguin-Landau-Verwey-Overbeek theory and retention profiles reveal the co-deposition mechanism of ACSi and UC(VI) in the column under different hydrochemical conditions. The nonequilibrium two-site model and the mathematical colloidal model successfully described the breakthrough data of UC(VI) and ACSi, respectively. These results are helpful for evaluating the pollution caused by UC(VI) migration in an environment rich in HA and formulating corresponding effective control strategies.

9.
JMIR Public Health Surveill ; 7(4): e23426, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881409

RESUMO

BACKGROUND: Opioid overdose-related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP) and opioid use disorder (OUD). OBJECTIVE: We aimed to discover geospatial patterns in nonmedical opioid use and its correlations with demographic features related to despair and economic hardship, most notably the US presidential voting patterns in 2016 at census tract level in New York State. METHODS: This cross-sectional analysis used data from New York Statewide Planning and Research Cooperative System claims data and the presidential voting results of 2016 in New York State from the Harvard Election Data Archive. We included 63,958 patients who had at least one OUD diagnosis between 2010 and 2016 and 36,004 patients with at least one OP diagnosis between 2012 and 2016. Geospatial mappings were created to compare areas of New York in OUD rates and presidential voting patterns. A multiple regression model examines the extent that certain factors explain OUD rate variation. RESULTS: Several areas shared similar patterns of OUD rates and Republican vote: census tracts in western New York, central New York, and Suffolk County. The correlation between OUD rates and the Republican vote was .38 (P<.001). The regression model with census tract level of demographic and socioeconomic factors explains 30% of the variance in OUD rates, with disability and Republican vote as the most significant predictors. CONCLUSIONS: At the census tract level, OUD rates were positively correlated with Republican support in the 2016 presidential election, disability, unemployment, and unmarried status. Socioeconomic and demographic despair-related features explain a large portion of the association between the Republican vote and OUD. Together, these findings underscore the importance of socioeconomic interventions in combating the opioid epidemic.

10.
BMC Oral Health ; 21(1): 153, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33757508

RESUMO

BACKGROUND: The quantity-quality trade-off theory indicates that an increase in siblings might decrease a child's well-being, but little is known about the impacts of sibling number on children's oral health-related quality of life (OHRQoL). This study aims to investigate the effects of presence of siblings on children's OHRQoL, and to further test whether there is an interaction effect between siblings' presence and locations on children's OHRQoL. METHODS: Data were obtained from an oral-health survey of 12-year-old children in Beijing, China, which was a part of the 4th National Oral Health Survey in the Mainland of China (2015-2016). This study included 2158 children data for analysis. OHRQoL was assessed by the child's Oral Impacts on Daily Performance (OIDP). OIDP prevalence served as an indicator of OHRQoL. Children with and without siblings were recorded as non-single and single children, respectively. Dental variables, including active caries, gingival bleeding, and calculus, were reported. A logistic regression model was applied to investigate the association of siblings' presence and OIDP prevalence. A synergy index was used to assess the possible interaction effect between siblings' presence and location on OIDP prevalence. RESULTS: Sixty percent of Chinese children reported suffering OIDP in the previous six months. OIDP prevalence for non-single and single children were 68.3% and 56.9%, respectively. The adjusted odds ratio (OR) of OIDP for non-single children was 1.31 (95% CI: 1.05, 1.63), and the adjusted OR of OIDP for non-single and rural children was 2.03 (95% CI: 1.47, 2.81). The synergy index between siblings' presence and location on OIDP was 2.18 (85% CI: 1.30, 3.67), which indicates that an excessive risk increase for OIDP was observed among non-single and rural children. CONCLUSIONS: Children with siblings are more likely to report OIDP and have lower OHRQoL, especially those from rural areas. These findings indicate that oral-health interventions should be given priority for non-single and rural children.


Assuntos
Cárie Dentária , Qualidade de Vida , Pequim , Criança , China/epidemiologia , Estudos Transversais , Cárie Dentária/epidemiologia , Humanos , Saúde Bucal , Irmãos
11.
Signal Transduct Target Ther ; 6(1): 134, 2021 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-33774649

RESUMO

To discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.


Assuntos
Antivirais/farmacologia , Catepsina L , Inibidores de Cisteína Proteinase/farmacologia , Desenvolvimento de Medicamentos , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos , Adolescente , Adulto , Idoso , Animais , /genética , Catepsina L/antagonistas & inibidores , Catepsina L/genética , Catepsina L/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/genética
12.
Medicine (Baltimore) ; 100(11): e25142, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725996

RESUMO

BACKGROUND: The hospital-acquired influenza (HAI) were usually contributed to severe outcomes among the inpatients. Here, we performed a meta-analysis to summarize and quantify the epidemiological and clinical characteristics of HAI. METHODS: We performed a literature search thorough PubMed, Web of Science, Cochrane Library, Embase, Scopus and China National Knowledge Infrastructure (CNKI), and Wanfang databases for observational studies. Random/fix-effects models were used to obtain pooled proportion, odds ratio (OR), and weighted mean difference (WMD). RESULTS: A total of 14 studies involving 1483 HAI and 71849 non-hospital-acquired influenza infections (NHAI) cases were included.The proportion of the HAI among the influenza cases was 11.38% (95% confidence interval [CI]: 5.19%-19.55%) and it was increased after 2012 (6.15% vs 12.72%). The HAI cases were significantly older (WMD = 9.51, 95% CI: 0.04-18.98) and the patients with chronic medical diseases were at increased risk of HAI (OR = 1.85, 95% CI: 1.57-2.19). Among them, metabolic disorders (OR = 8.10, 95% CI: 2.46-26.64) ranked the highest danger, followed by malignancy (OR = 3.18, 95% CI: 2.12-4.76), any chronic diseases (OR = 2.81, 95% CI: 1.08-9.31), immunosuppression (OR = 2.13, 95% CI: 1.25-3.64), renal diseases (OR = 1.72, 95% CI:1.40-2.10), heart diseases (OR = 1.52, 95% CI: 1.03-1.44), and diabetes (OR = 1.22, 95% CI: 1.03-1.44). The HAI cases were more likely to experience longer hospital stay (WMD = 10.23, 95% CI: 4.60-15.85) and longer intensive care unit (ICU) stay (WMD = 2.99, 95% CI: 1.50-4.48). In the outcomes within 30 days, those population was still more likely to receive hospitalization (OR = 6.55, 95% CI: 5.19-8.27), death in hospital (OR = 1.99, 95% CI: 1.65-2.40) but less likely to discharged (OR = 0.20, 95% CI: 0.16-0.24). CONCLUSION: The proportion of the HAI among the influenza cases was relatively high. Reinforcement of the surveillance systems and vaccination of the high-risk patients and their contacts are necessary for the HAI control.


Assuntos
Infecção Hospitalar/epidemiologia , Hospitalização/estatística & dados numéricos , Vírus da Influenza A , Influenza Humana/epidemiologia , Vigilância da População , Estudos de Casos e Controles , Infecção Hospitalar/virologia , Estudos Transversais , Feminino , Humanos , Incidência , Influenza Humana/etiologia , Masculino , Razão de Chances
13.
Sci Rep ; 11(1): 5152, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664282

RESUMO

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP). To discover trends and patterns of opioid poisoning and the demographic and regional disparities, we analyzed large scale patient visits data in New York State (NYS). Demographic, spatial, temporal and correlation analyses were performed for all OP patients extracted from the claims data in the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016, along with Decennial US Census and American Community Survey zip code level data. 58,481 patients with at least one OP diagnosis and a valid NYS zip code address were included. Main outcome and measures include OP patient counts and rates per 100,000 population, patient level factors (gender, age, race and ethnicity, residential zip code), and zip code level social demographic factors. The results showed that the OP rate increased by 364.6%, and by 741.5% for the age group > 65 years. There were wide disparities among groups by race and ethnicity on rates and age distributions of OP. Heroin and non-heroin based OP rates demonstrated distinct temporal trends as well as major geospatial variation. The findings highlighted strong demographic disparity of OP patients, evolving patterns and substantial geospatial variation.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(2): 200-206, 2021 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33678659

RESUMO

In recent years, in the absence of venous component, dilated, overlapping, and tortuous arteries forming a mass of arterial loops with a coil-like appearance have been defined as pure arterial malformation (PAM). It is extremely rare, and its etiology and treatment have not yet been fully elucidated. Here, we reported 2 cases of PAM with associated aneurysmal subarachnoid hemorrhage in this paper. Both patients had severe headache as the first symptom. Subarachnoid hemorrhage was found by CT and computed tomography angiography (CTA) and PAM with associated aneurysm was found by digital subtraction angiography (DSA). In view of the distribution of blood and the location of aneurysms, the aneurysm rupture was the most likely to be considered. Based on the involvement of the lesion in the distal blood supply, only the aneurysm was clamped during the operation. It used to be consider that PAM is safety, because of the presentation and natural history of previously reported cases. Through the cases we reported, we have doubted about "the benign natural history" and discussed its treatment. PAM can promote the formation of aneurysms and should be reviewed regularly. The surgical indications for PAM patients with aneurysm formation need to be further clarified. Management of PAM patients with ruptured aneurysm is the same as that of ruptured aneurysm. Whether there are indications needed to treat simple arterial malformations remains to be further elucidated with the multicenter, randomized controlled studies on this disease.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Angiografia Digital , Angiografia Cerebral , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia
15.
J Biomed Inform ; 116: 103725, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33711546

RESUMO

The US is experiencing an opioid epidemic, and opioid overdose is causing more than 100 deaths per day. Early identification of patients at high risk of Opioid Overdose (OD) can help to make targeted preventative interventions. We aim to build a deep learning model that can predict the patients at high risk for opioid overdose and identify most relevant features. The study included the information of 5,231,614 patients from the Health Facts database with at least one opioid prescription between January 1, 2008 and December 31, 2017. Potential predictors (n = 1185) were extracted to build a feature matrix for prediction. Long Short-Term Memory (LSTM) based models were built to predict overdose risk in the next hospital visit. Prediction performance was compared with other machine learning methods assessed using machine learning metrics. Our sequential deep learning models built upon LSTM outperformed the other methods on opioid overdose prediction. LSTM with attention mechanism achieved the highest F-1 score (F-1 score: 0.7815, AUCROC: 0.8449). The model is also able to reveal top ranked predictive features by permutation important method, including medications and vital signs. This study demonstrates that a temporal deep learning based predictive model can achieve promising results on identifying risk of opioid overdose of patients using the history of electronic health records. It provides an alternative informatics-based approach to improving clinical decision support for possible early detection and intervention to reduce opioid overdose.

16.
Trials ; 22(1): 214, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731199

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) is usually diagnosed at an advanced stage, and chemotherapy is the main treatment for this disease. Kanglaite injections (KLTi) have been widely used for the treatment of cancer in China. KLTi combined with chemotherapy could improve the short-term efficacy, quality of life, and performance status for NSCLC compared with chemotherapy alone. This trial aims to assess the long-term efficacy and safety of KLTi in combination with chemotherapy for the treatment of advanced NSCLC. METHODS: This will be an investigator-initiated multicenter open-label randomized controlled trial. We will randomly assign 334 eligible participants with stage IIIA-IV NSCLC to the treatment or control groups in a 1:1 ratio. Patients in both groups will be administered 4-6 cycles of first-line platinum-based double chemotherapy regimens. Patients with complete response, partial response, or stable disease after 4-6 cycles will receive non-platinum single-agent chemotherapy. Patients in the treatment group are to receive intravenous KLTi 200 ml per day continuously for 14 days, commencing on the first day of chemotherapy. The treatment will be discontinued at the time of disease progression or until unacceptable toxicity is noted. The follow-up will be conducted every 2 months until death, loss of follow-up, or 12 months from randomized enrollment. The primary outcome will be progression-free survival (PFS). The secondary outcomes will be the objective response rate, 1-year survival rate, quality of life, living ability, and blood lipids. The safety outcome will be the rate of adverse events. DISCUSSION: This study will be the first randomized controlled trial in which PFS is used as the primary outcome to test whether KLTi combined with first-line chemotherapy has superior efficacy and reduced toxicity compared to chemotherapy alone in advanced NSCLC. This will also be the first clinical study to observe the effects of KLTi on blood lipids. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986528 . Prospectively registered on 30 May 2019.

17.
Int J Med Sci ; 18(8): 1739-1745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746590

RESUMO

Objective: This study aimed to develop a machine learning algorithm to identify key clinical measures to triage patients more effectively to general admission versus intensive care unit (ICU) admission and to predict mortality in COVID-19 pandemic. Materials and methods: This retrospective study consisted of 1874 persons-under-investigation for COVID-19 between February 7, 2020, and May 27, 2020 at Stony Brook University Hospital, New York. Two primary outcomes were ICU admission and mortality compared to COVID-19 positive patients in general hospital admission. Demographic, vitals, symptoms, imaging findings, comorbidities, and laboratory tests at presentation were collected. Predictions of mortality and ICU admission were made using machine learning with 80% training and 20% testing. Performance was evaluated using receiver operating characteristic (ROC) area under the curve (AUC). Results: A total of 635 patients were included in the analysis (age 60±11, 40.2% female). The top 6 mortality predictors were age, procalcitonin, C-creative protein, lactate dehydrogenase, D-dimer and lymphocytes. The top 6 ICU admission predictors are procalcitonin, lactate dehydrogenase, C-creative protein, pulse oxygen saturation, temperature and ferritin. The best machine learning algorithms predicted mortality with 89% AUC and ICU admission with 79% AUC. Conclusion: This study identifies key independent clinical parameters that predict ICU admission and mortality associated with COVID-19 infection. The predictive model is practical, readily enhanced and retrained using additional data. This approach has immediate translation and may prove useful for frontline physicians in clinical decision making under time-sensitive and resource-constrained environment.


Assuntos
/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
mBio ; 12(2)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785615

RESUMO

Coronaviruses (CoVs) have caused severe diseases in humans and animals. Endocytic pathways, such as clathrin-mediated endocytosis (CME) and caveolae-mediated endocytosis (CavME), play an important role for CoVs to penetrate the cell membrane barrier. In this study, a novel CoV entry manner is unraveled in which clathrin and caveolae can cooperatively mediate endocytosis of porcine epidemic diarrhea coronavirus (PEDV). Using multicolor live-cell imaging, the dynamics of the fluorescently labeled clathrin structures, caveolae structures, and PEDV were dissected. During CavME of PEDV, we found that clathrin structures can fuse with caveolae near the cell plasma membrane, and the average time of PEDV penetrating the cell membrane was within ∼3 min, exhibiting a rapid course of PEDV entry. Moreover, based on the dynamic recruitment of clathrin and caveolae structures and viral motility, the direct evidence also shows that about 20% of PEDVs can undergo an abortive entry via CME and CavME. Additionally, the dynamic trafficking of PEDV from clathrin and caveolae structures to early endosomes, and from early endosomes to late endosomes, and viral fusion were directly dissected, and PEDV fusion mainly occurred in late endosomes within ∼6.8 min after the transport of PEDV to late endosomes. Collectively, this work systematically unravels the early steps of PEDV infection, which expands our understanding of the mechanism of CoV infection.IMPORTANCE Emerging and re-emerging coronaviruses cause serious human and animal epidemics worldwide. For many enveloped viruses, including coronavirus, it is evident that breaking the plasma membrane barrier is a pivotal and complex process, which contains multiple dynamic steps. Although great efforts have been made to understand the mechanisms of coronavirus endocytic pathways, the direct real-time imaging of individual porcine epidemic diarrhea coronavirus (PEDV) internalization has not been achieved yet. In this study, we not only dissected the kinetics of PEDV entry via clathrin-mediated endocytosis and caveolae-mediated endocytosis and the kinetics of endosome trafficking and viral fusion but also found a novel productive coronavirus entry manner in which clathrin and caveolae can cooperatively mediate endocytosis of PEDV. Moreover, we uncovered the existence of PEDV abortive endocytosis. In summary, the productive PEDV entry via the cooperation between clathrin and caveolae structures and the abortive endocytosis of PEDV provide new insights into coronavirus penetrating the plasma membrane barrier.


Assuntos
Cavéolas/metabolismo , Clatrina/metabolismo , Endocitose/fisiologia , Vírus da Diarreia Epidêmica Suína/metabolismo , Internalização do Vírus , Animais , Linhagem Celular , Membrana Celular/virologia , Chlorocebus aethiops , Infecções por Coronavirus , Suínos , Doenças dos Suínos/virologia , Células Vero
19.
Curr Oncol ; 28(1): 928-939, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33617509

RESUMO

Regulators of histone acetylation are promising epigenetic targets for therapy in breast cancer. In this study, we comprehensively analyzed the expression of histone acetylation modulator genes in breast cancer using TCGA data sources. A gene signature composed of eight histone acetylation modulators (HAMs) was found to be effective for the classification and prognosis of breast cancers, especially in the HER2-enriched and basal-like molecular subtypes. The eight genes consist of two histone acetylation writers (GTF3C4 and CLOCK), two erasers (HDAC2 and SIRT7) and four readers (BRD4, BRD7, SP100, and BRWD3). Both histone acetylation writer genes and eraser genes were found to be differentially expressed between the two groups indicating a close relationship exists between overall histone acetylation level and prognosis of breast cancer in HER2-enriched and basal-like breast cancer.

20.
Virulence ; 12(1): 615-629, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33538234

RESUMO

It is now clear that the intercellular transport on microtubules by dynein and kinesin-1 motors has an important role in the replication and spread of many viruses. Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded RNA virus of the Coronavirus family, which can infect swine of all ages and cause severe economic losses in the swine industry. Elucidating the molecular mechanisms of the intercellular transport of PEDV through microtubule, dynein and kinesin-1 will be crucial for understanding its pathogenesis. Here, we demonstrate that microtubule, dynein, and kinesin-1 are involved in PEDV infection and can influence PEDV fusion and accumulation in the perinuclear region but cannot affect PEDV attachment or internalization. Furthermore, we adopted a single-virus tracking technique to dynamically observe PEDV intracellular transport with five different types: unidirectional movement toward microtubule plus ends; unidirectional movement toward microtubule minus ends; bidirectional movement along the same microtubule; bidirectional movement along different microtubules and motionless state. Among these types, the functions of dynein and kinesin-1 in PEDV intercellular transport were further analyzed by single-virus tracking and found that dynein and kinesin-1 mainly transport PEDV to the minus and plus ends of the microtubules, respectively; meanwhile, they also can transport PEDV to the opposite ends of the microtubules different from their conventional transport directions and also coordinate the bidirectional movement of PEDV along the same or different microtubules through their cooperation. These results provided deep insights and references to understand the pathogenesis of PEDV as well as to develop vaccines and treatments.


Assuntos
Dineínas/metabolismo , Cinesina/metabolismo , Microtúbulos/metabolismo , Vírus da Diarreia Epidêmica Suína/fisiologia , Animais , Transporte Biológico , Chlorocebus aethiops , Citoplasma/metabolismo , Dineínas/antagonistas & inibidores , Cinesina/genética , Fusão de Membrana , Microscopia de Fluorescência , RNA Interferente Pequeno , Células Vero
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