A growing body of evidence now proposes that machine learning and deep learning techniques can serve as a vital foundation for the pharmacogenomics of antidepressant treatments in patients with major depressive disorder (MDD). In this review, we focus on the latest developments for pharmacogenomics research using machine learning and deep learning approaches together with neuroimaging and multi-omics data. First, we review relevant pharmacogenomics studies that leverage numerous machine learning and deep learning techniques to determine treatment prediction and potential biomarkers for antidepressant treatments in MDD. In addition, we depict some neuroimaging pharmacogenomics studies that utilize various machine learning approaches to predict antidepressant treatment outcomes in MDD based on the integration of research on pharmacogenomics and neuroimaging. Moreover, we summarize the limitations in regard to the past pharmacogenomics studies of antidepressant treatments in MDD. Finally, we outline a discussion of challenges and directions for future research. In light of latest advancements in neuroimaging and multi-omics, various genomic variants and biomarkers associated with antidepressant treatments in MDD are being identified in pharmacogenomics research by employing machine learning and deep learning algorithms.

OBJECTIVE: Depression is associated with various environmental risk factors such as stress, childhood maltreatment experiences, and stressful life events. Current approaches to assess the pathophysiology of depression, such as epigenetics and gene-environment (GxE) interactions, have been widely leveraged to determine plausible markers, genes, and variants for the risk of developing depression. METHODS: We focus on the most recent developments for genomic research in epigenetics and GxE interactions. RESULTS: In this review, we first survey a variety of association studies regarding depression with consideration of GxE interactions. We then illustrate evidence of epigenetic mechanisms such as DNA methylation, microRNAs, and histone modifications to influence depression in terms of animal models and human studies. Finally, we highlight their limitations and future directions. CONCLUSION: In light of emerging technologies in artificial intelligence and machine learning, future research in epigenetics and GxE interactions promises to achieve novel innovations that may lead to disease prevention and future potential therapeutic treatments for depression.
Artificial Intelligence ; Biomarkers ; Depression ; DNA Methylation ; Epigenomics ; Gene-Environment Interaction ; Histone Code ; Humans ; Machine Learning ; MicroRNAs ; Models, Animal ; Risk Factors

The novel coronavirus infection, COVID-19, is a pandemic that currently affects the whole world. During this period, Malaysians displayed a variety of behaviour changes as a response to COVID-19, including panic buying, mass travelling during movement restriction and even absconding from treatment facilities. This article attempts to explore some of these behaviour changes from a behaviourist perspective in order to get a better understanding of the rationale behind the changes.

AIMTo investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.

METHODSVES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1 cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis.

RESULTSThe MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen (PSA) at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR) expression increased after the addition of TOB.

CONCLUSIONOur data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; drug effects ; Humans ; Kinetics ; Male ; Prostate ; cytology ; Prostatic Neoplasms ; pathology ; Vitamin E ; analogs & derivatives ; pharmacology

Cytomegalovirus Infections/diagnosis* ; Humans ; Infant, Newborn ; Mass Screening ; Research ; Singapore

STUDY DESIGN: A retrospective review of patients who underwent 2-level anterior cervical discectomy and fusion (ACDF) with standalone polyetheretherketone (PEEK) cages for cervical spondylotic myelopathy (CSM). PURPOSE: To evaluate the efficacy of stand-alone PEEK cage in 2-level cervical interbody fusion for CSM. OVERVIEW OF LITERATURE: ACDF is a standard surgical procedure to treat degenerative disc disease. However, the use of additional anterior plating for 2-level ACDF remains controversial. METHODS: We reviewed outcomes of patients who underwent 2-level ACDF with stand-alone PEEK cages for CSM over a 7-year period (2007–2015) in a regional hospital. Japanese Orthopaedic Association (JOA) score, fusion rate, subsidence rate, cage migration, and cervical alignment by the C2–7 angle as well as the local segmental angle (LSA) of the cervical spine were assessed. RESULTS: In total, 31 patients (mean age, 59 years; range, 36–87 years) underwent 2-level ACDF with a cage-only construct procedure between 2007 and 2015. The minimum follow-up was 24 months; mean follow-up was 51 months. C3–5 fusion was performed in 45%, C4–6 fusion in 32%, and C5–7 fusion in 23%. Mean JOA score improved from 10.1±2.2 to 13.9±2.1 (p<0.01) at the 24-month follow-up. Fusion was achieved in all patients. Subsidence occurred in 22.5% of the cages but was not associated with differences in JOA scores, age, sex, or levels fused. Lordosis of the C2–7 angle and LSA increased after surgery, which were maintained for up to 1 year but subsequently disappeared after 2 years, yet the difference was not statistically significant. No cage migration was noted; two patients developed adjacent segment disease requiring posterior laminoplasty 3 years after ACDF. CONCLUSIONS: The use of a stand-alone PEEK cage in a 2-level cervical interbody fusion achieves satisfactory improvements in both clinical outcomes and fusion.
Animals ; Asian Continental Ancestry Group ; Diskectomy ; Follow-Up Studies ; Humans ; Laminoplasty ; Lordosis ; Retrospective Studies ; Spinal Cord Diseases ; Spine

Background: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. Methods: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. Results: There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). Conclusion Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

OBJECTIVE: Considering the different prevalence rates of diseases such as asthma and chronic obstructive pulmonary disease in Asians relative to other races, Koreans may have unique airway structure and lung function. This study aimed to investigate unique features of airway structure and lung function based on quantitative computed tomography (QCT)-imaging metrics in the Korean Asian population (Koreans) as compared with the White American population (Whites). MATERIALS AND METHODS: QCT data of healthy non-smokers (223 Koreans vs. 70 Whites) were collected, including QCT structural variables of wall thickness (WT) and hydraulic diameter (Dh) and functional variables of air volume, total air volume change in the lung (ΔVair), percent emphysema-like lung (Emph%), and percent functional small airway disease-like lung (fSAD%). Mann-Whitney U tests were performed to compare the two groups. RESULTS: As compared with Whites, Koreans had smaller volume at inspiration, ΔVair between inspiration and expiration (p < 0.001), and Emph% at inspiration (p < 0.001). Especially, Korean females had a decrease of ΔVair in the lower lobes (p < 0.001), associated with fSAD% at the lower lobes (p < 0.05). In addition, Koreans had smaller Dh and WT of the trachea (both, p < 0.05), correlated with the forced expiratory volume in 1 second (R = 0.49, 0.39; all p < 0.001) and forced vital capacity (R = 0.55, 0.45; all p < 0.001). CONCLUSION: Koreans had unique features of airway structure and lung function as compared with Whites, and the difference was clearer in female individuals. Discriminating structural and functional features between Koreans and Whites enables exploration of inter-racial differences of pulmonary disease in terms of severity, distribution, and phenotype.
Asian Continental Ancestry Group ; Asthma ; Continental Population Groups ; Female ; Forced Expiratory Volume ; Humans ; Lung ; Lung Diseases ; Phenotype ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Thorax ; Trachea ; Vital Capacity