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Backgruound: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes., Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models., Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity., Conclusion: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia., Competing Interests: Declaration of competing interest 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.)

Urban stormwater runoff is considered a key component of future water supply portfolios for water-stressed cities. Beneficial use of runoff, such as capture for recharge of drinking water aquifers, relies on improved stormwater treatment. Many dissolved constituents, including metals and trace organic contaminants (TrOCs) such as hydrophilic pesticides and poly- and perfluoroalkyl substances (PFASs), are of concern due to their toxicity, persistence, prevalence in stormwater runoff, and poor removal in conventional stormwater control measures. This study explores the operational flow rate limitations of black carbon (BC)-amended engineered media filters for removal of a wide suite of dissolved metals and TrOCs and provides validation for a previously developed predictive TrOC transport model. Column experiments were conducted with face velocities of 40 and 60 cm h -1 to assess Douglas Fir-based biochar and regenerated activated carbon (RAC) filter performance in light of media-contaminant removal kinetic limitations. This study found that increasing the face velocity in BC-amended filters to 40 and 60 cm h -1 , which are representative of field conditions, decreased the removal of total suspended solids, turbidity, dissolved hydrophilic TrOCs, and PFASs when expressed as volume treated relative to previous studies conducted at 20 cm h -1 . Dissolved metals and hydrophobic TrOCs removal were not substantially affected by the increased flow rates. A predictive 1-d intraparticle pore diffusion-limited sorption model with sorption and effective tortuosity parameters determined previously from experiments conducted at 20 cm h -1 was validated for these higher flow rates. This work provides insights to the kinetic limitations of contaminant removal within biochar and RAC filters and implications for stormwater filter design and operation., 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. Published by Elsevier Ltd.)

Purpose: In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively., Materials and Methods: Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data., Results: Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001)., Conclusion: According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Purpose: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU)., Materials and Methods: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW)., Results: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants., Conclusions: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors., Competing Interests: Disclosure The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for β2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group., (© 2024. The Author(s).)

Concomitant use of sodium glucose cotransporter-2 inhibitors (SGLT-2i) and overactive bladder (OAB) drugs potentially poses a risk of urinary tract infections (UTIs) due to the urinary retention of highly concentrated glucose in the urine. Thus, this study aimed to investigate the risk of UTIs among patients who initiated SGLT-2i treatment while taking OAB drugs. This population-based cohort study included new-users of SGLT-2i or comparator antidiabetics (dipeptidyl peptidase-4 inhibitor (DPP-4i); glucagon-like peptide-1 receptor agonist (GLP-1RA)) with OAB drugs between 2014 and 2020 using claim data from Korea. Primary outcome was a composite UTI event composite end point comprising pyelonephritis, cystitis, and urethritis, using both inpatient and outpatient diagnoses. Propensity score fine stratification was used to adjust for potential confounding factors. Weighted hazard ratios (HR) were calculated using the Cox proportional hazards model. In the first cohort, 796 and 9,181 new-users of SGLT-2i and DPP-4i with OAB drugs were identified, respectively. This study found a similar risk of UTIs in concomitant users of SGLT-2i and DPP-4i (weighted HR 1.08, 95% confidence interval: 0.88-1.32) with OAB drugs. In the second cohort, 2,387 and 280 new-users of SGLT-2i and GLP-1RA with OAB drugs were identified, respectively. Initiation of SGLT-2i while on OAB treatment was not associated with increased risk of UTI (0.89, 0.50-1.60), compared with initiation of GLP-1RA. These results show that the concomitant use of SGLT-2i with OAB drugs was not associated with an increased risk of UTI compared with the concomitant use of DPP-4i or GLP-1RA with OAB drugs., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype., Materials and Methods: Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population., Results: A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1-expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02)., Conclusion: Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.

Background: Despite the rising trend of tracheostomies in children, there is a lack of comprehensive resources for families to navigate the challenges of living with a tracheostomy, emphasising the need for evidence-based support in understanding postoperative care and long-term adjustments. This study aimed to examine the pattern of using healthcare services and nationwide medical outcomes in children who underwent a tracheotomy before the age of 2 years., Methods: This retrospective study used the National Health Insurance System database from 2008 to 2016 and included all children codified with tracheotomy procedure codes before their second birthday. Healthcare utilisation, such as medical costs, number of hospital visits, home healthcare nursing and medical diagnoses on readmission, in the first 2 years after tracheotomy was evaluated. Multivariable logistic regression analysis was used to determine the factors affecting mortality., Results: In total, 813 patients were included in this study. Their use of healthcare services and the accompanying expenses were higher than the national medians for similar age groups; however, both metrics decreased in the second year. The major causes of admission within 2 years of surgery were respiratory and neurological diseases. The mortality rate within 2 years was 37.8%. Higher risks of mortality were associated with having two or more complex chronic conditions. Use of home healthcare nursing services was associated with a lower mortality risk., Conclusion: Paediatric patients with more complex chronic conditions tended to have higher mortality rates within 2 years after surgery. However, receiving home healthcare nursing was significantly associated with a reduced risk of death. Many causes of hospitalisation may be preventable with education and supportive care. Therefore, further research for establishing an integrated care system for these patients and their caregivers is required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cadmium (Cd), a serious environmental contaminant, is associated with adverse health effects. However, the specific changes that the human body experiences in response to exposure to varying concentrations of cadmium remain unknown. The high levels of heavy metal contamination, especially Cd, in abandoned mines and smelter sites make them ideal locations to investigate the physiological manifestations of Cd exposure. This study found that individuals inhabiting abandoned mine and smelter areas had higher concentrations of Cd in their urine and blood compared to those living outside these areas (i.e., the controls). Furthermore, proteomic profiling of blood samples from all study groups was performed to identify proteomic biomarkers associated with chronic and severe Cd exposure. This analysis showed statistically significant correlations between urine Cd levels and sixteen proteins. Among these proteins, seven exhibited significantly altered expressions in samples from contaminated areas compared with those from control areas. Therefore, these proteins were selected as potential markers representing Cd-related protein alterations. Multiple reaction monitoring analysis was performed to validate the expression patterns of the proteins and four proteins were found to exhibit consistent trends. The findings show that Cd exposure significantly affects the expression of certain proteins in the human body. Understanding the underlying mechanisms and diseases associated with Cd-induced protein alterations can aid in the development of effective preventive and therapeutic strategies for individuals exposed to Cd-linked pollution., Competing Interests: Declaration of competing interest 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.)

Background: Multicentric reticulohistiocytosis (MRH) stands as a rare and challenging systemic granulomatous disease characterized by its predilection for skin and joint involvement, confounding clinicians with its infrequent presentation and systemic manifestations., Case Description: This compelling case presentation unravels the intricate complexity of MRH, exemplifying its unique clinical course. Following mild upper respiratory coronavirus disease 2019 (COVID-19) symptoms, the patient manifested purplish-pink papular lesions on both the skin and mucosa, accompanied by debilitating arthralgias. A diagnostic skin biopsy, a pivotal tool in MRH diagnosis, confirmed the presence of this granulomatous disorder, underlining its systemic impact. Strategic therapeutic intervention involving a combination of steroids and methotrexate demonstrated remarkable efficacy, culminating in the resolution of symptoms within 3-month. The absence of malignancy upon thorough screening further amplifies the perplexing nature of MRH., Conclusions: This seminal case not only bridges the realms of rare systemic disorders but also marks the first known instance of MRH emerging post-COVID-19. It underscores the imperative consideration of MRH in analogous scenarios and provides invaluable insights into the nuanced interplay of MRH symptoms, diagnosis, and therapeutic strategies following viral triggers. This comprehensive exploration enriches our scientific understanding, offering nuanced perspectives on the manifestations and intricate dynamics of MRH in the context of post-viral sequelae., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-144/coif). The authors have no conflicts of interest to declare., (2024 AME Case Reports. All rights reserved.)

Past research has shown that culture can form and shape our temporal orientation-the relative emphasis on the past, present, or future. However, there are mixed findings on how temporal orientations vary between North American and East Asian cultures due to the limitations of survey methodology and sampling. In this study, we applied an inductive approach and leveraged big data and natural language processing between two popular social media platforms-Twitter and Weibo-to assess the similarities and differences in temporal orientation in the United States of America and China, respectively. We first established predictive models from annotation data and used them to classify a larger set of English Twitter sentences (NTW = 1,549,136) and a larger set of Chinese Weibo sentences (NWB = 95,181) into four temporal catetories-past, future, atemporal present, and temporal present. Results show that there is no significant difference between Twitter and Weibo on past or future orientations; the large temporal orientation difference between North Americans and Chinese derives from their different prevailing focus on atemporal (e.g., facts, ideas) present (Twitter) or temporal present (e.g., the "here" and "now") (Weibo). Our findings contribute to the debate on cultural differences in temporal orientations with new perspectives following a new methodological approach. The study's implications call for a reevaluation of how temporal orientation is measured in cross-cultural studies, emphasizing the use of large-scale language data and acknowledging the atemporal present category. Understanding temporal orientations can guide effective cross-cultural communication strategies to tailor approaches for different audience based on temporal orientations, enhancing intercultural understanding and engagement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Unhealthy alcohol consumption is a severe public health problem. But low to moderate alcohol consumption is associated with high subjective well-being, possibly because alcohol is commonly consumed socially together with friends, who often are important for subjective well-being. Disentangling the health and social complexities of alcohol behavior has been difficult using traditional rating scales with cross-section designs. We aim to better understand these complexities by examining individuals' everyday affective subjective well-being language, in addition to rating scales, and via both between- and within-person designs across multiple weeks., Method: We used daily language and ecological momentary assessment on 908 US restaurant workers (12692 days) over two-week intervals. Participants were asked up to three times a day to "describe your current feelings", rate their emotions, and report their alcohol behavior in the past 24 hours, including if they were drinking alone or with others., Results: Both between and within individuals, language-based subjective well-being predicted alcohol behavior more accurately than corresponding rating scales. Individuals self-reported being happier on days when drinking more, with language characteristic of these days predominantly describing socializing with friends. Between individuals (over several weeks), subjective well-being correlated much more negatively with drinking alone (r = -.29) than it did with total drinking (r = -.10). Aligned with this, people who drank more alone generally described their feelings as sad, stressed and anxious and drinking alone days related to nervous and annoyed language as well as a lower reported subjective well-being., Conclusions: Individuals' daily subjective well-being, as measured via language, in part, explained the social aspects of alcohol drinking. Further, being alone explained this relationship, such that drinking alone was associated with lower subjective well-being., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Bisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA., Objectives: To investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children., Methods: A total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children's Hospital during 2015-2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected)., Results: The urinary BPS higher-half group had a higher BMI z-score (β = 0.160, P= 0.044), higher fat mass (β = 0.104, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (β = 0.074, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021)., Conclusions: Increased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time., 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. Published by Elsevier Ltd.)

Backgruound: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE., Methods: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM., Results: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower., Conclusion: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Background: This study aimed to understand the experiences of nurses working in the integrated nursing care service, a relatively recent addition to the Korean hospital infrastructure, to suggest ways in which to address their grievances and needs and improve their job satisfaction, thereby reducing turnover., Methods: This study adopted a qualitative approach to explore subjects' vivid experiences. Data were collected through in-depth interviews with 17 nurses with over one year of experience working in integrated nursing care wards. The main question asked was "Can you describe your experiences in the integrated nursing care ward?" All interviews were recorded, transcribed, and analyzed using Colaizzi's method for phenomenological research., Results: Six theme clusters were derived from the analysis: "distorted perceptions of the integrated nursing care ward," "challenges owing to distorted perceptions of the integrated nursing care ward," "loneliness and fighting alone," "being ridiculed," "practicing textbook holistic care," and "the satisfaction felt only in the integrated nursing care ward." For the overarching theme, we identified "Satisfaction in providing holistic care despite the challenges.", Conclusions: While working in the integrated nursing care ward, nurses practiced holistic nursing care, which in turn built their self-esteem. However, they experienced greater levels of stress as a result of misinformation. Therefore, dissemination of accurate information is necessary to correct public misunderstandings of the integrated nursing care wards. Further, adequate compensation and support systems are needed to relieve the stress nurses felt because of such misunderstandings. Additionally, nurses should be motivated to continue to provide quality care for the patients and take pride in their work. Future research should explore the physical and mental concerns of nurses working in integrated care wards., (© 2024. The Author(s).)

The widespread use of plastic materials, owing to their several advantageous properties, has resulted in a considerable increase in plastic consumption. Consequently, the production of primary and secondary microplastics has also increased. To identify, categorize, and quantify microplastics, several analytical methods, such as thermal analysis and spectroscopic methods, have been developed. They generally offer little insight into the size and shape of microplastics, require time-consuming sample preparation and classification, and are susceptible to background interference. Herein, we created a macroscale hyperspectral Raman method to quickly quantify and characterize large volumes of plastics. Using this approach, we successfully obtained Raman spectra of five different types of microplastics scattered over an area of 12.4 mm × 12.4 mm within just 550 s and perfectly classified these microplastics using a machine learning method. Additionally, we demonstrated that our system is effective for obtaining Raman spectra, even when the microplastics are suspended in aquatic environments or bound to metal-mesh nets. These results highlight the considerable potential of our proposed method for real-world applications., 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 B.V. All rights reserved.)

Introduction: Glucagon-like peptide-1 receptor agonists are well-established type 2 diabetes (T2D) treatments. As variations among populations and culture might influence treatment effects, this post hoc analysis evaluates the efficacy and safety of once-weekly (OW) semaglutide in a Korean population., Methods: Korean adults with T2D inadequately controlled on metformin included in a 30-week, phase 3a, international, multicentre trial (NCT03061214) compared OW subcutaneous semaglutide (0.5 mg and 1.0 mg) with once-daily sitagliptin (100 mg). Key endpoints included change in glycated haemoglobin (HbA 1c ) and body weight; additional endpoints assessed proportions of participants reaching targets of HbA 1c  < 7.0% and ≤ 6.5%, ≥ 5% weight loss, and a composite endpoint of HbA 1c  < 7.0% without severe/blood glucose-confirmed symptomatic hypoglycaemia and no weight gain., Results: Korean participants (n = 110) showed a greater reduction in HbA 1c and body weight with semaglutide 0.5 mg (-1.6%, -2.7 kg) and 1.0 mg (-1.8%, -4.8 kg) versus sitagliptin (-0.9%, 0.5 kg). HbA 1c targets of < 7.0% and ≤ 6.5% were achieved by more participants treated with semaglutide 0.5 mg (80.0% and 60.0%, respectively) and 1.0 mg (87.5% and 67.5%, respectively) versus sitagliptin (54.3% and 25.7%, respectively); ≥ 5% weight loss was observed in 42.9% and 65.0% of participants treated with semaglutide 0.5 mg and 1.0 mg versus 0.0% with sitagliptin. The composite endpoint was achieved by 71.4%, 77.5%, and 31.4% of the population in the semaglutide 0.5 mg, 1.0 mg, and sitagliptin group, respectively. No new safety concerns were observed., Conclusion: This analysis confirms efficacy and safety of OW semaglutide (0.5 and 1.0 mg) in a Korean population with T2D., Clinical Trial Registration Number: NCT03061214., (© 2024. The Author(s).)

While studies show links between smartphone data and affective symptoms, we lack clarity on the temporal scale, specificity (e.g., to depression vs. anxiety), and person-specific (vs. group-level) nature of these associations. We conducted a large-scale (n = 1013) smartphone-based passive sensing study to identify within- and between-person digital markers of depression and anxiety symptoms over time. Participants (74.6% female; M age = 40.9) downloaded the LifeSense app, which facilitated continuous passive data collection (e.g., GPS, app and device use, communication) across 16 weeks. Hierarchical linear regression models tested the within- and between-person associations of 2-week windows of passively sensed data with depression (PHQ-8) or generalized anxiety (GAD-7). We used a shifting window to understand the time scale at which sensed features relate to mental health symptoms, predicting symptoms 2 weeks in the future (distal prediction), 1 week in the future (medial prediction), and 0 weeks in the future (proximal prediction). Spending more time at home relative to one's average was an early signal of PHQ-8 severity (distal β = 0.219, p = 0.012) and continued to relate to PHQ-8 at medial (β = 0.198, p = 0.022) and proximal (β = 0.183, p = 0.045) windows. In contrast, circadian movement was proximally related to (β = -0.131, p = 0.035) but did not predict (distal β = 0.034, p = 0.577; medial β = -0.089, p = 0.138) PHQ-8. Distinct communication features (i.e., call/text or app-based messaging) related to PHQ-8 and GAD-7. Findings have implications for identifying novel treatment targets, personalizing digital mental health interventions, and enhancing traditional patient-provider interactions. Certain features (e.g., circadian movement) may represent correlates but not true prospective indicators of affective symptoms. Conversely, other features like home duration may be such early signals of intra-individual symptom change, indicating the potential utility of prophylactic intervention (e.g., behavioral activation) in response to person-specific increases in these signals., (© 2024. The Author(s).)

Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response., Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins., Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways., Conclusions: These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

This research group (forensic research via omics markers in environmental health vulnerable areas: FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areas-including refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matter-along with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.

This review describes the litifilimab (BIIB 059) development program to date for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). Plasmacytoid dendritic cells (pDCs), major producers of type I interferons (IFN-I), play a key role in SLE pathogenesis. Litifilimab, a humanized monoclonal antibody, binds to BDCA2, a protein uniquely expressed on pDCs. The consequence of BDCA2 ligation is the inhibition of IFN-I as well as IFN-III, cytokine and chemokine production. Phase I and II LILAC trial parts A and B achieved primary end points in SLE and CLE patients, confirming the importance of pDCs and IFN-I in SLE and CLE. Litifilimab is currently being evaluated in phase III trials in both SLE and CLE.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and/or pregnancy complications in the presence of persistently positive antiphospholipid antibodies (aPL). Although long-term anticoagulation with vitamin K antagonists is considered standard of care, there is an unmet need for safe therapeutics as primary thromboprophylaxis or adjuncts to standard of care in APS. APS is driven by oxidative stress, procoagulant, proinflammatory and angiogenic pathways. For these reasons there has been an increased interest into the investigation of antithrombotic, anti-inflammatory and anti-oxidant properties of natural supplements in APS. The objective of this review is to summarize the mechanistic, epidemiologic and clinical evidence behind the use of natural supplements in APS, with a specific focus on vitamin D, omega-3 fatty acids, coenzyme Q10, gingerol, and isoquercetin. This review should serve as a compelling argument for the future study of natural supplements in APS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To determine the potential association between the use of either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 (DPP-4) inhibitors, and the risk of thyroid cancer in individuals with type 2 diabetes., Materials and Methods: This population-based cohort study used claims data from the Korean National Health Insurance Database, 2014-2020. Two distinct cohorts were established to compare each incretin-based drug with sodium-glucose cotransporter-2 (SGLT2) inhibitors, chosen as active comparators because of their previous non-association with thyroid cancer, and their common usage as add-on therapy to metformin along with GLP-1RAs and DPP-4 inhibitors. The first cohort included 21 722 new users of GLP-1RAs and 326 993 new users of SGLT2 inhibitors, whereas the second cohort included 904 300 DPP-4 inhibitor new users and 112 017 SGLT2 inhibitor new users. The outcome was the time to incident thyroid cancer. Weighted Cox proportional models were used to estimate hazard ratios of thyroid cancer incidence associated with incretin-based drugs of interest., Results: The use of GLP-1RAs was not associated with an increased risk of thyroid cancer (weighted hazard ratio 0.98, 95% confidence interval 0.62-1.53) compared with that of SGLT2 inhibitors. Using DPP-4 inhibitors was also not associated with an increased risk of thyroid cancer (0.95, 0.79-1.14) compared with that of SGLT2 inhibitors. No significant effect modifications were observed across subgroup analyses. Sensitivity analyses, including alternative outcome definition analysis of medullary thyroid cancer, were consistent with the primary analysis results., Conclusions: GLP-1RAs and DPP-4 inhibitors were not associated with an increased risk of thyroid cancer in individuals with type 2 diabetes., (© 2023 John Wiley & Sons Ltd.)

In this study, the intrinsic brittleness of poly(lactic acid) (PLA) was overcome by chemical modification using ethyl acetate-extracted lignin (EL) via cationic ring-opening polymerization (CROP). The CROP was conducted to promote homopolymerization under starvation of the initiator (oxyrane). This method resulted in the formation of lignin-based polyether (LPE). LPE exhibited enhanced interfacial compatibility with nonpolar and hydrophobic PLA owing to the fewer hydrophilic hydroxyl groups and a long polyether chain. In addition, because of the UV-protecting and radical-scavenging abilities of lignin, LPE/PLA exhibited multifunctional properties, resulting in improved chemical properties compared with the neat PLA film. Notably, one of the LPE/PLA films (EL&#95;MCF) exhibited excellent elongation at break of 297.7 % and toughness of 39.92 MJ/m 3 . Furthermore, the EL&#95;MCF film showed superior UV-protective properties of 99.52 % in UVA and 88.95 % in UVB ranges, both significantly higher than those of the PLA film, without sacrificing significant transparency in 515 nm. In addition, the radical scavenging activity improved after adding LPE to the PLA film. These results suggest that LPEs can be used as plasticizing additives in LPE/PLA composite films, offering improved physicochemical properties., 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 B.V. All rights reserved.)

Mental health conversational agents (a.k.a. chatbots) are widely studied for their potential to offer accessible support to those experiencing mental health challenges. Previous surveys on the topic primarily consider papers published in either computer science or medicine, leading to a divide in understanding and hindering the sharing of beneficial knowledge between both domains. To bridge this gap, we conduct a comprehensive literature review using the PRISMA framework, reviewing 534 papers published in both computer science and medicine. Our systematic review reveals 136 key papers on building mental health-related conversational agents with diverse characteristics of modeling and experimental design techniques. We find that computer science papers focus on LLM techniques and evaluating response quality using automated metrics with little attention to the application while medical papers use rule-based conversational agents and outcome metrics to measure the health outcomes of participants. Based on our findings on transparency, ethics, and cultural heterogeneity in this review, we provide a few recommendations to help bridge the disciplinary divide and enable the cross-disciplinary development of mental health conversational agents.

The phosphorylated form of histone H2AX (γ-H2AX) serves as a commonly utilized biomarker for DNA damage. Based on our previous findings, which demonstrated the formation of γ-H2AX foci as a reliable biomarker for detecting bladder carcinogens in repeated dose 28-day study in rats, we hypothesized that γ-H2AX could also function as a biomarker for detecting hepatocarcinogens. However, we found that γ-H2AX foci formation was not effectively induced by hepatocarcinogens that did not stimulate hepatocyte proliferation. Therefore, we explored alternative biomarkers to detect chemical hepatocarcinogenicity and discovered increased expressions of epithelial cell adhesion molecule (EpCAM/CD326)- and aminopeptidase N (APN/CD13) in the hepatocytes of rats administered various hepatocarcinogens. Significant increases in EpCAM- and APN-positive hepatocytes were observed for eight and five of the 10 hepatocarcinogens, respectively. Notably, five and two of them, respectively, were negative for γ-H2AX foci. These results highlight the potential of EpCAM and APN as useful biomarkers in combination with γ-H2AX for the detection of chemical hepatocarcinogenicity., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Importance: Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain., Objective: To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD., Design, Setting, and Participants: This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023., Main Outcomes and Measures: The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD., Results: After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06])., Conclusions and Relevance: In this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.

Aim: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU)., Materials and Methods: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models., Results: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses., Conclusions: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes., (© 2023 John Wiley & Sons Ltd.)

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs., Competing Interests: Declaration of interests D.-M.S. cofounded Cell2in, a company focused on developing FreSHtracer-based GRC assays., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Prior literature links passively sensed information about a person's location, movement, and communication with social anxiety. These findings hold promise for identifying novel treatment targets, informing clinical care, and personalizing digital mental health interventions. However, social anxiety symptoms are heterogeneous; to identify more precise targets and tailor treatments, there is a need for personal sensing studies aimed at understanding differential predictors of the distinct subdomains of social anxiety. Our objective was to conduct a large-scale smartphone-based sensing study of fear, avoidance, and physiological symptoms in the context of trait social anxiety over time., Methods: Participants ( n  = 1013; 74.6 % female; M age = 40.9) downloaded the LifeSense app, which collected continuous passive data (e.g., GPS, communication, app and device use) over 16 weeks. We tested a series of multilevel linear regression models to understand within- and between-person associations of 2-week windows of passively sensed smartphone data with fear, avoidance, and physiological distress on the self-reported Social Phobia Inventory (SPIN). A shifting sensor lag was applied to examine how smartphone features related to SPIN subdomains 2 weeks in the future (distal prediction), 1 week in the future (medial prediction), and 0 weeks in the future (proximal prediction)., Results: A decrease in time visiting novel places was a strong between-person predictor of social avoidance over time (distal β  = -0.886, p  = .002; medial β  = -0.647, p  = .029; proximal β  = -0.818, p  = .007). Reductions in call- and text-based communications were associated with social avoidance at both the between- (distal β  = -0.882, p  = .002; medial β  = -0.932, p  = .001; proximal β  = -0.918, p  = .001) and within- (distal β  = -0.191, p  = .046; medial β  = -0.213, p  = .028) person levels, as well as between-person fear of social situations (distal β  = -0.860, p  < .001; medial β  = -0.892, p  < .001; proximal β  = -0.886, p  < .001) over time. There were fewer significant associations of sensed data with physiological distress. Across the three subscales, smartphone data explained 9-12 % of the variance in social anxiety., Conclusion: Findings have implications for understanding how social anxiety manifests in daily life, and for personalizing treatments. For example, a signal that someone is likely to begin avoiding social situations may suggest a need for alternative types of exposure-based interventions compared to a signal that someone is likely to begin experiencing increased physiological distress. Our results suggest that as a prophylactic means of targeting social avoidance, it may be helpful to deploy interventions involving social exposures in response to decreases in time spent visiting novel places., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Caitlin A. Stamatis has received salary and equity support from Akili Interactive Labs and Google. Jonah Meyerhoff has accepted consulting fees from Boehringer Ingelheim. David C. Mohr has accepted honoraria and consulting fees from Otsuka Pharmaceuticals, Optum Behavioral Health, Centerstone Research Institute, and the One Mind Foundation, royalties from Oxford Press, and has an ownership interest in Adaptive Health, Inc., (© 2023 Published by Elsevier B.V.)

Background: Rubber band ligation (RBL) is a widely accepted intervention for the treatment of haemorrhoids. However, post procedure pain is a common complaint. The aim of this study was to determine whether the addition of local anaesthetic (LA) to the haemorrhoid pedicle base, post RBL, aids in reducing early post-procedure pain. Additionally, to compare perceived perianal numbness, oral analgesia usage and total consumption, and adverse events., Methods: This study was a prospective, single-blinded randomised controlled trial. Patients were recruited from colorectal clinics in two Australian hospitals between 2018-2019. Patients randomised to the intervention (LA) group received 2mls bupivacaine 0.5% with adrenaline 1:200,000 to each haemorrhoid base. Patients in the control group were not administered LA. Pain scores were recorded over 48 h using visual analogue scales. Analgesia consumption was documented and other secondary objectives were recorded dichotomously (yes/no)., Results: At 1 h post-procedure, patient reported pain scores were significantly lower in the LA group compared to the control group (p = 0.04). There were no significant differences in pain scores between the groups at 4, 24 or 48 h. Additionally, there were no significant differences between groups with respect to oral analgesia usage, perianal numbness or adverse events., Conclusions: LA to the haemorrhoid pedicle post RBL may significantly reduce early post procedure pain without any increased risk of adverse effects., (© 2023. Springer Nature Switzerland AG.)

On-demand photo-steerable amphibious rolling motions are generated by the structural engineering of monolithic soft locomotors. Photo-morphogenesis of azobenzene-functionalized liquid crystal polymer networks (azo-LCNs) is designed from spiral ribbon to helicoid helices, employing a 270° super-twisted nematic molecular geometry with aspect ratio variations of azo-LCN strips. Unlike the intermittent and biased rolling of spiral ribbon azo-LCNs with center-of-mass shifting, the axial torsional torque of helicoid azo-LCNs enables continuous and straight rolling at high rotation rates (≈720 rpm). Furthermore, center-tapered helicoid structures with wide edges are introduced for effectively accelerating photo-motilities while maintaining directional controllability. Irrespective of surface conditions, the photo-induced rotational torque of center-tapered helicoid azo-LCNs can be transferred to interacting surfaces, as manifested by steep slope climbing and paddle-like swimming multimodal motilities. Finally, the authors demonstrate continuous curvilinear guidance of soft locomotors, bypassing obstacles and reaching desired destinations through real-time on-demand photo-steering., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Improved stormwater treatment is needed to prevent toxic and mobile contaminant transport into receiving waters and allow beneficial use of stormwater runoff. In particular, safe capture of stormwater runoff to augment drinking water supplies is contingent upon removing dissolved trace organic contaminants (TrOCs) not captured by conventional stormwater control measures. This study builds upon a prior laboratory-based column study investigating biochar and regenerated activated carbon (RAC) amendment for removing hydrophilic trace organic contaminants (HiTrOCs) and poly- and perfluoroalkyl substances (PFASs) from stormwater runoff. A robust contaminant transport model framework incorporating time-dependent flow and influent concentration is developed and validated to predict HiTrOC and PFAS transport in biochar- and RAC-amended stormwater filters. Specifically, parameters fit using a sorption-retarded intraparticle pore diffusion transport model were validated using data further along the depth of the column and compared to equilibrium batch isotherms. The transport model and fitted parameters were then used to estimate the lifetime of a hypothetical stormwater filter in Seal Beach, CA, to be 35 ± 6 years for biochar- and 51 ± 17 years for RAC-amended filters, under ideal conditions with no filter clogging. This work offers insights on the kinetics of HiTrOC and PFAS transport within biochar and RAC filters and on the impact of filter design on contaminant removal performance and longevity.

Importance: Postmenopausal individuals with type 2 diabetes are susceptible to fractures due to the interaction of elevated blood glucose levels and a deficiency of the hormone estrogen. Despite continued concerns of fracture risks associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), existing evidence in this high-risk population is lacking., Objective: To assess the risk of fractures associated with SGLT2i vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors (DPP4i) and glucagon-like peptide 1 receptor agonists (GLP1RA), separately, in postmenopausal individuals with type 2 diabetes., Design, Setting, and Participants: This active-comparator, new-user cohort study used nationwide claims data of Korea and took place from January 1, 2013, to December 31, 2020. Postmenopausal individuals (aged ≥45 years) with type 2 diabetes were included., Exposures: New users of SGLT2i or comparator drugs., Main Outcomes and Measures: The primary outcome was overall fractures, comprising vertebral, hip, humerus, and distal radius fractures. Patients were followed up from the day after drug initiation until the earliest of outcome occurrence, drug discontinuation (90-day grace period) or switch, death, or end of the study period. After propensity score fine stratification, hazard ratios (HRs) with 95% CIs were estimated using weighted Cox models., Results: Among 37 530 (mean [SD] age, 60.6 [9.7] years) and 332 004 (mean [SD] age, 60.6 [9.9] years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i vs DPP4i (weighted HR, 0.78; 95% CI, 0.72-0.84). Among 111 835 (mean [SD] age, 61.4 [9.8] years) and 8177 (mean [SD] age, 61.1 [10.3] years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i vs GLP1RA (weighted HR, 0.92; 95% CI, 0.68-1.24). Results from several subgroup and sensitivity analyses presented consistent results from main analysis., Conclusions and Relevance: This population-based cohort study suggests that SGLT2i was not associated with an increased rate of incident fractures compared with DPP4i and GLP1RA, separately, among postmenopausal individuals with type 2 diabetes.

Aim: To explore the risk of breakthrough infection among patients with type 2 diabetes (T2D) and risk of severe clinical outcomes after SARS-CoV-2 infection according to vaccination status., Materials and Methods: We conducted a population-based cohort study using South Korea's linked database of nationwide COVID-19 registry and claims data between 2018 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breakthrough infections were measured in 1:1 propensity-score (PS)-matched fully vaccinated patients with versus without T2D (full-vaccination cohort), and HRs for all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) use, and hospitalizations after SARS-CoV-2 infection were measured in 1:1 PS-matched T2D patients with versus without full-vaccination (T2D cohort)., Results: After 1:1 PS matching, 2 109 970 patients with and without T2D were identified (age 63.5 years; 50.9% male). Patients with T2D showed an increased risk of breakthrough infections compared to those without T2D (HR 1.10, 95% CI 1.06-1.14). The increased risk of breakthrough infections was more notable among T2D patients receiving insulin treatment. However, the risk of severe COVID-19 outcomes was lower in fully vaccinated T2D patients compared with unvaccinated T2D patients (all-cause mortality: HR 0.54, 95% CI 0.43-0.67; ICU admission/MV use: HR 0.31, 95% CI 0.23-0.41; hospitalization: HR 0.73, 95% CI 0.68-0.78)., Conclusions: While patients with T2D remain a vulnerable population to SARS-CoV-2 infection even after full-vaccination, full-vaccination was associated with a lower risk of adverse clinical outcomes after SARS-CoV-2 infection. These findings support the guidelines recommending patients with T2D as a priority vaccination group., (© 2023 John Wiley & Sons Ltd.)

Ecofriendly multifunctional films with only biomass-based components have gathered significant interest from researchers as next-generation materials. Following this trend, a TEMPO-oxidized cellulose nanofibril (TOCNF) film containing hydrophilic lignin (CL) was fabricated. To produce the lignin, peracetic acid oxidation was carried out, leading to the introduction of carboxyl groups into the lignin structure. By adding hydrophilic lignin, various characteristics (e.g., surface smoothness, UV protection, antimicrobial activity, and barrier properties) of the TOCNF film were enhanced. In particular, the shrinkage of CNF was successfully prevented by the addition of CL, which is attributed to the lower surface roughness (R a ) from 18.93 nm to 4.99 nm. As a result, the smooth surface of the TOCNF/CL film was shown compared to neat TOCNF film and TOCNF/Kraft lignin composite film. In addition, the TOCNF/CL film showed a superior UV blocking ability of 99.9 % with high transparency of 78.4 %, which is higher than that of CNF-lignin composite films in other research. Also, water vapor transmission rate was reduced after adding CL to TOCNF film. Consequently, the developed TOCNF/CL film can be potentially utilized in various applications, such as food packaging., 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 B.V. All rights reserved.)

Acrylamide, a common food contaminant, is metabolically activated to glycidamide, which reacts with DNA at the N7 position of dG, forming N7-(2-carbamoyl-2-hydroxyethyl)-dG (GA 7 dG). Owing to its chemical lability, the mutagenic potency of GA 7 dG has not yet been clarified. We found that GA 7 dG undergoes ring-opening hydrolysis to form N 6 -(2-deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-[N-(2-carbamoyl-2-hydroxyethyl)formamido]pyrimidine (GA-FAPy-dG), even at neutral pH. Therefore, we aimed to examine the effects of GA-FAPy-dG on the efficiency and fidelity of DNA replication using an oligonucleotide carrying GA-FAPy-9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)guanine (dfG), a 2'-fluorine substituted analog of GA-FAPy-dG. GA-FAPy-dfG inhibited primer extension by both human replicative DNA polymerase ε and the translesion DNA synthesis polymerases (Polη, Polι, Polκ, and Polζ) and reduced the replication efficiency by less than half in human cells, with single base substitution at the site of GA-FAPy-dfG. Unlike other formamidopyrimidine derivatives, the most abundant mutation was G:C > A:T transition, which was decreased in Polκ- or REV1-KO cells. Molecular modeling suggested that a 2-carbamoyl-2-hydroxyethyl group at the N 5 position of GA-FAPy-dfG can form an additional H-bond with thymidine, thereby contributing to the mutation. Collectively, our results provide further insight into the mechanisms underlying the mutagenic effects of acrylamide., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Trisomy 18 syndrome (T18) is the second most common autosomal trisomy and has a high risk of fetal loss and stillbirth. Aggressive surgical treatments for the respiratory, cardiac, or digestive systems of patients with T18 were previously futile, while the results of recent studies are controversial. Over the past decade, there have been approximately 300,000 to 400,000 births annually in the Republic of Korea; however, there have been no nationwide studies on T18. This nationwide retrospective cohort study aimed to determine the prevalence of T18 in Korea and its prognosis according to the presence of congenital heart disease and relevant interventions., Methods: This study utilized NHIS-registered data between 2008 and 2017. A child was defined as having T18 if the ICD-10 revision code Q91.0-3 was reported. Subgroup analysis was performed for children with congenital heart diseases, and survival rates were compared based on the history of cardiac surgical or catheter interventions. The primary outcomes in this study were the survival rate during the first hospitalization period and the 1-year survival rate., Results: Of the children born between 2008 and 2017, 193 were diagnosed with T18. Of these, 86 died, with a median survival of 127 days. The 1-year survival rate for children with T18 was 63.2%. The survival rate in the first admission of children with T18 who did and did not have congenital heart disease was 58.3% and 94.1%, respectively. Children with heart disease who underwent surgical or catheter intervention had a longer survival time than those who did not., Conclusions: We suggest these data could be used in ante- and postnatal counseling. Ethical concerns about the prolonged survival of children with T18 remain; however, the potential benefits of interventions for congenital heart disease in this population need further study., (© 2023. The Author(s).)

Background: Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids., Case Presentation: We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor., Conclusion: To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases., (© 2023. The Author(s).)

Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Purpose: Resectional Roux-en-Y gastric bypass (RRYGB) is considered an alternative bariatric surgery in countries with a high incidence of stomach cancer because there is no excluded stomach after RRYGB. This study aimed to evaluate the efficacy and safety of RRYGB., Materials and Methods: This study included patients who underwent RRYGB and sleeve gastrectomy (SG) between 2011 and 2021. Surgical complications and metabolic and nutritional profiles were compared between the patients preoperatively and at 1, 6, and 12 months after surgery., Results: Twenty and seventy-six patients underwent RRYGB and SG, respectively; 7 in the SG group were lost to follow-up within 1 year. Surgical complications and baseline characteristics were comparable between two groups, except for diabetes (90.0% vs. 44.7%, p < 0.001). The decrease of HbA1c levels and incidence of reflux esophagitis were lower in the RRYGB group compared to that of SG at 1-year postoperative (-3.0% vs. -1.8%, p = 0.014; 0% vs. 26.7%, p = 0.027). The percentage of total weight loss at 1- year postoperative and incidence of dumping syndrome were comparable between the two groups. The RRYGB group had significantly lower total cholesterol level (161.9 mg/dl vs. 196.4 mg/dl, p < 0.001), but higher incidence of vitamin B12 deficiency (30.0% vs. 3.6%, p = 0.003) at 1 year postoperative compared to those of the SG group., Conclusions: The RRYGB group had better postoperative outcomes for diabetes and dyslipidemia without increasing surgical complications compared to that of the SG group. Thus, RRYGB can be considered a safe and effective alternative in areas where gastric cancer is prevalent., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Public long-term care insurance (LTCI), which provides home and institutional care benefits, was introduced in July 2008 in South Korea. This study aims to evaluate the effects of the introduction of LTCI on older people's medical service use, including outpatient visits, inpatient services and longer stays (181 days or longer) in hospitals by implementing a quasi-experiment design with a generalised difference-in-difference method. The results showed that the introduction of LTCI did not change the use of outpatient medical services, although the medical costs of older people who used medical services at least once decreased by 9.4%. For the inpatient services, hospitalisation rates declined by 2.7% as a result of the LTCI. Length of stay and inpatient expenses decreased by 15.6 and 9.5%, respectively. For older people of LTC grade 2, eligible for long-term care facilities (LTCF), prolonged hospitalisation rates decreased by 1.6% due to the LTCI. In conclusion, the introduction of LTCI in South Korea has contributed to decreasing the use of inpatient services and longer stays in hospitals, which suggests that the utilisation of LTCF has become a substitute for some social admissions in hospitals.

In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status., Competing Interests: Conflict of Interest None declared., (International College of Angiology. This article is published by Thieme.)

Objective: Continuous glucose monitoring system (CGMS) is growing popular and preferred by diabetes over conventional methods of self-blood glucose monitoring (SBGM) systems. However, currently available commercial CGMS in the market is useful for few days to few months. This paper presents a durable, highly sensitive and minimally invasive implant type electromagnetic sensor for continuous glucose monitoring that is capable of tracking minute changes in blood glucose level (BGL)., Methods: The proposed sensor utilizes strong oscillating nearfield to detect minute changes in dielectric permittivity of interstitial fluid (ISF) and blood due to changes in BGL. A biocompatible packaging material is used to cover the sensor. It helps in minimizing foreign body reactions (FBR) and improves stability of the sensor., Results: The performance of the proposed sensor was evaluated on live rodent models (C57BL/6J mouse and Sprague Dawley rat) through intravenous glucose and insulin tolerance tests. Biocompatible polyolefin was used as the sensor packaging material, and the effect of packaging thickness on the sensitivity of sensor was examined in in-vivo test. Proposed sensor could track real-time BGL change measured with a commercial blood glucose meter. High linear correlation (R 2 > 0.9) with measured BGL was observed during in vivo experiments., Conclusion: The experimental results demonstrate that the proposed sensor is suitable for long term CGMS applications with a high accuracy., Significance: Present work offers a new perspective towards development of long term CGM system using electromagnetic based implant sensor. The in vivo evaluation of the sensor shows excellent tracking of BGL changes.