{"title":"The fourth scientific discovery paradigm for precision medicine and healthcare: Challenges ahead","authors":"Li Shen, Jinwei Bai, Jiao Wang, Bairong Shen","doi":"10.1093/pcmedi/pbab007","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab007","url":null,"abstract":"Abstract With the progression of modern information techniques, such as next generation sequencing (NGS), Internet of Everything (IoE) based smart sensors, and artificial intelligence algorithms, data-intensive research and applications are emerging as the fourth paradigm for scientific discovery. However, we face many challenges to practical application of this paradigm. In this article, 10 challenges to data-intensive discovery and applications in precision medicine and healthcare are summarized and the future perspectives on next generation medicine are discussed.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"1 1","pages":"80 - 84"},"PeriodicalIF":5.3,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89850637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ran Kang, Zhengtang Tan, Mei Lang, Linqi Jin, Yin Zhang, Yiming Zhang, T. Guo, Zhiyun Guo
{"title":"EnhFFL: A database of enhancer mediated feed-forward loops for human and mouse","authors":"Ran Kang, Zhengtang Tan, Mei Lang, Linqi Jin, Yin Zhang, Yiming Zhang, T. Guo, Zhiyun Guo","doi":"10.1093/pcmedi/pbab006","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab006","url":null,"abstract":"Abstract Feed-forward loops (FFLs) are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases. Enhancers are cis-regulatory elements that positively regulate protein-coding genes or microRNAs (miRNAs) by recruiting DNA-binding transcription factors (TFs). However, a comprehensive resource to identify, store, and analyze the FFLs of typical enhancer and super-enhancer FFLs is not currently available. Here, we present EnhFFL, an online database to provide a data resource for users to browse and search typical enhancer and super-enhancer FFLs. The current database covers 46 280/7000 TF-enhancer-miRNA FFLs, 9997/236 enhancer-miRNA-gene FFLs, 3 561 164/3 193 182 TF-enhancer-gene FFLs, and 1259/235 TF-enhancer feed-back loops (FBLs) across 91 tissues/cell lines of human and mouse, respectively. Users can browse loops by selecting species, types of tissue/cell line, and types of FFLs. EnhFFL supports searching elements including name/ID, genomic location, and the conservation of miRNA target genes. We also developed tools for users to screen customized FFLs using the threshold of q value as well as the confidence score of miRNA target genes. Disease and functional enrichment analysis showed that master miRNAs that are widely engaged in FFLs including TF-enhancer-miRNAs and enhancer-miRNA-genes are significantly involved in tumorigenesis. Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"46 1","pages":"129 - 135"},"PeriodicalIF":5.3,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83958699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blood purification for sepsis: an overview","authors":"Ling Zhang, Yuying Feng, P. Fu","doi":"10.1093/pcmedi/pbab005","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab005","url":null,"abstract":"Abstract Sepsis is a life-threatening organ failure exacerbated by a maladaptive infection response from the host, and is one of the major causes of mortality in the intensive care unit. In recent decades, several extracorporeal blood purification techniques have been developed to manage sepsis by acting on both the infectious agents themselves and the host immune response. This research aims to summarize recent progress on extracorporeal blood purification technologies applied for sepsis, discuss unanswered questions on renal replacement therapy for septic patients, and present a decision-making strategy for practitioners.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"49 1","pages":"45 - 55"},"PeriodicalIF":5.3,"publicationDate":"2021-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77924168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Checkpoint immunotherapy for NK/T cell lymphoma—Time for a showdown?","authors":"J. Chan, J. Lim, C. Ong","doi":"10.1093/pcmedi/pbab004","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab004","url":null,"abstract":"Editor's note A commentary on “Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma”.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"33 1","pages":"70 - 72"},"PeriodicalIF":5.3,"publicationDate":"2021-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88326614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms.","authors":"William Butler, Jiaoti Huang","doi":"10.1093/pcmedi/pbab003","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab003","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a common cause of cancer-related mortality in men worldwide. Although most men are diagnosed with low grade, indolent tumors that are potentially curable, a significant subset develops advanced disease where hormone therapy is required to target the androgen receptor (AR). Despite its initial effect, hormone therapy eventually fails and the tumor progresses to lethal stages even through continued inhibition of AR. This review article focuses on the role of PCa cellular heterogeneity in therapy resistance and disease progression. Although AR-positive luminal-type cells represent the vast majority of PCa cells, there exists a minor component of AR-negative neuroendocrine (NE) cells that are resistant to hormonal therapy and are enriched by the treatment. In addition, it is now well accepted that a significant subset of hormonally treated tumors recur as small cell neuroendocrine carcinoma (SCNC), further highlighting the importance of targeting NE cells in addition to the more abundant luminal-type cancer cells. Although it has been long recognized that NE cells are present in PCa, their underlying function in benign prostate and molecular mechanisms contributing to PCa progression remains poorly understood. In this article, we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular mechanisms. In addition, we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC, a significant clinical challenge in the management of advanced PCa.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"25-34"},"PeriodicalIF":5.3,"publicationDate":"2021-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbab003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Hosseini, Wanqiu Chen, Daliao Xiao, Charles Wang
{"title":"Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs.","authors":"Maryam Hosseini, Wanqiu Chen, Daliao Xiao, Charles Wang","doi":"10.1093/pcmedi/pbab001","DOIUrl":"https://doi.org/10.1093/pcmedi/pbab001","url":null,"abstract":"<p><p>The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins (NSP). Three non-structural proteins, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), are believed to have a crucial role in replication of the virus. We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"1-16"},"PeriodicalIF":5.3,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbab001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Strategies for advanced personalized tuberculosis diagnosis: Current technologies and clinical approaches.","authors":"Xuerong Chen, Tony Y Hu","doi":"10.1093/pcmedi/pbaa041","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa041","url":null,"abstract":"<p><p>Diagnosis of tuberculosis can be difficult as advances in molecular diagnosis approaches (especially nanoparticles combined with high-throughput mass spectrometry for detecting mycobacteria peptide) and personalized medicine result in many changes to the diagnostic framework. This review will address issues concerning novel technologies from bench to bed and new strategies for personalized tuberculosis diagnosis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"35-44"},"PeriodicalIF":5.3,"publicationDate":"2021-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RhoA and Cdc42 in T cells: Are they targetable for T cell-mediated inflammatory diseases?","authors":"Fukun Guo","doi":"10.1093/pcmedi/pbaa039","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa039","url":null,"abstract":"<p><p>Many inflammatory diseases are not curable, necessitating a better understanding of their pathobiology that may help identify novel biological targets. RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization, cell adhesion, migration, proliferation, and survival. Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types. In T lymphocytes, which play an important role in the pathogenesis of most, if not all, of the inflammatory diseases, we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus, peripheral T cell homeostasis, activation, and differentiation to effector and regulatory T cells, and on T cell-mediated allergic airway inflammation and colitis. Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"4 1","pages":"56-61"},"PeriodicalIF":5.3,"publicationDate":"2021-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25580336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Winston Wang, Charlotte L Zhang, K. Wei, Ye Sang, Jun Shen, Guangyu Wang, Alexander X. Lozano
{"title":"Clinical longitudinal evaluation of COVID-19 patients and prediction of organ-specific recovery using artificial intelligence","authors":"Winston Wang, Charlotte L Zhang, K. Wei, Ye Sang, Jun Shen, Guangyu Wang, Alexander X. Lozano","doi":"10.1093/pcmedi/pbaa040","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa040","url":null,"abstract":"Abstract Within COVID-19 there is an urgent unmet need to predict at the time of hospital admission which COVID-19 patients will recover from the disease, and how fast they recover to deliver personalized treatments and to properly allocate hospital resources so that healthcare systems do not become overwhelmed. To this end, we have combined clinically salient CT imaging data synergistically with laboratory testing data in an integrative machine learning model to predict organ-specific recovery of patients from COVID-19. We trained and validated our model in 285 patients on each separate major organ system impacted by COVID-19 including the renal, pulmonary, immune, cardiac, and hepatic systems. To greatly enhance the speed and utility of our model, we applied an artificial intelligence method to segment and classify regions on CT imaging, from which interpretable data could be directly fed into the predictive machine learning model for overall recovery. Across all organ systems we achieved validation set area under the receiver operator characteristic curve (AUC) values for organ-specific recovery ranging from 0.80 to 0.89, and significant overall recovery prediction in Kaplan-Meier analyses. This demonstrates that the synergistic use of an artificial intelligence (AI) framework applied to CT lung imaging and a machine learning model that integrates laboratory test data with imaging data can accurately predict the overall recovery of COVID-19 patients from baseline characteristics.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"62 - 69"},"PeriodicalIF":5.3,"publicationDate":"2020-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81067654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Making radiation therapy more effective in the era of precision medicine","authors":"Xingchen Peng, Zhi-Gong Wei, L. Gerweck","doi":"10.1093/pcmedi/pbaa038","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa038","url":null,"abstract":"Abstract Cancer has become a leading cause of death and constitutes an enormous burden worldwide. Radiation is a principle treatment modality used alone or in combination with other forms of therapy, with 50%–70% of cancer patients receiving radiotherapy at some point during their illness. It has been suggested that traditional radiotherapy (daily fractions of approximately 1.8–2 Gy over several weeks) might select for radioresistant tumor cell sub-populations, which, if not sterilized, give rise to local treatment failure and distant metastases. Thus, the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population. With continued technological advances including enhanced conformal treatment technology, radiation oncologists can increasingly maximize the dose to tumors while sparing adjacent normal tissues, to limit toxicity and damage to the latter. Increased dose conformality also facilitates changes in treatment schedules, such as changes in dose per treatment fraction and number of treatment fractions, to enhance the therapeutic ratio. For example, the recently developed large dose per fraction treatment schedules (hypofractionation) have shown clinical advantage over conventional treatment schedules in some tumor types. Experimental studies suggest that following large acute doses of radiation, recurrent tumors, presumably sustained by the most resistant tumor cell populations, may in fact be equally or more radiation sensitive than the primary tumor. In this review, we summarize the related advances in radiotherapy, including the increasing understanding of the molecular mechanisms of radioresistance, and the targeting of these mechanisms with potent small molecule inhibitors, which may selectively sensitize tumor cells to radiation.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"1 1","pages":"272 - 283"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77303209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}