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Volume 11
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J. Pers. Med., Volume 11, Issue 3 (March 2021) – 80 articles

Cover Story (view full-size image): Ideal cardiovascular health is determined by a composite of health factors (weight, blood pressure, blood sugar, and blood cholesterol) and health behaviors (avoiding tobacco, healthy diet, exercise). Digital health devices, including activity and step trackers, scales, and other devices, have become mainstream and are capable of measuring many of the health factors and behaviors that comprise ideal cardiovascular health. The aim of the current study was to compare participant self-reported data with objective weight and activity data recorded by digital health devices. The finding that incorporated objective digital health device data into an assessment of ideal cardiovascular health impacts the overall health score has implications for future studies of cardiovascular health and disease. View this paper
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11 pages, 1594 KiB  
Article
Gut Microbiota and Non-Alcoholic Fatty Liver Disease Severity in Type 2 Diabetes Patients
by Hui-Ju Tsai, Yi-Chun Tsai, Wei-Wen Hung, Wei-Chun Hung, Chen-Chia Chang and Chia-Yen Dai
J. Pers. Med. 2021, 11(3), 238; https://doi.org/10.3390/jpm11030238 - 23 Mar 2021
Cited by 14 | Viewed by 2487
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) remains an important health issue worldwide. The increasing prevalence of NAFLD is linked to type 2 diabetes (T2D). The gut microbiota is associated with the development of NAFLD and T2D. However, the relationship between gut microbiota and [...] Read more.
Introduction: Non-alcoholic fatty liver disease (NAFLD) remains an important health issue worldwide. The increasing prevalence of NAFLD is linked to type 2 diabetes (T2D). The gut microbiota is associated with the development of NAFLD and T2D. However, the relationship between gut microbiota and NAFLD severity has remained unclear in T2D patients. The aim of this study was to evaluate the relationship of gut microbiota with the severity of NAFLD in T2D patients. Methods: This cross-sectional study used transient elastography (FibroScan) to evaluate the severity of hepatic steatosis. We utilized qPCR to measure the abundance of Bacteroidetes, Firmicutes, Faecalibacterium prausnitzii, Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. Results: Of 163 T2D patients, 83 with moderate to severe NAFLD had higher abundance of bacteria of the phylum Firmicutes with respect to 80 patients without NAFLD or with mild NAFLD. High abundance of the phylum Firmicutes increased the severity of NAFLD in T2D patients. A positive correlation between NAFLD severity and the phylum Firmicutes was found in T2D male patients with body mass index ≥24 kg/m2 and glycated hemoglobin <7.5%. Conclusion: Enrichment of the fecal microbiota with the phylum Firmicutes is significantly and positively associated with NAFLD severity in T2D patients. The gut microbiota is a potential predictor of NAFLD severity in T2D patients. Full article
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17 pages, 546 KiB  
Review
Liquid Biopsy Biomarkers in Urine: A Route towards Molecular Diagnosis and Personalized Medicine of Bladder Cancer
by Matteo Ferro, Evelina La Civita, Antonietta Liotti, Michele Cennamo, Fabiana Tortora, Carlo Buonerba, Felice Crocetto, Giuseppe Lucarelli, Gian Maria Busetto, Francesco Del Giudice, Ottavio de Cobelli, Giuseppe Carrieri, Angelo Porreca, Amelia Cimmino and Daniela Terracciano
J. Pers. Med. 2021, 11(3), 237; https://doi.org/10.3390/jpm11030237 - 23 Mar 2021
Cited by 57 | Viewed by 5385
Abstract
Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, [...] Read more.
Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy. Full article
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13 pages, 420 KiB  
Review
A Review on the Value of Imaging in Differentiating between Large Vessel Vasculitis and Atherosclerosis
by Pieter H. Nienhuis, Gijs D. van Praagh, Andor W. J. M. Glaudemans, Elisabeth Brouwer and Riemer H. J. A. Slart
J. Pers. Med. 2021, 11(3), 236; https://doi.org/10.3390/jpm11030236 - 23 Mar 2021
Cited by 21 | Viewed by 3634
Abstract
Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk [...] Read more.
Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk assessment, and tailored treatment at a patient level. This paper reviews the current evidence of ultrasound (US), 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) to distinguish LVV from atherosclerosis. In this review, we identified a total of eight studies comparing LVV patients to atherosclerosis patients using imaging—four US studies, two FDG-PET studies, and two CT studies. The included studies mostly applied different methodologies and outcome parameters to investigate vessel wall inflammation. This review reports the currently available evidence and provides recommendations on further methodological standardization methods and future directions for research. Full article
(This article belongs to the Special Issue Systems Radiology and Personalized Medicine)
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18 pages, 3661 KiB  
Article
Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring
by Pune N. Paqué, Christopher Herz, Daniel B. Wiedemeier, Konstantinos Mitsakakis, Thomas Attin, Kai Bao, Georgios N. Belibasakis, John P. Hays, Joël S. Jenzer, Wendy E. Kaman, Michal Karpíšek, Philipp Körner, Johannes R. Peham, Patrick R. Schmidlin, Thomas Thurnheer, Florian J. Wegehaupt and Nagihan Bostanci
J. Pers. Med. 2021, 11(3), 235; https://doi.org/10.3390/jpm11030235 - 23 Mar 2021
Cited by 20 | Viewed by 4919
Abstract
This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), [...] Read more.
This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression. Full article
(This article belongs to the Special Issue Molecular Diagnosis and New Therapeutic Approach of Oral Diseases)
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24 pages, 5014 KiB  
Article
‘Statistical Irreproducibility’ Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research
by Abigail R. Basson, Fabio Cominelli and Alexander Rodriguez-Palacios
J. Pers. Med. 2021, 11(3), 234; https://doi.org/10.3390/jpm11030234 - 23 Mar 2021
Cited by 4 | Viewed by 2121
Abstract
Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause [...] Read more.
Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the ‘reproducibility of statistical results or direction of the effects’. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person–person differences and personalized medicine. 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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12 pages, 14453 KiB  
Article
Tumor Infiltrating Neutrophils Are Frequently Found in Adenocarcinomas of the Biliary Tract and Their Precursor Lesions with Possible Impact on Prognosis
by Vittorio Branchi, Benedict Jürgensen, Laura Esser, Maria Gonzalez-Carmona, Tobias J. Weismüller, Christian P. Strassburg, Jonas Henn, Alexander Semaan, Philipp Lingohr, Steffen Manekeller, Glen Kristiansen, Jörg C. Kalff, Marieta I. Toma and Hanno Matthaei
J. Pers. Med. 2021, 11(3), 233; https://doi.org/10.3390/jpm11030233 - 23 Mar 2021
Cited by 4 | Viewed by 2074
Abstract
Biliary tract cancer (BTC) is characterized by an intense stromal reaction and a complex landscape of infiltrating immune cells. Evidence is emerging that tumor-infiltrating neutrophils (TINs) have an impact on carcinogenesis and tumor progression. TINs have also been associated with outcomes in various [...] Read more.
Biliary tract cancer (BTC) is characterized by an intense stromal reaction and a complex landscape of infiltrating immune cells. Evidence is emerging that tumor-infiltrating neutrophils (TINs) have an impact on carcinogenesis and tumor progression. TINs have also been associated with outcomes in various solid malignant tumors but their possible clinical role in BTC is largely unknown. Tissue samples from patients with sporadic BTC (“spBTC” cohort, N = 53) and BTC in association with primary sclerosing cholangitis (“PSC-BTC” cohort, N = 7) were collected. Furthermore, tissue samples from 27 patients with PSC who underwent liver transplantation (“PSC-LTX” cohort) were investigated. All specimens were assessed for TIN density in invasive and precancerous lesions (biliary intraepithelial neoplasia, BilIN). Most spBTC showed low TIN density (LD, 61%). High TIN density (HD) was detected in 16% of the tumors, whereas 23% were classified as intermediate density (ID); the majority of both HD and ID groups were in T1–T2 tumors (83% and 100%, p = 0.012). TIN density in BilIN lesions did not significantly differ among the three groups. The HD group had a mean overall survival (OS) of 53.5 months, whereas the mean OS in the LD and ID groups was significantly shorter (LD 29.5 months vs. ID 24.6 months, log-rank p < 0.05). The results of this study underline the possible prognostic relevance of TINs in BTC and stress the complexity of the immune cell landscape in BTC. The prognostic relevance of TINs suggests a key regulator role in inflammation and immune landscape in BTC. Full article
(This article belongs to the Special Issue Personalized Medicine in Oncology)
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15 pages, 10793 KiB  
Article
A Comparative in Silico Analysis of CD24’s Prognostic Value in Human and Canine Prostate Cancer
by Antonio Fernando Leis-Filho, Patrícia de Faria Lainetti, Mayara Simão Franzoni, Chiara Palmieri, Priscila Emiko Kobayshi, Renee Laufer-Amorim and Carlos Eduardo Fonseca-Alves
J. Pers. Med. 2021, 11(3), 232; https://doi.org/10.3390/jpm11030232 - 23 Mar 2021
Cited by 6 | Viewed by 2490
Abstract
CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome; however, few studies have investigated CD24 expression in spontaneous animal models [...] Read more.
CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome; however, few studies have investigated CD24 expression in spontaneous animal models of human PC, such as canine PC. This study aimed to evaluate the expression of CD24 in human PC using the in silico analysis of the data obtained from The Cancer Genome Atlas (TCGA) and comparing it with the previously published prostatic canine transcriptome data. In addition, CD24 expression was confirmed by immunohistochemistry in an independent cohort of canine prostatic samples and its prognostic significance assessed. The systematic review identified 10 publications fitting with the inclusion criteria of this study. Of the 10 manuscripts, 5 demonstrated a direct correlation between CD24 overexpression and patient prognoses. CD24 expression was also associated with PSA relapse (2/5) and tumor progression (1/5). However, the in silico analysis did not validate CD24 as a prognostic factor of human PC. Regarding canine PC, 10 out of 30 normal prostates and 27 out of 40 PC samples were positive for CD24. As in humans, there was no association with overall survival. Overall, our results demonstrated a significant CD24 overexpression in human and canine prostate cancer, although its prognostic value may be questionable. However, tumors overexpressing CD24 may be a reliable model for new target therapies and dogs could be used of a unique preclinical model for these studies. 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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15 pages, 305 KiB  
Article
The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis
by Faven Butler, Ali Alghubayshi and Youssef Roman
J. Pers. Med. 2021, 11(3), 231; https://doi.org/10.3390/jpm11030231 - 22 Mar 2021
Cited by 55 | Viewed by 11175
Abstract
Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the [...] Read more.
Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising. Full article
(This article belongs to the Special Issue Personalized Therapy, Personalized Nutrition, and Chronic Disease)
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20 pages, 1550 KiB  
Review
Differences and Similarities in Neuropathy in Type 1 and 2 Diabetes: A Systematic Review
by Mar Sempere-Bigorra, Iván Julián-Rochina and Omar Cauli
J. Pers. Med. 2021, 11(3), 230; https://doi.org/10.3390/jpm11030230 - 22 Mar 2021
Cited by 15 | Viewed by 3601
Abstract
Background: Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, [...] Read more.
Background: Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level. Data sources: we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria. Conclusions: both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field. Full article
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17 pages, 3552 KiB  
Review
The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects
by Hiroshi Maeda
J. Pers. Med. 2021, 11(3), 229; https://doi.org/10.3390/jpm11030229 - 22 Mar 2021
Cited by 87 | Viewed by 5256
Abstract
This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history [...] Read more.
This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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12 pages, 616 KiB  
Article
The Link between Attachment and Gambling in Adolescence: A Multiple Mediation Analysis with Developmental Perspective, Theory of Mind (Friend) and Adaptive Response
by Grazia Terrone, Alessio Gori, Eleonora Topino, Alessandro Musetti, Alessia Scarinci, Camilla Guccione and Vincenzo Caretti
J. Pers. Med. 2021, 11(3), 228; https://doi.org/10.3390/jpm11030228 - 22 Mar 2021
Cited by 12 | Viewed by 2673
Abstract
Introduction: Several studies have supported the evidence that attachment styles are a central factor in adolescent gambling problems. On this theoretical basis, the aim of the present study is to analyze a hypothesized mediation model exploring both the direct and indirect effects [...] Read more.
Introduction: Several studies have supported the evidence that attachment styles are a central factor in adolescent gambling problems. On this theoretical basis, the aim of the present study is to analyze a hypothesized mediation model exploring both the direct and indirect effects of insecure attachment on gambling disorder by investigating the role of the developmental perspective, theory of mind (friend) and adaptive response in that relationship. Method: The sample consists of 178 adolescents who underwent the Measures: South Oaks Gambling Screen—Revised for Adolescents and Friends and Family Interview. Result: The mediation analysis was conducted following Hayes’ (2018) procedure, using Model 6. The results showed a significant association between insecure attachment and gambling disorder (β = 0.669; p < 0.001). The findings also highlighted a significant chained mediation model in which insecure attachment negatively influenced the developmental perspective (β = −0.742; p < 0.001), which affected the theory of mind toward one’s own best friend (β = 0.352; p < 0.001). Conclusions: The results highlighted a significant role of insecure attachment in predicting the symptomatic expression of gambling among adolescents, specifically impacting the development perspective, theory of mind toward one’s best friend and adaptive response to stress, which were linked to each other by a sequential influence. Therefore, our results showed that a poor developmental self-vision predicted a dysfunctional theory of mind toward the best friend. This could hinder the formation of positive peer relationships, which are crucial for the development of one’s identity. Full article
(This article belongs to the Special Issue Predicting Psychopathological Onset: Early Signs of Neuropsychiatric Diseases)
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15 pages, 2055 KiB  
Article
Predictive Biomarkers of COVID-19 Severity in SARS-CoV-2 Infected Patients with Obesity and Metabolic Syndrome
by Carles Perpiñan, Laia Bertran, Ximena Terra, Carmen Aguilar, Miguel Lopez-Dupla, Ajla Alibalic, David Riesco, Javier Camaron, Francesco Perrone, Anna Rull, Laia Reverté, Elena Yeregui, Anna Marti, Francesc Vidal and Teresa Auguet
J. Pers. Med. 2021, 11(3), 227; https://doi.org/10.3390/jpm11030227 - 22 Mar 2021
Cited by 5 | Viewed by 3707
Abstract
In SARS-CoV-2-infected patients, obesity, hypertension, and diabetes are dangerous factors that may result in death. Priority in detection and specific therapies for these patients are necessary. We wanted to investigate the impact of obesity and metabolic syndrome (MS) on the clinical course of [...] Read more.
In SARS-CoV-2-infected patients, obesity, hypertension, and diabetes are dangerous factors that may result in death. Priority in detection and specific therapies for these patients are necessary. We wanted to investigate the impact of obesity and metabolic syndrome (MS) on the clinical course of COVID-19 and whether prognostic biomarkers described are useful to predict the evolution of COVID-19 in patients with obesity or MS. This prospective cohort study included 303 patients hospitalized for COVID-19. Participants were first classified according to the presence of obesity; then, they were classified according to the presence of MS. Clinical, radiologic, and analytical parameters were collected. We reported that patients with obesity presented moderate COVID-19 symptoms and pneumonia, bilateral pulmonary infiltrates, and needed tocilizumab more frequently. Meanwhile, patients with MS presented severe pneumonia and respiratory failure more frequently, they have a higher mortality rate, and they also showed higher creatinine and troponin levels. The main findings of this study are that IL-6 is a potential predictor of COVID-19 severity in patients with obesity, while troponin and LDH can be used as predictive biomarkers of COVID-19 severity in MS patients. Therefore, treatment for COVID-19 in patients with obesity or MS should probably be intensified and personalized. Full article
(This article belongs to the Special Issue COVID-19 Related Complications)
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16 pages, 1412 KiB  
Article
Prevention of Covid-19 Infection and Related Complications by Ozonized Oils
by Alberto Izzotti, Enzo Fracchia, William Au, Monica Colombo, Ulrich Pfeffer, Laura Emionite, Simone Pavan, Daniele Miotto, Paola Lova, Elena Grasselli, Emanuela Faelli, Ruggeri Piero, Micaela Tiso and Alessandra Pulliero
J. Pers. Med. 2021, 11(3), 226; https://doi.org/10.3390/jpm11030226 - 22 Mar 2021
Cited by 12 | Viewed by 2466
Abstract
Background: The COVID-19 pandemic continues to ravage the human population; therefore, multiple prevention and intervention protocols are being rapidly developed. The aim of our study was to develop a new chemo-prophylactic/-therapeutic strategy that effectively prevents COVID-19 and related complications. Methods: In in vitro [...] Read more.
Background: The COVID-19 pandemic continues to ravage the human population; therefore, multiple prevention and intervention protocols are being rapidly developed. The aim of our study was to develop a new chemo-prophylactic/-therapeutic strategy that effectively prevents COVID-19 and related complications. Methods: In in vitro studies, COVID-19 infection-sensitive cells were incubated with human oropharyngeal fluids containing high SARS-CoV-2 loads. Levels of infection were determined via intra-cellular virus loads using quantitative PCR (qPCR). Efficacies for infection prevention were determined using several antiviral treatments: lipid-encapsulated ozonized oil (HOO), water-soluble HOO (HOOws), UV, and hydrogen peroxide. In in vivo studies, safety and efficacy of HOO in fighting COVID-19 infection was evaluated in human subjects. Results: HOO in combination with HOOws was the only treatment able to fully neutralize SARS-CoV-2 as well as its capacity to penetrate and reproduce inside sensitive cells. Accordingly, the feasibility of using HOO/HOOws was tested in vivo. Analysis of expired gas in healthy subjects indicates that HOO administration increases oxygen availability in the lung. For our human studies, HOO/HOOws was administered to 52 cancer patients and 21 healthy subjects at high risk for COVID-19 infection, and all of them showed clinical safety. None of them developed COVID-19 infection, although an incidence of at least 11 cases was expected. Efficacy of HOO/HOOws was tested in four COVID-19 patients obtaining recovery and qPCR negativization in less than 10 days. Conclusions: Based on our experience, the HOO/HOOws treatment can be administered at standard doses (three pills per day) for chemo-prophylactic purposes to healthy subjects for COVID-19 prevention and at high doses (up to eight pills per day) for therapeutic purposes to infected patients. This combined prevention strategy can provide a novel protocol to fight the COVID-19 pandemic. Full article
(This article belongs to the Special Issue COVID-19 Related Complications)
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10 pages, 241 KiB  
Article
Alterations of Left Ventricular Function Persisting during Post-Acute COVID-19 in Subjects without Previously Diagnosed Cardiovascular Pathology
by Mariana Tudoran, Cristina Tudoran, Voichita Elena Lazureanu, Adelina Raluca Marinescu, Gheorghe Nicusor Pop, Alexandru Silvius Pescariu, Alexandra Enache and Talida Georgiana Cut
J. Pers. Med. 2021, 11(3), 225; https://doi.org/10.3390/jpm11030225 - 22 Mar 2021
Cited by 22 | Viewed by 2895
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)
12 pages, 888 KiB  
Article
Elevated Monocyte to Lymphocyte Ratio and Increased Mortality among Patients with Chronic Kidney Disease Hospitalized for COVID-19
by Ramsés Dávila-Collado, Oscar Jarquín-Durán, Andrés Solís-Vallejo, Mai Anh Nguyen and J. Luis Espinoza
J. Pers. Med. 2021, 11(3), 224; https://doi.org/10.3390/jpm11030224 - 22 Mar 2021
Cited by 19 | Viewed by 3036
Abstract
Chronic kidney disease (CKD) constitutes a major health problem and one of the leading causes of death worldwide. Patients with CKD have impaired immune functions that predispose them to an increased risk of infections, as well as virus-associated cancers and a diminished vaccine [...] Read more.
Chronic kidney disease (CKD) constitutes a major health problem and one of the leading causes of death worldwide. Patients with CKD have impaired immune functions that predispose them to an increased risk of infections, as well as virus-associated cancers and a diminished vaccine response. In this study, we aimed to identify clinical and laboratory parameters associated with in-hospital mortality in patients evaluated in the department of emergency (ER) and admitted with the diagnosis of severe acute respiratory syndrome (SARS) caused by coronavirus disease 2019 (COVID-19) at the Baptist Hospital of Nicaragua (BHN). There were 37 patients with CKD, mean age 58.3 ± 14.1 years, admitted to BHN due to COVID-19, and among them, 24 (65.7%) were males (p = 0.016). During hospitalization, 23 patients with CKD (62.1%) died of complications associated with COVID-19 disease, which was a higher proportion (odds ratio (OR) 5.6, confidence interval (CI) 2.1–15.7, p = 0.001) compared to a group of 70 patients (64.8% males, mean age 57.5 ± 13.7 years) without CKD admitted during the same period in whom 28.5% died of COVID-19. In the entire cohort, the majority of patients presented with bilateral pneumonia, and the most common symptoms at admission were dyspnea, cough, and fever. Serum levels of D-dimer, ferritin and procalcitonin were significantly higher in patients with CKD compared with those without CKD. Multivariate analysis revealed that CKD, age (>60 years), and hypoxia measured in the ER were factors associated with increased in-hospital mortality. Among patients with CKD but not in those without CKD (OR 36.8, CI 1.5–88.3, p = 0.026), an increased monocytes-to-lymphocyte ratio (MLR) was associated with higher mortality and remained statistically significant after adjusting for confounders. The MLR measured in the ER may be useful for predicting in-hospital mortality in patients with CKD and COVID-19 and could contribute to early risk stratification in this group. Full article
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15 pages, 513 KiB  
Review
Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities
by Nikolaos Garmpis, Christos Damaskos, Anna Garmpi, Vasiliki E. Georgakopoulou, Panagiotis Sarantis, Efstathios A. Antoniou, Michalis V. Karamouzis, Afroditi Nonni, Dimitrios Schizas, Evangelos Diamantis, Evangelos Koustas, Paraskevi Farmaki, Athanasios Syllaios, Alexandros Patsouras, Konstantinos Kontzoglou, Nikolaos Trakas and Dimitrios Dimitroulis
J. Pers. Med. 2021, 11(3), 223; https://doi.org/10.3390/jpm11030223 - 22 Mar 2021
Cited by 22 | Viewed by 3239
Abstract
Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel [...] Read more.
Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC. Full article
(This article belongs to the Section Mechanisms of Diseases)
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14 pages, 1777 KiB  
Article
P2Y12 Antiplatelet Choice for Patients with Chronic Kidney Disease and Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
by Sohyun Park, Yeo Jin Choi, Ji Eun Kang, Myeong Gyu Kim, Min Jung Geum, So Dam Kim and Sandy Jeong Rhie
J. Pers. Med. 2021, 11(3), 222; https://doi.org/10.3390/jpm11030222 - 21 Mar 2021
Cited by 10 | Viewed by 3387
Abstract
This study aims to evaluate potentially appropriate antiplatelet therapy in patients with chronic kidney disease. A systematic analysis was conducted to identify the clinical outcomes of available antiplatelet therapy regimens with enhanced platelet inhibition activity (intervention of 5 regimens) over the standard dose [...] Read more.
This study aims to evaluate potentially appropriate antiplatelet therapy in patients with chronic kidney disease. A systematic analysis was conducted to identify the clinical outcomes of available antiplatelet therapy regimens with enhanced platelet inhibition activity (intervention of 5 regimens) over the standard dose of clopidogrel-based dual antiplatelet therapy in patients with renal insufficiency. An electronic keyword search was performed on Pubmed, Embase, and Cochrane Library per PRISMA guidelines. We performed a prespecified net clinical benefit analysis (a composite of the rates of all-cause or cardiac-related death, myocardial infarction, major adverse cardiac outcomes, and minor and major bleeding), and included 12 studies. The intervention substantially lowered the incidence of all-cause mortality (RR 0.67; p = 0.003), major adverse cardiac outcomes (RR 0.79; p < 0.00001), and myocardial infarction (RR 0.28; p = 0.00007) without major bleeding (RR 1.14; p = 0.33) in patients with renal insufficiency, but no significant differences were noticed with cardiac-related mortality and stent thrombosis. The subgroup analysis revealed substantially elevated bleeding risk in patients with severe renal insufficiency or on hemodialysis (RR 1.68; p = 0.002). Our study confirmed that the intervention considerably enhances clinical outcomes in patients with renal insufficiency, however, a standard dose of clopidogrel-based antiplatelet therapy is favorable in patients with severe renal insufficiency. Full article
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18 pages, 2589 KiB  
Article
Genetic Correction of IL-10RB Deficiency Reconstitutes Anti-Inflammatory Regulation in iPSC-Derived Macrophages
by Dirk Hoffmann, Johanna Sens, Sebastian Brennig, Daniel Brand, Friederike Philipp, Philippe Vollmer Barbosa, Johannes Kuehle, Doris Steinemann, Daniela Lenz, Theresa Buchegger, Michael Morgan, Christine S. Falk, Christoph Klein, Nico Lachmann and Axel Schambach
J. Pers. Med. 2021, 11(3), 221; https://doi.org/10.3390/jpm11030221 - 20 Mar 2021
Cited by 4 | Viewed by 2558
Abstract
Patient material from rare diseases such as very early-onset inflammatory bowel disease (VEO-IBD) is often limited. The use of patient-derived induced pluripotent stem cells (iPSCs) for disease modeling is a promising approach to investigate disease pathomechanisms and therapeutic strategies. We successfully developed VEO-IBD [...] Read more.
Patient material from rare diseases such as very early-onset inflammatory bowel disease (VEO-IBD) is often limited. The use of patient-derived induced pluripotent stem cells (iPSCs) for disease modeling is a promising approach to investigate disease pathomechanisms and therapeutic strategies. We successfully developed VEO-IBD patient-derived iPSC lines harboring a mutation in the IL-10 receptor β-chain (IL-10RB) associated with defective IL-10 signaling. To characterize the disease phenotype, healthy control and VEO-IBD iPSCs were differentiated into macrophages. IL-10 stimulation induced characteristic signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) downstream signaling and anti-inflammatory regulation of lipopolysaccharide (LPS)-mediated cytokine secretion in healthy control iPSC-derived macrophages. In contrast, IL-10 stimulation of macrophages derived from patient iPSCs did not result in STAT3 phosphorylation and subsequent SOCS3 expression, recapitulating the phenotype of cells from patients with IL-10RB deficiency. In line with this, LPS-induced cytokine secretion (e.g., IL-6 and tumor necrosis factor-α (TNF-α)) could not be downregulated by exogenous IL-10 stimulation in VEO-IBD iPSC-derived macrophages. Correction of the IL-10RB defect via lentiviral gene therapy or genome editing in the adeno-associated virus integration site 1 (AAVS1) safe harbor locus led to reconstitution of the anti-inflammatory response. Corrected cells showed IL-10RB expression, IL-10-inducible phosphorylation of STAT3, and subsequent SOCS3 expression. Furthermore, LPS-mediated TNF-α secretion could be modulated by IL-10 stimulation in gene-edited VEO-IBD iPSC-derived macrophages. Our established disease models provide the opportunity to identify and validate new curative molecular therapies and to investigate phenotypes and consequences of additional individual IL-10 signaling pathway-dependent VEO-IBD mutations. Full article
(This article belongs to the Special Issue Application of Induced Pluripotent Stem Cells in Personalized Medicine)
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16 pages, 5228 KiB  
Article
Expansion of CD4 T Lymphocytes Expressing Interleukin 17 and Tumor Necrosis Factor in Patients with Major Depressive Disorder
by Miguel Angel Alvarez-Mon, Ana Maria Gómez-Lahoz, Arancha Orozco, Guillermo Lahera, David Diaz, Miguel A. Ortega, Agustin Albillos, Javier Quintero, Enrique Aubá, Jorge Monserrat and Melchor Alvarez-Mon
J. Pers. Med. 2021, 11(3), 220; https://doi.org/10.3390/jpm11030220 - 19 Mar 2021
Cited by 33 | Viewed by 3221
Abstract
Background: We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4+ T lymphocytes and their naïve (TN), effector (TE), central (TCM) and effector memory (TEM) activation/differentiation stages in patients [...] Read more.
Background: We have investigated the distribution of the Th1, Th2 and Th17 subsets in circulating CD4+ T lymphocytes and their naïve (TN), effector (TE), central (TCM) and effector memory (TEM) activation/differentiation stages in patients with major depressive disorder (MDD). Methods: Thirty MDD patients and 30 healthy controls were studied. The counts of circulating CD4+ T lymphocytes and their distribution on the TN, TE, TCM and TEM activation/differentiation stages were analyzed by polychromatic flow cytometry. The intracytoplasmic interferon gamma (IFNγ), interleukin (IL)-4, IL-17A and tumor necrosis factor alpha (TNF-alpha) and membrane CD28 expression were also measured. The serum IFNγ, IL-4, Il-17A and TNF-alpha were measured by Luminex, respectively. Results: MDD patients had normal counts of CD4+ T lymphocytes and of their TN, TCM and TEM subsets but increased number and percentage of TE CD4+ subset. CD4+ T lymphocytes had significantly enhanced percentage of cells that express IL-17 and TNF-alpha explained by the expansions found in the TN, TCM and, TEM and TCM, TEM and TE activation/differentiation stages, respectively. A selective increase in the percentages of TCM and TEM expressing IFNγ was also observed. We found a significant correlation between the percentages of CD4+ T lymphocytes expressing IFNγ and TNF-alpha in these patients. MDD patients showed increased serum levels of IL-17 and TNF-alpha, but normal IFNγ and IL-4 concentration. Limitations: the cross-sectional nature of the study could be considered a limitation. Conclusions: MDD patients have abnormal circulating CD4+ T lymphocytes with expansion of the IL-17 and TNF-alpha expressing cells as well as increased levels of circulating IL-17 and TNF-alpha. Full article
(This article belongs to the Special Issue Personalized Medicine and Multidisciplinary Approach in a Clinical Research Hospital)
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19 pages, 2612 KiB  
Review
New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics
by Ya-Ling Yang, Yen-Hsiang Chang, Chia-Jung Li, Ying-Hsien Huang, Ming-Chao Tsai, Pei-Yi Chu and Hung-Yu Lin
J. Pers. Med. 2021, 11(3), 219; https://doi.org/10.3390/jpm11030219 - 18 Mar 2021
Cited by 15 | Viewed by 2820
Abstract
Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of [...] Read more.
Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a. Full article
(This article belongs to the Special Issue Personalized Medicine for Liver Disease: From Molecular Mechanisms to Potential Targeted Therapies)
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15 pages, 2106 KiB  
Review
Mitochondria May Mediate Prenatal Environmental Influences in Autism Spectrum Disorder
by Richard E. Frye, Janet Cakir, Shannon Rose, Raymond F. Palmer, Christine Austin, Paul Curtin and Manish Arora
J. Pers. Med. 2021, 11(3), 218; https://doi.org/10.3390/jpm11030218 - 18 Mar 2021
Cited by 21 | Viewed by 4726
Abstract
We propose that the mitochondrion, an essential cellular organelle, mediates the long-term prenatal environmental effects of disease in autism spectrum disorder (ASD). Many prenatal environmental factors which increase the risk of developing ASD influence mitochondria physiology, including toxicant exposures, immune activation, and nutritional [...] Read more.
We propose that the mitochondrion, an essential cellular organelle, mediates the long-term prenatal environmental effects of disease in autism spectrum disorder (ASD). Many prenatal environmental factors which increase the risk of developing ASD influence mitochondria physiology, including toxicant exposures, immune activation, and nutritional factors. Unique types of mitochondrial dysfunction have been associated with ASD and recent studies have linked prenatal environmental exposures to long-term changes in mitochondrial physiology in children with ASD. A better understanding of the role of the mitochondria in the etiology of ASD can lead to targeted therapeutics and strategies to potentially prevent the development of ASD. 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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17 pages, 2931 KiB  
Review
Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview
by Cristina Ferrari, Nicola Maggialetti, Tamara Masi, Anna Giulia Nappi, Giulia Santo, Artor Niccoli Asabella and Giuseppe Rubini
J. Pers. Med. 2021, 11(3), 217; https://doi.org/10.3390/jpm11030217 - 18 Mar 2021
Cited by 18 | Viewed by 3599
Abstract
Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, [...] Read more.
Immunotherapy is a promising therapeutic strategy both for solid and hematologic tumors, such as in Hodgkin (HL) and non-Hodgkin lymphoma (NHL). In particular, immune-checkpoint inhibitors, such as nivolumab and pembrolizumab, are increasingly used for the treatment of refractory/relapsed HL. At the same time, evidence of chimeric antigen receptor (CAR)-T-cell immunotherapy efficacy mostly in NHL is growing. In this setting, the challenge is to identify an appropriate imaging method to evaluate immunotherapy response. The role of 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), especially in early evaluation, is under investigation in order to guide therapeutic strategies, taking into account the possible atypical responses (hyperprogression and pseudoprogression) and immune-related adverse events that could appear on PET images. Herein, we aimed to present a critical overview about the role of 18F-FDG PET/CT in evaluating treatment response to immunotherapy in lymphoma patients. Full article
(This article belongs to the Special Issue Lymphoma and Cancer Therapy)
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20 pages, 1037 KiB  
Review
Translational Research in the Era of Precision Medicine: Where We Are and Where We Will Go
by Ruggero De Maria Marchiano, Gabriele Di Sante, Geny Piro, Carmine Carbone, Giampaolo Tortora, Luca Boldrini, Antonella Pietragalla, Gennaro Daniele, Maria Tredicine, Alfredo Cesario, Vincenzo Valentini, Daniela Gallo, Gabriele Babini, Marika D’Oria and Giovanni Scambia
J. Pers. Med. 2021, 11(3), 216; https://doi.org/10.3390/jpm11030216 - 18 Mar 2021
Cited by 40 | Viewed by 9323
Abstract
The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of “multi-omics” analysis [...] Read more.
The advent of Precision Medicine has globally revolutionized the approach of translational research suggesting a patient-centric vision with therapeutic choices driven by the identification of specific predictive biomarkers of response to avoid ineffective therapies and reduce adverse effects. The spread of “multi-omics” analysis and the use of sensors, together with the ability to acquire clinical, behavioral, and environmental information on a large scale, will allow the digitization of the state of health or disease of each person, and the creation of a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy in the individual person (high-definition medicine). Real world data-based translational applications represent a promising alternative to the traditional evidence-based medicine (EBM) approaches that are based on the use of randomized clinical trials to test the selected hypothesis. Multi-modality data integration is necessary for example in precision oncology where an Avatar interface allows several simulations in order to define the best therapeutic scheme for each cancer patient. Full article
(This article belongs to the Special Issue Personalized Medicine and Multidisciplinary Approach in a Clinical Research Hospital)
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13 pages, 2110 KiB  
Article
Body Composition Change, Unhealthy Lifestyles and Steroid Treatment as Predictor of Metabolic Risk in Non-Hodgkin’s Lymphoma Survivors
by A. Daniele, A. Guarini, S. De Summa, M. Dellino, G. Lerario, S. Ciavarella, P. Ditonno, A. V. Paradiso, R. Divella, P. Casamassima, E. Savino, M. D. Carbonara and C. Minoia
J. Pers. Med. 2021, 11(3), 215; https://doi.org/10.3390/jpm11030215 - 17 Mar 2021
Cited by 5 | Viewed by 2392
Abstract
Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin’s lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this [...] Read more.
Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin’s lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this study was to assess whether changes in body composition, unhealthy lifestyles and types of anti-cancer treatment could increase the risk of metabolic syndrome (MetSyn) and sarcopenia in long-term NHL survivors. We enrolled 60 consecutive NHL patients in continuous remission for at least 3 years. Nutritional status was assessed by anthropometry-plicometry, and a questionnaire concerning lifestyles and eating habits was administered. More than 60% of survivors exhibited weight gain and a change in body composition, with an increased risk of MetSyn. Univariate analysis showed a significantly higher risk of metabolic disorder in patients treated with steroids, and in patients with unhealthy lifestyles. These data suggest that a nutritional intervention, associated with adequate physical activity and a healthier lifestyle, should be indicated early during the follow-up of lymphoma patients, in order to decrease the risk of MetSyn’s onset and correlated diseases in the long term. Full article
(This article belongs to the Special Issue Lymphoma and Cancer Therapy)
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14 pages, 1915 KiB  
Article
Usability of a Psychotherapeutic Interactive Gaming Tool Used in Facial Emotion Recognition for People with Schizophrenia
by Roberto Pablo González, Ingrid Tortadès, Francesc Alpiste, Joaquín Fernandez, Jordi Torner, Mar Garcia-Franco, José Ramón Martin-Martínez, Sònia Vilamala, Maria Jose Escandell, Emma Casas-Anguera, Gemma Prat and Susana Ochoa
J. Pers. Med. 2021, 11(3), 214; https://doi.org/10.3390/jpm11030214 - 17 Mar 2021
Cited by 1 | Viewed by 2133
Abstract
The objective of the study was to test the usability of ‘Feeling Master’ as a psychotherapeutic interactive gaming tool with LEGO cartoon faces showing the five basic emotions, for the assessment of emotional recognition in people with schizophrenia in comparison with healthy controls, [...] Read more.
The objective of the study was to test the usability of ‘Feeling Master’ as a psychotherapeutic interactive gaming tool with LEGO cartoon faces showing the five basic emotions, for the assessment of emotional recognition in people with schizophrenia in comparison with healthy controls, and the relationship between face affect recognition (FER), attributional style, and theory of mind (ToM), which is the ability to understand the potential mental states and intentions of others. Nineteen individuals with schizophrenia (SZ) and 17 healthy control (HC) subjects completed the ‘Feeling Master’ that includes five basic emotions. To assess social cognition, the group with schizophrenia was evaluated with the Personal and Situational Attribution Questionnaire (IPSAQ) for the assessment of attributional style and the Hinting Task (ToM). Patients with SZ showed significant impairments in emotion recognition and their response time appeared to be slower than the HC in the recognition of each emotion. Taking into account the impairment in the recognition of each emotion, we only found a trend toward significance in error rates on fear recognition. The correlations between correct response on the ‘Feeling Master’ and the hinting task appeared to be significant in the correlation of surprise and theory of mind. In conclusion, this study demonstrated that the ‘Feeling Master’ could be useful for the evaluation of FER in people with schizophrenia. These results sustain the notion that impairments in emotion recognition are more prevalent in people with schizophrenia and that these are related with impairment in ToM. Full article
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8 pages, 588 KiB  
Article
Genetic Variants Allegedly Linked to Antisocial Behaviour Are Equally Distributed Across Different Populations
by Stefania Zampatti, Michele Ragazzo, Carlo Fabrizio, Andrea Termine, Giulia Campoli, Valerio Caputo, Claudia Strafella, Raffaella Cascella, Carlo Caltagirone and Emiliano Giardina
J. Pers. Med. 2021, 11(3), 213; https://doi.org/10.3390/jpm11030213 - 16 Mar 2021
Cited by 3 | Viewed by 2474
Abstract
Human behaviour is determined by a complex interaction of genetic and environmental factors. Several studies have demonstrated different associations between human behaviour and numerous genetic variants. In particular, allelic variants in SLC6A4, MAOA, DRD4, and DRD2 showed statistical associations with major depressive disorder, [...] Read more.
Human behaviour is determined by a complex interaction of genetic and environmental factors. Several studies have demonstrated different associations between human behaviour and numerous genetic variants. In particular, allelic variants in SLC6A4, MAOA, DRD4, and DRD2 showed statistical associations with major depressive disorder, antisocial behaviour, schizophrenia, and bipolar disorder; BDNF polymorphic variants were associated with depressive, bipolar, and schizophrenia diseases, and TPH2 variants were found both in people with unipolar depression and in children with attention deficit-hyperactivity disorder (ADHD). Independent studies have failed to confirm polymorphic variants associated with criminal and aggressive behaviour. In the present study, a set of genetic variants involved in serotoninergic, dopaminergic, and neurobiological pathways were selected from those previously associated with criminal behaviour. The distribution of these genetic variants was compared across worldwide populations. While data on single polymorphic variants showed differential distribution across populations, these differences failed to be significant when a comprehensive analysis was conducted on the total number of published variants. The lack of reproducibility of the genetic association data published to date, the weakness of statistical associations, the heterogeneity of the phenotype, and the massive influence of the environment on human behaviour do not allow us to consider these genetic variants as undoubtedly associated with antisocial behaviour. Moreover, these data confirm the absence of ethnic predisposition to aggressive and criminal behaviour. Full article
(This article belongs to the Special Issue Predicting Psychopathological Onset: Early Signs of Neuropsychiatric Diseases)
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18 pages, 2136 KiB  
Review
A Novel Precision Approach to Overcome the “Addiction Pandemic” by Incorporating Genetic Addiction Risk Severity (GARS) and Dopamine Homeostasis Restoration
by Kenneth Blum, Shan Kazmi, Edward J. Modestino, Bill William Downs, Debasis Bagchi, David Baron, Thomas McLaughlin, Richard Green, Rehan Jalali, Panayotis K. Thanos, Igor Elman, Rajendra D. Badgaiyan, Abdalla Bowirrat and Mark S. Gold
J. Pers. Med. 2021, 11(3), 212; https://doi.org/10.3390/jpm11030212 - 16 Mar 2021
Cited by 14 | Viewed by 4530
Abstract
This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of [...] Read more.
This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of the addiction risk severity (GARS) test. Based on both neurogenetic and epigenetic evidence, the test evaluates the presence of reward genes and risk alleles. Existing evidence demonstrates that the novel genetic risk testing system can successfully stratify the potential for developing opioid use disorder (OUD) related risks or before initiating opioid analgesic therapy and RDS risk for people in recovery. In the case of opioid use disorders, long-term maintenance agonist treatments like methadone and buprenorphine may create RDS, or RDS may have been in existence, but not recognized. The test will also assess the potential for benefit from medication-assisted treatment with dopamine augmentation. RDS methodology holds a strong promise for reducing the burden of addictive disorders for individuals, their families, and society as a whole by guiding the restoration of dopamine homeostasisthrough anti-reward allostatic neuroadaptations. WC 175. Full article
(This article belongs to the Special Issue Functional Genomics, Pharmacogenomics in Human Disease)
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26 pages, 8585 KiB  
Systematic Review
Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions
by Nadiya Bayeva, Erin Coll and Olga Piskareva
J. Pers. Med. 2021, 11(3), 211; https://doi.org/10.3390/jpm11030211 - 16 Mar 2021
Cited by 31 | Viewed by 7673
Abstract
A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. [...] Read more.
A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. Retinoic acid (RA), a vitamin A derivative, is a promising agent that can induce differentiation in NB cells. Its isoform, 13-cis RA or isotretinoin, is used in NB therapy; however, its effectiveness is limited to treating a minimal residual disease as maintenance therapy. As such, research focuses on RA derivatives that might increase the anti-NB action or explores the potential synergy between RA and other classes of drugs, such as cellular processes mediators, epigenetic modifiers, and immune modulators. This review summarises the in vitro, in vivo, and clinical data of RA, its derivatives, and synergising compounds, thereby establishing the most promising RA derivatives and combinations of RA for further investigation. Full article
(This article belongs to the Special Issue Precision Medicine for Neuroblastoma)
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12 pages, 1220 KiB  
Article
PharmaKU: A Web-Based Tool Aimed at Improving Outreach and Clinical Utility of Pharmacogenomics
by Sumi Elsa John, Arshad Mohamed Channanath, Prashantha Hebbar, Rasheeba Nizam, Thangavel Alphonse Thanaraj and Fahd Al-Mulla
J. Pers. Med. 2021, 11(3), 210; https://doi.org/10.3390/jpm11030210 - 16 Mar 2021
Cited by 6 | Viewed by 3062
Abstract
With the tremendous advancements in genome sequencing technology in the field of pharmacogenomics, data have to be made accessible to be more efficiently utilized by broader clinical disciplines. Physicians who require the drug–genome interactome information, have been challenged by the complicated pharmacogenomic star-based [...] Read more.
With the tremendous advancements in genome sequencing technology in the field of pharmacogenomics, data have to be made accessible to be more efficiently utilized by broader clinical disciplines. Physicians who require the drug–genome interactome information, have been challenged by the complicated pharmacogenomic star-based classification system. We present here an end-to-end web-based pharmacogenomics tool, PharmaKU, which has a comprehensive easy-to-use interface. PharmaKU can help to overcome several hurdles posed by previous pharmacogenomics tools, including input in hg38 format only, while hg19/GRCh37 is now the most popular reference genome assembly among clinicians and geneticists, as well as the lack of clinical recommendations and other pertinent dosage-related information. This tool extracts genetic variants from nine well-annotated pharmacogenes (for which diplotype to phenotype information is available) from whole genome variant files and uses Stargazer software to assign diplotypes and apply prescribing recommendations from pharmacogenomic resources. The tool is wrapped with a user-friendly web interface, which allows for choosing hg19 or hg38 as the reference genome version and reports results as a comprehensive PDF document. PharmaKU is anticipated to enable bench to bedside implementation of pharmacogenomics knowledge by bringing precision medicine closer to a clinical reality. Full article
(This article belongs to the Special Issue Functional Genomics, Pharmacogenomics in Human Disease)
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Article
Maternal Separation Followed by Chronic Mild Stress in Adulthood Is Associated with Concerted Epigenetic Regulation of AP-1 Complex Genes
by Lene Lundgaard Donovan, Kim Henningsen, Anne Flou Kristensen, Ove Wiborg, John Dirk Nieland and Jacek Lichota
J. Pers. Med. 2021, 11(3), 209; https://doi.org/10.3390/jpm11030209 - 16 Mar 2021
Cited by 5 | Viewed by 2205
Abstract
Depression is one of the most prevalent mental diseases worldwide. Patients with psychiatric diseases often have a history of childhood neglect, indicating that early-life experiences predispose to psychiatric diseases in adulthood. Two strong models were used in the present study: the maternal separation/early [...] Read more.
Depression is one of the most prevalent mental diseases worldwide. Patients with psychiatric diseases often have a history of childhood neglect, indicating that early-life experiences predispose to psychiatric diseases in adulthood. Two strong models were used in the present study: the maternal separation/early deprivation model (MS) and the chronic mild stress model (CMS). In both models, we found changes in the expression of a number of genes such as Creb and Npy. Strikingly, there was a clear regulation of expression of four genes involved in the AP-1 complex: c-Fos, c-Jun, FosB, and Jun-B. Interestingly, different expression levels were observed depending on the model, whereas the combination of the models resulted in a normal level of gene expression. The effects of MS and CMS on gene expression were associated with distinct histone methylation/acetylation patterns of all four genes. The epigenetic changes, like gene expression, were also dependent on the specific stressor or their combination. The obtained results suggest that single life events leave a mark on gene expression and the epigenetic signature of gene promoters, but a combination of different stressors at different life stages can further change gene expression through epigenetic factors, possibly causing the long-lasting adverse effects of stress. Full article
(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)
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