Precision Clinical Medicine最新文献

{"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}

{"title":"Long-term spaceflight and the cardiovascular system.","authors":"Nicholas A Vernice,&nbsp;Cem Meydan,&nbsp;Ebrahim Afshinnekoo,&nbsp;Christopher E Mason","doi":"10.1093/pcmedi/pbaa022","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa022","url":null,"abstract":"<p><p>While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%-15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 4","pages":"284-291"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38775507","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":"Vegetarian diets, circulating miRNA expression and healthspan in subjects living in the Blue Zone.","authors":"Tiantian Liu,&nbsp;Nicole M Gatto,&nbsp;Zhong Chen,&nbsp;Hongyu Qiu,&nbsp;Grace Lee,&nbsp;Penelope Duerksen-Hughes,&nbsp;Gary Fraser,&nbsp;Charles Wang","doi":"10.1093/pcmedi/pbaa037","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa037","url":null,"abstract":"<p><p>A long-term vegetarian diet plays a role in the longevity and maintenance of the healthspan, but the underlying mechanisms for these observations are largely unknown. Particularly, it is not known whether a long-term vegetarian dietary pattern may affect the circulating miRNA expression in such a way as to modulate the healthspan. The Adventist Health Study-2 (AHS-2) cohort includes a large number of older adults who primarily follow vegetarian dietary patterns and reside in Loma Linda, California, one of five \"Blue Zones\" in the world in which a higher proportion of the population enjoys a longer than average lifespan. We performed miRNA-seq in 96 subjects selected from the AHS-2 cohort with different dietary patterns. We identified several differentially expressed miRNAs between vegetarians and non-vegetarians, which are involved in immune response and cytokine signaling, cell growth and proliferation as well as age-related diseases such as cardiovascular diseases and neurodegenerative diseases. Overall, our study showed that a vegetarian diet modulates aging-associated circulating miRNAs in a sex-dependent manner of differential expression for certain miRNAs, which may be related in a beneficial manner to the healthspan. Further investigation is needed to validate these miRNAs as potential biomarkers for diet-modulated longevity in humans.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 4","pages":"245-259"},"PeriodicalIF":5.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38775506","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":"Bilateral simultaneous primary acute angle-closure glaucoma","authors":"Charlotte L. Zhang, Wico Lai, Ian Ziyar, L. Lau, Jie Xu","doi":"10.1093/pcmedi/pbaa035","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa035","url":null,"abstract":"Dear Editor, Acute primary angle-closure glaucoma (PACG) is an important cause of blindness in East Asia.1 It is estimated that the overall prevalence of PACG will increase from 1.44% to 2.01% from 2020 to 2050.2 Acute PACG is typically related to increased high intraocular pressure (IOP), with symptoms including red eye, blurred vision, nausea, vomiting, and headache. Delay in timely IOPlowering treatment can result in permanent optic nerve damage and vision loss.3 Axial hyperopia is the main ocular risk factor for development of primary closure of the anterior chamber angle, while its systemic risk factors include older age, east Asian ethnic origin, and female sex.4 Although generally deemed to be a bilateral condition, PACG often occurs unilaterally, and bilateral simultaneous onset is very rare. For patients with unilateral onset, even if the effect of treatment is not satisfactory, relatively good outcomes can be achieved by carrying out early intervention on the fellow eye. However, for bilateral cases, the condition is usually severe and often comes with a poor prognosis. Therefore, appropriate preventive measures are critical. Here, we present a case of bilateral simultaneous acute PACG related to hyperopia. A 58-year-old Chinese woman presented with intermittent headaches, nausea, vomiting, and acute pain in both eyes for 1 month, which had worsened recently. The patient reported no history of taking anticholinergic and sympathomimetic drugs, nor was any other cause identified. The vital signs included a body temperature of 37.4◦C, blood pressure 150/96 mmHg, and a pulse 90 beats/min. Visual acuities were CF in 50 cm in both eyes and IOP was 51 and 53 mmHg in the right and left eye, respectively. Slit lamp examination revealed conjunctiva hyperemia, corneal edema, mid-dilated pupils, and shallow anterior chambers peripherally and centrally (Fig. 1). Fundus examination had a hazy view. B-scan ultrasonography demonstrated that retinas were attached in both eyes. Initial treatments included systemic acetazolamide 250 mg twice a day, pilocarpine 2% four times a day, brinzolamide 1.0% twice-a-day, and fixed-combination eye drops containing timolol maleate 0.5% and brimonidine tartrate 0.2% twice-a-day. A few hours later, the IOPs reduced to 28 OD and 32 OS mmHg respectively. The patient underwent a laser peripheral iridotomy and was sent home with prednisolone acetate eye drops to be applied four times a day, acetazolamide 500 mg every","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"2 1","pages":"297 - 300"},"PeriodicalIF":5.3,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78610984","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":"Future directions for screening and treatment in congenital hearing loss.","authors":"Ryan K Thorpe, Richard J H Smith","doi":"10.1093/pcmedi/pbaa025","DOIUrl":"10.1093/pcmedi/pbaa025","url":null,"abstract":"<p><p>Hearing loss is the most common neurosensory deficit. It results from a variety of heritable and acquired causes and is linked to multiple deleterious effects on a child's development that can be ameliorated by prompt identification and individualized therapies. Diagnosing hearing loss in newborns is challenging, especially in mild or progressive cases, and its management requires a multidisciplinary team of healthcare providers comprising audiologists, pediatricians, otolaryngologists, and genetic counselors. While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before, a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality. In this review, we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 3","pages":"175-186"},"PeriodicalIF":5.1,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/64/pbaa025.PMC7653508.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38618794","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":"Recent advancements in PARP inhibitors-based targeted cancer therapy.","authors":"Ping Zhou,&nbsp;Justin Wang,&nbsp;Daniel Mishail,&nbsp;Cun-Yu Wang","doi":"10.1093/pcmedi/pbaa030","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa030","url":null,"abstract":"<p><p>Poly(ADP-ribose) polymerase inhibitors (PARPi) are a new class of agents with unparalleled clinical achievement for driving synthetic lethality in BRCA-deficient cancers. Recent FDA approval of PARPi has motivated clinical trials centered around the optimization of PARPi-associated therapies in a variety of BRCA-deficient cancers. This review highlights recent advancements in understanding the molecular mechanisms of PARP 'trapping' and synthetic lethality. Particular attention is placed on the potential extension of PARPi therapies from BRCA-deficient patients to populations with other homologous recombination-deficient backgrounds, and common characteristics of PARPi and non-homologous end-joining have been elucidated. The synergistic antitumor effect of combining PARPi with various immune checkpoint blockades has been explored to evaluate the potential of combination therapy in attaining greater therapeutic outcome. This has shed light onto the differing classifications of PARPi as well as the factors that result in altered PARPi activity. Lastly, acquired chemoresistance is a crucial issue for clinical application of PARPi. The molecular mechanisms underlying PARPi resistance and potential overcoming strategies are discussed.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 3","pages":"187-201"},"PeriodicalIF":5.3,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38429051","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":"Calling for a united action to defeat COVID-19.","authors":"Madison Overby, Qinqin Pu, Xiawei Wei, Min Wu","doi":"10.1093/pcmedi/pbaa027","DOIUrl":"10.1093/pcmedi/pbaa027","url":null,"abstract":"<p><p>The widespread and lingering pandemic of COVID-19 is partly due to disjointed international countermeasures and policies enforced by different countries. We have been witnessing disparity in policies and measures in different countries and regions: some are in much better control than others. To effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crises, and life and economic losses.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 3","pages":"235-239"},"PeriodicalIF":5.1,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38624382","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":"Recent advances of deep learning in psychiatric disorders","authors":"Lu Chen, C. Xia, Huaiqiang Sun","doi":"10.1093/pcmedi/pbaa029","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa029","url":null,"abstract":"ABSTRACT Deep learning (DL) is a recently proposed subset of machine learning methods that has gained extensive attention in the academic world, breaking benchmark records in areas such as visual recognition and natural language processing. Different from conventional machine learning algorithm, DL is able to learn useful representations and features directly from raw data through hierarchical nonlinear transformations. Because of its ability to detect abstract and complex patterns, DL has been used in neuroimaging studies of psychiatric disorders, which are characterized by subtle and diffuse alterations. Here, we provide a brief review of recent advances and associated challenges in neuroimaging studies of DL applied to psychiatric disorders. The results of these studies indicate that DL could be a powerful tool in assisting the diagnosis of psychiatric diseases. We conclude our review by clarifying the main promises and challenges of DL application in psychiatric disorders, and possible directions for future research.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"35 1","pages":"202 - 213"},"PeriodicalIF":5.3,"publicationDate":"2020-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91380846","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":"Whole-exome sequencing in a patient with synchronous triple primary malignancies involving lung cancer: a case report","authors":"Dan Li, M. Yu, P. Zhou, Jie Yang, Yongsheng Wang","doi":"10.1093/pcmedi/pbaa019","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa019","url":null,"abstract":"Abstract The incidence of multiple primary malignancies (MPMs) has been increasing rapidly in recent years, however, the genetic pathogenesis is largely unknown on account of rare cases, especially for those patients who are diagnosed with three or more tumors. Under these circumstances, whole-exome sequencing (WES) may help to provide more comprehensive genomic information and guidance to proper therapeutic strategies. Here, we presented a rare case of a 66-year-old Chinese male patient who was diagnosed with synchronous triple primary malignancies: esophageal squamous cell carcinoma (ESCC), lung adenocarcinoma (LA), and hepatocellular carcinoma (HCC). Tumors were surgically removed within 3 months. WES was performed when the patient suffered from cancer recurrence and tumor-specific neoantigens were predicted. Each tumor displayed a distinct somatic mutation profile, providing direct evidence of independent origins. No shared driver gene mutation or neoantigen was detected among the three tumors. Two germline alterations of cancer susceptibility genes—SPINK1 c.194 + 2T>C and JAK3 c.425G>A were identified. This case is the first report of synchronous primary triple cancers covering the esophagus, lung, and liver. Our findings highlight the complexities of MPMs that even when under identical germline genetic backgrounds, the occurrence of MPMs can be a random event and driven by distinct somatic gene mutations. Synchronous multiple primary cancers that originated from different organs may not have common therapeutic gene targets, and it can be difficult to find a treatment to cover all the tumors.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"73 1","pages":"306 - 310"},"PeriodicalIF":5.3,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83565510","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}