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J. Pers. Med., Volume 7, Issue 4 (December 2017)

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Research

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Open AccessArticle Psychiatric Disorders Differently Correlate with Physical Self-Rated Health across Ethnic Groups
J. Pers. Med. 2017, 7(4), 6; doi:10.3390/jpm7040006
Received: 3 March 2017 / Revised: 17 July 2017 / Accepted: 20 July 2017 / Published: 13 November 2017
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Abstract
In this study, we compared 10 ethnic groups for associations between psychiatric disorders and physical self-rated health (SRH) in the United States. Data came from the Collaborative Psychiatric Epidemiology Surveys (CPES), 2001–2003. The study included 7587 non-Latino White, 4746 African American, 1442 Mexican,
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In this study, we compared 10 ethnic groups for associations between psychiatric disorders and physical self-rated health (SRH) in the United States. Data came from the Collaborative Psychiatric Epidemiology Surveys (CPES), 2001–2003. The study included 7587 non-Latino White, 4746 African American, 1442 Mexican, 1106 other Hispanic, 656 other Asian, 600 Chinese, 577 Cuban, 520 Vietnamese, 508 Filipino, and 495 Puerto Rican individuals. The Composite International Diagnostic Interview (CIDI) was used to measure psychiatric disorders, including major depressive disorder (MDD), general anxiety disorder (GAD), social phobia, panic disorder, post-traumatic stress disorder (PTSD), alcohol abuse, and binge eating disorders. A single-item measure was used to estimate physical SRH. Demographic (age and gender) and socioeconomic (education and income) factors were also measured. Unadjusted and adjusted correlations between psychiatric disorders and physical SRH were calculated. Major ethnic variations were found in the correlation between psychiatric disorders and physical SRH; as well as the role of demographic and socioeconomic status (SES) factors in explaining these associations. non-Hispanic Whites, Cubans, and African Americans showed more correlations between psychiatric disorders and physical SRH than other ethnic groups. In non-Hispanic Whites, the associations between psychiatric disorders and physical SRH were explained by demographic factors. In African Americans, the link between psychiatric disorders and poor physical SRH were explained by SES indicators. In conclusion, although single-item physical SRH measures are traditionally assumed to reflect the physical health needs of populations, they may also indicate psychiatric disorders in some ethnic groups, such as non-Hispanic Whites, Cubans, and African Americans. Demographic and socioeconomic factors also have differential roles in explaining the link between psychiatric disorders and physical SRH. Physical SRH does not exclusively reflect physical health, and it may be more biased by mental health across some ethnic groups. Full article
Open AccessFeature PaperArticle Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children
J. Pers. Med. 2017, 7(4), 14; doi:10.3390/jpm7040014
Received: 6 October 2017 / Revised: 26 October 2017 / Accepted: 26 October 2017 / Published: 2 November 2017
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Abstract
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In
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Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone). For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole). For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children. Full article
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Open AccessArticle Polymorphisms in FFAR4 (GPR120) Gene Modulate Insulin Levels and Sensitivity after Fish Oil Supplementation
J. Pers. Med. 2017, 7(4), 15; doi:10.3390/jpm7040015
Received: 28 August 2017 / Revised: 11 October 2017 / Accepted: 31 October 2017 / Published: 6 November 2017
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Abstract
The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid
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The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid (EPA) and 1.1 g of docosahexaenoic acid (DHA)) during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene–diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0%) and HOMA-IR (2.03%) index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles. Full article
(This article belongs to the Special Issue Nutrigenomics)
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Open AccessArticle Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms
J. Pers. Med. 2017, 7(4), 16; doi:10.3390/jpm7040016
Received: 12 September 2017 / Revised: 6 November 2017 / Accepted: 8 November 2017 / Published: 10 November 2017
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Abstract
Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable
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Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern. Full article
(This article belongs to the Special Issue Nutrigenomics)
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Open AccessArticle Access to Guideline-Recommended Pharmacogenomic Tests for Cancer Treatments: Experience of Providers and Patients
J. Pers. Med. 2017, 7(4), 17; doi:10.3390/jpm7040017
Received: 4 October 2017 / Revised: 28 October 2017 / Accepted: 8 November 2017 / Published: 15 November 2017
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Abstract
Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers’ and patients’ experiences and views on test access
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Genomic tests are the fastest growing sector in medicine and medical science, yet there remains a dearth of research on access to pharmacogenomic tests and medications. The objective of this study is to explore providers’ and patients’ experiences and views on test access as well as strategies used for gaining access. We interviewed clinicians who prescribed medications that should be guided by pharmacogenomic testing and patients who received those prescriptions. We organized the themes into the four dimensions suggested by the World Health Organization framework on access to medications and health technologies. Guideline-recommended pharmacogenomic tests for cancer care are generally available, although the timeliness of return of test results is sometimes suboptimal. Accessibility of pharmacogenomic tests is made challenging by the process of ordering pharmacogenomic tests, which is time-consuming. Affordability is a barrier to some patients as expressed by both providers and patients, who noted that the cost of pharmacogenomic tests and medications is high. Acceptability of the tests is high as both providers and patients view the tests positively. Understanding challenges to accessing pharmacogenomic tests will allow policymakers to develop policies that streamline access to genomics-based technologies to improve population health. Full article
Open AccessArticle Fixed and Adaptive Parallel Subgroup-Specific Design for Survival Outcomes: Power and Sample Size
J. Pers. Med. 2017, 7(4), 19; doi:10.3390/jpm7040019
Received: 3 July 2017 / Revised: 30 October 2017 / Accepted: 27 November 2017 / Published: 4 December 2017
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Abstract
Biomarker-guided clinical trial designs, which focus on testing the effectiveness of a biomarker-guided approach to treatment in improving patient health, have drawn considerable attention in the era of stratified medicine with many different designs being proposed in the literature. However, planning such trials
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Biomarker-guided clinical trial designs, which focus on testing the effectiveness of a biomarker-guided approach to treatment in improving patient health, have drawn considerable attention in the era of stratified medicine with many different designs being proposed in the literature. However, planning such trials to ensure they have sufficient power to test the relevant hypotheses can be challenging and the literature often lacks guidance in this regard. In this study, we focus on the parallel subgroup-specific design, which allows the evaluation of separate treatment effects in the biomarker-positive subgroup and biomarker-negative subgroup simultaneously. We also explore an adaptive version of the design, where an interim analysis is undertaken based on a fixed percentage of target events, with the option to stop each biomarker-defined subgroup early for futility or efficacy. We calculate the number of events and patients required to ensure sufficient power in each of the biomarker-defined subgroups under different scenarios when the primary outcome is time-to-event. For the adaptive version, stopping probabilities are also explored. Since multiple hypotheses are being tested simultaneously, and multiple interim analyses are undertaken, we also focus on controlling the overall type I error rate by way of multiplicity adjustment. Full article
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Review

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Open AccessReview Personalized Nanomedicine: A Revolution at the Nanoscale
J. Pers. Med. 2017, 7(4), 12; doi:10.3390/jpm7040012
Received: 31 August 2017 / Revised: 4 October 2017 / Accepted: 4 October 2017 / Published: 12 October 2017
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Abstract
Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near
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Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to a cohort of patients. In the present review, the properties and requirements of pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been highlighted. An overview of the main current nanomedicines in pre-clinical and clinical development is presented, detailing the challenges to the personalization of these therapies. Next, the process of development of novel nanomedicines is described, from their design in research labs to their arrival on the market, including considerations for the design of nanomedicines adapted to the requirements of the market to achieve safe, effective, and quality products. Finally, attention is given to the point of view of the pharmaceutical industry, including regulation issues applied to the specific case of personalized medicine. The authors expect this review to be a useful overview of the current state of the art of nanomedicine research and industrial production, and the future opportunities of personalized medicine in the upcoming years. The authors encourage the development and marketing of novel personalized nanomedicines. Full article
(This article belongs to the Special Issue Personalized Nanomedicine)
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Open AccessReview Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy
J. Pers. Med. 2017, 7(4), 13; doi:10.3390/jpm7040013
Received: 22 September 2017 / Revised: 8 October 2017 / Accepted: 8 October 2017 / Published: 16 October 2017
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Abstract
Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising
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Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly results from mutations disrupting the reading frame of the dystrophin (DMD) gene. Among the therapeutic approaches employed, exon skipping using antisense oligonucleotides (AOs) is one of the most promising strategies. This strategy aims to restore the reading frame, thus producing a truncated, yet functioning dystrophin protein. In 2016, the Food and Drug Administration (FDA) conditionally approved the first AO-based drug, eteplirsen (Exondys 51), developed for DMD exon 51 skipping. An accurate and reproducible method to quantify exon skipping efficacy is essential for evaluating the therapeutic potential of different AOs sequences. However, previous in vitro screening studies have been hampered by the limited proliferative capacity and insufficient amounts of dystrophin expressed by primary muscle cell lines that have been the main system used to evaluate AOs sequences. In this paper, we illustrate the challenges associated with primary muscle cell lines and describe a novel approach that utilizes immortalized cell lines to quantitatively evaluate the exon skipping efficacy in in vitro studies. Full article
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Open AccessFeature PaperReview Variation in CYP2A6 Activity and Personalized Medicine
J. Pers. Med. 2017, 7(4), 18; doi:10.3390/jpm7040018
Received: 7 October 2017 / Revised: 17 November 2017 / Accepted: 27 November 2017 / Published: 1 December 2017
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Abstract
The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine—the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism
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The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine—the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism of nicotine and other CYP2A6 substrates including cotinine, tegafur, letrozole, efavirenz, valproic acid, pilocarpine, artemisinin, artesunate, SM-12502, caffeine, and tyrosol. CYP2A6 expression and activity are also impacted by non-genetic factors, including induction or inhibition by pharmacological, endogenous, and dietary substances, as well as age-related changes, or interactions with other hepatic enzymes, co-enzymes, and co-factors. As variation in CYP2A6 activity is associated with smoking behavior, smoking cessation, tobacco-related lung cancer risk, and with altered metabolism and resulting clinical responses for several therapeutics, CYP2A6 expression and enzyme activity is an important clinical consideration. This review will discuss sources of variation in CYP2A6 enzyme activity, with a focus on the impact of CYP2A6 genetic variation on metabolism of the CYP2A6 substrates. Full article
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Open AccessFeature PaperReview Pharmacogenomics Guided-Personalization of Warfarin and Tamoxifen
J. Pers. Med. 2017, 7(4), 20; doi:10.3390/jpm7040020
Received: 25 October 2017 / Revised: 23 November 2017 / Accepted: 7 December 2017 / Published: 13 December 2017
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Abstract
The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date
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The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy. Full article
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Open AccessReview Development of the Precision Link Biobank at Boston Children’s Hospital: Challenges and Opportunities
J. Pers. Med. 2017, 7(4), 21; doi:10.3390/jpm7040021 (registering DOI)
Received: 15 September 2017 / Revised: 30 November 2017 / Accepted: 12 December 2017 / Published: 15 December 2017
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Abstract
Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from
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Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders’ input and implemented initially in a pilot phase before hospital-wide expansion in 2016. In-person informed consent is obtained from all participants enrolling in the Biobank and provides permission to: (1) access EHR data for research; (2) collect and use residual specimens produced as by-products of routine care; and (3) share de-identified data and specimens outside of the institution. Participants are recruited throughout the hospital, across diverse clinical settings. We have enrolled 4900 patients to date, and 41% of these have an associated blood sample for DNA processing. Current efforts are focused on aligning the Biobank with other ongoing research efforts at our institution and extending our electronic consenting system to support remote enrollment. A number of pediatric-specific challenges and opportunities is reviewed, including the need to re-consent patients when they reach 18 years of age, the ability to enroll family members accompanying patients and alignment with disease-specific research efforts at our institution and other pediatric centers to increase cohort sizes, particularly for rare diseases. Full article

Other

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Open AccessCommentary Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine
J. Pers. Med. 2017, 7(4), 11; doi:10.3390/jpm7040011
Received: 23 August 2017 / Revised: 23 September 2017 / Accepted: 9 October 2017 / Published: 16 October 2017
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Abstract
Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision
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Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision medicine, as defined herein, characterizes unique biological characteristics of the individual or of specimens obtained from an individual to tailor diagnostics and therapeutics to a specific patient. These unique biological characteristics are defined by the tools of precision medicine: genomics, proteomics, metabolomics, epigenomics, pharmacogenomics, and other “-omics.” Personalized medicine, as defined herein, uses additional information about the individual derived from knowing the patient as a person. These unique personal characteristics are defined by tools known as personomics which takes into account an individual’s personality, preferences, values, goals, health beliefs, social support network, financial resources, and unique life circumstances that affect how and when a given health condition will manifest in that person and how that condition will respond to treatment. In this paradigm, precision medicine may be considered a necessary step in the evolution of medical care to personalized medicine, with personomics as the missing link. Full article
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