Explainable artificial intelligence for predicting red blood cell transfusion in geriatric patients undergoing hip arthroplasty: Machine learning analysis using national health insurance data.

This study uses machine learning and population data to analyze major determinants of blood transfusion among patients with hip arthroplasty. Retrospective cohort data came from Korea National Health Insurance Service claims data for 19,110 patients aged 65 years or more with hip arthroplasty in 2019. The dependent variable was blood transfusion (yes vs no) in 2019 and its 31 predictors were included. Random forest variable importance and Shapley Additive Explanations were used for identifying major predictors and the directions of their associations with blood transfusion. The random forest registered the area under the curve of 73.6%. Based on random forest variable importance, the top-10 predictors were anemia (0.25), tranexamic acid (0.17), age (0.16), socioeconomic status (0.05), spinal anesthesia (0.05), general anesthesia (0.04), sex (female) (0.04), dementia (0.03), iron (0.02), and congestive heart failure (0.02). These predictors were followed by their top-20 counterparts including cardiovascular disease, statin, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, peripheral vascular disease, liver disease, solid tumor, myocardial infarction and hypertension. In terms of max Shapley Additive Explanations values, these associations were positive, e.g., anemia (0.09), tranexamic acid (0.07), age (0.09), socioeconomic status (0.05), spinal anesthesia (0.05), general anesthesia (0.04), sex (female) (0.02), dementia (0.03), iron (0.04), and congestive heart failure (0.03). For example, the inclusion of anemia, age, tranexamic acid or spinal anesthesia into the random forest will increase the probability of blood transfusion among patients with hip arthroplasty by 9%, 7%, 9% or 5%. Machine learning is an effective prediction model for blood transfusion among patients with hip arthroplasty. The high-risk group with anemia, age and comorbid conditions need to be treated with tranexamic acid, iron and/or other appropriate interventions.

Identifying high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips: Impact of cooking parameters, including temperature, time, presoaking, and seasoning.

This study was conducted to identify high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips by studying the impact of various cooking parameters, including temperature, time, presoaking, and pre-seasoning treatments. The temperature and time had a surprisingly high impact on acrylamide formation. The chips prepared at high temperatures with longer cooking times contained an extremely high acrylamide content, reaching 12,786 ng/g (e.g., 170°C/19 min). A particularly concerning discovery was that the chips with extremely high acrylamide content (up to 17 times higher than the EU benchmark level for potato chips) did not appear overcooked or taste burnt. Higher cooking temperatures required shorter cooking times to properly cook lotus root chips for consumption. A high temperature with a short cooking time (170°C/13 min) greatly benefited acrylamide reduction compared to low temperature with a long cooking time (150°C/19 min). Presoaking in a 0.1% acetic acid solution and pre-seasoning with 1% salt reduced acrylamide levels by 61% and 47%, respectively. However, presoaking in water, vinegar solution, and citric acid solution did not significantly decrease the acrylamide content in the chips. Furthermore, some seasonings significantly increased acrylamide levels (up to 7.4 times higher). For the first time, these findings underscore the high risks associated with air-frying lotus root chips without considering these factors. This study also provides proper air-frying parameters and pretreatment strategies for minimizing acrylamide formation in air-fried lotus chips.

Pressure-garment therapy for preventing hypertrophic scarring after burn injury.

BACKGROUND: Burn damage to skin often results in scarring; however in some individuals the failure of normal wound-healing processes results in excessive scar tissue formation, termed 'hypertrophic scarring'. The most commonly used method for the prevention and treatment of hypertrophic scarring is pressure-garment therapy (PGT). PGT is considered standard care globally; however, there is continued uncertainty around its effectiveness. OBJECTIVES: To evaluate the benefits and harms of pressure-garment therapy for the prevention of hypertrophic scarring after burn injury. SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registers on 8 June 2023 with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing PGT (alone or in combination with other scar-management therapies) with scar management therapies not including PGT, or comparing different PGT pressures or different types of PGT. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion using predetermined inclusion criteria, extracted data, and assessed risk of bias using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 15 studies in this review (1179 participants), 14 of which (1057 participants) presented useable data. The sample size of included studies ranged from 17 to 159 participants. Most studies included both adults and children. Eight studies compared a pressure garment (with or without another scar management therapy) with scar management therapy alone, five studies compared the same pressure garment at a higher pressure versus a lower pressure, and two studies compared two different types of pressure garments. Studies used a variety of pressure garments (e.g. in-house manufactured or a commercial brand). Types of scar management therapies included were lanolin massage, topical silicone gel, silicone sheet/dressing, and heparin sodium ointment. Meta-analysis was not possible as there was significant clinical and methodological heterogeneity between studies. Main outcome measures were scar improvement assessed using the Vancouver Scar Scale (VSS) or the Patient and Observer Scar Assessment Scale (POSAS) (or both), pain, pruritus, quality of life, adverse events, and adherence to therapy. Studies additionally reported a further 14 outcomes, mostly individual scar parameters, some of which contributed to global scores on the VSS or POSAS. The amount of evidence for each individual outcome was limited. Most studies had a short follow-up, which may have affected results as the full effect of any therapy on scar healing may not be seen until around 18 months. PGT versus no treatment/lanolin We included five studies (378 participants). The evidence is very uncertain on whether PGT improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, adverse events, and adherence. No study used the POSAS or assessed quality of life. One additional study (122 participants) did not report useable data. PGT versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, adherence, and other scar parameters. It is possible that silicone may result in fewer adverse events or better adherence compared with PGT but this was also based on very low-certainty evidence. PGT plus silicone versus no treatment/lanolin We included two studies (200 participants). The evidence is very uncertain on whether PGT plus silicone improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, and adverse events. No study used the POSAS or assessed quality of life or adherence. PGT plus silicone versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT plus silicone compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. PGT plus scar management therapy including silicone versus scar management therapy including silicone We included one study (88 participants). The evidence is very uncertain on the effect of PGT plus scar management therapy including silicone versus scar management therapy including silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. High-pressure versus low-pressure garments We included five studies (262 participants). The evidence is very uncertain on the effect of high pressure versus low pressure PGT on adverse events and adherence. No study used the VSS or the POSAS or assessed pain, pruritus, or quality of life. Different types of PGT (Caroskin Tricot + an adhesive silicone gel sheet versus Gecko Nanoplast (silicone gel bandage)) We included one study (60 participants). The evidence is very uncertain on the effect of Caroskin Tricot versus Gecko Nanoplast on the POSAS, pain, pruritus, and adverse events. The study did not use the VSS or assess quality of life or adherence. Different types of pressure garments (Jobst versus Tubigrip) We included one study (110 participants). The evidence is very uncertain on the adherence to either Jobst or Tubigrip. This study did not report any other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend using either PGT or an alternative for preventing hypertrophic scarring after burn injury. PGT is already commonly used in practice and it is possible that continuing to do so may provide some benefit to some people. However, until more evidence becomes available, it may be appropriate to allow patient preference to guide therapy.

Analysis of Skin Regeneration and Barrier-Improvement Efficacy of Polydeoxyribonucleotide Isolated from Panax Ginseng (C.A. Mey.) Adventitious Root.

Polydeoxyribonucleotide (PDRN) has the ability to regenerate skin cells and improve the skin barrier and wound healing. This study investigated the possibility of replacing animal-derived PDRN with plant-derived PDRN. To test this, the adventitious roots of Korean ginseng (Panax ginseng C.A. Meyer), which is commonly used to treat various diseases, were suspension-cultivated through tissue culture; subsequently, PDRN was purified using microfluidization, an ultra-high-pressure physical grinding method. The results showed that purified Panax PDRN was effective in healing skin wounds and enhancing the skin barrier. Panax PDRN promoted the proliferation of keratinocytes and fibroblasts by increasing the expression of fibronectin, filaggrin, Ki-67, Bcl-2, inhibin beta A, and Cyclin D1. It also acted as an agonist of the adenosine A2A receptor and induced the phosphorylation of focal adhesion kinase, adenosine triphosphate-dependent tyrosine kinase, and mitogen-activated protein kinase. This activated signal transduction, thereby regenerating skin cells and strengthening the barrier. These results were not only observed in skin cells but also in an artificial skin model (KeraSkinTM). The use of plant-derived PDRN instead of animal-derived PDRN can promote animal welfare and environmental sustainability. Furthermore, Panax PDRN can potentially be a new plant-derived PDRN (PhytoPDRN) that may be utilized in the treatment of various skin diseases.

Effects of resection volume on postoperative micturition symptoms and retreatment after transurethral resection of the prostate.

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.

Weissella koreensis and Pediococcus pentosaceus bacterial ghosts induce inflammatory responses as immunostimulants.

In this study, bacterial ghosts (BGs) were generated from Weissella koreensis LKS42 (WKorGs) and Pediococcus pentosacues KA94 (PPGs) by chemically inducing lysis using substances such as hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), acetic acid (CH3COOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), n-butanol, and C6H8O7. HCl-induced WKorGs and PPGs exhibited complete removal of DNA and displayed transverse membrane dissolution tunnel structures under scanning electron microscopy (SEM). Cell viability assays showed high viability of RAW 264.7 cells exposed to HCl-induced WKorGs and PPGs. Additionally, treatment with HCl-induced WKorGs and PPGs elevated mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and the anti-inflammatory cytokine IL-10 in RAW 264.7 cells. These findings suggest that HCl-induced WKorGs and PPGs have the potential to be used as inactivated bacterial immunostimulants, highlighting their promising applications in immunization and immunotherapy.

Device-Algorithm Co-Optimization for an On-Chip Trainable Capacitor-Based Synaptic Device with IGZO TFT and Retention-Centric Tiki-Taka Algorithm.

Analog in-memory computing synaptic devices are widely studied for efficient implementation of deep learning. However, synaptic devices based on resistive memory have difficulties implementing on-chip training due to the lack of means to control the amount of resistance change and large device variations. To overcome these shortcomings, silicon complementary metal-oxide semiconductor (Si-CMOS) and capacitor-based charge storage synapses are proposed, but it is difficult to obtain sufficient retention time due to Si-CMOS leakage currents, resulting in a deterioration of training accuracy. Here, a novel 6T1C synaptic device using only n-type indium gaIlium zinc oxide thin film transistor (IGZO TFT) with low leakage current and a capacitor is proposed, allowing not only linear and symmetric weight update but also sufficient retention time and parallel on-chip training operations. In addition, an efficient and realistic training algorithm to compensate for any remaining device non-idealities such as drifting references and long-term retention loss is proposed, demonstrating the importance of device-algorithm co-optimization.

Associations of Preterm Birth with Dental and Gastrointestinal Diseases: Machine Learning Analysis Using National Health Insurance Data.

BACKGROUND: This study uses machine learning with large-scale population data to assess the associations of preterm birth (PTB) with dental and gastrointestinal diseases. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance claims for 124,606 primiparous women aged 25-40 and delivered in 2017. The 186 independent variables included demographic/socioeconomic determinants, disease information, and medication history. Machine learning analysis was used to establish the prediction model of PTB. Random forest variable importance was used for identifying major determinants of PTB and testing its associations with dental and gastrointestinal diseases, medication history, and socioeconomic status. RESULTS: The random forest with oversampling data registered an accuracy of 84.03, and the areas under the receiver-operating-characteristic curves with the range of 84.03-84.04. Based on random forest variable importance with oversampling data, PTB has strong associations with socioeconomic status (0.284), age (0.214), year 2014 gastroesophageal reflux disease (GERD) (0.026), year 2015 GERD (0.026), year 2013 GERD (0.024), progesterone (0.024), year 2012 GERD (0.023), year 2011 GERD (0.021), tricyclic antidepressant (0.020) and year 2016 infertility (0.019). For example, the accuracy of the model will decrease by 28.4%, 2.6%, or 1.9% if the values of socioeconomic status, year 2014 GERD, or year 2016 infertility are randomly permutated (or shuffled). CONCLUSION: By using machine learning, we established a valid prediction model for PTB. PTB has strong associations with GERD and infertility. Pregnant women need close surveillance for gastrointestinal and obstetric risks at the same time.

Synthetic colourants in capsule dietary supplements on the Korean market.

This study developed a rapid and easy analytical method for the simultaneous determination of nine synthetic colourants (SCs) in capsule dietary supplements. Sample pretreatment involved thermal treatment to dissolve gelatin, using the enzymes protease and amylase to prevent the gelation of gelatin and fat-soluble substances removal using petroleum ether. The method was linear (r2 ≥0.999), with LOD of 0.009-0.029 µg/mL and LOQ of 0.42-1.40 µg/g. Recovery ranged from 90.9 to 108.9%. The relative expanded measurement uncertainty ranged from 4.1 to 6.3%. Allura Red AC (R40) and Brilliant Blue FCF (B1) were commonly detected in 20 of the 28 samples. Up to six SCs such as Tartrazine (Y4), Sunset yellow (Y5), Amaranth (R2), Erythrosine B (R3), R40 and B1 were detected in a single sample, ranging from 30.5 to 40.2 µg/g. Total content of SCs in various capsule supplements ranged from 0.3 to 73.7 µg/g.

Gold nanostructure-integrated conductive microwell arrays for uniform cancer spheroid formation and electrochemical drug screening.

Cancer spheroids, which mimic distinct cell-to-cell and cell-extracellular matrix interactions of solid tumors in vitro, have emerged as a promising tumor model for drug screening. However, owing to the unique characteristics of spheroids composed of three-dimensionally densely-packed cells, the precise characterizations of cell viability and function with conventional colorimetric assays are challenging. Herein, we report gold nanostructure-integrated conductive microwell arrays (GONIMA) that enable both highly efficient uniform cancer spheroid formation and precise electrochemical detection of cell viability. A nanostructured gold on indium tin oxide (ITO) substrate facilitated the initial cell aggregation and further 3D cell growth, while the non-cytophilic polymer microwell arrays restricted the size and shape of the spheroids. As a result, approximately 150 human glioblastoma spheroids were formed on a chip area of 1.13 cm2 with an average diameter of 224 µm and a size variation of only 5% (±11.36 µm). The high uniformity of cancer spheroids contributed to the stability of electrical signals measuring cell viability. Using the fabricated GONIMA, the effects of a representative chemotherapeutic agent, hydroxyurea, on the glioblastoma spheroids were precisely monitored under conditions of varying drug concentrations (0-0.3 mg/mL) and incubation times (24-48 h). Therefore, we conclude that the newly developed platform is highly useful for rapid and precise in vitro drug screening, as well as for the pharmacokinetic analyses of specific drugs using 3D cellular cancer models.

Oat Seedlings Extract Inhibits RANKL-Induced c-Fos/NFATc1 Transcription Factors in the Early Stage of Osteoclast Differentiation.

Osteoporosis is a common disease that increases the risk of fractures due to decreased bone density and weakens the bone microstructure. Preventing and diagnosing osteoporosis using the available drugs can be a costly affair with possible side effects. Therefore, natural product-derived therapeutics are promising alternatives. Our study demonstrated that the oat seedlings' extract (OSE) inhibited the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis from the bone marrow-derived macrophages (BMMs). The OSE treatment significantly attenuated the RANKL-mediated induction of the tartrate-resistant acid phosphatase (TRAP) activity as well as the number of TRAP-positive (TRAP+) multinucleated cells (MNCs) counted through the TRAP staining in a dose-dependent manner. It was also confirmed that the OSE suppressed the formation of the TRAP + MNCs in the early stage of differentiation and not in the middle and late stages. The results of the real-time quantitative polymerase chain reaction (qPCR) and the western blotting showed that the OSE dramatically inhibited the mRNA and protein expressions of the osteoclastogenesis-mediated transcription factors such as the c-Fos and the nuclear factor-activated T cells c1 (NFATc1). In addition, the OSE strongly attenuated the mRNA induction of the c-Fos/NFATc1-dependent molecules such as the TRAP, the osteoclast-associatedimmunoglobulin-like receptor (OSCAR), the dendritic cell-specific transmembrane protein (DC-STAMP), and the cathepsin K. These results suggest that the naturally derived OSE may be useful for preventing bone diseases.

Changes in cesarean section rate before and after the end of the Korean Value Incentive Program.

BACKGROUND: The Korean government implemented a value incentive program providing incentives to providers based on C-section rates, with the rates being publicized. The program ended in 2014 after the administration decided that the effects of the incentive program were limited. In this report, we analyzed changes in C-section rates with the value incentive program. METHODS: The analysis used claim data from Korea's National Health Insurance. The study period (2011-2016) was divided into two phases: before and after the program. This study included 95 providers that were tertiary or general hospitals having more than 200 deliveries per year during the study period. The dependent variable was the risk-adjusted C-section rate. Independent variables included time and hospital characteristics such as hospital type, district, and ownership. Interrupted time series analysis was performed to analyze the data. RESULTS: Our results showed that risk-adjusted C-section rates increased immediately after the end of the incentive program for C-sections. The immediate effect of intervention, a change of 1.73% (P < .05), was statistically significant, as was the trend after intervention, at 0.21% (P < .0001). The slope showed an increase after the intervention to 0.25% per medical institution, which was contrary to the trend of the preintervention decline (negative slope). CONCLUSION: Risk-adjusted C-section rates increased immediately after the discontinuation of a value incentive program. Tertiary hospitals showed greater increases in C-section rates than general hospitals after the intervention.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

YY2 Promotes Osteoblast Differentiation by Upregulating Osterix Transcriptional Activity.

Yin Yang 2 (YY2) is a paralog of YY1, a well-known multifunctional transcription factor containing a C-terminal zinc finger domain. Although the role of YY1 in various biological processes, such as the cell cycle, cell differentiation and tissue development, is well established, the function of YY2 has not been fully determined. In this study, we investigated the functional role of YY2 during osteoblast differentiation. YY2 overexpression and knockdown increased and decreased osteoblast differentiation, respectively, in BMP4-induced C2C12 cells. Mechanistically, YY2 overexpression increased the mRNA and protein levels of Osterix (Osx), whereas YY2 knockdown had the opposite effect. To investigate whether YY2 regulates Osx transcription, the effect of YY2 overexpression and knockdown on Osx promoter activity was evaluated. YY2 overexpression significantly increased Osx promoter activity in a dose-dependent manner, whereas YY2 knockdown had the opposite effect. Furthermore, vectors containing deletion and point mutations were constructed to specify the regulation site. Both the Y1 and Y2 sites were responsible for YY2-mediated Osx promoter activation. These results indicate that YY2 is a positive regulator of osteoblast differentiation that functions by upregulating the promoter activity of Osx, a representative osteogenic transcription factor in C2C12 cells.

Effectiveness and safety of bee venom pharmacopuncture for rheumatoid arthritis: a systematic review protocol.

INTRODUCTION: Rheumatoid arthritis (RA) is the common autoimmune disease with low quality of life. The representative treatment is medication and medication usage has improved through update of clinical guidelines, however, there are still limitations. Bee venom (BV) has been reported to have meaningful therapeutic effects and the possibility of alternative options for RA through several types of studies, but there is no well-organised and recent published systematic review (SR). METHODS: We will search randomised controlled trials about the BV on RA from the inception to 31 May 2022 in various databases, manual research and contacting authors. Electronic databases will include MEDLINE, EMBASE, Cochrane library, China National Knowledge Infrastructure, CiNii, J-STAGE, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Digital Science Library, Korea Institute of Science and Technology Information and Oriental Medicine Advanced Searching Integrated System. With screening and reviewing process, we will identify the eligible studies and extract the needed data. The primary outcome will be the disease activity scores indicating the improvement of RA symptoms (American College of Rheumatology response criteria 20, 50, 70), functions (Health Assessment Questionnaire, Disease Activity Score of 28 joints), joint (Western Ontario and McMaster universities osteoarthritis index), pain (Visual Analogue Scale, Numerical Rating Scale) and effective rate. The secondary outcomes will be the RA-related blood test levels and adverse events. We will perform a meta-analysis by Review Manager software, the assessment of risk of bias by Cochrane Collaboration 'risk of bias' and the determination of quality of evidence by Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: Our SR will suggest the clinical evidence of the use of BV for RA to patient, clinicians and policymakers. We will publish our results in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42021238058.

Association of Preterm Birth with Inflammatory Bowel Disease and Salivary Gland Disease: Machine Learning Analysis Using National Health Insurance Data.

This study employs machine learning and population data for testing the associations of preterm birth with inflammatory bowel disease (IBD), salivary gland disease, socioeconomic status and medication history, including proton pump inhibitors. The source of population-based retrospective cohort data was the Korea National Health Insurance Service claims data for all women aged 25-40 years and who experience their first childbirths as singleton pregnancy during 2015 to 2017 (402,092 women). These participants were divided into the Ulcerative Colitis (UC) Group (1782 women), the Crohn Group (1954 women) and the Non-IBD Group (398,219 women). For each group, the dependent variable was preterm birth during 2015-2017, and 51 independent variables were included. Random forest variable importance was employed for investigating the main factors of preterm birth and testing its associations with salivary gland disease, socioeconomic status and medication history for each group. The proportion of preterm birth was higher for the UC Group and the Non-IBD Group than for the Crohn Group: 7.86%, 7.17% vs. 6.76%. Based on random forest variable importance, salivary gland disease was a top 10 determinant for the prediction of preterm birth for the UC Group, but this was not the case for the Crohn Group or the Non-IBD Group. The top 5 variables of preterm birth for the UC Group during 2015-2017 were socioeconomic status (8.58), age (8.00), proton pump inhibitors (2.35), progesterone (2.13) and salivary gland disease in 2014 (1.72). In conclusion, preterm birth has strong associations with ulcerative colitis, salivary gland disease, socioeconomic status and medication history including proton pump inhibitors.

Overexpression of the PanaxginsengCYP703 Alters Cutin Composition of Reproductive Tissues in Arabidopsis.

Cytochrome P450 (CYP) catalyzes a wide variety of monooxygenation reactions in plant primary and secondary metabolisms. Land plants contain CYP703, belonging to the CYP71 clan, which catalyzes the biochemical pathway of fatty acid hydroxylation, especially in male reproductive tissues. Korean/Asian ginseng (Panax ginseng Meyer) has been regarded as one of important medicinal plant for a long time, however the molecular mechanism is less known on its development. In this study, we identified and characterized a CYP703A gene in P. ginseng (PgCYP703A4), regarding reproductive development. PgCYP703A4 shared a high-sequence identity (81-83%) with predicted amino acid as CYP703 in Dancus carota, Pistacia vera, and Camellia sinensis as well as 76% of amino acid sequence identity with reported CYP703 in Arabidopsis thaliana and 75% with Oryza sativa. Amino acid alignment and phylogenetic comparison of P. ginseng with higher plants and known A. thaliana members clearly distinguish the CYP703 members, each containing the AATDTS oxygen binding motif and PERH as a clade signature. The expression of PgCYP704B1 was only detected in P. ginseng flower buds, particularly in meiotic cells and the tapetum layer of developing anther, indicating the conserved role on male reproduction with At- and Os- CYP703. To acquire the clue of function, we transformed the PgCYP703A4 in A. thaliana. Independent overexpressing lines (PgCYP703A4ox) increased silique size and seed number, and altered the contents of fatty acids composition of cutin monomer in the siliques. Our results indicate that PgCYP703A4 is involved in fatty acid hydroxylation which affects cutin production and fruit size.

Association of preterm birth with medications: machine learning analysis using national health insurance data.

PURPOSE: To use machine learning and population data for testing the associations of preterm birth with socioeconomic status, gastroesophageal reflux disease (GERD) and medication history including proton pump inhibitors, sleeping pills and antidepressants. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25-40 years and gave births for the first time as singleton pregnancy during 2015-2017 (405,586 women). The dependent variable was preterm birth during 2015-2017 and 65 independent variables were included (demographic/socioeconomic determinants, disease information, medication history, obstetric information). Random forest variable importance (outcome measure) was used for identifying major determinants of preterm birth and testing its associations with socioeconomic status, GERD and medication history including proton pump inhibitors, sleeping pills and antidepressants. RESULTS: Based on random forest variable importance, major determinants of preterm birth during 2015-2017 were socioeconomic status (645.34), age (556.86), proton pump inhibitors (107.61), GERD for the years 2014, 2012 and 2013 (106.78, 105.87 and 104.96), sleeping pills (97.23), GERD for the years 2010, 2011 and 2009 (95.56, 94.84 and 93.81), and antidepressants (90.13). CONCLUSION: Preterm birth has strong associations with low socioeconomic status, GERD and medication history such as proton pump inhibitors, sleeping pills and antidepressants. For preventing preterm birth, appropriate medication would be needed alongside preventive measures for GERD and the promotion of socioeconomic status for pregnant women.

ORIGINAL ARTICLE: Associations of antidepressant medication with its various predictors including particulate matter: Machine learning analysis using national health insurance data.

This study uses machine learning and population-based data to analyze major determinants of antidepressant medication including the concentration of particulate matter under 2.5 µm (PM2.5). Retrospective cohort data came from Korea National Health Insurance Service claims data for 43,251 participants, who were aged 15-79 years, lived in the same districts of Seoul and had no history of antidepressant medication during 2002-2012. The dependent variable was antidepressant-free months during 2013-2015 and the 30 independent variables for 2012 were included (demographic/socioeconomic information, health information, district-level information including PM2.5). Random forest variable importance, the contribution of a variable for the performance of the model, was used for identifying major predictors of antidepressant-free months. Based on random forest variable importance, the top 15 determinants of antidepressant medication during 2013-2015 included cardiovascular disease (0.0054), age (0.0047), household income (0.0037), gender (0.0027), the district-level proportion of recipients of national basic living security program benefits (0.0019), district-level social satisfaction (0.0013), diabetes mellitus (0.0012), January 2012 PM2.5 (0.0011), district-level street ratio (0.0010), drinker (0.0009), chronic obstructive pulmonary disease (0.0008), district-level economic satisfaction (0.0006), exercise (0.0005), March 2012 PM2.5 (0.0005) and November 2012 PM2.5 (0.0004). Besides these predictors, smoker and district-level deprivation index are found to be influential most widely, given that they ranked within the top 10 most often in sub-group analysis. In conclusion, antidepressant medication has strong associations with neighborhood conditions including socioeconomic satisfaction and the seasonality of particulate matter. Strong interventions for these factors are really needed for the effective management of major depressive disorder.

nc886, a Non-Coding RNA, Is a New Biomarker and Epigenetic Mediator of Cellular Senescence in Fibroblasts.

Functional studies of organisms and human models have revealed that epigenetic changes can significantly impact the process of aging. Non-coding RNA (ncRNA), one of epigenetic regulators, plays an important role in modifying the expression of mRNAs and their proteins. It can mediate the phenotype of cells. It has been reported that nc886 (=vtRNA2-1 or pre-miR-886), a long ncRNA, can suppress tumor formation and photo-damages of keratinocytes caused by UVB. The aim of this study was to determine the role of nc886 in replicative senescence of fibroblasts and determine whether substances capable of controlling nc886 expression could regulate cellular senescence. In replicative senescence fibroblasts, nc886 expression was decreased while methylated nc886 was increased. There were changes of senescence biomarkers including SA-ß-gal activity and expression of p16INK4A and p21Waf1/Cip1 in senescent cells. These findings indicate that the decrease of nc886 associated with aging is related to cellular senescence of fibroblasts and that increasing nc886 expression has potential to suppress cellular senescence. AbsoluTea Concentrate 2.0 (ATC) increased nc886 expression and ameliorated cellular senescence of fibroblasts by inhibiting age-related biomarkers. These results indicate that nc886 has potential as a new target for anti-aging and that ATC can be a potent epigenetic anti-aging ingredient.