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J. Pers. Med., Volume 11, Issue 9 (September 2021) – 114 articles

Cover Story (view full-size image): The generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming over a decade ago, has opened a new era in personalized medicine. iPSCs allow disease modeling, drug discovery, toxicity studies, cell and gene therapies. However, the unprecedented opportunities of using iPSCs in science and medicine are strongly influenced by environmental conditions. Among various environmental factors, oxygen plays an essential role in regulating the state of pluripotency, genome stability, metabolic profile and differentiation potential of iPSCs. In this review we summarize recent discoveries regarding the impact of oxygen concentration on the physiology of PSCs. We also highlight the major differences between PSCs and cancer stem cells (CSCs), in their responses to changes in oxygen levels. View this paper.
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Article
Focality-Oriented Selection of Current Dose for Transcranial Direct Current Stimulation
J. Pers. Med. 2021, 11(9), 940; https://doi.org/10.3390/jpm11090940 - 21 Sep 2021
Viewed by 406
Abstract
Background: In transcranial direct current stimulation (tDCS), the injected current becomes distributed across the brain areas. The objective is to stimulate the target region of interest (ROI) while minimizing the current in non-target ROIs (the ‘focality’ of tDCS). For this purpose, determining the [...] Read more.
Background: In transcranial direct current stimulation (tDCS), the injected current becomes distributed across the brain areas. The objective is to stimulate the target region of interest (ROI) while minimizing the current in non-target ROIs (the ‘focality’ of tDCS). For this purpose, determining the appropriate current dose for an individual is difficult. Aim: To introduce a dose–target determination index (DTDI) to quantify the focality of tDCS and examine the dose–focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of the average current density at the target ROI to the ROI with a maximum value (the peak region). Ideally, target ROI should be the peak region, so DTDI shall range from 0 to 1. The higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups: (a) young adults (20 ≤ x ˂ 40 years), (b) mid adults (40 ≤ x ˂ 60 years), and (c) older adults (60 ≤ x ˂ 80 years). DTDI’s were evaluated for the frontal montage with electrodes at F3 and the right supraorbital for three current doses of 1 mA, 2 mA, and 3 mA, with the target ROI at the left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals depending on the relationship (nonlinear or linear) between the injected tDCS current and the distribution of current density in the target ROI. The nonlinearity is predominant in older adults with a decrease in focality. The decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. The recommended DTDI dose should be prioritized based on the age (>40 years) and sex (especially for males) of an individual. The toolbox i-SATA(MNI) is freely available. Full article
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Article
Predictors of the CD24/CD11b Biomarker among Healthy Subjects
J. Pers. Med. 2021, 11(9), 939; https://doi.org/10.3390/jpm11090939 - 21 Sep 2021
Viewed by 465
Abstract
The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were [...] Read more.
The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population. Full article
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Article
A Novel Boot Camp Program to Help Guide Personalized Exercise in People with Parkinson Disease
J. Pers. Med. 2021, 11(9), 938; https://doi.org/10.3390/jpm11090938 - 20 Sep 2021
Viewed by 689
Abstract
Given the variety of exercise programs available for people with Parkinson’s disease (PD), such individuals may struggle to make decisions about what exercise to perform. The objective of this study was to assess the usefulness, satisfaction, and preferences regarding participation in a PD-personalized [...] Read more.
Given the variety of exercise programs available for people with Parkinson’s disease (PD), such individuals may struggle to make decisions about what exercise to perform. The objective of this study was to assess the usefulness, satisfaction, and preferences regarding participation in a PD-personalized educational and exercise boot camp program. Attendees participated in a four-day program consisting of exercise sessions, workshops, and social activities. We collected demographic and clinical information. We assessed satisfaction and preferences immediately after. At one-month follow-up, participants assessed usefulness and changes in exercise habits. Eight individuals diagnosed with PD, with a mean age of 59.5 ± 6.8 years, participated. All participants felt “very satisfied” and likely to attend future events. The two favorite sessions were: cognitive stepping and dance-based movements. At one-month follow-up, participants considered the program “very useful” and reported changes in their exercise routine. Our results suggest that the boot camp program was considered useful and capable of influencing participants’ exercise habits. Full article
(This article belongs to the Special Issue Personalized Care and Treatment Compliance in Chronic Conditions)
Article
Access to Prenatal Testing and Ethically Informed Counselling in Germany, Poland and Russia
J. Pers. Med. 2021, 11(9), 937; https://doi.org/10.3390/jpm11090937 - 20 Sep 2021
Viewed by 464
Abstract
The development of new methods in the field of prenatal testing leads to an expansion of information that needs to be provided to expectant mothers. The aim of this research is to explore opinions and attitudes of gynecologists in Germany, Poland and Russia [...] Read more.
The development of new methods in the field of prenatal testing leads to an expansion of information that needs to be provided to expectant mothers. The aim of this research is to explore opinions and attitudes of gynecologists in Germany, Poland and Russia towards access to prenatal testing and diagnostics in these countries. Semi-structured interviews were conducted with n = 18 gynecologists in Germany, Poland and Russia. The interviews were analyzed using the methods of content analysis and thematic analysis. Visible in all three countries is a connection of prenatal medicine with the politically and socially contentious issue of pregnancy termination. Respondents in Poland and Russia concentrated on the topic of inadequate resources. Quality of information for expectant mothers is an important point in all three countries. Only in Germany was the issue of language barriers in communication raised. With regard to non-invasive prenatal testing (NIPT) respondents in Germany focused on the ethical issues of routinization of testing; in Poland and Russia they concentrated on fair access to NIPT. Challenges in all three countries arise from structural factors such as imprecise and prohibitive regulations, lack of resources or organization of healthcare services. These should be addressed on a political and medico-ethical level. Full article
(This article belongs to the Special Issue Pregnancy Complication and Precision Medicine)
Article
Evaluation of Sarcopenia, Frailty, and Inflammation on Adverse Events and Survival Outcomes in Patients with Oral Cavity Squamous Cell Carcinoma under Adjuvant Chemoradiotherapy
J. Pers. Med. 2021, 11(9), 936; https://doi.org/10.3390/jpm11090936 - 19 Sep 2021
Viewed by 562
Abstract
In this study, we aimed to evaluate the prognostic impact of sarcopenia, five-item modified frailty index (mFI-5), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in patients with oral cavity squamous cell carcinoma (OSCC) treated with adjuvant chemoradiotherapy (CRT) and their survival outcomes. We [...] Read more.
In this study, we aimed to evaluate the prognostic impact of sarcopenia, five-item modified frailty index (mFI-5), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in patients with oral cavity squamous cell carcinoma (OSCC) treated with adjuvant chemoradiotherapy (CRT) and their survival outcomes. We retrospectively enrolled 175 patients with OSCC undergoing adjuvant CRT between 2011 and 2018, who were divided into groups with (n = 112) and without (n = 63) sarcopenia. Logistic regression analysis and Cox proportional hazards models were used to determine prognostic factors for CRT-related toxicity, three-year overall survival (OS), and disease-free survival (DFS). Sarcopenia and high PLR were independently associated with CRT-induced anemia (CIA); advanced tumor stage was related to poor three-year OS. CRT and survival did not differ by mFI-5 and NLR. Our results indicate that sarcopenia and high PLR are significant predictors of adjuvant CRT, increasing toxicity outcomes and indicating worse short-term OS. Accurately identifying sarcopenia and high PLR in patients with OSCC is critical to help better select candidates for adjuvant CRT to improve their outcomes. Full article
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Article
Colchicine Use and Risks of Stroke Recurrence in Acute Non-Cardiogenic Ischemic Stroke Patients: A Population-Based Cohort Study
J. Pers. Med. 2021, 11(9), 935; https://doi.org/10.3390/jpm11090935 - 19 Sep 2021
Viewed by 445
Abstract
Background: The objective is to study whether the cardiovascular protective effects of colchicines could be applied to non-cardiogenic ischemic stroke (IS) patients. Patients and Methods: Non-cardiogenic IS patients were identified from the National Health Insurance Research Database. Eligible patients were divided into chronic [...] Read more.
Background: The objective is to study whether the cardiovascular protective effects of colchicines could be applied to non-cardiogenic ischemic stroke (IS) patients. Patients and Methods: Non-cardiogenic IS patients were identified from the National Health Insurance Research Database. Eligible patients were divided into chronic and non-chronic use categories based on their long-term status of colchicine use. The non-chronic use category was subdivided into (1) non-user and (2) new user groups while the chronic use category was divided into (3) former user and (4) long-term user groups according to the patient’s recent status of colchicine use. Inverse probability of treatment weights for propensity scores was used to balance the baseline characteristics. The primary outcome was recurrent IS, which was compared within the non-chronic use and chronic use categories. Results: In the non-chronic use category, the number of patients was 355,498 and 912 in the non-user and new user groups, respectively. In the chronic use category, the number of patients was 4737 and 4354 in the former user and long-term user groups, respectively. In the non-chronic use category, patients in the new user group had a marginally lower risk of recurrent IS at 6-months (subdistribution hazard ratio [SHR], 0.95; 95% confidence interval [CI], 0.94–0.97) and 2-years (SHR, 0.92; 95% CI, 0.91–0.93) follow up. In the chronic use category, patients in the long-term user group also had a marginally lower risk of recurrent IS at 6-months (SHR, 0.87; 95% CI, 0.86–0.88) and 2-years (SHR, 0.87; 95% CI, 0.86–0.88) follow up. The effect of colchicine on the reduced risk of recurrent IS was more favorable in patients who also used statins. Conclusions: Recent colchicine use in acute non-cardiogenic IS patients is associated with marginal fewer incidences of recurrent IS. Patients with concurrent statin use may have more profound protective effects. Full article
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Article
Feature Explanations in Recurrent Neural Networks for Predicting Risk of Mortality in Intensive Care Patients
J. Pers. Med. 2021, 11(9), 934; https://doi.org/10.3390/jpm11090934 - 19 Sep 2021
Viewed by 568
Abstract
Critical care staff are presented with a large amount of data, which made it difficult to systematically evaluate. Early detection of patients whose condition is deteriorating could reduce mortality, improve treatment outcomes, and allow a better use of healthcare resources. In this study, [...] Read more.
Critical care staff are presented with a large amount of data, which made it difficult to systematically evaluate. Early detection of patients whose condition is deteriorating could reduce mortality, improve treatment outcomes, and allow a better use of healthcare resources. In this study, we propose a data-driven framework for predicting the risk of mortality that combines high-accuracy recurrent neural networks with interpretable explanations. Our model processes time-series of vital signs and laboratory observations to predict the probability of a patient’s mortality in the intensive care unit (ICU). We investigated our approach on three public critical care databases: Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III), MIMIC-IV, and eICU. Our models achieved an area under the receiver operating characteristic curve (AUC) of 0.87–0.91. Our approach was not only able to provide the predicted mortality risk but also to recognize and explain the historical contributions of the associated factors to the prediction. The explanations provided by our model were consistent with the literature. Patients may benefit from early intervention if their clinical observations in the ICU are continuously monitored in real time. Full article
(This article belongs to the Special Issue Personalized Medicine with Biomedical and Health Informatics)
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Article
The Effects of Different Types of Dual Tasking on Balance in Healthy Older Adults
J. Pers. Med. 2021, 11(9), 933; https://doi.org/10.3390/jpm11090933 - 18 Sep 2021
Viewed by 771
Abstract
Numerous of our daily activities are performed within multitask or dual task conditions. These conditions involve the interaction of perceptual and motor processes involved in postural control. Age-related changes may negatively impact cognition and balance control. Studies identifying changes related to dual-task actions [...] Read more.
Numerous of our daily activities are performed within multitask or dual task conditions. These conditions involve the interaction of perceptual and motor processes involved in postural control. Age-related changes may negatively impact cognition and balance control. Studies identifying changes related to dual-task actions in older people are need. This study aimed to determine the effects of different types of dual-tasking on the balance control of healthy older adults. The sample included 36 community-living older adults, performing two tests—a sway test and a timed up-and-go test—in three conditions: (a) single motor task; (b) dual motor task; and (c) dual motor task with cognitive demands. Cognitive processes (dual-task and cognition) affected static balance, increasing amplitude (p < 0.001) and frequency (p < 0.001) of the center of mass displacements. Dynamic balance revealed significant differences between the single motor condition and the other two conditions during gait phases (p < 0.001). The effect of dual-tasking in older adults suggests that cognitive processes are a main cause of increased variability in balance and gait when under an automatic control. During sit-to-stand, turning, and turn-to-sit movements under dual-tasking, the perceptive information becomes the most important focus of attention, while any cognitive task becomes secondary. Full article
(This article belongs to the Special Issue Personalized Care and Treatment Compliance in Chronic Conditions)
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Article
A Novel Digital Technique for Measuring the Accuracy of an Indirect Bonding Technique Using Fixed Buccal Multibracket Appliances
J. Pers. Med. 2021, 11(9), 932; https://doi.org/10.3390/jpm11090932 - 18 Sep 2021
Viewed by 496
Abstract
The aim of this study was to analyze the accuracy and predictability of the indirect bonding technique of fixed buccal multibracket appliances using a customized iterative closest point algorithm. Materials and Methods: A total of 340 fixed buccal multibracket appliances were virtually planned [...] Read more.
The aim of this study was to analyze the accuracy and predictability of the indirect bonding technique of fixed buccal multibracket appliances using a customized iterative closest point algorithm. Materials and Methods: A total of 340 fixed buccal multibracket appliances were virtually planned and bonded on 34 experimental anatomically based acrylic resin models by using orthodontic templates designed and manufactured to indirectly bond the fixed buccal multibracket appliances. Afterwards, the models were submitted to a three-dimensional impression technique by an intraoral scanner, and the standard tessellation language digital files from the virtual planning and the digital impression were aligned, segmented, and realigned using morphometric software. Linear positioning deviations (mm) of the fixed buccal multibracket appliances were quantified at mesio-distal, bucco-lingual/palatal, and gingival/occlusal (vertical) planes, and angular deviations (°) were also recorded by analyzing the torque, tip, and rotation using a customized iterative closest point algorithm, the script for which allowed for an accuracy measurement procedure by comparing the tessellation network positioning of both standard tessellation language digital files. Results: The mean mesio-distal deviation was −0.065 ± 0.081 mm, the mean bucco-lingual/palatal deviation was 0.129 ± 0.06 m, the mean vertical deviation was −0.094 ± 0.147 mm, the mean torque deviation was −0.826 ± 1.721°, the mean tip deviation was −0.271 ± 0.920°, and the mean rotation deviation was −0.707 ± 0.648°. Conclusion: The indirect bonding technique provides accurate and predictable positioning of fixed buccal multibracket appliances. Full article
(This article belongs to the Special Issue New Trends in Precision Medicine)
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Article
Dialectical Behaviour Therapy Improves Emotion Dysregulation Mainly in Binge Eating Disorder and Bulimia Nervosa: A Systematic Review and Meta-Analysis
J. Pers. Med. 2021, 11(9), 931; https://doi.org/10.3390/jpm11090931 - 18 Sep 2021
Viewed by 543
Abstract
Emotion dysregulation is a transdiagnostic phenomenon in Eating Disorders (ED), and Dialectical Behaviour Therapy (DBT) (which was developed for reducing dysregulated emotions in personality disorders) has been employed in patients with ED. This systematic review and meta-analysis investigated whether the effect of DBT [...] Read more.
Emotion dysregulation is a transdiagnostic phenomenon in Eating Disorders (ED), and Dialectical Behaviour Therapy (DBT) (which was developed for reducing dysregulated emotions in personality disorders) has been employed in patients with ED. This systematic review and meta-analysis investigated whether the effect of DBT was stronger on emotion dysregulation, general psychopathology, and Body Mass Index (BMI) in participants with ED, when compared to a control group (active therapy and waitlist). Eleven studies were identified in a systematic search in accordance with PRISMA guidelines. Most studies included participants with Binge Eating Disorder (BED) (n = 8), some with Bulimia Nervosa (BN) (n = 3), and only one with Anorexia Nervosa (AN). The pooled effect of DBT indicated a greater improvement in Emotion Regulation (ER) (g = −0.69, p = 0.01), depressive symptoms (g = −0.33, p < 0.00001), ED psychopathology (MD = −0.90, p = 0.005), Objective Binge Episodes (OBE) (MD = −0.27, p = 0.003), and BMI (MD = −1.93, p = 0.01) compared to the control group. No improvement was detected in eating ER following DBT (p = 0.41). DBT demonstrated greater efficacy compared with the control group in improving emotion dysregulation, ED psychopathology, and BMI in ED. The limitations included the small number of studies and high variability. Full article
(This article belongs to the Special Issue Biomarkers and Clinical Research in Eating Disorders)
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Review
Does 3D-Assisted Operative Treatment of Pelvic Ring Injuries Improve Patient Outcome?—A Systematic Review of the Literature
J. Pers. Med. 2021, 11(9), 930; https://doi.org/10.3390/jpm11090930 - 18 Sep 2021
Viewed by 318
Abstract
Background: There has been an exponential growth in the use of advanced technologies for three-dimensional (3D) virtual pre- and intra-operative planning of pelvic ring injury surgery but potential benefits remain unclear. The purpose of this study was to evaluate differences in intra- and [...] Read more.
Background: There has been an exponential growth in the use of advanced technologies for three-dimensional (3D) virtual pre- and intra-operative planning of pelvic ring injury surgery but potential benefits remain unclear. The purpose of this study was to evaluate differences in intra- and post-operative results between 3D and conventional (2D) surgery. Methods: A systematic review was performed including published studies between 1 January 2010 and 22 May 2020 on all available 3D techniques in pelvic ring injury surgery. Studies were assessed for their methodological quality according to the Modified McMaster Critical Review form. Differences in operation time, blood loss, fluoroscopy time, screw malposition rate, fracture reduction and functional outcome between 3D-assisted and conventional (2D) pelvic injury treatment were evaluated and a best-evidence synthesis was performed. Results: Eighteen studies fulfilled the inclusion criteria, evaluating a total of 988 patients. Overall quality was moderate. Regarding intra-operative results of 3D-assisted versus conventional surgery: The weighted mean operation time per screw was 43 min versus 52 min; for overall operation time 126 min versus 141 min; blood loss 275 ± 197 mL versus 549 ± 404 mL; fluoroscopy time 74 s versus 125 s and fluoroscopy frequency 29 ± 4 versus 63 ± 3. In terms of post-operative outcomes of 3D-assisted versus conventional surgery: weighted mean screw malposition rate was 8% versus 18%; quality of fracture reduction measured by the total excellent/good rate by Matta was 86% versus 82% and Majeed excellent/good rate 88% versus 83%. Conclusion: The 3D-assisted surgery technologies seem to have a positive effect on operation time, blood loss, fluoroscopy dose, time and frequency as well as accuracy of screw placement. No improvement in clinical outcome in terms of fracture reduction and functional outcome has been established so far. Due to a wide range of methodological quality and heterogeneity between the included studies, results should be interpreted with caution. Full article
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Review
Stratification by Sex and Hormone Level When Contrasting Men and Women in Schizophrenia Trials Will Improve Personalized Treatment
J. Pers. Med. 2021, 11(9), 929; https://doi.org/10.3390/jpm11090929 - 18 Sep 2021
Viewed by 305
Abstract
Background: Sex and gender differences have been reported in the prevalence, expression, treatment response, and outcome of schizophrenia, but most reports are based on relatively small samples that have not been stratified for the impact of sex hormone levels. This literature review aims [...] Read more.
Background: Sex and gender differences have been reported in the prevalence, expression, treatment response, and outcome of schizophrenia, but most reports are based on relatively small samples that have not been stratified for the impact of sex hormone levels. This literature review aims to show how women’s hormone levels can impact the results of male/female comparisons. Methods: This is a narrative review of data from publications of the last decade. Results: Epidemiologic evidence, reports of the impact of hormones on cognition, results of sexually dimorphic responses to treatment, and male/female trajectories of illness over time all suggest that female hormone fluctuations exert major effects on male/female differences in schizophrenia. Conclusions: Information on hormonal status in women participants is rarely available in clinical studies in schizophrenia, which makes male/female comparisons largely uninterpretable. These are the current challenges. Opportunities for individualized treatment are growing, however, and will undoubtedly result in improved outcomes for both women and men in the future. Full article
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Article
Deep-Learning-Based Smartphone Application for Self-Diagnosis of Scleral Jaundice in Patients with Hepatobiliary and Pancreatic Diseases
J. Pers. Med. 2021, 11(9), 928; https://doi.org/10.3390/jpm11090928 - 18 Sep 2021
Viewed by 477
Abstract
Outpatient detection of total bilirubin levels should be performed regularly to monitor the recurrence of jaundice in hepatobiliary and pancreatic disease patients. However, frequent hospital visits for blood testing are burdensome for patients with poor medical conditions. This study validates a novel deep-learning-based [...] Read more.
Outpatient detection of total bilirubin levels should be performed regularly to monitor the recurrence of jaundice in hepatobiliary and pancreatic disease patients. However, frequent hospital visits for blood testing are burdensome for patients with poor medical conditions. This study validates a novel deep-learning-based smartphone application for the self-diagnosis of scleral jaundice in such patients. The system predicts total serum bilirubin levels using the deep-learning-based regression analysis of scleral photos taken by the smartphone’s built-in camera. Enrolled patients were randomly assigned to either the training cohort (n = 90, 1034 photos) or the validation cohort (n = 40, 426 photos). The intraclass correlation coefficient value for predicted serum total bilirubin (PSB) derived from the images repeatedly taken at the same time for the same patient showed good reliability (0.86). A strong correlation between measured serum total bilirubin (MSB) and PSB was observed in the subgroup with MSB levels ≥1.5 mg/dL (Spearman rho = 0.70, p < 0.001). The receiver operating characteristic curve for PSB showed that the area under the curve was 0.93, demonstrating good test performance as a predictor of hyperbilirubinemia (p < 0.001). Using a cut-off PSB ≥1.5, the prediction sensitivity of hyperbilirubinemia was 80.0%, with a specificity of 92.6%. Hence, the tool is effective for patient monitoring. Full article
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Review
Physical Inactivity: A Modifiable Risk Factor for Morbidity and Mortality in Kidney Transplantation
J. Pers. Med. 2021, 11(9), 927; https://doi.org/10.3390/jpm11090927 - 18 Sep 2021
Viewed by 419
Abstract
In patients with chronic kidney disease, sedentary behavior is widely recognized as a significant risk factor for cardiovascular disease, diabetes, obesity, osteoporosis, cancer, and depression. Nevertheless, the real impact of physical inactivity on the health of kidney transplant (KT) recipients remains uncertain. Over [...] Read more.
In patients with chronic kidney disease, sedentary behavior is widely recognized as a significant risk factor for cardiovascular disease, diabetes, obesity, osteoporosis, cancer, and depression. Nevertheless, the real impact of physical inactivity on the health of kidney transplant (KT) recipients remains uncertain. Over the last decade, there has been a renewed interest in exploring the effects of regular physical exercise on transplant-related outcomes. There is now mounting evidence that physical activity may reduce the burden of cardiovascular risk factors, preserve allograft function, minimize immunosuppression requirement, and ameliorate the quality of life of KT recipients. Many positive feedbacks can be detected in the early stages of the interventions and with a minimal exercise load. Despite these encouraging results, the perceived role of physical activity in the management of KT candidates and recipients is often underrated. The majority of trials on exercise training are small, relatively short, and focused on surrogate outcomes. While waiting for larger studies with longer follow-up, these statistical limitations should not discourage patients and doctors from initiating exercise and progressively increasing intensity and duration. This narrative review summarizes current knowledge about the deleterious effects of physical inactivity after KT. The benefits of regular physical exercise are also outlined. Full article
(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)
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Review
A Systematic Review on the Contribution of Artificial Intelligence in the Development of Medicines for COVID-2019
J. Pers. Med. 2021, 11(9), 926; https://doi.org/10.3390/jpm11090926 - 18 Sep 2021
Viewed by 643
Abstract
Background: COVID-2019 pandemic lead to a raised interest on the development of new treatments through Artificial Intelligence (AI). Aim: to carry out a systematic review on the development of repurposed drugs against COVID-2019 through the application of AI. Methods: The Systematic Reviews and [...] Read more.
Background: COVID-2019 pandemic lead to a raised interest on the development of new treatments through Artificial Intelligence (AI). Aim: to carry out a systematic review on the development of repurposed drugs against COVID-2019 through the application of AI. Methods: The Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied. Keywords: [“Artificial intelligence” and (COVID or SARS) and (medicine or drug)]. Databases: PubMed®, DOAJ and SciELO. Cochrane Library was additionally screened to identify previous published reviews on the same topic. Results: From the 277 identified records [PubMed® (n = 157); DOAJ (n = 119) and SciELO (n = 1)], 27 studies were included. Among other, the selected studies on new treatments against COVID-2019 were classified, as follows: studies with in-vitro and/or clinical data; association of known drugs; and other studies related to repurposing of drugs. Conclusion: Diverse potentially repurposed drugs against COVID-2019 were identified. The repurposed drugs were mainly from antivirals, antibiotics, anticancer, anti-inflammatory, and Angiotensin-converting enzyme 2 (ACE2) groups, although diverse other pharmacologic groups were covered. AI was a suitable tool to quickly analyze large amounts of data or to estimate drug repurposing against COVID-2019. Full article
(This article belongs to the Special Issue Application of Artificial Intelligence in Personalized Medicine)
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Article
Differential Expression of Estrogen-Responsive Genes in Women with Psoriasis
J. Pers. Med. 2021, 11(9), 925; https://doi.org/10.3390/jpm11090925 - 17 Sep 2021
Viewed by 381
Abstract
In women, the flow of psoriasis is influenced by each phase of a woman’s life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to [...] Read more.
In women, the flow of psoriasis is influenced by each phase of a woman’s life cycle. According to previous findings, significant changes in the levels of sex hormones affect the severity of the disease. Aim: The aim of this study was to identify the estrogen-responsive genes that could be responsible for the exacerbation of psoriasis in menopausal women. Methods: Skin samples of lesional skin donated by psoriasis patients (n = 5) were compared with skin samples of healthy volunteers (n = 5) using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The set of differentially expressed proteins was subjected to protein ontology analysis to identify differentially expressed estrogen-responsive proteins. The expression of discovered proteins was validated by qPCR and ELISA on four groups of female participants. The first group included ten psoriasis patients without menopause; the second included eleven postmenopausal patients; the third included five healthy volunteers without menopause; and the fourth included six postmenopausal volunteers. Moreover, the participants’ blood samples were used to assess the levels of estradiol, progesterone, and testosterone. Results: We found that the levels of estradiol and progesterone were significantly lower and the levels of testosterone were significantly higher in the blood of patients compared to the control. The protein ontology analysis of LC–MS/MS data identified six proteins, namely HMOX1, KRT19, LDHA, HSPD1, MAPK1, and CA2, differentially expressed in the lesional skin of female patients compared to male patients. ELISA and qPCR experiments confirmed differential expression of the named proteins and their mRNA. The genes encoding the named proteins were differentially expressed in patients compared to volunteers. However, KRT19 and LDHA were not differentially expressed when we compared patients with and without menopause. All genes, except MAPK1, were differentially expressed in patients with menopause compared to the volunteers with menopause. HMOX1, KRT19, HSPD1, and LDHA were differentially expressed in patients without menopause compared to the volunteers without menopause. However, no significant changes were found when we compared healthy volunteers with and without menopause. Conclusion: Our experiments discovered a differential expression of six estrogen-controlled genes in the skin of female patients. Identification of these genes and assessment of the changes in their expression provide insight into the biological effects of estrogen in lesional skin. The results of proteomic analysis are available via ProteomeXchange with identifier PXD021673. Full article
(This article belongs to the Special Issue Personalized Medicine in the Field of Inflammatory Skin Disorders)
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Article
Dienogest and the Risk of Reoperation in Endometriosis
J. Pers. Med. 2021, 11(9), 924; https://doi.org/10.3390/jpm11090924 - 17 Sep 2021
Viewed by 345
Abstract
Background: This retrospective cohort study aimed to determine whether there is a difference in reoperation rates between patients who used dienogest (DNG) and patients who did not use DNG. Methods: Using Health Insurance Review and Assessment Service (HIRA) data generated between 1 January [...] Read more.
Background: This retrospective cohort study aimed to determine whether there is a difference in reoperation rates between patients who used dienogest (DNG) and patients who did not use DNG. Methods: Using Health Insurance Review and Assessment Service (HIRA) data generated between 1 January 2010 and 30 June 2018, we identified women with an endometriosis diagnosis code who used GnRH agonists after gynecological surgery. Among them, women prescribed DNG were selected as the DNG group, and those who did not receive DNG were selected as the control group. A survival analysis of the reoperation between the two groups was performed. Results: DNG and control groups were extracted from 9735 people each. The reoperation rates were 0.4% and 0.6% in the DNG and control groups, respectively, without adjusting. In the Cox proportional risk analysis, DNG use increased the reoperation rate {hazard ratio (HR), 1.599; 95% confidence interval (CI), 1.005–2.545}. The site of endometriosis and the number of GnRH agonist injections were not associated with reoperation (HR, 1.008; 95% CI, 0.739–1.374; HR, 1.062; 95% CI, 0.690–1.635). In the subgroup survival analysis, according to the period between the last GnRH agonist injection and the first DNG dose, DNG did not increase the reoperation rates up to 9 months (~3 months: HR, 0.968; 95% CI, 0.551–1.699; 4~6 months: HR, 1.094; 95% CI, 0.58–2.063; 7~9 months: HR, 2.419; 95% CI, 0.735–7.962), but DNG increased the reoperation rate from 10 months onwards (10~12 months: HR, 3.826; 95% CI, 1.164–12.579 and ~13 months: HR, 8.436; 95% CI, 4.722–15.072). Conclusions: Women who used DNG had a higher endometriosis reoperation rate than women who did not use DNG. However, the initiation of DNG treatment within nine months after the last GnRH agonist injection did not affect the endometriosis reoperation rate. Full article
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Article
αβ-T Cells Engineered to Express γδ-T Cell Receptors Can Kill Neuroblastoma Organoids Independent of MHC-I Expression
J. Pers. Med. 2021, 11(9), 923; https://doi.org/10.3390/jpm11090923 - 17 Sep 2021
Viewed by 470
Abstract
Currently ~50% of patients with a diagnosis of high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression of neuroblastoma represents a major challenge for T cell-mediated [...] Read more.
Currently ~50% of patients with a diagnosis of high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression of neuroblastoma represents a major challenge for T cell-mediated immunotherapy. Here, we propose a novel T cell-based immunotherapy approach for neuroblastoma, based on the use of TEG002, αβ-T cells engineered to express a defined γδ-T cell receptor, which can recognize and kill target cells independent of MHC-I. In a co-culture killing assay, we showed that 3 out of 6 neuroblastoma organoids could activate TEG002 as measured by IFNγ production. Transcriptional profiling showed this effect correlates with an increased activity of processes involved in interferon signaling and extracellular matrix organization. Analysis of the dynamics of organoid killing by TEG002 over time confirmed that organoids which induced TEG002 activation were efficiently killed independent of their MHC-I expression. Of note, efficacy of TEG002 treatment was superior to donor-matched untransduced αβ-T cells or endogenous γδ-T cells. Our data suggest that TEG002 may be a promising novel treatment option for a subset of neuroblastoma patients. Full article
(This article belongs to the Special Issue Precision Medicine for Neuroblastoma)
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Article
MicroRNA Expression Profiles in Autism Spectrum Disorder: Role for miR-181 in Immunomodulation
J. Pers. Med. 2021, 11(9), 922; https://doi.org/10.3390/jpm11090922 - 17 Sep 2021
Viewed by 358
Abstract
Background: MicroRNAs (miRNAs) are important regulators of molecular pathways in psychiatric disease. Here, we examine differential miRNAs expression in lymphoblastoid cell lines (LCLs) derived from 10 individuals with autism spectrum disorder (ASD) and compare them to seven typically developing unrelated age- and gender-matched [...] Read more.
Background: MicroRNAs (miRNAs) are important regulators of molecular pathways in psychiatric disease. Here, we examine differential miRNAs expression in lymphoblastoid cell lines (LCLs) derived from 10 individuals with autism spectrum disorder (ASD) and compare them to seven typically developing unrelated age- and gender-matched controls and 10 typically developing siblings. Small RNAseq analysis identified miRNAs, and selected miRNAs were validated using quantitative real-time polymerase reaction (qRT-PCR). KEGG analysis identified target pathways, and selected predicted mRNAs were validated using qRT-PCR. Results: Small RNAseq analysis identified that multiple miRNAs differentiated ASD from unrelated controls and ASD from typically developing siblings, with only one, hsa-miR-451a_R-1, being in common. Verification with qRT-PCR showed that miR-320a differentiated ASD from both sibling and unrelated controls and that several members of the miR-181 family differentiated ASD from unrelated controls. Differential expression of AKT2, AKT3, TNF α and CamKinase II predicted by KEGG analysis was verified by qRT-PCR. Expression of CamKinase II βwas found to be correlated with the severity of stereotyped behavior of the ASD participants. Conclusions: This study provides insight into the mechanisms regulating molecular pathways in individuals with ASD and identifies differentiated regulated genes involved in both the central nervous system and the immune system. Full article
(This article belongs to the Special Issue Disease Gene Identification and Personalized Medicine in Autism)
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Article
Trust and Trade-Offs in Sharing Data for Precision Medicine: A National Survey of Singapore
J. Pers. Med. 2021, 11(9), 921; https://doi.org/10.3390/jpm11090921 - 16 Sep 2021
Viewed by 493
Abstract
Background: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations about data sharing and establishing appropriate governance structures. [...] Read more.
Background: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations about data sharing and establishing appropriate governance structures. There is a lack of data on public attitudes towards PM in Asia. Methods: The aim of the research was to measure the priorities and preferences of Singaporeans for sharing health-related data for PM. We used adaptive choice-based conjoint analysis (ACBC) with four attributes: uses, users, data sensitivity and consent. We recruited a representative sample of n = 1000 respondents for an in-person household survey. Results: Of the 1000 respondents, 52% were female and majority were in the age range of 40–59 years (40%), followed by 21–39 years (33%) and 60 years and above (27%). A total of 64% were generally willing to share de-identified health data for IRB-approved research without re-consent for each study. Government agencies and public institutions were the most trusted users of data. The importance of the four attributes on respondents’ willingness to share data were: users (39.5%), uses (28.5%), data sensitivity (19.5%), consent (12.6%). Most respondents found it acceptable for government agencies and hospitals to use de-identified data for health research with broad consent. Our sample was consistent with official government data on the target population with 52% being female and majority in the age range of 40–59 years (40%), followed by 21–39 years (33%) and 60 years and above (27%). Conclusions: While a significant body of prior research focuses on preferences for consent, our conjoint analysis found consent was the least important attribute for sharing data. Our findings suggest the social license for PM data sharing in Singapore currently supports linking health and genomic data, sharing with public institutions for health research and quality improvement; but does not support sharing with private health insurers or for private commercial use. Full article
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Article
Quality Analysis of YouTube Videos Presenting Pelvic Floor Exercises after Prostatectomy Surgery
J. Pers. Med. 2021, 11(9), 920; https://doi.org/10.3390/jpm11090920 - 15 Sep 2021
Viewed by 456
Abstract
Background: Prostate cancer (PC) is a major cause of disease and mortality among men. Surgical treatment involving the removal of the prostate may result in temporary or permanent erectile dysfunction (ED) and urinary incontinence (UI), with considerable impact on quality of life. Pelvic [...] Read more.
Background: Prostate cancer (PC) is a major cause of disease and mortality among men. Surgical treatment involving the removal of the prostate may result in temporary or permanent erectile dysfunction (ED) and urinary incontinence (UI), with considerable impact on quality of life. Pelvic floor muscle training (PFMT) is one of the recommended techniques for the prevention, treatment, and rehabilitation of postoperative complications. The aim of this observational study was to assess the quality of YouTube videos—accessible to any patient—related to exercises after prostatectomy surgery. Methods: A systematic search was performed on YouTube on 24 September 2020. One hundred and fifty videos were selected and analyzed. Two statistical analyses were conducted based on machine-learning techniques, and videos were classified as ‘Relevant’ or ‘Non-Relevant’ using Principal Component Analysis (PCA) models. Two reviewers conducted independent analyses. Inter-observer agreement and individual correlations of video data were evaluated with the Intraclass Correlation Coefficient (ICC). Information quality, reliability, and accuracy were measured using the DISCERN Scale and Global Quality Score (GQS), while video popularity was evaluated using the Video Power Index (VPI). Results: DISCERN scored a mean of 3.35 and GQS scored 3.38. Average number of views was 124,354, mean duration was 14:42 min, mean days online was 1777, mean view ratio was 138.30, mean Likes was 1082, mean Dislikes was 68.58, and mean VPI was 92.28. Conclusions: The quality of the videos available on YouTube regarding the recommended pelvic floor exercises in PC surgery, according to the scores obtained, is High. Educational and health institutions, health professionals, government health authorities, and policy makers need to be involved in the proper development of policies to improve the information available on the web in order to have a positive impact on the healthy behavior of the population. Full article
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Article
Prediction of Sarcopenia Using Multiple Biomarkers of Neuromuscular Junction Degeneration in Chronic Obstructive Pulmonary Disease
J. Pers. Med. 2021, 11(9), 919; https://doi.org/10.3390/jpm11090919 - 15 Sep 2021
Viewed by 320
Abstract
Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin [...] Read more.
Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin fragment -22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of sarcopenia in COPD during pulmonary rehabilitation (PR). Male, 61–77-year-old healthy controls and patients of COPD (n = 77–84/group) were recruited for measurements of circulating CAF22, BDNF, and GDNF levels. Functional assessment and measurements of plasma biomarkers were performed at diagnosis and following six months of PR. CAF22 levels were elevated while BDNF and GDNF levels were reduced in COPD patients at diagnosis, which were incompletely restored to normal levels following PR. These biomarkers showed varying degrees of associations with indexes of sarcopenia and functional recovery during PR. Logistic regression revealed that the combined use of three biomarkers enhanced the diagnostic accuracy of sarcopenia better than single biomarkers. Altogether, measurements of plasma CAF22, BDNF, and GDNF may be helpful for the accurate diagnosis of sarcopenia and functional capacity in COPD during PR. Full article
(This article belongs to the Special Issue Personalized Medicine for Neuromuscular Atrophy)
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Article
Quality of Life, Sleep Quality, Depression, Anxiety, Stress, Eating Habits, and Social Bounds in Nurses during the Coronavirus Disease 2019 Pandemic in Qatar (The PROTECTOR Study): A Cross-Sectional, Comparative Study
J. Pers. Med. 2021, 11(9), 918; https://doi.org/10.3390/jpm11090918 - 15 Sep 2021
Viewed by 800
Abstract
There have been numerous concerns regarding the physical and mental health of nurses during the COVID-19 pandemic. Stress, sleep deprivation, anxiety, and depression potentiated nurses’ vulnerability to poor eating habits. Aims and Objectives: The purpose of this study was to explore the differences [...] Read more.
There have been numerous concerns regarding the physical and mental health of nurses during the COVID-19 pandemic. Stress, sleep deprivation, anxiety, and depression potentiated nurses’ vulnerability to poor eating habits. Aims and Objectives: The purpose of this study was to explore the differences between nurses’ characteristics with COVID-19 facility designation, and sleep quality, depression, anxiety, stress, eating habits, social bonds, and quality of life. Design: A cross-sectional, comparative study. Methods: An online survey was sent using the corporation’s email to nurses working in three hospitals in Qatar from September to December 2020. One of them is a designated COVID-19 facility. The sleep quality, depression, eating habits, social bonds, and quality of life were measured using The Insomnia Severity Index (ISI), Depression Anxiety and Stress Scale 21 (DASS-21), Emotional Eater Questionnaire (EEQ), Oslo Social Support Scale (OSSS-3), and the World Health Organization Quality of Life (WHOQOL-BREF), respectively. Results: A total of 200 nurses participated in the study (RR: 13.3%). No statistically significant association was found between designated facility (COVID-19 vs. not COVID-19) or nurses’ characteristics and ISI categories (OR 1.15; 95% CI 0.54, 2.44). Nurses working in COVID-19 facilities had increased odds of having higher EEQ categories by 2.62 times (95% CI 1.18, 5.83). Similarly, no statistically significant associations were found between any of the nurses’ characteristics and OSSS-3 categories. On the other hand, no statistically significant associations were found between any of the nurses’ characteristics and QOL domains except for the gender and social relationships’ domain. Conclusion: Overall, the quality of life of nurses in Qatar is on a positive level whether they are assigned to a COVID-19 facility or not. Although no significant difference was found with regard to the sleep quality, stress, anxiety, depression, and eating habits between nurses in a COVID-19 facility and in a non-COVID-19 facility, special interventions to diminish stressors need to be implemented and maintained. Full article
(This article belongs to the Special Issue Personalized Clinical and Community Nursing)
Article
Cancer Spectrum, Family History of Cancer and Overall Survival in Men with Germline BRCA1 or BRCA2 Mutations
J. Pers. Med. 2021, 11(9), 917; https://doi.org/10.3390/jpm11090917 - 15 Sep 2021
Viewed by 649
Abstract
BACKGROUND: Men with germline BRCA1/2 mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male BRCA1/2 mutation carriers. METHODS: All men with germline BRCA1/2 mutations who attended [...] Read more.
BACKGROUND: Men with germline BRCA1/2 mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male BRCA1/2 mutation carriers. METHODS: All men with germline BRCA1/2 mutations who attended genetic assessment between October 1995 and October 2019 at the Medical University of Vienna were identified. Clinicohistopathological features, family history of cancer, and outcomes were assessed by mutation status. RESULTS: Of the 323 men included, 45 (13.9%) had a primary cancer diagnosis, many of whom were BRCA2 carriers (75.5%). Breast cancer (BC) was the most common cancer (57.8%) followed by prostate cancer (15.6%). Invasive ductal carcinoma and hormone receptor positive tumors were the most common. Among 26 BC-affected patients, 42% did not have any relatives with cancer. Parent of origin was only known in half of the 26 men, with 42% of them inherited through the maternal lineage versus 8% through the paternal. BRCA2 carriers and those with a family history of BC had worse overall survival (20 y vs. 23 y BRCA1 carriers; P = 0.007; 19 y vs. 21 y for those without family history of BC; P = 0.036). CONCLUSION: Male BRCA2 carriers were most likely to develop cancer and had worse prognosis. In our dataset, BC was the most common cancer, likely due to referral bias. Not all mutation carriers present with BC or have a family history of cancer to warrant genetic testing. Full article
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Article
Should Age-Dependent Absolute Risk Thresholds Be Used for Risk Stratification in Risk-Stratified Breast Cancer Screening?
J. Pers. Med. 2021, 11(9), 916; https://doi.org/10.3390/jpm11090916 - 15 Sep 2021
Viewed by 695
Abstract
In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual’s estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- [...] Read more.
In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual’s estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- or ten-year) risk, is estimated from the age at assessment. These risk estimates vary by age; however, some clinical guidelines (e.g., enhanced breast cancer surveillance guidelines) and ongoing personalised breast screening trials, stratify women based on absolute risk thresholds that do not vary by age. We examine an alternative approach in which the risk thresholds used for risk stratification vary by age and consider the implications of using age-independent risk thresholds on risk stratification. We demonstrate that using an age-independent remaining lifetime risk threshold approach could identify high-risk younger women but would miss high-risk older women, whereas an age-independent 5-year or 10-year absolute risk threshold could miss high-risk younger women and classify lower-risk older women as high risk. With risk misclassification, women with an equivalent risk level would be offered a different screening plan. To mitigate these problems, age-dependent absolute risk thresholds should be used to inform risk stratification. Full article
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Article
Adipogenic Stimulation and Pyrrolidine Dithiocarbamate Induced Osteogenic Inhibition of Dental Pulp Stem Cells Is Countered by Cordycepin
J. Pers. Med. 2021, 11(9), 915; https://doi.org/10.3390/jpm11090915 - 14 Sep 2021
Viewed by 639
Abstract
Background: dental pulp-derived stem cells are easy to access and collect and are an excellent source of stem cells for regenerative therapy. These cells can interact with many biomolecules and scaffolds and can pass on the instructive signals to the sites of regeneration [...] Read more.
Background: dental pulp-derived stem cells are easy to access and collect and are an excellent source of stem cells for regenerative therapy. These cells can interact with many biomolecules and scaffolds and can pass on the instructive signals to the sites of regeneration where they are used. In this regard cordycepin, a potential biomolecule derived from medicinal mushrooms with a spectrum of bioactive properties such as antioxidant, anti-inflammatory, and anticancer has not yet been tested for its effect on human dental pulp stem cells. Objective: the objective of the present study was to assess the in vitro adipogenic and osteogenic differentiation potential of human dental pulp stem cells with or without induction after administration of cordycepin. Materials and methods: human dental pulp stem cells DPSCs were isolated from a healthy permanent tooth extracted for orthodontic purposes after obtaining informed consent. Flow cytometry technique was used to assess the surface markers of these cells such as CD73, CD90, and CD105, CD34, CD45, and HLA-DR. Further, an MTT assay was performed on the cells after subjecting them to various concentrations of cordycepin. Following this, the adipogenic and osteogenic potential of the dental pulp stem cells was assessed with or without induction under the influence/absence of 5 µM of cordycepin. The results obtained were statistically analyzed and documented. Results: it was found that the dental pulp stem cells showed strong positive expression for CD73, CD90, and CD105 and faint expression of CD34, CD45, and HLA-DR. MTT assay revealed that 5 µM was the optimum concentration of cordycepin for all the assays. Concerning adipogenesis experiments, there was a statistically significant lowering of all the 4 adipogenesis-related genes PPARγ, FABP4, LPL, and C/EBPα following cordycepin treatment in the presence of induction compared to the only induction group and untreated control cells (p < 0.05). In connection with osteogenesis, was found that there was a statistically significant increase in the expression of RUNX2, COL1A1, OSX and OCN genes along with the increase in alkaline phosphatase and alizarin red staining in the DPSC treated with cordycepin along with the presence of induction and simultaneous addition of PDTC compared to the control untreated cells and cells treated with induction and simultaneous addition of PDTC (p < 0.05). Conclusion: cordycepin can be exploited for its osteopromotive properties and can be used as a bioactive molecule alongside the administration of dental pulp stem cells in the area of regenerative biology and medicine. Full article
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From Anti-PD-1/PD-L1 to CTLA-4 and to MUC1—Is the Better Response to Treatment in Smokers of Cancer Patients Drug Specific?
J. Pers. Med. 2021, 11(9), 914; https://doi.org/10.3390/jpm11090914 - 13 Sep 2021
Viewed by 498
Abstract
Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. [...] Read more.
Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. Our results showed that among all non-small cell lung cancer (NSCLC) patients, when the data from anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs are combined, the mean hazard ratios (HR) of smokers and non-smokers were 0.751 and 1.016, respectively. A meta-analysis with a fixed effect (FE) model indicated that the smokers have an HR value of 0.023 lower than that of the non-smokers. A stratified subgroup meta-analysis indicated that when treated with anti-CTLA-4 drugs, smokers had reduced HR values of 0.152 and 0.165 on average and FE model meta-analysis, respectively. When treated with an anti-MUC1 drug, smokers had reduced HR values of 1.563 and 0.645, on average and FE model meta-analysis, respectively. When treated with a combination of nivolumab and ipilimumab drugs, smokers had, on average, reduced HR and FE model meta-analysis values (0.257 and 0.141), respectively. Smoking is a clinical response predictor for anti-PD/PD-L1 monotherapy or first-line treatment in lung, urothelial carcinoma, and head and neck cancer. Smokers treated with other drugs have shown worse responses in comparison to non-smokers. These data suggest that, along with the progress in the development of new drugs for cancer, drugs acting on specific genotypes of smokers likely will arise. Full article
(This article belongs to the Special Issue Precision Medicine for Immunology and Immunogenetics)
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Article
Quantifying Left Atrial Size in the Context of Atrial Fibrillation Ablation: Which Echocardiographic Method Correlates to Outcome of Pulmonary Venous Isolation?
J. Pers. Med. 2021, 11(9), 913; https://doi.org/10.3390/jpm11090913 - 13 Sep 2021
Viewed by 336
Abstract
Introduction: Multiple studies have shown that left atrial (LA) enlargement is a strong predictor of poor outcome after catheter ablation of atrial fibrillation (AF). LA size is commonly approximated as the diameter in the parasternal long axis. It remains unknown whether more precise [...] Read more.
Introduction: Multiple studies have shown that left atrial (LA) enlargement is a strong predictor of poor outcome after catheter ablation of atrial fibrillation (AF). LA size is commonly approximated as the diameter in the parasternal long axis. It remains unknown whether more precise echocardiographic measurements of LA size allow for better correlation with outcome after pulmonary vein isolation (PVI). Methods and results: We performed a retrospective study of 131 consecutive patients (43 females, 60% paroxysmal AF, mean CHA2DS2-Vasc score 1.6, mean age 61 ± 12 years) referred for PVI. Measurements of the LA were carried out by a single observer in transthoracic echocardiograms (TTE) performed prior to ablation. We calculated diameter of the LA in the parasternal long axis (PLAX), LA area in the 2- as well as 4-Chamber (CH) view. LA volume was computed using the disc summation technique (LAV) and indexed to body surface area (LAVI). Procedural and follow-up data were gathered from a prospective AF database. Ablation was performed exclusively using the second generation cryoballoon by the same operators. Follow-up visits at 3, 6 and 12 months showed freedom from AF in 76%, 73% and 73% respectively. Mean values of LA calculations were LAPLAX: 37.9 mm ± 6.3 mm, 2CH area: 22.5 cm2 ± 6.7 cm2, 4CH area: 21.4 cm2 ± 5.5 cm2, LAV: 73.7 mL ± 26.1 mL and LAVI: 36.2 mL/m2 ± 12.7 mL/m2, respectively. C statistic revealed the best concordance of LAVI with outcome after 12 months (C = 0.67), LAV also exhibited a satisfactory value (C = 0.61) in comparison to surfaces in 2CH (C = 0.59) and 4CH (C = 0.57). PLAX showed the worst correlation (C = 0.51). Additionally, different binary logistic regression models identified three independent predictors of AF outcome after cryoballoon PVI: gender (OR = 0.95 per year; p = 0.01); LAV (OR = 1.3/10mL; p = 0.02) and LAVI (OR = 1.58/10 mL/m2; p = 0.02). In all models, PLAX and area measurements were not predictive. Conclusions: Our data add further to evidence that LA size lends itself well as a predictor of PVI outcome. LAVI and LAV were independently predictive of rhythm outcome after PVI. This did not hold true for more commonly used measurements, such as PLAX diameter and surfaces of the LA, irrespective of the view chosen. Full article
(This article belongs to the Special Issue Personalized Cardiovascular Medicine)
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Article
Effect of Dexmedetomidine on Biochemical Recurrence in Patients after Robot-Assisted Laparoscopic Radical Prostatectomy: A Retrospective Study
J. Pers. Med. 2021, 11(9), 912; https://doi.org/10.3390/jpm11090912 - 13 Sep 2021
Viewed by 326
Abstract
The usage of dexmedetomidine during cancer surgery in current clinical practice is debatable, largely owing to the differing reports of its efficacy based on cancer type. This study aimed to investigate the effects of dexmedetomidine on biochemical recurrence (BCR) and radiographic progression in [...] Read more.
The usage of dexmedetomidine during cancer surgery in current clinical practice is debatable, largely owing to the differing reports of its efficacy based on cancer type. This study aimed to investigate the effects of dexmedetomidine on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer, who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). Using follow-up data from two prospective randomized controlled studies, BCR and radiographic progression were compared between individuals who received dexmedetomidine (n = 58) and those who received saline (n = 56). Patients with complete follow-up records between July 2013 and June 2019 were enrolled in this study. There were no significant between-group differences in the number of patients who developed BCR and those who showed positive radiographic progression. Based on the Cox regression analysis, age (p = 0.015), Gleason score ≥ 8 (p < 0.001), and pathological tumor stage 3a and 3b (both p < 0.001) were shown to be significant predictors of post-RALP BCR. However, there was no impact on the dexmedetomidine or control groups. Low-dose administration of dexmedetomidine at a rate of 0.3–0.4 μg/kg/h did not significantly affect BCR incidence following RALP. In addition, no beneficial effect was noted on radiographic progression. Full article
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Article
Lower Lean Mass Is Associated with Greater Arterial Stiffness in Patients with Lower Extremity Artery Disease
J. Pers. Med. 2021, 11(9), 911; https://doi.org/10.3390/jpm11090911 - 13 Sep 2021
Viewed by 434
Abstract
Background: Arterial stiffness is independently associated with lower extremity artery disease (LEAD). Although obesity is already known as an independent cardiovascular risk factor, it was found that, paradoxically, in patients diagnosed with cardiovascular disease, an increase in body mass index (BMI) was associated [...] Read more.
Background: Arterial stiffness is independently associated with lower extremity artery disease (LEAD). Although obesity is already known as an independent cardiovascular risk factor, it was found that, paradoxically, in patients diagnosed with cardiovascular disease, an increase in body mass index (BMI) was associated with a decrease in mortality. However, the underlying mechanism of this paradoxical association remain uncertain. In this study, we firstly hypothesize that arterial stiffness correlates with body mass; secondly, the underlying mechanism of the association for patients with LEAD is individual body composition, in particular, lean mass. Methods: The present study was performed as a single-center, prospective, observational analysis. A total of 412 patients with current or previously diagnosed LEAD (Rutherford Classification 2–4) were included, the cfPWV and AIx were measured as indices of arterial stiffness, and a body composition assessment was performed. Results: In male patients, there was a significantly negative correlation between the AIx and lean mass coefficient (p = 0.004, 95% CI: −0.28 (−0.48–0.09)). Conclusion: For patients with peripheral arterial disease, our data show that lower lean mass in male patients is associated with increased arterial stiffness as measured by the AIx. Therefore, progressive resistance training may be beneficial for the reduction in arterial stiffness in PAD patients in secondary prevention. Full article
(This article belongs to the Special Issue Cardiovascular Disease Prevention in the Era of Personalized Medicine)
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