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Volume 11
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J. Pers. Med., Volume 11, Issue 6 (June 2021) – 149 articles

Cover Story (view full-size image): Venetoclax is a highly selective and effective B-cell lymphoma-2 (BCL2) inhibitor, with a unique ability to reinstate the apoptotic potential of cancer cells. With its full potential yet to be explored and a promising risk–benefit profile, it has proven to be paradigm shifting in a range of haematological malignancies. Despite this, venetoclax is not curative, and treatment is inevitably hamstrung by disease relapse over time. Ongoing research continues to shed light on the complex genomic and epigenomic environment that gives rise to disease resistance. Understanding these mechanisms further will aid rational drug combinations to improve long-term outcomes in patients on venetoclax therapy. View this paper
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11 pages, 2549 KiB  
Article
Gender-Specific Risk Factors for the Development of Retinal Changes in Children with Type 1 Diabetes
by Marta Wysocka-Mincewicz, Joanna Gołębiewska, Marta Baszyńska-Wilk and Andrzej Olechowski
J. Pers. Med. 2021, 11(6), 588; https://doi.org/10.3390/jpm11060588 - 21 Jun 2021
Viewed by 1846
Abstract
The aim of the study was to determine gender-specific risk factor sets which could influence optical coherence tomography (OCT) results in children with type 1 diabetes (T1D). Material and Methods: 175 children with T1D without symptoms of diabetic retinopathy were enrolled, but 330 [...] Read more.
The aim of the study was to determine gender-specific risk factor sets which could influence optical coherence tomography (OCT) results in children with type 1 diabetes (T1D). Material and Methods: 175 children with T1D without symptoms of diabetic retinopathy were enrolled, but 330 eyes were used for the final analysis (168 children, mean age 12.81 ± 3.63 years, diabetes duration 4.59 ± 3.71 years). The multivariate regression models for retinal thickness (foveal FT, and parafoveal PFT) and vascular densities (superficial and deep) were carried out separately for both genders using all metabolic and demographic parameters. Results: In the statistically significant multiple regression models for all analyzed OCT parameters for both genders, pH at the onset of diabetes were in existence, as well as for retinal thickness current HbA1c. Duration of continuous insulin infusion (CSII) was an important factor in all parameters, except PFT. For the girls, the most significant factors were daily insulin dose, uric acid, and triglycerides, but for the boys, it was serum creatinine, systolic pressure, and free thyroxine level. Conclusions: We detected significant risk factors set for development of OCT parameters changes, and they were not identical for both genders. Current metabolic control, diabetic ketoacidosis at the disease onset, serum creatinine and longer use of CSII are the most important factors for retinal thickness and vessel densities in both genders in children with type 1 diabetes. For the girls, elements of metabolic syndrome (uric acid and triglycerides) and parameters of insulin amount were more pronounced. Full article
(This article belongs to the Section Mechanisms of Diseases)
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17 pages, 1155 KiB  
Article
Acceptability, Appropriateness, and Feasibility of Automated Screening Approaches and Family Communication Methods for Identification of Familial Hypercholesterolemia: Stakeholder Engagement Results from the IMPACT-FH Study
by Laney K. Jones, Nicole Walters, Andrew Brangan, Catherine D. Ahmed, Michael Gatusky, Gemme Campbell-Salome, Ilene G. Ladd, Amanda Sheldon, Samuel S. Gidding, Mary P. McGowan, Alanna K. Rahm and Amy C. Sturm
J. Pers. Med. 2021, 11(6), 587; https://doi.org/10.3390/jpm11060587 - 21 Jun 2021
Cited by 12 | Viewed by 4300
Abstract
Guided by the Conceptual Model of Implementation Research, we explored the acceptability, appropriateness, and feasibility of: (1) automated screening approaches utilizing existing health data to identify those who require subsequent diagnostic evaluation for familial hypercholesterolemia (FH) and (2) family communication methods including chatbots [...] Read more.
Guided by the Conceptual Model of Implementation Research, we explored the acceptability, appropriateness, and feasibility of: (1) automated screening approaches utilizing existing health data to identify those who require subsequent diagnostic evaluation for familial hypercholesterolemia (FH) and (2) family communication methods including chatbots and direct contact to communicate information about inherited risk for FH. Focus groups were conducted with 22 individuals with FH (2 groups) and 20 clinicians (3 groups). These were recorded, transcribed, and analyzed using deductive (coded to implementation outcomes) and inductive (themes based on focus group discussions) methods. All stakeholders described these initiatives as: (1) acceptable and appropriate to identify individuals with FH and communicate risk with at-risk relatives; and (2) feasible to implement in current practice. Stakeholders cited current initiatives, outside of FH (e.g., pneumonia protocols, colon cancer and breast cancer screenings), that gave them confidence for successful implementation. Stakeholders described perceived obstacles, such as nonfamiliarity with FH, that could hinder implementation and potential solutions to improve systematic uptake of these initiatives. Automated health data screening, chatbots, and direct contact approaches may be useful for patients and clinicians to improve FH diagnosis and cascade screening. Full article
(This article belongs to the Special Issue Genomic Medicine for Cardiovascular Disease)
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7 pages, 537 KiB  
Article
Depression Levels Influence the Rate of Asthma Exacerbations in Females
by Papaporfyriou Anastasia, Tseliou Eleni, Mizi Eleftheria, Ntontsi Xenia, Papathanasiou Eygenia, Souliotis Kyriakos, Dimakou Katerina, Bakakos Petros, Loukides Stelios and Hillas Georgios
J. Pers. Med. 2021, 11(6), 586; https://doi.org/10.3390/jpm11060586 - 21 Jun 2021
Cited by 9 | Viewed by 2395
Abstract
Background: Anxiety and depression are common psychological disturbances among asthmatic patients. The aim of the present study is the assessment of anxiety and depression in asthmatic patients and their correlation with symptoms control level and number of exacerbations per year. Methods: [...] Read more.
Background: Anxiety and depression are common psychological disturbances among asthmatic patients. The aim of the present study is the assessment of anxiety and depression in asthmatic patients and their correlation with symptoms control level and number of exacerbations per year. Methods: One hundred patients with asthma diagnosis, according to the Global Initiative for Asthma (GINA), aged > 18 years old, having a stable disease, were included. Emotional status was evaluated using the Hospital Anxiety Depression Scale (HADS). Patients were followed up for a year to assess the number and severity of exacerbations. Results: Most of our patients were female (58%), middle-aged (mean = 54 ± 13), and married (81%), with low frequency of smoking habits (smokers, ex-smokers and non-smokers were 26%, 30% and 37%, respectively) and low levels of both anxiety and depression [median (interquartile range (IQR)) = 4(2) and median (IQR) = 4(2), respectively]. At the low and moderate level of the depression subscale, female patients experienced asthma exacerbations more frequently compared to male patients (adjusted Incidence Rate Ratio (aIRR) = 4.30; 95% Confidence Interval (CI): 1.94–9.53 and aIRR = 1.82; 95% CI: 1.07–3.13, respectively). Conclusions. Clinicians should evaluate asthma patients for depression, as gender differentially influences outcomes among those with low and moderate levels of depression, with female asthmatics presenting more frequent exacerbations. Full article
(This article belongs to the Special Issue Personalized Medicine in Bronchial Asthma)
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17 pages, 1368 KiB  
Review
The Potential Role of Sildenafil in Cancer Management through EPR Augmentation
by Mohamed Haider, Amr Elsherbeny, Valeria Pittalà, Antonino N. Fallica, Maha Ali Alghamdi and Khaled Greish
J. Pers. Med. 2021, 11(6), 585; https://doi.org/10.3390/jpm11060585 - 21 Jun 2021
Cited by 16 | Viewed by 6404
Abstract
Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for [...] Read more.
Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the path for the emerging field of nanomedicine to become a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for the treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 has been reported in lung, colon, metastatic breast cancers, and bladder squamous carcinoma. Moreover, sildenafil has been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the downregulation of Bcl-xL and FAP-1 expression, enhancing reactive oxygen species (ROS) generation, phosphorylating BAD and Bcl-2, upregulating caspase-3,8,9 activities, and blocking cells at G0/G1 cell cycle phase. Sildenafil has also demonstrated inhibitory effects on the efflux activity of ATP-binding cassette (ABC) transporters such as ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing multidrug resistance. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. In this review, we critically examine the basic molecular mechanism of sildenafil related to cancer biology and discuss the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery, pointing to the outcomes of the most important related preclinical and clinical studies. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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16 pages, 285 KiB  
Review
Robotic Transanal Total Mesorectal Excision (RTaTME): State of the Art
by Fabio Rondelli, Alessandro Sanguinetti, Andrea Polistena, Stefano Avenia, Claudio Marcacci, Graziano Ceccarelli, Walter Bugiantella and Michele De Rosa
J. Pers. Med. 2021, 11(6), 584; https://doi.org/10.3390/jpm11060584 - 21 Jun 2021
Cited by 6 | Viewed by 1987
Abstract
Total mesorectal excision (TME) is the gold standard technique for the surgical management of rectal cancer. The transanal approach to the mesorectum was introduced to overcome the technical difficulties related to the distal rectal dissection. Since its inception, interest in transanal mesorectal excision [...] Read more.
Total mesorectal excision (TME) is the gold standard technique for the surgical management of rectal cancer. The transanal approach to the mesorectum was introduced to overcome the technical difficulties related to the distal rectal dissection. Since its inception, interest in transanal mesorectal excision has grown exponentially and it appears that the benefits are maximal in patients with mid-low rectal cancer where anatomical and pathological features represent the greatest challenges. Current evidence demonstrates that this approach is safe and feasible, with oncological and functional outcome comparable to conventional approaches, but with specific complications related to the technique. Robotics might potentially simplify the technical steps of distal rectal dissection, with a shorter learning curve compared to the laparoscopic transanal approach, but with higher costs. The objective of this review is to critically analyze the available literature concerning robotic transanal TME in order to define its role in the management of rectal cancer and to depict future perspectives in this field of research. Full article
(This article belongs to the Special Issue Update on Robotic Gastrointestinal Surgery)
12 pages, 625 KiB  
Article
Validation of the Patient-Centred Care Competency Scale Instrument for Finnish Nurses
by Riitta Suhonen, Katja Lahtinen, Minna Stolt, Miko Pasanen and Terhi Lemetti
J. Pers. Med. 2021, 11(6), 583; https://doi.org/10.3390/jpm11060583 - 21 Jun 2021
Cited by 6 | Viewed by 2310
Abstract
Patient-centredness in care is a core healthcare value and an effective healthcare delivery design requiring specific nurse competences. The aim of this study was to assess (1) the reliability, validity, and sensitivity of the Finnish version of the Patient-centred Care Competency (PCC) scale [...] Read more.
Patient-centredness in care is a core healthcare value and an effective healthcare delivery design requiring specific nurse competences. The aim of this study was to assess (1) the reliability, validity, and sensitivity of the Finnish version of the Patient-centred Care Competency (PCC) scale and (2) Finnish nurses’ self-assessed level of patient-centred care competency. The PCC was translated to Finnish (PCC-Fin) before data collection and analyses: descriptive statistics; Cronbach’s alpha coefficients; item analysis; exploratory and confirmatory factor analyses; inter-scale correlational analysis; and sensitivity. Cronbach’s alpha coefficients were acceptable, high for the total scale, and satisfactory for the four sub-scales. Item analysis supported the internal homogeneity of the items-to-total and inter-items within the sub-scales. Explorative factor analysis suggested a three-factor solution, but the confirmatory factor analysis confirmed the four-factor structure (Tucker–Lewis index (TLI) 0.92, goodness-of-fit index (GFI) 0.99, root mean square error of approximation (RMSEA) 0.065, standardized root mean square residual (SRMR) 0.045) with 61.2% explained variance. Analysis of the secondary data detected no differences in nurses’ self-evaluations of contextual competence, so the inter-scale correlations were high. The PCC-Fin was found to be a reliable and valid instrument for the measurement of nurses’ patient-centred care competence. Rasch model analysis would provide some further information about the item level functioning within the instrument. Full article
(This article belongs to the Special Issue Personalized Nursing and Health Care)
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15 pages, 2226 KiB  
Article
Body Mass Index and Birth Weight Improve Polygenic Risk Score for Type 2 Diabetes
by Avigail Moldovan, Yedael Y. Waldman, Nadav Brandes and Michal Linial
J. Pers. Med. 2021, 11(6), 582; https://doi.org/10.3390/jpm11060582 - 21 Jun 2021
Cited by 10 | Viewed by 4455
Abstract
One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can [...] Read more.
One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We present here a sex-specific integrated approach that combines PRS with additional measurements and age to define a new risk score. We show that such approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n = 290,584). Likewise, integrating PRS with self-reports on birth weight (n = 172,239) and comparative body size at age ten (n = 287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements. Full article
(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)
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9 pages, 471 KiB  
Article
A Personalized Approach to Percutaneous Coronary Interventions in the Left Main Coronary Artery—Is the Female Gender Associated with Worse Outcomes?
by Marta Kałużna-Oleksy, Wojciech Jan Skorupski, Marek Grygier, Aleksander Araszkiewicz, Włodzimierz Skorupski, Stefan Grajek, Przemysław Mitkowski, Małgorzata Pyda and Maciej Lesiak
J. Pers. Med. 2021, 11(6), 581; https://doi.org/10.3390/jpm11060581 - 20 Jun 2021
Cited by 4 | Viewed by 1794
Abstract
There is still controversy whether the female gender is associated with worse outcomes after the percutaneous coronary intervention within the left main (LM PCI). This study aimed to examine gender-based differences in real-life LM PCI patients and present a gender-personalized LM PCI approach. [...] Read more.
There is still controversy whether the female gender is associated with worse outcomes after the percutaneous coronary intervention within the left main (LM PCI). This study aimed to examine gender-based differences in real-life LM PCI patients and present a gender-personalized LM PCI approach. Consecutively, 613 patients underwent LM PCI in our department from January 2015 to June 2019. Five hundred and thirty-three patients, with at least a one-year follow-up, were included in the study. There were 130 (24.4%) women and 403 (75.6%) men. Compared with men, women were older (70.0 ± 9.4 vs. 67.7 ± 9.2; p = 0.006) and had higher diabetes, hypertension, and chronic kidney disease rates. Left ventricle ejection fraction was higher in women (53.5 ± 9.4 vs. 49.5 ± 11.2; p = 0.001). Euroscore II and SYNTAX scores did not differ between the genders. However, we observed a trend towards more frequent use of complex PCI techniques in women (26.2% vs. 19.4%; p = 0.098). The overall periprocedural complication rates (10.0% vs. 7.7%; p = 0.406) and the periprocedural myocardial infarction rates did not differ. Contrast-induced nephropathy was more frequent in women (6.9% vs. 3.0%; p = 0.044). Long-term all-cause mortality did not differ (20% vs. 22.5%; p = 0.069). Both genders presented similar rates of periprocedural complications, and no significant differences in long-term all-cause mortality were revealed. Our results suggest that the female gender in LM PCI is not a predictor of adverse outcomes. Further studies are required to determine the optimal revascularization strategy in women. Full article
(This article belongs to the Special Issue Personalized Cardiovascular Medicine)
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12 pages, 266 KiB  
Article
Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study
by Angela Toss, Amelia Spinella, Chrystel Isca, Caterina Vacchi, Guido Ficarra, Luca Fabbiani, Anna Iannone, Luca Magnani, Paola Castrignanò, Pierluca Macripò, Elisa Gasparini, Simonetta Piana, Laura Cortesi, Antonino Maiorana, Carlo Salvarani, Massimo Dominici and Dilia Giuggioli
J. Pers. Med. 2021, 11(6), 580; https://doi.org/10.3390/jpm11060580 - 20 Jun 2021
Cited by 5 | Viewed by 2205
Abstract
Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. [...] Read more.
Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients. Full article
(This article belongs to the Special Issue Precision Medicine in Breast Cancer: Challenges and Opportunities in Diagnostic and Therapeutic Purposes)
20 pages, 3464 KiB  
Article
A Type 2 Ryanodine Receptor Variant in the Helical Domain 2 Associated with an Impairment of the Adrenergic Response
by Malorie Blancard, Zahia Touat-Hamici, Yuriana Aguilar-Sanchez, Liheng Yin, Guy Vaksmann, Nathalie Roux-Buisson, Véronique Fressart, Isabelle Denjoy, Didier Klug, Nathalie Neyroud, Josefina Ramos-Franco, Ana Maria Gomez and Pascale Guicheney
J. Pers. Med. 2021, 11(6), 579; https://doi.org/10.3390/jpm11060579 - 20 Jun 2021
Cited by 3 | Viewed by 2250
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is triggered by exercise or acute emotion in patients with normal resting electrocardiogram. The major disease-causing gene is RYR2, encoding the cardiac ryanodine receptor (RyR2). We report a novel RYR2 variant, p.Asp3291Val, outside the four CPVT mutation [...] Read more.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is triggered by exercise or acute emotion in patients with normal resting electrocardiogram. The major disease-causing gene is RYR2, encoding the cardiac ryanodine receptor (RyR2). We report a novel RYR2 variant, p.Asp3291Val, outside the four CPVT mutation hotspots, in three CPVT families with numerous sudden deaths. This missense variant was first identified in a four-generation family, where eight sudden cardiac deaths occurred before the age of 30 in the context of adrenergic stress. All affected subjects harbored at least one copy of the RYR2 variant. Three affected sisters were homozygous for the variant. The same variant was found in two additional CPVT families. It is located in the helical domain 2 and changes a negatively charged amino acid widely conserved through evolution. Functional analysis of D3291V channels revealed a normal response to cytosolic Ca2+, a markedly reduced luminal Ca2+ sensitivity and, more importantly, an absence of normal response to 8-bromo-cAMP and forskolin stimulation in both transfected HEK293 and HL-1 cells. Our data support that the D3291V-RyR2 is a loss-of-function RyR2 variant responsible for an atypical form of CPVT inducing a mild dysfunction in basal conditions but leading potentially to fatal events through its unresponsiveness to adrenergic stimulation. Full article
(This article belongs to the Special Issue Ion Channels as Targets of Personalized Medicine)
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14 pages, 2806 KiB  
Article
The Downregulation of LSAMP Expression Promotes Lung Cancer Progression and Is Associated with Poor Survival Prognosis
by Chao-Yuan Chang, Kuan-Li Wu, Yung-Yun Chang, Yu-Wei Liu, Yung-Chi Huang, Shu-Fang Jian, Yi-Shiuan Lin, Pei-Hsun Tsai, Jen-Yu Hung, Ying-Ming Tsai and Ya-Ling Hsu
J. Pers. Med. 2021, 11(6), 578; https://doi.org/10.3390/jpm11060578 - 20 Jun 2021
Cited by 7 | Viewed by 2576
Abstract
Lung cancer has been a leading cause of cancer-related death for decades and therapeutic strategies for non-driver mutation lung cancer are still lacking. A novel approach for this type of lung cancer is an emergent requirement. Here we find that loss of LSAMP [...] Read more.
Lung cancer has been a leading cause of cancer-related death for decades and therapeutic strategies for non-driver mutation lung cancer are still lacking. A novel approach for this type of lung cancer is an emergent requirement. Here we find that loss of LSAMP (Limbic System Associated Membrane Protein), compared to other IgLON family of proteins NTM (Neurotrimin) and OPCML (OPioid-binding Cell adhesion MoLecule), exhibits the strongest prognostic and therapeutic significance in predicting lung adenocarcinoma (LUAD) progression. Lower expression of LSAMP and NTM, but not OPCML, were found in tumor parts compared with normal parts in six LUAD patients, and this was validated by public datasets, Oncomine® and TCGA. The lower expression of LSAMP, but not NTM, was correlated to shorter overall survival. Two epigenetic regulations, including hypermethylation and miR-143-3p upregulation but not copy number variation, were associated with downregulation of LSAMP in LUAD patients. Pathway network analysis showed that NEGR1 (Neuronal Growth Regulator 1) was involved in the regulatory loop of LSAMP. The biologic functions by LSMAP knockdown in lung cancer cells revealed LSMAP was linked to cancer cell migration via epithelial-mesenchymal transition (EMT) but not proliferation nor stemness of LUAD. Our result showed for the first time that LSAMP acts as a potential tumor suppressor in regulating lung cancer. A further deep investigation into the role of LSAMP in lung cancer tumorigenesis would provide therapeutic hope for such affected patients. Full article
(This article belongs to the Section Mechanisms of Diseases)
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11 pages, 1510 KiB  
Article
A Portable Biodevice to Monitor Salivary Conductivity for the Rapid Assessment of Fluid Status
by Chun-Hao Chen, Yen-Pei Lu, An-Ting Lee, Chun-Wu Tung, Yuan-Hsiung Tsai, Hsin-Pei Tsay, Chih-Ting Lin and Jen-Tsung Yang
J. Pers. Med. 2021, 11(6), 577; https://doi.org/10.3390/jpm11060577 - 19 Jun 2021
Cited by 4 | Viewed by 2381
Abstract
The evaluation of fluid status can save adults from life-threatening conditions, but the current methods are invasive or time-consuming. Therefore, we developed a portable device for measuring salivary conductivity. This prospective observational study enrolled 20 volunteers with no history of systemic diseases. Participants [...] Read more.
The evaluation of fluid status can save adults from life-threatening conditions, but the current methods are invasive or time-consuming. Therefore, we developed a portable device for measuring salivary conductivity. This prospective observational study enrolled 20 volunteers with no history of systemic diseases. Participants were observed for 13 h, including water restriction for 12 h followed by rehydration with 1000 mL water within 1 h. Serum and urine biomarkers for fluid status, thirst scales, and salivary conductivity were collected during dehydration and rehydration. No significant differences in age, body mass index, glycohemoglobin, and estimated glomerular filtration rate were noted between sexes. Salivary conductivity increased after water restriction and decreased after rehydration. Similarly, urine osmolality, urine specific gravity, thirst intensity scales, and body weight followed the same trend and were statistically significant. The angiotensin-converting enzyme and aldosterone levels showed the same trend, without reaching statistical significance. The red blood cell count and hemoglobin concentration also followed the same trend. Analyzing the receiver operating characteristic curves, the area under the curve was 0.707 (95% confidence interval 0.542–0.873, p = 0.025). Using the Youden index, the optimal cutoff determined as 2678.09 μs/cm (sensitivity: 90%, specificity: 55%). This biodevice effectively screened dehydration among healthy adults. Full article
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7 pages, 490 KiB  
Communication
Antibody Response Following a Two-Dose mRNA Vaccination Regimen, in Health Care Workers of a Tertiary Hospital in Athens, Greece
by Elissavet Kontou, Kyriaki Ranellou, Dimitrios Zoulas, Anastasia Bletsa, Eirini Rompola, Evangelia-Theophano Piperaki, Nikolaos Athanasiou, Kleio Ampelakiotou, Maria Pratikaki, Christina Stergiopoulou, Athina Argyropoulou, Androula Alevra, Aggeliki Megalou and Alexandra Tsirogianni
J. Pers. Med. 2021, 11(6), 576; https://doi.org/10.3390/jpm11060576 - 19 Jun 2021
Cited by 15 | Viewed by 3170
Abstract
We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals [...] Read more.
We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals and personnel working in COVID-19 clinics. Notably, individuals with a prior COVID-19 infection mounted a significantly higher antibody titer following the first dose than the rest of the population; the same was true for those working in COVID-19 clinics, even without history of previous infection. Full article
(This article belongs to the Special Issue Personalized Medicine for Covid-19 Patients-Clinical Considerations)
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13 pages, 2111 KiB  
Article
Detection of Aberrant Glycosylation of Serum Haptoglobin for Gastric Cancer Diagnosis Using a Middle-Up-Down Glycoproteome Platform
by Seunghyup Jeong, Unyong Kim, Myung Jin Oh, Jihyeon Nam, Se Hoon Park, Yoon Jin Choi, Dong Ho Lee, Jaehan Kim and Hyun Joo An
J. Pers. Med. 2021, 11(6), 575; https://doi.org/10.3390/jpm11060575 - 18 Jun 2021
Cited by 7 | Viewed by 2683
Abstract
Gastric cancer is a frequently occurring cancer and is the leading cause of cancer-related deaths. Recent studies have shown that aberrant glycosylation of serum haptoglobin is closely related to gastric cancer and has enormous potential for use in diagnosis. However, there is no [...] Read more.
Gastric cancer is a frequently occurring cancer and is the leading cause of cancer-related deaths. Recent studies have shown that aberrant glycosylation of serum haptoglobin is closely related to gastric cancer and has enormous potential for use in diagnosis. However, there is no platform with high reliability and high reproducibility to comprehensively analyze haptoglobin glycosylation covering microheterogeneity to macroheterogeneity for clinical applications. In this study, we developed a middle-up-down glycoproteome platform for fast and accurate monitoring of haptoglobin glycosylation. This platform utilizes an online purification of LC for sample desalting, and an in silico haptoglobin glycopeptide library constructed by combining peptides and N-glycans to readily identify glycopeptides. In addition, site-specific glycosylation with glycan heterogeneity can be obtained through only a single MS analysis. Haptoglobin glycosylation in clinical samples consisting of healthy controls (n = 47) and gastric cancer patients (n = 43) was extensively investigated using three groups of tryptic glycopeptides: GP1 (including Asn184), GP2 (including Asn207 and Asn211), and GP3 (including Asn241). A total of 23 individual glycopeptides were determined as potential biomarkers (p < 0.00001). In addition, to improve diagnostic efficacy, we derived representative group biomarkers with high AUC values (0.929 to 0.977) through logistic regression analysis for each GP group. It has been found that glycosylation of haptoglobin is highly associated with gastric cancer, especially the glycosite Asn241. Our assay not only allows to quickly and easily obtain information on glycosylation heterogeneity of a target glycoprotein but also makes it an efficient tool for biomarker discovery and clinical diagnosis. Full article
(This article belongs to the Special Issue Cancer Biomarker Research and Personalized Medicine)
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13 pages, 42073 KiB  
Article
A Personalized 3D-Printed Model for Obtaining Informed Consent Process for Thyroid Surgery: A Randomized Clinical Study Using a Deep Learning Approach with Mesh-Type 3D Modeling
by Jungirl Seok, Sungmin Yoon, Chang Hwan Ryu, Seok-ki Kim, Junsun Ryu and Yuh-Seog Jung
J. Pers. Med. 2021, 11(6), 574; https://doi.org/10.3390/jpm11060574 - 18 Jun 2021
Cited by 10 | Viewed by 2279
Abstract
The aim of this study was to evaluate the usefulness of a personalized 3D-printed thyroid model that characterizes a patient’s individual thyroid lesion. The randomized controlled prospective clinical trial (KCT0005069) was designed. Fifty-three of these patients undergoing thyroid surgery were randomly assigned to [...] Read more.
The aim of this study was to evaluate the usefulness of a personalized 3D-printed thyroid model that characterizes a patient’s individual thyroid lesion. The randomized controlled prospective clinical trial (KCT0005069) was designed. Fifty-three of these patients undergoing thyroid surgery were randomly assigned to two groups: with or without a 3D-printed model of their thyroid lesion when obtaining informed consent. We used a U-Net-based deep learning architecture and a mesh-type 3D modeling technique to fabricate the personalized 3D model. The mean 3D printing time was 258.9 min, and the mean price for production was USD 4.23 for each patient. The size, location, and anatomical relationship of the tumor and thyroid gland could be effectively presented using the mesh-type 3D modeling technique. The group provided with personalized 3D-printed models showed significant improvement in all four categories (general knowledge, benefits and risks of surgery, and satisfaction; all p < 0.05). All patients received a personalized 3D model after surgery and found it helpful to understand the disease, operation, and possible complications and their overall satisfaction (all p < 0.05). In conclusion, the personalized 3D-printed thyroid model may be an effective tool for improving a patient’s understanding and satisfaction during the informed consent process. Full article
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15 pages, 326 KiB  
Article
Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis
by Noelia Márquez Pete, María del Mar Maldonado Montoro, Cristina Pérez Ramírez, Fernando Martínez Martínez, Juan Enrique Martínez de la Plata, Abdelali Daddaoua and Alberto Jiménez Morales
J. Pers. Med. 2021, 11(6), 573; https://doi.org/10.3390/jpm11060573 - 18 Jun 2021
Cited by 6 | Viewed by 2433
Abstract
Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was [...] Read more.
Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01–5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19–8.66) and 12 months (OR = 6.62; 95% CI = 1.25–46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01–2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02–1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01–1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98–0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46–523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02–0.47), monotherapy (OR = 19.22; 95% CI = 2.05–343.00), lower initial patient’s visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92–0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87–0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results. Full article
(This article belongs to the Section Pharmacogenetics)
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12 pages, 4413 KiB  
Article
Individual Revision Knee Arthroplasty Is a Safe Limb Salvage Procedure
by Peter Savov, Lars-Rene Tuecking, Henning Windhagen and Max Ettinger
J. Pers. Med. 2021, 11(6), 572; https://doi.org/10.3390/jpm11060572 - 18 Jun 2021
Cited by 6 | Viewed by 4131
Abstract
Introduction: Revision total knee arthroplasty after multiple pre-surgeries is challenging. Due to severe bone defects, standard implants for metaphyseal and diaphyseal anchoring may no longer be suitable. The primary aim of this case series is to evaluate the early complication rate for individual [...] Read more.
Introduction: Revision total knee arthroplasty after multiple pre-surgeries is challenging. Due to severe bone defects, standard implants for metaphyseal and diaphyseal anchoring may no longer be suitable. The primary aim of this case series is to evaluate the early complication rate for individual knee implants with custom-made cones and stems after two-stage revision with severe bone defects. Methods: Ten patients who were treated with custom-made 3D-printed knee revision implants were included. Inclusion criteria were a two-stage revision due to late-onset or chronic periprosthetic joint infection as well as aseptic loosening. All severe bone defects were AORI type III. All procedure-related complications were evaluated. Postoperative range of motion after one year was measured. The time between the two surgeries was evaluated. Results: The mean follow-up was 21 months (range: 12–40). The mean time between the two-stage surgeries was 71.6 days. No fractures were observed intra- and postoperatively. Two patients were revised without changing metal components due to persistent hematoma (three weeks post-surgery) and persistent PJI (three months post-surgery). The mean passive postoperative range of motion was 92° (range: 80–110°). Conclusions: Individual custom-made implants for rTKA provide a safe procedure for patients with huge bone defects after several pre-surgeries. If standard knee systems with standard cones or sleeves are not suitable anymore, custom-made treatment offers the patient the last option for limb preservation. However, this is associated with increased costs. Full article
(This article belongs to the Special Issue Patient-Specific Implants in Musculoskeletal (Orthopedic) Surgery)
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27 pages, 1088 KiB  
Review
Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment
by Md Abdus Subhan, Satya Siva Kishan Yalamarty, Nina Filipczak, Farzana Parveen and Vladimir P. Torchilin
J. Pers. Med. 2021, 11(6), 571; https://doi.org/10.3390/jpm11060571 - 18 Jun 2021
Cited by 204 | Viewed by 8688
Abstract
Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood [...] Read more.
Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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12 pages, 604 KiB  
Article
Pediatric Oncologists’ Experiences Returning and Incorporating Genomic Sequencing Results into Cancer Care
by Rebecca L. Hsu, Amanda M. Gutierrez, Sophie K. Schellhammer, Jill O. Robinson, Sarah Scollon, Richard L. Street, Jr., Alyssa N. Salisbury, Stacey Pereira, Sharon E. Plon, Janet Malek, D. Williams Parsons and Amy L. McGuire
J. Pers. Med. 2021, 11(6), 570; https://doi.org/10.3390/jpm11060570 - 18 Jun 2021
Cited by 2 | Viewed by 2304
Abstract
Pediatric oncologists’ perspectives around returning and incorporating tumor and germline genomic sequencing (GS) results into cancer care are not well-described. To inform optimization of cancer genomics communication, we assessed oncologists’ experiences with return of genomic results (ROR), including their preparation/readiness for ROR, collaboration [...] Read more.
Pediatric oncologists’ perspectives around returning and incorporating tumor and germline genomic sequencing (GS) results into cancer care are not well-described. To inform optimization of cancer genomics communication, we assessed oncologists’ experiences with return of genomic results (ROR), including their preparation/readiness for ROR, collaboration with genetic counselors (GCs) during ROR, and perceived challenges. The BASIC3 study paired pediatric oncologists with GCs to return results to patients’ families. We thematically analyzed 24 interviews with 12 oncologists at two post-ROR time points. Oncologists found pre-ROR meetings with GCs and geneticists essential to interpreting patients’ reports and communicating results to families. Most oncologists took a collaborative ROR approach where they discussed tumor findings and GCs discussed germline findings. Oncologists perceived many roles for GCs during ROR, including answering families’ questions and describing information in lay language. Challenges identified included conveying uncertain information in accessible language, limits of oncologists’ genetics expertise, and navigating families’ emotional responses. Oncologists emphasized how GCs’ and geneticists’ support was essential to ROR, especially for germline findings. GS can be successfully integrated into cancer care, but to account for the GC shortage, alternative ROR models and access to genetics resources will be needed to better support families and avoid burdening oncologists. Full article
(This article belongs to the Special Issue Integrating Genomics into Basic and Clinical Research)
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10 pages, 704 KiB  
Article
The Relationship between Psychological Distress during the Second Wave Lockdown of COVID-19 and Emotional Eating in Italian Young Adults: The Mediating Role of Emotional Dysregulation
by Anna Guerrini Usubini, Roberto Cattivelli, Giorgia Varallo, Gianluca Castelnuovo, Enrico Molinari, Emanuele Maria Giusti, Giada Pietrabissa, Tommaso Manari, Maria Filosa, Christian Franceschini and Alessandro Musetti
J. Pers. Med. 2021, 11(6), 569; https://doi.org/10.3390/jpm11060569 - 17 Jun 2021
Cited by 33 | Viewed by 4539
Abstract
This cross-sectional study aims to investigate the impact of psychological distress experienced during the second wave of the COVID-19 pandemic on emotional eating and to assess the mediating role of emotional dysregulation in a sample of Italian young adults (20–35). A total of [...] Read more.
This cross-sectional study aims to investigate the impact of psychological distress experienced during the second wave of the COVID-19 pandemic on emotional eating and to assess the mediating role of emotional dysregulation in a sample of Italian young adults (20–35). A total of 437 participants provided demographical data and were assessed using the Depression Anxiety Stress Scale, the Difficulties in Emotion Regulation Scale, and the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire. Correlational analyses were performed to assess the relationship between continuous variables, while ANOVA was conducted to detect differences between males and females for emotional eating. To assess whether demographic and clinical data predicted emotional eating, hierarchical linear regression was performed. Then, a mediation analysis was conducted to assess whether emotional dysregulation was a mediator between psychological distress and emotional eating. Emotional eating was associated with psychological distress and emotional dysregulation. Moreover, higher levels of emotional eating were found in females than in males. Predictors of emotional eating were sex, psychological distress, and emotional dysregulation. Mediation analyses showed that the indirect effect of psychological distress on emotional eating through emotional dysregulation was significant (b = 0.0069; SE = 0.0024; CI = 0.0024–0.0118), confirming that the relationship between psychological distress and emotional eating was mediated by emotional dysregulation, controlling for sex. The model explained 26.8% (R2 = 0.2680) of the variance. These findings may help to plan and develop psychological interventions aimed at addressing emotional eating in young adults by targeting emotional dysregulation. Full article
(This article belongs to the Special Issue Predicting Psychopathological Onset: Early Signs of Neuropsychiatric Diseases)
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17 pages, 3418 KiB  
Review
Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part I: A Diagnostic Accuracy Meta-Analysis
by Óscar Rapado-González, Cristina Martínez-Reglero, Ángel Salgado-Barreira, Laura Muinelo-Romay, Juan Muinelo-Lorenzo, Rafael López-López, Ángel Díaz-Lagares and María Mercedes Suárez-Cunqueiro
J. Pers. Med. 2021, 11(6), 568; https://doi.org/10.3390/jpm11060568 - 17 Jun 2021
Cited by 14 | Viewed by 2625
Abstract
DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of [...] Read more.
DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis. Full article
(This article belongs to the Special Issue Cancer Biomarker Research and Personalized Medicine)
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11 pages, 790 KiB  
Article
Unique Polymorphisms at BCL11A, HBS1L-MYB and HBB Loci Associated with HbF in Kuwaiti Patients with Sickle Cell Disease
by Nagihan Akbulut-Jeradi, Maria Jinky Fernandez, Rasha Al Khaldi, Jalaja Sukumaran and Adekunle Adekile
J. Pers. Med. 2021, 11(6), 567; https://doi.org/10.3390/jpm11060567 - 17 Jun 2021
Cited by 4 | Viewed by 2295
Abstract
Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at BCL11A, HBS1L-MYB and HBB with HbF levels in 237 Kuwaiti SCD [...] Read more.
Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at BCL11A, HBS1L-MYB and HBB with HbF levels in 237 Kuwaiti SCD patients, divided into 3 subgroups according to their HbF levels. Illumina Ampliseq custom DNA panel was used for genotyping and confirmed by arrayed primer extension or Sanger sequencing. In the BCL11A locus, the CC genotype of rs7606173 [χ2 = 16.5] and (GG) of rs10195871 [χ2 = 15.0] were associated with Hb-F1 and HbF-2 subgroups, unlike rs1427404-T [χ2 = 17.3], which showed the highest association across the three subgroups. HBS1L-MYB locus revealed 2 previously-described SNPs (rs66650371 [χ2 = 9.5] and rs35795442 [χ2 = 9.2]) and 2 previously-unreported SNPs, (rs13220662 [χ2 = 6.2] and rs1406811 [χ2 = 6.7]) that were associated with the HbF-3 subgroup, making this the key locus elevating HbF to the highest levels. HBB cluster variants were associated with lower levels of HbF (β = −1.1). We report four previously-unpublished variants showing significant association with HbF. Each of the three quantitative trait loci affects HbF levels differently; unique SNPs, especially in HBS1L-MYB, elevate HbF to the highest levels. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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20 pages, 2938 KiB  
Review
In Situ Delivery and Production System (iDPS) of Anti-Cancer Molecules with Gene-Engineered Bifidobacterium
by Shun’ichiro Taniguchi
J. Pers. Med. 2021, 11(6), 566; https://doi.org/10.3390/jpm11060566 - 17 Jun 2021
Cited by 7 | Viewed by 2613
Abstract
To selectively and continuously produce anti-cancer molecules specifically in malignant tumors, we have established an in situ delivery and production system (iDPS) with Bifidobacterium as a micro-factory of various anti-cancer agents. By focusing on the characteristic hypoxia in cancer tissue for [...] Read more.
To selectively and continuously produce anti-cancer molecules specifically in malignant tumors, we have established an in situ delivery and production system (iDPS) with Bifidobacterium as a micro-factory of various anti-cancer agents. By focusing on the characteristic hypoxia in cancer tissue for a tumor-specific target, we employed a gene-engineered obligate anaerobic and non-pathogenic bacterium, Bifidobacterium, as a tool for systemic drug administration. This review presents and discusses the anti-tumor effects and safety of the iDPS production of numerous anti-cancer molecules and addresses the problems to be improved by directing attention mainly to the hallmark vasculature and so-called enhanced permeability and retention effect of tumors. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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21 pages, 3646 KiB  
Article
Efficient Genetic Safety Switches for Future Application of iPSC-Derived Cell Transplants
by Julia Dahlke, Juliane W. Schott, Philippe Vollmer Barbosa, Denise Klatt, Anton Selich, Nico Lachmann, Michael Morgan, Thomas Moritz and Axel Schambach
J. Pers. Med. 2021, 11(6), 565; https://doi.org/10.3390/jpm11060565 - 17 Jun 2021
Cited by 10 | Viewed by 2954
Abstract
Induced pluripotent stem cell (iPSC)-derived cell products hold great promise as a potential cell source in personalized medicine. As concerns about the potential risk of graft-related severe adverse events, such as tumor formation from residual pluripotent cells, currently restrict their applicability, we established [...] Read more.
Induced pluripotent stem cell (iPSC)-derived cell products hold great promise as a potential cell source in personalized medicine. As concerns about the potential risk of graft-related severe adverse events, such as tumor formation from residual pluripotent cells, currently restrict their applicability, we established an optimized tool for therapeutic intervention that allows drug-controlled, specific and selective ablation of either iPSCs or the whole graft through genetic safety switches. To identify the best working system, different tools for genetic iPSC modification, promoters to express safety switches and different safety switches were combined. Suicide effects were slightly stronger when the suicide gene was delivered through lentiviral (LV) vectors compared to integration into the AAVS1 locus through TALEN technology. An optimized HSV-thymidine kinase and the inducible Caspase 9 both mediated drug-induced, efficient in vitro elimination of transgene-positive iPSCs. Choice of promoter allowed selective elimination of distinct populations within the graft: the hOct4 short response element restricted transgene expression to iPSCs, while the CAGs promoter ubiquitously drove expression in iPSCs and their progeny. Remarkably, both safety switches were able to prevent in vivo teratoma development and even effectively eliminated established teratomas formed by LV CAGs-transgenic iPSCs. These optimized tools to increase safety provide an important step towards clinical application of iPSC-derived transplants. Full article
(This article belongs to the Special Issue Application of Induced Pluripotent Stem Cells in Personalized Medicine)
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14 pages, 1431 KiB  
Article
MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese
by Chin-Man Wang, Keng-Poo Tan, Yeong-Jian Jan Wu, Jing-Chi Lin, Jian-Wen Zheng, Alice L. Yu, Jian-Ming Wu and Ji-Yih Chen
J. Pers. Med. 2021, 11(6), 564; https://doi.org/10.3390/jpm11060564 - 16 Jun 2021
Cited by 6 | Viewed by 2167
Abstract
MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major [...] Read more.
MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS. Full article
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11 pages, 1208 KiB  
Article
The 6-Minute Walk Test and Anthropometric Characteristics as Assessment Tools in Patients with Obstructive Sleep Apnea Syndrome. A Preliminary Report during the Pandemic
by Vasileios T. Stavrou, George D. Vavougios, Kyriaki Astara, Dimitra I. Siachpazidou, Eirini Papayianni and Konstantinos I. Gourgoulianis
J. Pers. Med. 2021, 11(6), 563; https://doi.org/10.3390/jpm11060563 - 16 Jun 2021
Cited by 7 | Viewed by 2015
Abstract
Patients with obstructive sleep apnea syndrome (OSAS) exhibit low cardio-fitness impact, attributed to fragmented sleep architecture and associated pathophysiological sequelae. The purpose of our study was to investigate fitness indicators during 6-min walk test (6MWT) and oxidative stress markers in apnea-hypopnea index (AHI) [...] Read more.
Patients with obstructive sleep apnea syndrome (OSAS) exhibit low cardio-fitness impact, attributed to fragmented sleep architecture and associated pathophysiological sequelae. The purpose of our study was to investigate fitness indicators during 6-min walk test (6MWT) and oxidative stress markers in apnea-hypopnea index (AHI) in OSAS patients stratified by severity. A total of 37 newly diagnosed patients, comorbidity-free, were divided into two groups: (Moderate OSAS (n = 12), defined as ≥ 15 AHI < 30 events per hour; Age: 50.7 ± 7.2 years, BMI: 32.5 ± 4.0 kg/m2 vs. Severe OSAS (n = 25), defined as AHΙ ≥ 30 events per hour; Age: 46.3 ± 10.4 years, BMI: 33.3 ± 7.9 kg/m2). Measurements included demographics, anthropometric characteristics, body composition, blood sampling for reactive oxygen metabolites’ levels (d-ROM) and plasma antioxidant capacity (PAT), and followed by a 6MWT. AHI was significantly associated with d-ROMs levels, chest circumference in maximal inhalation and exhalation (Δchest), neck circumference, as well as 6MWT-derived indices. In conclusion, our study determines bidirectional interrelationships between OSAS severity and anthropometrics, body composition, and fitness metrics. These findings indicate that the impact of OSAS should be evaluated well beyond polysomnography-derived parameters. Full article
(This article belongs to the Special Issue Personalized Clinical and Community Nursing)
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22 pages, 884 KiB  
Review
Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns
by Olga María Diz, Rocio Toro, Sergi Cesar, Olga Gomez, Georgia Sarquella-Brugada and Oscar Campuzano
J. Pers. Med. 2021, 11(6), 562; https://doi.org/10.3390/jpm11060562 - 16 Jun 2021
Cited by 8 | Viewed by 6147
Abstract
Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, [...] Read more.
Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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10 pages, 1684 KiB  
Article
The Change of Fingolimod Patient Profiles over Time: A Descriptive Analysis of Two Non-Interventional Studies PANGAEA and PANGAEA 2.0
by Tjalf Ziemssen and Ulf Schulze-Topphoff
J. Pers. Med. 2021, 11(6), 561; https://doi.org/10.3390/jpm11060561 - 16 Jun 2021
Cited by 4 | Viewed by 2720
Abstract
(1) Background: Fingolimod (Gilenya®) was the first oral treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Since its approval, the treatment landscape has changed enormously. (2) Methods: Data of PANGAEA and PANGAEA 2.0, two German real-world studies, were descriptively analysed for [...] Read more.
(1) Background: Fingolimod (Gilenya®) was the first oral treatment for patients with relapsing-remitting multiple sclerosis (RRMS). Since its approval, the treatment landscape has changed enormously. (2) Methods: Data of PANGAEA and PANGAEA 2.0, two German real-world studies, were descriptively analysed for possible evolution of patient profiles and treatment behavior. Both are prospective, multi-center, non-interventional, long-term studies on fingolimod use in RRMS in real life. Data of 4229 PANGAEA patients (recruited 2011–2013) and 2441 PANGAEA 2.0 patients (recruited 2015–2018) were available. Baseline data included demographics, RRMS characteristics and disease severity. (3) Results: The mean age of PANGAEA and PANGAEA 2.0 patients was similar (38.8 vs. 39.2 years). Patients in PANGAEA 2.0 had shorter disease duration (7.1 vs. 8.2 years) and fewer relapses in the year before baseline (1.2 vs. 1.6). Disease severity at baseline estimated by EDSS and SDMT was lower in PANGAEA 2.0 patients compared to PANGAEA (EDSS difference 1.0 points; SDMT difference 3.3 points). (4) Conclusions: The results hint at an influence of changes in the treatment guidelines and the label on fingolimod patients profiles over time. Patients tended to have lower disease activity at fingolimod initiation, suggesting an earlier intervention. This indicates increased experience in using fingolimod for sub-optimally treated RRMS patients and a change in mindset towards an early treatment optimization. Full article
(This article belongs to the Special Issue Personalized Medicine for Multiple Sclerosis)
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17 pages, 1389 KiB  
Article
Mandible Segmentation of Dental CBCT Scans Affected by Metal Artifacts Using Coarse-to-Fine Learning Model
by Bingjiang Qiu, Hylke van der Wel, Joep Kraeima, Haye Hendrik Glas, Jiapan Guo, Ronald J. H. Borra, Max Johannes Hendrikus Witjes and Peter M. A. van Ooijen
J. Pers. Med. 2021, 11(6), 560; https://doi.org/10.3390/jpm11060560 - 16 Jun 2021
Cited by 12 | Viewed by 3013
Abstract
Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an important step for building a personalized 3D digital mandible model for maxillofacial surgery and orthodontic treatment planning because of the low radiation dose and short scanning duration. CBCT images, however, [...] Read more.
Accurate segmentation of the mandible from cone-beam computed tomography (CBCT) scans is an important step for building a personalized 3D digital mandible model for maxillofacial surgery and orthodontic treatment planning because of the low radiation dose and short scanning duration. CBCT images, however, exhibit lower contrast and higher levels of noise and artifacts due to extremely low radiation in comparison with the conventional computed tomography (CT), which makes automatic mandible segmentation from CBCT data challenging. In this work, we propose a novel coarse-to-fine segmentation framework based on 3D convolutional neural network and recurrent SegUnet for mandible segmentation in CBCT scans. Specifically, the mandible segmentation is decomposed into two stages: localization of the mandible-like region by rough segmentation and further accurate segmentation of the mandible details. The method was evaluated using a dental CBCT dataset. In addition, we evaluated the proposed method and compared it with state-of-the-art methods in two CT datasets. The experiments indicate that the proposed algorithm can provide more accurate and robust segmentation results for different imaging techniques in comparison with the state-of-the-art models with respect to these three datasets. Full article
(This article belongs to the Special Issue Application of Artificial Intelligence in Personalized Medicine)
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12 pages, 1807 KiB  
Article
Enhanced Anticancer Activity of Nanoformulation of Dasatinib against Triple-Negative Breast Cancer
by Fatemah Bahman, Valeria Pittalà, Mohamed Haider and Khaled Greish
J. Pers. Med. 2021, 11(6), 559; https://doi.org/10.3390/jpm11060559 - 15 Jun 2021
Cited by 16 | Viewed by 3234
Abstract
Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC lacks human epidermal growth factor receptor 2 (HER2) amplification, is hormone independent estrogen (ER) and progesterone receptors (PR) negative, and is not [...] Read more.
Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC lacks human epidermal growth factor receptor 2 (HER2) amplification, is hormone independent estrogen (ER) and progesterone receptors (PR) negative, and is not reactive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment, but in spite of an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases, and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA–dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA–dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management. Full article
(This article belongs to the Special Issue EPR Effect-Based Tumor Targeted Nanomedicine)
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