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J. Pers. Med., Volume 11, Issue 2 (February 2021) – 98 articles

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Article
Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas
J. Pers. Med. 2021, 11(2), 158; https://doi.org/10.3390/jpm11020158 - 23 Feb 2021
Cited by 5 | Viewed by 782
Abstract
Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis, treatment [...] Read more.
Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis, treatment strategies, and prognosis. In this study, considering the clinical and transcriptome data of three Renal Cell Carcinoma (RCC) subtypes (ccRCC, pRCC, and chRCC) retrieved from The Cancer Genome Atlas (TCGA) and the human protein interactome, the differential protein–protein interactions were identified in each RCC subtype. The approach enabled the identification of differentially interacting proteins (DIPs) indicating prominent changes in their interaction patterns during tumor formation. Further, diagnostic and prognostic performances were generated by taking into account DIP clusters which are specific to the relevant subtypes. Furthermore, considering the mesenchymal epithelial transition (MET) receptor tyrosine kinase (PDB ID: 3DKF) as a potential drug target specific to pRCC, twenty-one lead compounds were identified through virtual screening of ZINC molecules. In this study, we presented remarkable findings in terms of early diagnosis, prognosis, and effective treatment strategies, that deserve further experimental and clinical efforts. Full article
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Review
Individualized Hemodynamic Management in Sepsis
J. Pers. Med. 2021, 11(2), 157; https://doi.org/10.3390/jpm11020157 - 23 Feb 2021
Cited by 2 | Viewed by 976
Abstract
Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a [...] Read more.
Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a large international survey (FENICE study), physicians frequently use inadequate indices to guide fluid management in intensive care units. Goal-directed and “restrictive” infusion strategies have been recommended by guidelines over “liberal” approaches for several years. Unfortunately, these “fixed regimen” treatment protocols neglect the patient’s individual needs, and what is shown to be beneficial for a given population may not be so for the individual patient. However, applying multimodal, contextualized, and personalized management could potentially overcome this problem. The aim of this review was to give an insight into the pathophysiological rationale and clinical application of this relatively new approach in the hemodynamic management of septic patients. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Patients with Sepsis)
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Case Report
Invasive Ductal Breast Cancer with Osteoclast-Like Giant Cells: A Case Report Based on the Gene Expression Profile for Changes in Management
J. Pers. Med. 2021, 11(2), 156; https://doi.org/10.3390/jpm11020156 - 23 Feb 2021
Viewed by 598
Abstract
We report the case of a 49-year-old woman diagnosed with a rare histotype of early breast cancer (BC), invasive ductal carcinoma with osteoclast-like giant cells (OGCs), from the perspective of gene profile analysis tests. The patient underwent a quadrantectomy of the right breast [...] Read more.
We report the case of a 49-year-old woman diagnosed with a rare histotype of early breast cancer (BC), invasive ductal carcinoma with osteoclast-like giant cells (OGCs), from the perspective of gene profile analysis tests. The patient underwent a quadrantectomy of the right breast with removal of 2 cm neoplastic nodule and three ipsilateral sentinel lymph nodes. The Oncotype Dx gave a recurrence score (RS) of 23, and taking into account the patient’s age, an RS of 23 corresponds to a chemotherapy benefit of 6.5%. After a multidisciplinary collegial discussion, and in consideration of the patient’s age, the absence of comorbidity, the premenopausal state, the rare histotype and the Oncotype Dx report, the patient was offered adjuvant chemotherapy treatment followed by hormone therapy. This case may be an example of the utility of integrating gene expression profiling tests into clinical practice in the adjuvant treatment decision of a rare histotype BC. The Oncotype Dx test required to supplement the histological examination made us opt for the proposal of a combined treatment of adjuvant chemotherapy followed by adjuvant hormone therapy. It demonstrates the importance of considering molecular tests and, in particular, the Oncotype Dx, in estimating the risk of disease recovery at 10 years in order to identify patients who benefit from hormone therapy alone versus those who benefit from the addition of chemotherapy, all with a view toward patient-centered oncology. Here, we discuss the possible validity and limitations of the Oncotype Dx in a rare luminal A-like histotype with high infiltrate of stromal/inflammatory cells. Full article
(This article belongs to the Special Issue Innovations in the Integrated Management of Breast Cancer)
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Review
Treatment-Resistant Depression Revisited: A Glimmer of Hope
J. Pers. Med. 2021, 11(2), 155; https://doi.org/10.3390/jpm11020155 - 23 Feb 2021
Cited by 5 | Viewed by 1613
Abstract
Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, [...] Read more.
Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, and remission is obtained in approximately 30% of patients. This is known as Treatment-Resistant Depression (TRD). The burden of TRD exponentially increases the longer it persists, with a higher risk of impaired functional and social functioning, vast losses in quality of life and significant risk of somatic morbidity and suicidality. Different approaches have been suggested and utilized, but the results have not been encouraging. In this review article, we present new approaches to identify and correct potential causes of TRD, thereby reducing its prevalence and with it the overall burden of this disease entity. We will address potential contributory factors to TRD, most of which can be investigated in many laboratories as routine tests. We discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and thyroid and gonadal dysfunction. We address the role of Vitamin D in contributing to depression. Pharmacogenomic testing is being increasingly used to determine Single Nucleotide Polymorphisms in Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As the role of immune system dysregulation is being recognized as potentially a major contributory factor to TRD, the measurement of C-reactive protein (CRP) and select immune biomarkers, where testing is available, can guide combination treatments with anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. We focus on established and emerging test procedures, potential biomarkers and non-biologic assessments and interventions to apply personalized medicine to effectively manage treatment resistance in general and TRD specifically. Full article
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Article
Comprehensive Profiling of Genomic and Transcriptomic Differences between Risk Groups of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
J. Pers. Med. 2021, 11(2), 154; https://doi.org/10.3390/jpm11020154 - 23 Feb 2021
Cited by 5 | Viewed by 1061
Abstract
Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer [...] Read more.
Lung cancer is the second most frequently diagnosed cancer type and responsible for the highest number of cancer deaths worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are subtypes of non-small-cell lung cancer which has the highest frequency of lung cancer cases. We aimed to analyze genomic and transcriptomic variations including simple nucleotide variations (SNVs), copy number variations (CNVs) and differential expressed genes (DEGs) in order to find key genes and pathways for diagnostic and prognostic prediction for lung adenocarcinoma and lung squamous cell carcinoma. We performed a univariate Cox model and then lasso-regularized Cox model with leave-one-out cross-validation using The Cancer Genome Atlas (TCGA) gene expression data in tumor samples. We generated 35- and 33-gene signatures for prognostic risk prediction based on the overall survival time of the patients with LUAD and LUSC, respectively. When we clustered patients into high- and low-risk groups, the survival analysis showed highly significant results with high prediction power for both training and test datasets. Then, we characterized the differences including significant SNVs, CNVs, DEGs, active subnetworks, and the pathways. We described the results for the risk groups and cancer subtypes separately to identify specific genomic alterations between both high-risk groups and cancer subtypes. Both LUAD and LUSC high-risk groups have more downregulated immune pathways and upregulated metabolic pathways. On the other hand, low-risk groups have both up- and downregulated genes on cancer-related pathways. Both LUAD and LUSC have important gene alterations such as CDKN2A and CDKN2B deletions with different frequencies. SOX2 amplification occurs in LUSC and PSMD4 amplification in LUAD. EGFR and KRAS mutations are mutually exclusive in LUAD samples. EGFR, MGA, SMARCA4, ATM, RBM10, and KDM5C genes are mutated only in LUAD but not in LUSC. CDKN2A, PTEN, and HRAS genes are mutated only in LUSC samples. The low-risk groups of both LUAD and LUSC tend to have a higher number of SNVs, CNVs, and DEGs. The signature genes and altered genes have the potential to be used as diagnostic and prognostic biomarkers for personalized oncology. Full article
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Article
Immediate Prosthetic Breast Reconstruction after Nipple-Sparing Mastectomy: Traditional Subpectoral Technique versus Direct-to-Implant Prepectoral Reconstruction without Acellular Dermal Matrix
J. Pers. Med. 2021, 11(2), 153; https://doi.org/10.3390/jpm11020153 - 22 Feb 2021
Viewed by 1145
Abstract
Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast [...] Read more.
Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP. Results: 177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (p < 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR. Conclusions: Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM. Full article
(This article belongs to the Special Issue Innovations in the Integrated Management of Breast Cancer)
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Review
Targeted Treatment of Follicular Lymphoma
J. Pers. Med. 2021, 11(2), 152; https://doi.org/10.3390/jpm11020152 - 22 Feb 2021
Cited by 1 | Viewed by 1314
Abstract
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Advanced stage disease is considered incurable and is characterized by a prolonged relapsing/remitting course. A significant minority have less favorable outcomes, particularly those with transformed or early progressive disease. Recent advances in our [...] Read more.
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Advanced stage disease is considered incurable and is characterized by a prolonged relapsing/remitting course. A significant minority have less favorable outcomes, particularly those with transformed or early progressive disease. Recent advances in our understanding of the unique genetic and immune biology of FL have led to increasingly potent and precise novel targeted agents, suggesting that a chemotherapy-future may one day be attainable. The current pipeline of new therapeutics is unprecedented. Particularly exciting is that many agents have non-overlapping modes of action, offering potential new combinatorial options and synergies. This review provides up-to-date clinical and mechanistic data on these new therapeutics. Ongoing dedicated attention to basic, translational and clinical research will provide further clarity as to when and how to best use these agents, to improve efficacy without eliciting unnecessary toxicity. Full article
(This article belongs to the Special Issue Targeted Treatment of Lymphoma, Leukaemia and Myeloma)
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Review
Circulating Free DNA and Its Emerging Role in Autoimmune Diseases
J. Pers. Med. 2021, 11(2), 151; https://doi.org/10.3390/jpm11020151 - 20 Feb 2021
Cited by 2 | Viewed by 990
Abstract
Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid [...] Read more.
Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects. Full article
(This article belongs to the Special Issue Personalized Medicine in Autoimmune Diseases)
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Article
The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?
J. Pers. Med. 2021, 11(2), 150; https://doi.org/10.3390/jpm11020150 - 20 Feb 2021
Cited by 1 | Viewed by 707
Abstract
In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), [...] Read more.
In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), after pre-treatment with fluvoxamine 50 mg (12 h and 2 h prior to MDZ administration), and voriconazole 400 mg (2 h before MDZ administration) (inhibition session), and after a 7-day pre-treatment with the inducer rifampicin 600 mg (induction session). The 1β-OH-DCA/DCA UMR was measured at each session, and correlations with MDZ metrics were established. At baseline, the 1β-OH-DCA/DCA UMR correlated significantly with oral MDZ clearance (r = 0.652, p = 0.041) and Cmax (r = −0.652, p = 0.041). In addition, the modulation of CYP3A was reflected in the 1β-OH-DCA/DCA UMR after the intake of rifampicin (induction ratio = 11.4, p < 0.01). During the inhibition session, a non-significant 22% decrease in 1β-OH-DCA/DCA was observed (p = 0.275). This result could be explained by the short duration of CYP3A inhibitors intake fixed in our clinical trial. Additional studies, particularly involving CYP3A inhibition for a longer period and larger sample sizes, are needed to confirm the 1β-OH-DCA/DCA metric as a suitable CYP3A biomarker. Full article
(This article belongs to the Special Issue Personalized Medicine: Pharmacokinetics)
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Review
Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer
J. Pers. Med. 2021, 11(2), 149; https://doi.org/10.3390/jpm11020149 - 19 Feb 2021
Cited by 4 | Viewed by 1215
Abstract
The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. [...] Read more.
The underlying molecular heterogeneity of cancer is responsible for the dynamic clinical landscape of this disease. The combination of genomic and proteomic alterations, including both inherited and acquired mutations, promotes tumor diversity and accounts for variable disease progression, therapeutic response, and clinical outcome. Recent advances in high-throughput proteogenomic profiling of tumor samples have resulted in the identification of novel oncogenic drivers, tumor suppressors, and signaling networks; biomarkers for the prediction of drug sensitivity and disease progression; and have contributed to the development of novel and more effective treatment strategies. In this review, we will focus on the impact of historical and recent advances in single platform and integrative proteogenomic studies in breast and ovarian cancer, which constitute two of the most lethal forms of cancer for women, and discuss the molecular similarities of these diseases, the impact of these findings on our understanding of tumor biology as well as the clinical applicability of these discoveries. Full article
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Article
A Prospective Study: Highlights of Hippocampal Spectroscopy in Cognitive Impairment in Patients with Type 1 and Type 2 Diabetes
J. Pers. Med. 2021, 11(2), 148; https://doi.org/10.3390/jpm11020148 - 19 Feb 2021
Cited by 1 | Viewed by 695
Abstract
Diabetes mellitus type 1 and 2 is associated with cognitive impairment. Previous studies have reported a relationship between changes in cerebral metabolite levels and the variability of glycemia. However, the specific risk factors that affect the metabolic changes associated with type 1 and [...] Read more.
Diabetes mellitus type 1 and 2 is associated with cognitive impairment. Previous studies have reported a relationship between changes in cerebral metabolite levels and the variability of glycemia. However, the specific risk factors that affect the metabolic changes associated with type 1 and type 2 diabetes in cognitive dysfunction remain uncertain. The aim of the study was to evaluate the specificity of hippocampal spectroscopy in type 1 and type 2 diabetes and cognitive dysfunction. Materials and methods: 65 patients with type 1 diabetes with cognitive deficits and 20 patients without, 75 patients with type 2 diabetes with cognitive deficits and 20 patients without have participated in the study. The general clinical analysis and evaluation of risk factors of cognitive impairment were carried out. Neuropsychological testing included the Montreal Scale of Cognitive Dysfunction Assessment (MoCA test). Magnetic resonance spectroscopy (MRS) was performed in the hippocampal area, with the assessment of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and phosphocreatine (PCr) levels. Statistical processing was performed using the commercially available IBM SPSS software. Results: Changes in the content of NAA, choline Cho, phosphocreatine Cr2 and their ratios were observed in type 1 diabetes. More pronounced changes in hippocampal metabolism were observed in type 2 diabetes for all of the studied metabolites. Primary risk factors of neurometabolic changes in patients with type 1 diabetes were episodes of severe hypoglycemia in the history of the disease, diabetic ketoacidosis (DKA), chronic hyperglycemia, and increased body mass index (BMI). In type 2 diabetes, arterial hypertension (AH), BMI, and patient’s age are of greater importance, while the level of glycated hemoglobin (HbA1c), duration of the disease, level of education and insulin therapy are of lesser importance. Conclusion: Patients with diabetes have altered hippocampal metabolism, which may serve as an early predictive marker. The main modifiable factors have been identified, correction of which may slow down the progression of cognitive dysfunction. Full article
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Article
Methylene Blue and Proflavine as Intraarterial Marker for Functional Perforazome—Comparative Study
J. Pers. Med. 2021, 11(2), 147; https://doi.org/10.3390/jpm11020147 - 19 Feb 2021
Viewed by 488
Abstract
Methylene blue (MB) is both a dye and a medicine known and used for a long time including as lymphatic tracer in melanoma and breast cancer for revealing sentinel lymph nodes. Proflavine (PRO) is an acriflavine dye, used as bacteriostatic disinfectant against many [...] Read more.
Methylene blue (MB) is both a dye and a medicine known and used for a long time including as lymphatic tracer in melanoma and breast cancer for revealing sentinel lymph nodes. Proflavine (PRO) is an acriflavine dye, used as bacteriostatic disinfectant against many gram-positive bacteria that was also successfully applied to evaluate morphopathological changes in tissues. This study was performed on a group of twenty-eight Wistar rats and had as its main objective the in vivo evaluation of the use of MB and PRO as perforator tracers. The two dyes proved to be effective functional perforasome tracers with medium inflammatory infiltrate in the skin of the island perforator flap which heals perfectly at 14 days with complete absence of the inflammatory reaction. At the same injected amount, PRO seems to determine a greater inflammatory reaction compared with MB, but in smaller concentration, the inflammatory response is absent in the case of PRO. In conclusion, both substances tested within this in vivo study are good functional perforasome tracers, but PRO has the advantage of the absence of inflammatory reaction when using lower concentrations, while preserving unalerted its efficiency as tracer. Full article
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Article
Association of Sepsis Mortality with Specific Cancer Sites and Treatment Type: The Multiethnic Cohort Study
J. Pers. Med. 2021, 11(2), 146; https://doi.org/10.3390/jpm11020146 - 19 Feb 2021
Viewed by 640
Abstract
Sepsis is a severe dysregulated immune response to infection. Sepsis deaths represent 9% of cancer deaths in the U.S. Evidence of the effect of specific cancer sites on sepsis mortality risk remains limited, and no research has evaluated the effect of cancer treatment [...] Read more.
Sepsis is a severe dysregulated immune response to infection. Sepsis deaths represent 9% of cancer deaths in the U.S. Evidence of the effect of specific cancer sites on sepsis mortality risk remains limited, and no research has evaluated the effect of cancer treatment on the risk of sepsis death. We examined whether cancer sites and treatments differentially affect the risk of sepsis death compared to other-cause mortality, among the 94,784 Hawaii participants in the Multiethnic Cohort, including 29,255 cancer cases, using competing risk Cox proportional hazards regression. Cancer diagnosis at any site was associated with similar increases in sepsis and non-sepsis mortality risk (HR: 3.39 and 3.51, resp.). Colorectal cancer differentially affected the risk of sepsis and non-sepsis mortality with a 40% higher effect on the risk of sepsis death compared with non-sepsis mortality (RRR: 1.40; 95% CI: 1.14–1.72). Lung cancer was associated with a significantly lower increase in sepsis compared to non-sepsis mortality (HR: 1.22 and 3.0, resp.; RRR: 0.39). Radiation therapy had no effect on sepsis mortality but was associated with higher risk of non-sepsis mortality (HR: 0.90 and 1.16, resp.; RRR: 0.76), whereas chemotherapy was associated with higher risk of both sepsis and non-sepsis mortality (HR: 1.31 and 1.21, resp.). We conclude that the risk of sepsis-related mortality is differentially affected by cancer sites and treatments. These associations were consistent across sexes and ethnic groups. Full article
(This article belongs to the Section Mechanisms of Diseases)
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Article
The Role of SNP Interactions when Determining Independence of Novel Signals in Genetic Association Studies—An Application to ARG1 and Bronchodilator Response
J. Pers. Med. 2021, 11(2), 145; https://doi.org/10.3390/jpm11020145 - 19 Feb 2021
Viewed by 973
Abstract
Genome-wide association studies (GWAS) play a critical role in identifying many loci for common diseases and traits. There has been a rapid increase in the number of GWAS over the past decade. As additional GWAS are being conducted, it is unclear whether a [...] Read more.
Genome-wide association studies (GWAS) play a critical role in identifying many loci for common diseases and traits. There has been a rapid increase in the number of GWAS over the past decade. As additional GWAS are being conducted, it is unclear whether a novel signal associated with the trait of interest is independent of single nucleotide polymorphisms (SNPs) in the same region that has been previously associated with the trait of interest. The general approach to determining whether the novel association is independent of previous signals is to examine the association of the novel SNP with the trait of interest conditional on the previously identified SNP and/or calculate linkage disequilibrium (LD) between the two SNPs. However, the role of epistasis and SNP by SNP interactions are rarely considered. Through simulation studies, we examined the role of SNP by SNP interactions when determining the independence of two genetic association signals. We have created an R package on Github called gxgRC to generate these simulation studies based on user input. In genetic association studies of asthma, we considered the role of SNP by SNP interactions when determining independence of signals for SNPs in the ARG1 gene and bronchodilator response. Full article
(This article belongs to the Special Issue APAA: Asthma Pharmacogenetics across Ages)
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Article
Assessing Lifestyle Behaviours of People Living with Neurological Conditions: A Panoramic View of Community Dwelling Australians from 2007–2018
J. Pers. Med. 2021, 11(2), 144; https://doi.org/10.3390/jpm11020144 - 19 Feb 2021
Cited by 1 | Viewed by 1221
Abstract
Neurological disorders pose a substantial health and economic burden to the individual and society, necessitating strategies for effective prevention and disease management. Lifestyle behaviours play a role in risk and management of some neurological disorders; however, overlap between lifestyle behaviours across disorders has [...] Read more.
Neurological disorders pose a substantial health and economic burden to the individual and society, necessitating strategies for effective prevention and disease management. Lifestyle behaviours play a role in risk and management of some neurological disorders; however, overlap between lifestyle behaviours across disorders has not been well explored. We used log-binomial regression to assess associations of selected lifestyle behaviours in community-dwelling Australians (n = 192,091), some of whom self-reported Alzheimer’s disease (AD), motor neurone disease (MND), multiple sclerosis (MS), Parkinson’s disease (PD) or stroke. Of six lifestyle behaviours, undertaking physical activity was inversely associated with the presence of all neurological disorders except PD. Smoking was positively associated with MND and stroke, and inversely associated with PD. Participants with AD and stroke shared inverse associations with cognitive engagement, face-to-face social interaction and stress-reducing activities, and MS was positively associated with online social interaction and stress-reduction activities. Of eleven food and beverage consumption categories, no associations were seen in MND, ten categories were inversely associated with people with AD or stroke, and six of these with PD. Vegetable and soft drink consumption were associated with MS. Further detailed assessment of commonalities in lifestyle behaviours across neurological disorders may inform potential strategies for risk reduction across disorders. Full article
Article
The Assisi Think Tank Meeting Breast Large Database for Standardized Data Collection in Breast Cancer—ATTM.BLADE
J. Pers. Med. 2021, 11(2), 143; https://doi.org/10.3390/jpm11020143 - 19 Feb 2021
Viewed by 970
Abstract
Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and [...] Read more.
Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and Methods: The seven-step Breast LArge DatabasE (BLADE) project included data collection, analysis, application, and evaluation on a data-sharing platform. The multidisciplinary team developed a consensus-based ontology of validated variables with over 80% agreement. This English-language ontology constituted a breast cancer library with seven knowledge domains: baseline, primary systemic therapy, surgery, adjuvant systemic therapies, radiation therapy, follow-up, and toxicity. The library was uploaded to the BLADE domain. The safety of data encryption and preservation was tested according to General Data Protection Regulation (GDPR) guidelines on data from 15 clinical charts. The system was validated on 64 patients who had undergone post-mastectomy radiation therapy. In October 2018, the BLADE system was approved by the Ethical Committee of Fondazione Policlinico Gemelli IRCCS, Rome, Italy (Protocol No. 0043996/18). Results: From June 2016 to July 2019, the multidisciplinary team completed the work plan. An ontology of 218 validated variables was uploaded to the BLADE domain. The GDPR safety test confirmed encryption and data preservation (on 5000 random cases). All validation benchmarks were met. Conclusion:BLADE is a support system for follow-up and assessment of breast cancer care. To successfully develop and validate it as the first standardized data collection system, multidisciplinary collaboration was crucial in selecting its ontology and knowledge domains. BLADE is suitable for multi-center uploading of retrospective and prospective clinical data, as it ensures anonymity and data privacy. Full article
(This article belongs to the Special Issue Innovations in the Integrated Management of Breast Cancer)
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Systematic Review
Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: A Systematic Review
J. Pers. Med. 2021, 11(2), 140; https://doi.org/10.3390/jpm11020140 - 19 Feb 2021
Cited by 1 | Viewed by 1052
Abstract
Background and objectives: Exposure to ionizing radiation (IR) has increased immensely over the past years, owing to diagnostic and therapeutic reasons. However, certain radiosensitive individuals show toxic enhanced reaction to IR, and it is necessary to specifically protect them from unwanted exposure. [...] Read more.
Background and objectives: Exposure to ionizing radiation (IR) has increased immensely over the past years, owing to diagnostic and therapeutic reasons. However, certain radiosensitive individuals show toxic enhanced reaction to IR, and it is necessary to specifically protect them from unwanted exposure. Although predicting radiosensitivity is the way forward in the field of personalised medicine, there is limited information on the potential biomarkers. The aim of this systematic review is to identify evidence from a range of literature in order to present the status quo of our knowledge of IR-induced changes in protein expression in normal tissues, which can be correlated to radiosensitivity. Methods: Studies were searched in NCBI Pubmed and in ISI Web of Science databases and field experts were consulted for relevant studies. Primary peer-reviewed studies in English language within the time-frame of 2011 to 2020 were considered. Human non-tumour tissues and human-derived non-tumour model systems that have been exposed to IR were considered if they reported changes in protein levels, which could be correlated to radiosensitivity. At least two reviewers screened the titles, keywords, and abstracts of the studies against the eligibility criteria at the first phase and full texts of potential studies at the second phase. Similarly, at least two reviewers manually extracted the data and accessed the risk of bias (National Toxicology Program/Office for Health Assessment and Translation—NTP/OHAT) for the included studies. Finally, the data were synthesised narratively in accordance to synthesis without meta analyses (SWiM) method. Results: In total, 28 studies were included in this review. Most of the records (16) demonstrated increased residual DNA damage in radiosensitive individuals compared to normo-sensitive individuals based on γH2AX and TP53BP1. Overall, 15 studies included proteins other than DNA repair foci, of which five proteins were selected, Vascular endothelial growth factor (VEGF), Caspase 3, p16INK4A (Cyclin-dependent kinase inhibitor 2A, CDKN2A), Interleukin-6, and Interleukin-1β, that were connected to radiosensitivity in normal tissue and were reported at least in two independent studies. Conclusions and implication of key findings: A majority of studies used repair foci as a tool to predict radiosensitivity. However, its correlation to outcome parameters such as repair deficient cell lines and patients, as well as an association to moderate and severe clinical radiation reactions, still remain contradictory. When IR-induced proteins reported in at least two studies were considered, a protein network was discovered, which provides a direction for further studies to elucidate the mechanisms of radiosensitivity. Although the identification of only a few of the commonly reported proteins might raise a concern, this could be because (i) our eligibility criteria were strict and (ii) radiosensitivity is influenced by multiple factors. Registration: PROSPERO (CRD42020220064). Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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Article
Identification of Somatic Structural Variants in Solid Tumors by Optical Genome Mapping
J. Pers. Med. 2021, 11(2), 142; https://doi.org/10.3390/jpm11020142 - 18 Feb 2021
Cited by 5 | Viewed by 1206
Abstract
Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) [...] Read more.
Genomic structural variants comprise a significant fraction of somatic mutations driving cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid tumors. Using as little as 6.5 mg of input tumor tissue, we show successful extraction of high-molecular-weight genomic DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system’s utility in identifying somatic SVs affecting functional and cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid tumors to capture SVs across the entire genome with functional importance in cancer prognosis and treatment. Full article
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Article
Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader–Willi Syndrome
J. Pers. Med. 2021, 11(2), 141; https://doi.org/10.3390/jpm11020141 - 18 Feb 2021
Viewed by 781
Abstract
Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and [...] Read more.
Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients—with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea–hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients’ care. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
Article
Personalized Consideration of Admission-Glucose Gap between Estimated Average and Initial Glucose Levels on Short-Term Stroke Outcome
J. Pers. Med. 2021, 11(2), 139; https://doi.org/10.3390/jpm11020139 - 18 Feb 2021
Cited by 1 | Viewed by 562
Abstract
Background: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term [...] Read more.
Background: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term functional outcomes in acute ischemic stroke (AIS). Methods: We enrolled patients with AIS or transient ischemic attack who had been admitted within 7 days of symptom onset to three stroke centers from May 2016 to December 2019. The admission-glucose gap between estimated average glucose levels (eAG) and initial glucose level (eAG–initial glucose) was categorized into four groups. The short-term functional outcome was evaluated using the modified Rankin Scale (mRS) score at 3 months after stroke onset and was dichotomized. Results: Among 1332 included subjects, 548 (41.1%) had poor short-term functional outcomes. After adjusting for multiple variables, a severe negative glucose gap (eAG–initial glucose ≤ −50 mg/dL) was significantly associated with poor short-term functional outcome (OR, 1.573; 95% CI, 1.101–2.248). After dichotomizing glycemic control status, its significance was only maintained in the good glycemic control group (HbA1c < 6.5%) (OR, 1.914; 95% CI, 1.155–3.169). Conclusions: An elevated admission-glucose gap, in which the initial glucose level was much higher than the estimated glucose level was based on HbA1c, was associated with poor stroke prognosis. In addition to admission-glucose levels, glycemic control status at the time of stroke onset should be considered when predicting short-term stroke outcomes. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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Article
Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma
J. Pers. Med. 2021, 11(2), 138; https://doi.org/10.3390/jpm11020138 - 17 Feb 2021
Cited by 1 | Viewed by 796
Abstract
The ETS domain family of transcription factors is involved in a number of biological processes, and is commonly misregulated in various forms of cancer. Using microarray datasets from patients with different grades of glioma, we have analyzed the expression profiles of various ETS [...] Read more.
The ETS domain family of transcription factors is involved in a number of biological processes, and is commonly misregulated in various forms of cancer. Using microarray datasets from patients with different grades of glioma, we have analyzed the expression profiles of various ETS genes, and have identified ETV1, ELK3, ETV4, ELF4, and ETV6 as novel biomarkers for the identification of different glioma grades. We have further analyzed the gene regulatory networks of ETS transcription factors and compared them to previous microarray studies, where Elk-1-VP16 or PEA3-VP16 were overexpressed in neuroblastoma cell lines, and we identify unique and common regulatory networks for these ETS proteins. Full article
(This article belongs to the Special Issue Recent Developments in Cancer Systems Biology)
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Communication
Delivering Personalized Care at a Distance: How Telemedicine Can Foster Getting to Know the Patient as a Person
J. Pers. Med. 2021, 11(2), 137; https://doi.org/10.3390/jpm11020137 - 17 Feb 2021
Cited by 4 | Viewed by 885
Abstract
The promise of precision medicine is based on the use of new technologies to better characterize patients by defining individuals in the areas of genomics, proteomics, metabolomics and other aspects of biologic variability. Wise application of modern technology can similarly transform health visits [...] Read more.
The promise of precision medicine is based on the use of new technologies to better characterize patients by defining individuals in the areas of genomics, proteomics, metabolomics and other aspects of biologic variability. Wise application of modern technology can similarly transform health visits with patients, allowing for better characterization of the patient’s individual life circumstances than possible in a traditional office visit. The use of, and experience with, telemedicine have increased significantly during the COVID-19 pandemic. Patients and clinicians report high satisfaction with telemedicine, and the quality of communication and patient-centeredness experienced in this setting are both rated highly. In this article, we explore the benefits offered by telemedicine in facilitating personalized care with particular focus on telemedicine delivered by video platforms. We propose strategies and skills specific to the effective implementation of personalized telemedicine, drawing on literature in patient-centered communication and home visits. While traditional in-person office visits continue to offer important opportunities such as thorough physical examination and the potential for enhanced non-verbal communication, telemedicine offers many important advantages that can facilitate the process of getting to know the patient as a person. Full article
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Article
Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy
J. Pers. Med. 2021, 11(2), 136; https://doi.org/10.3390/jpm11020136 - 17 Feb 2021
Cited by 2 | Viewed by 846
Abstract
Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an [...] Read more.
Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent 1O2 generation under light irradiation because of micelle formation. However, 1O2 was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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Review
Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health
J. Pers. Med. 2021, 11(2), 135; https://doi.org/10.3390/jpm11020135 - 16 Feb 2021
Cited by 2 | Viewed by 1469
Abstract
The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high [...] Read more.
The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term. Full article
(This article belongs to the Special Issue Role of MicroRNA in Cancer Development and Treatment)
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Article
Acceptability of a Patient Portal (Opal) in HIV Clinical Care: A Feasibility Study
J. Pers. Med. 2021, 11(2), 134; https://doi.org/10.3390/jpm11020134 - 16 Feb 2021
Viewed by 1069
Abstract
Opal (opalmedapps.com), a patient portal in use at the Cedars Cancer Centre of the McGill University Health Centre (MUHC) (Montreal, Canada), gives cancer patients access to their medical records, collects information on patient-reported outcome measures (PROMs), and has demonstrated patient satisfaction with care. [...] Read more.
Opal (opalmedapps.com), a patient portal in use at the Cedars Cancer Centre of the McGill University Health Centre (MUHC) (Montreal, Canada), gives cancer patients access to their medical records, collects information on patient-reported outcome measures (PROMs), and has demonstrated patient satisfaction with care. This feasibility study aims to evaluate Opal’s potential acceptability in the context of HIV care. People living with HIV (PLWH) and their healthcare providers (HCPs) completed cross-sectional surveys from August 2019 to February 2020 at large HIV centers, including the Chronic Viral Illness Service of the MUHC, and other HIV clinical sites in Montreal and Paris, France. This study comprised 114 PLWH (mean age 48 years old, SD = 12.4), including 74% men, 24% women, and 2% transgender or other; and 31 HCPs (mean age 46.5 years old, SD = 11.4), including 32% men, 65% women, and 3% other. Ownership of smartphones and tablets was high (93% PLWH, 96% HCPs), and participants were willing to use Opal (74% PLWH, 68% HCPs). Participants were interested in most Opal functions and PROMs, particularly PROMs capturing quality of life (89% PLWH, 77% HCPs), experience of healthcare (86% PLWH, 97% HCPs), and HIV self-management (92% PLWH, 97% HCPs). This study suggests Opal has high acceptability and potential usefulness as perceived by PLWH and HCPs. Full article
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Review
PET/CT Imaging for Personalized Management of Infectious Diseases
J. Pers. Med. 2021, 11(2), 133; https://doi.org/10.3390/jpm11020133 - 16 Feb 2021
Cited by 3 | Viewed by 1398
Abstract
Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which is increasingly being used in infectious diseases. Because infection foci often consume more glucose than surrounding tissue, most infections can be diagnosed with PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analogue [...] Read more.
Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which is increasingly being used in infectious diseases. Because infection foci often consume more glucose than surrounding tissue, most infections can be diagnosed with PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analogue of glucose labeled with Fluorine-18. In this review, we discuss common infectious diseases in which FDG-PET/CT is currently applied including bloodstream infection of unknown origin, infective endocarditis, vascular graft infection, spondylodiscitis, and cyst infections. Next, we highlight the latest developments within the field of PET/CT, including total body PET/CT, use of novel PET radiotracers, and potential future applications of PET/CT that will likely lead to increased capabilities for patient-tailored treatment of infectious diseases. Full article
(This article belongs to the Special Issue Systems Radiology and Personalized Medicine)
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Brief Report
Intestinal Dysbiosis in Young Cystic Fibrosis Rabbits
J. Pers. Med. 2021, 11(2), 132; https://doi.org/10.3390/jpm11020132 - 16 Feb 2021
Viewed by 738
Abstract
Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model [...] Read more.
Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model of CF, which is shown to manifest many human patient-like pathological changes, including intestinal obstruction. Here, we investigated the feces microbiome in young CF rabbits in the absence of antibiotics treatment. Stool samples were collected from seven- to nine-week-old CF rabbits (n = 7) and age-matched wild-type (WT) rabbits (n = 6). Microbiomes were investigated by iTag sequencing of 16S rRNA genes, and functional profiles were predicted using PICRUSt. Consistent with reports of those in pediatric CF patients, the fecal microbiomes of CF rabbits are of lower richness and diversity than that of WT rabbits, with a marked taxonomic and inferred functional dysbiosis. Our work identified a new CF animal model with the manifestation of intestinal dysbiosis phenotype. This model system may facilitate the research and development of novel treatments for CF-associated gastrointestinal diseases. Full article
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Article
Common Treatment, Common Variant: Evolutionary Prediction of Functional Pharmacogenomic Variants
J. Pers. Med. 2021, 11(2), 131; https://doi.org/10.3390/jpm11020131 - 16 Feb 2021
Cited by 1 | Viewed by 692
Abstract
Pharmacogenomics holds the promise of personalized drug efficacy optimization and drug toxicity minimization. Much of the research conducted to date, however, suffers from an ascertainment bias towards European participants. Here, we leverage publicly available, whole genome sequencing data collected from global populations, evolutionary [...] Read more.
Pharmacogenomics holds the promise of personalized drug efficacy optimization and drug toxicity minimization. Much of the research conducted to date, however, suffers from an ascertainment bias towards European participants. Here, we leverage publicly available, whole genome sequencing data collected from global populations, evolutionary characteristics, and annotated protein features to construct a new in silico machine learning pharmacogenetic identification method called XGB-PGX. When applied to pharmacogenetic data, XGB-PGX outperformed all existing prediction methods and identified over 2000 new pharmacogenetic variants. While there are modest pharmacogenetic allele frequency distribution differences across global population samples, the most striking distinction is between the relatively rare putatively neutral pharmacogene variants and the relatively common established and newly predicted functional pharamacogenetic variants. Our findings therefore support a focus on individual patient pharmacogenetic testing rather than on clinical presumptions about patient race, ethnicity, or ancestral geographic residence. We further encourage more attention be given to the impact of common variation on drug response and propose a new ‘common treatment, common variant’ perspective for pharmacogenetic prediction that is distinct from the types of variation that underlie complex and Mendelian disease. XGB-PGX has identified many new pharmacovariants that are present across all global communities; however, communities that have been underrepresented in genomic research are likely to benefit the most from XGB-PGX’s in silico predictions. Full article
(This article belongs to the Special Issue Pharmacogenomics: From Basic Research to Clinical Implementation)
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Review
Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach
J. Pers. Med. 2021, 11(2), 130; https://doi.org/10.3390/jpm11020130 - 15 Feb 2021
Cited by 1 | Viewed by 1054
Abstract
The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial [...] Read more.
The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in RBM20 that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine. Full article
(This article belongs to the Special Issue Genetic Basis and Clinical Determinants of Inherited Heart Disease)
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Systematic Review
Blood Pressure Patterns in Patients with Parkinson’s Disease: A Systematic Review
J. Pers. Med. 2021, 11(2), 129; https://doi.org/10.3390/jpm11020129 - 15 Feb 2021
Cited by 1 | Viewed by 1353
Abstract
(1) Background: Cardiovascular autonomic dysfunction is a non-motor feature in Parkinson’s disease with negative impact on functionality and life expectancy, prompting early detection and proper management. We aimed to describe the blood pressure patterns reported in patients with Parkinson’s disease, as measured by [...] Read more.
(1) Background: Cardiovascular autonomic dysfunction is a non-motor feature in Parkinson’s disease with negative impact on functionality and life expectancy, prompting early detection and proper management. We aimed to describe the blood pressure patterns reported in patients with Parkinson’s disease, as measured by 24-h ambulatory blood pressure monitoring. (2) Methods: We conducted a systematic search on the PubMed database. Studies enrolling patients with Parkinson’s disease undergoing 24-h ambulatory blood pressure monitoring were included. Data regarding study population, Parkinson’s disease course, vasoactive drugs, blood pressure profiles, and measurements were recorded. (3) Results: The search identified 172 studies. Forty studies eventually fulfilled the inclusion criteria, with 3090 patients enrolled. Abnormal blood pressure profiles were commonly encountered: high blood pressure in 38.13% of patients (938/2460), orthostatic hypotension in 38.68% (941/2433), supine hypertension in 27.76% (445/1603) and nocturnal hypertension in 38.91% (737/1894). Dipping status was also altered often, 40.46% of patients (477/1179) being reverse dippers and 35.67% (310/869) reduced dippers. All these patterns were correlated with negative clinical and imaging outcomes. (4) Conclusion: Patients with Parkinson’s disease have significantly altered blood pressure patterns that carry a negative prognosis. Ambulatory blood pressure monitoring should be validated as a biomarker of PD-associated cardiovascular dysautonomia and a tool for assisting therapeutic interventions. Full article
(This article belongs to the Section Mechanisms of Diseases)
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