Vitamin D deficiency as a risk factor for sudden cardiac arrest: A multicenter case-control study.

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

Depressive Symptoms Feature-Based Machine Learning Approach to Predicting Depression Using Smartphone.

With the impact of the COVID-19 pandemic, the number of patients suffering from depression is rising around the world. It is important to diagnose depression early so that it may be treated as soon as possible. The self-response questionnaire, which has been used to diagnose depression in hospitals, is impractical since it requires active patient engagement. Therefore, it is vital to have a system that predicts depression automatically and recommends treatment. In this paper, we propose a smartphone-based depression prediction system. In addition, we propose depressive features based on multimodal sensor data for predicting depressive mood. The multimodal depressive features were designed based on depression symptoms defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The proposed system comprises a "Mental Health Protector" application that collects data from smartphones and a big data-based cloud platform that processes large amounts of data. We recruited 106 mental patients and collected smartphone sensor data and self-reported questionnaires from their smartphones using the proposed system. Finally, we evaluated the performance of the proposed system's prediction of depression. As the test dataset, 27 out of 106 participants were selected randomly. The proposed system showed 76.92% on an f1-score for 16 patients with depression disease, and in particular, 15 patients, 93.75%, were successfully predicted. Unlike previous studies, the proposed method has high adaptability in that it uses only smartphones and has a distinction of evaluating prediction accuracy based on the diagnosis.

Healthy lifestyle factors, cardiovascular comorbidities, and the risk of sudden cardiac arrest: A case-control study in Korea.

AIMS: We investigated the impact of healthy lifestyle factors and cardiovascular comorbidities for sudden cardiac arrest. METHODS: A case-control study, including patients with sudden cardiac arrest aged 20-79 years and community-based 1:2 matched controls, was conducted from September 2017 to December 2020. All participants completed a structured questionnaire. Using multivariable logistic regression, we assessed cardiovascular comorbidities (diabetes, hypertension, dyslipidaemia, myocardial infarction, congestive heart failure, arrhythmia, and stroke) and healthy lifestyle factors (low red meat consumption, low fish consumption, high fruit consumption, high vegetable consumption, current non-smoking, regular exercise, and adequate sleep duration) as sudden cardiac arrest risk factors. RESULTS: Among 3027 eligible cases, informed consent was obtained from 949 (31.3%) cases. A total of 1731 controls were enrolled. Cardiovascular comorbidities, except dyslipidaemia, were associated with an increased risk of sudden cardiac arrest, whereas all healthy lifestyle factors were associated with a decreased risk. Relative to patients in the 0-2 healthy lifestyle factors group, the adjusted odds ratio (95% confidence interval) for sudden cardiac arrest was 0.25 (0.16-0.40) in patients with 3 healthy lifestyle factors, 0.08 (0.05-0.13) in patients with 4 healthy lifestyle factors, and 0.04 (0.03-0.06) in patients with over 5 healthy lifestyle factors. When the number of healthy lifestyle factors was analysed as a continuous variable, each additional factor was associated with a significant decrease in the likelihood of sudden cardiac arrest (adjusted odds ratio [95% confidence interval]: 0.41 [0.36-0.46]). CONCLUSION: The increased risk of sudden cardiac arrest by cardiovascular comorbidities could be significantly reduced with healthy lifestyle factors.

Development of CRISPR technology for precise single-base genome editing: a brief review.

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a family of DNA sequences originally discovered as a type of acquired immunity in prokaryotes such as bacteria and archaea. In many CRISPR systems, the functional ribonucleoproteins (RNPs) are composed of CRISPR protein and guide RNAs. They selectively bind and cleave specific target DNAs or RNAs, based on sequences complementary to the guide RNA. The specific targeted cleavage of the nucleic acids by CRISPR has been broadly utilized in genome editing methods. In the process of genome editing of eukaryotic cells, CRISPRmediated DNA double-strand breaks (DSB) at specific genomic loci activate the endogenous DNA repair systems and induce mutations at the target sites with high efficiencies. Two of the major endogenous DNA repair machineries are non-homologous end joining (NHEJ) and homology-directed repair (HDR). In case of DSB, the two repair pathways operate in competition, resulting in several possible outcomes including deletions, insertions, and substitutions. Due to the inherent stochasticity of DSB-based genome editing methods, it was difficult to achieve defined single-base changes without unanticipated random mutation patterns. In order to overcome the heterogeneity in DSB-mediated genome editing, novel methods have been developed to incorporate precise single-base level changes without inducing DSB. The approaches utilized catalytically compromised CRISPR in conjunction with base-modifying enzymes and DNA polymerases, to accomplish highly efficient and precise genome editing of single and multiple bases. In this review, we introduce some of the advances in single-base level CRISPR genome editing methods and their applications. [BMB Reports 2021; 54(2): 98-105].

Effects of 6 Months of Dapagliflozin Treatment on Metabolic Profile and Endothelial Cell Dysfunction for Obese Type 2 Diabetes Mellitus Patients without Atherosclerotic Cardiovascular Disease.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular death in individuals with type 2 diabetes mellitus (T2DM) and cardiovascular disease, but the effect of these inhibitors on early cardiovascular disease remains unknown. This study evaluated the effect of dapagliflozin on the metabolic profiles and endothelial cell function in obese patients with T2DM without established cardiovascular disease. METHODS: We enrolled 140 patients with a mean age, weight, and body mass index (BMI) of 47 years, 83 kg, and 30.3 kg/m2, respectively. Dapagliflozin (10 mg daily for 6 months) was administered to obese patients with T2DM without established cardiovascular disease. Participants' weight, BMI, body fat mass (BFM), muscle mass, glycosylated hemoglobin (HbA1c), lipid profile, waist to hip ratio (WHR), and pulse wave velocity (PWV) were measured at baseline and after 6 months. RESULTS: Participants experienced statistically significant reductions in their HbA1c, fasting plasma glucose, low-density lipoprotein cholesterol, total cholesterol, body weight, BMI, WHR, BFM, and aortic PWV, without a significant change in their muscle mass, extracellular fluid, or intracellular volume. Statistically significant reductions in aortic PWV were associated with a decrease in BFM, visceral fat, WHR, and homeostatic model assessment of insulin resistance. CONCLUSION: Dapagliflozin may be beneficial in preventing early cardiovascular disease in obese patients with T2DM without established cardiovascular disease.

Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars.

BACKGROUND: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). METHODS: SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. RESULTS: The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. CONCLUSIONS: Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies.

Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma.

PURPOSE: The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensitymodulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. RESULTS: All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). CONCLUSION: Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

High-Dose Thoracic Re-irradiation of Lung Cancer Using Highly Conformal Radiotherapy Is Effective with Acceptable Toxicity.

PURPOSE: Thoracic re-irradiation (re-RT) of lung cancer has been challenged by the tolerance doses of normal tissues. We retrospectively analyzed local control, overall survival (OS) and toxicity after thoracic re-RT using highly conformal radiotherapy, such as intensity modulated radiotherapy and stereotactic body radiotherapy. MATERIALS AND METHODS: Thirty-one patients who received high-dose thoracic re-RT were analyzed. Doses were recalculated to determine biologically equivalent doses. The median interval to re-RT was 15.1 months (range, 4.4 to 56.3 months), the median initial dose was 79.2 Gy10 (range, 51.75 to 150 Gy10), and the median re-RT dose was 68.8 Gy10 (range, 43.2 to 132 Gy10). RESULTS: Eighteen (58.1%) and eleven (35.5%) patients showed loco-regional recurrence and distant metastasis, respectively, after 17.4 months of median follow-up. The 1-year and 2-year local control rates were 60.2% and 43.7%, respectively. The median loco-regional recurrence-free-survival (LRFS) was 15.4 months, and the median OS was 20.4 months. The cumulative and re-RT biologically equivalent dose for α/ß=10 (BED10) doses were the most significant prognostic factors. Cumulative BED10 ≥145 Gy10 and re-RT BED10≥68.7 Gy10 were significantly associated with longer OS (p=0.029 and p=0.012, respectively) and LRFS (p=0.003 and p=0.000, respectively). The most frequent acute toxicity was grade 1-2 pulmonary toxicity (41.9%). No acute grade 3 or higher toxicities occurred. CONCLUSION: Our results show that high-dose thoracic re-RT of lung cancer can be safely delivered using highly conformal radiotherapy with favorable survival and acceptable toxicity. An optimal strategy to select patients who would benefit from re-RT is crucial in extending the indications and improving the efficacy with a sufficiently high dose.

Overlapped seed localization in seed implant brachytherapy.

A procedure for the determination of the location of prostate implant seeds that are wholly overlapped in a projection view has been developed. The procedure mainly consists of a series of image processing and an in-house developed localization software based on a three-film technique. To verify the efficacy of the procedure, a simulation phantom was built and nine sets of simulation were performed. For the assessment of the location of the seeds in the phantom, three images, one in anterior-posterior direction and two others in oblique angles, were acquired and a series of image processing was applied to the images for the removal of unnecessary background and the improvement of imaging quality. In this study, three types were considered; first, when two seeds were overlapped in one of projection images, second, more than three seeds were overlapped in one of projection images, and the third, all images contained wholly overlapped seeds. The developed software separates wholly overlapped seeds by calculating the distance between seeds in each film. This software can provide valuable information for establishing effective quality assurance in permanent prostate brachytherapy.