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The concentration of micronutrients impacts fetal development and pregnancy outcome and has been suggested to be negatively correlated with the body-mass index (BMI). We evaluated the relationship between BMI and the serum folate concentration in 802 and 660 Korean pregnant women in mid- and late pregnancy, respectively, who participated in a multicenter prospective study. There was a significant negative correlation between BMI value and the serum folate concentration at mid- and late pregnancy (P for trend 0.001 and 0.024, respectively). A general linear model confirmed this correlation at both time points after adjusting for gestational age and total folate intake. These findings are important as the serum folate concentration is a rate-limiting factor for placental folate transport to the fetus, and an inadequate folate supply may cause various malformations. [ABSTRACT FROM AUTHOR]

Women have ubiquitous exposure to various endocrine disrupting chemicals (EDCs) present in personal care products, food packaging, and processing. Pregnancy is a phase of increased vulnerability to environmental stressors. Therefore, we aimed to identify questionnaire based variables of pregnant women's lifestyle factors affecting the prenatal concentrations of EDCs: bis-phenol A (BPA), triclosan (TCS), parabens, and phthalates. We also aimed to explore the association between these lifestyle factors and EDC exposure in pregnant women in South Korea. This study is a part of Korean CHildren's ENvironmental health Study (Ko-CHENS). The following lifestyle factors: usage of personal care products, eating habits, cooking practices, food storage practices, and chemical exposure were evaluated through questionnaire. We examined prenatal EDCs: phenols (BPA), TCS, parabens (MEP, ETP, and PRP), and phthalates (MEHHP, MEOHP, MECPP, MBZP, MCOP, MCPP, MCNP, and MNBP). The random forest and least absolute shrinkage and selection operator regression machine learning models were used to predict the important lifestyle factors affecting the prenatal EDC concentrations in pregnant women. Next, we calculated the lifestyle score and evaluated its association with prenatal EDCs, respectively. Our results show that pregnant women who used makeup [β: 1.01, 95% C.I.: 0.01,2.00] >6 times/week had a significant increase in early-pregnancy (EP) ΣParaben exposure. Using perfume up to 3 times/month was significantly associated with EP TCS exposure (β: 0.05, 95% C.I.: 0.01,0.23). While, using perfume >6 times/week was significantly associated to late-pregnancy (LP) ΣParaben exposure, and consuming cup noodles significantly increased LP ΣDEHP exposure. Linear model analysis showed that the lifestyle score significantly increased the EP (β: 0.24, 95% C.I.: 0.07,0.40) and LP (β:0.10, 95% C.I.: 0.01,0.20) ΣParaben exposure. Therefore, pregnant women's lifestyle factors, such as using makeup and perfume and eating habits (e.g., cup noodle consumption), were associated with prenatal EDC exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The understanding of cardiovascular-kidney-metabolic syndrome remains difficult despite recently performed large scale genome-wide association studies. Here, we identified beta-lactamase (LACTB), a novel gene whose expression is targeted by genetic variations causing kidney dysfunction and hyperlipidemia. Mice with LACTB deletion developed impaired glucose tolerance, elevated lipid levels, and increased sensitivity to kidney disease, while mice with tubule-specific overexpression of LACTB were protected from kidney injury. We show that LACTB is a novel mitochondrial protease cleaving and activating phospholipase A2 group VI (PLA2G6), a kidney-metabolic risk gene itself. Genetic deletion of PLA2G6 in tubule-specific LACTB-overexpressing mice abolished the protective function of LACTB. Via mouse and human lipidomic studies, we show that LACTB and downstream PLA2G6 convert oxidized phosphatidylethanolamine to lyso-phosphatidylethanolamine and thereby regulate mitochondrial function and ferroptosis. In summary, we identify a novel gene and a core targetable pathway for kidney-metabolic disorders., Competing Interests: Declaration of interests K. Susztak declares the following interests: research support from AstraZeneca, Bayer, Boehringer Ingelheim, Calico, Genentech, Gilead, GSK, Jnana, Lilly, Maze, Merck, Novartis, Novo Nordisk, Regeneron, Variant Bio, and Ventus; advisory board membership with Jnana Therapeutics and Pfizer; consultancy for AstraZeneca, Bayer, GSK, Jnana Therapeutics, Maze, Novo Nordisk, Pfizer, and Ventus; ownership of patents related to Jag1- and Notch-based targeting of chronic kidney disease; editorial board membership on Cell Metabolism, eBioMedicine, Journal of the American Society of Nephrology, Journal of Clinical Investigation, Kidney International, and Med. J.A.B. declares the following interests: research support from Pfizer, Elysium Health, and Metro International Biotech; consulting fees from Pfizer, Elysium Health, Cytokinetics, and Altimmune. D.J.R. declares the following interests: consultant/scientific advisory board for Alnylam, Novartis, and Verve. M.L.M. declares the following interests: shareholder and scientific adviser to Zenagem, LLC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ocular cystinosis is a disease in which accumulated cystine crystals cause damage to the eyes, necessitating timely treatment and ongoing monitoring of cystine levels. The current treatment involves frequent administration of cysteamine eye drops, which suffer from low bioavailability and can lead to drug toxicity, making it essential to prescribe an appropriate dosage based on the patient's condition. Additionally, cystine crystal levels are typically assessed subjectively via slit-lamp examination, requiring frequent clinical visits and causing discomfort for the patient. In this study, we propose a theranostic contact lens that simultaneously performs therapy and diagnosis on a single platform utilizing gold nanoparticles (GNPs). The binding interactions between GNPs and cystine were confirmed in solution, and thermodynamic analysis further elucidated the bonding force between the two substances. With a comprehensive understanding of these interactions, we investigated the potential of the theranostic GNP-loaded contact lens (GNP-CL). Upon exposure to various concentrations of cystine, the GNP-CL demonstrated distinct color changes, transitioning from red to blue. This color shift enabled quantitative monitoring of cystine levels. The treatment efficacy was validated by confirming a reduction in cystine concentration following the reaction. This platform has the potential to improve disease management in ocular cystinosis by reducing the reliance on cysteamine and offering an objective self-monitoring tool that does not require specialized equipment.

Renal cell carcinoma (RCC) is considered as a "metabolic disease" due to various perturbations in metabolic pathways that could drive cancer development. Glycine decarboxylase (GLDC) is a mitochondrial enzyme that takes part in the oxidation of glycine to support nucleotide biosynthesis via transfer of one-carbon units. Herein, we aimed to investigate the potential role of GLDC in RCC development. We found that GLDC depletion diminished nucleotide synthesis and promoted reactive oxygen species (ROS) generation to repress RCC progression, which was reversed by repletion of deoxynucleosides. Additionally, in vitro and in vivo studies revealed that GLDC plays an important role in regulation of proliferation and tumor growth via interferon stimulated gene factor 3 (ISGF3)-mediated pathway. Expressions of interferon regulatory factor 9 (IRF9) and signal transducer and activator of transcription 2 (STAT2) were elevated in GLDC knock-downed cells and decreased in GLDC over-expressed cells. Double knock-down of STAT2 and IRF9 in GLDC-deficient cells rescued GLDC depletion-induced decrease in cell proliferation. Furthermore, GLDC depletion increased cisplatin-and doxorubicin-induced DNA damage through ISGF3 pathway, leading to cell cycle dysregulation and increased mitotic catastrophe. These findings reveal that GLDC regulates RCC progression via ISFG3-mediated pathway and offers a promising strategy for RCC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Competing Interests: Declaration of competing interest MAP serves on the advisory boards of Abbott Vascular, Boston Scientific, and Medtronic. YK serves as a consultant to Abbott Vascular. Rest of the authors have none to disclose.

Background: Glutamatergic signaling is essential for modulating synaptic plasticity and cognition. However, the dynamics of glutamatergic activity over the 24-hour sleep-wake cycle, particularly in relation to sleep, remain poorly understood. This study aims to investigate diurnal variations in brain Glx levels-representing the combined concentrations of glutamate and glutamine-in humans and to explore their implications for cognitive performance and sleep pressure., Methods: We conducted two independent experiments to measure Glx levels across the sleep-wake cycle using proton magnetic resonance spectroscopy. In Experiment 1, 14 participants underwent 13 hours of Glx measurements during a typical sleep-wake cycle. Experiment 2 extended these measurements to an around-the-clock observation over a 6-day period. This period included two days of normal sleep-wake cycles, 24 hours of enforced wakefulness, and a three-day recovery phase. Seven participants took part in Experiment 2., Results: The study observed that brain Glx levels increased during wakefulness and decreased during sleep. Notably, Glx levels were lower during enforced wakefulness compared to those during normal wakefulness. Reduced Glx levels were associated with diminished cognitive performance, while greater Glx exposure over the preceding 24 hours correlated with increased sleep pressure., Conclusions: These findings suggest that Glx accumulation may contribute to increased sleep pressure, while its reduction appears to support wakefulness. These observations, together with the diurnal variations in Glx levels, underscore the dynamic nature of glutamatergic activity across the daily cycle. Further research is warranted to explore the potential role of sleep in regulating glutamatergic homeostasis., (Copyright © 2024. Published by Elsevier Inc.)

Genome-wide association studies (GWAS) have identified over 800 loci associated with kidney function, yet the specific genes, variants, and pathways involved remain elusive. By integrating kidney function GWAS with human kidney expression and methylation quantitative trait analyses, we identified Ten-Eleven Translocation (TET) DNA demethylase 2 (TET2) as a novel kidney disease risk gene. Utilizing single-cell chromatin accessibility and CRISPR-based genome editing, we highlight GWAS variants that influence TET2 expression in kidney proximal tubule cells. Experiments using kidney/tubule-specific Tet2 knockout mice indicated its protective role in cisplatin-induced acute kidney injury, as well as in chronic kidney disease and fibrosis induced by unilateral ureteral obstruction or adenine diet. Single-cell gene profiling of kidneys from Tet2 knockout mice and TET2-knockdown tubule cells revealed the altered expression of DNA damage repair and chromosome segregation genes, notably including INO80, another kidney function GWAS target gene itself. Remarkably, both TET2-null and INO80-null cells exhibited an increased accumulation of micronuclei after injury, leading to the activation of cytosolic nucleotide sensor cGAS-STING. Genetic deletion of cGAS or STING in kidney tubules, or pharmacological inhibition of STING, protected TET2-null mice from disease development. In conclusion, our findings highlight TET2 and INO80 as key genes in the pathogenesis of kidney diseases, indicating the importance of DNA damage repair mechanisms., (© 2024. The Author(s).)

Emerging evidence suggests that air pollution is a significant contributor to the global burden of kidney disease. Although acute kidney injury (AKI) is a common secondary event in ill patients, evidence regarding the association between air pollution and AKI accompanied by specific comorbidities is limited. This study aimed to estimate the association between short-term exposure to air pollution (fine particulate matter ≤2.5 μm [PM 2.5 ] and ozone [O 3 ]) and incident AKI by comorbid diseases using the Korea National Health Information Database (NHID). Total of 160,390 incident AKI cases, defined as an emergency department (ED) visit due to AKI, were observed within the period 2015-2021 in inland South Korea. A time-stratified case-crossover design was applied for PM 2.5 and O 3 individually, using a conditional logistic regression model within each case and its own control (three or four days of the same day of the week in the same month) to estimate the association between short-term air pollution exposure and ED visits due to AKI. Short-term exposure to PM 2.5 and O 3 was associated with ED visits due to AKI with ORs of 1.008 (95% confidence interval [CI]: 0.999, 1.017) and 1.019 (95% CI: 1.005, 1.033) for an interquartile range (IQR) increase in lag 0-1 day PM 2.5 and O 3 respectively, although OR for PM 2.5 was marginally significant. The odds of incident AKI associated with PM 2.5 was evident in conjunction with ischemic heart disease, cerebrovascular disease, gastrointestinal bleeding, and pneumonia. For O 3 , the estimated odds was prominent for AKI with ischemic heart disease. In addition, the comorbid disease-specific odds of AKI attributed to air pollution varied by sex and age. Our findings provide epidemiological evidence of a plausible mechanism between air pollution and incident AKI and suggest the need for personalized AKI prevention strategies attributed to air pollution., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Youngrin Kwag, Eunhee Ha reports financial support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications., Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI])., Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712])., Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In the digital age, large language models (LLMs) like ChatGPT have emerged as important sources of health care information. Their interactive capabilities offer promise for enhancing health access, particularly for groups facing traditional barriers such as insurance and language constraints. Despite their growing public health use, with millions of medical queries processed weekly, the quality of LLM-provided information remains inconsistent. Previous studies have predominantly assessed ChatGPT's English responses, overlooking the needs of non-English speakers in the United States. This study addresses this gap by evaluating the quality and linguistic parity of vaccination information from ChatGPT and the Centers for Disease Control and Prevention (CDC), emphasizing health equity., Objective: This study aims to assess the quality and language equity of vaccination information provided by ChatGPT and the CDC in English and Spanish. It highlights the critical need for cross-language evaluation to ensure equitable health information access for all linguistic groups., Methods: We conducted a comparative analysis of ChatGPT's and CDC's responses to frequently asked vaccination-related questions in both languages. The evaluation encompassed quantitative and qualitative assessments of accuracy, readability, and understandability. Accuracy was gauged by the perceived level of misinformation; readability, by the Flesch-Kincaid grade level and readability score; and understandability, by items from the National Institutes of Health's Patient Education Materials Assessment Tool (PEMAT) instrument., Results: The study found that both ChatGPT and CDC provided mostly accurate and understandable (eg, scores over 95 out of 100) responses. However, Flesch-Kincaid grade levels often exceeded the American Medical Association's recommended levels, particularly in English (eg, average grade level in English for ChatGPT=12.84, Spanish=7.93, recommended=6). CDC responses outperformed ChatGPT in readability across both languages. Notably, some Spanish responses appeared to be direct translations from English, leading to unnatural phrasing. The findings underscore the potential and challenges of using ChatGPT for health care access., Conclusions: ChatGPT holds potential as a health information resource but requires improvements in readability and linguistic equity to be truly effective for diverse populations. Crucially, the default user experience with ChatGPT, typically encountered by those without advanced language and prompting skills, can significantly shape health perceptions. This is vital from a public health standpoint, as the majority of users will interact with LLMs in their most accessible form. Ensuring that default responses are accurate, understandable, and equitable is imperative for fostering informed health decisions across diverse communities., (©Saubhagya Joshi, Eunbin Ha, Andee Amaya, Melissa Mendoza, Yonaira Rivera, Vivek K Singh. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.10.2024.)

The high prevalence of comorbid mental disorders (CMDs) in patients with inflammatory bowel disease (IBD) is well-documented. This study delves into the intricate CMD-IBD relationship through comprehensive analyses using human variants, gut microbiome, and anxiety/depression estimates from a cohort of 507 IBD patients and 75 controls. Notably, patients with IBD, especially those with CMD, exhibited lower diversity than controls. We identified 106 differentially abundant taxa (DATs) in IBD patients compared to controls and 21 DATs distinguishing CMD-affected from CMD-free IBD patients. Microbial IBD-risk scores, reflecting an individual's microbial burden for IBD, revealed a significant enrichment of IBD-risk signatures in CMD-affected patients compared to CMD-free patients. Additionally, there was an IBD-risk variant potentially regulating the abundance of an IBD/CMD-associated DAT, suggesting an interplay between IBD-risk variants and dysbiosis in CMD. Our investigation underscores the pivotal role of IBD-associated gut dysbiosis in predisposing IBD patients to CMD, partially through genetic variant-mediated mechanisms., (© 2024. The Author(s).)

Objectives: To assess the short term temporal variations in suicide risk related to the day of the week and national holidays in multiple countries., Design: Multicountry, two stage, time series design., Setting: Data from 740 locations in 26 countries and territories, with overlapping periods between 1971 and 2019, collected from the Multi-city Multi-country Collaborative Research Network database., Participants: All suicides were registered in these locations during the study period (overall 1 701  286 cases)., Main Outcome Measures: Daily suicide mortality., Results: Mondays had peak suicide risk during weekdays (Monday-Friday) across all countries, with relative risks (reference: Wednesday) ranging from 1.02 (95% confidence interval (CI) 0.95 to 1.10) in Costa Rica to 1.17 (1.09 to 1.25) in Chile. Suicide risks were lowest on Saturdays or Sundays in many countries in North America, Asia, and Europe. However, the risk increased during weekends in South and Central American countries, Finland, and South Africa. Additionally, evidence suggested strong increases in suicide risk on New Year's day in most countries with relative risks ranging from 0.93 (95% CI 0.75 to 1.14) in Japan to 1.93 (1.31 to 2.85) in Chile, whereas the evidence on Christmas day was weak. Suicide risk was associated with a weak decrease on other national holidays, except for Central and South American countries, where the risk generally increased one or two days after these holidays., Conclusions: Suicide risk was highest on Mondays and increased on New Year's day in most countries. However, the risk of suicide on weekends and Christmas varied by country and territory. The results of this study can help to better understand the short term variations in suicide risks and define suicide prevention action plans and awareness campaigns., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at URL www.icmje.org/disclosure-of-interest/ and declare no support for the present study; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. This study did not include plans to recruit participants and only used pre-existing datasets. All data used in this study were pre-recorded and completely de-identified., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study examined the impact of xylanases, focusing on the hydrolysis of water-extractable (WE-AX) and water-unextractable arabinoxylans (WU-AX) and on the quality and noodle-making performance of flours with varying gluten strengths. Flours categorized as strong (S), medium (M), and weak (W) were treated with two xylanases (WE and WU) at concentrations ranging from 0.01% to 0.2%. Parameters such as solvent retention capacity (SRC), SDS sedimentation volume, dough mixing properties, and noodle characteristics were measured. The SRC revealed that flour S had the highest water-holding capacity, gluten strength, and arabinoxylan content. Xylanase treatment reduced water SRC values in flour S and increased the SDS sedimentation volume, with a greater effect from xylanase WU, indicating the potential enhancement of gluten strength. The impact of xylanases was pronounced at higher enzyme concentrations, with differences in dough mixing properties, resistance, and extensibility of fresh noodles, producing softer and stretchable noodles. Cooked noodles made from flours treated with xylanase were softer and had decreased firmness and chewiness, especially those made from flours S and M. This study concludes that WE-AX and WU-AX influence noodle texture; therefore, controlling their degradation with xylanases can produce noodles with varied textures, depending on the gluten strength of the flour.

Background: The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex., Materials and Methods: This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers., Results: Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age., Conclusions: The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care., (© 2024 John Wiley & Sons Ltd.)

Study Objectives: Shift work interferes with circadian rhythms, affecting sleep quality and cognitive function. Poor sleep quality in shift worker (SW)s can impair psychomotor performance due to fatigue and sleepiness, increasing the risk of errors, accidents, and reduced productivity. Given the potential for atrophic changes in the hippocampus due to sleep disturbances, our study investigates how poor sleep quality correlates with hippocampal structural alterations and impacts psychomotor performance among SWs., Methods: We recruited 100 SWs, classifying them based on sleep quality into two groups: good sleep-SW group (n = 59) and poor sleep-SW group (n = 41). Sleep quality was assessed using both 7-day actigraphy for sleep efficiency and the Pittsburgh Sleep Quality Index. A control group of 106 non-SWs without sleep problems (non-SW group) was also included for comparison. The outcome measures were psychomotor speed and hippocampal volumes, both total and by subfield., Results: The poor sleep-SW group showed significantly smaller hippocampal volumes than both the good sleep-SW group (p < .001) and the non-SW group (p = .003). Longer shift work years correlated with greater reductions in hippocampal volume in this group (r = -0.42, p = .009), unlike in the good sleep-SW group (r = 0.08, p = .541). Furthermore, they demonstrated declines in psychomotor speed relative to the non-SW group (p = .006), which correlated with smaller hippocampal volumes (r = 0.37, p = .020)., Conclusions: SWs with poor sleep quality exhibit significant hippocampal volume reductions and psychomotor speed decline, underscoring the importance of early intervention and support for sleep issues in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation., Competing Interests: Declaration of interests K.S. receives research support from Gilead, GSK, Novo Nordisk, Bayer, Regeneron, Calico, and Novartis. K.S. is on the advisory board of Jnana Therapeutics and has received consulting fees from Pfizer and Jnana. Declaration of interests for the Renal Cancer Genetics Consortium, which contributed toward acquisition of the individual-level data, can be referred to as a part of Purdue et al.(10) The other named authors in the manuscript have no competing interests to declare. It is to be noted that the individual-level data contributed by The Renal Cancer Genetics Consortium is now publicly available, and the current analyses were conducted with summary-level data only., (Published by Elsevier Inc.)

Background: Although urinary tract infection (UTI) is a common and severe public health concern, and there are clear biological mechanisms between UTI and hot temperatures, few studies have addressed the association between hot temperatures and UTI., Methods: We designed a time-stratified case-crossover study using a population-representative sample cohort based on the National Health Insurance System (NHIS) in South Korea. We obtained all NHIS-based hospital admissions through the emergency room (ER) due to UTI (using a primary diagnostic code) from 2006 to 2019. We assigned satellite-based reanalyzed daily summer (June to September) average temperatures as exposures, based on residential districts of beneficiaries (248 districts in South Korea). The conditional logistic regression was performed to evaluate the association between summer temperature and UTI outcome., Results: A total of 4,436 ER visits due to UTI were observed during the summer between 2006 and 2019 among 1,131,714 NHIS beneficiaries. For 20% increase in summer temperatures (0-2 lag days), the odd ratio (OR) was 1.06 (95% CI: 1.02-1.10) in the total population, and the association was more prominent in the elderly (people aged 65 y or older; OR:1.11, 95% CI: 1.05-1.17), females (OR: 1.12, 95% CI: 1.05-1.19), and people with diabetes history (OR: 1.14, 95% CI: 1.07-1.23). The effect modification by household income was different in the total and elderly populations. Furthermore, the association between summer temperature and UTI increased during the study period in the total population., Conclusions: Our results are consistent with the hypothesis that higher summer temperatures increase the risk of severe UTIs, and the risk might be different by sub-populations., (© 2024. The Author(s).)

Background: Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women., Methods: The study population included 2324 pregnant women from the Korean Children's Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels., Results: Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = -2.41, -0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels ( P for subgroup difference < 0.05)., Conclusions: Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Context: A few studies evaluated all-cause mortality or risk of cardiovascular diseases according to the body mass index (BMI) level in patients with type 2 diabetes., Objective: We evaluated all-cause mortality and the incidence of cardiovascular diseases in lean patients with newly diagnosed type 2 diabetes in Korea. Additionally, we aimed to determine a difference in all-cause mortality and the incidence of cardiovascular diseases according to changes in BMI over time among patients with newly diagnosed type 2 diabetes in Korea., Methods: We analyzed 419,509 patients with newly diagnosed type 2 diabetes who underwent health screening between 2010 and 2014 and followed up until 2019. We conducted a multivariate Cox proportional hazards model to determine the association between BMI and all-cause mortality or risk of cardiovascular diseases., Results: Lean patients with type 2 diabetes had a higher risk of all-cause mortality (hazard ratio [HR]: 2.106, 95% confidence interval [CI]: 1.974-2.248), cardiovascular disease (HR: 1.132, 95% CI: 1.078, 1.189), coronary heart disease (HR: 1.219, 95% CI: 1.124-1.323), heart failure (HR: 1.405, 95% CI: 1.279-1.543), stroke (HR: 1.155, 95% CI: 1.024-1.302), and ischemic stroke (HR: 1.205, 95% CI: 1.045-1.388) compared to patients with type 2 diabetes and normal BMI. Patients with newly diagnosed type 2 diabetes had the highest all-cause mortality when they remained lean during the follow-up., Conclusion: Our findings underscore the critical role of maintaining an appropriate weight status to reduce all-cause mortality and incidence of cardiovascular diseases among lean patients with newly diagnosed type 2 diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background and Aim: The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea., Methods: We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 μg/m 3 increase in fine particulate matter (PM 2.5 ) and particulate matter (PM 10 ) and per 1 ppb increase in sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and ozone (O 3 )., Results: This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM 2.5 (HR: 1.019; 95% CI: 1.012, 1.027), PM 10 (HR: 1.009; 95% CI: 1.006, 1.013), SO 2 (HR: 1.037; 95% CI: 1.018, 1.055), and O 3 (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys., Conclusions: This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Maternal diet during pregnancy might influence the development of childhood allergic disorders. There are few studies on the association between processed food intake and infant atopic dermatitis (AD) during pregnancy. The aim of the present study was to investigate the association of ultra-processed food (UPF) intake during pregnancy with infantile AD., Methods: This study involved 861 pairs of pregnant women and their offspring from the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Dietary intake was estimated using a 24-h recall method at 12-28 weeks gestation. The NOVA classification was used to identify UPF, and UPF intake was calculated as the percentage of total energy consumption and categorized into quartiles. Infantile AD was assessed based on medical history and the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations were assessed by logistic regression with adjustment for confounding factors., Results: Children born to mothers in the highest quartile of UPF consumption (15.5% or more of the total energy) compared to the lowest quartile (6.8% or less) showed a higher risk of AD within 12 months [odds ratio (OR) = 1.69; 95% confidence interval (CI): 1.07-2.66, P for trend 0.0436]. After adjustment for the confounding factors under study, the association was strengthened; the adjusted OR between extreme quartiles was 2.19 (95% CI: 1.11-4.32, P for trend = 0.0418). This association was maintained even after an additional adjustment based on the Korean Healthy Eating Index (KHEI), an indicator of diet quality., Conclusions: Higher maternal consumption of UPF during pregnancy was associated with a greater risk of infantile AD within the first year of life., (© 2024. The Author(s).)

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.

Human pose estimation (HPE) is a technique used in computer vision and artificial intelligence to detect and track human body parts and poses using images or videos. Widely used in augmented reality, animation, fitness applications, and surveillance, HPE methods that employ monocular cameras are highly versatile and applicable to standard videos and CCTV footage. These methods have evolved from two-dimensional (2D) to three-dimensional (3D) pose estimation. However, in real-world environments, current 3D HPE methods trained on laboratory-based motion capture data encounter challenges, such as limited training data, depth ambiguity, left/right switching, and issues with occlusions. In this study, four 3D HPE methods were compared based on their strengths and weaknesses using real-world videos. Joint position correction techniques were proposed to eliminate and correct anomalies such as left/right inversion and false detections of joint positions in daily life motions. Joint angle trajectories were obtained for intuitive and informative human activity recognition using an optimization method based on a 3D humanoid simulator, with the joint position corrected by the proposed technique as the input. The efficacy of the proposed method was verified by applying it to three types of freehand gymnastic exercises and comparing the joint angle trajectories during motion.

ChatGPT is a popular information system (over 1 billion visits in August 2023) that can generate natural language responses to user queries. It is important to study the quality and equity of its responses on health-related topics, such as vaccination, as they may influence public health decision-making. We use the Vaccine Hesitancy Scale (VHS) proposed by Shapiro et al. 1 to measure the hesitancy of ChatGPT responses in English, Spanish, and French. We find that: (a) ChatGPT responses indicate less hesitancy than those reported for human respondents in past literature; (b) ChatGPT responses vary significantly across languages, with English responses being the most hesitant on average and Spanish being the least; (c) ChatGPT responses are largely consistent across different model parameters but show some variations across the scale factors (vaccine competency, risk). Results have implications for researchers interested in evaluating and improving the quality and equity of health-related web information., (©2024 AMIA - All rights reserved.)

The International Maritime Organization (IMO) is currently rolling out more restrictive regulations in order to achieve net-zero GHG emissions by 2050. In response, the shipping industry is planning to pivot to green energy sources such as hydrogen fuel. However, since hydrogen has an extremely low boiling point (-253 °C), materials for storing liquid hydrogen must be highly resistant to low-temperature brittleness and hydrogen embrittlement. A 316L stainless steel is a typical material that meets these requirements, and various welds have been studied. In this study, 3 pass butt welding was performed by applying the FCAW (flux cored arc welding) process to 10 mm thick ASTM-A240M-316L stainless steel, with the size of the fusion zone and HAZ investigated by mechanical testing and heat transfer FE analysis according to process variables, such as heat input, welding speed, and the number of passes. In all cases, the yield and tensile strengths were about 10% and 3% higher than the base metal, respectively. Furthermore, heat transfer FE analysis showed an average error rate of 1.3% for penetration and 10.5% for width and confirmed the size of the HAZ, which experienced temperatures between 500 °C and 800 °C.

Background and Objectives : Endoscopic epidural neuroplasty (EEN) facilitates adhesiolysis through direct epiduroscopic visualization, offering more precise neural decompression than that exhibited by percutaneous epidural neuroplasty (PEN). We aimed to compare the effects of EEN and PEN for 6 months after treatment with lower back and radicular pain in patients. Methods : This retrospective study compared the visual analog scale (VAS) and Oswestry disability index (ODI) scores in patients with low back and radicular pain who underwent EEN or PEN with a steering catheter. The medical records of 107 patients were analyzed, with 73 and 34 undergoing EEN and PEN, respectively. Results : The VAS and ODI scores decreased at all time points after EEN and PEN. VAS and ODI scores decreased more in the EEN group than those in the PEN group at 1 day and 1- and 6-months post-procedure, indicating superior pain relief for both lower back and radicular pain through EEN. Conclusions : EEN is a superior treatment of pain control than PEN in lower back and radicular pain patients.

Background: The presence of psychiatric disorders is widely recognized as one of the primary risk factors for suicide. A significant proportion of individuals receiving outpatient psychiatric treatment exhibit varying degrees of suicidal behaviors, which may range from mild suicidal ideations to overt suicide attempts. This study aims to elucidate the transdiagnostic symptom dimensions and associated suicidal features among psychiatric outpatients., Methods: The study enrolled patients who attended the psychiatry outpatient clinic at a tertiary hospital in South Korea (n = 1, 849, age range = 18-81; 61% women). A data-driven classification methodology was employed, incorporating a broad spectrum of clinical symptoms, to delineate distinctive subgroups among psychiatric outpatients exhibiting suicidality (n = 1189). A reference group of patients without suicidality (n = 660) was included for comparative purposes to ascertain cluster-specific sociodemographic, suicide-related, and psychiatric characteristics., Results: Psychiatric outpatients with suicidality (n = 1189) were subdivided into three distinctive clusters: the low-suicide risk cluster (Cluster 1), the high-suicide risk externalizing cluster (Cluster 2), and the high-suicide risk internalizing cluster (Cluster 3). Relative to the reference group (n = 660), each cluster exhibited distinct attributes pertaining to suicide-related characteristics and clinical symptoms, covering domains such as anxiety, externalizing and internalizing behaviors, and feelings of hopelessness. Cluster 1, identified as the low-suicide risk group, exhibited less frequent suicidal ideation, planning, and multiple attempts. In the high-suicide risk groups, Cluster 2 displayed pronounced externalizing symptoms, whereas Cluster 3 was primarily defined by internalizing and hopelessness symptoms. Bipolar disorders were most common in Cluster 2, while depressive disorders were predominant in Cluster 3., Discussion: Our findings suggest the possibility of differentiating psychiatric outpatients into distinct, clinically relevant subgroups predicated on their suicide risk. This research potentially paves the way for personalizing interventions and preventive strategies that address cluster-specific characteristics, thereby mitigating suicide-related mortality among psychiatric outpatients., Competing Interests: Declaration of competing interest All of the authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Despite the persistent primary care physician shortage over 2 decades of allopathic medical school expansion, some medical schools are absent a department of family medicine; these schools are designated as "target" schools. These absences are important because evidence has demonstrated the association between structured exposure to family medicine during medical school and the proportion of students who ultimately select a career in family medicine. In this study, we aimed to address part of this gap by defining and characterizing the current landscape of US allopathic target schools., Methods: We identified allopathic target schools by reviewing all Liaison Committee of Medical Education (LCME) accredited institutions for the presence of a family medicine department. To compare these schools in terms of family medicine representation and outcomes, we curated descriptive data from publicly available websites, previously published family medicine match results, and school rankings for primary care., Results: We identified 12 target schools (8.7% of all US allopathic accredited medical schools) with considerable heterogeneity in opportunities for family medicine engagement, leadership, and training. Target schools with greater family medicine representation had increased outcomes for family medicine workforce and primary care opportunities., Conclusion: With growing primary care workforce gaps, target schools have a responsibility to enhance family medicine presence and representation at their institutions. We provide recommendations at the institutional, specialty, and national level to increase family medicine representation at target schools, with the goal that all schools eventually establish a department of family medicine.

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, high-resolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex-a major region in the extended olfactory network-and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years' duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups' gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus ( r =0.316, p=0.001) and insular-opercular ( r =0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

Systemic lupus erythematosus (SLE) is a remitting-relapsing systemic autoantibody and immune complex disease with a similar clinical presentation to that of malignancy and infection. The authors report a case of newly diagnosed SLE and lupus nephritis in a 48-year-old woman with constitutional symptoms and unintentional weight loss. Her presentation was further complicated by pericardial effusion and methicillin-resistant Staphylococcus aureus (MRSA) facial cellulitis and bacteremia. In the context of nonspecific symptoms and a wide initial differential diagnosis, the early consideration of rheumatologic etiologies and the involvement of consultant services led to appropriate diagnostic testing and a timely diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, La et al.)

Convolutional neural networks (CNNs) have been used widely to predict biological brain age based on brain magnetic resonance (MR) images. However, CNNs focus mainly on spatially local features and their aggregates and barely on the connective information between distant regions. To overcome this issue, we propose a novel multi-hop graph attention (MGA) module that exploits both the local and global connections of image features when combined with CNNs. After insertion between convolutional layers, MGA first converts the convolution-derived feature map into graph-structured data by using patch embedding and embedding-distance-based scoring. Multi-hop connections between the graph nodes are modeled by using the Markov chain process. After performing multi-hop graph attention, MGA re-converts the graph into an updated feature map and transfers it to the next convolutional layer. We combined the MGA module with sSE (spatial squeeze and excitation)-ResNet18 for our final prediction model (MGA-sSE-ResNet18) and performed various hyperparameter evaluations to identify the optimal parameter combinations. With 2788 three-dimensional T1-weighted MR images of healthy subjects, we verified the effectiveness of MGA-sSE-ResNet18 with comparisons to four established, general-purpose CNNs and two representative brain age prediction models. The proposed model yielded an optimal performance with a mean absolute error of 2.822 years and Pearson's correlation coefficient (PCC) of 0.968, demonstrating the potential of the MGA module to improve the accuracy of brain age prediction.

Competing Interests: Conflict of interest: None.

Multienzyme-mimicking redox nanozymes capable of efficient reactive oxygen species (ROS) generation and cellular homeostasis disruption are highly pursued for cancer therapy. However, it still faces challenges from the complicate tumor microenvironment (TME) and high chance for tumor metastasis. Herein, well-dispersed PtMnIr nanozymes are designed with multiple enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx), which continuously produce ROS and deplete glutathione (GSH) concurrently in an "inner catalytic loop" way. With the help of electrodynamic stimulus, highly active "spark" species (Ir 3+ and Mn 3+ ) are significantly increased, resulting in an effective cascade enzymatic and electrodynamic therapy. Moreover, the cyclic generation of ROS can also facilitate ferroptosis and apoptosis in tumor cells, boosting synergistic therapy. Importantly, lung metastasis inhibition is found, which confirms efficient immunotherapy by the combined effect of immunogenic cell death (ICD) and Mn 2+ -induced cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway, contributing great potential in the treatment of malignant tumors., (© 2023 Wiley‐VCH GmbH.)

Background: Several studies have reported that climate change elevates heat exposure in pregnant women and high temperatures during pregnancy are associated with preterm births (PTBs). Although the association might be disproportionate, related evidence remains sparse. We evaluated the disproportionate risk of PTB associated with ambient temperature during pregnancy by individual and regional characteristics in South Korea., Methods: We collected data on birth certificates and daily mean temperatures during the period from 2011 to 2019. A time-stratified case-crossover design was used to investigate the association between temperature and PTB and stratified analyses were conducted to examine the effect modification of individual and regional characteristics., Results: A total of 160,067 singleton PTBs were recorded in Korea from 2011 to 2019. A 5℃ increase in the mean temperature during the last four weeks before delivery was associated with an increased risk of PTB with an odds ratio (OR) of 1.03 (95% confidence interval [CI]: 1.02, 1.05), and the association was more evident in mothers aged ≥35 years (OR: 1.06 [95% CI: 1.03, 1.10]) and with low education levels (OR: 1.04 [95% CI: 1.02, 1.05]). Additionally, the estimated risk was evident in districts with lower medical resources and more prominent disparities were shown by individual and regional characteristics in rural areas than in urban areas., Conclusions: This study provides evidence that the risk of PTB related to ambient temperature is disproportionate by individual and regional characteristics and suggests the need for public health policies to alleviate the disparities, especially in rural areas., (© 2024. The Author(s).)

Background: Particulate air pollution and residential greenness are associated with sleep quality in the general population; however, their influence on maternal sleep quality during pregnancy has not been assessed., Objective: This cross-sectional study investigated the individual and interactive effects of exposure to particulate matter (PM) air pollution and residential greenness on sleep quality in pregnant women., Methods: Pregnant women (n = 4933) enrolled in the Korean Children's Environmental Health Study with sleep quality information and residential address were included. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The average concentrations of PM (PM 2.5 and PM 10 ) during pregnancy were estimated through land use regression, and residential greenness in a 1000 m buffer area around participants' residences was estimated using the Normalized Difference Vegetation Index (NDVI 1000-m ). Modified Poisson regression models were used to estimate the associations between PM and NDVI and poor sleep quality (PSQI >5) after controlling for a range of covariates. A four-way mediation analysis was conducted to examine the mediating effects of PM., Results: After adjusting for confounders, each 10 μg/m 3 increase in PM 2.5 and PM 10 exposure was associated with a higher risk of poor sleep quality (relative risk [RR]: 1.06; 95% confidence interval [CI]: 1.01, 1.11; and RR: 1.09; 95% CI: 1.06, 1.13, respectively), and each 0.1-unit increase in NDVI 1000-m was associated with a lower risk of poor sleep quality (RR: 0.97; 95% CI: 0.95, 0.99). Mediation analysis showed that PM mediated approximately 37%-56% of the association between residential greenness and poor sleep quality., Conclusions: This study identified a positive association between residential greenness and sleep quality. Furthermore, these associations are mediated by a reduction in exposure to particulate air pollution and highlight the link between green areas, air pollution control, and human health., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Computational modeling has earned significant interest as an alternative to animal testing of toxicity assessment. However, the process of selecting an appropriate algorithm and fine-tuning hyperparameters for the developing of optimized models takes considerable time, expertise, and an intensive search. The recent emergence of automated machine learning (autoML) approaches, available as user-friendly platforms, has proven beneficial for individuals with limited knowledge in ML-based predictive model development. These autoML platforms automate crucial steps in model development, including data preprocessing, algorithm selection, and hyperparameter tuning. In this study, we used seven previously published and publicly available datasets for oxides and metals to develop nanotoxicity prediction models. AutoML platforms, namely Vertex AI, Azure, and Dataiku, were employed and performance measures such as accuracy, F1 score, precision, and recall for these autoML-based models were then compared with those of conventional ML-based models. The results demonstrated clearly that the autoML platforms produced more reliable nanotoxicity prediction models, outperforming those built with conventional ML algorithms. While none of the three autoML platforms significantly outperformed the others, distinctions exist among them in terms of the available options for choosing technical features throughout the model development steps. This allows users to select an autoML platform that aligns with their knowledge of predictive model development and its technical features. Additionally, prediction models constructed from datasets with better data quality displayed, enhanced performance than those built from datasets with lower data quality, indicating that future studies with high-quality datasets can further improve the performance of those autoML-based prediction models., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC 50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Due to the ongoing effects of climate change, the incidence of heatwave-related mortality is rising globally. Improved allocation and utilization of healthcare resources could help alleviate this issue. This study aimed to identify healthcare resource factors associated with heatwave-related mortality in seven major cities of South Korea., Methods: We analyzed daily time-series data on mean temperature and all-cause mortality from 2011 to 2019. Using principal component analysis (PCA), we clustered district-level healthcare resource indicators into three principal components (PCs). To estimate district-specific heatwave-mortality risk, we used a distributed lag model with a quasi-Poisson distribution. Furthermore, a meta-regression was performed to examine the association between healthcare resources and heatwave-mortality risk., Findings: A total of 310,363 deaths were analyzed in 74 districts. The lag-cumulative heatwave-related mortality (RRs) ranged from 1.12 (95% confidence interval [CI]: 1.07, 1.17) to 1.21 (95% CI 1.05, 1.38), depending on the definitions used for heatwaves. Of the three PCs for healthcare resources (PC1: pre-hospital emergency medical service, PC2: hospital resources, PC3: timely access), timely access was associated with reduced risk of heatwave-related mortality, particularly among the elderly. Specifically, timely access to any emergency room (ER) exhibited the strongest association with lower heatwave-related mortality., Interpretation: Our findings suggest that timely access to any ER is more effective in reducing heatwave-related mortality risk than access to higher-level healthcare facilities, especially among the elderly. Therefore, healthcare resource factors and ER accessibility should be prioritized when identifying vulnerable populations for heatwaves, along with known individual and socio-demographic factors., Funding: This work was supported by the Research Program funded by the Korea Disease Control and Prevention Agency (2022-12-303), the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C2092353) and the MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

Background and Aim: Decreased kidney function is a putative risk factor for various cancers. However, few studies have investigated the association between a decreased estimated glomerular filtration rate (eGFR) and incident pancreatic cancer. We aimed to investigate the risk of incident pancreatic cancer according to eGFR categories., Methods: In this retrospective cohort study, we included 359 721 adults who underwent health checkups in 2009 or 2010 by using the Korean National Health Insurance Database. The study population was categorized into four groups by eGFR (mL/min/1.73 m 2 ) using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR < 45), group 2 (eGFR ≥ 45 to < 60), group 3 (eGFR ≥ 60 to < 90), and group 4 (eGFR ≥ 90). Multivariate Cox proportional hazards models were used to determine the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pancreatic cancer until 2019 by comparing the eGFR groups., Results: During the 3 493 589.05 person-years of follow-up, 1702 pancreatic cancer cases were identified. Compared with group 4 (eGFR ≥ 90), HRs and 95% CIs for the incidence of pancreatic cancer were 1.39 (1.24-1.56) for group 3 (eGFR ≥ 60 to < 90), 1.79 (1.47-2.16) for group 2 (eGFR ≥ 45 to < 60), and 2.05 (1.62-2.60) for group 1 (eGFR < 45) in the multivariate adjusted model., Conclusions: Decreased eGFR was significantly associated with an increased risk of pancreatic cancer in Korean population. Further studies are needed to investigate the relationship between a decreased eGFR and the risk of pancreatic cancer in other ethnic groups., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Numerous studies have investigated the association between heat wave exposure increased heat-related hospitalizations in the general population. However, little is known about heat-related morbidity in young children who are more vulnerable than the general population. Therefore, we aimed to evaluate the association between hospitalization for heat-related illness in children and heat wave exposure in South Korea., Methods: We used the National Health Insurance Service (NHIS) database, which provides medical records from 2015 to 2019 in South Korea. We defined daily hospitalizations for heat-related illness of children younger than five years during the summer period (June to August). We considered the definition of heat waves considering the absolute temperature and percentile. A total of 12 different heat waves were used. A time-series analysis was used to investigate the association between heat wave exposure and heat-related hospitalization among children younger than five years. We used a two-stage design involving a meta-analysis after modeling by each region., Results: We included 16,879 daily heat-related hospitalizations among children younger than five years. Overall, heat wave exposure within two days was most related for heat-related hospitalizations in young children. The relative risk (RR) due to heat wave exposure within two days (lag2) (12 definitions: 70th to 90th percentile of maximum temperature) ranged from 1.038 (95% confidence interval (CI): 0.971, 1.110) to 1.083 (95% CI: 1.036, 1.133). We found that boys were more vulnerable to heat exposure than girls. In addition, we found that urban areas were more vulnerable to heat exposure than rural areas., Conclusions: In our study, heat wave exposure during summer was found to be associated with an increased risk of hospitalization for heat-related illness among children younger than five years. Our findings suggest the need for summer heat wave management and prevention for children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 μm (PM 2.5 ), ozone (O 3 ), and nitrogen dioxide (NO 2 )-and AKI-related mortality using a multi-country dataset., Methods: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines., Results: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m 3 increase in lag 0-28 days of PM 2.5 , warm-season O 3 , and NO 2 , respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM 2.5 and O 3 . We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM 2.5 , warm-season O 3 , and NO 2 concentrations above the WHO guidelines., Conclusions: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Youngrin Kwag reports administrative support was provided by Korea Ministry of Science and ICT. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population., Methods: We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019., Results: In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24)., Conclusions: Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Early childhood is important for neurodevelopment, and exposure to endocrine disruptors such as bisphenol A (BPA) and phthalates in this period may cause neurodevelopmental disorders and delays. The present study examined the association between exposure to mixtures of BPA and three metabolites of phthalates in early childhood and IQ at 5 years of age. The Mother and Children's Environmental Health (MOCEH) study is a prospective birth cohort study conducted in Korea with 1751 pregnant women enrolled from 2006 to 2010. After excluding those without relevant data, 47 children were included in the final analysis. We measured children's urinary concentrations of metabolites of endocrine-disrupting chemicals (Bisphenol A, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-butyl) phthalate) at ages of 24 and 36 months. We evaluated the children's IQ with the Korean Wechsler Intelligence Test at the age of 5 years. After adjusting for potential confounders, a multiple linear regression was conducted to examine the associations between individual endocrine-disrupting chemicals and the IQ of the children. Weighted Quantile Sum (WQS) regression and quantile-based g-computation were used to assess the association between IQ at age 5 and exposure to mixtures of BPA and phthalates. In the single-chemical analyses, mono-(2-ethyl-5-butyl) phthalate exposure at 36 months was adversely associated with children's IQ (β = -4.93, 95% confidence interval (CI): -9.22, -0.64). In the WQS regression and quantile-based g-computation analyses, exposure to the mixture of BPA and phthalates was associated with lower IQ [β = -9.13 (P-value = 0.05) and β = -9.18 (P-value = 0.05), respectively]. The largest contributor to the overall association was exposure to mono-(2-ethyl-5-butyl) phthalate at 36 months. In the present study, postnatal exposure to mixtures of BPA and three metabolites of phthalates was associated with decreased IQ of children at age 5., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Despite substantial progress in understanding the biology of axon regeneration in the CNS, our ability to promote regeneration of the clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single-cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise to a Regeneration Classifier, which can be broadly applied to predict the regenerative potential of diverse neuronal types across developmental stages or after injury. Network analyses highlighted the importance of antioxidant response and mitochondrial biogenesis. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of antioxidant response, in CST regeneration. Our data demonstrate a universal transcriptomic signature underlying the regenerative potential of vastly different neuronal populations and illustrate that deep sequencing of only hundreds of phenotypically identified neurons has the power to advance regenerative biology., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease.

Background: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive., Method: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount., Results: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy., Conclusions: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients., (© 2023 John Wiley & Sons Ltd.)