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1.
BMC Cancer ; 20(1): 383, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375706

RESUMO

BACKGROUND: The microbiome has been shown to affect the response to Immune Checkpoint Inhibitors (ICIs) in a small number of cancers and in preclinical models. Here, we sought to broadly survey cancers to identify those in which the microbiome may play a prognostic role using retrospective analyses of patients with advanced cancer treated with ICIs. METHODS: We conducted a retrospective analysis of 690 patients who received ICI therapy for advanced cancer. We used a literature review to define a causal model for the relationship between medications, the microbiome, and ICI response to guide the abstraction of electronic health records. Medications with precedent for changes to the microbiome included antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories and statins. We tested the effect of medication timing on overall survival (OS) and evaluated the robustness of medication effects in each cancer. Finally, we compared the size of the effect observed for different classes of antibiotics to taxa that have been correlated to ICI response using a literature review of culture-based antibiotic susceptibilities. RESULTS: Of the medications assessed, only antibiotics and corticosteroids significantly associated with shorter OS. The hazard ratios (HRs) for antibiotics and corticosteroids were highest near the start of ICI treatment but remained significant when given prior to ICI. Antibiotics and corticosteroids remained significantly associated with OS even when controlling for multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, and stage. When grouping antibiotics by class, ß-lactams showed the strongest association with OS across all tested cancers. CONCLUSIONS: The timing and strength of the correlations with antibiotics and corticosteroids after controlling for confounding factors are consistent with the microbiome involvement with the response to ICIs across several cancers.

2.
J Orthop Surg Res ; 15(1): 169, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393353

RESUMO

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common disease in infants and children, and the treatment of bilateral DDH remains controversial. This study aimed to evaluate the stability of one-stage bilateral Salter pelvic osteotomy for bilateral DDH in patients of walking age. METHODS: In total, nine child cadavers aged 2-6 years were included. A universal mechanical testing machine was used for stability test. We performed two different surgical procedures on the specimens: nine child cadavers underwent unilateral Salter pelvic osteotomy, and six child cadavers were randomly selected to undergo Salter pelvic osteotomy again to simulate one-stage bilateral Salter pelvic osteotomy. The stability of the bilateral sacroiliac joints, local stability of the operation area, ultimate load test, and axial stiffness were evaluated. RESULTS: Both unilateral and bilateral Salter osteotomy could destroy the integrity of the pelvic ring and increase the risk of pelvic instability. In this study, compared with unilateral Salter osteotomy, bilateral Salter osteotomy had similar pelvic stability, and there was no significant difference between unilateral and bilateral Salter osteotomy in sacroiliac joint stability (p > 0.05), local stability (p = 0.763), ultimate load (p = 0.328), and axial stiffness (p = 0.480). CONCLUSIONS: One-stage bilateral Salter pelvic osteotomy as a potential surgical method is viable and stable for children with bilateral DDH.

3.
Medicine (Baltimore) ; 99(18): e20107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358400

RESUMO

BACKGROUND: Intramedullary cervical spinal cord teratomas (ICTs) are extremely rare, and diagnosis and treatment are challenging. We conducted a systematic review of the literature on the diagnosis and treatment of ICT. METHOD: The presentation, imaging manifestations, diagnosis, management, surgery findings, prognosis and histology were reviewed following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. English-language studies and case reports published from inception to 2018 were retrieved. Data on presentation, imaging characteristics, diagnosis, management, surgery findings, outcomes, and histopathology were extracted. RESULTS: Ten articles involving 10 patients were selected. The lesions were located in the upper cervical vertebrae in 4 cases, whereas in the lower cervical vertebrae in the remaining 6 cases. In 5 cases, the lesions were located on the dorsal side of the spinal cord, and in the center of the spinal cord in the remaining 5 cases. Quadriparesis (60%), paraplegia (30%), monoplegia (10%), and neck pain (50%) were the main presentations. The lesion appeared as a intramedullary heterogeneous signal during an MRI scan, and the lesion signal would be partially enhanced after the contrast medium was applied. All patients underwent surgical intervention through a posterior approach. Neurological function improved postoperatively in all patients. Two patients with pathology confirmed to be immature teratomas experienced recurrence. CONCLUSION: ICTs are extremely rare entities that are mainly located in the center or dorsal part of the spinal cord which mainly manifest as quadriplegia and neck pain. MRI is a useful modality that provides diagnostic clues. Surgery from a posterior approach is the primary treatment, and the effect of adjuvant therapy remains uncertain. The prognosis is mainly related to the pathological nature of the tumor and not the method of resection.


Assuntos
Vértebras Cervicais/patologia , Neoplasias da Medula Espinal/patologia , Teratoma/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
4.
JACC Cardiovasc Interv ; 13(9): 1112-1122, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32381188

RESUMO

OBJECTIVES: The aim of this study was to determine whether an active side branch protection (SB-P) strategy is superior to the conventional strategy in reducing side branch (SB) occlusion in high-risk bifurcation treatment. BACKGROUND: Accurate prediction of SB occlusion after main vessel stenting followed by the use of specific strategies to prevent occlusion would be beneficial during bifurcation intervention. METHODS: Eligible patients who had a bifurcation lesions with high risk for occlusion as determined using the validated V-RESOLVE (Visual Estimation for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention) score were randomized to an active SB-P strategy group (elective 2-stent strategy for large SBs and jailed balloon technique for small SBs) or a conventional strategy group (provisional stenting for large SBs and jailed wire technique for small SBs) in a 1:1 ratio stratified by SB vessel size. The primary endpoint of SB occlusion was defined as an angiography core laboratory-assessed decrease in TIMI (Thrombolysis In Myocardial Infarction) flow grade or absence of flow in the SB immediately after full apposition of the main vessel stent to the vessel wall. RESULTS: A total of 335 subjects at 16 sites were randomized to the SB-P group (n = 168) and conventional group (n = 167). Patients in the SB-P versus conventional strategy group had a significantly lower rate of SB occlusion (7.7% [13 of 168] vs. 18.0% [30 of 167]; risk difference: -9.1%; 95% confidence interval: -13.1% to -1.8%; p = 0.006), driven mainly by the difference in the small SB subgroup (jailed balloon technique vs. jailed wire technique: 8.1% vs. 18.5%; p = 0.01). CONCLUSIONS: An active SB-P strategy is superior to a conventional strategy in reducing SB occlusion when treating high-risk bifurcation lesions. (Conventional Versus Intentional Strategy in Patients With High Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention [CIT-RESOLVE]; NCT02644434).

5.
BMC Pharmacol Toxicol ; 21(1): 31, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334636

RESUMO

BACKGROUND: In this meta-analysis, we aimed to systematically compare the post percutaneous coronary interventional (PCI) adverse bleeding events, stent thrombosis, stroke and other cardiovascular outcomes in a population of patients with and without thrombocytopenia at baseline who were followed up on dual antiplatelet therapy (DAPT). METHODS: Relevant English language articles which were published before June 2019 were retrieved from MEDLINE, http://www.ClinicalTrials.com, EMBASE, Cochrane central, and Google scholar briefly using specific terms such as percutaneous coronary intervention or dual antiplatelet therapy, and thrombocytopenia. All the participants were followed up on DAPT following discharge. Specific endpoints including bleeding events, stent thrombosis, stroke and other adverse cardiovascular events were assessed. The latest version of the RevMan software was used for the statistical assessment. Odd ratios (OR) with 95% confidence intervals (CI) based on a fixed or a random statistical model were used to represent the data graphically. RESULTS: A total number of 118,945 participants (from 8 studies) were included with 37,753 suffering from thrombocytopenia at baseline. Our results showed post procedural bleeding (OR: 1.89, 95% CI: 1.16-3.07; P = 0.01), access site bleeding (OR: 1.66, 95% CI: 1.15-2.39; P = 0.006), intra-cranial bleeding (OR: 1.78, 95% CI: 1.30-2.43; P = 0.0003), gastro-intestinal bleeding (OR: 1.44, 95% CI: 1.14-1.82; P = 0.002) and any major bleeding (OR: 1.67, 95% CI: 1.42-1.97; P = 0.00001) to be significantly higher in thrombocytopenic patients treated with DAPT after PCI. Total stroke (OR: 1.45, 95% CI: 1.18-1.78; P = 0.0004) specifically hemorrhagic stroke (OR: 1.67, 95% CI: 1.30-2.14; P = 0.0001) was also significantly higher in these patients with thrombocytopenia at baseline. All-cause mortality and major adverse cardiac events were also significantly higher. However, overall total stent thrombosis (OR: 1.18, 95% CI: 0.90-1.55; P = 0.24) including definite and probable stent thrombosis were not significantly different compared to the control group. CONCLUSIONS: According to the results of this analysis, DAPT might have to be cautiously be used following PCI in a population of patients with thrombocytopenia at baseline due to the significantly higher bleeding rate including gastro-intestinal, intra-cranial bleeding and hemorrhagic stroke. Hence, special care might have to be taken when considering anti-platelet agents following PCI in these high risk patients. However, considering the present limitations of this analysis, this hypothesis will have to be confirmed in future trials.

7.
Genes (Basel) ; 11(4)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316483

RESUMO

The International Association for Intelligent Biology and Medicine (IAIBM) is a nonprofit organization that promotes intelligent biology and medical science. It hosts an annual International Conference on Intelligent Biology and Medicine (ICIBM), which was established in 2012. The ICIBM 2019 was held from 9 to 11 June 2019 in Columbus, Ohio, USA. Out of the 105 original research manuscripts submitted to the conference, 18 were selected for publication in a Special Issue in Genes. The topics of the selected manuscripts cover a wide range of current topics in biomedical research including cancer informatics, transcriptomic, computational algorithms, visualization and tools, deep learning, and microbiome research. In this editorial, we briefly introduce each of the manuscripts and discuss their contribution to the advance of science and technology.

9.
BMC Med Genomics ; 13(Suppl 5): 45, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241267

RESUMO

BACKGROUND: Initially characterized as axon guidance factors, semaphorins also have been implicated to have critical roles in multiple physiological and developmental functions, including the regulation of immune responses, angiogenesis, organ formation, and the etiology of multiple forms of cancer. Moreover, their contribution in immunity and the regulation of tumour microenvironment is becoming increasingly recognized. Here, we provide a comprehensive analysis of class-3 semaphorins, the only secreted family of genes among veterbrate semaphorins, in terms of their expression profiles and their association with patient survival. We also relate their role with immune subtypes, tumour microenvironment, and drug sensitivity using a pan-cancer study. RESULTS: Expression profiles of class-3 semaphorins (SEMA3s) and their association with patient survival and tumour microenvironment were studied in 31 cancer types using the TCGA pan-cancer data. The expression of SEMA3 family varies in different cancer types with striking inter- and intra- cancer heterogeneity. In general, our results show that SEMA3A, SEMA3C, and SEMA3F are primarily upregulated in cancer cells, while the rest of SEMA3s are mainly down-regulated in the tested tumours. The expression of SEMA3 family members was frequently associated with patient overall survival. However, the direction of the association varied with regards to the particular SEMA3 isoform queried and the specific cancer type tested. More specifically, SEMA3A and SEMA3E primarily associate with a poor prognosis of survival, while SEMA3G typically associates with survival advantage. The rest of SEMA3s show either survival advantage or disadvantage dependent on cancer type. In addition, all SEMA3 genes show significant association with immune infiltrate subtypes, and they also correlate with level of stromal cell infiltration and tumour cell stemness with various degrees. Finally, our study revealed that SEMA3 genes, especially SEMA3C and SEMA3F may contribute to drug induced cancer cell resistance. CONCLUSIONS: Our systematic analysis of class-3 semaphorin gene expression and their association with immune infiltrates, tumour microenvironment and cancer patient outcomes highlights the need to study each SEMA3 member as a separate entity within each specific cancer type. Also our study validated the identification of class-3 semaphorin signals as promising therapeutic targets in cancer although further laboratory validation still needed.

10.
BMC Med Genomics ; 13(Suppl 5): 47, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241271

RESUMO

In this editorial, we briefly summarized the International Conference on Intelligent Biology and Medicine 2019 (ICIBM 2019) that was held on June 9-11, 2019 at Columbus, Ohio, USA. We further introduced the 19 research articles included in this supplement issue, covering four major areas, namely computational method development, genomics analysis, network-based analysis and biomarker prediction. The selected papers perform cutting edge computational research applied to a broad range of human diseases such as cancer, neural degenerative and chronic inflammatory disease. They also proposed solutions for fundamental medical genomics problems range from basic data processing and quality control to functional interpretation, biomarker and drug prediction, and database releasing.

11.
J Transl Med ; 18(1): 124, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160892

RESUMO

BACKGROUND: Research has associated human epidermal growth factor receptor (HER2) with glucose and lipid metabolism. However, the association between circulating HER2 levels and coronary artery disease (CAD) remains to be elucidated. METHODS: We performed a case-control study with 435 participants (237 CAD patients and 198 controls) who underwent diagnostic coronary angiography from September 2018 to October 2019. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CAD were calculated with multiple logistic regression models after adjustment for confounders. RESULTS: Overall, increased serum HER2 levels were independently associated with the presence of CAD (OR per 1-standard deviation (SD) increase: 1.438, 95% CI 1.13-1.83; P = 0.003) and the number of stenotic vessels (OR per 1-SD increase: 1.399, 95% CI 1.15-1.71; P = 0.001). In the subgroup analysis, a significant interaction of HER2 with body mass index (BMI) on the presence of CAD was observed (adjusted interaction P = 0.046). Increased serum HER2 levels were strongly associated with the presence of CAD in participants with BMI ≥ 25 kg/m2 (OR per 1-SD increase: 2.143, 95% CI 1.37-3.35; P = 0.001), whereas no significant association was found in participants with BMI < 25 kg/m2 (OR per 1-SD increase: 1.225, 95% CI 0.90-1.67; P = 0.201). CONCLUSION: Elevated HER2 level is associated with an increased risk of CAD, particularly in people with obesity. This finding yields new insight into the pathological mechanisms underlying CAD, and warrants further research regarding HER2 as a preventive and therapeutic target of CAD.

12.
J Healthc Eng ; 2020: 6053065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184979

RESUMO

Objectives: We have developed a pulsed xenon ultraviolet light-based real-time air disinfection system with rapid and effective disinfection by using high-intensity pulse germicidal UV. Disinfection of the ambulance's environment is critical in the prevention of infectious cross contamination. Methods: In this study, a pulsed xenon ultraviolet light-based air disinfection system was established for real-time air disinfection in ambulances. In this system, a pulsed xenon ultraviolet (PX-UV) was used to generate broad-spectrum (200-320 nm), high-intensity ultraviolet light to deactivate and kill bacteria and viruses. The results showed that the use of PX-UV could be effective in reducing E. coli, Staphylococcus albus, and environmental pathogens level in ambulances (≥90% reduction in 30 mins). Results: This device was relatively simple and easy to use and does not leave chemical residues or risk exposing patients and workers to toxic chemicals. Conclusions: This appears to be a practical alternative technology to achieve automated air disinfection in ambulances.

13.
Genes (Basel) ; 11(3)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121160

RESUMO

BACKGROUND: Large-scale screening of drug sensitivity on cancer cell models can mimic in vivo cellular behavior providing wider scope for biological research on cancer. Since the therapeutic effect of a single drug or drug combination depends on the individual patient's genome characteristics and cancer cells integration reaction, the identification of an effective agent in an in vitro model by using large number of cancer cell models is a promising approach for the development of targeted treatments. Precision cancer medicine is to select the most appropriate treatment or treatments for an individual patient. However, it still lacks the tools to bridge the gap between conventional in vitro cancer cell models and clinical patient response to inhibitors. METHODS: An optimal two-layer decision system model is developed to identify the cancer cells that most closely resemble an individual tumor for optimum therapeutic interventions in precision cancer medicine. Accordingly, an optimal grid parameters selection is designed to seek the highest accordance for treatment selection to the patient's preference for drug response and in vitro cancer cell drug screening. The optimal two-layer decision system model overcomes the challenge of heterology data comparison between the tumor and the cancer cells, as well as between the continual variation of drug responses in vitro and the discrete ones in clinical practice. We simulated the model accuracy using 681 cancer cells' mRNA and associated 481 drug screenings and validated our results on 315 breast cancer patients drug selection across seven drugs (docetaxel, doxorubicin, fluorouracil, paclitaxel, tamoxifen, cyclophosphamide, lapitinib). RESULTS: Comparing with the real response of a drug in clinical patients, the novel model obtained an overall average accordance over 90.8% across the seven drugs. At the same time, the optimal cancer cells and the associated optimal therapeutic efficacy of cancer drugs are recommended. The novel optimal two-layer decision system model was used on 1097 patients with breast cancer in guiding precision medicine for a recommendation of their optimal cancer cells (30 cancer cells) and associated efficacy of certain cancer drugs. Our model can detect the most similar cancer cells for each individual patient. CONCLUSION: A successful clinical translation model (optimal two-layer decision system model) was developed to bridge in-vitro basic science to clinical practice in a therapeutic intervention application for the first time. The novel tool kills two birds with one stone. It can help basic science to seek optimal cancer cell models for an individual tumor, while prioritizing clinical drugs' recommendations in practice. Tool associated platform website: We extended the breast cancer research to 32 more types of cancers across 45 therapy predictions. The website is set up and can be accessed by the link: https://pcm2019.shinyapps.io/drug_response_prediction/.

14.
J Mol Evol ; 88(4): 361-371, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32189025

RESUMO

The gene cox1 is one of the most reported mitochondrial genes involved in horizontal gene transfer among angiosperms. However, whether different cox1 copies exist in different populations of a species and whether any other novel way except intron homing exists for cox1 intron acquisition is less understood. In this study, we chose Cassytha filiformis, a parasitic plant from the angiosperm family Lauraceae, as an example to study cox1 variation and evolution. We identified the stable and inheritable co-occurrence of two copies of cox1 genes, which were different in base composition and insertion/deletion among samples of a single species, C. filiformis. The bioinformatic analyses revealed that Type I copy had intact open reading frames, but type II copy had premature stop codons and was a pseudogene. Further INDEL characterization, phylogenetic analyses, and CCT comparisons consistently support two different origins for the two types of C. filiformis cox1 genes. Type I cox1 was likely vertically inherited within the magnoliids but it has captured an intron from another species, whereas the entire type II intron-containing cox1 has most likely been transferred integrally from Cuscuta or other Convolvulaceae species. The finding of the two independent horizontal gene transfer events associated with C. filiformis cox1 genes not only promotes our understanding of the evolutionary history of C. filiformis, but also leaves intriguing evolutionary questions that merits further efforts.

15.
Med Sci Monit ; 26: e920721, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32165608

RESUMO

BACKGROUND This study aimed to investigate the association between serum levels of cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac function in patients with unstable angina pectoris (UAP). MATERIAL AND METHODS A cross-sectional observational study was conducted at a single center and recruited 300 patients (214 men and 86 women), who were diagnosed with UAP between June 2018 to December 2018. The patients had serum levels of NT-ProBNP measured and were divided into four groups according to the serum levels of cystatin C: Q1, 0.49-0.83 mg/L; Q2, 0.84-1.04 mg/L; Q3, 1.05-1.38 mg/L; Q4, 1.39-4.21 mg/L. Cardiac function was graded according to the New York Heart Association (NYHA) class I to IV criteria. RESULTS In the 300 patients with UAP, there were significant differences in cardiac function and NT-ProBNP levels between the four study groups (Q1 to Q4) (p<0.05). Univariate analysis showed that body weight, heart rate, treatment with aspirin, ticagrelor, angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker (ACE/ARB), diuretic use, uric acid level, and serum cystatin C levels were significantly associated with increased levels of NT-ProBNP. After adjusting for confounding factors screened in univariate analysis, multivariate regression analysis showed that increased serum cystatin C levels were significantly associated with increased levels of NT-ProBNP. CONCLUSIONS Increased serum levels of cystatin C were associated with poor cardiac function and increased levels of NT-ProBNP in patients with UAP.

16.
BMC Med Inform Decis Mak ; 20(Suppl 2): 50, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183790

RESUMO

BACKGROUND: Adverse drug events (ADEs) often occur as a result of drug-drug interactions (DDIs). The use of data mining for detecting effects of drug combinations on ADE has attracted growing attention and interest, however, most studies focused on analyzing pairwise DDIs. Recent efforts have been made to explore the directional relationships among high-dimensional drug combinations and have shown effectiveness on prediction of ADE risk. However, the existing approaches become inefficient from both computational and illustrative perspectives when considering more than three drugs. METHODS: We proposed an efficient approach to estimate the directional effects of high-order DDIs through frequent itemset mining, and further developed a novel visualization method to organize and present the high-order directional DDI effects involving more than three drugs in an interactive, concise and comprehensive manner. We demonstrated its performance by mining the directional DDIs associated with myopathy using a publicly available FAERS dataset. RESULTS: Directional effects of DDIs involving up to seven drugs were reported. Our analysis confirmed previously reported myopathy associated DDIs including interactions between fusidic acid with simvastatin and atorvastatin. Furthermore, we uncovered a number of novel DDIs leading to increased risk for myopathy, such as the co-administration of zoledronate with different types of drugs including antibiotics (ciprofloxacin, levofloxacin) and analgesics (acetaminophen, fentanyl, gabapentin, oxycodone). Finally, we visualized directional DDI findings via the proposed tool, which allows one to interactively select any drug combination as the baseline and zoom in/out to obtain both detailed and overall picture of interested drugs. CONCLUSIONS: We developed a more efficient data mining strategy to identify high-order directional DDIs, and designed a scalable tool to visualize high-order DDI findings. The proposed method and tool have the potential to contribute to the drug interaction research and ultimately impact patient health care. AVAILABILITY AND IMPLEMENTATION: http://lishenlab.com/d3i/explorer.html.

17.
Stat Med ; 39(10): 1458-1472, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32101641

RESUMO

Pharmacoinformatics research has experienced a great deal of successes in detecting drug-induced adverse events (AEs) using large-scale health record databases. In the era of polypharmacy, pharmacoinformatics faces many new challenges, and two significant challenges are to detect high-order drug interactions and to handle strongly correlated drugs. In this article, we propose a super-combo-drug test (SupCD-T) to address the aforementioned two challenges. SupCD-T detects drug interactions by identifying optimal drug combinations with increased AE risks. In addition, SupCD-T increases the statistical powers to detect single-drug effects by combining strongly correlated drugs. Although SupCD-T does not distinguish single-drug effects from their combination effects, it is noticeably more powerful in selecting an individual drug effect in the multiple regression analysis, where confounding justification between two correlated drugs reduces the power in testing the individual drug effects on AEs. Our simulation studies demonstrate that SupCD-T has generally better power comparing with the multiple regression analysis. In addition, SupCD-T is able to select meaningful drug combinations (eg, highly coprescribed drugs). Using electronic health record database, we illustrate the utility of SupCD-T and discover a number of drug combinations that have increased risk in myopathy. Some novel drug combinations have not yet been investigated and reported in the pharmacology research.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32029408

RESUMO

BACKGROUND: Currently, few studies focus on the treatment of Parkinson's disease (PD) patients after a fracture. The effect of PD on geriatric patients with intertrochanteric fracture remains unclear. Therefore, we performed a study to focus on two questions as follow: (1) would PD increase the operation difficulty and perioperative complications in Chinese elderly patients with intertrochanteric fracture? (2) is there any difference between the clinical outcome of patients with and without PD? HYPOTHESIS: PD would increase perioperative complications and influence the postoperative rehabilitation in elderly patients with intertrochanteric fracture. MATERIALS AND METHODS: There were 445 elderly intertrochanteric fracture patients treated with proximal femoral nail anti-rotation during January 2010 and December 2017. After propensity score matching, twenty-four geriatric intertrochanteric fracture patients with PD and forty-eight geriatric intertrochanteric fracture patients without PD were enrolled in this retrospective study. Intraoperative and postoperative comparison were conducted between patients with and without PD. RESULTS: Compared with 63 months for geriatric intertrochanteric fracture patients without PD, patients with PD had a median survival time of 31 months. The Harris Hip Score and Barthel Index of patients with PD were significantly lower than that of patients without PD. In addition, the Depression subscale score of patients with PD were significantly higher that of patients without PD. DISCUSSION: The effect of PD on geriatric patients with intertrochanteric fracture is not the operation itself, but the postoperative rehabilitation. In addition, multi-disciplinary treatment, personal rehabilitation training, more intensive outpatient care, and meticulous nursing were recommended in treatment for elderly patients with intertrochanteric fracture and PD. LEVEL OF EVIDENCE: III, Cohort comparative study.

19.
Bioinformatics ; 36(9): 2805-2812, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971579

RESUMO

MOTIVATION: Systematic identification of molecular targets among known drugs plays an essential role in drug repurposing and understanding of their unexpected side effects. Computational approaches for prediction of drug-target interactions (DTIs) are highly desired in comparison to traditional experimental assays. Furthermore, recent advances of multiomics technologies and systems biology approaches have generated large-scale heterogeneous, biological networks, which offer unexpected opportunities for network-based identification of new molecular targets among known drugs. RESULTS: In this study, we present a network-based computational framework, termed AOPEDF, an arbitrary-order proximity embedded deep forest approach, for prediction of DTIs. AOPEDF learns a low-dimensional vector representation of features that preserve arbitrary-order proximity from a highly integrated, heterogeneous biological network connecting drugs, targets (proteins) and diseases. In total, we construct a heterogeneous network by uniquely integrating 15 networks covering chemical, genomic, phenotypic and network profiles among drugs, proteins/targets and diseases. Then, we build a cascade deep forest classifier to infer new DTIs. Via systematic performance evaluation, AOPEDF achieves high accuracy in identifying molecular targets among known drugs on two external validation sets collected from DrugCentral [area under the receiver operating characteristic curve (AUROC) = 0.868] and ChEMBL (AUROC = 0.768) databases, outperforming several state-of-the-art methods. In a case study, we showcase that multiple molecular targets predicted by AOPEDF are associated with mechanism-of-action of substance abuse disorder for several marketed drugs (such as aripiprazole, risperidone and haloperidol). AVAILABILITY AND IMPLEMENTATION: Source code and data can be downloaded from https://github.com/ChengF-Lab/AOPEDF.

20.
Clin Pharmacol Ther ; 107(1): 76-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758700

RESUMO

In 2012, a new journal was launched from the ASCPT family, CPT: Pharmacometrics and Systems Pharmacology (PSP) as both quantitative system pharmacology (QSP) and pharmacometrics were growing fields in pharmacology, drug development, and drug use. In this Perspective, the present editors and associate editors of PSP want to share their strategic vision of where these two fields, separately and together, should, would, or could be 10 years from now.

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