Journal of Personalized Medicine

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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