Publications by authors named "C E Chen"

66,917 Publications

Machine learning of treadmill exercise test to improve selection for testing for coronary artery disease.

Atherosclerosis 2021 Nov 30;340:23-27. Epub 2021 Nov 30.

Center for Evidence-based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Public Health, National Yang Ming Chiao Tung University College of Medicine, Taipei, Taiwan; Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Background And Aims: The high false-positive rate of the treadmill exercise test (TET) may lead to unnecessary invasive coronary angiography. We aimed to develop a machine learning-based algorithm to improve the diagnostic performance of TET.

Methods: Study included 2325 patients who underwent TET and subsequent coronary angiography within one-year interval. The mean age was 58.7 (48.1-69.3) years, 1731 (74.5%) were male, 1858 (79.9%) had positive TET result, and 812 (34.9%) had obstructive coronary artery disease (≥70% stenosis in at least one vessel). The study population were randomly divided into training (70%) and testing (30%) groups for algorithm development. A total of 93 features, including exercise performance, hemodynamics and ST-segment changes were extracted from the TET results. Clinical features included comorbidity, smoking, height, weight, and Framingham risk score. Support vector machine, logistic regression, random forest, k-nearest neighbor and extreme gradient boosting machine learning algorithms were used to build the predictive models. The performance of each model was compared with that of conventional TET.

Results: Four of the five models exhibited comparable diagnostic performance and were better than conventional TET. The random forest algorithm had an area under the curve (AUC) of 0.73. When used with clinical features, the AUC improved to 0.74. The major advantage of the algorithm is the reduction of the false-positive rate compared with conventional TET (55% vs. 76.3%, respectively), while maintaining comparable sensitivity (85%).

Conclusions: Using the information obtained from conventional TET, a more accurate diagnosis can be made by incorporating an artificial intelligence-based model.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.11.028DOI Listing
November 2021

Clinical effectiveness of cefoperazone-sulbactam versus piperacillin-tazobactam for the treatment of pneumonia in the elderly population.

Int J Antimicrob Agents 2021 Dec 3:106491. Epub 2021 Dec 3.

Division of Chest Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Objectives: Both cefoperazone-sulbactam (CFP-SUL) and piperacillin-tazobactam (PIP-TAZ) are β-lactam/β-lactamase inhibitor antibiotics and have a similar antimicrobial spectrum. However, comparative clinical efficacy and safety between CFP-SUL and PIP-TAZ for pneumonia treatment remain largely unknown, especially in the elderly population.

Methods: Based on a multicenter, registry database, patients aged ≥65, diagnosed with severe community-acquired pneumonia (SCAP), hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP), and given empirical therapy with CFP-SUL or PIP-TAZ were included for analysis. The primary outcome of interest was the proportion of patients achieving clinical cure. Multivariate logistic regression was conducted to compare the odds ratios (OR) for the outcome between patients received CFP-SUL and PIP-TAZ.

Results: A total of 941 elderly patients, 624 with SCAP and 317 with either HAP or VAP, were included. The overall in-hospital mortality for the entire cohort was 19%. Clinical cure can be achieved in 81% and 83% of patients with SCAP and HAP/VAP, respectively. Multivariate logistic regression analysis showed similar odds for clinical cure between patients receiving CFP-SUL and PIP-TAZ whether they had SCAP (adjusted OR, 1.10; 95% CI, 0.71-1.70) or HAP/VAP (adjusted OR, 0.72; 95% CI, 0.30-1.76). Regarding the safety issue, both CFP-SUL and PIP-TAZ were generally well tolerated with few reported adverse events, even in this aged population.

Conclusions: Among the elderly patients with SCAP or HAP/VAP, empirical therapy with CFP-SUL is a viable alternative to PIP-TAZ, while considering antibiotic heterogeneity in antimicrobial stewardship.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106491DOI Listing
December 2021

Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination.

Nucleic Acids Res 2021 Dec 6. Epub 2021 Dec 6.

Ministry of Education Key Laboratory of Protein Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Homologous recombination (HR) is a primary DNA double-strand breaks (DSBs) repair mechanism. The recombinases Rad51 and Dmc1 are highly conserved in the RecA family; Rad51 is mainly responsible for DNA repair in somatic cells during mitosis while Dmc1 only works during meiosis in germ cells. This spatiotemporal difference is probably due to their distinctive mismatch tolerance during HR: Rad51 does not permit HR in the presence of mismatches, whereas Dmc1 can tolerate certain mismatches. Here, the cryo-EM structures of Rad51-DNA and Dmc1-DNA complexes revealed that the major conformational differences between these two proteins are located in their Loop2 regions, which contain invading single-stranded DNA (ssDNA) binding residues and double-stranded DNA (dsDNA) complementary strand binding residues, stabilizing ssDNA and dsDNA in presynaptic and postsynaptic complexes, respectively. By combining molecular dynamic simulation and single-molecule FRET assays, we identified that V273 and D274 in the Loop2 region of human RAD51 (hRAD51), corresponding to P274 and G275 of human DMC1 (hDMC1), are the key residues regulating mismatch tolerance during strand exchange in HR. This HR accuracy control mechanism provides mechanistic insights into the specific roles of Rad51 and Dmc1 in DNA double-strand break repair and may shed light on the regulatory mechanism of genetic recombination in mitosis and meiosis.
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http://dx.doi.org/10.1093/nar/gkab1141DOI Listing
December 2021

Ordered Packing of β-Sheet Nanofibrils into Nanotubes: Multi-hierarchical Assembly of Designed Short Peptides.

Nano Lett 2021 Dec 6. Epub 2021 Dec 6.

State Key Laboratory of Heavy Oil Processing and Center for Biotechnology and Bioengineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.

Although it is well-known proteins and their complexes are hierarchically organized and highly ordered structures, it remains a major challenge to replicate their hierarchical self-assembly process and to fabricate multihierarchical architectures with well-defined shapes and monodisperse characteristic sizes via peptide self-assembly. Here we describe an amphiphilic short peptide Ac-IGGHK-NH that first preassembles into thin, left-handed β-sheet nanofibrils, followed by their ordered packing into right-handed nanotubes. The key intermediate morphology and structures featuring the hierarchical process are simultaneously demonstrated. Further mechanistic exploration with the variants Ac-IGGGK-NH, Ac-IGGFK-NH, and Ac-IGGHK-NH reveals the vital role of multiple His-His side chain interactions between nanofibrils in mediating higher-order assembly and architectures. Altogether, our findings not only advance current understanding of hierarchical assembly of peptides and proteins but also afford a paradigm of how to take advantage of side chain interactions to construct higher-order assemblies with enhanced complexities.
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http://dx.doi.org/10.1021/acs.nanolett.1c02944DOI Listing
December 2021

Correction to: Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus.

Cancer Immunol Immunother 2021 Dec 6. Epub 2021 Dec 6.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

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http://dx.doi.org/10.1007/s00262-021-03112-1DOI Listing
December 2021
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