Journal of Personalized Medicine

22 pages, 852 KiB

Open AccessReview

The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development

by Michal Sima, Andrea Rossnerova, Zuzana Simova and Pavel Rossner, Jr.

J. Pers. Med. 2021, 11(1), 60; https://doi.org/10.3390/jpm11010060 - 19 Jan 2021

Cited by 22 | Viewed by 4726

Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be [...] Read more.

Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer. Full article

(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)

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9 pages, 1150 KiB

Open AccessArticle

Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

by Kirsten Voorhies, Joanne E. Sordillo, Michael McGeachie, Elizabeth Ampleford, Alberta L. Wang, Jessica Lasky-Su, Kelan Tantisira, Amber Dahlin, Rachel S. Kelly, Victor E. Ortega, Sharon M. Lutz and Ann C. Wu

J. Pers. Med. 2021, 11(1), 59; https://doi.org/10.3390/jpm11010059 - 19 Jan 2021

Cited by 5 | Viewed by 3187

Abstract

An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) [...] Read more.

An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10⁻⁸. Using a suggestive significance level of 5 × 10⁻⁶, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma. Full article

(This article belongs to the Special Issue APAA: Asthma Pharmacogenetics across Ages)

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15 pages, 1793 KiB

Open AccessReview

Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review

by Yu Gyung Kim, Sang Min Lee, Sungeun Bae, Taejun Park, Hyeonjin Kim, Yujeong Jang, Keonwoo Moon, Hyungmin Kim, Kwangmin Lee, Joonyoung Park, Jin-Seok Byun and Do-Yeon Kim

J. Pers. Med. 2021, 11(1), 58; https://doi.org/10.3390/jpm11010058 - 18 Jan 2021

Cited by 14 | Viewed by 8194

Abstract

Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks, including genomic instability, cellular senescence, and mitochondrial dysfunction, have been suggested, which often lead to the numerous aging disorders. The [...] Read more.

Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks, including genomic instability, cellular senescence, and mitochondrial dysfunction, have been suggested, which often lead to the numerous aging disorders. The periodontium, a complex structure surrounding and supporting the teeth, is composed of the gingiva, periodontal ligament, cementum, and alveolar bone. Supportive and protective roles of the periodontium are very critical to sustain life, but the periodontium undergoes morphological and physiological changes with age. In this review, we summarize the current knowledge of molecular and cellular physiological changes in the periodontium, by focusing on soft tissues including gingiva and periodontal ligament. Full article

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14 pages, 1677 KiB

Open AccessFeature PaperArticle

The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients

by Dinara E. Ivanoshchuk, Elena V. Shakhtshneider, Oksana D. Rymar, Alla K. Ovsyannikova, Svetlana V. Mikhailova, Veniamin S. Fishman, Emil S. Valeev, Pavel S. Orlov and Mikhail I. Voevoda

J. Pers. Med. 2021, 11(1), 57; https://doi.org/10.3390/jpm11010057 - 18 Jan 2021

Cited by 12 | Viewed by 4017

Abstract

Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific [...] Read more.

Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A. Full article

(This article belongs to the Special Issue Basic Research in Endocrinology: A Modern Strategy for the Development and Technologies of Personalized Medicine)

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15 pages, 283 KiB

Open AccessArticle

The Need of Personalized Medicine in Coping with Stress during Infertility Treatment

by Małgorzata Nagórska, Bogdan Obrzut, Dariusz Ulman and Dorota Darmochwał-Kolarz

J. Pers. Med. 2021, 11(1), 56; https://doi.org/10.3390/jpm11010056 - 18 Jan 2021

Cited by 11 | Viewed by 3258

Abstract

The term personalized medicine was created for oncological patients, but due to its positive clinical results it is now used in many other fields of medicine, including reproductive medicine. The aim of the study was to determine the level of stress and strategies [...] Read more.

The term personalized medicine was created for oncological patients, but due to its positive clinical results it is now used in many other fields of medicine, including reproductive medicine. The aim of the study was to determine the level of stress and strategies of coping with stress in patients treated for infertility. The study—using a questionnaire developed by the authors, the Perceived Stress Scale-10 (PSS-10), and the Coping Orientation to Problems Experienced Inventory (Mini-COPE)—was conducted among 456 people from infertile couples. Conclusions: More than half of the studied patients demonstrated a high level of stress. The choice of coping strategies was related to the respondents’ gender and level of stress as well as their experience with assisted reproductive technology. Full article

(This article belongs to the Special Issue Personalized Medicine in Women's Cancer)

11 pages, 3703 KiB

Open AccessArticle

Comparison of the Diagnostic Performance of Novel Slim Biopsy Forceps with Conventional Biopsy Forceps for Biliary Stricture: A Multicenter Retrospective Study

by Eun Suk Jung, Se Woo Park, Jung Hee Kim, Jang Han Jung, Min Jae Yang and Da Hae Park

J. Pers. Med. 2021, 11(1), 55; https://doi.org/10.3390/jpm11010055 - 17 Jan 2021

Viewed by 2390

Abstract

Novel slim biopsy forceps provide some technical advantages to facilitate a more accurate diagnosis, although we are not aware of any comparative studies. Therefore, we compared tissue acquisition and diagnostic accuracy between novel slim biopsy forceps and conventional biopsy forceps in cases with [...] Read more.

Novel slim biopsy forceps provide some technical advantages to facilitate a more accurate diagnosis, although we are not aware of any comparative studies. Therefore, we compared tissue acquisition and diagnostic accuracy between novel slim biopsy forceps and conventional biopsy forceps in cases with a biliary stricture. We reviewed 341 patients who underwent endoscopic retrograde cholangiopancreatography for the histological confirmation of biliary stricture at two tertiary hospitals between 2013 and 2020. The primary endpoint was the forceps’ diagnostic accuracies. We included 276 patients who underwent biopsy using the novel forceps (n = 130) or conventional forceps (n = 146). The novel forceps provided 81.7% sensitivity, 100.0% specificity, positive-predictive value (PPV) of 100.0%, and negative-predictive value (NPV) of 57.8%, with an accuracy of 85.4% when the diagnosis by endobiliary biopsy included suspected or positive malignancy. The conventional forceps provided 61.7% sensitivity, 100.0% specificity, PPV of 100.0%, and NPV of 36.1%, with an accuracy of 68.5%. Only novel forceps use was significantly associated with an accurate diagnosis (odds ratio: 2.70, 95% confidence interval: 1.52–5.00). There were no significant inter-group differences in the procedure-related rates of adverse events. Endobiliary biopsy using novel forceps offered better diagnostic performance and more acceptable procedure-related adverse events than conventional forceps. Full article

(This article belongs to the Special Issue Personalized Medicine and Multidisciplinary Approach in Biliopancreatic Endoscopy)

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12 pages, 1244 KiB

Open AccessArticle

Single-Pulse Transcranial Magnetic Stimulation-Evoked Potential Amplitudes and Latencies in the Motor and Dorsolateral Prefrontal Cortex among Young, Older Healthy Participants, and Schizophrenia Patients

by Yoshihiro Noda, Mera S. Barr, Reza Zomorrodi, Robin F. H. Cash, Pantelis Lioumis, Robert Chen, Zafiris J. Daskalakis and Daniel M. Blumberger

J. Pers. Med. 2021, 11(1), 54; https://doi.org/10.3390/jpm11010054 - 17 Jan 2021

Cited by 21 | Viewed by 4737

Abstract

Background: The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for non-invasive investigation of cortical response and connectivity in human cortex. This study aimed to examine the amplitudes and latencies of each TMS-evoked potential (TEP) component induced by single-pulse TMS (spTMS) [...] Read more.

Background: The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for non-invasive investigation of cortical response and connectivity in human cortex. This study aimed to examine the amplitudes and latencies of each TMS-evoked potential (TEP) component induced by single-pulse TMS (spTMS) to the left motor (M1) and dorsolateral prefrontal cortex (DLPFC) among healthy young participants (YNG), older participants (OLD), and patients with schizophrenia (SCZ). Methods: We compared the spatiotemporal characteristics of TEPs induced by spTMS among the groups. Results: Compared to YNG, M1-spTMS induced lower amplitudes of N45 and P180 in OLD and a lower amplitude of P180 in SCZ, whereas the DLPFC-spTMS induced a lower N45 in OLD. Further, OLD demonstrated latency delays in P60 after M1-spTMS and in N45-P60 over the right central region after left DLPFC-spTMS, whereas SCZ demonstrated latency delays in N45-P60 over the midline and right central regions after DLPFC-spTMS. Conclusions: These findings suggest that inhibitory and excitatory mechanisms mediating TEPs may be altered in OLD and SCZ. The amplitude and latency changes of TEPs with spTMS may reflect underlying neurophysiological changes in OLD and SCZ, respectively. The spTMS administered to M1 and the DLPFC can probe cortical functions by examining TEPs. Thus, TMS-EEG can be used to study changes in cortical connectivity and signal propagation from healthy to pathological brains. Full article

(This article belongs to the Special Issue Clinical Neurophysiology, Neuroimaging, and Neuromodulation of Neuropsychiatric Disorders)

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15 pages, 735 KiB

Open AccessReview

Radiation Response in the Tumour Microenvironment: Predictive Biomarkers and Future Perspectives

by Niall M. Byrne, Prajakta Tambe and Jonathan A. Coulter

J. Pers. Med. 2021, 11(1), 53; https://doi.org/10.3390/jpm11010053 - 16 Jan 2021

Cited by 17 | Viewed by 3230

Abstract

Radiotherapy (RT) is a primary treatment modality for a number of cancers, offering potentially curative outcomes. Despite its success, tumour cells can become resistant to RT, leading to disease recurrence. Components of the tumour microenvironment (TME) likely play an integral role in managing [...] Read more.

Radiotherapy (RT) is a primary treatment modality for a number of cancers, offering potentially curative outcomes. Despite its success, tumour cells can become resistant to RT, leading to disease recurrence. Components of the tumour microenvironment (TME) likely play an integral role in managing RT success or failure including infiltrating immune cells, the tumour vasculature and stroma. Furthermore, genomic profiling of the TME could identify predictive biomarkers or gene signatures indicative of RT response. In this review, we will discuss proposed mechanisms of radioresistance within the TME, biomarkers that may predict RT outcomes, and future perspectives on radiation treatment in the era of personalised medicine. Full article

(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)

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13 pages, 476 KiB

Open AccessArticle

Changes in the Prevalence of Metabolic Syndrome and Its Components as Well as in Relevant Preventive Medication between 2006 and 2018 in the Northeast Hungarian Population

by Peter Piko, Judit Dioszegi, Janos Sandor and Roza Adany

J. Pers. Med. 2021, 11(1), 52; https://doi.org/10.3390/jpm11010052 - 16 Jan 2021

Cited by 4 | Viewed by 2194

Abstract

Metabolic syndrome (MetS) is a worldwide problem with severe health consequences. In this study, we examine the changes in the prevalence of MetS and its components in two disadvantaged counties of Northeastern Hungary. Two health examination surveys were performed in the Hungarian population [...] Read more.

Metabolic syndrome (MetS) is a worldwide problem with severe health consequences. In this study, we examine the changes in the prevalence of MetS and its components in two disadvantaged counties of Northeastern Hungary. Two health examination surveys were performed in the Hungarian population aged 20–64 years in 2006 (n = 450) and 2018 (n = 397) and the data were compared to each other. It was found that the prevalence of MetS increased significantly in the period examined (from 34.9% to 42.2%, p = 0.035) due to the increased prevalence of raised blood pressure (from 45.6% to 57.0%, p = 0.002) and raised fasting glucose concentration (13.2% vs. 24.8%, p < 0.001). The increase mainly affects the younger (20–34 years old) age group (12.1% in 2006 vs. 31.6% in 2018, p = 0.001). It is quite alarming that the prevalence of MetS and its components has increased significantly in the last decade, while the prevalence of preventive medication is unchanged (antihypertensive and antidiabetic treatments) or even significantly decreased (lipid-lowering medication). Consequently, the number of individuals untreated for hypertension and metabolic disturbances is severely increased. A targeted public health strategy is desperately needed to prevent further worsening the situation. Full article

(This article belongs to the Section Epidemiology)

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14 pages, 1038 KiB

Open AccessArticle

Cognitive and Neuropsychiatric Profiles in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

by Francesca Assogna, Claudio Liguori, Luca Cravello, Lucia Macchiusi, Claudia Belli, Fabio Placidi, Mariangela Pierantozzi, Alessandro Stefani, Bruno Mercuri, Francesca Izzi, Carlo Caltagirone, Nicola B. Mercuri, Francesco E. Pontieri, Gianfranco Spalletta and Clelia Pellicano

J. Pers. Med. 2021, 11(1), 51; https://doi.org/10.3390/jpm11010051 - 16 Jan 2021

Cited by 13 | Viewed by 3423

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson’s disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD [...] Read more.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for developing Parkinson’s disease (PD) and may represent its prodromal state. We compared neuropsychological and neuropsychiatric phenotypes of idiopathic (i) RBD, PD and healthy comparators (HC) in order to identify iRBD specific characteristics. Thirty-eight patients with iRBD, 38 PD patients with RBD (PD + RBD), 38 PD patients without RBD (PD-RBD) and 38 HC underwent a comprehensive neurological, neuropsychological and neuropsychiatric evaluation. iRBD, PD + RBD and PD-RBD performed worse than HC in short-term verbal memory, praxia, language and executive functions. iRBD had higher levels of anxiety, depression, apathy and alexithymia than HC. iRBD had higher levels of apathy than PD + RBD. Both PD groups had higher levels of anxiety and depression than HC. Surprisingly, iRBD performed better than all groups in long-term verbal memory. Patients diagnosed with iRBD are characterized by poor global cognitive performance, but better long-term memory and higher levels of depression, anxiety, alexithymia and apathy. Alexithymia and apathy in patients diagnosed with iRBD may be the expression of precocious derangement of emotional regulation, subsequently observed also in PD. Cognitive and neuropsychiatric symptoms of iRBD are early clinical manifestations of widespread neurodegeneration. Full article

(This article belongs to the Special Issue Personalized Medicine for Neurodegenerative Dementia)

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17 pages, 3957 KiB

Open AccessArticle

High Expression Level of PPARγ in CD24 Knockout Mice and Gender-Specific Metabolic Changes: A Model of Insulin-Sensitive Obesity

by Shiran Shapira, Dina Kazanov, Rachel Dankner, Sigal Fishman, Naftali Stern and Nadir Arber

J. Pers. Med. 2021, 11(1), 50; https://doi.org/10.3390/jpm11010050 - 15 Jan 2021

Cited by 5 | Viewed by 6566

Abstract

Background: The heat-stable HSA/CD24 gene encodes a protein that shows high expression levels in adipocyte precursor cells but low levels in terminally differentiated adipocytes. Its high expression in many types of human cancer suggests an association between cancer, diabetes, and obesity, which is [...] Read more.

Background: The heat-stable HSA/CD24 gene encodes a protein that shows high expression levels in adipocyte precursor cells but low levels in terminally differentiated adipocytes. Its high expression in many types of human cancer suggests an association between cancer, diabetes, and obesity, which is currently unclear. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) is a regulator of adipogenesis that plays a role in insulin sensitivity, lipid metabolism, and adipokine expression in adipocytes. Aim: To assess gender-dependent changes in CD24 KO and its association with PPARγ expression. Experimental approach: WT and CD24 KO mice were monitored from birth up to 12 months, and various physiological and molecular characteristics were analysed. Mean body weight and adipose mass were higher in KO mice than in WT mice. Male, but not female, KO mice showed increased insulin sensitivity, glucose uptake, adipocyte size, and PPARγ expression than WT mice. In addition, enteric bacterial populations, assessed through high-throughput sequencing of stool 16S rRNA genes, were significantly different between male KO and WT mice. Conclusions: CD24 may negatively regulate PPARγ expression in male mice. Furthermore, the association between the CD24 and insulin sensitivity suggests a possible mechanism for diabetes as a cancer risk factor. Finally, CD24 KO male mice may serve as a model of obesity and insulin hyper-sensitivity. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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11 pages, 1406 KiB

Open AccessArticle

Genomic Screening Identifies Individuals at High Risk for Hereditary Transthyretin Amyloidosis

by Emily R. Soper, Sabrina A. Suckiel, Giovanna T. Braganza, Amy R. Kontorovich, Eimear E. Kenny and Noura S. Abul-Husn

J. Pers. Med. 2021, 11(1), 49; https://doi.org/10.3390/jpm11010049 - 15 Jan 2021

Cited by 10 | Viewed by 26558

Abstract

The TTR V142I variant associated with hereditary transthyretin amyloidosis (hATTR) is present in up to 4% of African American (AA) and 1% of Hispanic/Latinx (HL) individuals and increases risk for heart failure. Delayed and missed diagnoses could potentiate health disparities in these populations. [...] Read more.

The TTR V142I variant associated with hereditary transthyretin amyloidosis (hATTR) is present in up to 4% of African American (AA) and 1% of Hispanic/Latinx (HL) individuals and increases risk for heart failure. Delayed and missed diagnoses could potentiate health disparities in these populations. We evaluated whether population-based genomic screening could effectively identify individuals at risk for hATTR and prompt initiation of risk management. We identified participants of the BioMe Biobank in New York City who received TTR V142I results through a pilot genomic screening program. We performed a retrospective medical record review to evaluate for the presence hATTR-related systemic features, uptake of recommended follow-up, and short-term outcomes. Thirty-two AA (N = 17) and HL (N = 15) individuals received a TTR V142I result (median age 57, 81% female). None had a previous diagnosis of hATTR. Eighteen (56%) had hATTR-related systemic features, including 4 (13%) with heart failure, 10 (31%) with carpal tunnel syndrome, and 10 (31%) with spinal stenosis. Eighteen (56%) pursued follow-up with a cardiologist within 8 months. One person received a diagnosis of hATTR. Thus, we found that the majority of V142I-positive individuals had hATTR-related systemic features at the time of result disclosure, including well-described red flags. Genomic screening can help identify hATTR risk and guide management early on, avoiding potential delays in diagnosis and treatment. Full article

(This article belongs to the Special Issue Personalized Medicine for Cardiovascular Disease)

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11 pages, 2603 KiB

Open AccessArticle

Risk Reclassification of Patients with Endometrial Cancer Based on Tumor Molecular Profiling: First Real World Data

by Felicitas Oberndorfer, Sarah Moling, Leonie Annika Hagelkruys, Christoph Grimm, Stephan Polterauer, Alina Sturdza, Stefanie Aust, Alexander Reinthaller, Leonhard Müllauer and Richard Schwameis

J. Pers. Med. 2021, 11(1), 48; https://doi.org/10.3390/jpm11010048 - 15 Jan 2021

Cited by 15 | Viewed by 3938

Abstract

Recently, guidelines for endometrial cancer (EC) were released that guide treatment decisions according to the tumors’ molecular profiles. To date, no real-world data regarding the clinical feasibility of molecular profiling have been released. This retrospective, monocentric study investigated the clinical feasibility of molecular [...] Read more.

Recently, guidelines for endometrial cancer (EC) were released that guide treatment decisions according to the tumors’ molecular profiles. To date, no real-world data regarding the clinical feasibility of molecular profiling have been released. This retrospective, monocentric study investigated the clinical feasibility of molecular profiling and its potential impact on treatment decisions. Tumor specimens underwent molecular profiling (testing for genetic alterations, (immune-)histological examination of lymphovascular space invasion (LVSI), and L1CAM) as part of the clinical routine and were classified according to the European Society for Medical Oncology (ESMO) classification system and to an integrated molecular risk stratification. Shifts between risk groups and potential treatment alterations are described. A total of 60 cases were included, of which twelve were excluded (20%), and eight of the remaining 48 were not characterized (drop-out rate of 16.7%). Molecular profiling revealed 4, 6, 25, and 5 patients with DNA polymerase-epsilon mutation, microsatellite instability, no specific molecular profile, and TP53 mutation, respectively. Three patients had substantial LVSI, and four patients showed high L1CAM expression. Molecular profiling took a median of 18.5 days. Substantial shifts occurred between the classification systems: four patients were upstaged, and 19 patients were downstaged. Molecular profiling of EC specimens is feasible in a daily routine, and new risk classification systems will change treatment decisions substantially. Full article

(This article belongs to the Special Issue Molecular Pathology of Cancer: The Past, the Present, and the Future)

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18 pages, 2976 KiB

Open AccessArticle

Matching Clinical Diagnosis and Amyloid Biomarkers in Alzheimer’s Disease and Frontotemporal Dementia

by Giulia Giacomucci, Salvatore Mazzeo, Silvia Bagnoli, Matteo Casini, Sonia Padiglioni, Cristina Polito, Valentina Berti, Juri Balestrini, Camilla Ferrari, Gemma Lombardi, Assunta Ingannato, Sandro Sorbi, Benedetta Nacmias and Valentina Bessi

J. Pers. Med. 2021, 11(1), 47; https://doi.org/10.3390/jpm11010047 - 14 Jan 2021

Cited by 9 | Viewed by 3504

Abstract

Background: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer’s disease [...] Read more.

Background: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD); to compare concordance between biomarkers; and to provide an indication of their use and interpretation. Methods: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. Results: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF Aβ_1–42 but not Aβ_42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative Aβ biomarkers. Conclusions: CSF Aβ_42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including Aβ_42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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14 pages, 3965 KiB

Open AccessArticle

A Genotype-Phenotype Correlation Study of Exon Skip-Equivalent In-Frame Deletions and Exon Skip-Amenable Out-of-Frame Deletions across the DMD Gene to Simulate the Effects of Exon-Skipping Therapies: A Meta-Analysis

by Saeed Anwar, Merry He, Kenji Rowel Q. Lim, Rika Maruyama and Toshifumi Yokota

J. Pers. Med. 2021, 11(1), 46; https://doi.org/10.3390/jpm11010046 - 14 Jan 2021

Cited by 10 | Viewed by 4612

Abstract

Dystrophinopathies are caused by mutations in the DMD gene. Out-of-frame deletions represent most mutational events in severe Duchenne muscular dystrophy (DMD), while in-frame deletions typically lead to milder Becker muscular dystrophy (BMD). Antisense oligonucleotide-mediated exon skipping converts an out-of-frame transcript to an in-frame [...] Read more.

Dystrophinopathies are caused by mutations in the DMD gene. Out-of-frame deletions represent most mutational events in severe Duchenne muscular dystrophy (DMD), while in-frame deletions typically lead to milder Becker muscular dystrophy (BMD). Antisense oligonucleotide-mediated exon skipping converts an out-of-frame transcript to an in-frame one, inducing a truncated but partially functional dystrophin protein. The reading frame rule, however, has many exceptions. We thus sought to simulate clinical outcomes of exon-skipping therapies for DMD exons from clinical data of exon skip-equivalent in-frame deletions, in which the expressed quasi-dystrophins are comparable to those resulting from exon-skipping therapies. We identified a total of 1298 unique patients with exon skip-equivalent mutations in patient registries and the existing literature. We classified them into skip-equivalent deletions of each exon and statistically compared the ratio of DMD/BMD and asymptomatic individuals across the DMD gene. Our analysis identified that five exons are associated with significantly milder phenotypes than all other exons when corresponding exon skip-equivalent in-frame deletion mutations occur. Most exon skip-equivalent in-frame deletions were associated with a significantly milder phenotype compared to corresponding exon skip-amenable out-of-frame mutations. This study indicates the importance of genotype-phenotype correlation studies in the rational design of exon-skipping therapies. Full article

(This article belongs to the Special Issue Understanding Neuromuscular Health and Disease: Advances in Genetics, Omics, and Molecular Function)

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10 pages, 875 KiB

Open AccessArticle

The Potential Benefit of Expedited Development and Approval Programs in Precision Medicine

by Ariel Kantor and Susanne B. Haga

J. Pers. Med. 2021, 11(1), 45; https://doi.org/10.3390/jpm11010045 - 14 Jan 2021

Cited by 7 | Viewed by 4176

Abstract

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued [...] Read more.

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued growth of precision medicine drugs and devices. To facilitate the development and approval process of drugs for serious unmet needs, four expedited approval programs have been developed in the US: priority review, accelerated approval, fast track, and breakthrough therapy programs. Methods: To determine if expedited approval programs are fulfilling the intended goals, we reviewed drug approvals by the US Food and Drug Administration (FDA) between 2011 and 2017 for new molecular entities (NMEs). Results: From 2011 through 2017, the FDA approved 250 NMEs, ranging from 27 approvals in 2013 to 46 in 2017. The NME approvals spanned 22 different disease classes; almost one-third of all NMEs were for oncology treatments. Conclusions: As these pathways are utilized more, additional legislative changes may be needed to re-align incentives to promote continued development of innovative drugs for serious unmet needs in a safe, efficacious, and affordable manner. Full article

(This article belongs to the Special Issue Personalized Medicine in Clinical Practice)

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12 pages, 1065 KiB

Open AccessArticle

Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis

by Helen R. Gosselt, Maxime M. A. Verhoeven, Maja Bulatović-Ćalasan, Paco M. Welsing, Maurits C. F. J. de Rotte, Johanna M. W. Hazes, Floris P. J. G. Lafeber, Mark Hoogendoorn and Robert de Jonge

J. Pers. Med. 2021, 11(1), 44; https://doi.org/10.3390/jpm11010044 - 14 Jan 2021

Cited by 24 | Viewed by 4647

Abstract

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model [...] Read more.

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the “treatment in the Rotterdam Early Arthritis CoHort” (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68–0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67–0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61–0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression’s sensitivity significantly dropped from 83% to 69% (p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response. Full article

(This article belongs to the Special Issue The Interface between Human Physiology and Medical Device Development)

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8 pages, 1100 KiB

Open AccessReview

An Innovative Personalised Management Program for Older Adults with Parkinson’s Disease: New Concepts and Future Directions

by Piyush Varma, Lakshanaa Narayan, Jane Alty, Virginia Painter and Chandrasekhara Padmakumar

J. Pers. Med. 2021, 11(1), 43; https://doi.org/10.3390/jpm11010043 - 14 Jan 2021

Cited by 6 | Viewed by 3859

Abstract

Introduction: Parkinson’s disease is a heterogeneous clinical syndrome. Parkinson’s disease in older persons presents with a diverse array of clinical manifestations leading to unique care needs. This raises the need for the healthcare community to proactively address the care needs of older persons [...] Read more.

Introduction: Parkinson’s disease is a heterogeneous clinical syndrome. Parkinson’s disease in older persons presents with a diverse array of clinical manifestations leading to unique care needs. This raises the need for the healthcare community to proactively address the care needs of older persons with Parkinson’s disease. Though it is tempting to categorise different phenotypes of Parkinson’s disease, a strong evidence based for the same is lacking. There is considerable literature describing the varying clinical manifestations in old age. This article aims to review the literature looking for strategies in personalising the management of an older person with Parkinson’s disease. Full article

(This article belongs to the Special Issue Personalized Medicine for Parkinson's Disease: New Concepts and Future of Individualized Management)

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25 pages, 1990 KiB

Open AccessReview

Laboratory-Based Resources for COVID-19 Diagnostics: Traditional Tools and Novel Technologies. A Perspective of Personalized Medicine

by Boris G. Andryukov, Natalya N. Besednova, Tatyana A. Kuznetsova and Ludmila N. Fedyanina

J. Pers. Med. 2021, 11(1), 42; https://doi.org/10.3390/jpm11010042 - 13 Jan 2021

Cited by 9 | Viewed by 5274

Abstract

The coronavirus infection 2019 (COVID-19) pandemic, caused by the highly contagious SARS-CoV-2 virus, has provoked a global healthcare and economic crisis. The control over the spread of the disease requires an efficient and scalable laboratory-based strategy for testing the population based on multiple [...] Read more.

The coronavirus infection 2019 (COVID-19) pandemic, caused by the highly contagious SARS-CoV-2 virus, has provoked a global healthcare and economic crisis. The control over the spread of the disease requires an efficient and scalable laboratory-based strategy for testing the population based on multiple platforms to provide rapid and accurate diagnosis. With the onset of the pandemic, the reverse transcription polymerase chain reaction (RT-PCR) method has become a standard diagnostic tool, which has received wide clinical use. In large-scale and repeated examinations, these tests can identify infected patients with COVID-19, with their accuracy, however, dependent on many factors, while the entire process takes up to 6–8 h. Here we also describe a number of serological systems for detecting antibodies against SARS-CoV-2. These are used to assess the level of population immunity in various categories of people, as well as for retrospective diagnosis of asymptomatic and mild COVID-19 in patients. However, the widespread use of traditional diagnostic tools in the context of the rapid spread of COVID-19 is hampered by a number of limitations. Therefore, the sharp increase in the number of patients with COVID-19 necessitates creation of new rapid, inexpensive, sensitive, and specific tests. In this regard, we focus on new laboratory technologies such as loop mediated isothermal amplification (LAMP) and lateral flow immunoassay (LFIA), which have proven to work well in the COVID-19 diagnostics and can become a worthy alternative to traditional laboratory-based diagnostics resources. To cope with the COVID-19 pandemic, the healthcare system requires a combination of various types of laboratory diagnostic testing techniques, whodse sensitivity and specificity increases with the progress in the SARS-CoV-2 research. The testing strategy should be designed in such a way to provide, depending on the timing of examination and the severity of the infection in patients, large-scale and repeated examinations based on the principle: screening–monitoring–control. The search and development of new methods for rapid diagnostics of COVID-19 in laboratory, based on new analytical platforms, is still a highly important and urgent healthcare issue. In the final part of the review, special emphasis is made on the relevance of the concept of personalized medicine to combat the COVID-19 pandemic in the light of the recent studies carried out to identify the causes of variation in individual susceptibility to SARS-CoV-2 and increase the efficiency and cost-effectiveness of treatment. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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24 pages, 1163 KiB

Open AccessReview

Paving the Way toward Personalized Medicine: Current Advances and Challenges in Multi-OMICS Approach in Autism Spectrum Disorder for Biomarkers Discovery and Patient Stratification

by Areej G. Mesleh, Sara A. Abdulla and Omar El-Agnaf

J. Pers. Med. 2021, 11(1), 41; https://doi.org/10.3390/jpm11010041 - 13 Jan 2021

Cited by 27 | Viewed by 6212

Abstract

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by impairments in two main areas: social/communication skills and repetitive behavioral patterns. The prevalence of ASD has increased in the past two decades, however, it is not known whether the evident rise in [...] Read more.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by impairments in two main areas: social/communication skills and repetitive behavioral patterns. The prevalence of ASD has increased in the past two decades, however, it is not known whether the evident rise in ASD prevalence is due to changes in diagnostic criteria or an actual increase in ASD cases. Due to the complexity and heterogeneity of ASD, symptoms vary in severity and may be accompanied by comorbidities such as epilepsy, attention deficit hyperactivity disorder (ADHD), and gastrointestinal (GI) disorders. Identifying biomarkers of ASD is not only crucial to understanding the biological characteristics of the disorder, but also as a detection tool for its early screening. Hence, this review gives an insight into the main areas of ASD biomarker research that show promising findings. Finally, it covers success stories that highlight the importance of precision medicine and the current challenges in ASD biomarker discovery studies. Full article

(This article belongs to the Special Issue A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder)

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11 pages, 917 KiB

Open AccessArticle

Increased Heschl’s Gyrus Duplication in Schizophrenia Spectrum Disorders: A Cross-Sectional MRI Study

by Tsutomu Takahashi, Daiki Sasabayashi, Yoichiro Takayanagi, Atsushi Furuichi, Mikio Kido, Tien Viet Pham, Haruko Kobayashi, Kyo Noguchi and Michio Suzuki

J. Pers. Med. 2021, 11(1), 40; https://doi.org/10.3390/jpm11010040 - 12 Jan 2021

Cited by 7 | Viewed by 2676

Abstract

Duplicated Heschl’s gyrus (HG) is prevalent in patients with schizophrenia and may reflect early neurodevelopmental anomalies. However, it currently remains unclear whether patients with schizotypal disorder, a prototypic disorder within the schizophrenia spectrum, exhibit a similar HG gyrification pattern. In this magnetic resonance [...] Read more.

Duplicated Heschl’s gyrus (HG) is prevalent in patients with schizophrenia and may reflect early neurodevelopmental anomalies. However, it currently remains unclear whether patients with schizotypal disorder, a prototypic disorder within the schizophrenia spectrum, exhibit a similar HG gyrification pattern. In this magnetic resonance imaging study, HG gyrification patterns were examined in 47 patients with schizotypal disorder, 111 with schizophrenia, and 88 age- and sex-matched healthy subjects. HG gyrification patterns were classified as single, common stem duplication (CSD), or complete posterior duplication (CPD). The prevalence of the duplicated HG patterns (CSD or CPD) bilaterally was higher in the schizophrenia and schizotypal groups than in healthy controls, whereas no significant difference was observed between the schizophrenia and schizotypal groups. Schizophrenia patients with the right CPD pattern had less severe positive symptoms, whereas the right single HG pattern was associated with higher doses of antipsychotic medication in schizotypal patients. The present study demonstrated shared HG gyrification patterns in schizophrenia spectrum disorders, which may reflect a common biological vulnerability factor. HG patterns may also be associated with susceptibility to psychopathology. Full article

(This article belongs to the Special Issue Psychoneurobiology Research and Personalized Treatment of Schizophrenia)

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16 pages, 1095 KiB

Open AccessArticle

Association Analysis in Young and Middle-Aged Mothers—Relation between Expression of Cardiovascular Disease Associated MicroRNAs and Abnormal Clinical Findings

by Ilona Hromadnikova, Katerina Kotlabova and Ladislav Krofta

J. Pers. Med. 2021, 11(1), 39; https://doi.org/10.3390/jpm11010039 - 11 Jan 2021

Cited by 8 | Viewed by 2963

Abstract

The principal goal of the study was to map common postpartal alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases induced by most frequently occurring pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes, or [...] Read more.

The principal goal of the study was to map common postpartal alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases induced by most frequently occurring pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes, or spontaneous preterm birth). In addition, the association analyses between individual abnormal clinical findings (overweight/obesity, central obesity, hypertension, on blood pressure treatment, history of infertility treatment, actual hormonal contraceptive use, the presence of trombophilic gene mutations, actual smoking status, increased serum levels of total cholesterol, HDL (high density lipoprotein) cholesterol, LDL (low density lipoprotein) cholesterol, triglycerides, lipoprotein A, CRP (C-reactive protein), and uric acid, and increased plasma levels of homocysteine) and microRNA expression levels were performed in mothers with respect/regardless to previous course of gestation. The prior exposure to gestational hypertension, preeclampsia, fetal growth restriction, gestational diabetes mellitus, preterm prelabor rupture of membranes, or spontaneous preterm birth caused that a significant proportion of mothers (52.42% at 90.0% specificity) had substantially altered microRNA expression profile, which might originate lifelong cardiovascular risk. 26 out of 29 tested microRNAs were up-regulated in mothers with a history of such complicated pregnancies. MicroRNA expression profiles were also able to differentiate between mothers with normal and abnormal clinical findings (BMI (body mass index), waist circumference, systolic blood pressure, on blood pressure treatment, history of infertility treatment, and the presence of trombophilic gene mutations) irrespective of previous course of gestation. The treatment of hypertension even intensified upregulation of some microRNAs (miR-24-3p, and miR-342-3p) already present in women after complicated pregnancies. Newly, the presence of overweight/obesity (miR-155-5p), systolic hypertension (miR-92a-3p, and miR-210-3p), treatment for infertility (miR-155-5p), and treatment for hypertension (miR-210-3p) induced upregulation of several microRNAs. In general, mothers after complicated pregnancies are at increased risk of development of cardiovascular complications. Especially those mothers indicated to have postpartally altered microRNA expression profiles might be considered as a highly risky group that would benefit from dispensarization and implementation of primary prevention strategies. Full article

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16 pages, 2738 KiB

Open AccessFeature PaperArticle

Real-Time Implementation of EEG Oscillatory Phase-Informed Visual Stimulation Using a Least Mean Square-Based AR Model

by Aqsa Shakeel, Takayuki Onojima, Toshihisa Tanaka and Keiichi Kitajo

J. Pers. Med. 2021, 11(1), 38; https://doi.org/10.3390/jpm11010038 - 11 Jan 2021

Cited by 6 | Viewed by 3275

Abstract

It is a technically challenging problem to assess the instantaneous brain state using electroencephalography (EEG) in a real-time closed-loop setup because the prediction of future signals is required to define the current state, such as the instantaneous phase and amplitude. To accomplish this [...] Read more.

It is a technically challenging problem to assess the instantaneous brain state using electroencephalography (EEG) in a real-time closed-loop setup because the prediction of future signals is required to define the current state, such as the instantaneous phase and amplitude. To accomplish this in real-time, a conventional Yule–Walker (YW)-based autoregressive (AR) model has been used. However, the brain state-dependent real-time implementation of a closed-loop system employing an adaptive method has not yet been explored. Our primary purpose was to investigate whether time-series forward prediction using an adaptive least mean square (LMS)-based AR model would be implementable in a real-time closed-loop system or not. EEG state-dependent triggers synchronized with the EEG peaks and troughs of alpha oscillations in both an open-eyes resting state and a visual task. For the resting and visual conditions, statistical results showed that the proposed method succeeded in giving triggers at a specific phase of EEG oscillations for all participants. These individual results showed that the LMS-based AR model was successfully implemented in a real-time closed-loop system targeting specific phases of alpha oscillations and can be used as an adaptive alternative to the conventional and machine-learning approaches with a low computational load. Full article

(This article belongs to the Special Issue Clinical Neurophysiology, Neuroimaging, and Neuromodulation of Neuropsychiatric Disorders)

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11 pages, 310 KiB

Open AccessReview

Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review

by Johanna Raymond, Laurent Imbert, Thibault Cousin, Thomas Duflot, Rémi Varin, Julien Wils and Fabien Lamoureux

J. Pers. Med. 2021, 11(1), 37; https://doi.org/10.3390/jpm11010037 - 11 Jan 2021

Cited by 70 | Viewed by 7667

Abstract

Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments [...] Read more.

Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed. Full article

(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)

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18 pages, 982 KiB

Open AccessFeature PaperArticle

A Predictive Model and Risk Factors for Case Fatality of COVID-19

by Melchor Álvarez-Mon, Miguel A. Ortega, Óscar Gasulla, Jordi Fortuny-Profitós, Ferran A. Mazaira-Font, Pablo Saurina, Jorge Monserrat, María N. Plana, Daniel Troncoso, José Sanz Moreno, Benjamin Muñoz, Alberto Arranz, Jose F. Varona, Alejandro Lopez-Escobar and Angel Asúnsolo-del Barco

J. Pers. Med. 2021, 11(1), 36; https://doi.org/10.3390/jpm11010036 - 8 Jan 2021

Cited by 18 | Viewed by 6040

Abstract

This study aimed to create an individualized analysis model of the risk of intensive care unit (ICU) admission or death for coronavirus disease 2019 (COVID-19) patients as a tool for the rapid clinical management of hospitalized patients in order to achieve a resilience [...] Read more.

This study aimed to create an individualized analysis model of the risk of intensive care unit (ICU) admission or death for coronavirus disease 2019 (COVID-19) patients as a tool for the rapid clinical management of hospitalized patients in order to achieve a resilience of medical resources. This is an observational, analytical, retrospective cohort study with longitudinal follow-up. Data were collected from the medical records of 3489 patients diagnosed with COVID-19 using RT-qPCR in the period of highest community transmission recorded in Europe to date: February–June 2020. The study was carried out in in two health areas of hospital care in the Madrid region: the central area of the Madrid capital (Hospitales de Madrid del Grupo HM Hospitales (CH-HM), n = 1931) and the metropolitan area of Madrid (Hospital Universitario Príncipe de Asturias (MH-HUPA) n = 1558). By using a regression model, we observed how the different patient variables had unequal importance. Among all the analyzed variables, basal oxygen saturation was found to have the highest relative importance with a value of 20.3%, followed by age (17.7%), lymphocyte/leukocyte ratio (14.4%), CRP value (12.5%), comorbidities (12.5%), and leukocyte count (8.9%). Three levels of risk of ICU/death were established: low-risk level (<5%), medium-risk level (5–20%), and high-risk level (>20%). At the high-risk level, 13% needed ICU admission, 29% died, and 37% had an ICU–death outcome. This predictive model allowed us to individualize the risk for worse outcome for hospitalized patients affected by COVID-19. Full article

(This article belongs to the Special Issue COVID-19 Related Complications)

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19 pages, 5305 KiB

Open AccessArticle

Altered Gut Microbiota in Irritable Bowel Syndrome and Its Association with Food Components

by Zahra A. Barandouzi, Joochul Lee, Kendra Maas, Angela R. Starkweather and Xiaomei S. Cong

J. Pers. Med. 2021, 11(1), 35; https://doi.org/10.3390/jpm11010035 - 8 Jan 2021

Cited by 34 | Viewed by 7415

Abstract

The interplay between diet and gut microbiota has gained interest as a potential contributor in pathophysiology of irritable bowel syndrome (IBS). The purpose of this study was to compare food components and gut microbiota patterns between IBS patients and healthy controls (HC) as [...] Read more.

The interplay between diet and gut microbiota has gained interest as a potential contributor in pathophysiology of irritable bowel syndrome (IBS). The purpose of this study was to compare food components and gut microbiota patterns between IBS patients and healthy controls (HC) as well as to explore the associations of food components and microbiota profiles. A cross-sectional study was conducted with 80 young adults with IBS and 21 HC recruited. The food frequency questionnaire was used to measure food components. Fecal samples were collected and profiled by 16S rRNA Illumina sequencing. Food components were similar in both IBS and HC groups, except in caffeine consumption. Higher alpha diversity indices and altered gut microbiota were observed in IBS compared to the HC. A negative correlation existed between total observed species and caffeine intake in the HC, and a positive correlation between alpha diversity indices and dietary fiber in the IBS group. Higher alpha diversity and gut microbiota alteration were found in IBS people who consumed caffeine more than 400 mg/d. Moreover, high microbial diversity and alteration of gut microbiota composition in IBS people with high caffeine consumption may be a clue toward the effects of caffeine on the gut microbiome pattern, which warrants further study. Full article

(This article belongs to the Special Issue Targeting the Microbiome for Disease Diagnosis and Therapy: New Frontiers for Personalized Medicine)

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10 pages, 1291 KiB

Open AccessArticle

A Whole-Genome Sequencing Association Study of Low Bone Mineral Density Identifies New Susceptibility Loci in the Phase I Qatar Biobank Cohort

by Nadin Younes, Najeeb Syed, Santosh K. Yadav, Mohammad Haris, Atiyeh M. Abdallah and Marawan Abu-Madi

J. Pers. Med. 2021, 11(1), 34; https://doi.org/10.3390/jpm11010034 - 7 Jan 2021

Cited by 11 | Viewed by 2885

Abstract

Bone density disorders are characterized by a reduction in bone mass density and strength, which lead to an increase in the susceptibility to sudden and unexpected fractures. Despite the serious consequences of low bone mineral density (BMD) and its significant impact on human [...] Read more.

Bone density disorders are characterized by a reduction in bone mass density and strength, which lead to an increase in the susceptibility to sudden and unexpected fractures. Despite the serious consequences of low bone mineral density (BMD) and its significant impact on human health, most affected individuals may not know that they have the disease because it is asymptomatic. Therefore, understanding the genetic basis of low BMD and osteoporosis is essential to fully elucidate its pathobiology and devise preventative or therapeutic approaches. Here we sequenced the whole genomes of 3000 individuals from the Qatar Biobank and conducted genome-wide association analyses to identify genetic risk factors associated with low BMD in the Qatari population. Fifteen variants were significantly associated with total body BMD (p < 5 × 10⁻⁸). Of these, five variants had previously been reported by and were directionally consistent with previous genome-wide association study data. Ten variants were new: six intronic variants located at six gene loci (MALAT1/TALAM1, FASLG, LSAMP, SAG, FAM189A2, and LOC101928063) and four intergenic variants. This first such study in Qatar provides a new insight into the genetic architecture of low BMD in the Qatari population. Nevertheless, more studies are needed to validate these findings and to elucidate the functional effects of these variants on low BMD and bone fracture susceptibility. Full article

(This article belongs to the Section Omics/Informatics)

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11 pages, 2034 KiB

Open AccessArticle

Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

by Nayoung Han, Jung Mi Oh and In-Wha Kim

J. Pers. Med. 2021, 11(1), 33; https://doi.org/10.3390/jpm11010033 - 7 Jan 2021

Cited by 4 | Viewed by 2906

Abstract

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and [...] Read more.

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study. Full article

(This article belongs to the Special Issue Pharmacogenomics: From Basic Research to Clinical Implementation)

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22 pages, 2842 KiB

Open AccessReview

How Do Machines Learn? Artificial Intelligence as a New Era in Medicine

by Oliwia Koteluk, Adrian Wartecki, Sylwia Mazurek, Iga Kołodziejczak and Andrzej Mackiewicz

J. Pers. Med. 2021, 11(1), 32; https://doi.org/10.3390/jpm11010032 - 7 Jan 2021

Cited by 64 | Viewed by 12590

Abstract

With an increased number of medical data generated every day, there is a strong need for reliable, automated evaluation tools. With high hopes and expectations, machine learning has the potential to revolutionize many fields of medicine, helping to make faster and more correct [...] Read more.

With an increased number of medical data generated every day, there is a strong need for reliable, automated evaluation tools. With high hopes and expectations, machine learning has the potential to revolutionize many fields of medicine, helping to make faster and more correct decisions and improving current standards of treatment. Today, machines can analyze, learn, communicate, and understand processed data and are used in health care increasingly. This review explains different models and the general process of machine learning and training the algorithms. Furthermore, it summarizes the most useful machine learning applications and tools in different branches of medicine and health care (radiology, pathology, pharmacology, infectious diseases, personalized decision making, and many others). The review also addresses the futuristic prospects and threats of applying artificial intelligence as an advanced, automated medicine tool. Full article

(This article belongs to the Special Issue The Interface between Human Physiology and Medical Device Development)

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17 pages, 3522 KiB

Open AccessArticle

miR-210 and miR-152 as Biomarkers by Liquid Biopsy in Invasive Ductal Carcinoma

by Beatriz C. Lopes, Cristine Z. Braga, Fabrício V. Ventura, Jéssica G. de Oliveira, Edson M. Kato-Junior, Newton A. Bordin-Junior and Debora A. P. C. Zuccari

J. Pers. Med. 2021, 11(1), 31; https://doi.org/10.3390/jpm11010031 - 6 Jan 2021

Cited by 7 | Viewed by 3786

Abstract

Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of [...] Read more.

Detecting circulating microRNAs (miRNAs; miRs) by means of liquid biopsy is an important tool for the early diagnosis and prognosis of breast cancer (BC). We aimed to identify and validate miR-210 and miR-152 as non-invasive circulating biomarkers, for the diagnosis and staging of BC patients, confirming their involvement in tumor angiogenesis. Methods: RT-qPCR was performed and MiRNA expression analysis was obtained from plasma and fragments of BC and benign breast condition (BBC) women patients, plus healthy subjects. Additionally, the immunohistochemistry technique was carried out to analyze the expression of target proteins. Results: Tumor fragments showed increased expression of oncomiR-210 and decreased expression of miR-152 tumoral suppressor. Both miRNAs were increased in plasma samples from BC patients. The receiver operating characteristic (ROC) curve analysis revealed that only the expression of oncomiR-210 in tissue samples and only the expression of the miR-152 suppressor in plasma have the appropriate sensitivity and specificity for use as differential biomarkers between early/intermediate and advanced stages of BC patients. In addition, there was an increase in the expression of hypoxia-inducible factor 1-alpha (HIF-1α), insulin-like growth factor 1 receptor (IGF-1R), and vascular endothelial growth factor (VEGF) in BC patients. On the contrary, a decrease in Von Hippel–Lindau (VHL) protein expression was observed. Conclusions: This study showed that increased levels of miR-210 and decreased levels of miR152, in addition to the expressions of their target proteins, could indicate, respectively, the oncogenic and tumor suppressive role of these miRNAs in fragments. Both miRNAs are potential diagnostic biomarkers for BC by liquid biopsy. In addition, miR-152 proved to be a promising biomarker for disease staging. Full article

(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)

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