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Editor’s Choice Articles

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

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20 pages, 1584 KiB  
Review
Deep Learning-Based Prediction of Molecular Tumor Biomarkers from H&E: A Practical Review
by Heather D. Couture
J. Pers. Med. 2022, 12(12), 2022; https://doi.org/10.3390/jpm12122022 - 7 Dec 2022
Cited by 13 | Viewed by 4060
Abstract
Molecular and genomic properties are critical in selecting cancer treatments to target individual tumors, particularly for immunotherapy. However, the methods to assess such properties are expensive, time-consuming, and often not routinely performed. Applying machine learning to H&E images can provide a more cost-effective [...] Read more.
Molecular and genomic properties are critical in selecting cancer treatments to target individual tumors, particularly for immunotherapy. However, the methods to assess such properties are expensive, time-consuming, and often not routinely performed. Applying machine learning to H&E images can provide a more cost-effective screening method. Dozens of studies over the last few years have demonstrated that a variety of molecular biomarkers can be predicted from H&E alone using the advancements of deep learning: molecular alterations, genomic subtypes, protein biomarkers, and even the presence of viruses. This article reviews the diverse applications across cancer types and the methodology to train and validate these models on whole slide images. From bottom-up to pathologist-driven to hybrid approaches, the leading trends include a variety of weakly supervised deep learning-based approaches, as well as mechanisms for training strongly supervised models in select situations. While results of these algorithms look promising, some challenges still persist, including small training sets, rigorous validation, and model explainability. Biomarker prediction models may yield a screening method to determine when to run molecular tests or an alternative when molecular tests are not possible. They also create new opportunities in quantifying intratumoral heterogeneity and predicting patient outcomes. Full article
(This article belongs to the Special Issue Applications of Machine Learning and Deep Learning in Precision Medicine)
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13 pages, 1444 KiB  
Article
The Predictive Value of Systemic Immune-Inflammation Index and Symptom Severity Score for Sepsis and Systemic Inflammatory Response Syndrome in Odontogenic Infections
by Marius Pricop, Oana Ancusa, Serban Talpos, Horatiu Urechescu and Bogdan Andrei Bumbu
J. Pers. Med. 2022, 12(12), 2026; https://doi.org/10.3390/jpm12122026 - 7 Dec 2022
Cited by 13 | Viewed by 1887
Abstract
Acute Odontogenic Infections (OI) are the leading cause of emergency visits and hospitalizations to the maxillofacial department, and may induce systemic inflammatory complications. Increasing numbers of OI patients need extended hospitalizations, various treatments, and intensive care. The Symptom Severity score (SS) helps doctors [...] Read more.
Acute Odontogenic Infections (OI) are the leading cause of emergency visits and hospitalizations to the maxillofacial department, and may induce systemic inflammatory complications. Increasing numbers of OI patients need extended hospitalizations, various treatments, and intensive care. The Symptom Severity score (SS) helps doctors assess the likelihood of infection and admission complications. Systemic Immune-inflammation Index (SII) is a biomarker-based inflammatory prognosis score. It was hypothesized that greater SII and SS values might suggest a higher risk for sepsis and systemic inflammatory response syndrome (SIRS). Therefore, this research aims to discover whether SII and SS scores can reliably predict odontogenic infection severity and prognosis, and if they can be used to predict the development of SIRS and sepsis in OI using admission features. The study was designed as a retrospective cohort, with patients’ data being retrieved from medical records between January 2017 to April 2022. A total of 108 OI patients were matched 1:1 as low-severity and high-severity groups. Most individuals with severe infections had diabetes and smoking as comorbidities. Severe patients had longer hospital stays (12.0 days vs. 4.1 days), although mortality rates did not significantly differ. A total of 11.1% lower-severity patients (Group A) had SIRS during hospitalization, compared to Group B with 25.9%. Group A had 7.4% of patients that developed sepsis compared to Group B’s rate of 22.2%. The correlation between OI’s SS and SII index values was positive and statistically significant (r = 0.6314). The total SII index mean was 1303, whereas the mean values by severity were 696.3 in Group A and 2312.4 in Group B. Group A’s mean SS score was 6.1, while Group B’s was 13.6. According to the calculated AUC plots, SII and SS scores were accurate predictors of sepsis and SIRS development using OI admission parameters. The adjusted odds ratio for SIRS in OI patients was 2.09, and 2.27 for sepsis. Medical professionals and dentistry teams should be encouraged to use the SII and SS scores to diagnose and anticipate sepsis and SIRS, hence improving disease management decisions. Full article
(This article belongs to the Special Issue Prevention and Management of Oral Healthcare)
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16 pages, 1739 KiB  
Article
The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population
by Anurag Verma, Scott M. Damrauer, Nawar Naseer, JoEllen Weaver, Colleen M. Kripke, Lindsay Guare, Giorgio Sirugo, Rachel L. Kember, Theodore G. Drivas, Scott M. Dudek, Yuki Bradford, Anastasia Lucas, Renae Judy, Shefali S. Verma, Emma Meagher, Katherine L. Nathanson, Michael Feldman, Marylyn D. Ritchie, Daniel J. Rader and For The Penn Medicine BioBank
J. Pers. Med. 2022, 12(12), 1974; https://doi.org/10.3390/jpm12121974 - 29 Nov 2022
Cited by 32 | Viewed by 3458
Abstract
The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker [...] Read more.
The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker data in the PMBB to facilitate discoveries and translational science. To date, 174,712 participants have been enrolled into the PMBB, including approximately 30% of participants of non-European ancestry, making it one of the most diverse medical biobanks. There is a median of seven years of longitudinal data in the EHR available on participants, who also consent to permission to recontact. Herein, we describe the operations and infrastructure of the PMBB, summarize the phenotypic architecture of the enrolled participants, and use body mass index (BMI) as a proof-of-concept quantitative phenotype for PheWAS, LabWAS, and GWAS. The major representation of African-American participants in the PMBB addresses the essential need to expand the diversity in genetic and translational research. There is a critical need for a “medical biobank consortium” to facilitate replication, increase power for rare phenotypes and variants, and promote harmonized collaboration to optimize the potential for biological discovery and precision medicine. Full article
(This article belongs to the Special Issue Genomic Medicine Cohorts Based at U.S. Health Systems and Health Centers)
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20 pages, 2985 KiB  
Review
Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors
by Waliul Islam, Takuro Niidome and Tomohiro Sawa
J. Pers. Med. 2022, 12(12), 1964; https://doi.org/10.3390/jpm12121964 - 28 Nov 2022
Cited by 17 | Viewed by 4770
Abstract
In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with [...] Read more.
In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with accumulation of the parental drug NCS. This momentous result led to discovery of the enhanced permeability and retention effect (EPR effect) in 1986. Later, the EPR effect became known worldwide, especially in nanomedicine, and is still believed to be a universal mechanism for tumor-selective accumulation of nanomedicines. Some research groups recently characterized the EPR effect as a controversial concept and stated that it has not been fully demonstrated in clinical settings, but this erroneous belief is due to non-standard drug design and use of inappropriate tumor models in investigations. Many research groups recently provided solid evidence of the EPR effect in human cancers (e.g., renal and breast), with significant diversity and heterogeneity in various patients. In this review, we focus on the dynamics of the EPR effect and restoring tumor blood flow by using EPR effect enhancers. We also discuss new applications of EPR-based nanomedicine in boron neutron capture therapy and photodynamic therapy for solid tumors. Full article
(This article belongs to the Special Issue EPR Effect-Based Cancer Targeted Therapy: Commemorative Issue in Honor of Professor Hiroshi Maeda)
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21 pages, 624 KiB  
Review
Multimorbidity, Frailty and Diabetes in Older People–Identifying Interrelationships and Outcomes
by Alan J. Sinclair and Ahmed H. Abdelhafiz
J. Pers. Med. 2022, 12(11), 1911; https://doi.org/10.3390/jpm12111911 - 16 Nov 2022
Cited by 14 | Viewed by 2789
Abstract
Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in [...] Read more.
Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in older people with diabetes, which are proportionally related to the number of morbidities and to the severity of frailty. Although, the multimorbidity pattern or cluster of morbidities that have the most adverse effect are not yet well defined, it appears that mental health disorders enhance the multimorbidity-related adverse outcomes. Therefore, comprehensive diabetes guidelines that incorporate a holistic approach that includes screening and management of mental health disorders such as depression is required. The adverse outcomes predicted by multimorbidity and frailty appear to be similar and include an increased risk of health care utilisation, disability and mortality. The differential effect of one condition on outcomes, independent of the other, still needs future exploration. In addition, prospective clinical trials are required to investigate whether interventions to reduce multimorbidity and frailty both separately and in combination would improve clinical outcomes. Full article
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20 pages, 4380 KiB  
Article
Nontraumatic Spinal Cord Injury: Epidemiology, Etiology and Management
by Diana M. Molinares, David R. Gater, Scott Daniel and Nicole L. Pontee
J. Pers. Med. 2022, 12(11), 1872; https://doi.org/10.3390/jpm12111872 - 8 Nov 2022
Cited by 18 | Viewed by 4592
Abstract
The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a [...] Read more.
The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a traumatic spinal cord injury (SCI), supraspinal influences on the peripheral nervous system and autonomic nervous system (ANS) are disrupted, leading to spastic paralysis, sympathetic blunting, and parasympathetic dominance, resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions, and uncontrolled bowel, bladder, and sexual dysfunction. This article outlines the pathophysiology of the less reported nontraumatic SCI (NTSCI), its classification, its influence on sensory/motor function, and introduces the probable comorbidities associated with SCI that will be discussed in more detail in the accompanying manuscripts of this special issue. Finally, management strategies for NTSCI will be provided. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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14 pages, 3045 KiB  
Article
A Ready-to-Use Grading Tool for Facial Palsy Examiners—Automated Grading System in Facial Palsy Patients Made Easy
by Leonard Knoedler, Maximilian Miragall, Martin Kauke-Navarro, Doha Obed, Maximilian Bauer, Patrick Tißler, Lukas Prantl, Hans-Guenther Machens, Peter Niclas Broer, Helena Baecher, Adriana C. Panayi, Samuel Knoedler and Andreas Kehrer
J. Pers. Med. 2022, 12(10), 1739; https://doi.org/10.3390/jpm12101739 - 19 Oct 2022
Cited by 17 | Viewed by 2412
Abstract
Background: The grading process in facial palsy (FP) patients is crucial for time- and cost-effective therapy decision-making. The House-Brackmann scale (HBS) represents the most commonly used classification system in FP diagnostics. This study investigated the benefits of linking machine learning (ML) techniques with [...] Read more.
Background: The grading process in facial palsy (FP) patients is crucial for time- and cost-effective therapy decision-making. The House-Brackmann scale (HBS) represents the most commonly used classification system in FP diagnostics. This study investigated the benefits of linking machine learning (ML) techniques with the HBS. Methods: Image datasets of 51 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany, between June 2020 and May 2021, were used to build the neural network. A total of nine facial poses per patient were used to automatically determine the HBS. Results: The algorithm had an accuracy of 98%. The algorithm processed the real patient image series (i.e., nine images per patient) in 112 ms. For optimized accuracy, we found 30 training runs to be the most effective training length. Conclusion: We have developed an easy-to-use, time- and cost-efficient algorithm that provides highly accurate automated grading of FP patient images. In combination with our application, the algorithm may facilitate the FP surgeon’s clinical workflow. Full article
(This article belongs to the Special Issue Computer Assisted Maxillo-Facial Surgery)
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34 pages, 7954 KiB  
Article
Metabolomic Signatures of Autism Spectrum Disorder
by Danielle Brister, Shannon Rose, Leanna Delhey, Marie Tippett, Yan Jin, Haiwei Gu and Richard E. Frye
J. Pers. Med. 2022, 12(10), 1727; https://doi.org/10.3390/jpm12101727 - 17 Oct 2022
Cited by 14 | Viewed by 4529
Abstract
Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted [...] Read more.
Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis. Full article
(This article belongs to the Special Issue A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder: Beyond Genetic Syndromes)
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17 pages, 1273 KiB  
Review
A Review of Digital Health and Biotelemetry: Modern Approaches towards Personalized Medicine and Remote Health Assessment
by Ștefan Sebastian Busnatu, Adelina-Gabriela Niculescu, Alexandra Bolocan, Octavian Andronic, Anca Mihaela Pantea Stoian, Alexandru Scafa-Udriște, Ana Maria Alexandra Stănescu, Dan Nicolae Păduraru, Mihnea Ioan Nicolescu, Alexandru Mihai Grumezescu and Viorel Jinga
J. Pers. Med. 2022, 12(10), 1656; https://doi.org/10.3390/jpm12101656 - 5 Oct 2022
Cited by 11 | Viewed by 3147
Abstract
With the prevalence of digitalization in all aspects of modern society, health assessment is becoming digital too. Taking advantage of the most recent technological advances and approaching medicine from an interdisciplinary perspective has allowed for important progress in healthcare services. Digital health technologies [...] Read more.
With the prevalence of digitalization in all aspects of modern society, health assessment is becoming digital too. Taking advantage of the most recent technological advances and approaching medicine from an interdisciplinary perspective has allowed for important progress in healthcare services. Digital health technologies and biotelemetry devices have been more extensively employed for preventing, detecting, diagnosing, monitoring, and predicting the evolution of various diseases, without requiring wires, invasive procedures, or face-to-face interaction with medical personnel. This paper aims to review the concepts correlated to digital health, classify and describe biotelemetry devices, and present the potential of digitalization for remote health assessment, the transition to personalized medicine, and the streamlining of clinical trials. Full article
(This article belongs to the Special Issue Digital Health and Telemedicine: Their Contribution to Personalized and Precision Medicine)
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13 pages, 926 KiB  
Review
Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies
by Claudio Ponticelli, Francesco Reggiani and Gabriella Moroni
J. Pers. Med. 2022, 12(10), 1557; https://doi.org/10.3390/jpm12101557 - 21 Sep 2022
Cited by 25 | Viewed by 3890
Abstract
Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, [...] Read more.
Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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21 pages, 483 KiB  
Review
Application of Artificial Intelligence Techniques to Predict Risk of Recurrence of Breast Cancer: A Systematic Review
by Claudia Mazo, Claudia Aura, Arman Rahman, William M. Gallagher and Catherine Mooney
J. Pers. Med. 2022, 12(9), 1496; https://doi.org/10.3390/jpm12091496 - 13 Sep 2022
Cited by 11 | Viewed by 4049
Abstract
Breast cancer is the most common disease among women, with over 2.1 million new diagnoses each year worldwide. About 30% of patients initially presenting with early stage disease have a recurrence of cancer within 10 years. Predicting who will have a recurrence [...] Read more.
Breast cancer is the most common disease among women, with over 2.1 million new diagnoses each year worldwide. About 30% of patients initially presenting with early stage disease have a recurrence of cancer within 10 years. Predicting who will have a recurrence and who will not remains challenging, with consequent implications for associated treatment. Artificial intelligence strategies that can predict the risk of recurrence of breast cancer could help breast cancer clinicians avoid ineffective overtreatment. Despite its significance, most breast cancer recurrence datasets are insufficiently large, not publicly available, or imbalanced, making these studies more difficult. This systematic review investigates the role of artificial intelligence in the prediction of breast cancer recurrence. We summarise common techniques, features, training and testing methodologies, metrics, and discuss current challenges relating to implementation in clinical practice. We systematically reviewed works published between 1 January 2011 and 1 November 2021 using the methodology of Kitchenham and Charter. We leveraged Springer, Google Scholar, PubMed, and IEEE search engines. This review found three areas that require further work. First, there is no agreement on artificial intelligence methodologies, feature predictors, or assessment metrics. Second, issues such as sampling strategies, missing data, and class imbalance problems are rarely addressed or discussed. Third, representative datasets for breast cancer recurrence are scarce, which hinders model validation and deployment. We conclude that predicting breast cancer recurrence remains an open problem despite the use of artificial intelligence. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)
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18 pages, 1809 KiB  
Review
iPSCs in Neurodegenerative Disorders: A Unique Platform for Clinical Research and Personalized Medicine
by Shashank Pandey, Michal Jirásko, Jan Lochman, Alexandr Chvátal, Magdalena Chottova Dvorakova and Radek Kučera
J. Pers. Med. 2022, 12(9), 1485; https://doi.org/10.3390/jpm12091485 - 10 Sep 2022
Cited by 10 | Viewed by 2992
Abstract
In the past, several animal disease models were developed to study the molecular mechanism of neurological diseases and discover new therapies, but the lack of equivalent animal models has minimized the success rate. A number of critical issues remain unresolved, such as high [...] Read more.
In the past, several animal disease models were developed to study the molecular mechanism of neurological diseases and discover new therapies, but the lack of equivalent animal models has minimized the success rate. A number of critical issues remain unresolved, such as high costs for developing animal models, ethical issues, and lack of resemblance with human disease. Due to poor initial screening and assessment of the molecules, more than 90% of drugs fail during the final step of the human clinical trial. To overcome these limitations, a new approach has been developed based on induced pluripotent stem cells (iPSCs). The discovery of iPSCs has provided a new roadmap for clinical translation research and regeneration therapy. In this article, we discuss the potential role of patient-derived iPSCs in neurological diseases and their contribution to scientific and clinical research for developing disease models and for developing a roadmap for future medicine. The contribution of humaniPSCs in the most common neurodegenerative diseases (e.g., Parkinson’s disease and Alzheimer’s disease, diabetic neuropathy, stroke, and spinal cord injury) were examined and ranked as per their published literature on PUBMED. We have observed that Parkinson’s disease scored highest, followed by Alzheimer’s disease. Furthermore, we also explored recent advancements in the field of personalized medicine, such as the patient-on-a-chip concept, where iPSCs can be grown on 3D matrices inside microfluidic devices to create an in vitro disease model for personalized medicine. Full article
(This article belongs to the Special Issue Personalized Medicine in Neurodegenerative Diseases)
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21 pages, 3238 KiB  
Article
Image Analysis in Digital Pathology Utilizing Machine Learning and Deep Neural Networks
by Paris Amerikanos and Ilias Maglogiannis
J. Pers. Med. 2022, 12(9), 1444; https://doi.org/10.3390/jpm12091444 - 1 Sep 2022
Cited by 15 | Viewed by 3081
Abstract
Detection of regions of interest (ROIs) in whole slide images (WSIs) in a clinical setting is a highly subjective and a labor-intensive task. In this work, recent developments in machine learning and computer vision algorithms are presented to assess their possible usage and [...] Read more.
Detection of regions of interest (ROIs) in whole slide images (WSIs) in a clinical setting is a highly subjective and a labor-intensive task. In this work, recent developments in machine learning and computer vision algorithms are presented to assess their possible usage and performance to enhance and accelerate clinical pathology procedures, such as ROI detection in WSIs. In this context, a state-of-the-art deep learning framework (Detectron2) was trained on two cases linked to the TUPAC16 dataset for object detection and on the JPATHOL dataset for instance segmentation. The predictions were evaluated against competing models and further possible improvements are discussed. Full article
(This article belongs to the Special Issue Development and Application of Bioinformatics in Personalized Medicine)
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18 pages, 835 KiB  
Article
The Evolution of a Large Biobank at Mass General Brigham
by Natalie T. Boutin, Samantha B. Schecter, Emma F. Perez, Natasha S. Tchamitchian, Xander R. Cerretani, Vivian S. Gainer, Matthew S. Lebo, Lisa M. Mahanta, Elizabeth W. Karlson and Jordan W. Smoller
J. Pers. Med. 2022, 12(8), 1323; https://doi.org/10.3390/jpm12081323 - 17 Aug 2022
Cited by 20 | Viewed by 2387
Abstract
The Mass General Brigham Biobank (formerly Partners HealthCare Biobank) is a large repository of biospecimens and data linked to extensive electronic health record data and survey data. Its objective is to support and enable translational research focused on genomic, environmental, biomarker and family [...] Read more.
The Mass General Brigham Biobank (formerly Partners HealthCare Biobank) is a large repository of biospecimens and data linked to extensive electronic health record data and survey data. Its objective is to support and enable translational research focused on genomic, environmental, biomarker and family history associations with disease phenotypes. The Biobank has enrolled more than 135,000 participants, generated genomic data on more than 65,000 of its participants, distributed approximately 153,000 biospecimens, and served close to 450 institutional studies with biospecimens or data. Although the Biobank has been successful, based on some measures of output, this has required substantial institutional investment. In addition, several challenges are ongoing, including: (1) developing a sustainable cost model that doesn’t rely as heavily on institutional funding; (2) integrating Biobank operations into clinical workflows; and (3) building a research resource that is diverse and promotes equity in research. Here, we describe the evolution of the Biobank and highlight key lessons learned that may inform other efforts to build biobanking efforts in health system contexts. Full article
(This article belongs to the Special Issue Genomic Medicine Cohorts Based at U.S. Health Systems and Health Centers)
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23 pages, 1233 KiB  
Review
Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis
by Iris A. L. Silva, Onofrio Laselva and Miquéias Lopes-Pacheco
J. Pers. Med. 2022, 12(8), 1321; https://doi.org/10.3390/jpm12081321 - 16 Aug 2022
Cited by 15 | Viewed by 5579
Abstract
The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over [...] Read more.
The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over the last 30 years and they have been instrumental not only in enhancing the understanding of CF pathological mechanisms but also in developing therapies targeting the underlying defects in CFTR mutations with further validation in patient-derived samples. Furthermore, recent advances toward precision medicine in CF have been made possible by optimizing protocols and establishing novel assays using human bronchial, nasal and rectal tissues, and by progressing from two-dimensional monocultures to more complex three-dimensional culture platforms. These models also enable to potentially predict clinical efficacy and responsiveness to CFTR modulator therapies at an individual level. In parallel, advanced systems, such as induced pluripotent stem cells and organ-on-a-chip, continue to be developed in order to more closely recapitulate human physiology for disease modeling and drug testing. In this review, we have highlighted novel and optimized cell models that are being used in CF research to develop novel CFTR-directed therapies (or alternative therapeutic interventions) and to expand the usage of existing modulator drugs to common and rare CF-causing mutations. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis, Treatment, and Related Disorders)
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13 pages, 535 KiB  
Article
Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study
by Stefania Gallo, Paolo Castelnuovo, Luca Spirito, Marta Feduzi, Veronica Seccia, Dina Visca, Antonio Spanevello, Erica Statuti, Manuela Latorre, Claudio Montuori, Angela Rizzi, Cristina Boccabella, Matteo Bonini and Eugenio De Corso
J. Pers. Med. 2022, 12(8), 1304; https://doi.org/10.3390/jpm12081304 - 10 Aug 2022
Cited by 20 | Viewed by 3193
Abstract
Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint [...] Read more.
Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
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15 pages, 3290 KiB  
Review
Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases
by Yaron Ilan
J. Pers. Med. 2022, 12(8), 1303; https://doi.org/10.3390/jpm12081303 - 10 Aug 2022
Cited by 17 | Viewed by 2910
Abstract
Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. [...] Read more.
Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. This variability is associated with partial or complete loss of drug effectiveness. Regular drug dosing schedules do not comply with physiological variability and contribute to resistance to chronic therapies. In this review, we describe a three-phase platform for overcoming drug resistance: introducing irregularity for improving drug response; establishing a deep learning, closed-loop algorithm for generating a personalized pattern of irregularity for overcoming drug resistance; and upscaling the algorithm by implementing quantified personal variability patterns along with other individualized genetic and proteomic-based ways. The closed-loop, dynamic, subject-tailored variability-based machinery can improve the efficacy of existing therapies in patients with chronic diseases. Full article
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14 pages, 938 KiB  
Review
Digital Twins in Healthcare: Is It the Beginning of a New Era of Evidence-Based Medicine? A Critical Review
by Patrizio Armeni, Irem Polat, Leonardo Maria De Rossi, Lorenzo Diaferia, Severino Meregalli and Anna Gatti
J. Pers. Med. 2022, 12(8), 1255; https://doi.org/10.3390/jpm12081255 - 30 Jul 2022
Cited by 45 | Viewed by 8715
Abstract
Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of [...] Read more.
Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of connected care and alter the way lifestyle, health, wellness, and chronic disease will be managed in the future. To date, however, due to technical, regulatory and ethical roadblocks, there is no consensus as to what extent DTs in healthcare can introduce revolutionary applications in the next decade. In this review, we present the current applications of DTs covering multiple areas of healthcare (precision medicine, clinical trial design, and hospital operations) to identify the opportunities and the barriers that foster or hinder their larger and faster diffusion. Finally, we discuss the current findings, opportunities and barriers, and provide recommendations to facilitate the continuous development of DTs application in healthcare. Full article
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15 pages, 345 KiB  
Review
CD24: A Novel Target for Cancer Immunotherapy
by Emmanouil Panagiotou, Nikolaos K. Syrigos, Andriani Charpidou, Elias Kotteas and Ioannis A. Vathiotis
J. Pers. Med. 2022, 12(8), 1235; https://doi.org/10.3390/jpm12081235 - 28 Jul 2022
Cited by 35 | Viewed by 6375
Abstract
Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the [...] Read more.
Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the CD24/Siglec-10 interaction has been implicated in tumor immune evasion, inhibiting macrophage-mediated phagocytosis as well as natural killer (NK) cell cytotoxicity. CD24 blockade has shown promising results in preclinical studies. Although there are limited data on efficacy, monoclonal antibodies against CD24 have demonstrated clinical safety and tolerability in two clinical trials. Other treatment modalities evaluated in the preclinical setting include antibody–drug conjugates and chimeric antigen receptor (CAR) T cell therapy. In this review, we summarize current evidence and future perspectives on CD24 as a potential target for cancer immunotherapy. Full article
(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)
20 pages, 1537 KiB  
Review
Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases
by Alessandro Trentini, Maria Cristina Manfrinato, Massimiliano Castellazzi and Tiziana Bellini
J. Pers. Med. 2022, 12(8), 1196; https://doi.org/10.3390/jpm12081196 - 22 Jul 2022
Cited by 13 | Viewed by 2827
Abstract
It is now established that sex differences occur in clinical manifestation, disease progression, and prognosis for both cardiovascular (CVDs) and central nervous system (CNS) disorders. As such, a great deal of effort is now being put into understanding these differences and turning them [...] Read more.
It is now established that sex differences occur in clinical manifestation, disease progression, and prognosis for both cardiovascular (CVDs) and central nervous system (CNS) disorders. As such, a great deal of effort is now being put into understanding these differences and turning them into “advantages”: (a) for the discovery of new sex-specific biomarkers and (b) through a review of old biomarkers from the perspective of the “newly” discovered sex/gender medicine. This is also true for matrix metalloproteinases (MMPs), enzymes involved in extracellular matrix (ECM) remodelling, which play a role in both CVDs and CNS disorders. However, most of the studies conducted up to now relegated sex to a mere confounding variable used for statistical model correction rather than a determining factor that can influence MMP levels and, in turn, disease prognosis. Consistently, this approach causes a loss of information that might help clinicians in identifying novel patterns and improve the applicability of MMPs in clinical practice by providing sex-specific threshold values. In this scenario, the current review aims to gather the available knowledge on sex-related differences in MMPs levels in CVDs and CNS conditions, hoping to shed light on their use as sex-specific biomarkers of disease prognosis or progression. Full article
(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)
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17 pages, 596 KiB  
Review
Allergic Asthma in the Era of Personalized Medicine
by Niki Papapostolou and Michael Makris
J. Pers. Med. 2022, 12(7), 1162; https://doi.org/10.3390/jpm12071162 - 18 Jul 2022
Cited by 15 | Viewed by 4825
Abstract
Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied [...] Read more.
Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
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12 pages, 3969 KiB  
Review
Gender Differences in Acute Aortic Dissection
by Eduardo Bossone, Andreina Carbone and Kim A. Eagle
J. Pers. Med. 2022, 12(7), 1148; https://doi.org/10.3390/jpm12071148 - 15 Jul 2022
Cited by 10 | Viewed by 2555
Abstract
Cardiovascular disease (CVD) represents the most important cause of mortality and morbidity worldwide. There is heterogeneity in the epidemiology and management of CVD between male and female patients. In the specific case of acute aortic dissection (AAD), women, at the time of diagnosis, [...] Read more.
Cardiovascular disease (CVD) represents the most important cause of mortality and morbidity worldwide. There is heterogeneity in the epidemiology and management of CVD between male and female patients. In the specific case of acute aortic dissection (AAD), women, at the time of diagnosis, are older than men and complain less frequently of an abrupt onset of pain with delayed presentation to the emergency department. Furthermore, a history of hypertension and chronic obstructive pulmonary disease is more common among women. In type A AAD, women more often experience pleural effusion and coronary artery compromise, but experience less neurological and malperfusion symptoms. They undergo less frequent surgical treatment and have higher overall in-hospital mortality. Conversely, in type B AAD no significant differences were shown for in-hospital mortality between the two genders. However, it should be highlighted that further studies are needed in order to develop AAD gender specific preventive, diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)
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15 pages, 1252 KiB  
Article
Neurogenic Bowel and Management after Spinal Cord Injury: A Narrative Review
by Gianna M. Rodriguez and David R. Gater
J. Pers. Med. 2022, 12(7), 1141; https://doi.org/10.3390/jpm12071141 - 14 Jul 2022
Cited by 10 | Viewed by 7028
Abstract
People with spinal cord injury (SCI) suffer from the sequela of neurogenic bowel and its disabling complications primarily constipation, fecal incontinence, and gastrointestinal (GI) symptoms. Neurogenic bowel is a functional bowel disorder with a spectrum of defecatory disorders as well as colonic and [...] Read more.
People with spinal cord injury (SCI) suffer from the sequela of neurogenic bowel and its disabling complications primarily constipation, fecal incontinence, and gastrointestinal (GI) symptoms. Neurogenic bowel is a functional bowel disorder with a spectrum of defecatory disorders as well as colonic and gastrointestinal motility dysfunction. This manuscript will review the anatomy and physiology of gastrointestinal innervation, as well as the pathophysiology associated with SCI. It will provide essential information on the recent guidelines for neurogenic bowel assessment and medical management. This will allow medical providers to partner with their patients to develop an individualized bowel plan utilizing a combination of various pharmacological, mechanical and surgical interventions that prevent complications and ensure successful management and compliance. For people with SCI and neurogenic bowel dysfunction, the fundamental goal is to maintain health and well-being, promote a good quality of life and support active, fulfilled lives in their homes and communities. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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27 pages, 1888 KiB  
Article
Pressure Injuries and Management after Spinal Cord Injury
by Nicole M. Vecin and David R. Gater
J. Pers. Med. 2022, 12(7), 1130; https://doi.org/10.3390/jpm12071130 - 12 Jul 2022
Cited by 13 | Viewed by 14243
Abstract
Spinal cord injury (SCI) results in motor paralysis and sensory loss that places individuals at particularly high risk of pressure injuries. Multiple comorbidities associated with autonomic, cardiovascular, pulmonary, endocrine, gastrointestinal, genitourinary, neurological, and musculoskeletal dysfunction makes it even more likely that pressure injuries [...] Read more.
Spinal cord injury (SCI) results in motor paralysis and sensory loss that places individuals at particularly high risk of pressure injuries. Multiple comorbidities associated with autonomic, cardiovascular, pulmonary, endocrine, gastrointestinal, genitourinary, neurological, and musculoskeletal dysfunction makes it even more likely that pressure injuries will occur. This manuscript will review the structure and function of the integumentary system, and address the multidisciplinary approach required to prevent and manage pressure injuries in this vulnerable population. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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20 pages, 935 KiB  
Article
Pathophysiology, Classification and Comorbidities after Traumatic Spinal Cord Injury
by James Guest, Nilanjana Datta, George Jimsheleishvili and David R. Gater, Jr.
J. Pers. Med. 2022, 12(7), 1126; https://doi.org/10.3390/jpm12071126 - 11 Jul 2022
Cited by 30 | Viewed by 6918
Abstract
The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a [...] Read more.
The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a spinal cord injury (SCI), supraspinal influences on the spinal segmental control system and autonomic nervous system (ANS) are disrupted, leading to spastic paralysis, pain and dysesthesia, sympathetic blunting and parasympathetic dominance resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions and uncontrolled bowel, bladder, and sexual dysfunction. This article outlines the pathophysiology of traumatic SCI, current and emerging methods of classification, and its influence on sensory/motor function, and introduces the probable comorbidities associated with SCI that will be discussed in more detail in the accompanying manuscripts of this special issue. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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15 pages, 2787 KiB  
Article
Autonomic Dysfunction and Management after Spinal Cord Injury: A Narrative Review
by Austin M. Henke, Zackery J. Billington and David R. Gater, Jr.
J. Pers. Med. 2022, 12(7), 1110; https://doi.org/10.3390/jpm12071110 - 7 Jul 2022
Cited by 20 | Viewed by 7658
Abstract
The autonomic nervous system (ANS), composed of the sympathetic and parasympathetic nervous systems, acts to maintain homeostasis in the body through autonomic influences on the smooth muscle, cardiac muscles, blood vessels, glands and organs of the body. The parasympathetic nervous system interacts via [...] Read more.
The autonomic nervous system (ANS), composed of the sympathetic and parasympathetic nervous systems, acts to maintain homeostasis in the body through autonomic influences on the smooth muscle, cardiac muscles, blood vessels, glands and organs of the body. The parasympathetic nervous system interacts via the cranial and sacral segments of the central nervous system, and the sympathetic nervous system arises from the T1–L2 spinal cord segments. After a spinal cord injury (SCI), supraspinal influence on the ANS is disrupted, leading to sympathetic blunting and parasympathetic dominance resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions and uncontrolled bowel, bladder, and sexual dysfunction. Further, afferent signals to the sympathetic cord elicit unabated reflex sympathetic outflow in response to noxious stimuli below the level of SCI. This article outlines the pathophysiology of SCI on the ANS, clinical ramifications of autonomic dysfunction, and the potential long-term sequelae of these influences following SCI. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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17 pages, 2350 KiB  
Review
Management of Patients with Severe Asthma and Chronic Rhinosinusitis with Nasal Polyps: A Multidisciplinary Shared Approach
by Veronica Seccia, Maria D’Amato, Giulia Scioscia, Diego Bagnasco, Fabiano Di Marco, Gianluca Fadda, Francesco Menzella, Ernesto Pasquini, Girolamo Pelaia, Eugenio Tremante, Eugenio De Corso and Matteo Bonini
J. Pers. Med. 2022, 12(7), 1096; https://doi.org/10.3390/jpm12071096 - 1 Jul 2022
Cited by 16 | Viewed by 3975
Abstract
Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related [...] Read more.
Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related to severe asthma, especially in presence of nasal polyps (chronic rhinosinusitis with nasal polyps, CRSwNP). Moreover, asthma exacerbation has a higher occurrence in CRSwNP. From a pathologic point of view, CRS and asthma share similar and connected mechanisms (e.g., type-2 inflammation). A multidisciplinary approach represents a crucial aspect for the optimal management of patients with concomitant asthma and CRSwNP and improvement of patient quality of life. An Italian panel of clinicians with different clinical expertise (pulmonologists, ear, nose and throat specialists, immunologists and allergy physicians) identified three different profiles of patients with coexisting asthma and nasal symptoms and discussed the specific tracks to guide a comprehensive approach to their diagnostic and therapeutic management. Currently available biological agents for the treatment of severe asthma act either on eosinophil-centered signaling network or type-2 inflammation, resulting to be effective also in CRSwNP and representing a valid option for patients with concomitant conditions. Full article
(This article belongs to the Special Issue Personalized Medicine in Otorhinolaryngology)
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18 pages, 1067 KiB  
Review
Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice
by Konstantinos Porpodis, Ioanna Tsiouprou, Apostolos Apostolopoulos, Polyxeni Ntontsi, Evangelia Fouka, Despoina Papakosta, Harissios Vliagoftis and Kalliopi Domvri
J. Pers. Med. 2022, 12(7), 1093; https://doi.org/10.3390/jpm12071093 - 30 Jun 2022
Cited by 15 | Viewed by 6683
Abstract
Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key [...] Read more.
Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key feature of asthmatic eosinophilic endotypes. In addition, evidence of biomarkers is examined with a predictive value to identify patients with severe, uncontrolled asthma who may benefit from new treatment options. Finally, there will be a discussion on the results from clinical trials regarding severe eosinophilic asthma and how the inhibition of the eosinophilic pathway by targeted treatments has led to the reduction of recurrent exacerbations. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
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16 pages, 5564 KiB  
Review
Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems
by Stefano Marletta, Nicola Fusco, Enrico Munari, Claudio Luchini, Alessia Cimadamore, Matteo Brunelli, Giulia Querzoli, Maurizio Martini, Elena Vigliar, Romano Colombari, Ilaria Girolami, Fabio Pagni and Albino Eccher
J. Pers. Med. 2022, 12(7), 1073; https://doi.org/10.3390/jpm12071073 - 29 Jun 2022
Cited by 44 | Viewed by 6068
Abstract
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering [...] Read more.
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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21 pages, 664 KiB  
Review
The Current State of Radiotherapy for Pediatric Brain Tumors: An Overview of Post-Radiotherapy Neurocognitive Decline and Outcomes
by Nicholas Major, Neal A. Patel, Josiah Bennett, Ena Novakovic, Dana Poloni, Mickey Abraham, Nolan J. Brown, Julian L. Gendreau, Ronald Sahyouni and Joshua Loya
J. Pers. Med. 2022, 12(7), 1050; https://doi.org/10.3390/jpm12071050 - 27 Jun 2022
Cited by 10 | Viewed by 2452
Abstract
Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total [...] Read more.
Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total resection with adjuvant chemotherapy or radiotherapy. The current body of literature is largely inconclusive regarding the overall benefit of adjuvant chemo- or radiotherapy. However, it is known that both are associated with conditions that lower the quality of life in children who undergo those treatments. Chemotherapy is often associated with nausea, emesis, significant fatigue, immunosuppression, and alopecia. While radiotherapy can be effective for achieving local control, it is associated with late effects such as endocrine dysfunction, secondary malignancy, and neurocognitive decline. Advancements in radiotherapy grant both an increase in lifetime survival and an increased lifetime for survivors to contend with these late effects. In this review, the authors examined all the published literature, analyzing the results of clinical trials, case series, and technical notes on patients undergoing radiotherapy for the treatment of tumors of the central nervous system with a focus on neurocognitive decline and survival outcomes. Full article
(This article belongs to the Special Issue Personalized Treatment Approaches for Paediatric Tumours of the Central Nervous System)
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12 pages, 284 KiB  
Review
Biologic Therapies in Pediatric Asthma
by Evanthia P. Perikleous, Paschalis Steiropoulos, Evangelia Nena and Emmanouil Paraskakis
J. Pers. Med. 2022, 12(6), 999; https://doi.org/10.3390/jpm12060999 - 18 Jun 2022
Cited by 14 | Viewed by 2995
Abstract
Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced [...] Read more.
Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced and very promising treatment alternative, eventually directing toward a successful precision medicine approach. The application of currently approved add-on treatments for severe asthma in children, namely omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab have been shown to be effective in terms of asthma control and exacerbation rate. However, to date, information is still lacking regarding its long-term use. As a result, data are frequently extrapolated from adult studies. Thus, the selection of the appropriate biologic agent, the potential predictors of good asthma response, and the long-term outcome in the pediatric population are still to be further investigated. The aim of the present study was to provide an overview of the current status of the latest evidence about all licensed monoclonal antibodies (mAbs) that have emerged and been applied to the field of asthma management. The innovative future targets are also briefly discussed. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
12 pages, 285 KiB  
Article
Pediatric Spina Bifida and Spinal Cord Injury
by Joslyn Gober, Sruthi P. Thomas and David R. Gater
J. Pers. Med. 2022, 12(6), 985; https://doi.org/10.3390/jpm12060985 - 17 Jun 2022
Cited by 11 | Viewed by 4258
Abstract
Pediatric spina bifida (SB) and spinal cord injury (SCI) are unfortunately common in our society, and their unique findings and comorbidities warrant special consideration. This manuscript will discuss the epidemiology, pathophysiology, prevention, and management strategies for children growing and developing with these unique [...] Read more.
Pediatric spina bifida (SB) and spinal cord injury (SCI) are unfortunately common in our society, and their unique findings and comorbidities warrant special consideration. This manuscript will discuss the epidemiology, pathophysiology, prevention, and management strategies for children growing and developing with these unique neuromuscular disorders. Growth and development of the maturing child places them at high risk of spinal cord tethering, syringomyelia, ascending paralysis, pressure injuries, and orthopedic abnormalities that must be addressed frequently and judiciously. Similarly, proper neurogenic bladder and neurogenic bowel management is essential not just for medical safety, but also for optimal psychosocial integration into the child’s expanding social circle. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
14 pages, 292 KiB  
Review
Biological Therapy of Severe Asthma and Nasal Polyps
by Agamemnon Bakakos, Florence Schleich and Petros Bakakos
J. Pers. Med. 2022, 12(6), 976; https://doi.org/10.3390/jpm12060976 - 16 Jun 2022
Cited by 18 | Viewed by 4742
Abstract
Chronic rhinosinusitis is a common disease worldwide and can be categorized into chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps. Chronic rhinosinusitis with nasal polyps is common in patients with asthma and, particularly, severe asthma. Severe asthma is effectively treated [...] Read more.
Chronic rhinosinusitis is a common disease worldwide and can be categorized into chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps. Chronic rhinosinusitis with nasal polyps is common in patients with asthma and, particularly, severe asthma. Severe asthma is effectively treated with biologics and the coexistence of severe asthma with chronic rhinosinusitis with nasal polyps presents a phenotype that is more likely to respond to such treatment. In this review, we focus on the link between asthma and nasal polyps, and we review the treatment effect of various monoclonal antibodies in patients with severe asthma and nasal polyps as well as in patients with nasal polyps without asthma or with mild-to-moderate asthma. With the enhancement of our armamentarium with new monoclonal antibodies the right choice of biologic becomes an important target and one that is difficult to achieve due to the lack of comparative head-to-head studies. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
15 pages, 1014 KiB  
Article
Neurogenic Bladder Physiology, Pathogenesis, and Management after Spinal Cord Injury
by Nathalie Elisabeth Perez, Neha Pradyumna Godbole, Katherine Amin, Raveen Syan and David R. Gater, Jr.
J. Pers. Med. 2022, 12(6), 968; https://doi.org/10.3390/jpm12060968 - 14 Jun 2022
Cited by 16 | Viewed by 8711
Abstract
Urinary incontinence is common after spinal cord injury (SCI) due to loss of supraspinal coordination and unabated reflexes in both autonomic and somatic nervous systems; if unchecked, these disturbances can become life-threatening. This manuscript will review normal anatomy and physiology of the urinary [...] Read more.
Urinary incontinence is common after spinal cord injury (SCI) due to loss of supraspinal coordination and unabated reflexes in both autonomic and somatic nervous systems; if unchecked, these disturbances can become life-threatening. This manuscript will review normal anatomy and physiology of the urinary system and discuss pathophysiology secondary to SCI. This includes a discussion of autonomic dysreflexia, as well as its diagnosis and management. The kidneys and the ureters, representing the upper urinary tract system, can be at risk related to dyssynergy between the urethral sphincters and high pressures that lead to potential vesicoureteral reflux, urinary tract infections, and calculi associated with neurogenic lower urinary tract dysfunction (NLUTD). Recent guidelines for diagnosis, evaluation, treatment and follow up of the neurogenic bladder will be reviewed and options provided for risk stratification and management. Mechanical, pharmacological, neurolysis and surgical management will be discussed. Full article
(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)
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15 pages, 750 KiB  
Article
Robustness Evaluation of a Deep Learning Model on Sagittal and Axial Breast DCE-MRIs to Predict Pathological Complete Response to Neoadjuvant Chemotherapy
by Raffaella Massafra, Maria Colomba Comes, Samantha Bove, Vittorio Didonna, Gianluca Gatta, Francesco Giotta, Annarita Fanizzi, Daniele La Forgia, Agnese Latorre, Maria Irene Pastena, Domenico Pomarico, Lucia Rinaldi, Pasquale Tamborra, Alfredo Zito, Vito Lorusso and Angelo Virgilio Paradiso
J. Pers. Med. 2022, 12(6), 953; https://doi.org/10.3390/jpm12060953 - 10 Jun 2022
Cited by 18 | Viewed by 2496
Abstract
To date, some artificial intelligence (AI) methods have exploited Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to identify finer tumor properties as potential earlier indicators of pathological Complete Response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, they work either for sagittal [...] Read more.
To date, some artificial intelligence (AI) methods have exploited Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to identify finer tumor properties as potential earlier indicators of pathological Complete Response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, they work either for sagittal or axial MRI protocols. More flexible AI tools, to be used easily in clinical practice across various institutions in accordance with its own imaging acquisition protocol, are required. Here, we addressed this topic by developing an AI method based on deep learning in giving an early prediction of pCR at various DCE-MRI protocols (axial and sagittal). Sagittal DCE-MRIs refer to 151 patients (42 pCR; 109 non-pCR) from the public I-SPY1 TRIAL database (DB); axial DCE-MRIs are related to 74 patients (22 pCR; 52 non-pCR) from a private DB provided by Istituto Tumori “Giovanni Paolo II” in Bari (Italy). By merging the features extracted from baseline MRIs with some pre-treatment clinical variables, accuracies of 84.4% and 77.3% and AUC values of 80.3% and 78.0% were achieved on the independent tests related to the public DB and the private DB, respectively. Overall, the presented method has shown to be robust regardless of the specific MRI protocol. Full article
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18 pages, 2347 KiB  
Article
Machine Learning-Assisted FTIR Analysis of Circulating Extracellular Vesicles for Cancer Liquid Biopsy
by Riccardo Di Santo, Maria Vaccaro, Sabrina Romanò, Flavio Di Giacinto, Massimiliano Papi, Gian Ludovico Rapaccini, Marco De Spirito, Luca Miele, Umberto Basile and Gabriele Ciasca
J. Pers. Med. 2022, 12(6), 949; https://doi.org/10.3390/jpm12060949 - 10 Jun 2022
Cited by 20 | Viewed by 3446
Abstract
Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers [...] Read more.
Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers for cancer liquid biopsy and personalized medicine. Despite this potential, none of the discovered biomarkers has entered the clinical practice so far, and novel approaches for the label-free characterization of EVs are highly demanded. In this regard, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides a quick, reproducible, and informative biomolecular fingerprint of EVs. In this pilot study, we investigated, for the first time in the literature, the capability of FTIR spectroscopy to distinguish between EVs extracted from sera of cancer patients and controls based on their mid-IR spectral response. For this purpose, EV-enriched suspensions were obtained from the serum of patients diagnosed with Hepatocellular Carcinoma (HCC) of nonviral origin and noncancer subjects. Our data point out the presence of statistically significant differences in the integrated intensities of major mid-IR absorption bands, including the carbohydrate and nucleic acids band, the protein amide I and II bands, and the lipid CH stretching band. Additionally, we used Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) for the automated classification of spectral data according to the shape of specific mid-IR spectral signatures. The diagnostic performances of the proposed spectral biomarkers, alone and combined, were evaluated using multivariate logistic regression followed by a Receiving Operator Curve analysis, obtaining large Areas Under the Curve (AUC = 0.91, 95% CI 0.81–1.0). Very interestingly, our analyses suggest that the discussed spectral biomarkers can outperform the classification ability of two widely used circulating HCC markers measured on the same groups of subjects, namely alpha-fetoprotein (AFP), and protein induced by the absence of vitamin K or antagonist-II (PIVKA-II). Full article
(This article belongs to the Special Issue Cancer Biomarker Research and Personalized Medicine 2.0)
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16 pages, 612 KiB  
Review
Gender and Autoimmune Liver Diseases: Relevant Aspects in Clinical Practice
by Federica Invernizzi, Marta Cilla, Silvia Trapani, Maria Guarino, Valentina Cossiga, Martina Gambato, Maria Cristina Morelli, Filomena Morisco, Patrizia Burra and Annarosa Floreani
J. Pers. Med. 2022, 12(6), 925; https://doi.org/10.3390/jpm12060925 - 2 Jun 2022
Cited by 15 | Viewed by 2934
Abstract
Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a [...] Read more.
Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a highly variable clinical course. These diseases significantly influence quality of life and can progress toward liver decompensation or the onset of hepatocellular or cholangiocarcinoma; a significant number of patients eventually progress to end-stage liver disease, requiring liver transplantation. In this review, we focus on the sex characteristics and peculiarities of AILD patients and highlight the relevance of a sex-specific analysis in future studies. Understanding the sex differences underlying AILD immune dysregulation may be critical for developing more effective treatments. Full article
(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)
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17 pages, 784 KiB  
Review
Sex-Related Differences in Pharmacological Response to CNS Drugs: A Narrative Review
by Mirabela Romanescu, Valentina Buda, Adelina Lombrea, Minodora Andor, Ionut Ledeti, Maria Suciu, Corina Danciu, Cristina Adriana Dehelean and Liana Dehelean
J. Pers. Med. 2022, 12(6), 907; https://doi.org/10.3390/jpm12060907 - 31 May 2022
Cited by 20 | Viewed by 5517
Abstract
In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men [...] Read more.
In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs’ intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones’ metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs. Full article
(This article belongs to the Special Issue Personalized Treatment and Diagnosis Strategies in Psychiatry)
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13 pages, 1849 KiB  
Review
Digital Anthropometry for Body Circumference Measurements: European Phenotypic Variations throughout the Decades
by Marco Alessandro Minetto, Angelo Pietrobelli, Chiara Busso, Jonathan P. Bennett, Andrea Ferraris, John A. Shepherd and Steven B. Heymsfield
J. Pers. Med. 2022, 12(6), 906; https://doi.org/10.3390/jpm12060906 - 30 May 2022
Cited by 20 | Viewed by 4648
Abstract
This review summarizes body circumference-based anthropometrics that are in common use for research and in some cases clinical application. These include waist and hip circumference-based central body indices to predict cardiometabolic risk: waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, [...] Read more.
This review summarizes body circumference-based anthropometrics that are in common use for research and in some cases clinical application. These include waist and hip circumference-based central body indices to predict cardiometabolic risk: waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, a body shape index (ABSI), hip index (HI), and body roundness index (BRI). Limb circumference measurements are most often used to assess sarcopenia and include: thigh circumference, calf circumference, and mid-arm circumference. Additionally, this review presents fascinating recent developments in optic-based imaging technologies that have elucidated changes over the last decades in average body size and shape in European populations. The classical apple and pear shape concepts of body shape difference remain useful, but novel and exciting 3-D optical “e-taper” measurements provide a potentially powerful new future vista in anthropometrics. Full article
(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)
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22 pages, 855 KiB  
Review
From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine
by Laura Maintz, Thomas Bieber, Helen D. Simpson and Anne-Laure Demessant-Flavigny
J. Pers. Med. 2022, 12(6), 893; https://doi.org/10.3390/jpm12060893 - 28 May 2022
Cited by 13 | Viewed by 4208
Abstract
Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal [...] Read more.
Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient’s age and disease stage. Full article
(This article belongs to the Special Issue Precision Medicine in Childhood Asthma)
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16 pages, 3109 KiB  
Article
MDMF: Predicting miRNA–Disease Association Based on Matrix Factorization with Disease Similarity Constraint
by Jihwan Ha
J. Pers. Med. 2022, 12(6), 885; https://doi.org/10.3390/jpm12060885 - 27 May 2022
Cited by 18 | Viewed by 2551
Abstract
MicroRNAs (miRNAs) have drawn enormous attention owing to their significant roles in various biological processes, as well as in the pathogenesis of human diseases. Therefore, predicting miRNA–disease associations is a pivotal task for the early diagnosis and better understanding of disease pathogenesis. To [...] Read more.
MicroRNAs (miRNAs) have drawn enormous attention owing to their significant roles in various biological processes, as well as in the pathogenesis of human diseases. Therefore, predicting miRNA–disease associations is a pivotal task for the early diagnosis and better understanding of disease pathogenesis. To date, numerous computational frameworks have been proposed to identify potential miRNA–disease associations without escalating the costs and time required for clinical experiments. In this regard, I propose a novel computational framework (MDMF) for identifying potential miRNA–disease associations using matrix factorization with a disease similarity constraint. To evaluate the performance of MDMF, I calculated the area under the ROC curve (AUCs) in the framework of global and local leave-one-out cross-validation (LOOCV). In conclusion, MDMF achieved reliable AUC values of 0.9147 and 0.8905 for global and local LOOCV, respectively, which was a significant improvement upon the previous methods. Additionally, case studies were conducted on two major human cancers (breast cancer and lung cancer) to validate the effectiveness of MDMF. Comprehensive experimental results demonstrate that MDMF not only discovers miRNA–disease associations efficiently but also deciphers the underlying roles of miRNAs in the pathogenesis of diseases at a system level. Full article
(This article belongs to the Topic Big Data in Healthcare, Bioinformatics and Precision Medicine)
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15 pages, 38588 KiB  
Article
Diagnostic Challenge of Invasive Lobular Carcinoma of the Breast: What Is the News? Breast Magnetic Resonance Imaging and Emerging Role of Contrast-Enhanced Spectral Mammography
by Melania Costantini, Rino Aldo Montella, Maria Paola Fadda, Vincenzo Tondolo, Gianluca Franceschini, Sonia Bove, Giorgia Garganese and Pierluigi Maria Rinaldi
J. Pers. Med. 2022, 12(6), 867; https://doi.org/10.3390/jpm12060867 - 25 May 2022
Cited by 13 | Viewed by 3171
Abstract
Invasive lobular carcinoma is the second most common histologic form of breast cancer, representing 5% to 15% of all invasive breast cancers. Due to an insidious proliferative pattern, invasive lobular carcinoma remains clinically and radiologically elusive in many cases. Breast magnetic resonance imaging [...] Read more.
Invasive lobular carcinoma is the second most common histologic form of breast cancer, representing 5% to 15% of all invasive breast cancers. Due to an insidious proliferative pattern, invasive lobular carcinoma remains clinically and radiologically elusive in many cases. Breast magnetic resonance imaging (MR) is considered the most accurate imaging modality in detecting and staging invasive lobular carcinoma and it is strongly recommended in pre-operative planning for all ILC. Contrast-enhanced spectral mammography (CESM) is a new diagnostic method that enables the accurate detection of malignant breast lesions similar to that of breast MR. CESM is also a promising breast imaging method for planning surgeries. In this study, we compare the ability of contrast-enhanced spectral mammography (CESM) with breast MR in the preoperative assessment of the extent of invasive lobular carcinoma. All patients with proven invasive lobular carcinoma treated in our breast cancer center underwent preoperative breast MRI and CESM. Images were reviewed by two dedicated breast radiologists and results were compared to the reference standard histopathology. CESM was similar and in some cases more accurate than breast MR in assessing the extent of disease in invasive lobular cancers. Further evaluation in larger prospective randomized trials is needed to validate our preliminary results. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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22 pages, 1899 KiB  
Review
CFTR and Gastrointestinal Cancers: An Update
by Rahul Bhattacharya, Zachary Blankenheim, Patricia M. Scott and Robert T. Cormier
J. Pers. Med. 2022, 12(6), 868; https://doi.org/10.3390/jpm12060868 - 25 May 2022
Cited by 12 | Viewed by 3694
Abstract
Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown [...] Read more.
Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis, Treatment, and Related Disorders)
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22 pages, 3223 KiB  
Review
Precision Medicine in Head and Neck Cancers: Genomic and Preclinical Approaches
by Giacomo Miserocchi, Chiara Spadazzi, Sebastiano Calpona, Francesco De Rosa, Alice Usai, Alessandro De Vita, Chiara Liverani, Claudia Cocchi, Silvia Vanni, Chiara Calabrese, Massimo Bassi, Giovanni De Luca, Giuseppe Meccariello, Toni Ibrahim, Marco Schiavone and Laura Mercatali
J. Pers. Med. 2022, 12(6), 854; https://doi.org/10.3390/jpm12060854 - 24 May 2022
Cited by 16 | Viewed by 3523
Abstract
Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not [...] Read more.
Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not yet been found. In this scenario, personalised medicine is showing its efficacy. To study the reliability and the effects of personalised treatments, preclinical research can take advantage of next-generation sequencing and innovative technologies that have been developed to obtain genomic and multi-omic profiles to drive personalised treatments. The crosstalk between malignant and healthy components, as well as interactions with extracellular matrices, are important features which are responsible for treatment failure. Preclinical research has constantly implemented in vitro and in vivo models to mimic the natural tumour microenvironment. Among them, 3D systems have been developed to reproduce the tumour mass architecture, such as biomimetic scaffolds and organoids. In addition, in vivo models have been changed over the last decades to overcome problems such as animal management complexity and time-consuming experiments. In this review, we will explore the new approaches aimed to improve preclinical tools to study and apply precision medicine as a therapeutic option for patients affected by HNCs. Full article
(This article belongs to the Special Issue Personalized Medicine in Cancer Therapy: Mechanism, Approaches and Techniques)
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22 pages, 982 KiB  
Review
Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement
by Eugenio De Corso, Maria Beatrice Bilò, Andrea Matucci, Veronica Seccia, Fulvio Braido, Matteo Gelardi, Enrico Heffler, Manuela Latorre, Luca Malvezzi, Girolamo Pelaia, Gianenrico Senna, Paolo Castelnuovo and Giorgio Walter Canonica
J. Pers. Med. 2022, 12(5), 846; https://doi.org/10.3390/jpm12050846 - 23 May 2022
Cited by 16 | Viewed by 4494
Abstract
Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current [...] Read more.
Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug–exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients. Full article
(This article belongs to the Special Issue Personalized Medicine in Otorhinolaryngology)
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13 pages, 869 KiB  
Review
Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management
by Andriana I. Papaioannou, Evangelia Fouka, Polyxeni Ntontsi, Grigoris Stratakos and Spyridon Papiris
J. Pers. Med. 2022, 12(5), 850; https://doi.org/10.3390/jpm12050850 - 23 May 2022
Cited by 10 | Viewed by 3360
Abstract
Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it [...] Read more.
Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
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28 pages, 2862 KiB  
Review
Diffuse Intrinsic Pontine Glioma: Molecular Landscape, Evolving Treatment Strategies and Emerging Clinical Trials
by Sudarshawn Damodharan, Montserrat Lara-Velazquez, Brooke Carmen Williamsen, Jeffrey Helgager and Mahua Dey
J. Pers. Med. 2022, 12(5), 840; https://doi.org/10.3390/jpm12050840 - 20 May 2022
Cited by 22 | Viewed by 7935
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population [...] Read more.
Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population of cells with multiple genetic mutations and high infiltrative capacity. The most common mutation seen in this group is a lysine to methionine point mutation seen at position 27 (K27M) within histone 3 (H3). Tumors with the H3 K27M mutation, are considered grade 4 and are now categorized within the H3 K27-altered diffuse midline glioma category by World Health Organization classification. Due to its critical location and aggressive nature, DIPG is resistant to the most eradicative treatment and is universally fatal; however, modern advances in the surgical techniques resulting in safe biopsy of the lesion have significantly improved our understanding of this disease at the molecular level. Genomic analysis has shown several mutations that play a role in the pathophysiology of the disease and can be targeted therapeutically. In this review, we will elaborate on DIPG from general aspects and the evolving molecular landscape. We will also review innovative therapeutic options that have been trialed along with new promising treatments on the horizon. Full article
(This article belongs to the Special Issue Personalized Medicine in Brain Tumors)
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16 pages, 988 KiB  
Systematic Review
BMI at Discharge from Treatment Predicts Relapse in Anorexia Nervosa: A Systematic Scoping Review
by Stein Frostad, Natalia Rozakou-Soumalia, Ştefana Dârvariu, Bahareh Foruzesh, Helia Azkia, Malina Ploug Larsen, Ehsan Rowshandel and Jan Magnus Sjögren
J. Pers. Med. 2022, 12(5), 836; https://doi.org/10.3390/jpm12050836 - 20 May 2022
Cited by 14 | Viewed by 5731
Abstract
Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were [...] Read more.
Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. Results: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11–73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. Conclusions: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking. Full article
(This article belongs to the Special Issue Biomarkers and Clinical Research in Eating Disorders)
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29 pages, 1462 KiB  
Review
Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases
by Giulia Gentile, Giovanna Morello, Valentina La Cognata, Maria Guarnaccia, Francesca Luisa Conforti and Sebastiano Cavallaro
J. Pers. Med. 2022, 12(5), 770; https://doi.org/10.3390/jpm12050770 - 10 May 2022
Cited by 30 | Viewed by 5793
Abstract
Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well as the lack of effective biomarkers and therapeutic treatments. In the last decade, microRNAs (miRNAs) have gained considerable interest [...] Read more.
Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well as the lack of effective biomarkers and therapeutic treatments. In the last decade, microRNAs (miRNAs) have gained considerable interest in diagnostics and therapy of NDs, owing to their aberrant expression and their ability to target multiple molecules and pathways. Here, we provide an overview of dysregulated miRNAs in fluids (blood or cerebrospinal fluid) and nervous tissue of AD, PD, and ALS patients. By emphasizing those that are commonly dysregulated in these NDs, we highlight their potential role as biomarkers or therapeutical targets and describe the use of antisense oligonucleotides as miRNA therapies. Full article
(This article belongs to the Section Omics/Informatics)
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22 pages, 3314 KiB  
Article
Deep Convolutional Gated Recurrent Unit Combined with Attention Mechanism to Classify Pre-Ictal from Interictal EEG with Minimized Number of Channels
by WooHyeok Choi, Min-Jee Kim, Mi-Sun Yum and Dong-Hwa Jeong
J. Pers. Med. 2022, 12(5), 763; https://doi.org/10.3390/jpm12050763 - 9 May 2022
Cited by 15 | Viewed by 2610
Abstract
The early prediction of epileptic seizures is important to provide appropriate treatment because it can notify clinicians in advance. Various EEG-based machine learning techniques have been used for automatic seizure classification based on subject-specific paradigms. However, because subject-specific models tend to perform poorly [...] Read more.
The early prediction of epileptic seizures is important to provide appropriate treatment because it can notify clinicians in advance. Various EEG-based machine learning techniques have been used for automatic seizure classification based on subject-specific paradigms. However, because subject-specific models tend to perform poorly on new patient data, a generalized model with a cross-patient paradigm is necessary for building a robust seizure diagnosis system. In this study, we proposed a generalized model that combines one-dimensional convolutional layers (1D CNN), gated recurrent unit (GRU) layers, and attention mechanisms to classify preictal and interictal phases. When we trained this model with ten minutes of preictal data, the average accuracy over eight patients was 82.86%, with 80% sensitivity and 85.5% precision, outperforming other state-of-the-art models. In addition, we proposed a novel application of attention mechanisms for channel selection. The personalized model using three channels with the highest attention score from the generalized model performed better than when using the smallest attention score. Based on these results, we proposed a model for generalized seizure predictors and a seizure-monitoring system with a minimized number of EEG channels. Full article
(This article belongs to the Special Issue Artificial Intelligence Application in Health Care System)
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