Advanced parametrization for the production of high-energy solid-state lithium pouch cells containing polymer electrolytes.

Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg-1 (corresponding to an energy density of 600 Wh L-1) and 310 Wh kg-1 (corresponding to an energy density of 650 Wh L-1) respectively.

Development of a lesbian, gay, bisexual, and transgender cultural competence scale for nurses in South Korea: a methodological study.

PURPOSE: This study was conducted to develop a cultural competence scale for nurses regarding the lesbian, gay, bisexual, and transgender (LGBT) community and to test its validity and reliability. METHODS: The study adhered to the 8-step process outlined by DeVellis, with an initial set of 25 items derived through a literature review and individual interviews. Following an expert validity assessment, 24 items were validated. Subsequently, a preliminary survey was conducted among 23 nurses with experience caring for LGBT patients. Data were then collected from a final sample of 322 nurses using the 24 items. Item analysis, item-total score correlation, examination of construct and convergent validity, and reliability testing were performed. RESULTS: The item-level content validity index exceeded .80, and the explanatory power of the construct validity was 63.63%. The factor loadings varied between 0.57 and 0.80. The scale comprised five factors: cultural skills, with seven items; cultural awareness, with five items; cultural encounters, with three items; cultural pursuit, with three items; and cultural knowledge, with three items; totaling 21 items. Convergent validity demonstrated a high correlation, affirming the scale's validity. Internal consistency analysis yielded an overall reliability coefficient of 0.97, signifying very high reliability. Each item is scored from 1 to 6 (total score range, 21-126), with higher scores reflecting greater cultural competence in LGBT care. CONCLUSION: This scale facilitates the measurement of LGBT cultural competence among nurses. Therefore, its use should provide foundational data to support LGBT-focused nursing education programs.

Effects of aquatic versus land-based exercise on irisin and fibroblast growth factor 21 expression and triiodothyronine and free fatty acid levels in elderly women.

BACKGROUND: This study investigated the impacts of exercise on irisin and fibroblast growth factor 21 (FGF-21) expression, as well as triiodothyronine (T3 ) and free fatty acid (FFA) levels in elderly women. METHODS: Thirty women aged 65 to 70 years (10 per group) were randomly assigned to aquatic exercise, land exercise, and control groups. The aquatic and land groups engaged in 3 exercise sessions per week (60 min/session) for 16 weeks. The intensity was progressively increased every 4 weeks. RESULTS: Irisin and FGF-21 levels significantly increased in the aquatic exercise group. In the posttest, the aquatic exercise group had the highest irisin levels. Significant findings were observed for irisin and FGF-21 for the main effect between aquatic and band exercise groups (p<0.05 for both), the main effect between measurement times (p<0.01 and p<0.001, respectively), and the interaction effect (p<0.05 and p<0.001, respectively). The irisin level was significantly higher in the aquatic than in the land group 30 minutes after the last session (p<0.05). In both exercise groups, T3 levels were significantly higher 30 minutes after the final session (p<0.05) than before the program. The FFA level was significantly higher in the aquatic exercise group than the others. In the aquatic group, FFA levels were significantly higher 30 minutes after both the first (p<0.01) and the last (p<0.001) session compared to pre-program values. CONCLUSION: Differences in exercise type and environment can promote fat metabolism by stimulating hormonal changes that induce brown fat activity and browning.

Comorbid physical health outcomes in patients with bipolar disorder: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled. OBJECTIVE: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence. METHODS: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or cross-sectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant. RESULTS: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69-5.17]; CE=suggestive), Parkinson's disease (3.35 [1.72-6.53]; CE=suggestive), asthma (1.86 [1.42-2.42]; CE=weak), toxoplasmosis (1.69 [1.21-2.37]; CE=weak), hypertension (1.28 [1.02-1.60]; CE=convincing), breast cancer (1.33 [1.15-1.55]; CE=weak), obesity (1.64 [1.30-1.99]; CE=suggestive), and type 2 diabetes mellitus (1.98 [1.55-2.52]; CE=weak). CONCLUSION: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them.

Impact of automated alerts on discharge opioid overprescribing after general surgery.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The objectives of this study were to identify the most performed surgical procedures associated with the highest rates of discharge opioid overprescribing and to implement an electronic health record (EHR) alert to reduce discharge opioid overprescribing. METHODS: This quality improvement, before-and-after study included patients undergoing one of the identified target procedures-laparoscopic cholecystectomy, unilateral open inguinal hernia repair, and laparoscopic appendectomy-at an academic medical center. The alert notified providers when the prescribed opioid quantity exceeded guideline recommendations. The preimplementation cohort included surgical encounters from January 2020 to December 2021. The EHR alert was implemented in May 2022 following provider education via email and in-person presentations. The postimplementation cohort included surgical encounters from May to August 2022. The primary outcome was the proportion of patients with a discharge opioid supply exceeding guideline recommendations (overprescribing). RESULTS: A total of 1,478 patients were included in the preimplementation cohort, and 141 patients were included in the postimplementation cohort. The rate of discharge opioid overprescribing decreased from 48% in the preimplementation cohort to 3% in the postimplementation cohort, with an unadjusted absolute reduction of 45% (95% confidence interval, 41% to 49%; P < 0.001) and an adjusted odds ratio of 0.03 (95% confidence interval, 0.01 to 0.08; P < 0.001). Among patients who received opioids, the mean (SD) opioid supply at discharge decreased from 92 (43) oral morphine milligram equivalents (MME) (before implementation) to 57 (20) MME (after implementation) (P < 0.001). The proportion of patients who received additional opioid prescriptions within 1 to 14 days of hospital discharge did not change (P = 0.76). CONCLUSION: Implementation of an EHR alert along with provider education can reduce discharge opioid overprescribing following general surgery.

Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo.

Protein kinases are critical regulatory proteins in both prokaryotes and eukaryotes. Accordingly, protein kinases represent a common drug target for a wide range of human diseases. Therefore, understanding protein kinase function in human pathogens such as the fungus Candida albicans is likely to extend our knowledge of its pathobiology and identify new potential therapies. To facilitate the study of C. albicans protein kinases, we constructed a library of 99 non-essential protein kinase homozygous deletion mutants marked with barcodes in the widely used SN genetic background. Here, we describe the construction of this library and the characterization of the competitive fitness of the protein kinase mutants under 11 different growth and stress conditions. We also screened the library for protein kinase mutants with altered filamentation and biofilm formation, two critical virulence traits of C. albicans. An extensive network of protein kinases governs these virulence traits in a manner highly dependent on the specific environmental conditions. Studies on specific protein kinases revealed that (i) the cell wall integrity MAPK pathway plays a condition-dependent role in filament initiation and elongation; (ii) the hyper-osmolar glycerol MAPK pathway is required for both filamentation and biofilm formation, particularly in the setting of in vivo catheter infection; and (iii) Sok1 is dispensable for filamentation in hypoxic environments at the basal level of a biofilm but is required for filamentation in normoxia. In addition to providing a new genetic resource for the community, these observations emphasize the environmentally contingent function of C. albicans protein kinases.IMPORTANCECandida albicans is one of the most common causes of fungal disease in humans for which new therapies are needed. Protein kinases are key regulatory proteins and are increasingly targeted by drugs for the treatment of a wide range of diseases. Understanding protein kinase function in C. albicans pathogenesis may facilitate the development of new antifungal drugs. Here, we describe a new library of 99 protein kinase deletion mutants to facilitate the study of protein kinases. Furthermore, we show that the function of protein kinases in two virulence-related processes, filamentation and biofilm formation, is dependent on the specific environmental conditions.

Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Functional Impact of the FADS1 rs174546 Single Nucleotide Polymorphism on Serum Lipid Levels: Insights from Molecular Mechanisms and Therapeutic Perspectives in Korean Population.

SCOPE: Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome-wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed. METHODS AND RESULTS: FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84 mg dL-1) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR-6728-3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR-6728-3p inhibitor. Formononetin is selected as binding molecule to 3'-UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR-6728-3p. Formononetin also increases endogenous FADS1 expression and long-chain polyunsaturated fatty acid (LC-PUFA) ratio. CONCLUSION: FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR-6728-3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations.

Improvement in Performance and Stability of PbS QD/IGZO Phototransistors Through the Introduction of Ga2O3 Film for Broadband Sensor Applications.

The development of broadband photosensors has become crucial in various fields. Indium-gallium-zinc oxide (IGZO, In:Ga:Zn = 1:1:1) phototransistors with PbS quantum dots (QDs) have shown promising features for such sensors, such as reasonable mobility, low leakage current, good photosensitivity, and low-cost fabrication. However, the instability of PbS QD/IGZO phototransistors under an air atmosphere and prolonged storage remain serious concerns. In this article, two concepts to improve the reliability of PbS QD/IGZO phototransistors were implemented. P-type doping in the PbS QD layer through oxidation allows increasing the built-in potential between IGZO and PbS QDs, leading to enhancement in photoinduced electron-hole pair creation. Second, agglomeration and fusion of a PbS QDs layer were controlled via thermal annealing, which facilitated the transport of photocreated carriers. The p-type doping and interconnection of a PbS QD layer can be achieved by deposition and subsequent thermal annealing of gallium oxide (Ga2O3) on PbS QD/IGZO stacks. The resulting Ga2O3/PbS QD/IGZO phototransistors exhibited high-performance switching characteristics under dark conditions. Notably, they showed a remarkable photoresponsivity of 196.69 ± 4.05 A/W and a detectivity of (5.47 ± 1.4) × 1012 Jones even at a long-wavelength illumination of 1550 nm. While the unpassivated PbS/IGZO phototransistor suffered serious degradation in optical performance after 2 weeks of storage, the Ga2O3/PbS QD/IGZO phototransistor demonstrated enhanced stability, maintaining high performance for over 5 weeks. These findings suggest that Ga2O3/PbS QD/IGZO phototransistors offer a feasible approach for the fabrication of large-scale active matrix broadband photosensor arrays, potentially revolutionizing optical sensing in various cutting-edge applications.

Childhood adversity and suicidal ideation in older Korean adults: unraveling the mediating mechanisms of mental health, physical health, and social relationships.

BACKGROUND: Suicide rates in older adults are much higher than those in younger age groups. Given the rapid increase in the proportion of older adults in Korea and the high suicide rate of this age group, it is worth investigating the mechanism of suicidal ideation for older adults. Generally, adverse childhood experiences are positively associated with suicidal ideation; however, it is not fully understood what mediating relationships are linked to the association between these experiences and current suicidal ideation. METHODS: The data from 685 older Korean adults were analyzed utilizing logistic regression, path analyses, and structural equation modeling. Based on our theoretical background and the empirical findings of previous research, we examined three separate models with mental health, physical health, and social relationship mediators. After that, we tested a combined model including all mediators. We also tested another combined model with mediation via mental health moderated by physical health and social relationships. RESULTS: The univariate logistic regression results indicated that childhood adversity was positively associated with suicidal ideation in older adults. However, multivariate logistic regression results demonstrated that the direct effect of childhood adversity became nonsignificant after accounting all variables. Three path models presented significant mediation by depression and social support in the association between childhood adversity and suicidal ideation. However, combined structural equation models demonstrated that only mediation by a latent variable of mental health problems was statistically significant. Social relationships moderated the path from mental health problems to suicidal ideation. CONCLUSIONS: Despite several limitations, this study has clinical implications for the development of effective strategies to mitigate suicidal ideation. In particular, effectively screening the exposure to adverse childhood experiences, early identification and treatment of depressive symptoms can play a crucial role in weakening the association between childhood adversity and suicidal ideation in older adults.

Waist-height ratio and body mass index as indicators of obesity and cardiometabolic risk in Korean children and adolescents.

PURPOSE: We assessed the clinical relevance of waist-height ratio (WHtR) as an indicator of cardiometabolic risk and body fat mass measured by dual-energy x-ray absorptiometry (DXA) among Korean children and adolescents. METHODS: Data from 1,661 children and adolescents aged 10-18 years who participated in the Korea National Health and Nutrition Examination Survey were analyzed. Unadjusted Pearson correlation, age- and sex-adjusted Pearson correlation, and multiple linear regression analyses were performed to investigate the relationships between WHtR standard deviation score (SDS) and cardiometabolic risk factors, as well as DXA-assessed parameters. RESULTS: WHtR SDS was correlated with cardiometabolic risk factors, including systolic blood pressure, glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as DXA-assessed parameters such as lean mass SDS, fat mass SDS, and fat mass percentage SDS in both whole body and trunk using an adjusted Pearson correlation analyses among all participants (p<0.001). WHtR SDS was strongly correlated with whole-body fat mass and trunk fat mass (r=0.792, p<0.001 and r=0.801, p<0.001, respectively) whereas WHtR SDS had a low correlation coefficient with whole-body lean mass and trunk lean mass SDS (r=0.512, p<0.001 and r=0.487, p<0.001, respectively). In multiple linear regression analyses, WHtR SDS was significantly associated with whole-body and trunk fat mass after adjustment for confounders. CONCLUSION: Cardiometabolic risk factors and body fat mass assessed by DXA in Korean children and adolescents were highly correlated with WHtR. Additionally, WHtR has an advantage in distinguishing fat-free mass. WHtR can be a useful and convenient clinical indicator of cardiometabolic risk factors.

Development of Low-Pressure Die-Cast Al-Zn-Mg-Cu Alloy Propellers-Part â : Hot Tearing Simulations for Alloy Optimization.

Recent advances in the leisure boat industry have spurred demand for improved materials for propeller manufacturing, particularly high-strength aluminum alloys. While traditional Al-Si alloys like A356 are commonly used due to their excellent castability, they have limited mechanical properties. In contrast, 7xxx series alloys (Al-Zn-Mg-Cu based) offer superior mechanical characteristics but present significant casting challenges, including hot-tearing susceptibility (HTS). This study investigates the optimization of 7xxx series aluminum alloys for low-pressure die-casting (LPDC) processes to enhance propeller performance and durability. Using a constrained rod-casting (CRC) method and finite element simulations, we evaluated the HTS of various alloy compositions. The results indicate that increasing Zn and Cu contents generally increase HTS, while a sufficient Mg content of 2 wt.% mitigates this effect. Two optimized quaternary Al-Zn-Mg-Cu alloys with relatively low HTS were selected for LPDC propeller production. Simulation and experimental results demonstrated the effectiveness of the proposed alloy compositions, highlighting the need for further process optimization to prevent hot tearing in high Mg and Cu content alloys.

Amplifying Photochromic Response in Tungsten Oxide Films with Titanium Oxide and Polyvinylpyrrolidone.

Tungsten oxide (WO3) is known for its photochromic properties, making it useful for smart windows, displays, and sensors. However, its small bandgap leads to rapid recombination of electron-hole pairs, resulting in poor photochromic performance. This study aims to enhance the photochromic properties of WO3 by synthesizing hexagonal tungsten oxide via hydrothermal synthesis, which increases surface area and internal hydrates. Titanium oxide (TiO2) was adsorbed onto the tungsten oxide to inject additional charges and reduce electron-hole recombination. Additionally, polyvinylpyrrolidone (PVP) was used to improve dispersion in organic solvents, allowing for the fabrication of high-quality films using the doctor blade method. Characterization confirmed the enhanced surface area, crystal structure, and dispersion stability. Reflectance and transmittance measurements demonstrated significant improvements in photochromic properties due to the composite structure. These findings suggest that the introduction of TiO2 and PVP to tungsten oxide effectively enhances its photochromic performance, broadening its applicability in various advanced photochromic applications.

Association between Alcohol Use Disorder and Suicidal Ideation Using Propensity Score Matching in Chungcheongnam-do, South Korea.

Objectives: This study aimed to analyze the association between alcohol use disorder (AUD) and suicidal ideation (SI) in the general Korean population. Methods: The 2022 Mental Health Awareness Survey was collected from the Chungcheongnam-do Mental Health Welfare Center (CHMHC). Before Propensity Score Matching (PSM), 823 participants were included in this study. After 1:4 PSM, the 255 participants were analyzed using the chi-square test and matched conditional logistic regression. Results: The AUD group had higher odds of experiencing SI than the non-AUD (adjusted odds ratio [AOR]: 2.40, 95% confidence intervals [CI]: 1.10-5.22). Stratified matched conditional logistic regression showed that, among the female, <40 years and single group, the AUD group was more likely to experience SI compared with the non-AUD, respectively (AOR:3.53, 95% CI: 1.20-10.44/AOR:3.45, 95% CI: 1.03-11.55/AOR:4.83, 95% CI: 1.18-19.69). However, among the male, ≥40 years and married group, we discovered no association between AUD and SI. Conclusions: Through this study, we found a strong association between the AUD group and SI. This association was particularly strong among female, <40 years, and single groups. This study elucidates the relationship between AUD and SI in the Chungnam region, which had not been previously identified in Korea, and it is expected to serve as foundational data for reducing the high suicide rate in this region. However, due to the limitation of being a cross-sectional study, future longitudinal research is required.

Korean Black Goat Extract Exerts Estrogen-like Osteoprotective Effects by Stimulating Osteoblast Differentiation in MC3T3-E1 Cells and Suppressing Osteoclastogenesis in RAW 264.7 Cells.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE's mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography-mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERß, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/ß-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

Comorbid health conditions in people with attention-deficit/hyperactivity disorders: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS: We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION: We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.

Prediction of hydroxyl radical exposure during ozonation using different machine learning methods with ozone decay kinetic parameters.

The abatement of micropollutants by ozonation can be accurately calculated by measuring the exposures of molecular ozone (O3) and hydroxyl radical (•OH) (i.e., ∫[O3]dt and ∫[•OH]dt). In the actual ozonation process, ∫[O3]dt values can be calculated by monitoring the O3 decay during the process. However, calculating ∫[•OH]dt is challenging in the field, which necessitates developing models to predict ∫[•OH]dt from measurable parameters. This study demonstrates the development of machine learning models to predict ∫[•OH]dt (the output variable) from five basic input variables (pH, dissolved organic carbon concentration, alkalinity, temperature, and O3 dose) and two optional ones (∫[O3]dt and instantaneous ozone demand, IOD). To develop the models, four different machine learning methods (random forest, support vector regression, artificial neural network, and Gaussian process regression) were employed using the input and output variables measured (or determined) in 130 different natural water samples. The results indicated that incorporating ∫[O3]dt as an input variable significantly improved the accuracy of prediction models, increasing overall R2 by 0.01-0.09, depending on the machine learning method. This suggests that ∫[O3]dt plays a crucial role as a key variable reflecting the •OH-yielding characteristics of dissolved organic matter. Conversely, IOD had a minimal impact on the accuracy of the prediction models. Generally, machine-learning-based prediction models outperformed those based on the response surface methodology developed as a control. Notably, models utilizing the Gaussian process regression algorithm demonstrated the highest coefficients of determination (overall R2 = 0.91-0.95) among the prediction models.

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SUBJECTS: VigiBase, a World Health Organization (WHO) global safety report database DESIGN: Pharmacovigilance study METHODS: The individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47-1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14-5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.