Editor's Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article
Alterations of Left Ventricular Function Persisting during Post-Acute COVID-19 in Subjects without Previously Diagnosed Cardiovascular Pathology
J. Pers. Med. 2021, 11(3), 225; https://doi.org/10.3390/jpm11030225 - 22 Mar 2021
Cited by 4
Abstract
(1) Background: Coronavirus infection (Covid-19) has emerged as a severe medical condition, associated with high pulmonary morbidity and often with cardiovascular (CV) complications. This study aims to evidence the persistence of left ventricular (LV) systolic function (LV-SF) alterations and diastolic dysfunction (DD) in [...] Read more.
(1) Background: Coronavirus infection (Covid-19) has emerged as a severe medical condition, associated with high pulmonary morbidity and often with cardiovascular (CV) complications. This study aims to evidence the persistence of left ventricular (LV) systolic function (LV-SF) alterations and diastolic dysfunction (DD) in COVID-19 patients without history of cardiovascular (CV) diseases by transthoracic echocardiography (TTE). (2) Methods: 125 patients, aged under 55 years, hospitalized during the first outbreak of Covid-19 for moderate pneumonia, underwent a comprehensive cardiologic examination and TTE at 6–10 weeks after discharge. Their initial in-hospital laboratory data and thorax computer tomography (TCT) were accessed from the electronic database of the hospital. (3) Results: with TTE, we documented alterations of LV-SF and DD in 8.8% of patients and in 16.8% only patterns of DD, statistically correlated with the initial levels of creatin-kinase (CK-MB) and inflammatory factors. Multivariate regression analysis evidenced that CK-MB levels, age, and body mass index (BMI) are responsible for 65% of LV-SF decrease. (4) Conclusions: Alterations of LV-SF and DD are frequent in post-acute COVID-19 infection and are responsible for the persistence of symptoms. Elevated myocardial necrosis markers during the acute phase seem to predict subsequent alteration of cardiac performance. Full article
(This article belongs to the Special Issue COVID-19 Related Complications)
Article
Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer
J. Pers. Med. 2020, 10(4), 265; https://doi.org/10.3390/jpm10040265 - 04 Dec 2020
Cited by 1
Abstract
The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment [...] Read more.
The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8–10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions. Full article
(This article belongs to the Special Issue Stereotactic Body Radiotherapy)
Article
Hybrid PET–MRI Imaging in Paediatric and TYA Brain Tumours: Clinical Applications and Challenges
J. Pers. Med. 2020, 10(4), 218; https://doi.org/10.3390/jpm10040218 - 09 Nov 2020
Cited by 1
Abstract
(1) Background: Standard magnetic resonance imaging (MRI) remains the gold standard for brain tumour imaging in paediatric and teenage and young adult (TYA) patients. Combining positron emission tomography (PET) with MRI offers an opportunity to improve diagnostic accuracy. (2) Method: Our single-centre experience [...] Read more.
(1) Background: Standard magnetic resonance imaging (MRI) remains the gold standard for brain tumour imaging in paediatric and teenage and young adult (TYA) patients. Combining positron emission tomography (PET) with MRI offers an opportunity to improve diagnostic accuracy. (2) Method: Our single-centre experience of 18F-fluorocholine (FCho) and 18fluoro-L-phenylalanine (FDOPA) PET–MRI in paediatric/TYA neuro-oncology patients is presented. (3) Results: Hybrid PET–MRI shows promise in the evaluation of gliomas and germ cell tumours in (i) assessing early treatment response and (ii) discriminating tumour from treatment-related changes. (4) Conclusions: Combined PET–MRI shows promise for improved diagnostic and therapeutic assessment in paediatric and TYA brain tumours. Full article
(This article belongs to the Special Issue Biomedical Imaging and Cancers)
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Article
GWAS of Post-Orthodontic Aggressive External Apical Root Resorption Identified Multiple Putative Loci at X-Y Chromosomes
J. Pers. Med. 2020, 10(4), 169; https://doi.org/10.3390/jpm10040169 - 14 Oct 2020
Cited by 2
Abstract
Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption [...] Read more.
Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption secondary to orthodontic forces (aEARR). A genome-wide association study of aEARR was conducted with 480 patients [ratio~1:3 case/control]. Genomic DNA was extracted and analyzed using the high-throughput Axiom platform with the GeneTitan® MC Instrument. Up to 14,377 single nucleotide polymorphisms (SNPs) were selected at candidate regions and clinical/diagnostic data were recorded. A descriptive analysis of the data along with a backward conditional binary logistic regression was used to calculate odds ratios, with 95% confidence intervals [p < 0.05]. To select the best SNP candidates, a logistic regression model was fitted assuming a log-additive genetic model using R software [p < 0.0001]. In this sample the top lead genetic variants associated with aEARR were two novel putative genes located in the X chromosome, specifically, STAG 2 gene, rs151184635 and RP1-30E17.2 gene, rs55839915. These variants were found to be associated with an increased risk of aEARR, particularly restricted to men [OR: 6.09; 95%CI: 2.6–14.23 and OR: 6.86; 95%CI: 2.65–17.81, respectively]. Marginal associations were found at previously studied variants such as SSP1: rs11730582 [OR: 0.54; 95%CI: 0.34–0.86; p = 0.008], P2RX7: rs1718119 [OR: 0.6; 95%CI: 0.36–1.01; p = 0.047], and TNFRSF11A: rs8086340 [OR: 0.6; 95%CI: 0.38–0.95; p = 0.024]), found solely in females. Multiple putative genetic variants located at chromosomes X and Y are potentially implicated in an extreme phenotype of aEARR. A gender-linked association was noted. Full article
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Article
Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy
J. Pers. Med. 2020, 10(4), 152; https://doi.org/10.3390/jpm10040152 - 02 Oct 2020
Cited by 3
Abstract
Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this [...] Read more.
Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82–88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites. Full article
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Article
Validation of the Italian Version of the Educational Needs Assessment Tool in Rheumatoid Arthritis Patients and Factors Associated with Educational Needs
J. Pers. Med. 2020, 10(4), 150; https://doi.org/10.3390/jpm10040150 - 01 Oct 2020
Cited by 2
Abstract
The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in [...] Read more.
The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in people with RA. The original English ENAT version was translated into Italian according to Beaton’s method and subjected to Rasch analysis for validity testing. Socio-demographic and clinical variables were tested for associations with the ENAT domain scores using a multivariable linear regression model. The ENAT translated well into Italian and retained its construct validity. Some adjustments were needed when pooling the Italian and English datasets. The overall score of the ENAT had a high median: 82.8 (interquartile range (IQR): 57.5 to 100) i.e., 72.4% of the maximum score. The highest score was observed in the domain “Arthritis process” and the lowest was in “Support systems”. Only gender was independently associated with EN (females having higher EN than males). The Italian ENAT is feasible for the use in the clinical setting and may help the health care practitioners to tailor educational interventions for RA patients. The characteristics of the patients, particularly female gender, may be associated with higher EN. Full article
(This article belongs to the Special Issue Use of Clinical Decision Support Software within Health Care Systems)
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Article
Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
J. Pers. Med. 2020, 10(4), 146; https://doi.org/10.3390/jpm10040146 - 25 Sep 2020
Cited by 9
Abstract
Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase [...] Read more.
Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. The distribution and expression of many of these genes across cell types representing multiple organ systems in healthy individuals has recently been demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and are associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remains unclear. Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals. Additionally, we found the increased expression of viral entry-related genes in the settings of hypertension, cancer, or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and we suggest new therapeutic targets to improve outcomes in vulnerable patient populations. Full article
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Article
XGBoost Improves Classification of MGMT Promoter Methylation Status in IDH1 Wildtype Glioblastoma
J. Pers. Med. 2020, 10(3), 128; https://doi.org/10.3390/jpm10030128 - 15 Sep 2020
Cited by 35
Abstract
Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. [...] Read more.
Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM. Full article
(This article belongs to the Special Issue Biomedical Imaging and Cancers)
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Article
Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1
J. Pers. Med. 2020, 10(2), 43; https://doi.org/10.3390/jpm10020043 - 25 May 2020
Cited by 4
Abstract
Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy [...] Read more.
Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI. Evidence to date suggests that these nutritional compounds can work independently to optimize the neurocognitive environment, primarily due to their antioxidant and anti-inflammatory properties. To date, however, no interventional studies have examined the potential synergistic effects of a combination of ω-3FAs, carotenoids and vitamin E on the cognitive function of patients with MCI. Individuals with clinically confirmed MCI consumed an ω-3FA plus carotenoid plus vitamin E formulation or placebo for 12 months. Cognitive performance was determined from tasks that assessed global cognition and episodic memory. Ω-3FAs, carotenoids, and vitamin E were measured in blood. Carotenoid concentrations were also measured in tissue (skin and retina). Individuals consuming the active intervention (n = 6; median [IQR] age 73.5 [69.5–80.5] years; 50% female) exhibited statistically significant improvements (p < 0.05, for all) in tissue carotenoid concentrations, and carotenoid and ω-3FA concentrations in blood. Trends in improvements in episodic memory and global cognition were also observed in this group. In contrast, the placebo group (n = 7; median [IQR] 72 (69.5–75.5) years; 89% female) remained unchanged or worsened for all measurements (p > 0.05). Despite a small sample size, this exploratory study is the first of its kind to identify trends in improved cognitive performance in individuals with MCI following supplementation with ω-3FAs, carotenoids, and vitamin E. Full article
(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)
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Article
Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network
J. Pers. Med. 2020, 10(2), 38; https://doi.org/10.3390/jpm10020038 - 13 May 2020
Cited by 3
Abstract
A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine [...] Read more.
A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging. Full article
(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)
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Article
Returning Results in the Genomic Era: Initial Experiences of the eMERGE Network
J. Pers. Med. 2020, 10(2), 30; https://doi.org/10.3390/jpm10020030 - 27 Apr 2020
Cited by 14
Abstract
A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE [...] Read more.
A goal of the 3rd phase of the Electronic Medical Records and Genomics (eMERGE3) Network was to examine the return of results (RoR) of actionable variants in more than 100 genes to consenting participants and their healthcare providers. Each of the 10 eMERGE sites developed plans for three essential elements of the RoR process: Disclosure to the participant, notification of the health care provider, and integration of results into the electronic health record (EHR). Procedures and protocols around these three elements were adapted as appropriate to individual site requirements and limitations. Detailed information about the RoR procedures at each site was obtained through structured telephone interviews and follow-up surveys with the clinical investigator leading or participating in the RoR process at each eMERGE3 institution. Because RoR processes at each of the 10 sites allowed for taking into account differences in population, disease focus and institutional requirements, significant heterogeneity of process was identified, including variability in the order in which patients and clinicians were notified and results were placed in the EHR. This heterogeneity in the process flow for eMERGE3 RoR reflects the “real world” of genomic medicine in which RoR procedures must be shaped by the needs of the patients and institutional environments. Full article
Article
Pharmacogenomic (PGx) Counseling: Exploring Participant Questions about PGx Test Results
J. Pers. Med. 2020, 10(2), 29; https://doi.org/10.3390/jpm10020029 - 23 Apr 2020
Cited by 2
Abstract
As pharmacogenomic (PGx) use in healthcare increases, a better understanding of patient needs will be necessary to guide PGx result delivery. The Coriell Personalized Medicine Collaborative (CPMC) is a prospective study investigating the utility of personalized medicine. Participants received online genetic risk reports [...] Read more.
As pharmacogenomic (PGx) use in healthcare increases, a better understanding of patient needs will be necessary to guide PGx result delivery. The Coriell Personalized Medicine Collaborative (CPMC) is a prospective study investigating the utility of personalized medicine. Participants received online genetic risk reports for 27 potentially actionable complex diseases and 7 drug–gene pairs and could request free, telephone-based genetic counseling (GC). To explore the needs of individuals receiving PGx results, we conducted a retrospective qualitative review of inquiries from CPMC participants who requested counseling from March 2009 to February 2017. Eighty out of 690 (12%) total GC inquiries were focused on the discussion of PGx results, and six salient themes emerged: “general help”, “issues with drugs”, “relevant disease experience”, “what do I do now?”, “sharing results”, and “other drugs”. The number of reported medications with a corresponding PGx result and participant engagement were significantly associated with PGx GC requests (p < 0.01 and p < 0.02, respectively). Our work illustrates a range of questions raised by study participants receiving PGx test results, most of which were addressed by a genetic counselor with few requiring referrals to prescribing providers or pharmacists. These results further support a role for genetic counselors in the team-based approach to optimal PGx result delivery. Full article
(This article belongs to the Special Issue Pharmacogenomics: From Basic Research to Clinical Implementation)
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Article
A Research on the Classification and Applicability of the Mobile Health Applications
J. Pers. Med. 2020, 10(1), 11; https://doi.org/10.3390/jpm10010011 - 27 Feb 2020
Cited by 17
Abstract
Mobile health applications are applied for different purposes. Healthcare professionals and other users can use this type of mobile applications for specific tasks, such as diagnosis, information, prevention, treatment, and communication. This paper presents an analysis of mobile health applications used by healthcare [...] Read more.
Mobile health applications are applied for different purposes. Healthcare professionals and other users can use this type of mobile applications for specific tasks, such as diagnosis, information, prevention, treatment, and communication. This paper presents an analysis of mobile health applications used by healthcare professionals and their patients. A secondary objective of this article is to evaluate the scientific validation of these mobile health applications and to verify if the results provided by these applications have an underlying sound scientific foundation. This study also analyzed literature references and the use of mobile health applications available in online application stores. In general, a large part of these mobile health applications provides information about scientific validation. However, some mobile health applications are not validated. Therefore, the main contribution of this paper is to provide a comprehensive analysis of the usability and user-perceived quality of mobile health applications and the challenges related to scientific validation of these mobile applications. Full article
(This article belongs to the Special Issue Use of Clinical Decision Support Software within Health Care Systems)
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Article
Access to Genetic Counselors in the Southern United States
J. Pers. Med. 2019, 9(3), 33; https://doi.org/10.3390/jpm9030033 - 01 Jul 2019
Cited by 13
Abstract
The expansion of genetic and genomic testing across medical specialties and the changing workforce demographics of certified genetic counselors (CGCs) have led to concerns of a workforce shortage. We assessed the number of genetic counselors working in the Southern United States—a rural and [...] Read more.
The expansion of genetic and genomic testing across medical specialties and the changing workforce demographics of certified genetic counselors (CGCs) have led to concerns of a workforce shortage. We assessed the number of genetic counselors working in the Southern United States—a rural and medically underserved region—using various online and professional resources. We identified 683 practicing genetic counselors across the Southern U.S. and 160 specializing in prenatal genetics. CGCs were concentrated in urban areas; counties with a CGC had a significantly higher proportion of minority residents and median household income than counties without a CGC. There is an average of 2.97 prenatal CGCs per 5000 high-risk births in the South. Alternative delivery models are needed to increase access to counseling services in the Southern U.S., particularly for low income households and those of high risk pregnancies. Increased provider education and patient educational materials can help facilitate informed decision-making in prenatal settings as genetic technologies gain a stronger foothold and bring value to medical practice. Full article
(This article belongs to the Collection Genomic Medicine and Policy)
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Article
Primary Care Physicians’ Knowledge, Attitudes, and Experience with Personal Genetic Testing
J. Pers. Med. 2019, 9(2), 29; https://doi.org/10.3390/jpm9020029 - 24 May 2019
Cited by 19
Abstract
Primary care providers (PCPs) will play an important role in precision medicine. However, their lack of training and knowledge about genetics and genomics may limit their ability to advise patients or interpret or utilize test results. We evaluated PCPs’ awareness of the role [...] Read more.
Primary care providers (PCPs) will play an important role in precision medicine. However, their lack of training and knowledge about genetics and genomics may limit their ability to advise patients or interpret or utilize test results. We evaluated PCPs’ awareness of the role of genetics/genomics in health, knowledge about key concepts in genomic medicine, perception/attitudes towards direct-to-consumer (DTC) genetic testing, and their level of confidence/comfort in discussing testing with patients prior to and after undergoing DTC testing through the 23andMe Health + Ancestry Service. A total of 130 PCPs completed the study. Sixty-three percent were board-certified in family practice, 32% graduated between 1991 and 2000, and 88% had heard of 23andMe prior to the study. Seventy-two percent decided to participate in the study to gain a better understanding about testing. At baseline, 23% of respondents indicated comfort discussing genetics as a risk factor for common diseases, increasing to 59% after undergoing personal genetic testing (PGT) (p < 0.01). In summary, we find that undergoing PGT augments physicians’ confidence, comfort, and interest in DTC testing. Full article
(This article belongs to the Collection Genomic Medicine and Policy)
Article
Feasibility of a Comprehensive Home Monitoring Program for Sarcoidosis
J. Pers. Med. 2019, 9(2), 23; https://doi.org/10.3390/jpm9020023 - 05 May 2019
Cited by 13
Abstract
Sarcoidosis is a chronic, heterogeneous disease which most commonly affects the lungs. Currently, evidence-based and individually tailored treatment options in sarcoidosis are lacking. We aimed to evaluate patient experiences with a home monitoring program for sarcoidosis and assess whether home monitoring is a [...] Read more.
Sarcoidosis is a chronic, heterogeneous disease which most commonly affects the lungs. Currently, evidence-based and individually tailored treatment options in sarcoidosis are lacking. We aimed to evaluate patient experiences with a home monitoring program for sarcoidosis and assess whether home monitoring is a feasible tool to enhance personalized treatment. Outpatients with pulmonary sarcoidosis tested the home monitoring program “Sarconline” for one month. This is a secured personal platform which consists of online patient-reported outcomes, real-time wireless home spirometry, an activity tracker, an information library, and an eContact option. Patients wore an activity tracker, performed daily home spirometry, and completed patient-reported outcomes at baseline and after one month. Patient experiences were evaluated during a phone interview. Ten patients were included in the study. Experiences with the home monitoring program were positive; 90% of patients considered the application easy to use, none of the patients found daily measurements burdensome, and all patients wished to continue the home monitoring program after the study. Mean adherence to daily spirometry and activity tracking was, respectively, 94.6% and 91.3%. In conclusion, a comprehensive home monitoring program for sarcoidosis is feasible and can be used in future research and clinical practice. Full article
(This article belongs to the Special Issue Wearable (or Electronic) Devices to Enhance Personalized Medicine)
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Editorial

Editorial
Colon Cancer Biomarkers: Implications for Personalized Medicine
J. Pers. Med. 2020, 10(4), 167; https://doi.org/10.3390/jpm10040167 - 13 Oct 2020
Abstract
The heterogeneity of colon cancers and their reactions presents both a challenge and promise for personalized medicine. The challenge is to develop effective biologically personalized therapeutics guided by predictive and prognostic biomarkers. Presently, there are several classes of candidate biomarkers, including genomic probes, [...] Read more.
The heterogeneity of colon cancers and their reactions presents both a challenge and promise for personalized medicine. The challenge is to develop effective biologically personalized therapeutics guided by predictive and prognostic biomarkers. Presently, there are several classes of candidate biomarkers, including genomic probes, inhibitory RNAs, assays for immunity dysfunction and, not to be forgotten, specific histopathologic and histochemical features. To develop effective therapeutics, candidate biomarkers must be qualified and validated in comparable independent cohorts, no small undertaking. This process and subsequent deployment in clinical practice involves not only the strong association of the biomarker with the treatment but also careful attention to the prosaic aspects of representative tumor site selection, obtaining a fully adequate sample which is preserved and prepared to optimize high quality analysis. In the future, the clinical utility of biomarker analytical results will benefit from associated clinical and basic science data with the assistance of artificial intelligence techniques. By application of an individualized, selected suite of biomarkers, comprehensively interpreted, individualized, more effective and less toxic therapy for colon cancer will be enabled, thereby fulfilling the promise of personalized medicine. Full article
Editorial
Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
J. Pers. Med. 2020, 10(4), 158; https://doi.org/10.3390/jpm10040158 - 08 Oct 2020
Cited by 1
Abstract
Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene expression and, ultimately, protein [...] Read more.
Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene expression and, ultimately, protein functionality in vivo, the effects of mutations/polymorphisms and the different sources of interindividual phenotypic variability. A remarkable example of our advances in these challenging tasks is the highly polymorphic CYP2D6 gene, which encodes a cytochrome P450 enzyme involved in the metabolization of many of the most marketed drugs (including SARS-Cov-2 therapies such as hydroxychloroquine). Since the introduction of simple activity scores (AS) over 10 years ago, its ability to establish genotype–phenotype correlations on the drug metabolizing capacity of this enzyme in human population has provided lessons that will help to improve this type of score for this, and likely many other human genes and proteins. Multidisciplinary research emerges as the best approach to incorporate additional concepts to refine and improve such functional/activity scores for the CYP2D6 gene, as well as for many other human genes associated with simple and complex genetic diseases. Full article
Editorial
Molecular Diagnosis and Novel Therapies for Neuromuscular Diseases
J. Pers. Med. 2020, 10(3), 129; https://doi.org/10.3390/jpm10030129 - 16 Sep 2020
Cited by 1
Abstract
With the development of novel targeted therapies, including exon skipping/inclusion and gene replacement therapy, the field of neuromuscular diseases has drastically changed in the last several years. Until 2016, there had been no FDA-approved drugs to treat Duchenne muscular dystrophy (DMD), the most [...] Read more.
With the development of novel targeted therapies, including exon skipping/inclusion and gene replacement therapy, the field of neuromuscular diseases has drastically changed in the last several years. Until 2016, there had been no FDA-approved drugs to treat Duchenne muscular dystrophy (DMD), the most common muscular dystrophy. However, several new personalized therapies, including antisense oligonucleotides eteplirsen for DMD exon 51 skipping and golodirsen and viltolarsen for DMD exon 53 skipping, have been approved in the last 4 years. We are witnessing the start of a therapeutic revolution in neuromuscular diseases. However, the studies also made clear that these therapies are still far from a cure. Personalized genetic medicine for neuromuscular diseases faces several key challenges, including the difficulty of obtaining appropriate cell and animal models and limited its applicability. This Special Issue “Molecular Diagnosis and Novel Therapies for Neuromuscular/Musculoskeletal Diseases” highlights key areas of research progress that improve our understanding and the therapeutic outcomes of neuromuscular diseases in the personalized medicine era. Full article
Editorial
Personalized Dentistry: Approaching a New Way for Diagnosis and Treatment of Oral Diseases
J. Pers. Med. 2020, 10(2), 35; https://doi.org/10.3390/jpm10020035 - 01 May 2020
Cited by 2
Abstract
For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in [...] Read more.
For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in dentistry. Recent studies have begun to shed light on the effect of the oral microbiota on general health and on the crucial role of dentistry in its maintenance. In this way, we came to understand that the bacterial populations that make up the oral microbiota can vary profoundly between individuals and that contribute in a fundamental way to outlining the so-called “oral signature”. This characteristic is called into question to evaluate the susceptibility, or lack thereof, of the subject to the contraction of a wide range of pathologies, apparently not connected with oral health. From this evidence, it will also be possible to study therapeutic approaches aimed at the eradication of species considered at risk or colonization with species considered protective; thus, giving life to so-called “personalized dentistry”. Therefore, this Special Issue is aimed at spreading the scientific knowledge over the current limits in terms of new molecular and culturomic approaches towards the diagnosis of oral microbiota and the treatment techniques of eventually associated systemic diseases. In vivo studies and systematic literature reviews with quantitative analysis of results, when possible, will be given a high priority. Full article
(This article belongs to the Special Issue Molecular Diagnosis and New Therapeutic Approach of Oral Diseases)
Editorial
Omics Meeting Onics: Towards the Next Generation of Spectroscopic-Based Technologies in Personalized Medicine
J. Pers. Med. 2019, 9(3), 39; https://doi.org/10.3390/jpm9030039 - 01 Aug 2019
Cited by 7
Abstract
This article aims to discuss the recent development of integrated point-of-care spectroscopic-based technologies that are paving the way for the next generation of diagnostic monitoring technologies in personalized medicine. Focusing on the nuclear magnetic resonance (NMR) technologies as the leading example, we discuss [...] Read more.
This article aims to discuss the recent development of integrated point-of-care spectroscopic-based technologies that are paving the way for the next generation of diagnostic monitoring technologies in personalized medicine. Focusing on the nuclear magnetic resonance (NMR) technologies as the leading example, we discuss the emergence of -onics technologies (e.g., photonics and electronics) and how their coexistence with -omics technologies (e.g., genomics, proteomics, and metabolomics) can potentially change the future technological landscape of personalized medicine. The idea of an open-source (e.g., hardware and software) movement is discussed, and we argue that technology democratization will not only promote the dissemination of knowledge and inspire new applications, but it will also increase the speed of field implementation. Full article
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Editorial
Preface to Special Issue on ‘Cytochrome P450 Variation in Pharmacogenomics’
J. Pers. Med. 2018, 8(3), 23; https://doi.org/10.3390/jpm8030023 - 04 Jul 2018
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Editorial
Implementing Personalized Medicine in the Academic Health Center
J. Pers. Med. 2016, 6(3), 18; https://doi.org/10.3390/jpm6030018 - 21 Sep 2016
Cited by 4
Abstract
Recently we at Partners Health Care had a series of articles in the Journal of Personalized Medicine describing how we are going about implementing Personalized Medicine in an academic health care system [1–10].[...] Full article
(This article belongs to the Special Issue Implementing Personalized Medicine in a Large Health Care System)

Review

Review
Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target
J. Pers. Med. 2021, 11(7), 619; https://doi.org/10.3390/jpm11070619 - 30 Jun 2021
Abstract
As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with [...] Read more.
As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers. Other HSD17B13 variants were also later linked with either lower inflammation scores among NAFLD patients or protection against NAFLD (rs6834314, A > G and rs9992651, G > A) respectively. HSD17B13 is a lipid droplet-associated protein, but its function is still ambiguous. Compared to the other genetic variants that increase risk for FLD, HSD17B13 variants serve a protective role, making this gene a potential therapeutic target. However, the mechanism by which these variants reduce the risk of developing FLD is still unclear. Because studies in cell lines and mouse models have produced conflicting results, human liver tissue modeling using induced pluripotent stem cells may be the best way to move forward and solve this mystery. Full article
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Review
Personalized Medicine for Neuroblastoma: Moving from Static Genotypes to Dynamic Simulations of Drug Response
J. Pers. Med. 2021, 11(5), 395; https://doi.org/10.3390/jpm11050395 - 11 May 2021
Abstract
High-risk neuroblastoma is an aggressive childhood cancer that is characterized by high rates of chemoresistance and frequent metastatic relapse. A number of studies have characterized the genetic and epigenetic landscape of neuroblastoma, but due to a generally low mutational burden and paucity of [...] Read more.
High-risk neuroblastoma is an aggressive childhood cancer that is characterized by high rates of chemoresistance and frequent metastatic relapse. A number of studies have characterized the genetic and epigenetic landscape of neuroblastoma, but due to a generally low mutational burden and paucity of actionable mutations, there are few options for applying a comprehensive personalized medicine approach through the use of targeted therapies. Therefore, the use of multi-agent chemotherapy remains the current standard of care for neuroblastoma, which also conceptually limits the opportunities for developing an effective and widely applicable personalized medicine approach for this disease. However, in this review we outline potential approaches for tailoring the use of chemotherapy agents to the specific molecular characteristics of individual tumours by performing patient-specific simulations of drug-induced apoptotic signalling. By incorporating multiple layers of information about tumour-specific aberrations, including expression as well as mutation data, these models have the potential to rationalize the selection of chemotherapeutics contained within multi-agent treatment regimens and ensure the optimum response is achieved for each individual patient. Full article
(This article belongs to the Special Issue Precision Medicine for Neuroblastoma)
Review
Drug Response Diversity: A Hidden Bacterium?
J. Pers. Med. 2021, 11(5), 345; https://doi.org/10.3390/jpm11050345 - 25 Apr 2021
Abstract
Interindividual heterogeneity in response to treatment is a real public health problem. It is a factor that can be responsible not only for ineffectiveness or fatal toxicity but also for hospitalization due to iatrogenic effects, thus increasing the cost of patient care. Several [...] Read more.
Interindividual heterogeneity in response to treatment is a real public health problem. It is a factor that can be responsible not only for ineffectiveness or fatal toxicity but also for hospitalization due to iatrogenic effects, thus increasing the cost of patient care. Several research teams have been interested in what may be at the origin of these phenomena, particularly at the genetic level and the basal activity of organs dedicated to the inactivation and elimination of drug molecules. Today, a new branch is being set up, explaining the enigmatic part that could not be explained before. Pharmacomicrobiomics attempts to investigate the interactions between bacteria, especially those in the gut, and drug response. In this review, we provide a state of the art on what this field has brought as new information and discuss the challenges that lie ahead to see the real application in clinical practice. Full article
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Review
Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back
J. Pers. Med. 2020, 10(4), 258; https://doi.org/10.3390/jpm10040258 - 28 Nov 2020
Cited by 3
Abstract
Neuromuscular disorders are a large group of rare pathologies characterised by skeletal muscle atrophy and weakness, with the common involvement of respiratory and/or cardiac muscles. These diseases lead to life-long motor deficiencies and specific organ failures, and are, in their worst-case scenarios, life [...] Read more.
Neuromuscular disorders are a large group of rare pathologies characterised by skeletal muscle atrophy and weakness, with the common involvement of respiratory and/or cardiac muscles. These diseases lead to life-long motor deficiencies and specific organ failures, and are, in their worst-case scenarios, life threatening. Amongst other causes, they can be genetically inherited through mutations in more than 500 different genes. In the last 20 years, specific pharmacological treatments have been approved for human usage. However, these “à-la-carte” therapies cover only a very small portion of the clinical needs and are often partially efficient in alleviating the symptoms of the disease, even less so in curing it. Recombinant adeno-associated virus vector-mediated gene transfer is a more general strategy that could be adapted for a large majority of these diseases and has proved very efficient in rescuing the symptoms in many neuropathological animal models. On this solid ground, several clinical trials are currently being conducted with the whole-body delivery of the therapeutic vectors. This review recapitulates the state-of-the-art tools for neuron and muscle-targeted gene therapy, and summarises the main findings of the spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD) and X-linked myotubular myopathy (XLMTM) trials. Despite promising efficacy results, serious adverse events of various severities were observed in these trials. Possible leads for second-generation products are also discussed. Full article
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Review
Advances in Genetic Characterization and Genotype–Phenotype Correlation of Duchenne and Becker Muscular Dystrophy in the Personalized Medicine Era
J. Pers. Med. 2020, 10(3), 111; https://doi.org/10.3390/jpm10030111 - 03 Sep 2020
Cited by 6
Abstract
Currently, Duchenne muscular dystrophy (DMD) and the related condition Becker muscular dystrophy (BMD) can be usually diagnosed using physical examination and genetic testing. While BMD features partially functional dystrophin protein due to in-frame mutations, DMD largely features no dystrophin production because of out-of-frame [...] Read more.
Currently, Duchenne muscular dystrophy (DMD) and the related condition Becker muscular dystrophy (BMD) can be usually diagnosed using physical examination and genetic testing. While BMD features partially functional dystrophin protein due to in-frame mutations, DMD largely features no dystrophin production because of out-of-frame mutations. However, BMD can feature a range of phenotypes from mild to borderline DMD, indicating a complex genotype–phenotype relationship. Despite two mutational hot spots in dystrophin, mutations can arise across the gene. The use of multiplex ligation amplification (MLPA) can easily assess the copy number of all exons, while next-generation sequencing (NGS) can uncover novel or confirm hard-to-detect mutations. Exon-skipping therapy, which targets specific regions of the dystrophin gene based on a patient’s mutation, is an especially prominent example of personalized medicine for DMD. To maximize the benefit of exon-skipping therapies, accurate genetic diagnosis and characterization including genotype–phenotype correlation studies are becoming increasingly important. In this article, we present the recent progress in the collection of mutational data and optimization of exon-skipping therapy for DMD/BMD. Full article
Review
Postulated Adjuvant Therapeutic Strategies for COVID-19
J. Pers. Med. 2020, 10(3), 80; https://doi.org/10.3390/jpm10030080 - 05 Aug 2020
Cited by 13
Abstract
The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, [...] Read more.
The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at <10 kDa; Imuno TF®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms. Full article
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Review
Molecular and Imaging Biomarkers in Alzheimer’s Disease: A Focus on Recent Insights
J. Pers. Med. 2020, 10(3), 61; https://doi.org/10.3390/jpm10030061 - 10 Jul 2020
Cited by 8
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and [...] Read more.
Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques. Full article
(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)
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Review
Wise Management of Ovarian Cancer: On the Cutting Edge
J. Pers. Med. 2020, 10(2), 41; https://doi.org/10.3390/jpm10020041 - 21 May 2020
Cited by 36
Abstract
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. [...] Read more.
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20–40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations. Full article
(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)
Review
Applications of Machine Learning Predictive Models in the Chronic Disease Diagnosis
J. Pers. Med. 2020, 10(2), 21; https://doi.org/10.3390/jpm10020021 - 31 Mar 2020
Cited by 27
Abstract
This paper reviews applications of machine learning (ML) predictive models in the diagnosis of chronic diseases. Chronic diseases (CDs) are responsible for a major portion of global health costs. Patients who suffer from these diseases need lifelong treatment. Nowadays, predictive models are frequently [...] Read more.
This paper reviews applications of machine learning (ML) predictive models in the diagnosis of chronic diseases. Chronic diseases (CDs) are responsible for a major portion of global health costs. Patients who suffer from these diseases need lifelong treatment. Nowadays, predictive models are frequently applied in the diagnosis and forecasting of these diseases. In this study, we reviewed the state-of-the-art approaches that encompass ML models in the primary diagnosis of CD. This analysis covers 453 papers published between 2015 and 2019, and our document search was conducted from PubMed (Medline), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) libraries. Ultimately, 22 studies were selected to present all modeling methods in a precise way that explains CD diagnosis and usage models of individual pathologies with associated strengths and limitations. Our outcomes suggest that there are no standard methods to determine the best approach in real-time clinical practice since each method has its advantages and disadvantages. Among the methods considered, support vector machines (SVM), logistic regression (LR), clustering were the most commonly used. These models are highly applicable in classification, and diagnosis of CD and are expected to become more important in medical practice in the near future. Full article
(This article belongs to the Special Issue Use of Clinical Decision Support Software within Health Care Systems)
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Review
Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges
J. Pers. Med. 2019, 9(3), 40; https://doi.org/10.3390/jpm9030040 - 07 Aug 2019
Cited by 26
Abstract
Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the [...] Read more.
Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams—including physicians, nurses, genetic counsellors, and pharmacists—will need to combine their expertise to deliver optimal pharmacogenomically-informed care. Full article
Review
Barriers and Facilitators to Genetic Testing for Familial Hypercholesterolemia in the United States: A Review
J. Pers. Med. 2019, 9(3), 32; https://doi.org/10.3390/jpm9030032 - 01 Jul 2019
Cited by 13
Abstract
Familial Hypercholesterolemia (FH) is an underdiagnosed condition in the United States (US) and globally, affecting an estimated 1/250 individuals. It is a genetic risk factor for premature cardiovascular disease and is responsible for an estimated 600,000 to 1.2 million preventable vascular events. Studies [...] Read more.
Familial Hypercholesterolemia (FH) is an underdiagnosed condition in the United States (US) and globally, affecting an estimated 1/250 individuals. It is a genetic risk factor for premature cardiovascular disease and is responsible for an estimated 600,000 to 1.2 million preventable vascular events. Studies show that FH genetic testing can identify a causal gene variant in 60 to 80% of clinically suspected FH cases. However, FH genetic testing is currently underutilized in clinical settings in the US despite clinical recommendations and evidence supporting its use. Reasons for underutilization are not well understood. We conducted a literature review in the PubMed/MEDLINE database and eight peer-reviewed journals. After filtering for and reviewing 2340 articles against our inclusion criteria, we included nine commentaries or expert opinions and eight empirical studies reported between January 2014 and March 2019 in our review. After applying the Consolidated Framework for Implementation Research (CFIR), we identified a total of 26 potential barriers and 15 potential facilitators (estimated barrier to facilitator ratio of 1.73). We further estimated ratios of potential barriers to facilitators for each CFIR domain (Characteristics of Intervention, Outer Setting, Inner Setting, Characteristics of Individuals, and Process). Findings derived from our systematic approach to the literature and calculations of estimated baseline ratios of barriers and facilitators can guide future research to understand FH genetic testing implementation in diverse clinical settings. Our systematic approach to the CFIR could also be used as a model to understand or compare barriers and facilitators to other evidence-based genetic testing processes in health care settings in the US and abroad. Full article
(This article belongs to the Collection Genomic Medicine and Policy)
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Review
Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer
J. Pers. Med. 2019, 9(1), 15; https://doi.org/10.3390/jpm9010015 - 01 Mar 2019
Cited by 14
Abstract
Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and [...] Read more.
Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and BRCA2, for the purpose of identifying high-risk individuals who would benefit from earlier screening and more sensitive methods such as magnetic resonance imaging. We also consider risk-based screening in the general population, including whether every woman should be genetically tested for high-risk genes and the potential use of polygenic risk scores. In addition to enabling early detection, the results of genetic screens of breast cancer susceptibility genes can be utilized to guide decision-making about when to elect prophylactic surgeries that reduce cancer risk and the choice of therapeutic options. Variants of uncertain significance, especially missense variants, are being identified during panel testing for hereditary breast and ovarian cancer. A finding of a variant of uncertain significance does not provide a basis for increased cancer surveillance or prophylactic procedures. Given that variant classification is often challenging, we also consider the role of multifactorial statistical analyses by large consortia and functional tests for this purpose. Full article
(This article belongs to the Special Issue Risk-stratified Cancer Screening)
Review
The Developing Story of Predictive Biomarkers in Colorectal Cancer
J. Pers. Med. 2019, 9(1), 12; https://doi.org/10.3390/jpm9010012 - 07 Feb 2019
Cited by 54
Abstract
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the [...] Read more.
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
Review
Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants
J. Pers. Med. 2019, 9(1), 7; https://doi.org/10.3390/jpm9010007 - 17 Jan 2019
Cited by 31
Abstract
Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a [...] Read more.
Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a relatively new area of research. There is a need to understand the role of pharmacogenomics in the interpatient variability of the four most commonly prescribed DOACs, namely dabigatran, rivaroxaban, apixaban, and edoxaban. We performed an extensive search of recently published research articles including clinical trials and in-vitro studies in PubMed, particularly those focusing on genetic loci, single nucleotide polymorphisms (SNPs), and DNA polymorphisms, and their effect on inter-individual variation of DOACs. Additionally, we also focused on commonly associated drug-drug interactions of DOACs. CES1 and ABCB1 SNPs are the most common documented genetic variants that contribute to alteration in peak and trough levels of dabigatran with demonstrated clinical impact. ABCB1 SNPs are implicated in alteration of plasma drug levels of rivaroxaban and apixaban. Studies conducted with factor Xa, ABCB1, SLCOB1, CYP2C9, and VKORC1 genetic variants did not reveal any significant association with plasma drug levels of edoxaban. Pharmacokinetic drug-drug interactions of dabigatran are mainly mediated by p-glycoprotein. Strong inhibitors and inducers of CYP3A4 and p-glycoprotein should be avoided in patients treated with rivaroxaban, apixaban, and edoxaban. We conclude that some of the inter-individual variability of DOACs can be attributed to alteration of genetic variants of gene loci and drug-drug interactions. Future research should be focused on exploring new genetic variants, their effect, and molecular mechanisms that contribute to alteration of plasma levels of DOACs. Full article
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Review
The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer
J. Pers. Med. 2019, 9(1), 5; https://doi.org/10.3390/jpm9010005 - 16 Jan 2019
Cited by 18
Abstract
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit [...] Read more.
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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Review
Colorectal Cancer Biomarkers in the Era of Personalized Medicine
J. Pers. Med. 2019, 9(1), 3; https://doi.org/10.3390/jpm9010003 - 14 Jan 2019
Cited by 23
Abstract
The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears [...] Read more.
The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results. Full article
Review
Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches
J. Pers. Med. 2019, 9(1), 1; https://doi.org/10.3390/jpm9010001 - 07 Jan 2019
Cited by 48
Abstract
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into [...] Read more.
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into two groups: therapies that aim to restore dystrophin expression, and those that aim to compensate for the lack of dystrophin. Therapies that restore dystrophin expression include read-through therapy, exon skipping, vector-mediated gene therapy, and cell therapy. Of these approaches, the most advanced are the read-through and exon skipping therapies. In 2014, ataluren, a drug that can promote ribosomal read-through of mRNA containing a premature stop codon, was conditionally approved in Europe. In 2016, eteplirsen, a morpholino-based chemical capable of skipping exon 51 in premature mRNA, received conditional approval in the USA. Clinical trials on vector-mediated gene therapy carrying micro- and mini- dystrophin are underway. More innovative therapeutic approaches include CRISPR/Cas9-based genome editing and stem cell-based cell therapies. Here we review the current status of therapeutic approaches for DMD, focusing on therapeutic approaches that can restore dystrophin. Full article
Review
The Role of Next-Generation Sequencing in Precision Medicine: A Review of Outcomes in Oncology
J. Pers. Med. 2018, 8(3), 30; https://doi.org/10.3390/jpm8030030 - 17 Sep 2018
Cited by 43
Abstract
Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in [...] Read more.
Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies. Full article
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Review
Ten Years’ Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics
J. Pers. Med. 2018, 8(2), 15; https://doi.org/10.3390/jpm8020015 - 17 Apr 2018
Cited by 68
Abstract
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data [...] Read more.
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities. In this review, we provide an overview of sources in addition to CYP2D6 genotype that contribute to the variability in CYP2D6-mediated drug metabolism and discuss other factors, genetic and non-genetic, that likely contribute to the observed variability in CYP2D6 enzymatic activity. Full article
(This article belongs to the Special Issue Cytochrome P450 Variation in Pharmacogenomics)
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Case Report
The Temple Grandin Genome: Comprehensive Analysis in a Scientist with High-Functioning Autism
J. Pers. Med. 2021, 11(1), 21; https://doi.org/10.3390/jpm11010021 - 29 Dec 2020
Abstract
Autism spectrum disorder (ASD) is a heterogeneous condition with a complex genetic etiology. The objective of this study is to identify the complex genetic factors that underlie the ASD phenotype and other clinical features of Professor Temple Grandin, an animal scientist and woman [...] Read more.
Autism spectrum disorder (ASD) is a heterogeneous condition with a complex genetic etiology. The objective of this study is to identify the complex genetic factors that underlie the ASD phenotype and other clinical features of Professor Temple Grandin, an animal scientist and woman with high-functioning ASD. Identifying the underlying genetic cause for ASD can impact medical management, personalize services and treatment, and uncover other medical risks that are associated with the genetic diagnosis. Prof. Grandin underwent chromosomal microarray analysis, whole exome sequencing, and whole genome sequencing, as well as a comprehensive clinical and family history intake. The raw data were analyzed in order to identify possible genotype-phenotype correlations. Genetic testing identified variants in three genes (SHANK2, ALX1, and RELN) that are candidate risk factors for ASD. We identified variants in MEFV and WNT10A, reported to be disease-associated in previous studies, which are likely to contribute to some of her additional clinical features. Moreover, candidate variants in genes encoding metabolic enzymes and transporters were identified, some of which suggest potential therapies. This case report describes the genomic findings in Prof. Grandin and it serves as an example to discuss state-of-the-art clinical diagnostics for individuals with ASD, as well as the medical, logistical, and economic hurdles that are involved in clinical genetic testing for an individual on the autism spectrum. Full article
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